Epigenetics provides a molecular mechanism of inheritance that is not solely dependent on DNA sequence and that can account for non-Mendelian inheritance patterns. Epigenetic changes underlie many normal developmental processes, and can lead to disease development as well. While epigenetic effects have been studied in well-characterized rodent models, less research has been done using agriculturally important domestic animal species. This review will present the results of current epigenetic research using farm animal models . Much of the work has focused on the epigenetic effects that environmental exposures to toxicants, nutrients and infectious agents has on either the exposed animals themselves or on their direct offspring. Only one porcine study examined epigenetic transgenerational effects; namely the effect diet micronutrients fed to male pigs has on liver DNA methylation and muscle mass in grand-offspring (F2 generation). Healthy viable offspring are very important in the farm and husbandry industry and epigenetic differences can be associated with production traits. Therefore further epigenetic research into domestic animal health and how exposure to toxicants or nutritional changes affects future generations is imperative. Mendelian genetic theories have guided much of the biological research preformed in recent history. It has long been assumed that specific phenotypes arise only from DNA sequence. However, non-Mendelian inheritance patterns challenge these theories and suggest that an alternate process might exist to account for certain mechanisms of inheritance. Epigenetics provides a molecular mechanism that can account for these non-Mendelian observations–3. EpigeDespite the amount of epigenetic and transgenerational epigenetic inheritance research being done on a multitude of mammal, insect, and plant models, 16–21, et al. found that during lactation the (STAT)5-binding lactation enhancer, which is part of the αS1-casein encoding gene, is hypomethylated[Escherichia coli infection of the mammary gland, this region becomes methylated at three CpG dinucleotides which accompanies a shut down of αS1-casein synthesis[Streptococcus uberis[et al. preformed a generational study to see if a mother dairy cow affected the milk production of her offspring[The relationship of DNA methylation and milk production in dairy cattle has been investigated. During lactation the bovine αS1-casein gene is hypomethylated. Researcthylated. Howeverynthesis. These ous uberis. In addius uberis. Gonzáleffspring. They foffspring. Becauseet al.[More research has been done on histone modification related to nutritional changes than on DNA methylation. Short-chain fatty acids are particularly important in ruminant digestion, and are used for cell energy production and use. Butyratet al. show thaet al., but hiset al.[in vitro fertilized, and somatic-cell nuclear transfer embryos, and suggests that these methylation differences may account for the different success rates and health of calves born from these reproductive technologies[et al.[The influence of epigenetics on disease has been studied in many animal models such as rats, mice, and humans, but very little has been done with cattle. One bovine developmental disease called large-offspring syndrome (LOS) has been found to have epigenetic components during embryonic growth. LOS has largely been associated with reproductive technologies commonly used with cattle such as in vitro fertilization and somatic-cell nuclear transfer. Symptomet al. has reponologies. A numbenologies and bovinologies, which i[et al. looked a[et al..No studies have been published showing epigenetic transgenerational inheritance in cattle.Swine are often used as animal models to study human disease because of the similar physiology between the two species. Because of this, much of the epigenetic porcine research involves exposure and response, with very little of the current research being transgenerational.et al.[et al.[Epigenetic effects due to histone modification and acetylation have been studied in a porcine model both in order to increase meat production and to develop a potential treatment for muscular degenerative disease. Sulforaphane is a bioactive histone deacetylase inhibitor often found in edible vegetation like broccoli. Fan et et al. treated et al.. Liu et [et al. also loo[et al.. Another[et al.. Researc[et al.. However[et al.. This st[et al..et al. demonstrated that neonatal estrogen exposure in piglets can lead to epigenetic changes that affect uterine capacity and environment[Research conducted by Tarletan ironment. This leironment. Anotherironment. Howeverironment.et al. preformed a three generational study to look at the effect of feeding on male epigenetic inheritance. The experimental group F0 generation males were fed a diet high in methylating micronutrients, and the resulting F2 generation had a lower fat percentage and higher shoulder muscle percentage as compared to controls. They also found significant differences in DNA methylation between the control and experimental groups, especially in the liver, which was proposed to epigenetically affect fat metabolism pathways[One recent transgenerational porcine study has been reported, Table pathways.et al.[As shown in the bovine model and porcine model, maternal nutritional impact is a common topic in epigenetic research, and ovine studies are no exception. Zhang et al. looked iet al.. Other net al., 52. HowNo studies have been published showing epigenetic transgenerational inheritance in sheep.et al.[in vitro the propagation in the infected cells was slowed. Observations suggested that DNA methylation in the host may be associated with virus resistance or susceptibility[Marek’s disease in chickens is a manifestation of Marek’s disease virus and progresses to become a T-cell lymphoma that affects chickens and other birds. Vaccines have been developed but they are not completely successful. Tian etet al. set to ftibility.Different developmental epigenetic patterns have been studied between chicken types. One study looked at differential DNA methylation in breast muscle between slow-growing and fast-growing broiler chickens. They foAs one review indicated, many poultry studies indicate that there may be epigenetic effects, and even transgenerational epigenetic inheritance, though very few studies actually test for DNA methylation or histone modification in their research.No studies have been published showing epigenetic transgenerational inheritance in chicken.While a good amount of epigenetic research has been preformed on domesticated farm animals still more needs to be done, Table Epigenetics: Molecular factors/processes around the DNA that regulate genome activity independent of DNA sequence, and are mitotically stable.absence of direct environmental influences, that leads to phenotypic variation.Epigenetic: Transgenerational Inheritance: Germline-mediated inheritance of epigenetic information between generations in the Epimutation: Differential presence of epigenetic marks that lead to altered genome activity.


Ixodes scapularis ticks collected in Texas and Mexico were infected with the Lyme disease spirochete Borrelia burgdorferi . However, our analyses of their initial data  and a recent response by Esteve-Gassent et al.  provide evidence that the positive PCR results obtained from both ribosomal RNA intergenic sequences and the flagellin gene flaB are highly likely due to contamination by the B. burgdorferi B31 positive control strain.Feria-Arroyo et al. had reported previously that, based on PCR analysis, 45 % of  Ixodes scapularis ticks collected in Texas and Mexico were infected with the Lyme disease spirochete Borrelia burgdorferi, based on nested PCR amplification and sequencing of the 16S rDNA-23S rDNA intergenic spacer region (IGS). Positive PCR results were also reported for the B. burgdorferi flagellin gene flaB, but no flaB sequences were provided in the article. The results reported by Feria-Arroyo et al. [Borrelia of any kind. In a comprehensive reanalysis of their data [B. burgdorferi B31, used in their study. This commonly used strain was the first isolate of B. burgdorferi, and was obtained from ticks collected on Shelter Island, New York in 1981 [flaB sequences from several of the tick specimens from Texas and claimed that “Infection levels using a second genetic marker (flaB), confirmed the results originally obtained by the 16S rRNA-23S rRNA gene intergenic spacer (IGS) of B. burgdorferi”. However, a simple comparison of these flaB sequences to existing genomic sequences indicated that they are essentially identical to the B. burgdorferi B31 sequence, contrary to their conclusions [1) The findings reported by Feria-Arroyo and coworkers [B. burgdorferi in their sample of ticks from Texas and Mexico are erroneous; and (2) The inaccurate information, most plausibly, was the consequence of laboratory contamination of the samples in the chain of possession and faulty analysis of their results and the scientific literature. Our presumption is that the contamination was not intentional but inadvertent. . The inThe Esteve-Gassent et al. response does not address the IGS sequence identity between the Texas samples and the positive control strainIn particular, we bring attention to the following points.Ixodes scapularis ticks collected in Texas and Mexico were infected with Borrelia burgdorferi. This conclusion was based on positive PCR results obtained with these samples using primers for the 16S rDNA-23S rDNA intergenic spacer region (IGS). In our prior Letter to the Editor [B. burgdorferi B31, indicating cross-contamination of the Texas samples with B31 DNA. Extensive regions (664 to 925 bp) were identical to the corresponding B31 sequence in 10 specimens, and were ≥98.9 % identical in the remaining 11 specimens , confirmed the results originally obtained by the 16S rRNA-23S rRNA gene intergenic spacer (IGS) of B. burgdorferi.” It should first be noted that the flagellin protein gene flaB is highly conserved in B. burgdorferi, so it is useful for detecting B. burgdorferi strains but not for distinguishing between them. Indeed, Figure one in the Esteve-Gassent et al. response [et al. argued that the infected ticks reported in our study were found infected with B. burgdorferi likely due to contamination of the PCR reactions with DNA from the strain B31 of B. burgdorferi, the positive control used in the study. Nevertheless, B. burgdorferi B31 flaB has a cytosine (C) at position 75 in this alignment  while the Texas isolates had an adenine (A). The A in the Texas isolate makes them more similar to strains N40 and 297 than to B31. Contamination of our samples with strains N40 and 297 is impossible, since these strains are not present in the laboratory in which molecular analyses were carried out”.“Norris In their response, Esteve-Gassent et al.  state thresponse  indicateresponse  go on toB. burgdorferi B31 chromosome sequence (GenBank Accession No. AE000783.1) has an adenine (A) at the indicated position. A recent resequencing of the B31 genome (CP009656) has the same sequence. In fact, nearly all of the reported B. burgdorferi flaB sequences (over 100) have an adenine at this position. The only exceptions are three reported sequences: two from Dr. Reinhardt Wallich in Germany (X15661 and X16833) and one from a group in the United Kingdom (Y15088). Because the sequence difference is restricted to this one nucleotide, the particular clone used by these groups likely had a point mutation at this position.We were puzzled by this statement in that the widely accepted flaB. In the B31 genomic sequence, the gene is annotated as BB0147 and the descriptor used is “P41”, one of the initial descriptions of this protein as a 41-kDa protein antigen. Esteve-Gassent et al. [BB0147 is the same as flaB, although a simple BLAST search would have demonstrated this fact.Esteve-Gassent et al.  apparentflaB sequences from Texas samples in the GenBank database; three sequences included in their response  have not been provided to GenBank. These GenBank sequences are longer than those provided in Fig. one of their response, and are 234 to 238 nt in length. An alignment of the GenBank sequences with the corresponding flaB region from the B. burgdorferi B31 genome sequence (nt 147949–148187) is shown in Fig. flaB sequences reported by Esteve-Gassent et al. [flaB gene, with the exception of a few differences (apparent sequence errors) at the ends of their sequences and one near the middle of one of their sequences (MMWMA69-70). The comparable sequences from B. burgdorferi N40 and 297 and the GenBank entry from Dr Wallich’s group (X15661) are shown at the bottom of the alignment. The position of the cytosine in question (nt 67) in X15661 is indicated.Esteve-Gassent et al.  have depflaB sequences reported by Esteve-Gassent et al. [B. burgdorferi B31 flaB has a cytosine (C) at position 75 in this alignment  while the Texas isolates had an adenine (A)” is incorrect. In fact, we have confirmed experimentally by Sanger sequencing that low-passage B31 contains an adenine at this position, in order to further rule out the possibility of a sequence error at this nucleotide. The flaB sequences are the only new information provided in the response by Esteve-Gassent et al. [flaB sequences are the same as those in the positive control (strain B31). The flaB results in no way affect the interpretation of the IGS results, which are much more important because of the heterogeneity in IGS sequences observed among B. burgdorferi strains.3.The reverse complement of the BWTX12-16 DNA sequence is mistakenly displayed in Fig. oneThese results clearly demonstrate that the t et al.  are indet et al. , yet theB. burgdorferi in the regions sampled likely exceed the values found by Feria-Arroyo et al. study [“BWTX12-16, a questing tick, has a significantly different sequence from either of the controls or the other Texan samples, suggesting that the degree of genetic variation of l. study , which oIn this figure in the response from Esteve-Gassent et al. , the BWTB. burgdorferi strains 297, N40 and B31, and most of the other Texas samples. Indeed, the reverse complement of the BWTX12-16 sequence was mistakenly used in Fig. one, resulting in the appearance of many nucleotide differences. In addition, the last 12 nucleotides of BWTX12-16 sequence in Fig. one do not match any sequence, including the BWTX12-16 sequence from GenBank that Esteve-Gassent et al. [4.Figure two of the Esteve-Gassent et al. response reinforces sequence identity with B31 in most tick samples from Texas, but also indicates the presence of sequence errors in some of the sequences from Texas samplesHowever, Figure two of their response shows that the predicted amino acid sequence of BWTX12-16 is identical to those of the B. burgdorferi B31 sequence from “T” to “N”, most of the Texas samples have identical sequences to B31. However, two samples (GE64 and MM68) have extensive regions that are different from the FlaB sequence in B. burgdorferi strains. The GE64 nucleotide sequence has two frameshifts and MM68 has a single frameshift, which result in the aberrant amino acid sequences shown in Fig. two of Esteve-Gassent et al. [5.Figure three of the response by Esteve-Gassent et al.  inappropWith correction of amino acid 22 in the mples GE6 and MM68http://phylogeny.lirmm.fr/phylo_cgi/index.cgi and shows that all of the sequences from GenBank are identical, except for single nucleotide differences in the Texas sample MM69-10, the Wallich et al. flaB sequence X15661 and strain N40. The corresponding Figure from Esteve-Gassent et al. [6.B. burgdorferi strainsThe conclusions of Esteve-Gassent et al.  are contOnly nucleotide or amino acid sequences that cover the same range of sequence and are free from sequence errors can be utilized to construct reliable phylogenetic trees. In Fig. three-a of the response , both N4B. burgdorferi with identical or nearly identical IGS genotypes.The following paragraph indicates their resistance to consider the possibility of DNA contamination and sequence errors in their results, with the conclusion that samples acquired from ticks feeding on white-tailed deer, gembok and dogs in a large geographical area harbour et al. stated in their letter that due to the low variability observed in the IGS from the Texas samples most, if not all of them, were likely to have been originated from the same clone which they assume could be the product of contamination with the B31 strain. We disagree with the interpretation put forward by Norris et al. and instead think it is more likely that the lack of variability reported in Feria-Arroyo et al. reflects the level of B. burgdorferi variability present in the Texas-Mexico transboundary region. Several of the ticks included in the Feria-Arroyo study were collected from white-tailed deer, gemsbok and dog. These mammalian hosts, particularly white-tailed deer, harbour ticks from several lineages. Thus, ticks collected from white-tailed deer, even if collected from the same individual, are likely to carry a representation of the B. burgdorferi strains present in a particular location. Thus, the B. burgdorferi genetic diversity reported by Feria-Arroyo et al., likely represents the genetic variation present in the Texas-Mexico transboundary region”.“Norris Esteve-Gassent et al.  state:“NB. burgdorferi isolates in other geographical regions. They also do not address the overall high sequence identity of the IGS sequences (99.8 % to 100 %) and random distribution of sequence differences shown in Table one of the Letter to the Editor from Norris et al. [−17. These points are addressed thoroughly in the prior Letter [7.B. burgdorferi infection in Texas and MexicoThe article by Feria-Arroyo et al.  providesHere, the authors provide no citations that indicate a similar sequence homogeneity among s et al. . In conts et al. ). In ours et al. , we had r Letter  and are B. burgdorferi was detected in 45 % of I. scapularis ticks…”.To quote the Feria-Arroyo et al. article , “Infect“Norris et al. suggest that the Feria-Arroyo et al.  publicatThis degree of positivity is contrary to all prior Texas studies (except for one prior article by members of this group) and would indicate a tick infection rate as high as that found in the ‘hot spots’ of Lyme disease in the Northeastern United States , to which BioMedCentral adheres, states that “Journal editors should consider retracting a publication if they have clear evidence that the findings are unreliable, either as a result of misconduct  or honest error .” We believe that the latter assessment is the case. Therefore, we recommend the retraction of the Feria-Arroyo et al. article [Parasites & Vectors.We conclude that, as in the case of the article by Feria-Arroyo et al. , the dat article  from Par


We identified three issues with the study by Second, the Revised Center for Epidemiologic Studies Depression Scale  is not tThird, Wang et al. did not address health status in their reported association. There isconvincing evidence supporting the association between cardiovascular disease (CVD) andboth ambient air pollution e.g.,  and depr


Electrical properties of living cells have been proven to play significant roles in understanding of various biological activities including disease progression both at the cellular and molecular levels. Since two decades ago, many researchers have developed tools to analyze the cell’s electrical states especially in single cell analysis (SCA). In depth analysis and more fully described activities of cell differentiation and cancer can only be accomplished with single cell analysis. This growing interest was supported by the emergence of various microfluidic techniques to fulfill high precisions screening, reduced equipment cost and low analysis time for characterization of the single cell’s electrical properties, as compared to classical bulky technique. This paper presents a historical review of single cell electrical properties analysis development from classical techniques to recent advances in microfluidic techniques. Technical details of the different microfluidic techniques are highlighted, and the advantages and limitations of various microfluidic devices are discussed. Study of the cell has emerged as a distinct new field, and acknowledged to be one of the fundamental building blocks of life. Moreover, the cells have unique biophysical and biochemical properties to maintain and sense the physiological surrounding environment to fulfill its specific functions ,2. CelluSingle cell analysis (SCA) has become a trend and major topic to engineers and scientists in the last 20 years to develop the experimental tools and technologies able to carry out single cell measurement. In addition, in depth analysis and more fully described activities of cell differentiation and cancer can only be accomplished with single cell analysis . In convElectrical properties of cells provide some insight and vital information to aid the understanding of complex physiological states of the cell. Cells that experience abnormalities or are infected by bacteria may have altered ion channel activity , cytoplaThe classical technique for a cell’s electrical properties analysis was originated in 1791, when Luigi Galvani conducted the first experiment for measuring electrical activity in animals, which is evoking muscular contractions in frog nerve muscle preparations by electrical stimulation with metal wires . From thThe patch clamp technique is unique in enabling high-resolution recording of the ionic currents flowing through a cell’s plasma membrane. Since the introduction of the patch-clamp technique by Neher and Sakmann in 1976, patch-clamp was adopted by researchers in cellular and molecular biology research areas for studying and providing valuable information of biological cell electrical properties ,27. The et al. sparked an approach for obtaining information about the characteristics and distribution of ion channels in living cells [et al. combined the whole-cell patch clamp with fluorescence ratio imaging for measuring the electric properties of a cell membrane [The work of Hamill ng cells . They usmembrane . FluoresThe conventional patch clamp technique has several disadvantages. First, the patch clamp technique is time consuming process ,35. The et al. developed a dual nanoprobe integrated with nanomanipulator units inside environmental scanning electron microscope (ESEM) to perform electrical probing on single cells for novel single cell viability detection [Salmonella typhimurium, Escherichia coli, Lactobacillus sakei and Listeria innocua), which were well correlated with the hydration state of bacteria. Nanoprobes could potentially be used to perform single cell’s electrical characterization. The nanoprobe capable to measure direct electrical properties of single cell and quantitatively determine the viability of single cells. M. R. Ahmad etection . Figure etection . This teetection . Recentletection . They deAn advance in microfabrication technique, such as soft lithography, creates new opportunities for producing structures at micrometer scale inexpensively and rapidly . For thiA cell shows a rotated ability when it is placed into a rotating electric field within a medium with a non-uniform electric field. Analysis of these phenomena called an electrorotation (ROT), is commonly used for measuring the dielectric properties of cells without invasion. ROT measurement theory is based on rotational speed of cells/particles when the cell and the suspending medium have different electric polarizability, by referring to the frequency of a rotational electric field. This electric field is generated by quadrupole (arranged in a crisscross pattern) electrodes and each electrode is connected to an AC signal with a 90° phase difference from each other.The quadrupole electrodes connected to sine wave was a famous design in ROT technique ,49,50. Fversus frequency of the applied field. Jun Yang et al. [i.e., T- and B-lymphocytes, monocytes, and granulocytes. From this experiment, ROT was capable to characterize the dielectric properties of cell subpopulations within a cell mixture. In addition, ROT was utilized to determine the cell viability at real time assessment [i.e., Giardia Intestinalis and Cyclospora Cayetanensis [In the ROT technique, the amplitude of the electric field remains unchanged because the cells are only rotated at a certain position in an electric field . Therefog et al.  used fresessment ,60,61. Ctanensis . An ellitanensis  was utilet al. and M. Cristofanilli et al., utilized ROT technique to analyze single cells and it took approximately 30 min to test a single cell [Recently, the concept of negative quadrupole dielectrophoresis (nQDEP) and ROT signals superposed on each other in electrorotation technique was reported b. An accgle cell ,63. Thesgle cell . Neverthgle cell . Table 1et al. [Flow cytometry is a fundamental and powerful analytical tool in cell biology and cellular disease diagnosis for many years. Flow cytometry has an ability to address some problems in single cell analysis such as identifiying, counting and sorting cells ,69. Baseet al.  developeet al. [et al. [et al. [et al. [Gawad et al.  develope [et al.  designed [et al. . In addi [et al.  to monit [et al. . Recentl [et al. . The devet al. [Holmes et al.  demonstret al.  and RBC et al. . In ordeet al.  developeE. coli and B. subtilis was well achieved. T. Sun et al. extends impedance measurements from one dimension to two or three dimensions by utilized electrical impedance tomography (EIT) [A label-free cell cytometry based on electrophysiological response to stimulus was reported . This mehy (EIT) . A circuhy (EIT) . Table 2Micro electrical impedance spectroscopy (µ-EIS) is a technique where dielectric properties in a frequency domain of a cell is measured to characterize and differentiate the various types of cell. Mainly this technique analyzed the current response when a single cell was trapped in a trapping system where an alternating current (AC) was applied across the trapping zone. A trapping system is a major contribution and significant part in µ-EIS device. For this reason, development of a trapping system is very crucial and varieties of the trapping system have been developed, such as hydrodynamic traps, negative pressure traps and DEP traps.et al. [First development of micro electrical impedance spectroscopy (µ-EIS) was reported in 2006 . They deet al.  developeet al. [et al. performed impedance measurement of HeLa cell based on two geometry structures of micropillars trapping system, namely, parallel and elliptical geometry [et al. demonstrated a hydrodynamic trapping device which has a differential electrode arrangement that measures multiple signals from multiple trapping sites. Measurements was performed by recording the current from two electrode pairs, one empty (reference) and one containing HeLa cells [Furthermore, the concept of vertical trapping system in µ-EIS has been used to monitor the dynamic change of single cell electrical properties over a period of time ,99. Hydret al. . Figure geometry . Malleo La cells . The devet al. to capture a single HeLa cell, then impedance measurement was performed [Recently, the concept of dielectrophoresis (DEP) for trapping system was reported . The nonerformed . Figure erformed . Despiteerformed  and timeerformed . Table 3−1 and is capable of testing a large number of cells for obtain statistically meaningful data [The rapid development of single cell analysis tools  can be seen based on the hundreds of review and technical papers currently published every year . Clearlyful data . Microflet al. utilized magnetically activated cell sorting (MACS) for obtaining the subpopulations from human peripheral blood (B-lymphocytes and monocytes), thus performing the single cell electrical properties measurement by electrorotation techniques [Electrical measurements can also be incorporated with a cell sorting unit to collect cells having different physical properties for further biochemical assaying. AC dielectrophoretic (DEP) for sorting live cells from interfering particles of similar sizes by their polarizabilities under continuous flow was reported . DEP forchniques .Microfluidic devices have demonstrated great potential in realizing electrical measurements on single cells at a higher testing speed and label free approach. Electrical measurements on single cells can be used to indicate possible diseases and it suitable for disease prescreening application. From prescreening processes, future examinations can be done to evaluate the disease condition. in situ observation of the cell response [The presented review of selected research works on single cell electrical properties provides information on technological development in single cell electrical characterization from traditional approaches to current microfluidic approaches. Microfluidics technology opens a new paradigm in cellular and microbiology research for early disease detection and provides critical information needed by research scientists and clinicians for improved clinical diagnosis and patient outcome. The recent excellent achievements in microfabrication techniques have enabled the rapid development of microfluidic technologies for further practical applications for the benefit of mankind. Furthermore, microfluidic technological progress has provided additional advantages such as reduced complexity of experiment handling, lower voltage on the electrodes, faster heat dissipation, small volume of reagents used, and response .


We are in the era of precision medicine, but I am not sure whether we are at the beginning, in the middle, or at the end. On the one hand, we have only a few targets in certain cancer types for which we have precise drugs, like the tyrosine kinase inhibition in chronic myeloid leukemia; on the other hand, it seems that targeting most cancers requires action towards several different pathways. This review indicates that our knowledge accumulates fast, but that simple solutions might not be expected anymore. Nevertheless, I do think that we are on the right path, but it will be a long one.high and BCRlow) subsets of patients: higher levels of BTK/SYK/BLNK/CARD11/PLCG and lower expression of MALT1/BCL10 genes was considered indicative of low BCR activation, amplified expression of TLR6/TLR7/TLR9 was regarded as BCRhigh; the latter group had also enhanced expression of genes associated with NF-κB pathway and a poorer clinical outcome. Also in follicular lymphoma (FL) BCR signaling is critical. In fact, there is aberrant glycosylation of the immunoglobulin receptor in FL as a result of which DC-SIGN can activate the lymphoma cells. Linley et al. [A fine example of complexity but nevertheless potential new treatment options is given by the work of Thijssen et al. . It is wy et al.  show thaTrying to understand the process of transformation of FL also does not result in an easy answer. Extensive work on many cases of transformed FL  by Kridel et al.  resultedUsing large data sets in a clever way can provide insight in the complexity of lymphoma-immune response interaction and Care et al.  provide n > 150)) identified somatic mutations in PCBP1 in 3/17 (18 %) BL . They confirmed the recurrence of PCBP1 mutations by Sanger sequencing in an independent validation cohort, finding mutations in 3/28 (11 %) BL (still not a lot of cases….) and in 6/16 (38 %) BL cell lines. In silico evaluation of the mutations indicates that these alter the function of the gene, which includes nuclear trafficking and pre-mRNA splicing. How this affects BL pathogenesis remains elusive. A subset of the collaborative group Doose et al. ([Burkitt lymphoma (BL) remains an intriguing lymphoma, for which we know already a lot of the molecular background and it is already well curable in children but not in adults. The genetic hallmark of BL is the translocation t, or one of its light chain variants, resulting in IG-MYC juxtaposition, but other genetic alterations and Epstein-Barr virus (EBV) play a role as well. Piccaluga et al.  compared in 3/28  % BL (stFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. Then, they developed IL-21 receptor (IL21R)-deficient SJL mice, which appeared to have reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and did not develop B cell tumors. Surprisingly, they also noted features similar to human angioimmunoblastic T cell lymphoma (AITL), which is a malignancy of TFH cells. Subsequently, they performed gene expression analyses of human AITL samples and showed that all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. So, unexpectedly, they have developed a mouse model with features of AITL based on which they suggest that patients with this disease might benefit from therapeutic interventions that interrupt IL-21 signaling.Hypothesis-driven research sometimes leads to unexpected findings. Jain et al.  set off Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) is unusual among the lymphoma types, since it has a clear driver mechanism that it shares with other malignancies, especially ALK-positive lung cancer. Therefore, targeted treatments are studied across cell of origin concepts, but there appear to be still cell type-dependent resistance mechanisms. Crizotinib is the best known ALK tyrosine kinase inhibitor and is used to treat ALK-associated cancers. Mitou et al.  showed tn = 21,372) and reviewed pathology reports from a regional subset of 2007 through 2011. cHL rates were stable until 2007 and then decreased. Nodular sclerosis rates declined after 2007 by 6 % annually, with variation by gender, age, and race/ethnicity. In 1992 through 2011, mixed cellularity rates declined, whereas not otherwise specified (NOS) rates rose. Eighty-eight of 165 reviewed NOS pathology reports addressed classification choice. Twenty (12 %) justified the classification, 21 (13 %) described insufficient biopsy material, and specific subtype information was missing for 27 (16 %). They conclude that recent nodular sclerosis rate declines largely represent true incidence changes but that rate decreases for mixed cellularity and other less common subtypes, and increases for NOS (comprising ∼30 % of cHL cases in 2011!!), likely reflect changes in diagnostic and/or classification practice.Cancer incidence changes, due to different reasons, one of them being changes in diagnostic criteria. To understand whether Hodgkin lymphoma (HL) really is changing in appearance or that diagnostic criteria give that impression, Glaser et al.  analyzedOne of the most serious consequences of organ transplantation is the occurrence of post-transplant lymphoproliferative disease (PTLD), especially problematic in heart and lung transplantation. Kuramarasinge et al.  describeLymphomas are classified based on morphology, phenotype, genotype, and clinical features, and mediastinal (m)DLBCL is one of the entities in which localisation is key for its recognition  or the leg-type DLBCL that can present anywhere in the skin). It therefore does make sense to investigate whether mDLBCL can present at other sites, where it should then be diagnosed as mDLBCL type. Yuan et al.  used theLu et al.  as well Pathologists like to see what happens in a tumor rather that relying on something that comes out of a sequencing machine or is seen in a dark room with fluorescence and actually that makes some sense: the results of genetic changes are what counts for a cell. Agarwal et al.  studied As discussed above, extranodal NK/T cell lymphoma, nasal type, may present outside of the nasal region. Fang et al.  describeRecognizing the leg-type DLBCL of the skin requires a set of antibodies but remains sometimes problematic. Robson et al.  investigTumors like to confuse pathologists, especially those who rely very heavily on immunohistochemistry to classify lymphomas. Experienced pathologists of course know that lymphomas do not read our books and cancer cells do have aberrations, including aberrant phenotypes. It is therefore of no surprise that CD10-positive MCL exists and Akhter et al.  wonderedAnother example of an aberrant feature in MCL is plasma cell differentiation. Ribera-Cortada et al.  investigMagro et al.  did a laDeng et al.  go for aThe diagnosis of BL can be challenging in adults, especially in case there is expression of BCL2. A few authors from the group that studied BL for gene and MYC expression in a relatively small series of cases (see above) present the expression of BCL2 in 150 cases of conventionally diagnosed BL using two different BCL2 antibodies . BCL2 exFH differentiation  and enrichment of an interleukin 12-induced gene signature. Tissue samples with IDH2 mutations displayed a prominent increase in H3K27me3 and DNA hypermethylation of gene promoters. However, data regarding clinical features were not presented, so it is not clear whether this is just a phenomenon of variation within an entity or a real subgroup.Classification of T cell lymphomas is difficult, but the AILD-type has relatively well defined criteria. Wang et al.  complicaWith the increasing availability of whole genome sequencing increasingly also rarer tumor types are completely sequenced. Ungewickell et al.  report rDiagnosing lymphomas after treatment can be quite difficult, but sometimes the clinical situation is such that a biopsy can only be taken after some treatment. This may especially be the case in primary central nervous system lymphomas (PCNSL). Onder et al.  analyzedIn my previous review of the literature , I was pCencini et al.  investigSuppressor of cytokine signaling 1 (SOCS1) mutations are among the most frequent somatic mutations in HL, yet their prognostic relevance is unexplored; for Lennerz et al.  sufficiePastore et al.  performeThe work of Novak et al.  brings nAlso, exome sequencing is a powerful tool, and Jiang et al.  hereby iOkamata et al.  investign = 73). Cases with high FOXP1 and low HIP1R expression frequency exhibited poorer survival. They conclude that HIP1R expression is strongly indicative of survival when utilized on its own or in combination with FOXP1, and the molecule is potentially applicable for subtyping of DLBCL cases. This latter conclusion goes a bit far, since the expression of these markers is not a better classifier that the previously published classifiers.Huntingtin-interacting protein 1-related (HIP1R) is an endocytic protein involved in receptor trafficking, including regulating cell surface expression of receptor tyrosine kinases. Wong et al.  had showWang et al.  evaluateSeveral techniques can detect very low levels of tumor cells . Drandi et al.  used DroHurabielle et al.  investigDeep learning, an approach combing Big Data and novel bioinformatics tools (3 buzz words in only 10 words!), is increasingly popular: it uses large amounts of data to create new knowledge without the bias of a hypothesis (at least that is the theory). Deeb (nomen est omen) et al.  present Insuasti-Beltran et al.  developeRyan et al.  used a nhttp://www.bioinformatics.leeds.ac.uk/labpages/softwares/ or on github https://github.com/Sharlene/BDC.Sha et al.  use a biAll and this selection from the vast literature hopefully provides you with some new insights and some helpful new tools but probably also with the realization that the world of lymphomas is not loosing its complexity.


The rapid accumulation of whole-genome data has renewed interest in the study of using gene-order data for phylogenetic analyses and ancestral reconstruction. Current software and web servers typically do not support duplication and loss events along with rearrangements.MLGO  is a web tool for the reconstruction of phylogeny and/or ancestral genomes from gene-order data. MLGO is based on likelihood computation and shows advantages over existing methods in terms of accuracy, scalability and flexibility.To the best of our knowledge, it is the first web tool for analysis of large-scale genomic changes including not only rearrangements but also gene insertions, deletions and duplications. The web tool is available from http://www.geneorder.org/server.php. Comparative genomics, evolutionary biology, and cancer research all require tools to elucidate the history and consequences of the large-scale genomic changes, such as rearrangements, duplications, losses. However, using gene-order data has proved far more challenging than using sequence data and numerous problems plague existing methods: oversimplified models, poor accuracy, poor scaling, lack of robustness, lack of statistical assessment, etc.As whole genomes are sequenced at increasing rates, using gene-order datainversion operation  reverses both the order and orientation of a segment of a chromosome. A transposition is an operation that swaps two adjacent segments of a chromosome. In case of multiple chromosomes, a translocation breaks a chromosome and reattaches a part to another chromosome, while a fusion joins two chromosomes and a fission splits one chromosome into two. Yancopoulos et al. [double-cut-and-join (DCJ) operation that accounts for all rearrangements used to date. None of these operations alter the gene content of genomes, whereas deletions (or losses) delete segments of (one or more) contiguous genes from a chromosome, while insertions introduce a segment of (one or more) contiguous genes from external sources into a chromosome. and duplications copies an existing segment within the genome and inserts into a chromosome. Finally, whole genome duplication (WGD) creates an additional copy of the entire genome of a species.Genome rearrangement operations change the ordering of genes on chromosomes. An s et al.  proposedet al. [et al. [et al. [et al. [et al. [As phylogenies play a central role in biological research, over the past decade many methods were developed to reconstruct phylogenies from gene-order data. The first algorithm for phylogeny inference from gene-order data was BPAnalysis based on breakpoint distances . Moret eet al.  later exet al.  develope [et al.  have dem [et al.  and Fast [et al.  with an  [et al. . Instead [et al.  first pr [et al.  develope [et al.  with MLWIf the tree is fixed, then computing its parsimony score is known as the Small Parsimony Problem (SPP). Ancestral reconstruction has been studied through several optimization schemes for SPP on gene-order data—using adjacencies –15, usinet al. [Relatively few of these tools are offered through web servers. Lin et al.  had deveWe present a new tool MLGO for the reconstruction of phylogeny and/or ancestral genomes from gene-order data. MLGO relies on two methods we have developed: MLWD  for phylMLGO preprocesses the gene-order data, configures the transition model, reconstructs a phylogeny, and finally solves the SPP on that phylogeny.n genes labeled as {1,2,⋯,n}, gene-order data for a genome consists of lists of genes in the order in which they are placed along one or more chromosomes. Each gene is assigned with an orientation that is either positive, written i, or negative, written −i. Two genes i and j form an adjacency  if i is immediately followed by j, or, equivalently, −j is immediately followed by −i. If gene k lies at one end of a linear chromosome, we let k be adjacent to an extremity o to mark the beginning or ending of the chromosome, written as  or , and called telomere.Given a set of et al. [n genes and O(1) chromosomes has n+O(1) adjacencies and telomeres, the transition probability from 1 to 0 is n times less likely than that from 1 to 0. Despite the restrictive assumption that all DCJ operations are equally likely, this result is in line with the observed bias in transitions of adjacencies given by Sankoff and Blanchette [The data preprocessing and the configuration of the transition model follow the approach of MLWD . Each adet al.  gave theanchette : the proanchette  for its n distinct genes presents a single character (the ordering) with 2n×n! possible states (the first term is for the strandedness of each gene and the second for the possible permutations in the ordering). This single character is equivalent to an alignment with a single column, albeit one where each character can take any of a huge number of states—we cannot meaningfully resample a single character. The binary encoding effectively maps this single character into a high-dimensional binary vector, so that the standard phylogenetic bootstrap [A distinct advantage of using sequence encoding is the ability to use the bootstrap method to assess the robustness of the inferred phylogeny. Doing so with gene-order data is not possible, because a chromosome with ootstrap  can be uootstrap .et al. [et al. [Using the phylogeny thus computed, we then proceed to solve the SPP, now following the approach of Hu et al. . The fir [et al. . If such [et al. .MLGO is written in C++ and Perl as a web tool. Figure et al. [D. simulans, D. sechellia and the rest. The total running time for reconstructing the phylogeny of 12 drosophila species is less than 1 minute, while ancestral reconstruction adds less than 30 minutes. We also tested the performance of MLGO on 15 Metazoan genomes from the eGOB (Eukaryotic Gene Order Browser) database [We used the genomes of 12 fully sequenced drosophila species to demonstrate the performance of MLGO. Figure et al. , all majdatabase , and thedatabase .Figure 2As whole genomes are sequenced at increasing rates, using gene-order data for phylogenetic analyses and ancestral reconstruction is attracting increasing interest, especially coupled with the recent advances in identifying conserved synteny blocks among multiple species –34.MLGO  is the first web tool for likelihood-based inference of both the phylogeny and ancestral genomes. It provides fast and scalable analyses with bootstrap support of large-scale genomic changes including not only rearrangements but also gene insertions, deletions and duplications.Project name: MLGOProject home page:http://www.geneorder.org/server.phpOperating system(s): Platform independentProgramming language: PerlOther requirements: NoneLicense: GNURestrictions for use by non-academics: NoneThe web tool is available from http://www.geneorder.org/server.php.a We use the term “gene” as this is in fact a common form of syntenic blocks, but other kinds of markers could be used.


The development of diabetes mellitus is the interplay between insulin secretion and insulin resistance, while insufficient compensatory beta cell function plays a major role during the natural progression of the disease. In the past decades, a lot of work had been carried out to investigate the initiation and regulation of beta cell dysfunction, yet the underlying mechanism is largely unknown. In this issue, 11 interesting papers are compiled to discuss from experimental and clinical aspects the mechanism of beta cell dysfunction in the development of diabetes. in vitro and investigated its effect on beta cell apoptosis. In another paper, the attenuating effect of metformin against high glucose-induced suppression of cell proliferation and osteogenic-related gene expression in osteoblast was investigated by X. Shao et al.MicroRNAs (miRNAs) are small noncoding 18–25 nucleotides that bind to the complementary 3′UTR regions of target mRNAs and function in transcriptional and posttranscriptional regulation of gene expression. In recent years, miRNAs were reported to regulate several metabolic pathways including insulin secretion, cholesterol biosynthesis, carbohydrate, and lipid metabolism. In this issue, 3 papers touched upon the regulatory effect of some miRNAs on beta cell function from different points of view. Dr. X. Chang et al. reported that the mean level of miR-375 methylation was significantly lower in T2DM patients from Kazak population than Han population, which might partly explain from genetic background that even though Kazak population clusters more risk factors for T2DM, prevalence rate of T2DM is 6 times less than that of the Han population in the same region. Q. Zhang et al. showed that 8-week treatment of Tianmai Xiaoke Tablet, a chromium picolinate hypoglycemic agent, in diabetic rat significantly upregulated the expression of multiple miRNAs such as miR-375 and miR-30d, which might be part of its effect on improving glucose control. X. Lin et al. investigated the direct suppression of Bcl-2 by miR-34a, which might account for palmitate-induced apoptosis in MIN6 cell, the latter of which is believed to be the most important mechanism of beta cell dysfunction. Another 2 manuscripts also discussed beta cell apoptosis. Dr. L. Zhou et al. examined the 3 signaling pathways of MAPKs in INS-1 cells treated with glucolipotoxicity conditions and concluded that P38 might be involved in the regulation of beta cell apoptosis through phosphorylation of IRS-2. Z. Zhang et al. simulated intermittent high glucose situationThree papers in this issue presented with unique clinical picture of diabetes in the Chinese population. W. Tang et al. investigate the relationship between serum uric acid and residual beta cell function in 1021 T2DM patients. They concluded that patients with higher serum uric acid had greater insulin secretion at the early stage, but their residual beta cell function decayed more rapidly. Y. Ma et al. compared newly diagnosed T2DM patients with or without hyperlipidemia and found that the former were younger and had worse beta cell function. H. Lu et al. reported that ketosis onset type 2 diabetic patients had better beta cell function and were more insulin resistant. in vitro.Two manuscripts brought new exploration in the treatment of type 1 diabetes. Dr. W. Li et al. revealed that, apart from higher density of insulin-producing beta cells, small islets transplantation expressed less angiotensin and more angiotrophic VEGF-A, which might be beneficial for the facilitation of microcirculation and revascularization in small islets. H. Luo et al. presented with a novel protocol that reprogrammed primary hepatocytes into functional insulin-producing cells using multicistronic vectors carrying Pdx1, Ngn3, and MafA. These cells activated multiple beta cell gene expression, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated mannerWe hope to bring about extensive concern and energetic discussion about beta cell function from experimental as well as clinical aspects. We wish that our readers enjoy this special issue.Yanbing LiYanbing LiLi ChenLi ChenChen WangChen WangDongqi TangDongqi Tang


Transcutaneous electric nerve stimulation (TENS) is a non-pharmacological method which is widely used by medical and paramedical professionals for the management of acute and chronic pain in a variety of conditions. Similarly, it can be utilized for the management of pain during various dental procedures as well as pain due to various conditions affecting maxillofacial region. This review aims to provide an insight into clinical research evidence available for the analgesic and non analgesic uses of TENS in pediatric as well as adult patients related to the field of dentistry. Also, an attempt is made to briefly discuss history of therapeutic electricity, mechanism of action of TENS, components of TENs equipment, types, techniques of administration, advantages and contradictions of TENS. With this we hope to raise awareness among dental fraternity regarding its dental applications thereby increasing its use in dentistry. Key words:Dentistry, pain, TENS. Pain has been a constant tormentor of mankind since time immemorial. Techniques used to control pain are broadly divided into pharmacological and non pharmacological methods. Most common pharmacological means to curb pain in dentistry is the use of local anesthesia during dental procedures and analgesics for the postoperative pain. Use of local anesthesia instills fear in a many patients as it requires the use of the ‘horrifying’ syringe. A non-pharmacological method for pain control is the use of transcutaneous electrical nerve stimulation [TENS] . FDA , a type of electric fish for pain relief. In modern era, John Wesley in 18th century introduced electrotherapy for the relief of pain from sciatica, headache, kidney stone, gout, and angina pectoris. Use of electricity for relief of dental pain was first described in 19th century by a physician named Francis. In 20th century, various dental handpieces that provided an electrical current to the tooth via the bur were used to relieve pain during cavity preparation. After a lot of research, TENS or electronic dental anesthesia as it is called in dentistry has established itself as an anesthetic agent .Analgesic effect of TENS is based on two main theories- Gate control theory of pain and endogenous opiod theory.Gate control theory of pain proposed by Melzack and Wall  in 1965,In 1969, Reynolds  showed tClinically, TENS is applied at varying frequencies, intensities, and pulse durations of stimulation. Depending upon frequency of stimulation, TENS is broadly classified into 2 categories: [1] High frequency TENS [>50Hz]. [2] Low frequency TENS [<10 Hz] -11. High- Tens EquipmentMain parts of TENS system are: [1] TENS unit. [2] Lead wires. [3] Electrodes- TENS unitIt is an electric pulse generator. It has two variations: 1] “Clinical” model- This is used by dentist in the clinic and is connected to the buildings electrical outlet to generate power . [2] “Pa “Clinica- Lead WireThese connect electrodes to TENS unit to establish electrical connection Fig. .- ElectrodesBy means of electrodes, electric flow from TENS unit is converted into an ionic current flow in the living tissue. Electrodes can be placed extraorally or intraorally. Extraoral electrodes are of two types: [1] Carbon- impregnated silicone rubber electrodes- They are flexible and coupled to the skin surface through the use of electrically conductive gel. They are retained in place with surgical tape. [2] Tin plate or aluminum electrodes- These don’t conform to the body and are coupled to the skin surface with tap water retained within cotton pad or sponge.The intraoral electrodes are cotton roll electrodes, clamp electrodes and adhesive electrodes. Adhesive electrodes are the most widely used type nowadays. These electrodes are thin and flexible so can adapt easily to the oral mucosa  Fig. 1)1).Three main types of TENS are described in the literature – 1. Conventional TENS 2.Acupuncture-like TENS [AL-TENS] and 3. Intense TENS. Different TENS techniques are used to selectively activate different afferent nerve fibers .1. Conventional TENS`It is the most commonly used method for delivering currents in clinical practice. It uses high frequency [between 10-200 pulses per second [pps]], low intensity [amplitude] pulsed currents to activate the large diameter Aβ fibers without concurrently activating small diameter Aβ and C [pain-related] fibres or muscle efferents . It prod2. Acupuncture-like TENS [AL-TENS]It uses low frequency , high intensity pulsed currents to activate the smaller diameter Aδ fibers arising from muscles [ergoreceptors] by the induction of phasic muscle twitches. It produces extrasegmental analgesia which has a delayed onset [> 30 min after switch-on] and offset [>1 h after switch-off]. AL-TENS can be used for about 30 minutes at a time as fatigue may develop with ongoing muscle contractions.3. Intense TENSIt uses high frequency [upto 200 pps], high intensity pulsed currents which are just bearable to the patient. It activates small diameter Aδ cutaneous afferents and produces extrasegmental analgesia which has a rapid onset [< 30 min after switch-on] and delayed offset [>1 h after switch-off]. Intense TENS can be used for about 15 minutes at a time as the stimulation may be uncomfortable.1. It is non-invasive, safe  and can 2. As compared to local anesthesia there is no postoperative anesthesia after the TENS unit is turned off .3. Patients are able to self-administer TENS treatment and learn to titrate dosages accordingly to manage their painful condition. This results in positive acceptance by the patients .1. Apprehensive patients- usage of TENS requires patient co-operation, hence the procedure shouldn’t be at-tempted in patients with a communication handicap or a mental disability.2. Patients with cardiac pacemakers-,13. If t3. Patients with cerebrovascular problems- patients with a history of aneurysm, stroke and transient ischaemia shouldn’t be treated using TENS, as it stimulates peripheral blood flow which can be fatal in such cases .4. Epileptic patients- TENS “pulses” have the potential to trigger a seizure .5. Pregnant patients- As such there are no specific side effects. However, since there has been no FDA approval, the usage is frowned upon .6. Acute pain cases/pain of unknown etiology- usage of TENS in undiagnosed cases may hinder in the diagnosis (Apart from its analgesic effect, TENS can also be used to produce non-analgesic physiological effects and has been found to be beneficial in the management of xerostomia. Various applications of TENS in dentistry are summarized below1. Dental treatment in pediatric patientsA commonly observed negative behavior in pediatric patients is fear towards syringes. Use of TENS has positive effects on the behavior of pediatric patient which in turn decreases the anxiety levels as it removes the “fear of needle”. Studies have shown that 53 -78% children prefer TENS over local anesthesia -16. In pet al. (Abdulhameed et al.  in 1989 et al. (et al. (teDuits et al.  in 1993  (et al.  in 1997 Harvey and Elliott  in 1995 Baghdadi  in 1999 et al. (Munshi et al.  in 2000 et al. (P>0.05]. They concluded that TENS can be a useful adjunct in pediatric patients during various minor dental procedures.Dhindsa et al.  in 2011 2. Dental treatment in adult patientsIn adults TENS has been used successfully as an excellent analgesia during various procedures like rubber dam placement, cavity preparation, pulp capping and other endodontic procedures, prosthetic tooth preparations, oral prophylaxis as well as extractions. It is also used to reduce the discomfort from injection of local anesthesia and to alleviate periodontal pain associated with orthodontic separation.Roth and Thrash  in 1986 et al. (Malamed et al.  in 1989 William Stenberg  in 1994 Yap and Ho  in 1996 Quanstrom and Libed  in 1994 et al. (Meechan et al.  in 1998 According to Hochman , TENS isTENS has also been used in combination with nitrous oxide-oxygen or diazepam to achieve analgesia during dental treatment. Quanstrom and Milgrom  in 1989 3. In chronic pain of maxillofacial regionTENS has been used successfully to alleviate chronic pain of TMJ syndrome, trigeminal neuralgia, and post herpetic neuralgia.- In TMJ syndromeKatch  reported- In trigeminal neuralgiaet al. (Singla et al.  conducteet al. (Yameen et al.  used TENThorsen and Lumsden  reported- In post-herpetic neuralgiaIn post-herpetic neuralgia most of the larger myelinated afferent nerve fibers are destroyed and therefore, normal presynaptic inhibition of inputs of C fibers does not occur . This isNathan and Wall  in 1974 et al. (Mittal et al.  in1998 u4. In acute orofacial painHansson and Ekblom  studied 5. In patients with xerostomiaet al. (Application of TENS increases the salivary flow rate in healthy individuals as well as in xerostomic patients. Hargitai et al.  in 2005 et al. (Pattipati et al.  in 2013 et al. (Weiss et al.  in 1986 et al. (Steller et al.  in 1988 et al. (Talal et al.  in 1992 et al. (Wong et al.  in 2003 et al. (Wong et al.  in 2012 In conclusion, though TENS can’t replace local anesthesia, it can be used for pain relief during various dental procedures. Its analgesic and non analgesic physiologic effect can be used in the management of a variety of conditions affecting maxillofacial region.


Salinity is a stressful environmental factor that limits the productivity of crop plants, and roots form the major interface between plants and various abiotic stresses. Rice is a salt-sensitive crop and its polyploid shows advantages in terms of stress resistance. The objective of this study was to investigate the effects of genome duplication on rice root resistance to salt stress.+ content, H+ (proton) flux at root tips, and the microstructure and ultrastructure in rice roots were examined. We found that tetraploid rice showed less root growth inhibition, accumulated higher proline content and lower MDA content, and exhibited a higher frequency of normal epidermal cells than diploid rice. In addition, a protective gap appeared between the cortex and pericycle cells in tetraploid rice. Next, ultrastructural analysis showed that genome duplication improved membrane, organelle, and nuclei stability. Furthermore, Na+ in tetraploid rice roots significantly decreased while root tip H+ efflux in tetraploid rice significantly increased.Both diploid rice (HN2026-2x and Nipponbare-2x) and their corresponding tetraploid rice (HN2026-4x and Nipponbare-4x) were cultured in half-strength Murashige and Skoog medium with 150 mM NaCl for 3 and 5 days. Accumulations of proline, soluble sugar, malondialdehyde (MDA), Na+ entrance into the roots.Our results suggest that genome duplication improves root resistance to salt stress, and that enhanced proton transport to the root surface may play a role in reducing Na Plants Flowers ; Glenn a Flowers ; Blumwal Flowers ; Munns a Flowers ; Horie e Flowers ). During Flowers ; Shinoza Flowers ; Kronzuc Flowers ; Horie e Flowers ; Hauser  Flowers ). Among h et al. ; Brini ah et al. ), and pla et al. ; Anil eta et al. ) and exta et al. ). Plantsnd Munns ; Kavi Kind Munns ; Yamada nd Munns ; Chyzhyknd Munns ; Jayaseknd Munns ); Xu andnd Munns ; ). Ion am et al. ; Gorham m et al. ); Glenn m et al. ; ). Osmotm et al. ).+ enters the shoots of plants remain unclear . Plantsd Britto ), but apd Britto ; Ochiai d Britto ). The apd Britto ; Anil etd Britto ; Gong etd Britto ). The mae et al. ), bypasse et al. ; Gong ete et al. ). In rice et al. ; Ranathue et al. ). Caspare et al. ; Krishnae et al. ; Zhou ete et al. ). Charace et al. ; Steudlee et al. ; Steudlee et al. ; Barrowce et al. ; Miyamote et al. ; Lee et e et al. ); Zimmere et al. ). Furthee et al. ).Triticum macha and the endemic tetraploid wheat Triticum timopheevii were among the most tolerant to salt stress . In tetnd James ). Other nd James ). In othnd James ; Mouhayand James ). In hexl et al. ). Rice il et al. ; Lutts el et al. ; Hasanuzl et al. ). Few stl et al. ; Cai et l et al. ; He et al et al. ; He et al et al. ). Some rl et al. ). PolyplThe length, fresh weight, dry weight, and number of roots of polyploid rice cultivars were investigated to characterize the effects of genome duplication under salt stress. Our results demonstrated that salt stress significantly restricted rice root growth, irrespective of being diploid or tetraploid rice, and genome duplication improved root resistance in tetraploid rice by contributing to faster and better root growth in the presence of 150 mM NaCl  and reached 120.99 μg g–1 in Nipponbare-4x. However, the increase in free proline in Nipponbare-4x compared with Nipponbare-2x was 23.30%. In addition, the increase in HN2026-4x was 19.55%.Free proline in roots of diploid and tetraploid rice subjected to 150 mM NaCl for 5 days was measured Figure . The amoGenome duplication led to a similar increase in different rice cultivars in terms of soluble sugar accumulation under salt stress, and the difference was significant between tetraploid and diploid rice subjected to salt stress. However, no significant changes were found between the two different cultivars for tetraploid or diploid rice Figure . The amo–1) and HN2026-4x (60.10 μmol g–1) accumulated less MDA in their roots compared to the corresponding diploid cultivars under normal condition. Under salt stress, the amount of MDA in HN2026-4x conditioned with salt was lowest among all cultivars  accumulated to similar levels in all rice cultivars tested, and no significant difference was detected between diploid and tetraploid rice cultivars without salt stress. However, the amount of MDA in the roots of various rice cultivars under salt stress was significantly greater than in the control Figure . In contTo increase our understanding of the root response in polyploid rice, the anatomical structure of roots in Nipponbare-2x and -4x cultivars were observed on plants under salt stress for 3 and 5 days because Nipponbare-4x was thought to be more resistant to salt. Histological analysis indicated that genome duplication regulated the root response to salt stress. The root microstructure in diploid and tetraploid rice was similar without salt stress, and no evident morphological differences in the epidermis, cortex, vascular system, or aerenchyma were observed to facilitate oxygen transport. However, the diameter of the longest root in tetraploid rice was larger than that in the corresponding diploid  Figure A. The rep Figure B. We obs+ in the soil . Salinid Tester ; Hasanuzd Tester ; Brini ad Tester ). As we d Tester ; Al-Khayd Tester ; Yamada d Tester ; Jayasekd Tester ; Munns ad Tester ; Krishnad Tester ; Szabadod Tester ).The ricd Tester ). Osmotid Tester ; Munns [d Tester ; Ranathud Tester ; Ranathud Tester ; Munns ad Tester ). On thed Tester ); Radic d Tester ; ). Our r+ accumulate in plants, particularly when transport from root to leaves is over the threshold  damage ; Glenn  Flowers ; Zhu [20 Flowers ). Roots s et al. ); Läuchls et al. ; ). Baseds et al. ). In moss (Munns ). Howeveo et al. ; Yadav eo et al. ; Garcia o et al. ; Gong eto et al. ), which l et al. ). Casparl et al. ; Schreibl et al. ; Schreibl et al. ). In thind Heydt ; Barrowcnd Heydt ; Miyamotnd Heydt ; Lee et nd Heydt ). Howeved Wendel ). We nexd Wendel ; Blanc ad Wendel ; Saleh ed Wendel ). Adaptai et al. ; Gersteii et al. ; Saleh ei et al. ); Dhar ei et al. ). Polypli et al. ). Howeve+-ATPase is inhibited and may contribute to a weaker acidification of the apoplast, and thus to growth inhibition ). Na+ sg et al. ; Brini ag et al. ). The ceb et al. ). At a 2d Boutry ; Palmgred Boutry ; Gaxiolad Boutry ; Cosgrovd Boutry ; Gaxiolad Boutry ). The hi+ “exclusion” are now known to reside on different chromosomes in various genomes of species in the Triticeae, further studies are required to identify the underlying mechanisms controlling genes for the various traits that could act additively or even synergistically, which may enable substantial gains in salt tolerance . The reh et al. ; Yildiz h et al. ; Mouhayah et al. ). Severah et al. ; Chinnush et al. ; Sahi eth et al. ). Polypl+ absorption, and Na+ content in Nipponbare-2x greatly increased compared to that in Nipponbare-4x under salt stress. The high H+ efflux in tetraploid rice led to low pH conditions and may have contributed to increased root growth, the length of the root, and the fresh and dry weights of the root, which were restricted in the diploid compared to the tetraploid under salt stress. Overall, our results suggest that genome duplication improved root resistance to salt stress and enhanced proton transport to the root surface, which may play a role in reducing Na+ entry into the roots.Rice is a very important and salt-sensitive crop. Previous reports have suggested that polyploid rice has some superiority in stress resistance. However, few studies have focused on the effect of genome duplication on rice root response under salt stress. The objective of this study was to investigate how genome duplication regulates the rice root response to salt stress. Our results demonstrated that salt stress significantly restricted rice root growth in both diploid and tetraploid rice, and that genome duplication improved the root growth in tetraploid rice, with faster and better root growth in the presence of 150 mM NaCl. Free proline accumulated in tetraploid rice cultivars under salt stress varied greatly, which increased compared to that in the diploid cultivars. Genome duplication significantly decreased the MDA content in tetraploid rice compared to diploid cultivars subjected to salt stress, which suggests that the membrane integrity improved in the tetraploid compared to the diploid. Investigation of the anatomical structure of roots under salt stress showed a high frequency of epidermis cells maintaining their normal structure, and a gap appeared between the cortex and pericycle cells in tetraploid rice roots. These protective mechanisms improved the root adaptability to salt stress. Ultrastructural analysis showed that genome duplication also improved the root response, including the epidermis cell protective mechanism formation, and membrane organelle and nuclei stability. Anatomical structure and ultrastructure of roots in Nipponbare-4x may play critical roles in counteracting Na–2 s-–1 using fluorescent lighting with a day and night cycle of 12 h each. Seedlings were then cultured in ½ MS medium . Seeds nd Skoog ) with 15We choosed the longest root ) of eveThe proline content in roots in the presence of 150 mM NaCl for 5 days was investigated. The free proline content was extracted and quantified using the acid ninhydrin method as described by Bates et al. . The co–1) = 6.45 (A532–A600) – 0.56 A450. All samples were tested in three independent experiments with three replicates each.The content of MDA in roots subjected to 150 mM NaCl for 5 days was calculated. The method was in accordance with the results of Hodges et al. . BrieflThe soluble reducing sugar content in roots exposed to salt treatment for 5 days was measured as described previously . Briefl4 (Sigma) in PBS (pH 7.2). The tissues were washed in PBS, dehydrated in a graded ethanol series, and embedded in EPON812 . Half-thin sections (100 nm) were examined at every stage, and observations and photographic recordings were performed with a BX51 microscope . Ultrathin sections (50–70 nm) were double-stained with 2% (w/v) uranyl acetate (Sigma) and 2.6% (w/v) lead citrate (Sigma) aqueous solution and examined with a transmission electron microscope  at 100 kV.Rice roots exposed to salt treatment for 3 and 5 days were dissected and vacuum-infiltrated with 3% (w/v) paraformaldehyde  and 0.25% glutaraldehyde (Sigma) in phosphate-buffered saline (PBS) for 30 min (pH 7.2). The fixed roots were renewed with fresh solution and post-fixed in 1% OsO3 and the concentration of Na+ was determined using ICP-AES . All samples were tested in three independent experiments with three replicates each.After seedlings were cultured in ½ MS medium (Murashige and Skoog ) with 15+ fluxes were measured noninvasively using SIET . Rice plants were equilibrated in measuring solution for 20–30 min, and these equilibrated rice plants were transferred to the measuring chamber, which was a small plastic dish (3 cm diameter) containing 2–3 ml of fresh measuring solution. When the root became immobilized at the bottom of the dish, the microelectrode was vibrated in the measuring solution between two positions (5 μm and 35 μm from the root surface) along an axis perpendicular to the root. The background was recorded based by vibrating the electrode in measuring solution not containing roots. The microelectrode was made and silanized by Xuyue Science and Technology Co., Ltd. . All samples were tested in three independent experiments with three replicates each.HAll values are shown as the mean of five replicates, and the average was calculated. The results were analyzed for variance using the SAS/STAT statistical analysis package  to determine significant differences. Means followed by common letters are not significantly different at P = 0.05 using a protected least-significant difference.The authors declare that they have no competing interests.Yi Tu and Aiming Jiang contribute equally to this paper, they cooperted to finish all experiments. Lu Gan, Md. Mokter Hossain and Jinming Zhang made contribution of making figure and table. Bo Peng, Yuguo Xiong and Zhaojian Song were responsible for materails planting , nursing and data analysis. Detian Cai and Jianhua Zhang gave this research important guidance and revised the manuscript. Yuchi He and Weifeng Xu cooperated to design the the whole research and write the manuscript, they are sharing the corresponding person for giving final approval of the version to be submitted. All authors read and approved the final manuscript.


Day surgery, coming to and leaving the hospital on the same day as surgery as well as ambulatory surgery, leaving hospital within twenty-three hours is increasingly being adopted. There are several potential benefits associated with the avoidance of in-hospital care. Early discharge demands a rapid recovery and low incidence and intensity of surgery and anaesthesia related side-effects; such as pain, nausea and fatigue. Patients must be fit enough and symptom intensity so low that self-care is feasible in order to secure quality of care. Preventive multi-modal analgesia has become the gold standard. Administering paracetamol, NSIADs prior to start of surgery and decreasing the noxious influx by the use of local anaesthetics by peripheral block or infiltration in surgical field prior to incision and at wound closure in combination with intra-operative fast acting opioid analgesics, e.g., remifentanil, have become standard of care. Single preoperative 0.1 mg/kg dose dexamethasone has a combined action, anti-emetic and provides enhanced analgesia. Additional α-2-agonists and/or gabapentin or pregabalin may be used in addition to facilitate the pain management if patients are at risk for more pronounced pain. Paracetamol, NSAIDs and rescue oral opioid is the basic concept for self-care during the first 3–5 days after common day/ambulatory surgical procedures. Day or ambulatory surgery; coming and leaving the hospital the same day or within 23-hours after surgery is becoming increasingly adopted. There are several potential benefits associated with the avoidance of in-hospital care. The risk for hospital acquired infections and the potential negative effects of increased immobilization and subsequent risk for thrombo-embolic and anenergetic sequalae are also lowered. Enhanced recovery and shortened hospital stay has also been shown to reduce the risk for cognitive side effects.Early discharge demands a rapid recovery and low incidence and intensity of surgery and anaesthesia related side-effects; such as pain, nausea and fatigue. Patients must be fit enough and symptom intensity so low that self-care is a feasible in order to secure quality of care. Multi-modal or balanced analgesia  has becoet al. } and 24 h [MD −0.48 ] after surgery. Dexamethasone-treated patients used less opioids at 2 h [MD −0.87 mg morphine equivalents (95% CI: −1.40 to −0.33)] and 24 h [MD −2.33 mg morphine equivalents ], required less rescue analgesia for intolerable pain [relative risk 0.80 ], had longer time to first dose of analgesic [MD 12.06 min ], and shorter stays in the post-anaesthesia care unit [MD −5.32 min (95% CI: −10.49 to −0.15)]. There was no dose-response with regard to the opioid-sparing effect. There was no increase in infection or delayed wound healing with dexamethasone, but blood glucose levels were higher at 24 h [MD 0.39 mmol L−1 ]. Higher dose, 0.2 mg may however increase the risk for postoperative cognitive dysfunction as suggested in a study by Fang et al. [Single intra venous 0.1 mg per kilogram preoperative dose of dexamethasone has been shown to have combined anti-emetic and enhance analgesia . De Olivet al.  conclude [et al.  conducteg et al. .et al. [et al. [−1 provided effective postoperative analgesia and reduced morphine requirement when administered intravenously or in wound infiltration with bupivacaine. However, the incidence of complications was less with wound infiltration. Patients receiving i.v. clonidine had more hypotension (p < 0.01) and sedation (p < 0.001) compared with other groups.Both clonidine and dexmedetomidine has been studied as adjutants to paediatric general anaesthesia in order to reduce and ameliorate emergence agitation. A meta-analysis by Dahmani et al.  from 201 [et al.  found inet al. [He et al.  found inet al. [p < 0.001). Systolic blood pressure was significantly lower in group D compared with group P from the beginning of the operation. HR, RR, and SpO(2) were comparable between the two groups. There were 8 cases (25.8%) of hypertension in group P, and 1 case (3.2%) in group D (p < 0.05). In contrast, 1 case (3.2%) of hypotension and 1 case (3.2%) of bradycardia occurred in group D. Whether the favourable effects seen from the use of dexmedetomidine as a complement to anaesthesia for cardiac surgery can be translated into day surgery for the elderly needs much further studies. Ji et al. [et al. [Dexmedetomidine has been studies not only as an adjunct to nerve block but as an alternative to propofol for sedation. Na et al.  studied i et al.  recently [et al.  found shet al. [There is a meta-analysis evaluating the addition of α-2-agonists on postopetive pain not explicitly following day surgery by Blaudszun et al. . This reTawfic  made a ret al. [et al. [et al. [p < 0.001) in Pregabalin versus control. Pregabalin was also associated to significantly less (p < 0.001) patients with postoperative nausea, vomiting, sedation and dizziness versus control. Overall patient satisfaction with pain management was significantly higher (p < 0.001) in the pregabalin group. Sarakatsianou et al. [et al. [Peng et al.  did not  [et al.  found 15 [et al.  studied u et al.  found li [et al.  showed iet al. [et al. [There is rather sparse data around the use, benefits from gabapentin as part of the pain management after ambulatory surgery. Kazak et al.  found be [et al.  found a et al. [Duari et al.  conducte4 50 mg/kg in 100 mL of normal saline over 15 min before anesthesia induction, followed by an infusion of 15 mg/kg/h) has been shown by De Oliveiera et al. [There are also other drugs, substances, that have been studied showing potential positive effects. Magnesium sulphate  in the control group (p < 0.001). Similarly, the severity of pain was six-fold less in the treatment group than in the control group. The incidence of nausea in the PACU was significantly less in the treatment group; 4.7% vs. 29.5% in the control group (p < 0.05). Patients from the treatment group satisfied Postanaesthesia Discharge Score significantly earlier than those in the control group . They concluded that concomitant use of local anaesthetic, NSAID and opioid drugs proved to be highly effective in our patients, resulting in faster recovery and discharge. One of the goals is to reduce opioid related side effects and subsequently facilitate adequate pain relief but with a minimum of side effects. Zhao et al. [The concept of multi-modal analgesia was shown effective for cholecystectomi already in 1996 by the Chung group in Toronto . Patiento et al.  from theo et al.  one of tThere is still no strong evidence for a pre-emptive effect from preoperative start of analgesia administration in clinical practice. Providing pain relief in order to secure adequate concentrations, effect after surgery, preventing pain to become severe is sound. Thus starting administration of paracetamol and an oral NSAID as premed has subsequently become well-accepted practice in many day surgical programs . The aimet al. [Aluri et al.  conducteet al. [p < 0.001. Postoperative rise in individual creatinine levels demonstrated a non-significant rise in the multimodal group, 33.0 ± 53.4 vs. 19.9 ± 48.5, p = 0.133. Patients in the multimodal group suffered less major in-hospital events in crude numbers: myocardial infarction (MI) , stroke , dialysis , and gastrointestinal (GI) bleeding . 30-day mortality was 1 vs. 2, p = 0.54. The authors conclude that in patients undergoing cardiac surgery, a multimodal regimen offered significantly better analgesia than a traditional opiate regimen. Nausea and vomiting complaints were significantly reduced. No safety issues were observed with the multimodal regimen.Multi modal analgesia has also been shown safe and effective for the management of pain following major surgery. Rafiq et al.  studied et al. [et al. [Although the classical papers by Eriksson et al.  and Michet al.  suggest  [et al.  around p [et al. .In conclusion, a multi-modal procedure specific analgesic strategy facilitates the postoperative course following day surgery; improves quality of care, reduce experience of PONV and shorten time to discharge. The exact impact of multi-modal—balanced analgesia on resumption of daily living and quality of life is not well-documented. Providing paracetamol in standard dose, adding an NSAID when feasible and not contra-indicated in lowest effective dose fort short period  and furt


Biology has become the land of the “-omics,” including genomics , transcrThe Peer-reviewed papers are collected in the special issue. They are approximately divided into three areas: bioinformatics, functional genomics, and functional genetics. The majority of the papers are purely bioinformatics related papers. We define bioinformatics papers as those using computational tools or developing methods to analyze functional “-omics” data without using wet labs. Two papers fell into the category of functional genomics, which is focused on using whole genome level wet-lab technology to find important molecules and investigate their potential functions. Five papers are considered as functional genetics papers. Functional genetics is a broad concept here and these papers are concentrated on studying the molecular functions and mechanisms of individual molecules using wet-lab experimental approaches.Bioinformatics. In the bioinformatics papers, four papers deal with transcriptomics data. F. Wang et al. developed a novel approach for coexpression analysis of E2F1-3 and MYC target genes in chronic myelogenous leukemia (CML); they found a significant difference in the coexpression patterns of those candidate target genes between the normal and the CML groups. It is challenging to analyze the quantity of image data on gene expression. A. Shlemov et al. developed a method called 2D singular spectrum analysis (2D-SSA) for application to 2D and 3D datasets of embryo images related to gene expression; it turned out to work pretty well. J. Li et al. characterized putative cis-regulatory elements (CREs) associated with male meiocyte-expressed genes using in silico tools. They found that the upstream regions (1 kb) of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs, which were potential binding sites of transcription factors. NAGNAG alternative splicing plays an important role in biological processes and represents a highly adaptable system for posttranslational regulation of gene function. Interestingly, X. Sun et al. identified about 31 NAGNAG alternative splicing sites that were identified in human large intergenic noncoding RNAs (lincRNAs). N. meningitidis and N. gonorrhoeae, which belong to Neisseria, a genus of gram-negative bacteria. D. Yu et al. selected 18 Neisseria genomes, preformed a comparative genome analysis, and identified 635 genes with recombination signals and 10 genes that showed significant evidence of positive selection. Further functional analyses revealed that no functional bias was found in the recombined genes. The data help us to understand the adaptive evolution in Neisseria.Three papers are focused on the deification of new gene family members and gene evolution. Conotoxins are small disulfide-rich neurotoxic peptides, which can bind to ion channels with very high specificity and regulate their activities. H. Ding et al. developed a novel method called iCTX-Type, which is a sequence-based predictor that can be used to identify the types of conotoxins in targeting ion channels. A user-friendly web tool is also available. Y.-Z. Zhou et al. analyzed the evolution pattern and function diversity of PPAR gene family members based on 63 homology sequences of PPAR genes from 31 species. They found that gene duplication events, selection pressures on HOLI domain, and the variants on promoter and 3′UTR are critical for PPARs evolution and acquiring diversity functions. There has recently been considerable focus on its two human pathogenic species Azospirillum amazonense could have been acquired from distantly related bacteria from horizontal transfer. They also demonstrated that the coding sequence related to production of phytohormones, such as flavin monooxygenase and aldehyde oxidase, is likely to represent the tryptophan-dependent TAM pathway for auxin production in this bacterium. They conclude that the genomic structure of the bacteria has evolved to meet the requirement for adaptation to the rhizosphere and interaction with host plants.One paper tried to solve the key algorithm issue called the all-pairs suffix-prefix matching problem, which is crucial for de novo genome assembly. M. H. Rachid et al. developed a space-economical solution to the problem using the generalized Sadakane compressed suffix tree. One paper conducted a comparative genomics analysis. R. Cecagno et al. found that the versatile gene repertoire in the genome of rhizosphere bacteriumα structure of porcine reproductive and respiratory syndrome virus PRRSV.One article conducted a meta-analysis. H. Ye et al. have demonstrated that rs2228671 is a protective factor of CHD in Europeans. One paper is concentrated on the microorganism bioinformatics. Y. Ding et al. recognized the roles of the synonymous codon usage in the formation of nsp1Functional Genomics. There are two papers that conducted gene association studies based on genome wide data. J. Li et al. found that the presence of ATTε4haplotype was associated with an increased risk of mental retardation (MR) in children but did not find any significant association between single loci of the four common ApoE polymorphisms  and MR or borderline MR. J. Zhou et al. did not find an association between rs7529229 and chronic heart disease (CHD) in Han Chinese. However, their meta-analyses indicated that rs7529229 was associated with the CHD risk in Europeans.Functional Genetics. There are 5 articles that investigate the individual gene function in different areas. Two papers are related to neural diseases. G.-M. Chang et al. found that activating NF-κB signaling pathway can protect intestinal epithelial cell No. 6 against fission neutron irradiation. X.-S. Liu et al. demonstrated that hepatocyte growth factor (HGF) could promote the regeneration of damaged Parkinson's disease (PD) cells at higher efficacy than the supernatant from hUC-MSCs alone. Thus, the combination of hUC-MSC with HGF could potentially be a new biological treatment for PD. One paper is focused on cancer. N. Ji et al. found that celastrol had antiprostate cancer effects partially through the downregulation of the expression level of hERG channel in DU145 cells, suggesting that celastrol may be a potential agent against prostate cancer with a mechanism of blocking the hERG channel. One paper is studying heart disease. Z. Lu et al. reported that the levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for heart failure (HF). Meanwhile, there was a significant negative correlation between the levels of NT-proBNP and CCR. One interesting paper is trying to understand the function of Japanese encephalitis virus (JEV), and they have demonstrated that RNA recombination in JEV occurs unequally in different cell types. They conclude that the adjustment of viral RNA to an appropriately lower level in mosquito cells prevents overgrowth of the virus and is beneficial for cells to survive the infection.In summary, this special issue presents a broad range of topics from functional genomics, genetics, and bioinformatics. It covers a variety of diseases such as cancer, heart, and neural and infectious diseases. The study organisms include human, mouse, plant, and microorganisms. We hope that the readers will find interesting knowledge and methods in the issue.Youping DengHongwei WangRyuji HamamotoDavid SchafferShiwei Duan


Dear Editor,et al.[ADIPOQ gene is more associated with the increasing risk of coronary artery disease (CAD) in subjects with type 2 diabetes. Adipocytes were described in myocardial tissue of CAD patients and their role recently discussed[Q gene of adiponectin has been reported for 3’-UTR, which harbours some genetic loci associated with metabolic risks and atherosclerosis[etal.[et al.[ADIPOQ SNPs in diagnosing susceptibility to CAD and the relationship with plasma adiponectin level. In normal, non diabetic, normoglycemic subject, this relationship does not seem to work. Therefore the question is how much predictive this SNP haplotype may be to foresee metabolic syndrome and CAD onset risk in young health subjects? Maybe, the role of adiponectin in cardiovascular physiology depends on its ability to target adiponectin receptors and to negatively regulate obesity. Some authors reported in healthy volunteers an absence of correlation between circulating adiponectin levels and biochemical markers, particularly lipoproteins and suggested that SNP +276G>T was related to an independent effect on adiponectin levels and on lipoprotein metabolism[The recent article by Mohammadzadeh et al. on the ldiscussed. Susceptsclerosis. Actuallsclerosis. This evsclerosis. Moreovesclerosis. CAD is sclerosis. In the is[etal., T allelis[etal. or a diris[etal.. The papl.[et al. assessesetabolism. On the etabolism.et al.[ADIPOQ +276G>T should be related to susceptibility to glucose metabolism, while indirectly to lipid metabolism and fat-related cardiovascular damage.The interesting study by Mohammadzadeh et al. suggests


Methods for the detection of specific interactions between diverse proteins and various small-molecule ligands are of significant importance in understanding the mechanisms of many critical physiological processes of organisms. The techniques also represent a major avenue to drug screening, molecular diagnostics, and public safety monitoring. Terminal protection assay of small molecule-linked DNA is a demonstrated novel methodology which has exhibited great potential for the development of simple, sensitive, specific and high-throughput methods for the detection of small molecule–protein interactions. Herein, we review the basic principle of terminal protection assay, the development of associated methods, and the signal amplification strategies adopted for performance improving in small molecule–protein interaction assay. Speciet al. as well as researchers from other groups have developed a series of methods for sensitive and specific detection of the interactions between proteins and small molecules 3−/4−, accordingly resulting in an increased electrochemical signal. The method was demonstrated to have a detection range of 0.3–20 ng/mL for FR and can be used for the investigation of small molecule–protein pairs with nanomolar dissociation constants.Nucleases, both of endonucleases and exonucleases, are useful tools in developing DNA signal amplification methods. Nickase is a kind of endonuclease which needs a specific recognition site in dsDNA but only cleaves one strand of the duplex . If thereraction . In this3.3.2.In Zhou’s study, they developed a strategy of Exo III-assisted recycling cleavage of fluorescent probe for SA–biotin interaction detection . Based o3.4.et al. [Combining the RCA technique with an exonuclease-assisted recycling cleavage of fluorescent probe in terminal protection assay, Chu et al.  have rea4.4.1.et al. constructed a small molecule-linked DNA conversion for screening the small molecule–protein interaction [et al. [The terminal protection assay strategies proposed by Jiang and his group utilized the unique properties of exonucleases. Without the participation of exonuclease, Wu eraction . This no [et al.  have acc4.2.et al. [et al. [The foundation of terminal protection assay of DNA is that binding a protein to small molecule-labeled DNA will dramatically increase the steric hindrance around the binding site and thus inhibit the action of exonucleases. According to the principle of altering work environment of enzymes, Jiang et al.  proposedet al. . Fok I iet al. . Like ot [et al. have demo [et al. .5.et al. [The review traces the recent development in the field of small molecule–protein interaction assays upon the terminal protection of small molecule-labeled DNA. Terminal protection is a generalized discovery demonstrated by Jiang et al. , that sm


Clinical laboratory tests are the scientific basis for the diagnosis and management of diseases. In addition to the traditional areas of laboratory testing, including clinical chemistry, hematology, microbiology, immunology, and transfusion medicine, genetic testing is also broadening its role in the clinical laboratory field. While many new research procedures and analytical methods are becoming available, they all should be strictly validated before being adopted in the clinical practice as routine assays. Clinical laboratories have an important role to play in this translational process from bench to bedside. K-ras wild-type patients. Y. Liu and G. Shi review the recent advances regarding the role of chemotactic G protein-coupled receptors in control of migration of subsets of dendritic cells.Based on the success of the inaugural issue in 2013, Biomed Research International annualized the special issue on laboratory medicine, and this special issue is the second one succeeding the first success. This issue includes a wide variety of laboratory-related topics as illustrated by four review articles and 15 research papers. A review article by J.-L. Choi et al. provides a comprehensive review on progresses in clinical application of platelet function tests. I. Mozos describes laboratory markers of ventricular arrhythmia risk in renal failure. Another review by T.-K. Er et al. deals with current approaches for predicting a lack of response to anti-EGFR therapy inTwo interesting papers cover the basic field of laboratory medicine. The paper by H. Jin et al. was the first to compare the characteristics of erythrocytes derived from cord blood and granulocyte colony-stimulating factor-mobilized adult peripheral blood. H.-Y. Kim et al. showed that increased mitochondrial DNA copy number might be a useful biomarker associated with polycyclic aromatic hydrocarbons toxicity and hematotoxicity. Candida guilliermondii and Candida famata correctly by using matrix-assisted laser desorption/ionization-time of flight mass spectrometry and gene sequencing. Y. J. Hong et al. evaluated a multiplex real-time PCR and melting curve analysis for the detection of herpes simplex and varicella-zoster virus in clinical specimens. Y. Kim et al. evaluated three automated nucleic acid extraction systems for identification of respiratory viruses in clinical specimens by multiplex real-time PCR. An interesting paper by S. Kim et al. showed differences in disease risk estimations among three commercial genetic-testing services, implying that the genetic services need further evaluation and standardization. Another paper by S. Kim et al. analyzed in vivo expressions of the pharmacodynamic marker inosine monophosphate dehydrogenase (IMPDH) mRNA to investigate its usefulness in assessing effects of mycophenolic acid. Y. J. Hong et al. reported the significance of Lewis phenotyping in various tissues and concluded that the gastric Lewis phenotype must be used for the study on the association between the Lewis phenotype and Helicobacter pylori. C.-W. Park et al. proposed that the degree of hepatitis C virus (HCV) quasispecies measured by ultradeep pyrosequencing might be useful to predict progression of hepatocellular carcinoma in the patients with chronic HCV.Seven papers deal with the growing area of molecular diagnostic applications. The paper by S. H. Kim et al. identifiesSix papers come from the conventional areas of hematology and chemistry. L. A. S. Nunes et al. established reference intervals for the hemogram and iron status biomarkers in a physically active male population. T.-D. Jeong et al. investigated the association between the reduction in the estimated glomerular filtration rate and the prevalence of monoclonal gammopathy of undetermined significance in healthy Korean males. Another paper by T.-D. Jeong et al. indicated that total cholesterol concentration is correlated with the levels of bone turnover markers, suggesting that it might predict osteoporosis in premenopausal women. T. Ruskovska et al. emphasized that the variability of results of total (anti)oxidants which are obtained using different assays should be taken into account when interpreting data from clinical studies of oxidative stress, especially in complex pathologies such as chronic hemodialysis. E. Gruszewska et al. concluded that the changes in concentrations of total sialic acid and free sialic acid during the same liver diseases indicate significant disturbances in sialylation of serum glycoproteins. Lastly, B. De Berardinis et al., on behalf of GREAT international, reported the usefulness of combining Galectin-3 and bioimpedance vector analysis in predicting short and long term events in patients admitted for acute heart failure.Given that laboratory medicine plays a vital role in translating research findings into clinical practice, we hope that this special issue would broaden the readership of Biomed Research International and contribute to the scientific development in this field.Mina  HurPatrizia  CardelliGiulio  Mengozzi