Among the most intriguing molecular factors that have been uncovered are the sirtuins, a family of NAD to flies. Mammalser et al.010 add tAging in the heart is characterized by hypertrophy and fibrosis, although its exact causes are unknown. Employing SIRT3−/− mice, Hafner et al. present intriguing evidence linking these aging phenotypes to mitochondrial dysfunction and SIRT3. The aut+, the aging phenotypes of SIRT3−/− mice are only apparent when the mice are older [This study combined with recent work by Someya et al. 2010), Kim et al. (2010), and Sundaresan et al. 2009) show that SIRT3 can delay the onset of age-related pathologies in multiple tissues 010, Kim -7. The p show tha


Vaccination against human papillomavirus (HPV), predominantly targeting young females, has been introduced in many countries. Decisions to implement programs, which have involved substantial investment by governments, have in part been based on findings from cost-effectiveness models. Now that vaccination programs have been in place for some years, it is becoming possible to observe their effects, and compare these with model effectiveness predictions made previously.Australia introduced a publicly-funded HPV vaccination program in 2007. Recently reported Australian data from a repeat cross-sectional survey showed a substantial (77%) fall in HPV16 prevalence in women aged 18–24 years in 2010–2011, compared to pre-vaccination levels. We have previously published model predictions for the population-wide reduction in incident HPV16 infections post-vaccination in Australia. We compared prior predictions from the same model (including the same assumed uptake rates) for the reduction in HPV16 prevalence in women aged 18–24 years by the end of 2010 with the observed data. Based on modelled vaccine uptake which is consistent with recent data on three-dose uptake , we had predicted a 70% reduction in prevalence in 18–24 year old females by the end of 2010. Based on modelled vaccine uptake consistent with recent national data for two-dose coverage and similar to that reported by women in the cross-sectional study, we had predicted a 79% reduction.A close correspondence was observed between the prior model predictions and the recently reported findings on the rapid drop in HPV prevalence in Australia. Because broadly similar effectiveness predictions have been reported from other models used for cost-effectiveness predictions, this provides reassurance that the substantial public investment in HPV vaccination has been grounded in valid estimates of the effects of vaccination. Vaccination against human papillomavirus (HPV), predominantly targeting young females, has been introduced in many countries. Implementation of publicly-funded programs has involved substantial investment by governments. In Australia, for example, the government budgeted approximately A$580 million over the first five years of its National HPV Vaccination Program for females 2007–2011) . Now that vaccination programs have been in place for some years, it is becoming possible to observe their effects on health outcomes , outside of the context of clinical trials. Australia implemented a National HPV Vaccination Program in 2007, with routine vaccination of 12–13 year old females and catch-up in females aged 13–26 years to 2009 with the quadrivalent vaccine . The National HPV Vaccination Program is primarily delivered through schools, although missed doses can be obtained from primary care. The catch-up program was delivered through schools for school-aged girls, and through primary care for older 18–26 years) females or females who were no longer at school. Commencing from 2013, the National HPV Vaccination Program was extended to include routine vaccination of 12–13 year old males and a two year catch-up program for boys aged 14–15 years during 2013 and 2014. Australia offers unique opportunities to observe the early impacts of HPV vaccination, as its program commenced earlier and its catch-up component was more extensive than in most other countries. Post-vaccination reductions have already been documented in Australia in genital warts [–26 yearset al. recently reported a substantial fall in HPV prevalence in a repeat cross-sectional study in Australian women aged 18–24 years recruited during 2010–2011, compared to women of the same age recruited in 2005–2007, which was prior to the commencement of the vaccination program [Tabrizi  program . HPV16 p program . Self-re program -11. The  program ,11. Undeet al., which required specific examination of the prior model predictions for HPV prevalence in the specific age group and at the specific timepoint reported by Tabrizi et al.[et al.[We have previously published model predictions for the reduction in incident HPV16 infections post-vaccination in Australia, across the female population ,13. The zi et al.. We alsol.[et al.,12.et al. also comprised the subset of women from WHINURS who were 18–24 years of age at the time of recruitment.In line with methods used by several other groups , we usedet al.[et al.[To compare model predictions with the findings of Tabrizi et al., we extrl.[et al.) among wWe had modelled uptake in terms of effective vaccination; initially we had assumed three vaccine doses would be needed to achieve the efficacy levels observed in clinical trials . Howeveret al.[et al.[et al.  [et al. (70.6%) [et al.  were unchanged compared to our previous analysis . The earet al.. Table 1l.[et al.. Full del.[et al.. In the l.[et al.-11,19), eported) . The hig (70.6%) . The lowet al. (70.6%) [et al. ), the model predicted a reduction in HPV16 prevalence of 70% by the end of 2010  [et al. (70.6%) [et al. (70.6%) [In the main scenario examined , but lower than self-reported uptake in Tabrizi  (70.6%) ), we had (70.6%) . When we et al.) . Based ot period 10–2011), (70.6%) ), we pre (70.6%) ), we preet al., who reported a 77% reduction in HPV16 prevalence, [This predicted 64%-79% fall in HPV16 infections in 18–24 year old females by the end of 2010 accords well with the data from Tabrizi et al., where three-dose uptake was potentially somewhat higher than average for other females of the same age [et al. was substantial, after adjusting for differences in age and hormonal contraceptive use in the pre- and post-vaccination study samples [While our model incorporated the best estimates of uptake available at the time, and attempted to encompass a broad feasible range, there are now more data available on both uptake achieved by the program and the efficacy of two versus three doses of quadrivalent vaccine. The uptake we assumed for our original predictions  is genersame age . Two-dos samples .Models of HPV vaccination typically assume high vaccine efficacy in the base case , based oet al. noted that, as far as they were aware, their findings “were the first genoprevalence-based evidence of the protective effect of HPV vaccination outside the setting of a clinical trial”[The joint task force of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the Society for Medical Decision Making recommended as best practice for medical decision-making models that model predictions of future events should be tested against observed data, when these data subsequently become available . This isal trial”.The investments in HPV vaccination programs around the world have been substantial. Such investments in affluent countries have been made, in part, on the basis of predictions from cost-effectiveness models. However, prior model predictions for vaccine effectiveness in a 'real world’ population have not previously been compared to observed data after the vaccination program has been implemented.The close correspondence between these prior model predictions and the recently reported findings on the rapid drop in HPV prevalence rates in Australia  providesHPV: Human papillomavirus; NHVPR: National HPV vaccination program register.MS: has no commercial or other association that might pose a conflict of interest. KC: declares that she is involved as a principal investigator in a new trial of primary HPV screening in Australia, which is supported by Roche Molecular Systems and Ventana, CA, USA. KC receives salary support from the NHMRC Australia (CDF1007994).MS: Designed the study; analysed and interpreted the data; drafted the manuscript. KC: Conceived and designed the study; helped draft the manuscript. Both authors read and approved the final manuscript.Age-specific vaccine uptake in females in modelled scenarios versus reported uptake in Australian female population.Click here for file


ABCA1 gene. In this study we evaluated the single nucleotide polymorphisms (SNPs) of ABCA1 gene. We analyzed SNPs in chromosome 9 such as rs2230806 (R219K) in the position 107620867, rs2230808 (R1587K) in the position 106602625 and rs4149313 (I883M) in the position 106626574 according to gender and lipid profile of Greek nurses.One of the important proteins involved in lipid metabolism is the ATP-binding cassette transporter A1 (ABCA1) encoding by ABCA1 gene polymorphisms. Additionally, lipid profile  was evaluated.The study population consisted of 447 (87 men) unrelated nurses who were genotyped for ABCA1 gene polymorphisms did not differ according to gender. However, only R219K genotype distribution bared borderline statistical significance (p = 0.08) between the two studied groups. Moreover, allele frequencies of R219K, R1587K and I88M polymorphisms did not differ according to gender. In general, blood lipid levels did not seem to vary according to ABCA1 gene polymorphisms, when testing all subjects or when testing only men or only women. However, a significant difference of LDL-C distribution was detected in all subjects according to R1587K genotype, indicating lower LDL-C levels with KK polymorphism (p = 0.0025). The above difference was solely detected on female population (p = 0.0053).The distribution of all three studied ABCA1 gene polymorphisms frequency, distribution and lipid profile did not differ according to gender. However, in the female population the KK genotype of R1587K gene indicated lower LDL-C levels. Further studies, involving a higher number of individuals, are required to clarify genes and gender contribution.The  ABCA1 gene in macrophages increases atherosclerotic lesions in hyperlipidemic mice . This study in line with our previous work [ABCA1 gene polymorphisms mention above and lipid profile in Greek male and female nurses.ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to lipid-poor apolipoproteins. Animals and human studies documented that defects in the ABCA1 pathway are significant determinants of coronary artery disease (CAD) [mic mice ,3, and omic mice ,5. The AThe genotyping of 447  nurse students median age 22 (21–25) years old, who were attended to the University of Nursing of Technological and Educational Institution, was performed. All students had no personal history of CAD and were not taking any drugs. Other exclusion criteria were diabetes mellitus, thyroid and liver disease, high alcohol consumption, professional athleticism and any chronic disease.All students were attended to the University every day and were staying for 8–10 hours. Students were eating  at the school canteen which served typical Mediterranean food. Only one meal daily (dinner) was most likely to be different in each student.The University of Nursing of Technological and Educational Institution Ethics Committee approved the protocol of this study. All subjects signed an informed consent form.Plasma total cholesterol (TC), triglycerides (TGs), high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (Apo A1) were measured using enzymatic colorimetric methods on Roche Integra Biochemical analyzer with commercially available kits (Roche). The serum low density lipoprotein cholesterol (LDL-C) concentration was calculated using the Friedewald formula only in subjects with TGs concentration < 400 mg/dl.et al.[et al.[The ABCA1 gene polymorphisms  were detected using polymerase chain reaction (PCR) and restricted fragment length polymorphism analysis (RFLP’s). The PCR was performed using Taq polymerase KAPATaq. The oligonucleotide primers used for R219K and R1587K polymorphisms were described by Saleheen D et al.[οC for 5 min, thirty cycles of 95 οC for 30 s, 65 οC for 30 s and 72 οC for 30 s and final extension to 72 οC for 7 min, producing a fragment of 132 bp. This fragment was subsequently cleaved by EcorV, creating fragments for I allele 97 bp and 35 bp and for M allele 132 bp, which were subjected to electrophoresis on an agarose gel 4% and visualized with ethidium bromide . The Kruskal – Wallis H statistic was employed in order to detect differences in lipid levels according to three different polymorphisms of ABCA1 gene . ABCA1 polymorphisms’ distribution according to lipid profile was tested using the Kruskal Wallis test in men, in women and in all patients. All results were corrected for multiple testing (Bonferroni correction). All tests were two-tailed and statistical significance was established at 5% (p < 0.05). Data were analysed using Stata ™ .The Shapiro-Wilk test was performed to test for normal distribution of continuous variables. The results are given as median and interquartile range (IQR), whereas, all qualitative variables are presented as absolute or relative frequencies. The Mann–Whitney Comparison of various characteristics according to gender showed that the study group was homogenous regarding age (p > 0.05) Table . HoweverABCA1 gene polymorphisms studied did not differ according to gender .In previous study we evaluated the influence of et al.[et al. [ABCA1 gene as risk factor for ischemic stroke. Srinivasan et al.[et al. [et al. [et al.[et al.[ABCA1 gene polymorphisms was not different according to gender. Noteworthy to mention is that the R219K distribution bared borderline statistical significance (p = 0.08) between two studied groups. In general, blood lipid levels did not seem to vary according to ABCA1 gene polymorphisms, when testing all subjects or when testing only men or only women.One of the first study which evaluated the R219K polymorphism and lipid profile in man was published by Clee SM et al.,9-16. Co.[et al.  did not an et al. found th.[et al.  found th [et al.  found a . [et al. did not l.[et al. studied et al.[et al.[et al.[Clee et al. in the set al. associatl.[et al. did not l.[et al. found thl.[et al. where onl.[et al.. Howeveret al.[et al.[et al.[et al.[et al.[et al.[I883M gene, which were also present between the highest and lowest HDL-C concentration groups . On the contrary, Kitjaroentham et al.[et al.[et al.[et al.[ABCA1 gene polymorphisms i27943 (rs2575875) and R219K (rs2230806) have a lower postprandial response as compared to minor allele carriers. The fact that in current study blood lipid levels did not seem to vary according to ABCA1 gene polymorphism could be influence, at least in part, because they were measured in the fasting state.Tan et al. studied l.[et al. did not l.[et al. correlatl.[et al. among yol.[et al. in popull.[et al. found soam et al. did not l.[et al. found thl.[et al. found thl.[et al. suggestiA limitation of this study is the relatively small number of men’s group. However, the effort was put for sample to be homogenous, living in the similar conditions as it happened with our study population.Another limitation of this type of study is that, studies based on the candidate-gene approach, which have been demonstrated genotype-phenotype associations, are not always replicable.ABCA1 gene polymorphisms on lipid profile in accordance to gender. The ABCA1 gene polymorphisms frequency, distribution and lipid profile did not differ according to gender. However, in the female population the KK genotype of R1587K gene indicated lower LDL-C levels.There are only few studies which compare the influence of The authors declare that they have no competing interests.VK participated in the development of hypothesis, drafting of the manuscript and carried out the genetic analysis, AM participated in the molecular genetic studies, AK performed the statistical analysis and drafting of the manuscript, GV and AK collected the blood samples, SM participated in the drafting and revising the manuscript, DD participated in revising the manuscript critically for important intellectual content, CM participated in the study design and its coordination and GK conceived the study and participated in the development of the hypothesis, the study design and drafting of the manuscript. All authors read and approved the final manuscript.


An association between fluid intake and limb swelling has been described for 100-km ultra-marathoners. We investigated a potential development of peripheral oedemata in Ironman triathletes competing over 3.8 km swimming, 180 km cycling and 42.2 km running.In 15 male Ironman triathletes, fluid intake, changes in body mass, fat mass, skeletal muscle mass, limb volumes and skinfold thickness were measured. Changes in renal function, parameters of skeletal muscle damage, hematologic parameters and osmolality in both serum and urine were determined. Skinfold thicknesses at hands and feet were measured using LIPOMETER® and changes of limb volumes were measured using plethysmography.p <0.05), fat mass, skinfold thicknesses and the volume of the arm remained unchanged (p >0.05). The decrease in skeletal muscle mass was associated with the decrease in body mass (p <0.05). The decrease in the lower leg volume was unrelated to fluid intake (p >0.05). Haemoglobin, haematocrit and serum sodium remained unchanged (p >0.05). Osmolality in serum and urine increased (p <0.05). The change in body mass was related to post-race serum sodium concentration ([Na+])  and post-race serum osmolality .The athletes consumed a total of 8.6 ± 4.4 L of fluids, equal to 0.79 ± 0.43 L/h. Body mass, skeletal muscle mass and the volume of the lower leg decreased (ad libitum fluid intake maintained plasma [Na+] and plasma osmolality and led to no peripheral oedemata. The volume of the lower leg decreased and the decrease was unrelated to fluid intake. Future studies may investigate ultra-triathletes competing in a Triple Iron triathlon over 11.4 km swimming, 540 km cycling and 126.6 km running to find an association between fluid intake and the development of peripheral oedemata.In these Ironman triathletes,  Specific gravity was analysed using Clinitek Atlas® Automated Urine Chemistry Analyzer . Creatinine and urea were measured using COBAS INTEGRA® 800. Electrolytes were determined using ISE IL 943 Flame Photometer .Pre- and post-race, venous blood samples were drawn and urine samples were collected. Two Sarstedt S-Monovettes  for chemical and one Sarstedt S-Monovette   for haematological analysis were drawn the afternoon before the start of the race and upon arrival at the finish line. Monovettes for plasma were centrifuged at 3,000 g for 10 min at 4 °Celsius. Plasma was collected and stored on ice. Urine was collected in Sarstedt monovettes for urine (10 ml). Blood and urine samples were transported immediately after collection to the laboratory and were analysed within six hours. Immediately after arrival at the finish line, identical measurements were applied. In the venous blood samples, haemoglobin, haematocrit,  (p >0.05). The change in body mass was related to both post-race serum [Na+] . The decrease of the volume of the lower leg was unrelated to fluid intake (p >0.05). Fluid intake was neither related to the changes in the thickness of adipose subcutaneous tissue nor to the changes in skin-fold thicknesses (p >0.05). Sodium intake was not related to post-race serum [Na+] (p >0.05). Post-race serum [Na+] was unrelated to both the change in the potassium-to-sodium ratio in urine and TTKG (p >0.05). The increase in serum urea was not related to the increase in serum osmolality (p >0.05). The change in serum urea was unrelated to the change in skeletal muscle mass (p >0.05). The change in the thickness of the adipose subcutaneous tissue at the medial border of the tibia was significantly and positively associated with the change in creatinine clearance . The increase in the thickness of adipose subcutaneous tissue at the medial border of the tibia was not related to the non-significant change in skin-fold thickness of the calf (p >0.05). The non-significant changes in skin-fold thicknesses were neither related to overall race time nor to the split times (p >0.05).Fluid intake was unrelated to the decrease in body mass  ,41,42. Rer et al., Speedy l.[et al., and Noal.[et al. describiKavouras  and ShirKavouras  describeKavouras ,48.A further finding was that the circumferences of the thigh and the calf decreased by 2.7% and 2.4%, respectively, whereas the circumference of the upper arm remained unchanged. This indicates that the estimated skeletal muscle mass at the lower limbs became reduced. Since the change in the estimated skeletal muscle mass showed no association with the change in plasma urea, we presume that no substantial degradation of myofibrillar proteins must have occurred, and the loss in estimated skeletal muscle mass might be due to a depletion of intramyocellular stored energy, such as muscle glycogen and intramyocellular lipids . We furtet al.[et al.[et al.[et al.[However, the reduction in limb circumference could also be due to a reduction in interstitial fluid. The decrease in the lower leg volume might also suggest an action of the ‘muscle pump’ during exercise helping to clear pre-race swelling. Perhaps the tapered athlete started with oedemata, the result of being relatively inactive in a pre-race taper. If so, perhaps the muscle pump cleared this oedemata during the race, and perhaps clearing was aided by compression socks. Regarding the results concerning the decrease in the circumferences of both the thigh and the calf, we expected that the main areas of decrease would occur in the muscles used most, meaning in the lower leg and thigh muscles. Because the thigh has a larger skeletal muscle mass than the calf, it is likely that the change in the thigh muscle mass influenced the change in estimated skeletal muscle mass more than the change in calf muscle mass did. Another possible explanation could be that there actually would have been a correlation between the decrease of the lower leg volume and the estimated skeletal muscle mass, but that this correlation was influenced due to a non-quantified change in tissue fluid in the lower leg. As we were using plethysmography for measuring the volumes of the whole limbs, we were not able to differentiate a change in volume between arm and hand or between lower leg and foot, respectively. This could have influenced our results. Lund-Johansen et al. measuredl.[et al. measuredl.[et al. describel.[et al. measuredet al.[et al.[Another interesting finding was that the change in the thicknesses of adipose subcutaneous tissue at medial border of the tibia was significantly and positively associated with the change in creatinine clearance. However, correlation analysis does not prove cause and effect; therefore this correlation must be questioned. In case of an impairment of renal function, we would expect a development of peripheral oedemata ,51. Howeet al. describil.[et al. showed, et al.[et al.[Na or FeUrea is also an argument against any association between a change of the adipose subcutaneous tissue and a change in renal function. FeNa and FeUrea are parameters which can be used to detect an impairment of the renal function [In the present study, a reason why the thickness of the adipose subcutaneous tissue of the lower leg showed no increase might be due to the compression, which might be induced by wearing socks and running shoes. Knechtle et al. also desl.[et al. describifunction ,54. Sincet al.[et al.[et al.[et al.[et al.[et al.[et al.[et al.[The present Ironman triathlon with a mean average race time of about eleven hours was rather short when compared to the studies from Milledge et al., Williaml.[et al. and the l.[et al. where thl.[et al., Irving l.[et al. and Knecl.[et al. showing l.[et al., the eccl.[et al. also deml.[et al. that theThe type of oedemata that develops following an Ironman triathlon is not necessarily the result of frank rhabdomyolysis. Leg swelling is often of oedematous nature  where biIt should also be noted that this kind of oedema cannot be said to be due to aggressive overdrinking completely unrelated to thirst. Excess water is ingested because the debris of prolonged exercise increases the osmolality of body water, appropriately increasing thirst. The mean fluid intake in these Ironman triathletes was 0.79 ± 0.43 L/h. In a recent study on 100-km ultra-marathoners showing an association between fluid intake and limb swelling, the athletes consumed 0.63 ± 0.20 L/h . Obvious. An implication for future research would therefore be to measure the volume of hands and feet separately from the arms and the legs using plethysmography. It would as well be useful to have a measurement method that allows us to differentiate the volume changes occurring in a body part into the different body compositions. Bioelectrical impedance analysis [et al.[et al.[et al.[et al.[A strength of this study was that anthropometric measurements were performed immediately upon arrival at the finish line. A limitation of the present study was that by measuring the entire lower leg volume, or arm volume, we could not precisely quantify nor locate specifically where the changes in volume occurredanalysis  for examanalysis . Howeveranalysis  since planalysis ,65. Regas [et al., Milledgl.[et al. and Willl.[et al. describil.[et al.,2,6,66 il.[et al.. Furtherl.[et al.,68. NSAIl.[et al.. Hew et l.[et al. reportedl.[et al. and athll.[et al.. Finally+ was maintained and serum osmolality increased because body mass decreased. Considering the findings of Milledge et al.[et al.[To summarize, the volume of the lower extremity decreased and this decrease was unrelated to fluid intake in the present male Ironman triathletes. We found no increase in the thickness of adipose subcutaneous tissue of the hands and feet. Renal function was altered. Serum [Nage et al. and Willl.[et al., the durl.[et al.. For futl.[et al..The authors declare that they have no competing interests.MM drafted and wrote the manuscript. BK designed the study and assisted the manuscript preparation. BK, JB, PK, CM, AM and BE conducted all the measurements during two field study for data collection before and after the race. CAR and TR assisted in data analyses, statistical analyses, data interpretation and manuscript preparation. All authors have read and approved the final version of the manuscript.


As knowledge of the structure and function of nucleic acid molecules has increased, sequence-specific DNA detection has gained increased importance. DNA biosensors based on nucleic acid hybridization have been actively developed because of their specificity, speed, portability, and low cost. Recently, there has been considerable interest in using nano-materials for DNA biosensors. Because of their high surface-to-volume ratios and excellent biological compatibilities, nano-materials could be used to increase the amount of DNA immobilization; moreover, DNA bound to nano-materials can maintain its biological activity. Alternatively, signal amplification by labeling a targeted analyte with nano-materials has also been reported for DNA biosensors in many papers. This review summarizes the applications of various nano-materials for DNA biosensors during past five years. We found that nano-materials of small sizes were advantageous as substrates for DNA attachment or as labels for signal amplification; and use of two or more types of nano-materials in the biosensors could improve their overall quality and to overcome the deficiencies of the individual nano-components. Most current DNA biosensors require the use of polymerase chain reaction (PCR) in their protocols. However, further development of nano-materials with smaller size and/or with improved biological and chemical properties would substantially enhance the accuracy, selectivity and sensitivity of DNA biosensors. Thus, DNA biosensors without PCR amplification may become a reality in the foreseeable future. Detection of specific DNA sequences is needed in many fields: the Human Genome Project is providing massive amounts of genetic information that should revolutionize our understanding and diagnosis of inherited diseases ; pathogeConventional methods for the analysis of specific gene sequences are carried out using gel electrophoresis of DNA fragments amplified by the polymerase chain reaction (PCR) using primers that are sequence-specific for the chosen region of DNA. Although it is simple and effective for the detection of PCR products, gel electrophoresis fails to provide any sequence information about the amplified DNA. Furthermore, the use of PCR is limited to laboratories because of its complexity in obtaining proper primers design and the corresponding empirical conditions for consistent amplification . SoutherIn recent years, DNA biosensors based on nucleic acid hybridization have been vigorously pursued. DNA biosensors are defined as analytical devices incorporating a single-stranded oligonucleotide (probe) intimately associated with or integrated within a physicochemical transducer or transducing microsystem, which may be optical, electrochemical, thermometric, piezoelectric, magnetic or micromechanical. The aim of a DNA biosensor usually is to produce either discrete or continuous measurable signals, which are proportional to the concentration of complementary (target) DNA sequence. Because of their specificity, speed, portability, and low cost, DNA biosensors offer exciting opportunities for sequence-specific DNA detection. However, the concentration of genetic targets is very low in biological samples, making it unsuitable for detection by a DNA biosensor. Therefore, an ultrasensitive method of detecting nucleic acids is clearly essential.In order to achieve high detection sensitivity, researchers have developed many techniques to enhance the response of DNA biosensors by modifying the sensors with different functional materials. Within the growing and increasingly complex area of nanotechnology, great attention has been paid in recent years to nano-structured materials of different chemical composition, produced as nanoparticles, nanowires or nanotubes. Nano-materials are larger than individual atoms and molecules but are smaller than bulk solids, therefore they obey neither absolute quantum chemistry nor the laws of classical physics and have properties that differ markedly from those expected. There are two major phenomena that are responsible for these differences. First is the high dispersity of nanocrystalline systems . As the The nano-materials used in DNA biosensors including nanoparticles, like gold (Au) nanoparticles, Cadmium sulfide (CdS) nanoparticles; nanowires like silicon (Si) nanowires, nanotubes like carbon nanotubes, etc. There are mainly two purposes of using nano-materials in DNA biosensors: as substrates for DNA attachment and as signal amplifiers for hybridization. The aim of this article is to summarize the various nano-materials used in DNA biosensors based on the two purposes in recent years, including the information on applications and future prospects.2.As we know, the most critical step while preparing a DNA biosensor is the immobilization of DNA probe on the surface of a sensing device such as an electrode. The amount of immobilized DNA probe will influence the accuracy, sensitivity, selectivity, and life of a DNA biosensor directly. Because of the high surface-to-volume ratio and excellent biological compatibility, nano-materials can enlarge the sensing surface area to increase the amount of immobilized DNA greatly, and the DNA mixed with nano-materials can keep its biological activity well.2.1.Over the past decade, the unique properties of nanoparticles have continued to attract considerable research attention. Nanoparticles, especially metal nanoparticles, offer excellent prospects for chemical and biological sensing because of their unique optical, electrical, and thermal properties as well as catalytic properties –19. The 2.1.1.et al. [et al. [Gold (Au) nanoparticles are a hot study topic lately and they play a key role in DNA biosensors. Thiol–Au (SH–Au) linkages usually were used to bind Au nanoparticles covalently with solid electrodes or DNA because of the strong affinity of covalent bonds between sulfur atoms and gold atoms. Jin et al.  immobili [et al.  also fab [et al. –33 have et al. [2O3) substrates by a physical method to prepare a DNA biosensor. Pan [et al. [et al. [Au nanoparticles as substrates for DNA attachment though other linkages were also reported in several publications. Spadavecchia et al.  depositesor. Pan  prepared [et al.  fabricat [et al.  deposite2.1.2.et al. [Platinum (Pt) nanoparticles were also used as substrates to improve DNA immobilization due to their high catalytic activities. Zhu et al.  fabricat2.1.3.2) is a thermally stability, chemically inert, non- toxicity inorganic oxide with affinity for the groups containing oxygen, and therefore it is an ideal candidate material for immobilization of biomolecules containing oxygen or phosphate groups. Thus, ZrO2 is an ideal material for immobilization of DNA. Zhu et al. [2 thin films onto the bare gold electrode by cycling the potential between −1.1 and +0.7 V (versus Ag/AgCl) at a scan rate of 20 mV/s. Oligonucleotide probes with phosphate group at the 5′ end were attached onto the ZrO2 thin films. Yang et al. [2 coupled with carbon nanotubes to improve DNA attachment to the electrode.Zirconia  has many unique properties, such as a high dielectric constant, a large band gap, high electron affinity, and it is also relatively easy to present as a thin film. Shrestha et al. [6O11 surface. Pr6O11 was deposited on a tin-doped indium oxide (ITO) surface to form an ultrathin layer with a larger internal surface area, and then the thiol-modified oligonucleotide attached to an amine-modified Pr6O11 surface.Praseodymium oxide  were first noticed and characterized in 1991 by Iijima  of NEC C2.2.1.et al. [N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimido-biotin (NHS), then the synthesized ssDNA was covalently immobilized on the CNTs modified gold electrodes. Abdullin et al. [et al. [et al. [et al. [Tang et al.  modifiedn et al.  modified [et al. , Erdem e [et al.  and Lian [et al. .2.2.2.et al. [et al. [et al. [Polypyrrole (PPy) is a common material which acts as a bridge to connect DNA with CNTs. Xu et al. ,52 repor [et al.  and Qi e [et al.  also repet al. [2 for chitosan-CNTs-modified electrodes and chitosan-modified electrodes, respectively). Bollo et al. [Chitosan is another material used as a bridge for DNA attachment to CNTs. Li et al.  fabricato et al.  also diset al. [et al. [et al. [Other materials used for DNA attachment to CNTs were also reported. Guo et al.  describe [et al.  covalent [et al.  studied 2.3.Nanowires fabricated by polyaniline were utilized as substrates for DNA attachment in some literatures ,61. Nanoet al. [2 sensor areas and superior DNA bonding stability over 30 hybridization/denaturation cycles.Nebel et al.  introduc2.4.et al. [Nanoclusters also reported as substrates for DNA attachment. Zhu et al.  synthesi3.When we detect small-molecule ligands of biomedical interest, ligand binding may not significantly perturb the biosensor interface. In this situation, signal amplification may be useful. Signal amplification by labeling the analyte with nano-materials has been reported for DNA biosensors in many literatures.3.1.3.1.1.et al. [2, whereas no change could be observed for goat antifluorescein without the Au nanoparticle conjugate. This allowed construction of high-sensitivity electrochemical impedance biosensors at a single low frequency, where the signal was sensitive to the interfacial Rct. This change in the electrochemical impedance signal of binding to goat antifluorescein conjugated with Au nanoparticles could be attributed to the much higher electrochemical activity of Au surfaces relative to the underlying organic layer. Amplification of voltammetric signal was also characterized by many researchers [Due to their electrochemical properties, Au nanoparticles have been used as signal amplifiers in many electrochemical DNA biosensors. Wang et al.  demonstrearchers –67. Li aearchers  developeet al. [et al. [et al. [Optical properties of Au nanoparticles were also used for optical DNA biosensor. Yao et al.  used Oli [et al.  and Mart [et al. .Au nanoparticles were also reported to be used as signal amplifiers for quartz crystal microbalance (QCM) biosensors ,72–75. A3.1.2.et al. [+ with concentrated HNO3 then released from the hybrids, but complete dissolution of a gold tag required more severe conditions (1 M HBr containing 0.1 mM Br2) and the electrode might be damaged in this medium. Similar electrochemical characterizations of Ag nanoparticles used in DNA biosensors were done by Fu et al. [et al. [Ag nanoparticles have desirable compositions as oligonucleotides labels in electrochemical detection assays because Ag nanoparticles exhibit better electrochemical activity than Au ones. Cai et al.  reportedu et al.  and K’Ow [et al. .3.1.3.et al. [et al. [Cadmium sulfide (CdS) nano-material is a semiconductor material with attractive electrochemical properties. CdS as oligonucleotide labeling tags for detection of DNA hybridization have been reported by several researchers. Xu et al.  used a t [et al.  also use3.2.et al. [3Fe(CN)6 at a bare glassy carbon electrode and an electrochemically activated glassy carbon electrode which was treated in the absence or presence of multi-walled CNTs under identical experimental conditions. The results indicate that the electrochemical response of the K3Fe(CN)6 at the CNTs activated electrode was the strongest among these three kinds of electrodes.The conductive properties of CNTs suggest that they could mediate electron transfer reactions and enhance the relative electrochemical reactivity with electroactive species in solution when used as the electrode material or substrates modified on solid electrodes. As electrode or substrates modified materials, CNTs show better electrochemical behavior than traditional glass carbon electrodes, carbon paste electrodes and any other carbon electrodes . Therefoet al.  comparedet al. [Escherichia coli were used as a target and a control, respectively. Southern blotting, which used photostable Raman signals of nanotubes instead of fluorescent dyes, demonstrated excellent sensitivity and specificity of the probes. Their results showed that SWCNTs may be used as generic nano-biomarkers for the precise detection of specific kinds of genes. Cao et al. [The unique optical properties make CNTs ideal optical probes for tagging biomolecules. CNTs exhibit strong Raman signals as well as fluorescence emissions in the near infrared region. And such signals do not blink or photobleach under prolonged excitation, which is an advantage in optical nano-biomarker applications. The intense Raman scattering from CNTs provides a large amount of information about the structure and properties of nanotubes with some of the highest known cross-sections for single molecules. Hwang et al.  presenteo et al.  developeet al. [et al. [et al. [Recently, CNTs have also been utilized as a novel support material to concentrate nanoparticles or enzyme molecules on it as a more powerful DNA hybridization indicator than using a single nanoparticle or enzyme molecule indicating DNA hybridization  with embedded Au nanoclusters. It was shown that the sensitivity of the SPR biosensor could be improved by adjusting the size and volume fraction of the embedded Au nanoclusters in order to control the surface plasmon effect. The DNA hybridization experimental results could achieve 10-fold improvement in the resolution performance compared with the conventional SPR biosensors.Hu et al.  develope4.In conclusion, different nano-materials have been successfully applied to DNA biosensors as substrates for DNA attachment and as labels for signal amplification, specifically. (1) When nano-materials are used as substrates for DNA attachment, the smaller size the nano-material is, the better result a DNA biosensor can provide. As the size of a crystal is reduced, the surface-to-volume ratio of a crystal is increased, thus it can enlarge the electrode surface area to greatly enhance the amount of immobilized DNA. But this conclusion is only applicable under the condition that the shape of nano-materials is regular, otherwise we cannot obtain a repeatable result. Similar conclusion holds true when nano-materials are used as signal amplifiers.et al. [(2) Due to the diverse properties of different nano-materials, utilizing two or more types of nano-materials could enhance the good qualities as well as offset the insufficiency of each individual nano-material, which could produce better results than that using only one type of nano-materials. For example, Cai et al.  describeet al. ,96, incl(3) Although great efforts have been made in all DNA biosensor technologies in order to eliminate the role of the PCR from their protocols, this goal has not yet been achieved . Many sc


The ongoing retreat of glaciers globally is one of the clearest manifestations of recent global warming associated with rising greenhouse gas concentrations. By comparison, the importance of greenhouse gases in driving glacier retreat during the most recent deglaciation, the last major interval of global warming, is unclear due to uncertainties in the timing of retreat around the world. Here we use recently improved cosmogenic-nuclide production-rate calibrations to recalculate the ages of 1,116 glacial boulders from 195 moraines that provide broad coverage of retreat in mid-to-low-latitude regions. This revised history, in conjunction with transient climate model simulations, suggests that while several regional-scale forcings, including insolation, ice sheets and ocean circulation, modulated glacier responses regionally, they are unable to account for global-scale retreat, which is most likely related to increasing greenhouse gas concentrations. The extent to which greenhouse gases forced glacier retreat during the last deglaciation remains unclear. Here, the authors recalculate cosmogenic nuclide ages for 195 glacier moraines and show that deglacial glacier retreat was broadly globally synchronous with rising levels of atmospheric CO2. Goehring et al.et al.3He. However, recent advances have pointed out shortcomings in previous scaling models, and more recent 10Be calibrations are yielding values that are consistently and significantly lower than those included in Balco et al.10Be and 3He production rates.Accurate cosmogenic-nuclide production-rate estimates are critical for surface-exposure dating applications, particularly for global comparisons such as in this study. In addition to reliable calibrations of production rates at sites covering as wide a spatial and temporal range as possible, one needs consistent implementation of accurate production-rate scaling models to transform those rates to other sites of interest. The online calculator of Balco et al.et al.in situ cosmogenic nuclides. All scaling calculations here were done using nuclide-specific formulations and the atmospheric, geomagnetic and solar framework considered in Lifton et al.A new scaling modelet al.RC) to describe the dependence of the cosmic-ray flux on position within the geomagnetic field (including both dipolar and non-dipolar components). Cutoff rigidity is defined as the minimum rigidity  that an incident primary cosmic-ray particle may possess and still be able to interact with the atmosphere at a given location . Calculating whole-sky cutoffs globally is prohibitively computationally expensive for our purposes . This value is similar to that arrived at by Heymanχ2), or excluding sites with ambiguously defined ‘too large scatter' while including sites with much larger apparent scatter. We did, of course, focus solely on post-2005 calibration data sets, that is, those not contained within Balco et al.et al.et alet al.10Be at g−1 per year with or without it.A number of high-quality  results . As a wh3He analysis, combining new data sets from Amidon and Farleyet al.et al.et al.3He data tend to be more scattered than the 10Be data set, both within and between sites, but all site results pass Chauvenet's criterion and thus are included. Grouping the data by study yields an arithmetic mean and s.d. for the sea-level and high-latitude 3He production rate for LSD scaling of 122±14 3He at g−1 per year (1σ).We did a similar calculation for our et al.10Be and 11.5% for 3He. We excluded cosmogenic ages deemed outliers by the original authors . All exposure age calculations used the new 10Be and 3He calibrated global-production rates described above with nuclide-specific LSD scaling and the atmospheric, geomagnetic and solar framework described in Lifton et al.There is a considerable literature on how best to model moraine ages from individual boulder ages in the typical case that the scatter exceeds analytical uncertainty and thus must reflect geomorphic processes. Two competing processes are likely to dominate on deglacial-age moraines: prior exposure contributes inherited nuclides that lead to overestimates of moraine age, while boulder exhumation yields underestimates of the true moraine age. Applegate The four single-forcing transient simulations  of the TraCE simulationsHow to cite this article: Shakun, J. D. et al. Regional and global forcing of glacier retreat during the last deglaciation. Nat. Commun. 6:8059 doi: 10.1038/ncomms9059 (2015).Supplementary Figures 1-9, Supplementary Tables 1-2, Supplementary Notes 1-2 and Supplementary ReferencesCosmogenic surface exposure age data for all reconstructed glaciers


Viral polymerases replicate and transcribe the genomes of several viruses of global health concern such as Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Ebola virus. For this reason they are key targets for therapies to treat viral infections. Although there is little sequence similarity across the different types of viral polymerases, all of them present a right-hand shape and certain structural motifs that are highly conserved. These features allow their functional properties to be compared, with the goal of broadly applying the knowledge acquired from studying specific viral polymerases to other viral polymerases about which less is known. Here we review the structural and functional properties of the HCV RNA-dependent RNA polymerase (NS5B) in order to understand the fundamental processes underlying the replication of viral genomes. We discuss recent insights into the process by which RNA replication occurs in NS5B as well as the role that conformational changes play in this process. Polymerases are crucial in the viral life cycle. They have an essential role in replicating and transcribing the viral genome and as a result are key targets for therapies to treat viral infection. A virus may not need to encode its own polymerase depending on where it spends most of its life cycle. Some small DNA viruses that spend all their time in the cell nucleus can make use of the host cell’s polymerases. However, viruses that remain in the cytoplasm do need to encode their own .in vitro without accessory factors. This is primarily because the sizes of genomes that can be packaged in the viral capsid are limited . ,7. 1,7].channel) ,10 (see vs. deoxyribose NTPs (dNTP) is regulated by the interaction of the polymerase with the 2′-OH of the NTP. In general, DNA polymerases that incorporate dNTP in the growing daughter strand have a large side chain that prevents binding of an rNTP with a 2′-OH. However, RNA polymerases utilize amino acids with a small side chain and form H-bonds with the 2′-OH of the rNTP. The polymerase active site often binds the correct NTP with 10–1000-fold higher affinity than incorrect NTPs [In the active site, the correct NTP to be added to the daughter strand is selected by Watson-Crick base-pairing with the template base. The selectivity for ribose (rNTP) ect NTPs .While viThere are several structural motifs  necessary for catalysis. Motif B contains a consensus sequence of SGxxxT and is located at the junction of the fingers and palm domains [de novo initiating RdRps such as that present in HCV [Motifs A and C have been closely studied because they are located in the active site. Motif C includes the GDD amino acid sequence that is the hallmark of RdRps. These conserved residues are bound to the metal ions  and dsRNA viruses see . Genome et al. [The first X-ray structure of an RdRp was generated for Poliovirus (PV) polymerase in 1997 . X-ray set al. .A characteristic trait of RdRps is the extensive interaction between fingers and palm domains . RdRps hRdRps were originally thought to be found uniquely in viruses. However, in 1971 the first eukaryotic RdRp was found in Chinese Cabbage . Later oThe Flaviviridae family has been widely studied because many members of this family cause diseases in humans. Within this family there are three genera: Flaviviruses, Hepaciviruses and Pestiviruses see . HCV is n”. Residues at the “n” and “n + 1” positions of the template define the P-site and N-site.All known polymerases synthesize nucleic acid in the 5′ to 3′ direction . Thus, rde novo) if this hydroxyl group is provided by the first NTP [de novo mechanism. Most viruses in Picornaviridae and Caliciviridae families utilize a primer-dependent mechanism, but exceptions are found, such as noroviruses in the Caliciviridae family, that synthesize the (−) strand de novo [de novo mechanism has a large thumb domain and narrower template channel suited to accommodate only the ssRNA and NTP [de novo polymerases can be induced to become primer dependent [At the initiation stage, the formation of the first phosphodiester bond is key for polymerization of the nucleotides to begin. To form this phosphodiester bond a hydroxyl group corresponding to a nucleotide 3′-OH is needed. Depending on how this 3′-OH is supplied two mechanisms are differentiated: primer dependent in the case that a primer provides the required hydroxyl group, or primer independent  is dictated by the template. Both HCV and BVDV from the Flaviviridae family have been observed to require high concentrations of GTP for the initiation of RNA synthesis regardless of the RNA template nucleotide [et al. [et al. [de novo initiation or in allosterically regulating the conformational changes needed for replication [When the cleotide ,33 which [et al.  also sug [et al.  pointed  [et al. . We notelication .Because base-pairing alone is insufficient to stabilize the dinucleotide product in the “P-site”, specialized structural elements are employed . Besidesde novo mechanism the first dinucleotide is not sufficiently stable and an initiation platform is needed to provide additional stabilization. This reduced stability sometimes results in abortive cycling for the de novo mechanism. However, an advantage of the de novo mechanism is that no additional enzymes are needed to generate the primer [An advantage of the primer-dependent mechanism is that a stable elongation complex is formed more easily. There is limited abortive cycling, if any, and no requirement for large conformational rearrangements . In conte primer .(1)incorporation of the incoming NTP into the growing daughter strand by formation of the phosphodiester bond(2)release of pyrophosphate(3)translocation along the template.After the template and primer or initiating NTP are bound to the enzyme, the steps required for single-nucleotide addition are :(1)incoThese three steps are repeated cyclically during elongation until the full RNA strand is replicated.2+ or Mn2+) in the active site bound to two conserved aspartic acid residues. These metal ions have been shown to be essential for catalysis via the so-called “two metal ions” mechanism. This mechanism was proposed by Steiz in 1998 [In order to facilitate nucleotide addition, all polymerases have two metal ions  ,14,38,42ng RdRps   and non-nucleoside inhibitors (NNIs) see . NIs binet al. [Four NNI sites have been identified: two in the thumb (NNI-1 and NNI-2) and two in the palm (NNI-3 and NNI-4) see . Brown aet al.  studied This may facilitate their use in combination therapies by degrading complementary functionalities in the enzyme. Understanding the molecular mechanisms by which small molecules in general and NNIs in particular inhibit the function of NS5B is essential for rationally design NS5B inhibitors. Such molecules may ultimately serve as a basis for more efficacious or cost-effective HCV therapies, either individually or in combination.et al. [et al. [et al. [et al. [One informative example that illustrates the useful interplay between determining the roles of structural and functional elements of NS5B and understanding the efficacy of NNIs is provided by recent studies of Gilead pharmaceuticals. Boyce et al.  assessed [et al.  discover [et al. ,47. Boyc [et al.  found th [et al. .et al. [et al. [et al. [et al. [et al. [Simulation studies by Davis and Thorpe suggest that the enzyme C-terminus reduces conformational sampling in NS5B, likely eliminating transitions between the closed and open conformations necessary for the initiation and elongation phases of replication respectively . These oet al. . Other s [et al. ,47 indic [et al. . However [et al.  indicate [et al.  measuredet al. [et al. [In contrast to NNI-2, Boyce et al.  observedet al. ,71. This [et al.  that suget al. [et al. [With regard to palm inhibitors, Boyce et al.  observed [et al.  observed [et al. .et al. [in vitro using enzyme variants without the C-terminus. It is likely that any ligands employing the inhibitory mechanisms described by Boyce et al. [The findings of Boyce et al.  are impoe et al.  would noet al. [Studies such as those of Boyce et al.  or Daviset al. ,47,69 maet al. ,74. We net al. ,47,69.Understanding the molecular mechanisms involved in inhibition by NNIs could facilitate the design and deployment of these molecules. The insights acquired may also be transferable to other polymerases to better understand the relationship between structure, function and dynamics in these enzymes. Due to the fact that individual NNIs can have distinct sites of binding, it should be possible to combine multiple NNIs such that their total inhibitory effect is enhanced relative to applying any given inhibitor on its own . It may Flaviviridae viruses are (+) RNA viruses with RdRp polymerases that utilize the de novo mechanism for initiation. While Flaviviridae polymerases possess elements common to other RdRps such as the fingertips region, they are also unique in possessing the β-flap that may be used as an initiation platform during genome replication.Flaviviridae family within the Hepacivirus genus and employs NS5B as the RdRp that replicates its genome. There are two key steps involved in the replication process: (1) the formation of the initial dinucleotide and (2) the transition from initiation to processive elongation. Structural elements of NS5B that likely have a crucial role in these steps are the C-terminal linker and the β-flap (see The important pathogen HCV is a member of the flap see . Initiatflap see . FinallyThus, the available evidence suggests that NS5B possesses an intrinsic capacity to be regulated via allosteric effectors including NNIs, the β-flap and the C-terminal linker. In addition, the role of these effectors seems to be strongly modulated by the specific context of the interaction. Understanding how these structural elements govern enzyme activity and how they interface with inhibitors is important for understanding the molecular mechanisms of allosteric inhibition in NS5B. Such knowledge paves the way for rational design of inhibitors and combination therapies both for NS5B and for the polymerases to which these insights can be generalized. This information may also be useful in designing enzymes with attenuated activity, as would be required if one sought to develop a strain of HCV that could serve as the basis for a vaccine. Attenuating HCV by degrading the activity of NS5B is one strategy that could prove useful in this regard. One potential drawback to such efforts is the high mutation rate of HCV that results from the error-prone nature of NS5B. However, it is possible that one could circumvent this issue by generating a polymerase that not only possesses reduced efficacy, but also displays increased fidelity and thus faithfully replicates the viral genome.Viral polymerases and, specifically, RdRps share many common structural, functional and dynamic features. Thus, the knowledge obtained in understanding how NS5B functions may be transferable to polymerases from closely related viruses such as Dengue or West Nile virus, or even to other more distantly related polymerases such as reverse transcriptase from HIV and 3D-pol from poliovirus.


Medical image analysis is performed in order to facilitate medical research and ultimately provide better healthcare. It is critical to the advancement of imaging-based medical research, for example, using magnetic resonance (MR) imaging to probe brain structural and functional changes related to a disease or cognitive process.This special issue highlights new methods of signal and image processing, computer vision, machine learning, and statistical analysis and their application in medical image analysis. It is organized into two groups of papers: predictive modeling and image processing.In the first group, we include a set of papers for imaging-derived biomarker detection and clinical decision support systems. The overall theme is how to detect biomarkers characterizing a disease and to build decision support systems using computer algorithms. B. Tay et al. propose a classification scheme for identifying healthy individuals and patients with spinal cord injuries based on fractional anisotropy values obtained from diffusion tensor imaging data. H. Liu et al. address cirrhosis classification based on multimodality imaging and propose a new method to extract texture features for multilabel classification . G.-P. Liu et al. employ deep learning and multilabel learning to construct the syndrome diagnostic model for chronic gastritis. M. Yang et al. describe a method to automatically detect corticospinal tract damage in chronic stroke patients and demonstrate that the detected biomarker is associated with motor impairment. Y. Liu et al. describe a novel machine learning algorithm which combines tract-based spatial statistics and Bayesian data mining to quantify white matter changes in mild traumatic brain injury.The second group of papers consists of a wide range of medical image processing algorithms, including segmentation, visualization, and enhancement. For brain tissue segmentation, S. Ji et al. describe a multistage method based on superpixel and fuzzy clustering for brain MRI segmentation. Y. Zhong et al. propose a method for regularization of fMRI data to address the limitations of traditional spatial independent component analysis. J. Gao et al. describe a global search algorithm based method to separate MR images blindly. Y. P. Du et al. develop a method to reduce partial volume effect with voxel-shifted interpolation and this algorithm substantially improves the detection of BOLD signal in fMRI. Z. Jin et al. use a high-pass filter based method to enhance the visibility of the venous vasculature and reduce the artifacts in the venography. A framework for tracking left ventricular endocardium through 2D echocardiography image sequence is proposed by H. Ketout and J. Gu. E. Bengtsson and P. Malm review automated analysis of the cell samples to screen for cervical cancer.This special issue is selective. Among 27 submissions, 12 were selected. It is our hope that this impressive group of papers will help the medical image analysis community in their efforts to advance imaging-based medical research.Rong ChenRong ChenZhongqiu WangZhongqiu WangYuanjie ZhengYuanjie Zheng


Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity.Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the  Adipose tissue, the largest organ in the human body, was historically considered to be metabolically inert. However, white adipose tissue is now considered an endocrine organ as it secretes adipokines (and hormones) which act locally and distally through autocrine, paracrine and endocrine effects . Althougn-3 (or ω-3) fatty acids, specifically those derived from marine sources. n-3 fatty acids have been suggested to lower the risk of a number of non-communicable metabolic diseases including cardiovascular disease, obesity and diabetes [n-3 polyunsaturated fatty acids (LCPUFA), specifically eicosapentaenoic acid  and docosahexaenoic acid  on white adipose tissue metabolism and function. Although other n-3 fatty acids such as α-linolenic acid  and docosapentanoic acid  are of potential interest, data are limited. A number of reviews on the effect of fish oil or n-3 fatty acids on adipose tissue have previously been undertaken [in vitro cellular studies regarding the specific effects EPA and DHA have on the metabolism and function of white adipose tissue from different depots. Specifically, we will discuss the mechanisms by which EPA and DHA are proposed to reduce adiposity along with discussion regarding how n-3 fatty acids may influence markers of adipose tissue inflammation and cytokine production.A class of fatty acids that has received a lot of attention over the last 30 years is the diabetes ,13,14. Hdertaken ,18,19,20de novo by fish. Fish accumulate them through consumption of water plants, such as plankton and algae, which are part of the marine food chain [n-6) and oleic acid (18:1n-9) may be given, the EPA and DHA content of the fish will decrease [EPA and DHA, commonly referred to as fish oil fatty acids, are not synthesized od chain . Therefodecrease ,23. Maridecrease .Within the human diet, EPA and DHA can be produced from ALA but the capacity of conversion is low in humans, although higher in women of child-bearing age than men . Thus, iAs the fatty acid composition of adipose tissue has a half-life between 6 months and 2 years, it reflects long-term dietary intake along with endogenous metabolism . The abun-3 supplementation are limited and findings inconsistent with some [et al. [et al. [n-3 fatty acid supplementation. However, as visceral adipose tissue samples are often obtained during elective surgery, it would be challenging to undertake a well-controlled study. Taken together, the data presented in n-3 fatty acid intake, over the weight maintenance period [Studies measuring the change in adipose tissue fatty acid composition, as a marker of compliance to ith some ,30,31,32ith some ,34 notin [et al. . Of notee period . These ci.e., body weight, BMI, waist circumference or waist to hip ratio). From the 21 studies  they found no evidence to support an anti-obesity role of n-3 LCPUFA [et al. [Measuring an anti-obesity effect of increased EPA and DHA consumption in humans is challenging, not least as there are many other factors to control for  and methodology sensitive to small changes in adipose tissue mass needs to be used. In 2009, Buckley and Howe  reviewed3 LCPUFA . It is p [et al.  noted th [et al. , as well [et al. . Moreove [et al. ,46,47,48 [et al. ,53,54,55 [et al. ,67,68,69de novo lipogenesis or re-esterification of fatty acids within the tissue; alternatively it may occur due to a lower flux of fatty acids to the tissue. In the latter situation, fatty acids could be repartitioned to other tissues (such as muscle) for disposal, rather than going to adipose tissue for storage. In humans, the absolute contribution of de novo synthesized fatty acids to adipose tissue triacylglycerol is potentially small [de novo lipogenesis (or fatty acid esterification/re-esterification) in vivo in humans is challenging. Therefore, it is not surprising that studies have not been undertaken investigating how EPA and DHA supplementation influence these processes in humans. Although not a direct measure of fatty acid synthesis or esterification/re-esterification within the tissue, the measurement of the expression of genes related to these processes provides some insight to the effect of EPA and DHA on these processes. Camargo et al. [A decrease in fatty acid deposition within adipose tissue may occur due to a decrease in triacylglycerol synthesis via decreased ly small  and measo et al.  reportedet al. [-/-) mouse model whilst others have typically used C57Bl/6 mice or Wistar rats.Work in animal models has typically found EPA and DHA to limit lipid accumulation in adipose tissue . The majet al.  did not et al. . This diet al. [et al. [Studies investigating the effects of dietary EPA and DHA on adipose tissue function have also been undertaken in fish . Todorceet al.  demonstret al. . Diet coet al. . Further [et al.  in grassn-3 fatty acids may decrease adipogenesis and lipogenesis and thus exposure in utero to these fatty acids may lower the risk of obesity in offspring. In 2011 Muhlhausler and colleagues [n-3 LCPUFA supplementation during pregnancy and lactation on postnatal body composition of offspring. Although 13 potential studies were identified, only four met the inclusion criteria and the authors found from albeit limited data that there was a suggestion that the offspring from n-3 LCPUFA supplemented dams had a lower fat mass [n-3 LCPUFA [n-3 fatty acids decreases adipogenesis and lipogenesis and is an area that warrants further investigation.The process of adipogenesis (or an increase in fat mass) involves the differentiation of preadipocytes to mature adipocytes, is a complex and tightly regulated process involving a cascade of transcription factors which are sensitive to the nutritional environment . In a colleagues  reviewedfat mass . In cont3 LCPUFA . Thus itin vitro evidence regarding the mechanistic effects of EPA and DHA on triacylglycerol accumulation/lipid deposition comes from the clonal murine cell line, 3T3-L1  the cells were exposed to, along with the duration of exposure.Overall, the effects of EPA and DHA as well as EPA n-3 fatty acids on adipocyte apoptosis and only limited work has been undertaken in animal and in vitro cellular models. Although outside the scope of this review, there have been a large number of studies investigating the effect of n-3 fatty acids and cancer in relation to apoptosis, as reviewed by Wendel and Heller [To our knowledge, there have been no studies in humans investigating the effect of d Heller .in vitro and in vivo studies have reported apoptosis in white adipose tissue along with alternations in adipose tissue mass. Thus consideration is required when looking at adipose tissue mass in relation to cell number as they might be partly regulated by pre-adipocyte/adipocyte apoptosis [et al. [et al. [n-3 fatty acids and regulation of cellularity in adipose tissue. Using a rodent model the authors suggested that increased intakes of EPA and DHA  but alsiewed by , there am et al.  reported [et al.  treated in vitro studies suggests that high doses of EPA and DHA may induce adipocyte apoptosis. How targeting the apoptotic pathway in white adipose tissue would decrease obesity and influence adipose tissue function and overall metabolic health in humans remains to be elucidated.Taken together, the available data from animal and n-3 fatty acids [n-3 fatty acids (EPA and DHA) improved adipose tissue insulin sensitivity compared to diets high saturated or monounsaturated fat in individuals with the metabolic syndrome [in vitro studies, translation to the appropriate dose, along with duration required to see an effect in humans needs to be elucidated.Although an increase in fatty acid oxidation, via β-oxidation has been suggested to play a role in a reduction of triacylglycerol accumulation in adipocytes, evidence for this in white adipose tissue is limited; fatty acid oxidation and mitochondrial function has been studied more often in brown adipose tissue. The number and activity of mitochondria within adipocytes has been suggested to contribute to insulin resistance and type 2 diabetes . Changesty acids   has been reported to increase in young, healthy men (n = 5) after 3 weeks of supplementation with fish oil (6 g/day) when compared to a control diet containing equal amounts of total dietary fat [et al. [et al. [tary fat . Only a  [et al.  reported [et al.  reportedIn vitro cellular studies have found increased β-oxidation in 3T3-L1 adipocytes after incubation with 100 µM of EPA for 24 h [et al. [et al. [n-3 fatty acids on mitochondrial oxidative phosphorylation (OXPHOS) and fatty acid oxidation in white adipose tissue. In this comprehensive review they reported that in a murine model, supplementation with n-3 fatty acids in combination with mild calorie restriction induced mitochondrial OXPHOS in epididymal white adipose tissue only, independent of UCP1 induction; other studies in rodents have reported increased levels of UCP1 mRNA and/or protein in BAT in response to n-3 fatty acid supplementation [in vitro cellular model of isolated stromal-vascular (SV) cells from inguinal adipose tissue of suggested that EPA enhanced energy dissipation capacity by recruiting brite adipocytes to stimulate oxidative metabolism. From the limited data available it appears that EPA and DHA increase fatty acid β-oxidation in adipocytes, however the mechanisms responsible and the effect on mitochondrial OXPHOS and thermogenesis in human adipose tissue remains to be elucidated.for 24 h . The incfor 24 h . As EPA for 24 h . EPA andfor 24 h . Todorce [et al.  demonstr [et al. . In 2013 [et al.  reviewedentation . Recentlentation  using anAn expansion of adipose tissue mass, is often associated with macrophage infiltration which may lead to inflammatory responses, which have been implicated in the development of pathological changes in adipose tissue physiology ,7,8,9. Tn-3 fatty acid supplementation, for periods between 8 weeks up to 6 months, on the expression of genes related to inflammation in human subcutaneous white adipose tissue have been undertaken. Overall results are variable, with some suggesting consumption of EPA and DHA decreases the expression of genes related to inflammation, whilst other report no change  of individuals with chronic kidney disease (CKD) who were randomised to take either a low (n = 6) or high (n = 6) dose of MaxEPA for 10 weeks. In contrast, Itariu et al. [Studies investigating the effect of o change . For exa  per gram of fat for 6 weeks resulted in a reduction in macrophage infiltration in combination with decreased expression of inflammatory genes in white adipose tissue [et al. [−/− mice and showed similar results to Todoric et al. [α, metalloprotease 3 (MMP3), and serum amyloid A3 (SAA3) in white adipose tissue [n-3 fatty acids have the potential to modulate immune response in adipose tissue.Work in murine models has found consumption of e depots . Todoric  or in measuring the effects of n-3 fatty acids on leptin at different stages of adipogenesis. Culturing human primary adipocytes in either EPA or DHA resulted in a down-regulation of IL6 and TNFα secretion [et al. [in vivo, as the anti-inflammatory effects of EPA and DHA on TNFα expression would be modulated through the direct effect of these fatty acids on macrophages; cells that were not present in their in vitro culture [The effects of ipocytes  and primipocytes . Reselan [et al.  reported [et al.  and Pere [et al. , where e [et al. . Thus, tecretion . In contecretion ; the und [et al.  who note culture . It remavs. cell-lines). Moreover, in vitro cellular cells often investigate the effects of EPA and DHA on adipocytes and it is plausible a different response may be found in whole adipose tissue due to the presence of other cell types  and their interaction with adipocytes. Although the effects of n-3 fatty acid supplementation on the fatty acid composition of subcutaneous abdominal and gluteal adipose tissue have been investigated, mechanistic studies (in vivo and in vitro) appears to be limited to primarily subcutaneous abdominal adipose tissue and/or adipocytes. Evidence for an effect of n-3 fatty acids in human visceral adipose tissue is sparse and therefore not well understood. Evidence for a reduction in fat accumulation in animal models, along with an anti-inflammatory effect appears to be consistent when intakes of EPA and DHA are high ; however recommendations for human intakes are between 0.5% and 2% of total energy intake [In recent years evidence demonstrating that an increased consumption of EPA and DHA may have a beneficial effect on white adipose tissue function and metabolism is starting to emerge. Although current literature cannot support an exact mechanistic role of EPA and DHA on adipose tissue biology it is apparent that these fatty acids have the potential to be potent modulators of adipose tissue and adipocyte function. More work has been undertaken using animal and cell models therefore consideration is required regarding the dose and duration of EPA and DHA, the animal and cell model used (e.g., primary y intake . Thus, t


The starting point of modern biosensing was the application of actual biological species for recognition. Increasing understanding of the principles underlying such recognition , however, has triggered a dynamic field in chemistry and materials sciences that aims at joining the best of two worlds by combining concepts derived from nature with the processability of manmade materials, e.g., sensitivity and ruggedness. This review covers different biomimetic strategies leading to highly selective (bio)chemical sensors: the first section covers molecularly imprinted polymers (MIP) that attempt to generate a fully artificial, macromolecular mold of a species in order to detect it selectively. A different strategy comprises of devising polymer coatings to change the biocompatibility of surfaces that can also be used to immobilized natural receptors/ligands and thus stabilize them. Rationally speaking, this leads to self-assembled monolayers closely resembling cell membranes, sometimes also including bioreceptors. Finally, this review will highlight some approaches to generate artificial analogs of natural recognition materials and biomimetic approaches in nanotechnology. It mainly focuses on the literature published since 2005. One could regard the advent of plastics as the starting point of this development. Whereas in the beginning, the main fascination arose from being able to generate unprecedented materials, the aspect of studying natural structures as a model for technologically processed materials has been gaining increasing importance. This is perfectly reflected in the following statement: “The inspiration from nature is expected to continue leading to technological improvements and the impact is expected to be felt in every aspect of our lives” . One of Molecular imprinting actually aims at designing “artificial receptors” or “artificial antibodies” that show biological functionality, despite consisting of a fully artificial, synthetic matrix. Binding to the target analytes occurs by the same non-covalent interactions as in biological systems, but still the backbone is completely different. In the case of membrane mimics, two different strategies are currently followed: the first uses artificial polymers that either repel biospecies or attract them and hence, establish affinity layers for biosensors. These are sometimes combined with natural or nature-analogous receptor/indicator materials to make use of specific interactions in an artificial environment and thus, stabilize the receptor of interest. The second one aims at mimicking natural cell membranes, e.g., with Langmuir–Blodgett techniques and immobilizing  receptors within them. Compared to polymers, this should immobilize the respective target receptor in an environment that is much closer to its original one.etc. aim at focusing on the functional part of a biomolecule and reproducing only this functional part to make synthesis simpler. Nanoparticles and nanostructures themselves are not necessarily biomimetic, but, in combination with different receptor strategies, they open the way for novel biosensing approaches. Within this review, we will highlight sensor strategies falling into these categories and discuss the different aspects of recognition within the systems.Artificial peptides, DNAzymes, Molecular imprinting is a very straightforward technique to achieve artificial receptors based on highly cross-linked polymers for a wide range of analytes in almost any dimensions ,4. In deAfter a groundbreaking paper by Alexander and Vulfson , the litet al. [d) of MIP for the template peptide was similar to that of monoclonal antibodies, namely 3.17 nM, calculated through Scatchard analysis. A limit of detection (LoD) of 2 ng/mL was achieved and practical performance was tested on real samples of human urine with satisfactory results. According to the authors, these LoD of HIV-1 gp41 were comparable to the reported ELISA method. On the basis of high its hydrophilicity and biocompatibility, dopamine excels over other functional monomers for this application. Furthermore, this simple epitope method can be adapted to other biomolecules. A further diagnostically important protein is myoglobin, which, among others, can be utilized as a cardiac marker. Rather than going for conventional epitope imprinting, Liao et al. [et al. [Firstly, let us regard “straightforward” protein imprinting: human immunodeficiency virus type 1 (HIV-1) related protein , for instance, has attracted scientific interest, because it is the transmembrane protein of HIV-1 and plays a crucial role in membrane fusion between individual virions and T cells during infection. As such, it plays an important role in the efficacy of therapeutic intervention, because it indicates the extent of HIV-1 disease progression. By implementing the epitope imprinting strategy—where only a substructure of the analyte of interest is used as a template—Lu et al.  developeo et al.  presente [et al. , for ins−1 enzyme and response times of a few minutes. The highest sensitivity was achieved in the case of solution-based imprinting with native trypsin: this system could differentiate denatured trypsin from the native form of enzyme. As already mentioned above, in the case of entire cells, so-called “plastic” copies of the original cells are promising templates for imprinting. For instance, Saccharomyces cerevisiae—baker’s yeast—undergoes a range of growth stages, each of which may be recognized biomimetically. Seidler et al. [et al. [S. cerevisiae and S. bayanus, which strongly corroborates the claim that the functional pattern of the initial yeast cells is correctly reproduced within the polymeric matrix; both native and “plastic” cells yielded the same sensitivity while selectivity exceeded a factor of three in the second case.Sensors reached detection limits of 100 ng·mLr et al.  produced [et al.  fabricatet al. [MIP can withstand harsh environments and yet retain recognition abilities for the detection of species in complex media. In this connection, Hayden et al.  further et al. .et al. [Double imprinting approaches can also be applied to literally generate “plastic antibodies” that are inherently robust and selective. For instance, Schirhagl et al.  developeet al. [Of course, such double-imprinting techniques are especially interesting for generating antibody replica. If immunoglobulin is applied as a template in the MIP, and the resulting substrates as stamps in a second imprinting procedure, this leads to “positive images” of natural antibodies in the polymer. Inherently, such double-imprinted layers can be produced in bulk for industrial processing and are more robust as compared to natural counterparts. Additionally, cost-efficiency increases, because the templates are required only in the first step. MIPs have also been proposed for cell surface proteins, such as wheat germ agglutinin (WGA) lectin, a model compound for interactions between viruses and cells. Wangchareansak et al.  developeWhen comparing MIP-based and natural recognition materials with one another, the following conclusions can be drawn: typically. the selectivity of MIP is in the same order of magnitude as that of natural antibodies or ligand–receptor interactions, or they may even reach it. Mass sensitive measurements revealed that in the case of proteins, MIP functions as a “condensation nuclei”, thus, those systems feature a strongly increasing sensitivity. BET analysis of the WGA MIP mentioned above revealed that the sensor signal at 160 µg/mL WGA corresponds to an average of ten molecular layers on the MIP, whereas affinity to NIP is low. However, the overall sensitivity of any given biosensor is determined by the combination of the recognition material and the respective transducer.et al. [et al. [2-glycoprotein-I (β2GP-I): β2GP-I binds to negatively charged membranes and exposes the correct epitopes only in this bound state. Otherwise, the binding sites are hidden within the protein, which makes immunoassays with the whole protein useless. To provide an environment comparable to the physiological conditions in the human body, the authors co-immobilized a multilayer assembly of covalently attached polymeric DCPEG/PEG (lipid anchor) and a liposome membrane on the transducer. Quantification of anti-β2GP-I antibodies and calibration of the sensor chip in buffer was done using reflectometric interference spectroscopy. This strategy can be extended to distinguish between healthy and ill individuals within routine clinical diagnostics. Furthermore, it is an impressive example for the fact that in bioanalysis not only the target analyte plays a role, but also its environment. In this way, the sensor surface mimics not “only” an antibody or binding site, but also the membrane structure necessary to ensure biological activity.A different approach suggests synthesizing MIP membranes have been reported based on self-assembly to more closely mimic natural functionality, a huge amount of which actually happens in (cell) membranes. For example, Zhao et al.  used sucet al. . However [et al.  further  [et al.  have devet al. [in vivo diagnostics without showing any significant response to the anti-Salm-functionalized surface . Astonishingly, high selectivity and sensitivity (<3 ng/cm2 for undiluted blood plasma) was achieved for an activated leukocyte cell adhesion molecule , a potential carcinoma biomarker. Such combinations of artificial and natural materials have also been reported by other groups. Henry et al. [Membranes play a key role for life, as they are interfaces between cells and their surroundings. As such, they are also interesting starting points for biomimetic sensor development. Here, two seemingly contradictory goals are of main interest: on the one hand—and as mentioned already in the previous section—the design of artificial receptors, and on the other hand, effectively preventing nonspecific protein adsorption from real-life media , which is absolutely key for implanted medical devices. Addressing this issue, Vaisocherova et al.  applied y et al. , for insi.e., not in combination with natural materials, the aim can also be facilitating the formation of adhered biolayers rather than preventing them. One example for this strategy has been reported by Mueller et al. [et al. [When using pure polymer films, r et al. , who mod [et al.  applied et al. [et al. [6 particles/mL after short incubation and can be monitored by naked eye or readily available scanners. Although, detection limits are a few order of magnitudes higher than in modern PCR strategies, the technique offers unparalleled simplicity in its approach.Polymer films can also function as “affinity receptors” themselves: Ibrišimović et al.  for inst [et al. , who con [et al.  used glaet al. [−6 M to 10−2 M. In a related, yet completely different approach, Yang et al. [Such straightforward receptor materials, of course, allow for evaluating novel transducers, e.g., derived from modern nanotechnology as bio(mimetic) sensors. Chang et al. , for insg et al.  synthesiet al. [et al. [Salmonella typhimurium can be detected in situ with highly selectivity at 90% relative humidity by using a lead zirconatetitanate (PZT)/gold-coated glass cantilever. Its sensitivity was found to be 1 × 103 and 500 cells/ml in 2 mL of liquid with a 1 and 1.5 mm dipping depth, respectively. Such a limit of detection is more than one order of magnitude lower than that of the commercial Raptor sensor.Generally speaking, electrochemical impedance spectrometry is gaining increasing importance in the detection of bioanalytes down to viruses  due to iet al. , chlorid [et al.  showed tet al. [2O2 produced in situ can trigger ECL reaction in the sensing layer. In another approach of using supported lipid bilayers (SLB) mimicking natural structures, Choi et al. [in vitro by label-free surface plasmon resonance spectroscopy (SPRS). Biomimetic sensor chips were fabricated by the fusion of unilamellar lipid vesicles on a hydrophilic Au surface for SPRS. This setup enables real-time measurements of protein aggregation. Self-assembly is one of the fundamental driving forces of life that leads, for example, to the phospholipid bilayers constituting cell membranes. The Langmuir–Blodgett technique is a way to build up artificial membranes. It makes it possible, for instance, to immobilize lipid bilayers (LB) that themselves can stabilize biomolecules to achieve biomimetic “cell membranes.” In contrast to the methods previously mentioned, the biomolecule is therefore immobilized in an artificial membrane that more closely resembles a natural one, as compared to a polymer thin film. Using this approach, Jiao et al.  demonstri et al.  demonstrThe respective membrane behavior was analyzed by investigating specific types of Cu/Zn-superoxide dismutase (SOD1) species, which are linked to neurodegenerative disease. In an unusual manner, SOD1 aggregates degenerate membranes closely related with aberrant characteristics of conformationally disordered and/or mostly aggregated proteins. The presented biomimetic sensor build-up can be further applied for the development of biomarkers to analyze different injured cells.In recent years, peptide-based sensors have been developed, including a range of different strategies. One of these can be regarded as biomimetic, namely synthesizing peptides that are designed to make use of well-known interactions between a single or a few amino acids and the respective target compounds. However, selecting them can be difficult, when the target molecule is small and/or it considerably changes its conformation upon immobilization . Other b9 hematologic cells). To cope with the challenge, Myung et al. [2. Hence, they can be separated from one another and detected finally by CTC devices that offer enhanced selectivity and sensitivity without involving complex fabrication processes. These differences are governed by the fact that the ratio of cell rolling and stationary binding on the surface depends on the respective immobilized artificial peptide. When designing artificial recognition sequences, applying molecular modeling of the actual interaction center usually substantially improves the overall experimental time, as candidate receptors can be selected “in silico.” An example for this is the rapid and direct QCM detection of the mussel heat shock protein HSP70 in crude extracts of the mussel mantle by artificial heptapeptides [The detection of circulating tumor cells (CTCs) is clinically important for diagnosis and prognosis of cancer metastasis. Separation and detection of these cells are challenging due to extremely low quantity in patient blood  of that species and immobilized it onto a streptavidin-coated dextran sensor surface. Employing surface plasmon resonance (SPR), detection limits of 0.5 nM were obtained with linearity from 5 to 1,000 nM. Escherichia coli and S. aureus yield no significant signal in selectivity pattern studies. Salmonella detection.An example for a biomimetic DNA-based system has been presented by Pelossof et al. . They cog et al.  developeet al. [Molecular self-assembly processes are crucial for generating new functional materials with suitable prosperities for sensor development. This concept is biomimetic to its core, as nature has, for example, constructed thousands of nanostructures from 20 amino acids . Chemicaet al.  discusseet al. ,43,44.et al. [Motivated by biological processes, Sundh et al.  developeet al. [10) onto the modified electrode simultaneously. Using cyclic voltammetry, a sensitivity of −0.04988 μA/mM for NADH with the modified electrode could be achieved.The outstanding effect of nanoparticles (NP) has been demonstrated by Lee et al.  through 3O4 nanoparticles (CMNP) as signal amplifiers, Lin et al. [Escherichia coli as a target. For this purpose, CMNP were functionalized with a chitosan layer for binding negatively charged E. coli via electrostatic attraction. The CMNPs binding to the sensor resulted in increased mass loading ultimately decreasing its resonance frequency without interference by serum proteins. The method can be extended further to other bacteria. For example, slightly varying the NP approach, the immobilized Au nanoparticles were functionalized with single-strand DNA (ssDNA) probes specific to the eaeA gene of E. coli O157:H7 [et al. [Similarly, employing chitosan-modified magnetic Fen et al.  reported O157:H7 . First r O157:H7 . In a di [et al.  demonstret al. [2O2. Combining the above two strategies , Kim et al. [et al. [3O4) and multi-walled carbon nanotubes (CNT) coated onto indium tin oxide (ITO) coated glass plate by electrochemical synthesis of polyaniline (see N. gonorrhoeae) genosensors leading to detection limits of 1 × 10−19 M bacteria within 45 s of hybridization time at 298 K.Mesoporous materials constitute another interesting class of substrates for biomimetic sensor setups. For instance, Li et al.  synthesim et al.  employed [et al. : they deline see . The reset al. [et al. [et al. [2O3 magnetic nanoparticles and fluorescent quantum dots were embedded together into single swelling poly(styrene/acrylamide) copolymer nanospheres. In this way, fluorescent-magnetic bifunctional nanospheres can be generated. Their approach included the fabrication of smart wheat germ agglutinin (WGA)- trifunctional nanobiosensors (TFNS), peanut agglutinin (PNA)-TFNS and Dolichos biflorus agglutinin (DBA)-TFNS composites that combine high fluorescence yield, magnetic properties and selective detection of N-acetylglucosamine, D-galactosamine and N-acetylgalactosamine residues on the A549 cell surface. Such biomimetic lectin-modified nano biosensors (lectin-TFNS) can thus be employed for analysis of glycoconjugates on A549 cell surface.Being a comparably new class of nanomaterials, quantum dots (QDs) are considered to be promising matrices for sensor layers. For example, employing QDs as biomimetic material, Huang et al.  develope [et al.  applied  [et al. . Fe2O3 mAs can be seen, mimicking biological functionality has become a field of substantial scientific interest and has generated a range of different strategies for actually reaching that goal. Whereas, the idea behind molecular imprinting is to generate as high selectivity as possible in a fully artificial material, polymer thin-film coatings and self-assembled monolayers follow different goals and strategies: first, they are optimized to tune the affinity between cells and surfaces, which can lead both to materials preventing cell adhesion, as well as to ones supporting it. Furthermore, such systems are useful to incorporate and stabilize biological receptors, hence, generating a monofunctional surface containing a specified interaction center.Diagnostics and healthcare, as well as security topics  are the main driving forces behind biosensing. Those fields do not necessarily require reversible sensors, but disposable systems. Therefore, they do not require the main advantages of biomimetic materials, which are their ruggedness and re-usability.Sensitivity of biomimetic materials reaches, or even exceeds, that of e.g., antibody-based test formats. However, polymerase chain reaction (PCR) has made substantial progress during the last two decades allowing for extremely low detection limits for microorganisms due to its amplification properties.The market of diagnostic tools is inherently conservative and thus reluctant to replace well-established techniques with novel ones due to lack of experience or expertise.Especially in MIP, studies on batch-to-batch reproducibility and upscaling to (pilot) plant level still have to be done.Compared to the substantial scientific effort, however, such systems are commercially not (yet) very successful. It is difficult to attribute these to concrete reasons. However, the following points definitely do play a role:In conclusion, biomimetic sensing is still a matter of research at the academic level, rather than commercial development. Replacing—or at least complementing—bioreceptors will thus not be possible in the immediate future. However, the main advantages of artificial systems will make them interesting candidates for measuring applications requiring long-term stability, such as process control or monitoring air/water quality over extended periods of time. Once established in those markets, application in the diagnostic area seems more realistic, as artificial materials offer inherent cost advantages.