Plant is endowed with sessile habit and nutrient acquisition mainly through the root organ, which also provides an excellent model to study stem cell fate and asymmetric division due to well-organized cell layers and relatively simple cell types in root meristem. Besides genetic material DNA wrapped around histone octamer, chromatin structure determined by chromatin modification including DNA methylation, histone modification and chromatin remodeling also contributes greatly to the regulation of gene expression. In this review, we summarize the current progresses on the molecular mechanisms of chromatin modification in regulating root development. The root system constitutes the underground world of a plant, and it takes charge of nutrient and water supply for the whole plant under normal and stress environments. The developmental status of the root system directly determines the plant survival and performance of leaves, stems, flowers, fruits, and seeds, which are closely related to animal and human life. Compared with the aerial part, the building unit of a root system is simple and mainly consists of primary and lateral roots (LRs) without substantial difference in appearance. An intact root system is derived from the tiny root apical meristem (RAM). Proliferation and differentiation of RAM give rise to different types of root cells and tissues.Transcription factors combined with phytohormones, small signaling molecules, and miRNAs play an essential role in regulating the stem cell fate and RAM maintenance during root development . For instance, active marker histone acetylation and repressive marker histone deacetylation are catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively  homologs , three Su(z)12 homologs , a single ESC homolog (FIE), and five p55 homologs (MSI1–MSI5). PRC1 core subunits consist of two RING1 homologs (AtRING1a/b), three Psc homologs (AtBMI1a/b/c), a Pc equivalent (LHP1), and a plant-specific component EMF1, without the Ph counterpart  proteins associated with repressive genes and the trithorax group (TrxG) proteins associated with active genes  and atrichoblast/non-hair cell (N) in an alternative arrangement, providing a well-characterized system for studying the relationship between root epidermal cell fate decision and positional cue from underlying cortical cells /IAA14 (mIAA14) protein with enhanced inhibiting capacity on the downstream targets ARF7/19 , which is a core component of several HDAC corepressor complexes , resulting in formation of decreased CDF4 protein gradient from differentiated columella, CSCs to QC, which is opposite to the WOX5 protein gradient and permits the exit of stem cell descendants from the stem cell state  in roots  family ; it downregulates auxin maxima in roots, thereby inhibiting the establishment of founder cells during LR initiation  display a certain proportion of “pkl-root” phenotype , FUSCA3 (FUS3), LEAFY COTYLEDON2 (LEC2), and LEAFY COTYLEDON1 (LEC1)  and H3K4me3 through the CW domain or PHD domain and H3K27me3 through the PHD domain  and reduction in levels of gene repression mark H3K27me3 in seedling  and cysteine and tryptophan residue-containing domain (CW), which usually act as histone code reader modules, and the ethylene-responsive element binding factor-associated amphiphilic repression (EAR) domain that functions as a repressive motif to recruit corepressors  but is enhanced by GA biosynthesis inhibitor paclobutrazol  can recognize the active mark H3K4me3 through the PHD-domain and interact with the RAWUL domain of PRC1 RING-finger proteins through the PAL domain  and many additional types  pathway by directly targeting the chromatin of several PIN genes  and affecting auxin distribution. PLT2 overexpression can partially rescue a brm SCN defect  in distinct plants will deepen our understanding of root function and phylogenesis. Root developmental progresses is closely associated with stem cell fate transition during RAM differentiation, where the dynamic change and action mechanism of epigenetic marks in specific cell lineage need to be addressed.clf mutant with curly leaf, early flowering and homeotic conversion of floral organ /Cas (CRISPR-associated) system provides an extremely powerful and labor-saving tool for targeted gene editing. This tool can be used to target several genes simultaneously for fast and efficient generation of high-order mutants (Cong et al., D-HC and YH wrote the manuscript. CJ collected the raw materials. J-PS provided important suggestions.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Family members and friends are the main providers of care for persons living with dementia. However, dementia caregivers are at greater risk than other caregivers of experiencing negative caregiving consequences. Despite the development of evidence-based programs to support dementia caregivers, few health or social service organizations offer any of these programs due, in part, to a lack of knowledge about their availability. Best Practice Caregiving is a newly launched website where professionals can get detailed information about these programs. Data collected to develop Best Practice Caregiving are analyzed for a sample of 42 evidence-based dementia caregiving programs to describe similarities and differences among programs including gaps in assistance available from these programs. Results show 64% of programs are delivered to caregivers only while the remaining are delivered to the caregiver and/or persons with dementia. Nearly half (43%) of the 42 programs are delivered in-person, 38% by phone, with 17% delivered all or in part online. Most programs are delivered by professionals (86%) followed by trained lay leaders (40%) and self-guided (12%). Most programs (95%) provide assistance with coping with illness/caregiving and the relationship of the dyad. Fewer than half of the programs assist caregivers with issues regarding finances (45%), end-of-life care (43%), and medical care (40%). Data from 233 delivery organizations show the most common challenge was getting caregivers to accept and complete the program (86%). Delivery sites reported more success with funding the program  than with marketing and recruiting participants (mean=6.7).


Type 2 diabetes mellitus (T2DM) and Heart Failure (HF) are two complex multifactorial diseases that can coexist and strongly amplify each other, suggesting overlapping mechanisms contributing to disease state. T2DM patients with HF have a higher risk of mortality and hospitalization for HF than HF patients without T2DM. Therefore, there is an increasing necessity to find new diagnostic instruments and treatments to improve clinical outcomes in T2DM subjects with HF , current research demonstrate many additional important and possibly beneficial direct effects of these drugs on endothelial cells and cardiomyocytes. SGLT2 inhibitors can normalize elevated sodium and calcium levels in cardiomyocytes through inhibition of the cardiac sodium-hydrogen exchanger, improve vascular function and activate anti-oxidant systems and intracellular stress signals such as AMPK and reduce inflammatory pathways. Further research will have to demonstrate to what extent these cellular cardiac mechanisms contribute to the large beneficial effects of SGLT2i's in clinical trials. Despa then goes on to describe that sodium is often increased in the failing and diabetic cardiac cell. Elevated intracellular sodium can then cause oxidative stress and augments the sarcoplasmic reticulum Ca2+ leak, thus amplifying the risk for arrhythmias and promoting heart dysfunction. Alterations in Na+ extrusion and/or Na+ uptake that underlie the [Na+]i increase in heart failure and diabetes are discussed, and emphasis is placed on the emerging role of Na+ -glucose cotransporters in the diabetic heart. Doliba et al. subsequently demonstrate the functional and energetics consequences of elevated sodium in the diabetic cardiomyocyte in their pioneering studies in this field. Their work clearly indicates that raising sodium in the cardiac cell will directly result in impaired mitochondrial function, possibly explaining the often observed energetic problems in the diabetic heart. These reviews all point to the importance of ionic homeostasis and disturbances in the setting of diabetic cardiomyopathy, cardiac arrhythmias, and the elevated incidence of heart failure in T2DM patients.Liu et al. evaluated the clinical effects of Black garlic in patients with ischemic heart failure. They found that black garlic treatment improved cardiac function in terms of left ventricular ejection fraction and the scores of quality of life (QOL) and decreased circulating BNP precursor N-terminal (Nt-proBNP) by increasing antioxidant levels.The article by Koyani et al. studied the effects of saxagliptin and sitagliptin (anti-hyperglycemic drugs that have been shown to inhibit dipeptidyl peptidase 4 -DPP4) in mouse ventricular cardiomyocytes. The authors showed that saxagliptin (but not sitagliptin) impaired Ca2+ transient relaxation and prolonged action potential duration in cardiomyocytes. They suggested that these results are linked to saxagliptin-DPP9 interaction and following impairment in Ca2+/calmodulin- dependent protein kinase II (CaMKII)- phospholamban (PLB) and protein kinase C (PKC) signaling.Trotta et al. investigated the anti-hypertrophic effect of the melanocortin receptor 5 (MC5R) stimulation in cardiomyocytes exposed to high glucose. The authors showed that MC5R agonists increased viability and reduced total protein in cell stimulated with high glucose via reduced GLUT1/GLUT4 ratio at the plasma membrane and increased intracellular phosphoinositide 3-kinase (PI3K) activity. In addition, MC5R stimulation showed beneficial effects on cardiac function and hypertrophy paralleled by significantly reduced blood glucose levels in a rat model of diabetes (streptozotocin-induced).We have arrived at exciting times in the world of diabetes and heart failure. At last, several novel antidiabetic drugs have shown large cardiovascular benefits in T2DM patients. Understanding the causal mechanism of these effects are now crucial in order to further our understanding of the interaction between diabetes and heart failure, possibly also offering new therapeutic strategies to combat heart failure in the absence of diabetes.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This study is a secondary analysis of the Outcome and Assessment Information Set (OASIS) and administrative billing records of 6,153 adults ≥ 65 years old who received home health (HH) from a not-for-profit HH agency in upstate New York in CY 2017. We evaluated the association between the use of home health services (HH) with the hazard of unplanned facility admissions among Medicare patients with and without Alzheimer’s disease and related dementia (ADRD). Outcome was time from HH start of care to an unplanned facility admission of any type, including the hospital, nursing home, or rehabilitation facility. Independent variables included weekly intensity  of each discipline, including skilled nursing (SN), physical therapy (PT), occupational therapy (OT), social work (SW), and home health aide (HA), separately. ADRD was identified by diagnosis (ICD-10 codes) and cognitive impairment . In multivariable Cox Proportional hazard models that adjusted for time-varying effects of HH intensity, receiving the highest intensity of SN (3.3 visits of 2.78 hours per week) and PT (2.5 visits of 2 hours per week) was related to up to a 54% and 86% decrease, respectively, in the hazard of unplanned facility admission among patients with ADRD , and decreases of 56% and 90% respectively among patients without ADRD . This is the first study in the United States showing that receiving a sufficient amount and appropriate mix of HH services was associated with substantially reduced risk of unplanned facility admission among patients with ADRD by up to 86%.


The oomycete-specific ITS primers published by Oomycetes, which probably results in a lower proportion of this group in metabarcoding studies. We hereby provide the updated figure (Figure Closer examination revealed that the sequence of primer ITS1oo in Figure PageBreak


Therapeutic strategies to restore hearing and balance in mouse models of inner ear disease aim to rescue sensory function by gene replacement, augmentation, knock down or knock out. Modalities to achieve therapeutic effects have utilized virus-mediated transfer of wild type genes and small interfering ribonucleic acids; systemic and focal administration of antisense oligonucleotides (ASO) and designer small molecules; and lipid-mediated transfer of Cas 9 ribonucleoprotein (RNP) complexes. This work has established that gene or drug administration to the structurally and functionally immature, early neonatal mouse inner ear prior to hearing onset is a prerequisite for the most robust therapeutic responses. These observations may have significant implications for translating mouse inner ear gene therapies to patients. The human fetus hears by gestational week 19, suggesting that a corollary window of therapeutic efficacy closes early in the second trimester of pregnancy. We hypothesize that fetal therapeutics deployed prior to hearing onset may be the most effective approach to preemptively manage genetic mutations that cause deafness and vestibular dysfunction. We assert that gene therapy studies in higher vertebrate model systems with fetal hearing onset and a comparable acoustic range and sensitivity to that of humans are an essential step to safely and effectively translate murine gene therapies to the clinic. Gene replacement, augmentation, knock down and knock out strategies have been elucidated to ameliorate the effects of deleterious mutations that cause hearing loss and vestibular dysfunction in mouse models of human inner ear disease. Table Vglut3 knockout mouse after round window membrane inoculation at postnatal day 1–3 , compound action potentials (CAP) and acoustic startle -mediated gene transfer to the sensory epithelium by delivery through the round window membrane  introduces a cryptic splice site in exon 3 of the PDZ  domain scaffolding protein, harmonin and generates a frameshift with premature stop codon. The splicing machinery strongly prefers the cryptic splice site though wild type splicing is not precluded. The Ush1c c.G216A knock-in mouse accurately models the hearing and vestibular abnormalities seen in USH1C patients  to interfere with pre-mRNA splicing from the cryptic splice site and enhance wild type splicing. ASO therapy restored functionally relevant levels of protein expression, improved hair cell survival, rescued ABR thresholds at low and intermediate frequencies, and corrected vestibular dysfunction . The French-Acadian mutation  of the transmembrane channel-like 1 (TMC1) gene is dominantly inherited and causes progressive hearing loss in mice  from 8 kHz to 22.6 kHz  thresholds, a sensitive measure of outer hair cell function  protein joins SANS cause Usher syndrome type 1G (Ush1g) characterized by congenital profound sensorineural hearing loss and vestibular dysfunction at birth with onset of retinitis pigmentosa by adolescence -GFP at P2.5 improved stereociliary bundle morphology in auditory and vestibular hair cells. In addition, Sans rescued mechanoelectrical transduction currents in inner and outer hair cells, modestly improved ABR thresholds from 5 kHz to 15 kHz, and completely restored vestibular function measured by circling behavior and vestibulo-ocular reflex (VOR) testing  designed against the Beethoven allele was delivered by lipid-mediated transfer to the mouse inner ear at P0–P2 -GFP mouse cochlea at 6 weeks of age to test the efficiency of inner ear genome editing in adult hair cells. Encouragingly, GFP expression was perturbed in 25% of the adult, Atoh1-GFP hair cells /Cas9 nuclease genome editing system further validates the early neonatal window of efficacy while offering potential for adult inner ear genetic modulation. The The literature discussed thus far demonstrates that AAV-, ASO- and CRISPR/Cas9 RNP-based therapies achieve maximal benefit for recessively and dominantly inherited forms of deafness and vestibular dysfunction when initiated from P0–P5. Furthermore, initiating therapeutic strategies after P5 shows reduced efficacy or the elimination of therapeutic benefit entirely Table . The thoClarin 1 is expressed in inner and outer hair cells as well as spiral ganglion neurons in the mouse cochlea  mouse under the control of the Atoh1 3’ enhancer/β-globin basal promoter sequence  family are potent transcriptional repressors of Atoh1 expression preventing hair cell fate commitment  is one of four connexins expressed in the inner ear that link all supporting cells with adjacent epithelial cells but not hair cells  and the auditory sensory epithelium degrades at P18  and the EP was significantly improved (n = 5 mutant mice). An alternative model system was developed due to the difficulty in obtaining sufficient numbers of mutant mice for extensive analysis. A plasmid encoding four short hairpin RNAs (shRNAs) against Cx-30 was electroporated into wild type mice at E11.5 that knocked down Cx-30, elevated ABR thresholds to over 90 dB SPL from 4 KHz to 20 KHz, and depleted the EP. Co-electroporation of a shRNA-resistant sequence encoding Cx-30 along with the shRNAs against wild type Cx-30 in wild type mice resulted in improved ABR thresholds and EP  is a nuclear-localized, long noncoding RNA robustly expressed in a diverse array of tissues that is nonessential for mouse pre- and postnatal development (Zhang et al., MALAT1 RNA effectively reduced expression in most mouse tissues analyzed (Wheeler et al., MALAT1 ASO into the E13-E13.5 mouse amniotic cavity reduced MALAT1 RNA abundance in the inner ear through P15 establishing that the ASO gains entry into embryonic tissues and exerts its bioactive effects through the second postnatal week (Depreux et al., Ush1c mutant mice generated correctly spliced harmonin RNA in the inner ear at P22 (Depreux et al., While direct injection of bioactive reagents into the developing inner ear is formally a plausible gene therapy strategy, it is unlikely that targeted injections will be conducted into the human otic vesicle which first forms by GA 6 not long after most pregnancies are first verified (Streeter, The therapeutic modulation of inner ear gene expression by systemic and focal injections of bioactive reagents has defined authentic gene therapy strategies in mouse models of hearing loss and vestibular dysfunction. The literature establishes that therapeutic intervention in the functionally immature mouse inner ear by 5 days postnatal age leads to optimal recovery of hearing and balance. This early neonatal window of therapeutic efficacy holds irrespective of the molecular strategy, delivery modality, or viral vector serotype deployed. Moreover, a corollary prenatal window of therapeutic efficacy in humans is predicted to close by 19 weeks of GA before the onset of fetal hearing. The efficacy of fetal gene therapy to preemptively correct deleterious genetic mutations in the organogenesis stage mouse embryo before the onset of inner ear disease is an emerging research focus that has promising potential. The process of defining and validating fetal and postnatal gene therapies will be critically enhanced by rigorous evaluation in higher vertebrate model systems in which the fetal onset of hearing is a defining feature.LW, JK and JB identified the need for a comprehensive review of the literature on gene therapy to treat inner ear disease. LW, JK and JB compiled the necessary literature and wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Kweni, Cengkir, Palmer and Kent). Near infrared spectral data were collected and recorded as absorbance (Log(1/R)) data in wavelength range of 1000–2500 nm. Those spectral data are potential to be re-used and analysed for the prediction of mango quality attributes in form of vitamin C, soluble solids content (SSC) and total acidity (TA). Spectra data can be corrected and enhanced using several algorithms such as multiplicative scatter correction (MSC) and de-trending (DT). Prediction models can be established using common regression approach like partial least square regression (PLSR).Presented dataset contains spectral data on near infrared region for a total of 186 intact mango fruit samples from 4 different cultivars ( Spectra/R in wavSpectra data set were then used to establish prediction model for the determination of inner quality attributes on intact mangos using regression approach. One of the most promising and common regression method in NIRS practices is partial least square regression (PLSR) . This me22.1The NIR instrument used to obtain spectral data is Fourier transform near infrared (FT-NIR) (Thermo Nicolet Antaris II TM). It was configured and controlled under integrated software Thermo Integration® and Thermo Operation®. The workflow has been developed and set up to run specified tasks for spectra data acquisition of intact mango samples. High resolution measurement with integrating sphere was chosen as a basic measurement ..spa) and comma separated value (.csv). Standard laboratory method also prepared for inner quality attributes measurements of mango as vitamin C, soluble solids content (SSC) and total acidity (TA). Hand held refractometer  was used for SSC, automatic titrator equipment  for TA and standard manual titration method for vitamin C measurement respectively. The centrifuge was also used to obtain clarified sample juice and separate suspended solids.Sample naming and labelling was required automatically for each spectra acquisition in order to distinct all 186 mango samples. Background spectra correction was carried out every hour automatically. Spectra data were recorded in form of absorbance (Log(1/R)) in wavelength range from 1000 to 2500 nm and saved in two different file extension formats: Nicolet  [Once after spectra data acquisitions are completed, fruit samples were directly sliced and some part of mango pulp were taken. To measure vitamin C, a total 5g of mango pulp samples were macerated, mixed and homogenized with addition of 20 ml of meta-phosphoric acid into a beaker to prevent oxidation. Distilled water were added until 50 ml of volume was reached. Vitamin C was obtained and quantified based on its reaction with the ass (FM) .oBrix while automatic titration method with 0.1 N NaOH to an end point of pH 8.1 was used to measure TA of intact mango and expressed as mg∙100g−1 fresh mass [On the other hand, SSC and TA quality attributes were measured by making another juices from 20 g of pulp sample and maximum of 100 ml distilled water. A little filtered juice was squeezed and dropped into a hand-held refractometer to record SSC in form of esh mass ,6. Descr2.4The Unscrambler X 10.1 software  with network client license.It is highly recommended to perform spectra correction and enhancement prior to prediction model development. There are several methods and approaches that can be used to enhance spectra data, among of them are Multiplicative scatter correction (MSC) and de-trending (DT). Spectra enhancements were used to correct additive and multiplicative effects in the spectra. The MSC and DT spectra corrections were carried out using 2.5The main part of NIRS application is to develop models used to predict desired quality attributes of intact mango simultaneously. Prediction models were constructed to reveal information about mango quality attributes buried in absorbance spectra data. These models were developed commonly by regressing spectra data (as X variable) and actual measured quality attributes (as Y variable) through multivariate analysis. Partial least squares regression (PLSR) was applied to develop those models and validated using full cross validation approach.2) between predicted and measured quality attributes, prediction error which is defined as the root mean square error (RMSE) and the residual predictive deviation (RPD), defined as the ratio between standard deviation (SD) of the population's actual value of Vitamin C, SSC and TA, and the RMSE of predicted quality attributes. The higher value of RPD, the greater probability of models to predict desired quality parameters or chemical constituent of samples dataset accurately [The prediction performances were evaluated by means of these following statistical parameters: the coefficient of correlation (r) and determination (Rcurately .


Two multimetric indices have been developed to help address fish community (reservoir fish assemblage index [RFAI]) and individual population quality (sport fishing index [SFI]) in Tennessee River reservoirs. The RFAI, with characteristics similar to the index of biotic integrity (IBI) used in stream fish community determinations, was developed to monitor the existing condition of resident fish communities. The index, which incorporates standardized electrofishing of littoral areas and experimental gill netting for limnetic bottom-dwelling species, has been used to determine residential fish community response to various anthropogenic impacts in southeastern reservoirs.The SFI is a multimetric index designed to address the quality of the fishery for individual resident sport fish species in a particular lake or reservoir[4]. The SFI incorporates measures of fish population aspects and angler catch and pressure estimates. This paper proposes 70% of the maximum RFAI score and 10% above the average SFI score for individual species as “screening” endpoints for balanced indigenous populations (BIP) or adverse environmental impact (AEI). Endpoints for these indices indicate: (1) communities/populations are obviously balanced indigenous populations (BIP) indicating no adverse environmental impact (AEI), or are “screened out”; (2) communities/populations are considered to be potentially impacted; and (3) where the resident fish community/population should be considered adversely impacted. Suggestions are also made concerning how examination of individual metric scores can help determine the source or cause of the impact.


To assess the link between the risks of most frequent cancer sites in Poland and selected socioeconomic variables that potentially affect health outcomes throughout the life course.p < 0.05 (two-tailed tests).This is a cross-sectional ecological study. Incidence of lung, breast, and colon cancer by voivodeships in 2014 was calculated based on Polish National Cancer Registry. Socioeconomic variables in individual voivodeships were assessed based on Polish Social Cohesion Survey for 2015. Spearman’s rank correlation coefficient was used to test the association of incidence rates and socioeconomic variables. The significance level was set at Statistically significant negative correlation exists between: (1) friend-/neighbour-based social capital and colon and breast cancer, (2) association-based social capital and lung cancer, (3) high religiousness and lung and breast cancer, and (4) income poverty and breast cancer. Statistically significant positive correlation exists between: (1) social isolation, living conditions poverty, poverty resulting from the lack of budget balance, and lung cancer; (2) low/no involvement in religious activity and lung and breast cancer.Our findings support public health concerns over the implication of socioeconomic environment for cancer. Cancer is one of the major contributors to health burden worldwide. In 2012 14.1 million new cases and 8.2 million deaths were reported. Lung, breast and colorectal were the most frequently diagnosed cancers  have rarely been analysed. Only one study, performed in the Opole province, found statistically significant positive correlation between unemployment rate and lung cancer incidence rates among male population  is conceptualized as an area-level attribute. Socioeconomic determinants are conceptualized as a group attribute that affects all individuals living within the community and the interest is drawing inferences regarding differences between areas.http://onkologia.org. Data storage enables analysis of cancer incidence and mortality by type of cancer (classified according to ICD-10), age, sex and voivodeship, as well as creating custom reports. The average completeness of the Cancer Registry in Poland has been continuously improving and is currently estimated to be 94% .The cancer risk in each of 16 Polish voivodeships was calculated as incidence rates and expressed as the number of newly registered cases of cancer in 2014 per a population of 100,000. The absolute numbers of newly registered cases of lung, breast and colon cancer in Poland by voivodeships were retrieved from the Polish National Cancer Registry (NCR). NCR is a principal data source for cancer incidence in the Polish population. Healthcare providers are legally obliged to provide annual reports to NCR about every case of cancer diagnosed within the Polish population. Principles of data collecting and institutions responsible for cancer registries in Poland are specified in two acts: the Act on Public Statistics and the Act on the Health Care Information System and an ordinance issued on the basis of the said Act. The unit responsible for the registry is the National Cancer Registration Office, which is an organizational unit of the Cancer Centre and Institute of Oncology. New cases of cancer are collected via specific cancer registration forms (MZ/N-1a form) and each voivodeship is obliged to deliver the data to a shared NCR database. The data is validated using rules enforced to the system. An online database is available at Area-based socioeconomic measurements were retrieved from the Polish Social Cohesion Survey for the year 2015 . The effect of potential confounders such as sex, age and completeness of cancer registration distribution across regions was accounted for by Spearman’s partial rank correlation. The basis for the evaluation of the completeness of cancer registration in particular voivodeships was the ratio of mortality to incidence (M/I–Index) calculated for each cancer site in the same period of time  was used to examine the link between incidence rates of particular types of cancer and socioeconomic determinants. A significance level of The ranking of voivodeships according to incidence rates of particular cancers differs considerably Table . The higSocial isolation, social capital, religious activity and poverty in individual voivodeships is presented in Table Voivodeships showed wide disparities in social capital levels. The lowest ratio for high degree of association-based social capital was recorded in Pomeranian, Swietokrzyskie (16%), Lodz (14%) and Warmian-Masurian (13%), whereas the highest in Podlaskie (31%), Opole (25%) and Lublin (24%). The share of persons with high level of familial capital was lowest in West Pomeranian (19%) and highest in Swietokrzyskie (34%), Opole (31%), Lesser Poland (31%), Subcarpathian (31%), Lublin (31%). The lowest value for the indicator for high level of friends- and neighbours-based social occurred in Kuyavian-Pomeranian (21%), Lodz and Lower Silesian (23%), the highest in Lesser Poland (34%), Subcarpathian (33%) and Swietokrzyskie (32%).The attitude to faith varied from one voivodeship to another. Percentage of people who declared to be “profound believers” was highest in Opole (16%), Subcarpathian (15%), Podlaskie (15), Lublin (14%), and lowest—in Lubusz (6%), Lodz (7%), Kuyavian-Pomeranian (7%), and West-Pomeranian (7%). In 7 voivodeships the percentage of religiously uncommitted and nonclerical people is lower than the mean for entire Poland (39%), voivodeships with the topmost percentage of religiously uncommitted inhabitants are West Pomeranian (56%), Warmian-Masurian (54%) and Lubusz (50%).Income poverty affects inhabitants of Lublin (27%), Swietokrzyskie (24%) and Subcarpathian (21%) more often, whereas those residing in the southwest part of Poland are at a lower risk: Silesian (7%), Lubusz, Opole, Lower Silesian (11%). The same value (11%) was observed in the Mazovian voivodeship as well. Voivodeship proved to have a different impact on the risk of living conditions poverty than on income poverty. The highest rates of living conditions poverty were recorded in Warmian-Masurian (12%), West Pomeranian (12%), Świętokrzyskie (11%) and Łódź (11%), and the lowest in Podlaskie (5%), Greater Poland (6%) and Silesian (7%). Poverty in terms of lack of budget balance more often affects the West Pomeranian households (18%). Other voivodeships with high shares of households experiencing difficulties with balancing their budgets included Lubusz (15%), Lodz (15%), Pomeranian (14%) and Warmian-Masurian (14%). The lowest values were reported in Subcarpathian (6%) and Podlaskie (7%).p = 0.007), (2) two types of poverty: living conditions poverty  and poverty following a lack of budget balance , and (3) low/no involvement in religious activity . A statistically significantly strong negative correlation was found between risk of lung cancer and: (1) high level of association-based social capital , and (2) high religiousness . After age and sex adjustment the Spearman’s correlation coefficients remained similar, with the exception of correlation with association-based social capital which was stronger after correcting for sex . Adjustment for completeness of cancer registry strengthened the positive association between lung cancer incidence and low/no involvement in religious activity , and made the negative associations between lung cancer incidence, family based social capital and friend- and neighbour-based social capital stronger and statistically significant . After adjustment for completeness of cancer registry the correlations between lung cancer incidence, living conditions poverty and association-based social capital were no longer statistically relevant.The relevance and magnitude of associations between cancer risk and socioeconomic variables varies greatly by cancer site Table . Spearmap = 0.04), (2) high level of friend- and neighbour-based social capital , and (3) high religiousness , and positively related to low/no involvement in religious activity . After sex, age and completeness of data adjustment the correlations between breast cancer incidence and socioeconomic variables were not substantially modified, only correlation with income poverty became statistically insignificant.The risk of breast cancer was statistically significantly negatively related to: (1) income poverty . Adjustment for age, sex and data completeness produced fairly similar coefficients.The only statistically relevant for colon cancer was a negative correlation between colon cancer risk and high level of friend- and neighbour-based social capital  imply that a low income situation (determined by revenue) does not necessarily signify other poverty forms. Time factor is, therefore, extremely important, because poor living conditions and budget difficulties result from unfavourable income situation continuing for a longer period. The strong relationship with material situation  observed for association-based capital and social isolation suggests a coexistence of these factors. All of these determinants were correlated with lung cancer risk. However, the question whether poverty caused social isolation and low level of association-based social capital, or if, conversely, social isolation and low level of association-based capital caused poverty, is still to be answered.These results should be interpreted in light of relationships that may exist between the socioeconomic variables selected to the analysis. Theoretically these determinants have different meaning, but there are correlations between them, except for relationships between income poverty and other socioeconomic determinants, various forms of social capital, as well as social isolation and informal social capital . Lack of correlation between income poverty and other poverty forms and strong correlation between living conditions poverty and poverty following a lack of budget balance  is well known and repeatedly discussed  and influencing health care accessibility, use of cancer screening programmes and effective treatments. National policy actions which can have an important effect on the magnitude of social inequalities in cancer incidence might significantly reduce the burden and disparities in various populations and geographic areas. Our study showed that the relevance and magnitude of associations between socioeconomic variables and cancer risk vary greatly by cancer site. It provides important additional information about how socioeconomic mechanisms work. Social and economic inequalities can be avoided; therefore their limitation constitutes an achievable goal and an ethical imperative.


Overall growth and development of a plant is regulated by complex interactions among various hormones, which is critical at different developmental stages. Some of the key aspects of plant growth include seed development, germination and plant survival under unfavorable conditions. Two of the key phytohormones regulating the associated physiological processes are gibberellins (GA) and abscisic acid (ABA). GAs participate in numerous developmental processes, including, seed development and seed germination, seedling growth, root proliferation, determination of leaf size and shape, flower induction and development, pollination and fruit expansion. Despite the association with abiotic stresses, ABA is essential for normal plant growth and development. It plays a critical role in different abiotic stresses by regulating various downstream ABA-dependent stress responses. Plants maintain a balance between GA and ABA levels constantly throughout the developmental processes at different tissues and organs, including under unfavorable environmental or physiological conditions. Here, we will review the literature on how GA and ABA control different stages of plant development, with focus on seed germination and selected abiotic stresses. The possible crosstalk of ABA and GA in specific events of the above processes will also be discussed, with emphasis on downstream stress signaling components, kinases and transcription factors (TFs). The importance of several key ABA and GA signaling intermediates will be illustrated. The knowledge gained from such studies will also help to establish a solid foundation to develop future crop improvement strategies. Overall growth and different developmental stages of plants are under strict regulation by several classes of plant hormones. Hormone molecules are present at low concentrations in plants, and they function either at the sites of synthesis or after they are transported to different tissues  of crop plants  enzyme  and abscisic aldehyde oxidase (AAO), respectively  and AAO3 (AAO3/ABA3/LOS5) were upregulated in Arabidopsis. Furthermore, transcript levels of NCED3, ABA3/LOS5, and AAO3 were induced by abiotic stresses  catalyze the deactivation reaction resulting in phaseic acid (PA) and dihydro phaseic acid (DPA) as the main ABA catabolites  and in turn regulate transcription of several downstream ABA-responsive genes  infection in rice by Teijiro Yabuta and co-workers  was the result of an investigation of fungal  from the precursor compound geranylgeranyl diphosphate (GGDP), which is aided by terpene synthases (TPSs), cytochrome P450 monooxygenases (P450s), and 2-oxoglutarate–dependent dioxygenases (2ODDs)  and ent-kaurene synthase (KS), which are located in the plastids are responsible for the first few steps of GA biosynthesis (conversion of GGDP to ent-kaurene). Then two P450 enzymes, namely, ent-kaurene oxidase (KO) and ent-kaurenoic acid oxidase (KAO) convert ent-kaurene to GA12. Finally, three active GAs are formed by reactions catalyzed by GA 20-oxidase (GA20ox) and GA 3-oxidase (GA3ox), that belong to 2ODDs  showed drought tolerance phenotype and overexpression of GA20ox confers drought sensitivity in Arabidopsis  genes and growth arrest by activating a basic leucine zipper transcription factor, ABSCISIC ACID INSENSITIVE 5 (ABI5)  and activates a GA catabolic gene (GA2ox2) indirectly  and represses an ABA catabolic gene (CYP707A2)  which acts downstream to PIL5, leads to repression of GA biosynthesis and activation of ABI3 and ABI5  which leads to increased dormancy   and hence increases the ABA level whereas it decreases the GA level by repressing GA biosynthesis genes in Arabidopsis seeds  lead to changes in the plant response and therefore alter the balance of endogenous levels of GA and ABA. High temperature induces ABA biosynthesis genes   module , which results in stabilization of the receptor. Conversely, opposite effect has been shown by GA by inhibiting rice SnRK2  has a link between GA and ABA signaling in rice via SnRK2-APC/CCYP707A1 and CYP707A2)  -domain containing transcription factors (ATFs), Arabidopsis ABA-INSENSITIVE 4 (ABI4) and rice OsAP2-39, have key roles in the antagonistic crosstalk between ABA and GA. ABI4 positively regulates primary seed dormancy by downregulating GA biosynthesis and by inhibiting ABA catabolic genes  and indirectly repressing GA biosynthesis genes (GA3ox1 and GA20ox1) , B3 domain factors LEC2, and FUSCA3 (FUS3)  and modulating expression of GA metabolic genes   as well as signaling cascades that regulate downstream target genes (of different classes) further add to the complexity of the already elaborate cellular communication network. This has been highlighted here with the examples of ABA and GA metabolism and their regulation. Selected genes that play significant roles in the regulation of seed dormancy and germination and various abiotic stresses were also discussed. It is evident that several positive and negative regulators of ABA and GA have direct or indirect impacts on germination and abiotic stresses. Many transcription factors and signaling components of these two phytohormones help to maintain an intricate balance between endogenous levels of bioactive ABA and GA. Furthermore, studies have identified several ABA and GA crosstalk points showing positive and negative regulation of different molecular modules associated with their metabolism and signaling. There are a few open questions that can help in formulating the future research directions. Despite the fact that there are some studies on ABA transport in different cell types and tissues, there might be many unknown pathways/transporters that are yet to be explored. Moreover, very few reports on the transport mechanism of GA are available. The antagonistic roles of GA and ABA in controlling developmental processes have been established by several pieces of evidence; however, there could be synergistic crosstalk between GA and ABA in some instances whose underlying molecular mechanisms remain undiscovered. Although several target genes of a few TFs have been established  (Yaish et al., BV and PK conceived the idea and wrote the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Escherichia coli (aEPEC) has been increasing worldwide. Here, we report the draft whole-genome sequences of 10 aEPEC strains isolated in Brazil.The number of diarrhea cases caused by atypical enteropathogenic  Escherichia coli (aEPEC) has been increasing worldwide. Here, we report the draft whole-genome sequences of 10 aEPEC strains isolated in Brazil. These sequences will provide an important source for future studies concerning aEPEC pathogenicity and genetic markers of potentially virulent strains.The number of diarrhea cases caused by atypical enteropathogenic  Escherichia coli (EPEC), which is one of the diarrheagenic E. coli pathotypes. EPEC is subdivided into typical EPEC (tEPEC) and atypical EPEC (aEPEC) based on the presence of the EPEC adherence factor (EAF) plasmid in the former group and its absence in the latter group  lesions in the intestinal epithelium, in which intimate adherence between bacteria and host cells occurs –8. The g–The number of cases of diarrhea caused by aEPEC has increased even in industrialized countries. This information reveals the need for a thorough knowledge of the genetic traits of aEPEC organisms and their mechanisms of pathogenicity in order to develop appropriate control strategies , 10, 11.The 10 aEPEC strains we sequenced were isolated from feces of children under 5 years old during epidemiological studies carried out in São Paulo, Brazil (1985 to 1986 and 1989 to 1990) by the Laboratory of Microbiology of the Universidade Federal de São Paulo (UNIFESP) and in Salvador (2003 to 2004) by the Laboratory of Bacteriology of the Butantan Institute , 13. Allde novo assembly and annotation of the genomes were performed using the software SPAdes version 3.9.1 (with the –careful flag) (DNA extraction was performed using the QIAamp DNA minikit (Qiagen) according to the manufacturer’s instructions. DNA libraries from each aEPEC genome were prepared using the Nextera XT library prep kit  and sequenced at MicrobesNG  on the Illumina HiSeq 2500 platform using 2- × 250-bp paired-end reads, achieving between 34 and 157× depth . Trimmomul flag) , respectThese sequences will provide an important source for futures studies concerning aEPEC pathogenicity and genetic markers of potentially virulent strains. Furthermore, these data will permit comparative studies to be carried out with aEPEC strains isolated in Brazil and others isolated in different countries.PRJNA490882, and the whole-genome shotgun sequences were deposited in the GenBank database under the accession numbers shown in The reads used for assembly of the 10 aEPEC genomes were deposited in the Sequence Read Archive (SRA) at the National Center for Biotechnology Information (NCBI) under the accession number


This paper focus to examine the best molecular interaction between Polyamide Thin Film Composite (PA TFC) layers with different properties of the support membrane. The support membrane of Nylon 66 (N66) and Polyvinylidene fluoride (PVDF) was chosen to represent the hydrophilic and hydrophobic model respectively in the Molecular Dynamic (MD) simulation. The Condensed-Phase Optimized Molecular Potential for Atomistic Simulation Studies (COMPASS) force field was used with the total simulation runs were set 1000 picoseconds run production ensembles. The temperature and pressure set for both ensembles were 298 K and 1 atm respectively. The validity of our model densities data was check and calculated where the deviation must be less than 6%. The comparison between hydrophobic and hydrophilic of the support membrane data was examined by the distance and magnitude of intensity of the Radial Distribution Function (RDF's) trends. The interactions of binary system (MPD/TMC) were comparing with both the tertiary system, (N66/MPD/TMC) and (PVDF/MPD/TMC)[10]. Where:N (MPD) – C (TMC): Intermolecular interaction (crosslink) between nitrogen in the MPD molecules with carbon in the TMC group There were also interactions detected between TMC-subtracts presented inwhich contributes to the better attachment of TFC layer onto support membrane. Where:Cl (TMC) – O (N66): Intermolecular interaction between chlorides in the MPD molecules with the oxygen atom in the N66 group.O (TMC) – H (N66): Intermolecular interaction between oxygen in the MPD molecules with the hydrogen atom in the N66 group.Cl (TMC) – F (PVDF): Intermolecular interaction between chlorides in the MPD molecules with the fluorine atom in the PVDF group.Cl (TMC) – H (PVDF): Intermolecular interaction between chlorides in the MPD molecules with the hydrogen atom in the PVDF group.2All simulations were performed using Material Studio (version 7.0) software from Accelrys, Inc. Models were firstly undergoing the geometry optimization and then the energy started to minimized. The molecules of the models chosen represent in


Bos gaurus hubbacki), locally known as the seladang, from two captive centers. Thirty fecal samples of Malayan gaur were collected from Jenderak Selatan Wildlife Conservation Center (Pahang) and the Sungkai Wildlife Reserve (Perak) for DNA extraction and amplification with polymerase chain reactions. DNA sequences were then analyzed using neighbor joining (NJ) and maximum parsimony (MP) methods. Based on the 652 base pairs obtained, we found seven variable characters with a value of 1%. The genetic distance between the two captive centers was 0.001. Haplotype analyses detected only four haplotypes between these two captive centers. Both NJ and MP trees demonstrate that all individuals in the Jenderak and Sungkai captive centers are in the same clade. Genetic variation of the Malayan gaur in these centers is considered low, possibly because individuals share the same common parent. This sequence variation data are of paramount importance for designing a proper breeding and management program of the Malayan gaur in the future.This article contains data of the sequence variation in the mitochondrial DNA D-loop region of the Malayan gaur ( Specifications tableValue of the data•The data presented here provide sequence variations of Malayan gaur in captivity.•Genetic relationships among captive Malayan gaur individuals.•Revealing inbreeding in which they might share the same common parent.•The data are useful for decision-making in the breeding and management program of the Malayan gaur.1We present D-loop region sequence data 2The DNA chromatograms  of the s


Scientific Reports 10.1038/s41598-018-35051-w, published online 12 November 2018Correction to: This Article contains typographical errors in the Results section where,20), Marinimicrobium, Marinobacter and Acinetobacter (Table 1). A decrease in biodiversity is observed as the salinity of the lagoons increase (Table 1), revealing the higher salinity tolerance of Marinimicrobium and Marinobacter species compared to that of Halomonas and Acinetobacter species here reported.”“Massive parallel sequencing of 16S ribosomal RNA gene amplicons showed that more than 60% of the sequences found in the lagoons belonged to only four main OTUs , specifically to the Class Gammaproteobacteria: Halomonas (found worldwideshould read:20), Marinimicrobium, Marinobacter and Acinetobacter (Table 2). A decrease in biodiversity is observed as the salinity of the lagoons increase (Table 2), revealing the higher salinity tolerance of Marinimicrobium and Marinobacter species compared to that of Halomonas and Acinetobacter species here reported.”“Massive parallel sequencing of 16S ribosomal RNA gene amplicons showed that more than 60% of the sequences found in the lagoons belonged to only four main OTUs , specifically to the Class Gammaproteobacteria: Halomonas (found worldwide


As the age of the US population increases, so does cognitive impairment (CI); therefore early detection of CI is critical for ensuring its appropriate management. As part of a NINDS Consortium to detect CI and dementia in primary care (DetectCID), we are implementing and evaluating a brief 2-step CI detection paradigm (MyCog), that can be delivered in clinics with diverse populations via the electronic health record (step 1) and iPad (step 2). We conducted focus groups with 25 clinicians and administrative leaders from academic and community primary care practices to 1) understand how CI is being assessed, and 2) evaluate the feasibility of implementing the MyCog paradigm into existing primary care workflows. Several key themes emerged from the discussions. No proactive detection strategy for CI was regularly used outside of the Medicare Annual Wellness Visits (AWV); variable assessments including the Minicog, MoCA, or MMSE were used to fulfill the AWV requirement. Regarding the feasibility of our MyCog Paradigm, our 2-step process was positively received, with the brief case-finding step 1 satisfying AWV requirements and replacing the longer assessments currently being used. Clinicians preferred that step 2 be self-administered due to limited clinician time for wellness visits, and highlighted logistical challenges such as room availability and storage and maintenance of the iPad. Overall, clinicians felt that the identification of CI was valuable and supported standardization, but indicated regular case finding was unlikely without clear guidance on clinical decision-making.


TOX3 (16q) at 1.5% frequency, as well as for CCND2 (12p) and ANXA11 (10q) at 1% frequency, in addition to the well-known targets ERBB2 (17q) and MYC (8q). Focal amplifications with ≥15 or ≥5 additional copies of at least one of these regions were associated with a poor overall survival among patients with stage I-III MSS CRCs . All high-level amplifications were focal and had a more consistent relationship with gene expression than lower amplitude and/or broad-range amplifications, suggesting specific targeting during carcinogenesis. Genome-wide, copy number driven gene expression was enriched for pathways characteristic of the CMS2-epithelial/canonical subtype, including DNA repair and cell cycle progression. Furthermore, 50% of upregulated genes in CMS2-epithelial/canonical MSS CRCs were driven by CNAs, an enrichment compared with the other CMS groups, and associated with the stronger correspondence between CNAs and gene expression in malignant epithelial cells than in the cells of the tumor microenvironment . In conclusion, we identify novel recurrent amplifications with impact on gene expression in CRC and provide the first evidence that CMS2 may have a stronger copy-number related genetic basis than subtypes more heavily influenced by gene expression signals from the tumor microenvironment.About 80% of colorectal cancers (CRCs) have chromosomal instability, which is an integral part of aggressive malignancy development, but the importance of specific copy number aberrations (CNAs) in modulating gene expression, particularly within the framework of clinically relevant molecular subtypes, remains mostly elusive. We performed DNA copy number profiling of 257 stage I-IV primary CRCs and integrative gene expression analysis in 151 microsatellite stable (MSS) tumors, focusing on high-level amplifications and the effect of CNAs on the characteristics of the gene expression-based consensus molecular subtypes (CMS). The results were validated in 323 MSS tumors from TCGA. Novel recurrent high-level amplifications  with a major impact on gene expression were found for  BRAF mutation in CMS1 and KRAS mutation in CMS3, and the low frequency of somatic copy number aberrations (CNAs) in MSI is well established. However, little is in general known about the genetic basis for the distinct gene expression-based subtypes.Colorectal cancers (CRC) can be classified into four biologically distinct and clinically relevant consensus molecular subtypes (CMS) based on their global gene expression patterns . A few gChromosomal instability is an integral part of canonical CRC pathogenesis, and the majority of CRCs are characterized by a large burden of CNAs. Chromosomal instability is associated with poor patient prognosis  and resiERBB2 amplification, is a druggable target, and the HERACLES trial demonstrated a 30% response rate to dual HER2 blockade in the 5% subpopulation of HER2 positive and KRAS wild-type metastatic cancers  samples on gene expression (or among top five samples on gene expression when fewer than five samples displayed amplification). Similar correspondence analyses were also performed for recurrent high-level amplifications, defined as ≥15 additional copies in >1 tumor. For selected amplified genes the gene expression was additionally assessed by Wilcoxon tests .p < 0.05 and fold change > 1.2) and calculated the proportion of upregulated genes that overlapped with in cis genes. To control for the potential impact of different numbers of samples in the subtypes, we performed random sampling (n = 1000) of 20 tumors from each CMS group and repeated analyses for each iteration. Enrichment was assessed in pairwise comparisons among the subtypes. For a gene to be assessed in the in cis analysis, at least three tumors had to be found in the copy number gain and copy number neutral group. For robustness, the analysis was done in three different ways: (i) by identifying significant in cis genes  for the 40 tumors (20 tumors in each of the subtypes included in the pairwise comparison) and performing differential expression analysis  for the 20 versus 20 tumors per re-sampling, (ii) by identifying significant gain/upregulated genes for the 40 tumors per re-sampling and using the differential expression results from the original analyses including all samples, and (iii) by identifying significant in cis genes for the 40 tumors and randomly sampling 250 genes from the original differential expression results. Furthermore, to test if the variable number of genes that were differentially upregulated in each subtype affected the analysis we also performed repeated (n = 1000) re-samplings of 250 genes from the original gain/upregulated gene list and among the genes originally found to be upregulated in each CMS group (CMSx versus remaining CMS classified tumors).To investigate a potential enrichment of genes with in cis-association (gain/upregulation) among upregulated genes in each of the four CMSs we identified differentially expressed genes between each subtype and the remaining subtypes using limma  were used for integration analyses with CNAs. Prior to data integration, the same fraction of low-variance genes as in the inhouse dataset was excluded prior to Wilcoxon-testing. The amplification analyses  were performed on 320 out of 323 tumors due to segmentation failure in 3 samples.Gene expression data from four different colon cancer cell populations


To determine how intrusion of O2 into iron mound sediments influences microbial community composition and Fe metabolism, we incubated samples of these sediments in a column format. O2 was only supplied through the top of the columns, and microbiological, geochemical, and electrochemical changes at discrete depths were determined with time. Despite the development of dramatic gradients in dissolved Fe(II) concentrations, indicating Fe(II) oxidation in shallower portions and Fe(III) reduction in the deeper portions, microbial communities varied little with depth, suggesting the metabolic versatility of organisms in the sediments with respect to Fe metabolism. Additionally, the availability of O2 in shallow portions of the sediments influenced Fe metabolism in deeper, O2-free sediments. Total potential  measurements at discrete depths in the columns indicated that Fe transformations and electron transfer processes were occurring through the sediments and could explain the impact of O2 on Fe metabolism past where it penetrates into the sediments. This work shows that O2 availability (or lack of it) minimally influences microbial communities, but influences microbial activities beyond its penetration depth in AMD-derived Fe(III) rich sediments. Our results indicate that O2 can modulate Fe redox state and solubility in larger volumes of iron mound sediments than only those directly exposed to O2.Fe(III)-rich deposits referred to as “iron mounds” develop when Fe(II)-rich acid mine drainage (AMD) emerges at the terrestrial surface, and aeration of the fluids induces oxidation of Fe(II), with subsequent precipitation of Fe(III) phases. As Fe(III) phases accumulate in these systems, O Centuries of coal extraction in the Appalachian region of the United States has left a legacy of acid mine drainage (AMD), which remains the region’s greatest threat to surface water quality . The maj2, while Fe(II) oxidation might occur under conditions of severe O2 depletion .(DOCX)Click here for additional data file.S2 Fig]. Values in parentheses in depth legend indicate Shanon Indices of microbial communities at each of those depths. Values in parentheses of axis labels indicate the percentage of variation explained by a PCo.Appl Environ Microbiol 2007; 73: 1576–1585.(DOCX)Click here for additional data file.


Mission: to urge all relevant entities within the international cardiac surgery, industry and government sectors to commit to develop and implement an effective strategy to address the scourge of rheumatic heart disease in the developing world through increased access to life-saving cardiac surgery. Twelve years after cardiologists and cardiac surgeons from all over the world issued the Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa, calling on the world community to address the prevention and treatment of rheumatic heart disease (RHD) through improving living conditions, to develop pilot programmes at selected sites for control of rheumatic fever and rheumatic heart disease, and to periodically review progress made and challenges that remain,2Prevention efforts have been important but have failed to eradicate the disease. At the present time, the only effective treatment for symptomatic RHD is open-heart surgery, yet that life-saving cardiac surgery is woefully absent in many endemic regions. In this declaration, we propose a framework structure to create a co-ordinated and transparent international alliance to address this inequality.Elimination of RHD and relief from its debilitating consequences can only occur through interdisciplinary effort, as outlined in the Cairo Accord.Progress in the prevention of RHD has been slow during the past 15 years,6Although there is one cardiac centre per 120 000 people in the United States, there is only one centre per 33 million in Africa. Furthermore, RHD is not restricted to sub-Saharan Africa. India, Pakistan, China and Indonesia together account for 72% of the mortality rate of RHD cases worldwide.2We strongly endorse the position that building local capacity is the best solution for this serious public health problem. Many lives have been saved by humanitarian ‘fly-in’ missions, but these efforts are neither sustainable nor cost effective. The non-governmental organisations associated with these programmes are shifting focus towards building long-term partnerships with host countries to develop autonomous local services with government buy-in.It is not sufficient for governments and non-governmental organisations to support the training of cardiologists and cardiac surgeons from these regions at high-income country facilities, because they will not be trained in most of the pathologies awaiting them in their own countries and will be unfamiliar with resource-constrained circumstances.There is an urgent need for a concerted effort by all stakeholders to address the plight of the poor in these regions, who need cardiac surgery. As signatories and endorsing organisations of the Cape Town Declaration, we propose a comprehensive solution with two principal aims.Aim 1: To establish an international working group  of individuals from cardiac surgery societies and representatives from industry, cardiology and government to evaluate and endorse the development of cardiac care in low- to middle-income countries.It is proposed that the international coalition will have two representatives from each of the major cardiac surgery societies , and ideally, two additional committed members. There will be at least one representative from industry and at least one appointee to represent cardiology/the World Heart Federation. The responsibilities of the coalition will include establishing criteria for centres for clinical care and training as well as selecting and endorsing the centres. The coalition will derive metrics of quality and performance for the endorsed centres of training and clinical care and will encourage standardisation of care to the extent possible.The coalition will advocate mutually agreed policies and prescriptions to relevant governmental bodies. In addition, the coalition will engage with industry and private sources of philanthropy for financial assistance with large-scale initiatives.Aim 2: To advocate for the training of cardiac surgeons and other key specialised caregivers at identified and endorsed centres in lowto middle-income countries.The case has been made above for critical providers obtaining training in settings and conditions and dealing with the cardiac pathologies that they will be encountering in their practice in their countries of origin.It is preferred that centres endorsed by this coalition be based on an alliance of four stakeholders: a programme initiator , an audited training centre in a low- to middle-income country, a committed partner institution in a high-income country, and a consortium of industry that would sign on as benefactors to the specific programme. Because regional centres in low- to middleincome countries typically operate within a resource-scarce environment, resulting in lower case numbers than needed for the training of outside residents, a facilitated capacity increase to help achieve higher case numbers would benefit all participants.Summary: It is imperative that action be taken urgently. A nucleus of one to three centres should be identified and endorsed, with co-ordination by global stakeholders, as quickly as possible. The implementation of this initiative will only be made possible by the endorsement of all the relevant cardiothoracic societies and agencies subscribing to clearly defined targets and timelines, and committing appropriate resources. The time to act is now.For Cardiothoracic Societies Joseph Bavaria Friedhelm Beyersdorf R Morton Bolman, III Kumud Dhital Robert SD Higgins James Kirklin Robert Kleinloog Bongani Mayosi Juan Mejia Jose Pomar Karen Sliwa Shinichi Takamoto Wei Wang David Wood Charles Yankah , Ghana/Germany]Liesl Zuhlke Humanitarian and government organisations Alain Carpentier Sylvain Chauvaud Afksendiyos Kalangos Richard Kamwi René Prêtre Nicole Sekarski Magdi Yacoub Industry and health economy representatives Iraj Abedian Francois Bonnici Lenias Hwenda Sidhant Jena Samukeliso Dube Jacques Kpodonu  Salah Malek Markus Stirner-Schilling Patrice Matchaba Lee Chuen Neng Michael P Phalen Tim Ring Kathryn Gleason Devi Prassad Shetty Alistair Simpson Raenette Taljaard Helmut Straubinger Barry Wilson For major journals and publications Friedhelm Beyersdorf Sampath Kumar Dan Ncayiyana JP van Niekerk G Alexander Patterson Marko Turina David Williams Other signatory delegates to the Cape Town Dialogue Elena Aikawa (USA)Masanori Aikawa (USA)Henning Rud Andersen (Denmark)Manuel Antunes Eduardo Becerra (Chile)Solomon Benatar (South Africa/Canada)Richard Bianco (USA)Bojan Biocina (Croatia)Carlijn Bouten (Netherlands)Abdelmalek Bouzid (Algeria)Luke Brewster (USA)Johan Brink (South Africa)Taweesak Chotivatanapong (Thailand)Patrick Commerford (South Africa)David Cooper (USA)John Curci (USA)Manfred Deutsch (Austria)Richard Daly (USA)Frederick C de Beer (USA)Norberto de Vega (Spain)Howard Eisen (USA)Max Emmert (Switzerland)Giuseppe Faggian Volkmar Falk (Germany)Ted Feldman (USA)Giovanni Ferrari (USA)Teddy Fischlein (Germany)Robert Frater (USA)Glen Gaudette (USA)Gino Gerosa Bernard Gersh (USA)Allan Glanville Craig Goergen (USA)Claudia Goettsch (Germany)Mervyn Gotsman (Israel)Martin Grabenwoeger (Austria)Andrea Griesmacher (Austria)Christian Hagl (Germany)Ulf Hedin (Sweden)Simon Hoerstrup (Switzerland)Saeid Hosseini (Iran)Joshua Hutcheson (USA)Willie Koen (South Africa)Gennadiy Khubulava (Russia)Robin Kleinloog (South Africa)Walter Klepetko (Austria)Michael Knaut (Germany)Theodoros Kofidis (Singapore)Guenther Laufer (Austria)Nicolas l’Heureux (France)Georg Lutter (Germany)Simon Maltais (USA)Simon Matskeplishvili (Russia)Jo Meinhart (Austria)Ana Olga Mocumbi (Mozambique)Elmi Muller (South Africa)Mathias Mueller (Austria)Paul Mohacsi (Switzerland)Ivan Netuka (Czech Republic)Mpiko Ntsekhe (South Africa)Minoru Ono (Japan)Otmar Pachinger (Austria)Timothy Pennel (South Africa)Olga Plattner (Austria)Bruno Podesser (Austria)Darshan Reddy (South Africa)Bruno Reichart (Germany)Hermann Reichenspurner (Germany)Hector Sanchez (Argentina)Jacques Scherman (South Africa)Stephan Schueller (United Kingdom)Jim Schurman (USA)Rainald Seitelberger (Austria)Toshi Shinoka (USA)Agneta Simionescu (USA)Dan Simionescu (USA)Francis Smit (South Africa)Ulrich Steinseifer (Germany)Cynthia St Hilaire (USA)Justiaan Swanevelder (South Africa)Hendrik Treede (Germany)Nir Uriel (USA)Devagourou Velayodamu (India)David Vorp (USA)Susan Vosloo (South Africa)Beath Walpoth (Switzerland)Georg Wieselthaler (USA)Mike Wolf (USA)Andreas Zuckermann (Austria)


The use of video-recording offers important advantages in observing and assessing the relationships between specific behaviors in health care settings. The purpose of this systematic review is to investigate and synthesize the methodological characteristics of studies using video-technology for measuring interactions between the older persons with dementia and staff in long-term care facilities. We searched Medline, Embase and CINHAL databases for published articles in English using a video-recording method for both staff and persons with dementia. Quantitative research design studies  were included. Among 5,605 searched papers, a total of 20 studies were selected for this review. Situations of video-recording were providing personal care (n=12), mealtime (n=6), and conversation (n=3). Concepts of measuring by video-recording were classified into two groups: 1) Staff [care practice by staff (n=13) and communication by staff (n=11)] and 2) residents . This review demonstrates that video technologies are actively used to evaluate the relationship between quality of care and health outcomes of the elderly with dementia in many international nursing studies. This study provides the foundation for a future research using video-recording technologies to examine the interactions and relationship between staff and the residents in long-term care settings.


We detected 2936 large and rare CNVs events . Case-control burden analysis and generalized linear regression models revealed significant association of CNVs with GSD in men, with the strongest effect observed with CNVs overlapping lipid metabolism genes . Our results indicate a clear link between CNVs and GSD in men and provides additional evidence that the genetic components of risk for GSD are complex, can be sex specific and include CNVs affecting genes involved in lipid metabolism.Gallstones Disease (GSD) is one of the most common digestive diseases requiring hospitalization and surgical procedures in the world. GSD has a high prevalence in populations with European or Amerindian ancestry (10–20%) and the influence of genetic factors is broadly acknowledged. However, known genetic variants do not entirely explain the disease heritability suggesting that additional genetic variants remain to be identified. Here, we examined the association of copy number variants (CNVs) with GSD in a sample of 4778 individuals (1929 GSD cases and 2849 controls) including two European cohorts from Germany ( Gallstones disease (GSD) is a multifactorial chronic metabolic disease characterized by the development of calculi inside the gallbladder composed mainly by cholesterol. GSD features a long silent progression where the accumulation of stones in the affected gallbladder can lead to clinical symptoms such as recurrent episodes of intense abdominal pain (biliary colic) and major complications, like obstruction and infection of the biliary tree (cholestasis and cholangitis), acute pancreatitis, and gallbladder cancer . At leasABCG5/8 gene  ATP8B1) gene [RB1) gene [HNF1A) gene [SULT2A1) gene [APOL1 and APOL2) involved in lipid transport. In addition, we note that the 23 candidate genes were enriched with 7 genes extremely intolerant to loss-of-function genetic variation  and variants within these genes are rarely found in the general population [The observed associations could not be attributed to one CNV nor to an specific gene and thus CNVs may confer risk to GSD through multiple highly rare and penetrants events. In an effort to identify genes with the strongest potential to be involved in the development of GSD by a CNV-related mechanism, we highlight 23 genes involved in lipid metabolic process, which are expressed in the small intestine and exclusively affected by CNV in cases. Direct functional links between the candidate genes and the etiology of GSD is available for: the lipid transporter ATPase phospholipid transporting 8B1, (B1) gene , the RB B1) gene , the hep1A) gene , the bilA1) gene , and thepulation . We hypoAs suggested by CNVs overlapping nonlipid metabolic process genes that are expressed in the small intestine Fig.  and the In summary, our study provides the first evidence of association of CNVs with GSD and will contribute to better understand the etiology of this complex and common metabolic disorder.Supplementary Material


Investigators from Calico Life Sciences LLC and AbbVie report the effects of a novel drug targeting the genetic basis of Vanishing White Matter Disease (VWMD). Investigators from Calico Life Sciences LLC and AbbVie report the effects of a novel drug targeting the genetic basis of Vanishing White Matter Disease (VWMD). VWMD is caused by homozygous or compound heterozygous variants in any of five genes . Collectively the five genes encode a portion of the eukaryotic translation inhibition factor 2 (eIF2) termed eIF2B that is required for normal protein translation. VWMD-causing variants are though to cause a partial reduction in eIF2B activity. Prior studies by members of the group from Calico Life Sciences had shown that ISR-inhibitor (ISRIB), a small molecule, was able to activate and stabilize eIF2B [COMMENTARY. VWMD is a chronic, episodic and progressive leukoencephalopathy with highly variable presentation. Features include essentially normal early life development followed by progressive ataxia, cognitive impairment, and spasticity. In 1997 Van Der Knapp et al., proposed four criteria for diagnosis (1) essentially normal initial motor and cognitive development, (2) chronic, progressive deterioration that often follows a mild infection or head trauma, 3) progressive cerebellar ataxia and spasticity are prominent features; epilepsy and optic atrophy may be present; cognitive impairments are less significant than motor impairments and (4) MRI findings are symmetric, with white matter signal intensity similar to cerebrospinal fluid on multiple sequences [ progressWhen clinical suspicion is high, the diagnosis of VWMD is confirmed by genetic testing for homozygous or compound heterozygous variants in genes encoding the five eIF2B subunits. Normal protein expression requires function of eIF2B to extend translated RNA sequences . While tThe other important function of eIF2B is regulation of the integrated stress response (ISR), a reprogramming of protein expression that is common for a variety of cellular stress signals. ISR both shuts down normal protein expression, and activates specific transcription factors to help protect a stressed cell. Prior work demonstrated that suppression of eIF2B activates the ISR. ISRIB efficiently activates and stabilizes eIF2B to block the ISR .VWMD is caused by diminished eIF2B activity and often worsens in the setting of illness, which may be related to improper regulation of the ISR. The current investigation examined whether ISRIB can utilize the hypoactive eIF2B found in VWMD to properly inhibit the ISR. The authors selectively edited the eIF2B gene with CRISPR-Cas9 in otherwise normal cells to recreate patient derived mutations. Cells were then treated with ISRIB. Consistent with a properly inhibited ISR, global protein expression was increased and ISR-specific transcription factors were decreased [The author(s) have declared that no competing interests exist.


A 78-year-old patient with a recent history of transitory ischemic attack with right upper extremity weakness was referred for computed tomographic angiography (CTA) of the neck arteries. No significant stenosis was found, but systematic 3D study of the circle of Willis Figure  revealedThe vocable of “fetal posterior cerebral artery” (FPCA) encompasses a group of developmental variants of the posterior cerebral artery (PCA) in which a significant portion of the distal PCA remains perfused through a branch of the internal carotid artery (ICA).When a FPCA variant is present, thromboembolism in the ICA may result in paradoxical PCA territory infarction  .During the choroidal stage of embryogenesis (at five weeks of gestation) the anterior brain circulation is constituted by two main branches of the ICA: the rostral branch (rICA) and the caudal branch (cICA) which prefigures the future posterior communicating artery (PcoA).The rICA feeds the anterior carotid artery (ACA) and the anterior choroidal artery (AchoA) and the cICA feeds the posterior choroidal artery (PchoA) and the future P1 segment of the PCA.During growth of the posterior cerebrum, cerebellum and brainstem acceleration arises in the development of the posterior arterial network. It progressively becomes independent from the anterior circulation and the primitive transitory carotid-basilar anastomoses completely regress.Different scenarios explain the pattern of the future definitive PCA. Most commonly Figure  the middAnother scenario produces the common FPCA variants Figure , C and DA third but extremely rare scenario called the “true fetal PCA” variant Figure  is repor


The Research article “Jurassic-Cretaceous boundary bioevents and magnetochrons: A stratigraphic experiment” , describes the Lower Cretaceous 2016 Chronostratigraphic Database (LOK2016CS). This database comprises the first and last occurrences of key fossil ranges in forty-one global stratigraphic sections (Table 1). This data has been published by qualified biostratigraphers in selected worldwide sections that have been carefully measured, collected and fossil species consistently identified. Regional reference sections and approved or proposed Global Boundary Stratotype Section and Point (GSSP) are included. This data set is composed of lowermost and uppermost positions of species measured in meters or feet by the research team in each section, which represent the first and last occurrences of the species. These data sets were composited into the numerical age chart, LOK2016CS (Table 2), by graphic correlation. The 2016 Geologic Time Scale was the X-axis section on the first X/Y plot so that the numerical ages were calibrated consistently with that scale. The numerical ages of each event estimate the First and Last Appearance Datums  within the geographic area encompassed by the sampled sections.


Cardioglossa schioetzi and Leptodactylodon bicolor (both in the Arthroleptidae), in and around Ngel Nyaki Forest Reserve on the Mambilla Plateau in eastern Nigeria. The landscape comprises continuous forest on steep slopes and small riparian forest fragments in a grassland matrix. While increased fragmentation is well documented for these and other forests in the mountains of Cameroon and Nigeria over the past century, there are no previous assessments of the impact of forest fragmentation on montane amphibian populations in this region. Our estimates of genetic diversity are similar across populations within each species with levels of heterozygosity values consistent with local population declines. Except for a pair of populations (C. schioetzi) we did not observe genetic differentiation between forest and riparian forest fragment populations, nor across sites within continuous forest (L. bicolor). Our results demonstrate recent gene flow between forest fragments and the adjacent protected forests and suggest that small forest corridors connecting these may lessen the genetic consequences of at least 30 years of intense and severe fragmentation in Ngel Nyaki.Amphibians are the vertebrate group with the highest number of species threatened with extinction, and habitat loss and fragmentation are considered to be among the leading causes of their declines and extinctions. Little is known of the population biology of amphibian species inhabiting montane forests in Central and West Africa, where anthropogenic activities such as farming and cattle raising are major threats to native biodiversity. We used Amplified Fragment Length Polymorphisms (AFLPs) to assess the population genetic structure of two poorly known species,  Globally, amphibians face the most extreme population declines of all major vertebrate groups –3. ContrAs is the case with many other taxa, habitat fragmentation likely has long-term effects on the genetic viability of amphibian populations because of the combined effects of reduced population size and increased isolation . IncreasTo begin to redress the paucity of population genetics studies of African amphibians, we focused on populations of frogs within the forests of the Nigerian Highlands of the Cameroon Volcanic Line . This isCardioglossa schioetzi and Leptodactylodon bicolor, are endemic to the montane forests of Cameroon and Nigeria, they are small (<30 mm snout–vent length), have stream-adapted tadpoles, and live in leaf litter and rocky areas . Our results suggest that despite considerable habitat degradation  gene flow is still occurring (or occurred recently) among forest patches in two Afromontane frog species. This illustrates the importance of these degraded riparian forest fragments to amphibian communities.In Nigeria and all along the Cameroon Volcanic Line ,89, as eS1 FigK based on the Ln(K) K = 5, whereas graph B) and bar plot D) show the better K based on Evanno‘s method ΔK = 2. Each vertical bar represents an individual for which is shown the proportional genetic assignment to each cluster.Graph A) and bar plot C) depict the optimal (TIF)Click here for additional data file.S2 FigK based on the Ln(K) K = 7, whereas graph (B) and bar plot (D) show the better K based on Evanno‘s method ΔK = 2. Each vertical bar represents an individual for which is shown the proportional genetic assignment to each cluster.Graph (A) and bar plot (C) depict the optimal (TIF)Click here for additional data file.S1 TableTogether, the two preferred primer combinations ESP1B/MSP3 and ESP1B/MSP6 yielded 275 loci for the 198 samples representing both species.(XLSX)Click here for additional data file.


Of 103 serum samples collected from dogs in South Korea, 3 (2.9%) were positive for severe fever with thrombocytopenia syndrome virus (SFTSV) and 22 (21.4%) were positive for antibodies against SFTSV. A dog-derived isolate of SFTSV clustered with many South Korea SFTSV strains in the Japanese clade. Phenuiviridae family (previously Bunyaviridae), causes severe fever with thrombocytopenia syndrome (SFTS) in China, Japan, and the Republic of Korea (South Korea) (Severe fever with thrombocytopenia syndrome virus (SFTSV), a new tickborne phlebovirus of the Haemaphysalis longicornis tick is the main vector for SFTSV, promoting its circulation and transmission , obtained from dog 16, a German shepherd; dog 22, a Belgian Malinois; and dog 56, a German shepherd were positive for the small (S [346 bp]), medium (M [859 bp]), and L  segments of SFTSV by reverse transcription PCR (the L segment of dog 16 was not amplified). The sequences of the SFTSV S, M, and L segments differed from each other. The results of phylogenetic analysis of partial S, M, and L segments showed that sequences of SFTSV obtained from dogs were more related to strains from Japan than to strains from China . MoreoveWe used Vero cells to isolate the virus from positive serum. We observed cytopathic effect in only 1 of 3 positive samples. The results of phylogenetic analysis of the complete S segment indicated that the SFTSV strain isolated from dog 22 had not previously been isolated; this strain clustered with many SFTSV strains from South Korea and Japan .H. longicornis ticks are the main vector of SFTSV and the dominant tick species collected from vegetation and animals in South Korea (The detection rates of SFTSV RNA and antibodies in our study were 2.9% and 21.4%, respectively, which were higher than those observed in shelter dogs in South Korea (Although we isolated only a few SFTSV strains from animals and our results could not represent all characteristics of SFTSV, our findings could indicate that SFTSV might not be host-specific and that various SFTSV clades circulate and are distributed in South Korea. Further studies continuously surveilling animals for SFTSV, along with whole-genome analysis of dog-derived Korean isolates of SFTSV, would help clarify the mechanisms of transmission and molecular evolution of SFTSV.Additional information for severe fever with thrombocytopenia syndrome virus in dogs, South Korea.


We analyze possible future trends in dissolved inorganic nitrogen (DIN) export by world rivers and associated emissions of nitrous oxide (N2O). Our scenarios either assume that current trends continue or that nitrogen (N) inputs to aquatic systems are reduced as a result of changes in agriculture practices and fuel combustion technologies. The results indicate that moderate changes in the human diet in North America and Europe, reducing worldwide fertilizer use by only 16%, relative to Business-as-Usual (BAU) levels, may reduce DIN export rates to the North Atlantic and European Seas by about one third and associated N2O emissions by 36 to 77%. We furthermore calculate that relatively large reductions in NOy deposition rates in Europe (of about 80%) may reduce DIN export by rivers by a moderate 8% or less, relative to BAU levels. The potential effect of reduced NOy deposition on riverine DIN export is moderate, because most N in European rivers stems from agriculture, and not from fuel combustion. Nevertheless, the calculated 9% reduction (relative to BAU) in DIN inputs to the North Sea as a potential side effect of air pollution control may help achieve the international policy targets for reduced N inputs to the North Sea.


Scientific Reports 10.1038/s41598-018-28912-x, published online 17 July 2018Correction to: The original version of this Article contained errors.In the Abstract,“The clean and stable experimental platform permits the visualisation of the structure and orientation of microvilli present at the apical cell membrane under standard laboratory conditions together with registering subcellular details within a microvillus.”now reads:“The clean and stable experimental platform permits the visualisation of the structure and orientation of microvilli present at the apical cell membrane under standard laboratory conditions together with registering topographical features within a microvillus.”In the main text,24), which are visible in the zoomed-in phase image  and in the overlay image .”“In particular, we observe lateral striations running along the length of the microvillus unit (previously observed only using high-resolution electron microscopy at cryogenic temperaturesnow reads:24), which are visible in the zoomed-in phase image  and in the overlay image .”“In particular, we observe lateral striations along the entire length of the microvillus unit (previously observed only using high-resolution electron microscopy at cryogenic temperaturesThese errors have now been corrected in the PDF and HTML versions of the Article.


Transforming nursing home (NH) cultures—from impersonal institutions to enriching communities where residents and employees thrive—requires multifaceted change. NHs deploy an array of culture change (CC) practices, in three core domains: resident-centered care, staff empowerment, and physical environment. This study uses novel data on CC practice from a nationally representative panel of NHs  surveyed in 2009/2010 and 2016/2017. To understand how changes in practice adoption may relate to quality changes we linked longitudinal data on the CC practice domain scores for resident-centered care, staff empowerment, and physical environment and on NH deficiencies relating to health and quality of life (QoL) and combined these with Certification and Survey Provider Enhanced Reporting baseline data. Multinomial logistic regressions incorporating survey weights and inverse probability of weight (to address CC selection) estimated the relative risk ratios (RRR) of increased CC practice corresponding with NHs having fewer or no change in deficiencies, versus increased deficiencies. NHs with much increase in staff empowerment scores had a higher likelihood of no change (compared to an increase) in health deficiencies  and severe health deficiencies . With a RRR of 1.63, NHs with any improvement in resident-centered care scores appeared to have a higher likelihood of no change (compared to an increase) in QoL deficiencies but statistical significance was not reached (p=0.11). This study provides some support for the benefits of CC practices, and in particular, supports the importance of staff empowerment practices in NHs.


Studies of aging rarely include the older adults themselves in the process of conceptualizing questions, implementing the research, and evaluating the results. To provide opportunities for community members to become engaged in research, researchers and community stakeholders developed “Engaging Older Adult Learners as Health Researchers (ENGOAL).” This program educates older adults from underserved and underresourced communities about geriatric health and research methods, enabling them to become Research Partners. Two cohorts of African-American seniors (N=21) aged 53-79 have participated or are currently participating in six months of weekly classes followed by 4-6 months of research apprenticeships. Content and structure of classes  will be described. Challenges and successes in providing research apprenticeships  will be discussed.