Miracle-dz/UniFAR-FTUs huggingface dataset:
Correction: Engineered protein disaggregases mitigate toxicity of aberrant prion-like fusion proteins underlying sarcoma.

FUS and EWSR1 are RNA-binding proteins with prion-like domains (PrLDs) that aggregate in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The FUS and EWSR1 genes are also prone to chromosomal translocation events, which result in aberrant fusions between portions of the PrLDs of FUS and EWSR1 and the transcription factors CHOP and FLI. The resulting fusion proteins, FUS-CHOP and EWS-FLI, drive aberrant transcriptional programs that underpin liposarcoma and Ewing's sarcoma, respectively. The translocated PrLDs alter the expression profiles of these proteins and promote their phase separation and aggregation. Here, we report the development of yeast models of FUS-CHOP and EWS-FLI toxicity and aggregation. These models recapitulated several salient features of sarcoma patient cells harboring the FUS-CHOP and EWS-FLI translocations. To reverse FUS and EWSR1 aggregation, we have explored Hsp104, a hexameric AAA+ protein disaggregase from yeast. Previously, we engineered potentiated Hsp104 variants to suppress the proteotoxicity, aggregation, and mislocalization of FUS and other proteins that aggregate in ALS/FTD and Parkinson's disease. Potentiated Hsp104 variants that robustly suppressed FUS toxicity and aggregation also suppressed the toxicity and aggregation of FUS-CHOP and EWS-FLI. We suggest that these new yeast models are powerful platforms for screening for modulators of FUS-CHOP and EWS-FLI phase separation. Moreover, Hsp104 variants might be employed to combat the toxicity and phase separation of aberrant fusion proteins involved in sarcoma.
Prevalence and Etiology of Subclinical Mastitis in Ewes of the Tabriz Region, Iran

To investigate the period prevalence, etiology and some epidemiological features of subclinical mastitis in buffaloes from the Tabriz region, milk samples from 51 lactating buffaloes were aseptically collected for bacterial and California mastitis test and somatic cell counte. An association was observed between the occurrence of subclinical mastitis and lactation number of buffaloes. The periodic prevalence rate of SCM was 27.36%. Staphylococci were the most prevalent bacteria, representing 48.55% of the isolates. Coagulase-negative staphylococci (CNS) (36.18%), was the most prevalent species followed by staphylococcus aurous (14%). Lactobacillus, Corynebacterium bovis and Bacillus subtilis was the subsequent bacterial groups in importance according with the distribution among flocks representing 14%, 8% and 7% of the isolates. Coagulase-negative Staphylococci were the most prevailing isolates from samples that showed positve CMT results. (Rahim Beheshti, Behrad Eshratkhah, Jalal Shayegh, Jamshid Giasi Ghalehkandi, Vahid Dianat, Kambiz Valiei. Prevalence and etiology of subclinical mastitis in Buffalo of the Tabriz region, Iran. Journal of American Science 2011;7(5):642-645). (ISSN: 1545-1003). http://www.americanscience. org .
Negative predictive value (NPV) of FDG PET-CT for nodal disease in clinically node-negative early stage lung cancer (AJCC 7 th ed T1-2aN0) and identification of risk factors for occult nodal (pN1-N2) metastasis: implications for SBRT

Non-surgical methods are increasingly employed in the management of early stage lung cancer, but do not afford histological confirmation of nodal status. We sought to assess the incidence, pattern, and predictors of occult nodal involvement (pN1-pN2) in non-small cell lung cancer (NSCLC) patients with negative nodal uptake on fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in early stage lung cancer (clinical stage I AJCC 7 th edition). All patients treated surgically over a 3-year period at Dartmouth Hitchcock Medical Center who were AJCC 7th ed. clinical stage I by pre-operative PET-CT were included in this analysis. The agreement between the clinical stage based on PET-CT and true stage based on pathologic dissection was assessed. Multivariate logistic regression was used to analyze predictors of occult nodal metastasis. Of 144 clinically node-negative patients, 125 were pathologically nodenegative. For all 144 patients, the negative predictive values (NPVs) of PET-CT were 92% for mediastinal disease, 90% for N1 disease, and 87% for overall nodal metastases. The NPVs for mediastinal metastases were 95% in T1 disease and 87% in T2 disease. In multivariate analysis, tumor size (adjusted OR: 3.28, 95% CI: 1.41-7.57), central tumor location (adjusted OR: 7.3, 95% CI: 2.22-24.3), and age at surgery (adjusted OR: 0.95, 95% CI: 0.92-0.98) were significant predictors of occult nodal metastasis. The NPV of PET-CT in nodal staging has implications for the non-surgical treatment of lung cancer, such as stereotactic body radiotherapy, where routine pathologic nodal staging is not performed. Our data suggest PET-CT more accurately rules out the presence of nodal disease in smaller, peripherally located primary tumors.
Donor-Recipient Relationship and Risk of ESKD in Live Kidney Donors of Varied Racial Groups.

RATIONALE & OBJECTIVE Risk factors for kidney failure are the basis of live kidney donor candidate evaluation. We quantified risk for end-stage kidney disease (ESKD) by the biological relationship of the donor to the recipient, a risk factor that is not addressed by current clinical practice guidelines. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS A cohort of 143,750 US kidney donors between 1987 and 2017. EXPOSURE Biological relationship of donor and recipient. OUTCOME ESKD. Donors' records were linked to national dialysis and transplantation registries to ascertain development of the outcome. ANALYTIC APPROACH Donors were observed over a median of 12 (interquartile range, 6-18; maximum, 30) years. Survival analysis methods that account for the competing risk for death were used. RESULTS Risk for ESKD varied by orders of magnitude across donor-recipient relationship categories. For Asian donors, risks compared with unrelated donors were 259.4-fold greater for identical twins (95% CI, 19.5-3445.6), 4.7-fold greater for full siblings (95% CI, 0.5-41.0), 3.5-fold greater for offspring (95% CI, 0.6-39.5), 1.0 for parents, and 1.0 for half-sibling or other biological relatives. For black donors, risks were 22.5-fold greater for identical twin donors (95% CI, 4.7-107.0), 4.1-fold for full siblings (95% CI, 2.1-7.8), 2.7-fold for offspring (95% CI, 1.4-5.4), 3.1-fold for parents (95% CI, 1.4-6.8), and 1.3-fold for half-sibling or other biological relatives (95% CI, 0.5-3.3). For white donors, risks were 3.5-fold greater for identical twin donors (95% CI, 0.5-25.3), 2.0-fold for full siblings (95% CI, 1.4-2.8), 1.4-fold for offspring (95% CI, 0.9-2.3), 2.9-fold for parents (95% CI, 2.0-4.1), and 0.8-fold for half-sibling or other biological relatives (95% CI, 0.3-1.6). LIMITATIONS Insufficient sample size in some race and relationship groups. Absence of data for family history of kidney disease for donors biologically unrelated to their recipients. CONCLUSIONS Marked differences in risk for ESKD across types of donor-recipient relationship were observed for Asian, black, and white donors. These findings warrant further validation with more robust data to better inform clinical practice guidelines.
Body Fluid-Independent Effects of Dietary Salt Consumption in Chronic Kidney Disease

The average dietary salt (i.e., sodium chloride) intake in Western society is about 10 g per day. This greatly exceeds the lifestyle recommendations by the WHO to limit dietary salt intake to 5 g. There is robust evidence that excess salt intake is associated with deleterious effects including hypertension, kidney damage and adverse cardiovascular health. In patients with chronic kidney disease, moderate reduction of dietary salt intake has important renoprotective effects and positively influences the efficacy of common pharmacological treatment regimens. During the past several years, it has become clear that besides influencing body fluid volume high salt also induces tissue remodelling and activates immune cell homeostasis. The exact pathophysiological pathway in which these salt-induced fluid-independent effects contribute to CKD is not fully elucidated, nonetheless it is clear that inflammation and the development of fibrosis play a major role in the pathogenic mechanisms of renal diseases. This review focuses on body fluid-independent effects of salt contributing to CKD pathogenesis and cardiovascular health. Additionally, the question whether better understanding of these pathophysiological pathways, related to high salt consumption, might identify new potential treatment options will be discussed.
Intracellular Environment Improvement of Mycobacterium neoaurum for Enhancing Androst-1,4-Diene-3,17-Dione Production by Manipulating NADH and Reactive Oxygen Species Levels

As one of the most significant steroid hormone precursors, androst-1,4-diene-3,17-dione (ADD) could be used to synthesize many valuable hormone drugs. The microbial transformation of sterols to ADD has received extensive attention in recent years. In a previous study, Mycobacterium neoaurum JC-12 was isolated and converted sterols to the major product, ADD. In this work, we enhanced ADD yield by improving the cell intracellular environment. First, we introduced a nicotinamide adenine dinucleotide (NADH) oxidase from Bacillus subtilis to balance the intracellular NAD+ availability in order to strengthen the ADD yield. Then, the catalase gene from M. neoaurum was also over-expressed to simultaneously scavenge the generated H2O2 and eliminate its toxic effects on cell growth and sterol transformation. Finally, using a 5 L fermentor, the recombinant strain JC-12yodC-katA produced 9.66 g/L ADD, which increased by 80% when compared with the parent strain. This work shows a promising way to increase the sterol transformation efficiency by regulating the intracellular environment.
Blockchain Authentication for AODV Routing Protocol

recently, wireless ad-hoc networks have become a significant component in the digital revolution and smart cities. The heterogeneity and high-mobility in smart city systems have arisen the need for the mobile ad-hoc network (MANET). Ad hoc On-Demand Distance Vector (AODV) emerges as an efficient routing protocol in MANET is based on the less overhead by reducing message exchange with limited information. However, this creates a weakness as nodes have limited knowledge about other nodes’ identity inside the path beyond the neighboring node (node in transmission range). That prevents the participant from authenticating others and has limited capability to check the integrity of the exchanged information. To accomplish this, it requires a further exchange of messages that defeat the AODV main principle and causes extra overhead that drains the portable devices’ limited battery energy inside the network. This paper used the blockchain concept to generate a hashed identifier from the node’s IP and passed between nodes inside the path during the route discovery that provides assurance about the identity of the node and keeps the integrity of the exchanged information. Additionally, Simulation results using (Riverbed/Opnet) of the attack scenario show that the proposed algorithm prevents impersonation and black-hole attacks by eliminating the path that involves malicious nodes with a (4 millisecond) increase in route discovery time.
The Acidic Tumor Microenvironment as a Driver of Cancer.

Acidic metabolic waste products accumulate in the tumor microenvironment because of high metabolic activity and insufficient perfusion. In tumors, the acidity of the interstitial space and the relatively well-maintained intracellular pH influence cancer and stromal cell function, their mutual interplay, and their interactions with the extracellular matrix. Tumor pH is spatially and temporally heterogeneous, and the fitness advantage of cancer cells adapted to extracellular acidity is likely particularly evident when they encounter less acidic tumor regions, for instance, during invasion. Through complex effects on genetic stability, epigenetics, cellular metabolism, proliferation, and survival, the compartmentalized pH microenvironment favors cancer development. Cellular selection exacerbates the malignant phenotype, which is further enhanced by acid-induced cell motility, extracellular matrix degradation, attenuated immune responses, and modified cellular and intercellular signaling. In this review, we discuss how the acidity of the tumor microenvironment influences each stage in cancer development, from dysplasia to full-blown metastatic disease. Expected final online publication date for the Annual Review of Physiology, Volume 82 is February 10, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Powerful rare variant association testing in a copula‐based joint analysis of multiple phenotypes

In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single‐marker association test called C‐JAMP (Copula‐based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single‐marker and multi‐marker rare‐variant tests in extensive simulation studies. C‐JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C‐JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C‐JAMP or competing approaches had higher power depended on the effect size. When C‐JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real‐data application, we analyzed sequencing data using C‐JAMP and performed the first genome‐wide association studies of high‐molecular‐weight and medium‐molecular‐weight adiponectin plasma concentrations. C‐JAMP identified 20 rare variants with p‐values smaller than 10−5, while all other tests resulted in the identification of fewer variants with higher p‐values. In summary, the results indicate that C‐JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C‐JAMP is implemented as an R package and freely available from https://cran.r‐project.org/package=CJAMP.
Zebrafish Models of Cancer—New Insights on Modeling Human Cancer in a Non-Mammalian Vertebrate

Zebrafish (Danio rerio) is a valuable non-mammalian vertebrate model widely used to study development and disease, including more recently cancer. The evolutionary conservation of cancer-related programs between human and zebrafish is striking and allows extrapolation of research outcomes obtained in fish back to humans. Zebrafish has gained attention as a robust model for cancer research mainly because of its high fecundity, cost-effective maintenance, dynamic visualization of tumor growth in vivo, and the possibility of chemical screening in large numbers of animals at reasonable costs. Novel approaches in modeling tumor growth, such as using transgene electroporation in adult zebrafish, could improve our knowledge about the spatial and temporal control of cancer formation and progression in vivo. Looking at genetic as well as epigenetic alterations could be important to explain the pathogenesis of a disease as complex as cancer. In this review, we highlight classic genetic and transplantation models of cancer in zebrafish as well as provide new insights on advances in cancer modeling. Recent progress in zebrafish xenotransplantation studies and drug screening has shown that zebrafish is a reliable model to study human cancer and could be suitable for evaluating patient-derived xenograft cell invasiveness. Rapid, large-scale evaluation of in vivo drug responses and kinetics in zebrafish could undoubtedly lead to new applications in personalized medicine and combination therapy. For all of the above-mentioned reasons, zebrafish is approaching a future of being a pre-clinical cancer model, alongside the mouse. However, the mouse will continue to be valuable in the last steps of pre-clinical drug screening, mostly because of the highly conserved mammalian genome and biological processes.
Depletion of KNL2 Results in Altered Expression of Genes Involved in Regulation of the Cell Cycle, Transcription, and Development in Arabidopsis

Centromeres contain specialized nucleosomes at which histone H3 is partially replaced by the centromeric histone H3 variant cenH3 that is required for the assembly, maintenance, and proper function of kinetochores during mitotic and meiotic divisions. Previously, we identified a KINETOCHORE NULL 2 (KNL2) of Arabidopsis thaliana that is involved in the licensing of centromeres for the cenH3 recruitment. We also demonstrated that a knockout mutant for KNL2 shows mitotic and meiotic defects, slower development, reduced growth rate, and fertility. To analyze an effect of KNL2 mutation on global gene transcription of Arabidopsis, we performed RNA-sequencing experiments using seedling and flower bud tissues of knl2 and wild-type plants. The transcriptome data analysis revealed a high number of differentially expressed genes (DEGs) in knl2 plants. The set was enriched in genes involved in the regulation of the cell cycle, transcription, development, and DNA damage repair. In addition to comprehensive information regarding the effects of KNL2 mutation on the global gene expression, physiological changes in plants are also presented, which provides an integrated understanding of the critical role played by KNL2 in plant growth and development.
Effect of Lipid-Encapsulated Acacia Tannin Extract on Feed Intake, Nutrient Digestibility and Methane Emission in Sheep

Simple Summary Enteric methane is not just a contributor to anthropogenic greenhouse gas emission, it also represents a loss of potential feed energy. The use of Acacia tannin extracts as a dietary additive effectively reduced methane production while also modulating nitrogen loss. The reduction in methane output in sheep receiving the encapsulated-Acacia tannin extract (ATE), as compared to the crude-ATE diet, suggests the potential use of encapsulation to improve tannin inclusion in ruminant diets, by enabling the sustained release of the tannin to the rumen environment. Abstract Tannins have become important phytochemicals in ruminant production, due to their wide range of biological activities. The use of a crude extract often comes with limitations, such as reduced feed intake and fibre digestibility, which could be overcome by the use of encapsulated tannin extract. In this study, four rumen-cannulated Merino wethers were used in a 4 × 4 Latin square design to determine the effect of encapsulating Acacia mearnsii tannin extract on intake, nutrient digestibility, and methane emission. The animals were placed on one of the following diets: control diet only, diet + silvafeed (Silvafeed ByPro, 10 g/kg feed), diet + Acacia tannin extract (ATE), 40 g/kg feed), and, diet + lipid-encapsulated-ATE (palm oil encapsulated ATE, 50 g/kg feed) in 4 cycles. Wethers were offered an Eragrotis and Lucerne hay-based total mixed ration diet above maintenance requirement with forage: concentrate ratio 50:50. Silvafeed, a commercial tannin additive, was used as a positive control. Nutrient intake was not different across the treatments, but nutrient digestibility was affected by dietary additives (p < 0.05). Compared to the control, and unlike the crude extract, encapsulated-ATE and silvafeed did not reduce dry matter, organic matter, and neutral detergent fibre digestibility. While the overall N-retention and total N-excretion (g/d) were not affected by dietary additives, ATE and encapsulated-ATE diets reduced urine-N excretion (g/d) and only a slight reduction was observed in silvafeed diet. The faecal-N proportion was highest in the ATE diet (388 g/kg N-intake), followed by encapsulated-ATE (317 g/kg), and silvafeed (267 g/kg), with the control diet having the lowest proportion (230 g/kg). The acetate:propionate (A:P) ratio reduced as a result of the inclusion of dietary additives with crude ATE and silvafeed having lower A:P ratio compared to the control diet. Methane production expressed in g/kg dry matter (DM) intake was reduced by 12%, 30% and 19% in the silvafeed, crude ATE and encapsulated-ATE diets, respectively (p < 0.05). The reduced methane production with higher neutral detergent fibre (NDF) digestibility in the encapsulated-ATE, compared to the crude-ATE, confirms that encapsulated-tannin can be used as an additive in ruminant diets.
lower extremity Burns, complications and outcome.

BACKGROUND we have encountered many burn cases with lower extremity burn with adverse outcome. MATERIALS & METHODS the study was a retrospective cohort study in two years, mean (SD) of follow up was 12(7) months. All demographic data, cause burn, time, TBSA (total burn surface area), presence lower extremity burn and its BSA (burn surface area), foot burn, delay in treatment, smoking, infection, morbidity, co-morbid diseases, length of stay (LOS), amputation, mortality and outcome were gathered from patients' files. Statistical analysis was done with SPSS 21software. RESULTS we had 14215 burn patients, of them 995 were admitted according to criteria of ABA. 610(61.3%) were male and 358 (37%) female. Male to female ratio was 1.58:1. The mean age +/- SD was 33.64 +/-23.45. Mean (SD) of lower extremity BSA was 12.09 ± 9.18 %The patients who had 10-19% burn, had 3 times more risk of mortality than patients with 0-9% burn (p<0.018). And those with 20-29%$ burn had 35 times more risk of mortality comparing to patients with 0-9% burn. The difference was significant too. (p<0.000). Delay in treatment, presence of co-morbid diseases and Diabetes would not do any increase in mortality. The sex, weight, cause of burn, diabetes and delay in treatment have not any influence on the death risk. But age and lower extremity BSA have influence on the risk of death. According to statistical study: with every one-year increase in age, death rate increased by 4%(p<0.0001). With every 1% increase in lower extremity BSA, death rate increase by 9% (p<0.0005) and with every one day increase in LOS, the death rate increase by 4%. CONCLUSIONS statistical study shows lower extremity burn, TBSA, age and length of stay have great influence on the outcome of these patients. Sex, weight, cause of burn and delay in treatment have not affected the risk of mortality.