Miracle-dz/UniFAR-FTUs huggingface dataset:
NHR‐49/HNF4 integrates regulation of fatty acid metabolism with a protective transcriptional response to oxidative stress and fasting

Endogenous and exogenous stresses elicit transcriptional responses that limit damage and promote cell/organismal survival. Like its mammalian counterparts, hepatocyte nuclear factor 4 (HNF4) and peroxisome proliferator‐activated receptor α (PPARα), Caenorhabditis elegans NHR‐49 is a well‐established regulator of lipid metabolism. Here, we reveal that NHR‐49 is essential to activate a transcriptional response common to organic peroxide and fasting, which includes the pro‐longevity gene fmo‐2/flavin‐containing monooxygenase. These NHR‐49‐dependent, stress‐responsive genes are also upregulated in long‐lived glp‐1/notch receptor mutants, with two of them making critical contributions to the oxidative stress resistance of wild‐type and long‐lived glp‐1 mutants worms. Similar to its role in lipid metabolism, NHR‐49 requires the mediator subunit mdt‐15 to promote stress‐induced gene expression. However, NHR‐49 acts independently from the transcription factor hlh‐30/TFEB that also promotes fmo‐2 expression. We show that activation of the p38 MAPK, PMK‐1, which is important for adaptation to a variety of stresses, is also important for peroxide‐induced expression of a subset of NHR‐49‐dependent genes that includes fmo‐2. However, organic peroxide increases NHR‐49 protein levels, by a posttranscriptional mechanism that does not require PMK‐1 activation. Together, these findings establish a new role for the HNF4/PPARα‐related NHR‐49 as a stress‐activated regulator of cytoprotective gene expression.
Solid state fermentation of Jatropha curcas kernel cake: Proximate composition and antinutritional components

Five fungi ( Aspergillus niger, Penicillium chrysogenum, Rhizopus oligosporus, Rhizopus nigricans and Trichoderma longibrachitum) were used in the fermentation of Jatropha curcas kernel cake for a 7 days period in a completely randomized design model. The results revealed significant increase in the crude protein content of all the fungi treated samples with Aspergillus niger and T. longbrachitum treated cake recorded higher value compared to other treated samples. There was no significant difference in the crude fiber content among all the samples. With the exception of ether extract content of sample treated with Rhizopus nigricans which was similar to that of the control (untreated sample) other samples showed lower significant values than the untreated (control) sample. Contrarily, the ash content was significantly lower in the control sample compared to other fungi treated samples. The content of the trypsin inhibitor was highest (18.6 mg/kg) in the control but reduced significantly in the fungi treated samples (6.50 - 8.23). The lectin, saponins, phytate and phorbolester contents followed similar trend. It could be concluded from this study that solid state fermentation of Jatropha kernel cake detoxified and inactivate almost 100% of the antinutrient contents expect phorbolester to a tolerable level in the A. niger treated sample.
Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB

ABSTRACT RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173–1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6–17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae, which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae, which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae.
Association of the Cold Shock DEAD-Box RNA Helicase RhlE to the RNA Degradosome in Caulobacter crescentus

ABSTRACT In diverse bacterial lineages, multienzyme assemblies have evolved that are central elements of RNA metabolism and RNA-mediated regulation. The aquatic Gram-negative bacterium Caulobacter crescentus, which has been a model system for studying the bacterial cell cycle, has an RNA degradosome assembly that is formed by the endoribonuclease RNase E and includes the DEAD-box RNA helicase RhlB. Immunoprecipitations of extracts from cells expressing an epitope-tagged RNase E reveal that RhlE, another member of the DEAD-box helicase family, associates with the degradosome at temperatures below those optimum for growth. Phenotype analyses of rhlE, rhlB, and rhlE rhlB mutant strains show that RhlE is important for cell fitness at low temperature and its role may not be substituted by RhlB. Transcriptional and translational fusions of rhlE to the lacZ reporter gene and immunoblot analysis of an epitope-tagged RhlE indicate that its expression is induced upon temperature decrease, mainly through posttranscriptional regulation. RNase E pulldown assays show that other proteins, including the transcription termination factor Rho, a second DEAD-box RNA helicase, and ribosomal protein S1, also associate with the degradosome at low temperature. The results suggest that the RNA degradosome assembly can be remodeled with environmental change to alter its repertoire of helicases and other accessory proteins. IMPORTANCE DEAD-box RNA helicases are often present in the RNA degradosome complex, helping unwind secondary structures to facilitate degradation. Caulobacter crescentus is an interesting organism to investigate degradosome remodeling with change in temperature, because it thrives in freshwater bodies and withstands low temperature. In this study, we show that at low temperature, the cold-induced DEAD-box RNA helicase RhlE is recruited to the RNA degradosome, along with other helicases and the Rho protein. RhlE is essential for bacterial fitness at low temperature, and its function may not be complemented by RhlB, although RhlE is able to complement for rhlB loss. These results suggest that RhlE has a specific role in the degradosome at low temperature, potentially improving adaptation to this condition.
The Role of Ellis‐Van Creveld 2(EVC2) in Mice During Cranial Bone Development

EvC syndrome is a type of autosomal‐recessive chondrodysplasia. Previous case studies in patients suggest abnormal craniofacial development, in addition to dwarfism and tooth abnormalities. To investigate how craniofacial development is affected in EvC patients, surface models were generated from micro‐CT scans of control mice, Evc2 global mutant mice and Evc2 neural crest‐specific mutant mice. The anatomic landmarks were placed on the surface model to assess the morphological abnormalities in the Evc2 mutants. Through analyzing the linear and angular measurements between landmarks, we identified a smaller overall skull, shorter nasal bone, shorter frontal bone, and shorter cranial base in the Evc2 global mutants. By comparing neural crest‐specific Evc2 mutants with control mice, we demonstrated that the abnormalities within the mid‐facial regions are not accounted for by the Evc2 mutation within these regions. Additionally, we also identified disproportionate length to width ratios in the Evc2 mutants at all levels from anterior to posterior of the skull. Overall, this study demonstrates a more comprehensive analysis on the craniofacial morphological abnormalities in EvC syndrome and provides the developmental insight to appreciate the impact of Evc2 mutation within the neural crest cells on multiple aspects of skull deformities. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:46–55, 2018. © 2017 Wiley Periodicals, Inc.
Portability of an algorithm to identify rheumatoid arthritis in electronic health records

OBJECTIVES Electronic health records (EHR) can allow for the generation of large cohorts of individuals with given diseases for clinical and genomic research. A rate-limiting step is the development of electronic phenotype selection algorithms to find such cohorts. This study evaluated the portability of a published phenotype algorithm to identify rheumatoid arthritis (RA) patients from EHR records at three institutions with different EHR systems. MATERIALS AND METHODS Physicians reviewed charts from three institutions to identify patients with RA. Each institution compiled attributes from various sources in the EHR, including codified data and clinical narratives, which were searched using one of two natural language processing (NLP) systems. The performance of the published model was compared with locally retrained models. RESULTS Applying the previously published model from Partners Healthcare to datasets from Northwestern and Vanderbilt Universities, the area under the receiver operating characteristic curve was found to be 92% for Northwestern and 95% for Vanderbilt, compared with 97% at Partners. Retraining the model improved the average sensitivity at a specificity of 97% to 72% from the original 65%. Both the original logistic regression models and locally retrained models were superior to simple billing code count thresholds. DISCUSSION These results show that a previously published algorithm for RA is portable to two external hospitals using different EHR systems, different NLP systems, and different target NLP vocabularies. Retraining the algorithm primarily increased the sensitivity at each site. CONCLUSION Electronic phenotype algorithms allow rapid identification of case populations in multiple sites with little retraining.
Population structure of a vector‐borne plant parasite

Parasites are among the most diverse groups of life on Earth, yet complex natural histories often preclude studies of their speciation processes. The biology of parasitic plants facilitates in situ collection of data on both genetic structure and the mechanisms responsible for that structure. Here, we studied the role of mating, dispersal and establishment in host race formation of a parasitic plant. We investigated the population genetics of a vector‐borne desert mistletoe (Phoradendron californicum) across two legume host tree species (Senegalia greggii and Prosopis velutina) in the Sonoran desert using microsatellites. Consistent with host race formation, we found strong host‐associated genetic structure in sympatry, little genetic variation due to geographic site and weak isolation by distance. We hypothesize that genetic differentiation results from differences in the timing of mistletoe flowering by host species, as we found initial flowering date of individual mistletoes correlated with genetic ancestry. Hybrids with intermediate ancestry were detected genetically. Individuals likely resulting from recent, successful establishment events following dispersal between the host species were detected at frequencies similar to hybrids between host races. Therefore, barriers to gene flow between the host races may have been stronger at mating than at dispersal. We also found higher inbreeding and within‐host individual relatedness values for mistletoes on the more rare and isolated host species (S. greggii). Our study spanned spatial scales to address how interactions with both vectors and hosts influence parasitic plant structure with implications for parasite virulence evolution and speciation.
Performance of 3 Enthesitis Indices in Patients with Peripheral Spondyloarthritis During Treatment with Adalimumab

Objective. To evaluate the validity of enthesitis indices in patients with peripheral spondyloarthritis (pSpA). Methods. The ABILITY-2 study evaluated the efficacy of adalimumab (ADA) versus placebo (PBO) in patients with active pSpA over 12 weeks. Patients received open-label ADA for an additional 144 weeks. Twenty-nine enthesitis sites used in 3 enthesitis scoring systems [Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index, Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)] were assessed; discriminatory capacity and treatment response at Week 12 were calculated by standardized mean difference (SMD) and Guyatt’s effect size (ES). Sites showing resolution or new-onset enthesitis from baseline to Week 12 were analyzed. Results. Overall, 165 patients (ADA, n = 84; PBO, n = 81) were randomized; 143 had ≥ 1 enthesitis site at baseline. The LEI (SMD −0.73, ES −1.07) and SPARCC (SMD −0.56, ES −0.99) enthesitis indices showed higher discriminatory ability and treatment response than MASES (SMD −0.32, ES −0.81). At Week 12, among sites that were positive at baseline, significantly more (p < 0.05) showed resolution among patients treated with ADA versus PBO in the Achilles tendon (60.4% and 36.5%, respectively), medial epicondyle (73.2%, 48.7%), lateral epicondyle (80.6%, 52.8%), and iliac crest (73.5%, 47.2%). Among negative sites at baseline, significantly less (p < 0.05) new-onset enthesitis was observed with ADA versus PBO for Achilles tendon (3.6% and 10.9%, respectively), greater trochanter (3.4%, 14.4%), lateral epicondyle humerus (4.7%, 15.1%), medial femoral condyle (1.6%, 9.2%), and quadriceps insertion superior patella (1.5%, 7.0%). Conclusion. The LEI and SPARCC enthesitis indices showed better discriminatory capacity and treatment response in patients with pSpA versus MASES, likely because these indices contain more peripheral sites. Trial registration number: ClinicalTrials.gov NCT01064856.
Ultraviolet radiation enhances Arctic net plankton community production

In this study we report the response of net community production (NCP) of plankton communities in the Arctic surface waters exposure to natural ultraviolet radiation (UVR) conditions. A possible bias in previous measurements performed using borosilicate glass bottles (opaque to most UVR) can underestimate NCP. Here we show that 77% of the sampled communities suffer, on average, 38.5% of net increase in NCP when exposed to natural UV‐B condition, relative to values when UV‐B radiation is excluded. UV‐B tends to shift communities toward autotrophy, with the most autotrophic communities responding the strongest. This is likely explained by the inhibition of bacterial respiration during the continuous day period of the Arctic summer, corroborated by experiments where bacterial production influenced by UV‐B directly affect NCP. Whereas Arctic warming is expected to lead to lower NCP, our results show that increased UV‐B radiation may partially compensate this negative effect in surface waters.
Taxonomic models of individual differences: a guide to transdisciplinary approaches

Models and constructs of individual differences are numerous and diverse. But detecting commonalities, differences and interrelations is hindered by the common abstract terms (e.g. ‘personality’, ‘temperament’, ‘traits’) that do not reveal the particular phenomena denoted. This article applies a transdisciplinary paradigm for research on individuals that builds on complexity theory and epistemological complementarity. Its philosophical, metatheoretical and methodological frameworks provide concepts to differentiate various kinds of phenomena (e.g. physiology, behaviour, psyche, language). They are used to scrutinize the field's basic concepts and to elaborate methodological foundations for taxonomizing individual variations in humans and other species. This guide to developing comprehensive and representative models explores the decisions taxonomists must make about which individual variations to include, which to retain and how to model them. Selection and reduction approaches from various disciplines are classified by their underlying rationales, pinpointing possibilities and limitations. Analyses highlight that individuals' complexity cannot be captured by one universal model. Instead, multiple models phenotypically taxonomizing different kinds of variability in different kinds of phenomena are needed to explore their causal and functional interrelations and ontogenetic development that are then modelled in integrative and explanatory taxonomies. This research agenda requires the expertise of many disciplines and is inherently transdisciplinary. This article is part of the theme issue ‘Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
Characterization In Vitro and In Vivo of Pandemic (H1N1) 2009 Influenza Viruses Isolated from Patients

ABSTRACT The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. Molecular evolutionary analyses of the 2009 pandemic influenza A H1N1 [A(H1N1)pdm09] virus revealed two major clusters, cluster I and cluster II. Although the pathogenicity of viruses belonging to cluster I, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster II, which has spread more widely in the world, has not been studied in this animal model. Here, we characterized two Norwegian isolates belonging to cluster II, namely, A/Norway/3568/2009 (Norway3568) and A/Norway/3487-2/2009 (Norway3487), which caused distinct clinical symptoms, despite their genetic similarity. We observed more efficient replication in cultured cells and delayed virus clearance from ferret respiratory organs for Norway3487 virus, which was isolated from a severe case, compared with the efficiency of replication and time of clearance of Norway3568 virus, which was isolated from a mild case. Moreover, Norway3487 virus to some extent caused more severe lung damage in nonhuman primates than did Norway3568 virus. Our data suggest that the distinct replicative and pathogenic potentials of these two viruses may result from differences in their biological properties (e.g., the receptor-binding specificity of hemagglutinin and viral polymerase activity).
Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6.

BACKGROUND The spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant ataxias: some mutations, including SCA1, SCA2, and SCA3, are multisystemic disorders characterized by a variety of noncerebellar symptoms while others, like SCA6, give rise to a pure cerebellar syndrome. OBJECTIVE To identify impairments of the dopaminergic system and regional changes of glucose metabolism in SCA1, SCA2, SCA3, and SCA6. METHODS We used [11C]d-threo-methylphenidate and [18F]fluorodeoxyglucose positron emission tomography to identify cerebral dopamine terminal loss and specific regional metabolic patterns in SCA1, SCA2, SCA3, and SCA6. RESULTS The binding potential of [11C]d-threo-methylphenidate was reduced in the striatum in SCA2 and SCA3; in contrast to patients with Parkinson disease, no increased susceptibility of the putamen was evident. Decreased regional cerebral glucose metabolism was found in the cerebellum of all patients with SCA, the brainstem of SCA1, SCA2, SCA3, the thalamus and putamen of SCA3, and the parietal cortex of patients with SCA2. A trend toward increased regional cerebral glucose metabolism was found in the temporal cortex of all patients with SCA, pronounced in SCA6. CONCLUSIONS Specific biochemical patterns point to different mechanisms of neuronal dysfunction in SCA1, SCA2, SCA3, and SCA6; dopamine terminal loss is severe in SCA2 but distinct from Parkinson disease.
Best practices in exploratory factor analysis: four recommendations for getting the most from your analysis.

Exploratory factor analysis (EFA) is a complex, multi-step process. The goal of this paper is to collect, in one article, information that will allow researchers and practitioners to understand the various choices available through popular software packages, and to make decisions about ”best practices” in exploratory factor analysis. In particular, this paper provides practical information on making decisions regarding (a) extraction, (b) rotation, (c) the number of factors to interpret, and (d) sample size.
Closed-Loop Autonomous Pilot and Compressive CSIT Feedback Resource Adaptation in Multi-User FDD Massive MIMO Systems

Acquisition of accurate channel state information (CSI) at the transmitter (CSIT) is a major challenge of deploying frequency-division duplexing massive MIMO systems. Although compressive sensing (CS)-based CSIT estimation approaches have been proposed to reduce the pilot training overhead for massive MIMO systems, the existing schemes cannot properly dimension the minimum required pilot symbols to estimate the CSIT of all users at the required CSIT quality, because of the loose bounds on the required number of measurements for successful CS recovery and the unknown sparsity levels of user channels. In this paper, we propose a robust closed-loop pilot and CSIT feedback resource adaptation framework which not only exploits the joint sparsity of the multiuser massive MIMO channels to improve the CSIT estimation performance, but also has the built-in learning capability to adapt to the minimum pilot and feedback resources needed for successful CSIT recovery under unknown and time-varying channel sparsity levels. We establish the convergence of the proposed closed-loop adaptation algorithm under certain conditions. Simulations show that the proposed framework has substantial performance gain over conventional schemes with a fixed number of pilots and is very robust to dynamic sparsity as well as model mismatch.