Miracle-dz/UniFAR-FTUs huggingface dataset:
Fruits and migrant health: Consequences of stopping over in exotic- vs. native-dominated shrublands on immune and antioxidant status of Swainson's Thrushes and Gray Catbirds

ABSTRACT Migration is a physiologically demanding activity. Recent studies suggest that migrating birds can improve their immune and antioxidant status during stopover, implying that variation in stopover habitat can affect migrants' health. We studied 2 species that are strongly frugivorous during fall migration, Swainson's Thrushes (Catharus ustulatus) and Gray Catbirds (Dumetella carolinensis). We asked whether birds that used shrubland dominated by exotic plants experienced differences in mass change, immune function, and antioxidant status relative to conspecifics in native-dominated shrubland during fall stopover in Michigan, USA, in 2012–2013. We found no habitat-related differences in any of the measured health parameters for Swainson's Thrushes. However, Gray Catbirds using native-dominated shrubland retained mass while those in exotic-dominated shrubland lost mass in 2013. Gray Catbirds in exotic-dominated habitat that year also had poorer immune status (elevated granulocyte:lymphocyte ratio and reduced hemagglutination and haptoglobin) and had lower plasma total carotenoids (immunostimulatory antioxidants) relative to conspecifics in native-dominated shrubland. While these findings were not replicated in 2012, circulating antioxidant capacity was lower in both years in Gray Catbirds captured in exotic habitat. Habitat-specific estimates of dietary energy, carotenoid, and antioxidant content per unit mass of fruit were similar between habitat types for Swainson's Thrushes. For Gray Catbirds, however, the fruit diet was lower in carotenoids and antioxidant capacity, but not in energy, in exotic habitat. Our results provide evidence that differential use of stopover habitats may affect the immune and antioxidant status of migrating landbirds. Furthermore, our results suggest that habitat may affect health status based on the complex relationships among quality and abundance of food, food preferences, and refueling performance, which vary among species. We suggest that future studies measure immune and antioxidant metrics in addition to refueling performance to better understand the effects of stopover habitat use on landbird migrant health. This information may improve assessment of habitat quality for migrants.
Melanoma proteomics unravels major differences related to mutational status

The aim of the study was to explore the molecular differences between melanoma tumor subtypes, based on BRAF and NRAS mutational status. Fourteen formalin-fixed, paraffin- embedded melanoma samples were analyzed using a high-throughput proteomics approach, coupled with probabilistic graphical models and Flux Balance Analysis, to characterize these differences. Proteomics analyses showed differences in expression of proteins related with fatty acid metabolism, melanogenesis and extracellular space between BRAF mutated and BRAF non-mutated melanoma tumors. Additionally, probabilistic graphical models showed differences between melanoma subgroups at biological processes such as melanogenesis or metabolism. On the other hand, Flux Balance Analysis predicts a higher tumor growth rate in BRAF mutated melanoma samples. In conclusion, differential biological processes between melanomas showing a specific mutational status can be detected using combined proteomics and computational approaches.
Roles of the Nedd4 Family E3 Ligases in Glial Function and Nerve Cell Development

Protein ubiquitination is one of the core regulatory post-translational modification in neuronal development. In this study, we used brain specific KO mice to identify novel substrate proteins of several Nedd4 family E3 ligases, i.e. Nedd4-1, Nedd4-2, WWP1 and WWP2. We developed a highly reliable approach to identify transmembrane substrate proteins of Nedd4-1 and Nedd4-2 by combining iTRAQ quantitative mass spectrometry with synaptic membrane purification. We showed that levels of the main inwardly rectifier potassium channel in astrocytes, Kir4.1, and the main gap junction protein in astrocytes, Connexin-43, are upregulated in Nedd4-1 and Nedd4-2 brain specific double KO mice. Furthermore, we showed that Kir4.1 is ubiquitinated in vivo and in vitro by Nedd4-1 and Nedd4-2 whereas Connexin-43 is ubiquitinated by Nedd4-2 in vivo via a K63-linked polyubiquitin chains. In addition, we showed that glial loss of Nedd4-1 and Nedd4-2 leads to the reduced averaged power of gamma oscillatory activity in the CA3 region of the hippocampus in Nedd4-1; Nedd4-2 double KO and Nedd4-2 single KO as compared control mice, indicating that Nedd4-1 and Nedd4-2 play a crucial role in the regulation of neuronal network through astrocytic network in the hippocampus. Moreover, we showed that Prr7 is a novel substrate of Nedd4-2 at postsynapses and Nedd4-2 conjugates K63-linked polyubiquitin chains to cytoplasmic region of Prr7. Such ubiquitination of Prr7 might play a role in spine maturation during the development. Additionally, we identified CAPZA1, VCP and PKM2 as the novel substrate proteins of WWP1 and WWP2 E3 ligases. We showed that genetic deletion of WWP1 and WWP2 conditionally in neurons leads to enhanced dendrite growth in hippocampal neurons, indicating that WWP1 and WWP2 are negative regulator of dendrite development. Overexpression of CAPZA1 in wild type hippocampal neurons phenocopies the enhanced dendrite growth in WWP1; WWP2 double knockout neurons indicating that ubiquitination of CAPZA1 by WWP1 and WWP2 might play a crucial role in regulation of CAPZA1 activity thereby regulation of dendrite development.
ReadFilter - Filtering reads of interest for quicker downstream analysis

Whole-genome sequencing is becoming the method of choice but provides redundant data for many tasks. ReadFilter (https://github.com/ssi-dk/serum_readfilter) is offered as a way to improve run time of these tasks by rapidly filtering reads against user-specified sequences in order to work with a small fraction of original reads while maintaining accuracy. This can noticeably reduce mapping time and substantially reduce de novo assembly time.
Ekspresija gena za beta-katenin i p53 u meningeomima

Meningeomi su primarni tumori sredisnjeg živcanog sustava. Beta-katenin je citoplazmatski protein kodiran genom CTNNB1. Sudjeluje u nastanku i održavanju međustanicnih veza i signalnom putu Wnt. Signalni put Wnt ima važnu ulogu tijekom embrionalnog razvojna, posebice razvoja sredisnjeg živcanog sustava. Osim stoga, neispravno funkcioniranje puta prijenosa signala Wnt odgovorno je za proces tumorigeneze. Neispravna akumulacija beta-katenina karakteristicna je za razlicite tipove tumora. Postoje dokazi da su signalni putevi Wnt i p53 povezani te da divlji tip proteina p53 djeluje inhibitorno na Wnt signalizaciju. Željeli smo analizirati razinu izraženosti gena CTNNB1 (beta-katenin) i p53 u uzorcima meningeoma covjeka te odrediti njihovu lokalizaciju u stanicama tumora. Također smo nastojali odrediti povezanost između ovih dvaju proteina i tako pokazati jesu li signalni putevi Wnt i p53 ukljuceni u nastanak meningeoma. Proteinske produkte gena CTNNB1 i p53 detektirali smo imunohistokemijom jer nam ova metoda omogucuje vizualizaciju antigena u preparatu sto omogucuje samu vizualizaciju specificnog proteina. Razinu ekspresije proteina beta-katenina i p53 odredili smo semikvantitativnom metodom tj. dodjeljivanjem znakova (+) Statistickom analizom razine ekspresije utvrdili smo da postoji inverzna korelacija izraženosti beta-katenina i p53 (P=-0,410; hi-kvadrat=0,002), sto upucuje da gubitak ekspresije p53 dovodi do povisene razine beta-katenina i aktivacije signalnog puta Wnt.
Investigation of pathogenic determinants in vibrio harveyi and screening of antogonistic bacteria for control of its infection

Vibrio harveyi is the causative agent of luminous vibriosis, which leads to a massive loss in shrimp industry worldwide. However, virulence factors of this bacterium are not completely understood. In this study, V. harveyi from marine samples were isolated and confirmed by PCR targeted to gyrB gene. Thirty-six out of 40 bacterial isolates were positive. These V. harveyi, V. harveyi HY01 isolated from a shrimp that died from vibriosis and an ocean isolate of V. harveyi BAA-1116 were investigated for their pathogenicity in shrimp. Correlations between shrimp mortality, hemolysis, the presence of a hemolysin gene (vhh), and a gene involved in the type III secretion system (the Vibrio calcium response gene vcrD) were also determined. Thirteen isolates including V. harveyi HY01 caused shrimp death within 12 h after injection. Most V. harveyi isolates in this group (designated as Group A) caused hemolysis on prawn blood agar. None of the shrimp died after injection with V. harveyi BAA-1116. Molecular analysis of all V. harveyi isolates revealed the presence of vhh in all V. harveyi isolates however some isolates did not cause hemolysis, indicating that vhh gene expression might be regulated. Moreover, vcrD was detected in both pathogenic and non-pathogenic strains. Analysis of the V. harveyi HY01 genome revealed a homologue (86% homology) of hlyA gene (designated as hhl), encoded for hemolysin, of the human pathogenic bacteria V. cholerae. Specific primers designed for hhl detected this gene in 3 additional V. harveyi isolates but the presence of this gene was not correlated with pathogenicity in shrimp. This is the first report to demonstrate the presence of hlyA-like hemolysin gene in V. harveyi, although our result indicated that presence of this gene did not correlate at least with fatality in shrimp. The presence of this gene and its correlation in V. harveyi pathogenicity should be further investigated. Random amplified polymorphic DNA (RAPD) analysis revealed a high degree of genetic diversity in all V. harveyi isolates, and there were no correlations among the hhl-positive isolates or the pathogenic strains. To confirm correlation between hemolytic activity and mortality of shrimp caused by V. harveyi, transposon mutagenesis was performed. Out of 1,764 mutants screened, five mutants caused low hemolytic activity on sheep blood agar and exhibited virulence attenuation in the shrimp.
Trends in Antifungal Susceptibility among Clinical Isolates of Candida spp. Resistant to Antifungals and Natural Products

A collection of 260 Candida strains isolates recovered from 198 patients from 13 different medical centers in Jabalpur over a period of 5 years. Â These were tested for resistance to various antifungals according to the guidelines of NCCLS documents M 38-P by various methods. The isolates which were found to be resistant to synthetic antifungals were selected and subjected to antifungal testing against natural herbs and spices.Amongst all the spices and natural herbs tested garlic was found to the most effective against Candida strains.
Abstract B022: Metabolic and immunologic effects of the fasting mimicking diet in cancer patients

Background: The fasting mimicking diet (FMD), a plant-based, low-calorie, low-protein, low-carbohydrate diet, modulates systemic metabolism and anticancer immunity, and displays anticancer activity in many preclinical tumor models. However, safety, metabolic, and activity data in the clinical setting are lacking. Methods: At Fondazione IRCCS Istituto Nazionale dei Tumori, a prospective study is ongoing to assess feasibility, tolerability, and metabolic effects of the FMD in cancer patients (pts) following a 5-day FMD (700 Kcal on day 1 and 300 kCal on days 2-5) every 21-28 days. This study is enrolling pts with any cancer type (except for small cell lung cancer), stage, and concomitantly administered anticancer treatment. Main exclusion criteria are: insulin-dependent diabetes, severe comorbidities, BMI 5%. We are regularly collecting blood and urine samples before FMD initiation and at diet completion to measure diet-induced changes of metabolites and growth factors. Here we report data on metabolic modifications detected in 38 pts after the first FMD cycle, and preliminary peripheral blood immunomonitoring in selected cases. Results: 38 pts were enrolled from January 2017 to July 2017. 29 had advanced disease, and 34 were receiving concomitant anticancer therapy at study enrollment. The most represented tumor types were breast (14), prostate (4), pancreatic (4), and lung (5) cancer. All pts completed at least one cycle of FMD, and no G3-G4 adverse event (AE) were reported. After the first FMD cycle, median glycemia was reduced by 15% (p Citation Format: Filippo de Braud, Claudio Vernieri, Veronica Huber, Agata Cova, Paola Squarcina, Monica Milano, Giovanni Fuca, Valter Longo, Licia Rivoltini. Metabolic and immunologic effects of the fasting mimicking diet in cancer patients [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B022.
Muscle specific stress fibers give rise to sarcomeres and are mechanistically distinct from stress fibers in non-muscle cells

The sarcomere is the basic contractile unit within cardiomyocytes driving heart muscle contraction. We sought to test the mechanisms regulating thin (i.e., actin) and thick (i.e., myosin) filament assembly during sarcomere formation. Thus, we developed an assay using human cardiomyocytes to test de novo sarcomere assembly. Using this assay, we report a population of muscle-specific stress fibers are essential sarcomere precursors. We show sarcomeric actin filaments arise directly from these muscle stress fibers. This process requires formin-mediated but not Arp2/3-mediated actin polymerization and nonmuscle myosin IIB but not non-muscle myosin IIA. Furthermore, we show a short species of β cardiac myosin II filaments grows to form ~1.5 long filaments that then “stitch” together to form the stack of filaments at the core of the sarcomere (i.e., A-band). Interestingly, these are different from mechanisms that have previously been reported during stress fiber assembly in non-muscle cells. Thus, we provide a new model of cardiac sarcomere assembly based on distinct mechanisms of stress fiber regulation between non-muscle and muscle cells.
Characterising two genomic islands involved in metabolism in Neisseria meningitidis

Meningococcal meningitis is endemic in sub-Saharan Africa while sporadic outbreaks burden the developed world by preying on the young and immunocompromised. The causal pathogen Neisseria meningitidis exclusively colonises the human nasopharynx. With a relatively concise genome, it can invade across multiple bodily compartments, which can be highly debilitating and life-threatening. Nine genomic “islands” have been identified in N. meningitidis and N. gonorrhoeae, absent from their commensal cousin N. lactamica. Many are predicted to have roles in bacterial transport, metabolism and regulation. Genomic Island 5 contains three genes and was correctly annotated to encode enzymes involved in the synthesis of the polyamine putrescine, protecting bacteria from oxidative stress. Mutant N. meningitidis lacking these genes grew poorly in rich media. The lesion can be restored by putrescine supplementation or gene complementation. Genomic Island 3 contains two genes poorly annotated to be spermidine-synthesising – a higher polyamine. Mutant N. meningitidis lacking these genes, however, grew poorly in chemically-defined media. Shuffling amino acid profiles and culturing with a labelled arginine isotope suggest a role in the acquisition and metabolism of arginine and glutamine, which are key to meningococcal maintenance. Enhanced systems circumventing host resource-denial, scavenging amino acids and resisting challenges from free radicals are examples of virulence. These islands are believed to support the general fitness of N. meningitidis as a highly competitive commensal but paradoxically “accidental” pathogen, where disease is a likely a result of risk-taking lifestyles in response to complex microenvironment changes. This behaviour is contrasted by N. gonorrhoeae which prefers recurrent infection episodes and long-term establishment. The closely-related but phenotypically diverse members of the Neisseria genus hence serve as research foci of much interest. In a broader sense, investigating why meningococci conserve such pathogen-specific sequences may help inspire new clinical strategies and provide alternative perspectives towards the biology of similar organisms.
ngsReports: An R Package for managing FastQC reports and other NGS related log files

Motivation High throughput next generation sequencing (NGS) has become exceedingly cheap facilitating studies to be undertaken containing large sample numbers. Quality control (QC) is an essential stage during analytic pipelines and can be found in the outputs of popular bioinformatics tools such as FastQC and Picard. Although these tools provide considerable power when carrying out QC, large sample numbers can make identification of systemic bias a challenge. Results We present ngsReports, an R package designed for the management and visualization of NGS reports from within an R environment. The available methods allow direct import into R of FastQC output as well as that from aligners such as HISAT2, STAR and Bowtie2. Visualization can be carried out across many samples using heatmaps rendered using ggplot2 and plotly. Moreover, these can be displayed in an interactive shiny app or a HTML report. We also provide methods to assess observed GC content in an organism dependent manner for both transcriptomic and genomic datasets. Importantly, hierarchical clustering can be carried out on heatmaps with large sample sizes to quickly identify outliers and batch effects. Availability and Implementation ngsReports is available at https://github.com/UofABioinformaticsHub/ngsReports.
Empirical Bayes Meets Information Theoretical Network Reconstruction from Single Cell Data

Gene expression is controlled by networks of transcription factors and regulators, but the structure of these networks is as yet poorly understood and is thus inferred from data. Recent work has shown the efficacy of information theoretical approaches for network reconstruction from single cell transcriptomic data. Such methods use information to estimate dependence between every pair of genes in the dataset, then edges are inferred between top-scoring pairs. Dependence, however, does not indicate significance, and the definition of “top-scoring” is often arbitrary and a priori related to expected network size. This makes comparing networks across datasets difficult, because networks of a similar size are not necessarily similarly accurate. We present a method for performing formal hypothesis tests on putative network edges derived from information theory, bringing together empirical Bayes and work on theoretical null distributions for information measures. Thresholding based on empirical Bayes allows us to control network accuracy according to how we intend to use the network. Using single cell data from mouse pluripotent stem cells, we recover known interactions and suggest several new interactions for experimental validation (using a stringent threshold) and discover high-level interactions between sub-networks (using a more relaxed threshold). Furthermore, our method allows for the inclusion of prior information. We use in-silico data to show that even relatively poor quality prior information can increase the accuracy of a network, and demonstrate that the accuracy of networks inferred from single cell data can sometimes be improved by priors from population-level ChIP-Seq and qPCR data.
Regulation von intrazellulären Transportwegen in Arabidopsis

Membrane trafficking is essential to fundamental processes in eukaryotic life, including cell growth and division. In plant cytokinesis, post-Golgi trafficking mediates a massive flow of vesicles that form the partitioning membrane but its regulation remains poorly understood. Here, we identify functionally redundant Arabidopsis ARF guanine-nucleotide exchange factors (ARFGEFs) BIG1–BIG4 as regulators of post-Golgi trafficking, mediating late secretion from the transGolgi network but not recycling of endocytosed proteins to the plasma membrane, although the TGN also functions as an early endosome in plants. In contrast, BIG1-4 are absolutely required for trafficking of both endocytosed and newly synthesized proteins to the cell–division plane during cytokinesis, counteracting recycling to the plasma membrane. This change from recycling to secretory trafficking pathway mediated by ARF-GEFs confers specificity of cargo delivery to the division plane and might thus ensure that the partitioning membrane is completed on time in the absence of a cytokinesis-interphase checkpoint. DOI: 10.7554/eLife.02131. 00
Discovery of a novel stereospecific β-hydroxyacyl-CoA lyase/thioesterase shared by three metabolic pathways in Mycobacterium tuberculosis

The vast number of poorly characterised enzymes in Mycobacterium tuberculosis (Mtb) is one of the key barriers precluding a better understanding of the biology that underpins pathogenesis. Here, we investigated the Mtb orphan enzyme Rv2498c to delineate its physiological role. Our results from in vitro enzymatic assays, phylogenetic analysis, X-ray crystallography and in vivo Mtb experiments, de-orphan Rv2498c as a multi-functional β-hydroxyacyl-CoA lyase/thioesterase (β-HAClyase/thioesterase) that participates in three different metabolic pathways: L-leucine catabolism, itaconate dissimilation, and glyoxylate shunt. Moreover, the deletion of the rv2498c gene from the Mtb genome resulted in attenuation in the mouse model compared to infection with the parent strain. To the best of our knowledge, this is the first report of an (R)-3-hydroxyl-3-methylglutaryl-CoA for leucine catabolism and an itaconate-specific resistance mechanism in Mtb.
The caffeine 8-hydroxylation in humans, a predominantly intestinal phenomenon

THE CAFFEINE 8-HYDROXYLATION IN HUMANS: A PREDOMINANTLY INTESTINAL PHENOMENON Charles Haigh Master of Science, 200 1 Department of Pharmacology University of Toronto The importance of the intestine as a site of dnig biotransforrnation, particu1arly during drug absorption, is now genedly acknowledged. However, development of a method to measure the intestinal drug metabolizing ciipacity in an individual has been problernatic for investigators, A finding of this thesis indicates a possible rnethod to distinguish intestinal drug rnetabolism fmm its hepatic counterpart. A traditional pharmacokinetic study of the caffeine 8-hydroxylation to 137U in vivo indicated chat this merabolite was formed immediately after caffeine ingestion, prior to the major CYPlA2 mediated N-demethylations. Furthemore, the majority of 137U formation appears to be mediated within the intestine. However, no consistent inhibition of 137U formation by grapefruit juice, an accepteâ cytochmme P4503A4 inhibitor, was observed. As such, the rote of CYP3A4 in 137U formation appem unlikely. Recent evidence of extensive caffeine metabolism by CYPl Al, in combination with documented CYPl Al presence in the intestine, supports this hypothesis. In conclusion, the relatively earlier formation of 137U as compared to other caffeine metabolites is a novel finding which may be of use in distinguishing between intestinal dmg metabolism and its hepatic