Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy in collagen induced arthritis models with a selective, reversible covalent Bruton’s tyrosine kinase inhibitor PRN473 is driven by durable target occupancy rather than extended plasma exposure (THER5P.904)

Bruton’s Tyrosine Kinase (BTK) is an essential signaling element downstream of the B-cell receptor (BCR). Inhibition of BTK activity in B cells produces phenotypic changes consistent with blockade of the BCR, including inhibition of cell proliferation, differentiation, maturation, and survival. A selective BTK inhibitor has the potential to treat diseases involving inflammation and autoimmunity. Using Principia Biopharma’s proprietary Tailored Covalency™ technology, we discovered PRN473, a reversible covalent BTK inhibitor that selectively binds BTK with a slow off-rate as assessed in biochemical and cell based assays. A slow off-rate molecule with rapid systemic clearance may lead to a long duration of action and high efficacy, while reducing the potential for off target toxicities. The duration of binding of PRN473 was measured in vivo, with prolonged BTK occupancy confirmed after drug was cleared from plasma. In mouse and rat collagen-induced arthritis (CIA) models, PRN473 when dosed therapeutically demonstrated dose-dependent inhibition, reversal of arthritis, with almost complete abrogation of clinical scores and preservation of joint integrity and histology. BTK occupancy in splenocytes was found to be a robust measure of BTK inhibition and correlated with efficacy in the CIA models. These data in combination with GLP toxicology studies, where no organ specific toxicities were observed, validate using a reversible covalent BTK inhibitor to treat autoimmune diseases.
Biochemical assessment of oxidative stress by the use of açai (Euterpe oleracea Martius) gel in physically active individuals

The relation between oxidative stress and inflammation induced by diseases and exercise has increased the interest in the benefits of antioxidant supplements in the improvement of health and physical and mental performance. The aim of this study was to evaluate the effectiveness of acai gel in reducing oxidative stress in individuals engaged in physical activities as well as their acceptance. Sensory evaluation was performed to determine its acceptability and the biochemical parameters related to immune profile and biomarkers of muscle, liver and oxidative stress, with and without the use of gel were evaluated. The appearance, sweetness and overall impression of the acai gel were considered good. It was observed a significant increase in CK enzyme, without the gel as well as the oxidative stress biomarkers, it was observed that the MDA (with and without gel) a significant increase (p < 0.05). Through biochemical evaluation, it is concluded that the gel provided protection for some of parameters studied, since it modulated the immunological parameter reducing the lymphocyte activity and muscular stress. However, more studies must be carried out with a larger number of individuals to confirm the gel functionality.
CGLAD: GLAD en problemas de Big Crowdsourced Data

Resumen—En este artı́culo proponemos una mejora del algoritmo GLAD con el fin de mejorar su funcionamiento en problemas con grandes conjuntos de datos, en términos de eficiencia y de precisión del modelo resultante. El algoritmo GLAD permite aprender a partir de datos procedentes de múltiples anotadores, teniendo en cuenta su capacidad y la dificultad de las instancias que se predicen. Sin embargo, debido al número de parámetros del modelo, este no escala bien a grandes cantidades de datos, sobre todo si se requiere que el tiempo de ejecución sea bajo. Nuestra propuesta, que llamamos CGLAD, resuelve en gran medida estos problemas mediante clustering a partir de vectores procedentes de factorización de matrices, lo que permite reducir el número de parámetros del modelo y, en general, facilitar el aprendizaje de modelos que siguen la estrategia de GLAD.
[Cloning and detailed mapping of the fra-ymt region of the Yersinia pestis pFra plasmid].

: The genetical libraries of the pFra plasmid of Yersinia pestis genes were obtained by insertion into the PstI, SalGI, EcoRI, XhoI restriction sites of the cosmid vector pHC79. The immunochemical analysis of the recombinant clones has revealed the clones synthesizing the antigen Fl (fraction I) and mouse toxin (Ymt--Yersinia pestis murine toxin). The restriction analysis of the plasmids from antigen synthesizing clones has permitted to construct the detailed physical map of the fra-ymt region of the pFra plasmid the size of 22 kb. The recombinant F1 positive clones of Escherichia coli are able to form at 37 degrees C the capsule-like structure peculiar for Yersinia pestis. The antigen F1 and the mouse toxin were isolated, purified and characterized. The antigen F1 is an 1-2 Md polymer containing a 16 kDa protein subunit. The mouse toxin a 240 kDa protein consisting of 61 kDa subunits. The nucleotide sequence of ymt gene has been defined.
Drying as a primary hydrological determinant of biodiversity in river systems: a broad‐scale analysis

Determining and understanding relationships between biodiversity and hydrology is a critical goal in ecology, particularly given biodiversity in the freshwater realm is in crisis. Despite the prevalence of rivers experiencing natural drying disturbances (which we collectively refer to as intermittent rivers), and projections of increased frequency and duration of drying events, the importance of drying relative to other flow-related determinants of river biodiversity remains understudied. We assessed the influence of drying on alpha- and beta-diversity using discharge and macroinvertebrate data collated from Australia and southwest Europe over broad spatial and temporal scales, providing information on current and past drying events, and combining a wide variety of flow metrics. We found clear evidence that drying acts as a strong environmental filter and is a primary hydrological determinant of alpha-diversity; even when considering both intermittent and perennial rivers, drying-event conditions were its most important predictors. Macroinvertebrate richness declined with increasing durations of drying over the long-term (Australia) and recent (Australia and southwest Europe) history of river discharge, and with decreasing predictability of event timing (Australia). Our analysis also revealed that: responses can be taxon specific due to variation in traits of resistance and resilience to drying; some taxa may respond just as or more strongly to variation in other discharge components (e.g. high- or low-flow events) than to drying; and together these phenomena may result in differing community-level responses within and across regions. Patterns of beta-diversity across the wide biogeographical range of our study suggested that convergent and divergent niche-selection processes may act in combination on aquatic communities of rivers experiencing drying disturbances. However, strong ability to disperse by flight (not by water) weakened beta-diversity patterning among rivers. Our findings can be used to improve understanding of biodiversity organisation in disturbed systems, notably in those with dendritic features, including intermittent rivers.
Honoring Ole Maaløe

The city of Copenhagen has honored one of the most distinguished Danish microbiologists, Ole Maaloe, by naming a street after him. Ole Maaloes Vej is not far from the Institute of Microbiology he founded, and where he presided over the Copenhagen School of Bacterial Growth Physiology. The name of the street (“Vej” translates into “Way”) seems particularly apt because Ole showed the way to a precise and deeper understanding of growth as a fundamental biological response. His “big picture” view of the bacterial cell was fueled by his passion for quantitative measurements. His constant questions were: “How fast? ,” “How many? ,” “How long? ” All who went through his lab, which includes the undersigned, learned to regard bacteria as integrated systems—cells—rather than to focus solely on their component parts. It is gratifying that the accomplishments of Ole's lab are becoming increasingly relevant to the scientists who are fashioning Systems Biology.
Patterns of reproduction, dispersal and recruitment in seaweeds

Reproductive processes of seaweeds and patterns of propagule production and release, dispersal, settlement and recruitment are reviewed. Present interpretations of the adaptive values of life history aspects such as sexual and asexual reproduction, alternation of generations, isomorphic and heteromorphic cycles and relative allocation of resources to reproduction are discussed. The evidence concerning the abiotic control and the ontogenic, specific and seasonal patterns of propagule production and release are evaluated. The nature of the propagule releasing mechanisms, the morpho-physiological characteristics of the released propagules, their dispersability by biotic and abiotic agents and the factors influencing their settlement, attachment, germination and recruitment are analysed.Overall, the evidence indicates that concepts derived from studies with land plants do not completely explain the reproductive processes of seaweeds. Similarly, the ecophysiological responses of the freefloating propagules are also conspicuously different from the free living plankton to which they have been compared. The literature describes numerous processes that remain poorly understood. Examples are: the mechanisms of spore release; the biological basis for the reduced viability of algal spores; the roles of grazers on spore release and dispersal and the ecological importance of positive interspecific and intraspecific interactions on settlement and recruitment. In addition, numerous ecologically important phenomena have not been reported or studied. These include the nature and dynamics of the spore clouds, the turnover rates and ecological roles of the bank of microscopic forms, alternative ways of spore attachment and the adaptive significance of spore germination. A more realistic understanding of the reproduction, dispersal and recruitment processes of seaweeds will result if ecological concepts and methods are applied to them, with due consideration for their morphological, physiological and life-history characteristics.
Différenciation et reconnaissance des gamétophytes mâle et femelle chez Larix leptolepis : étude structurale

Etude structurale des gamethophytes femelle et male et leur differenciation chez larix leptilepis, parent male de l'hybride forestier larix eurolepis et dans le cadre d'un programme d'amelioration de l'espece forestiere caracterisee par un faible rendement en semences sexuees
Cloning and Characterization of Glycolate Oxidase and NADH-Dependent Hydropyruvate Reductase Genes in Pachysandra terminalis

Photorespiration provides a protection mechanism in plants by diverting excessive energy accumulated from photochemical reaction, metabolizing toxic products and producing some protective molecules. The authors report cloning and characterization of a glycolate oxidase gene (GOX; NCBI accession DQ442286) and a NADH-dependent hydroxypyruvate reductase gene (HPR; NCBI DQ442287) from Pachysandra terminallis. The DQ442286 had the predicted GOX-like-Riboflavin-5'-phosphate (FMN) conserved domain and the DQ442287 had the predicted adenosine 5'-(alpha-thio)diphospho-5'-ribofuranosylnicotinamide nicotinamide adenine dinucleotide (NAD) binding domain (2-Hacid_DH_C). C-terminal peroxisome targeting signal was predicted to be -ARL for DQ442286 and -SKL for DQ442287. Both genes encoded enzyme proteins that are located in peroxisome and are involved in the photorespiration process. Real-time quantitative reverse-transcriptase polymerase chain reaction was performed to compare transcript level of the cloned genes after cold treatment. The 18s Ribosomal RNA (rRNA) was included to calibrate the data. The relative cycle threshold values (gene/18s rRNA) were 1.4, 1.5, and 1.5 for GOX and 1.2, 1.3, and 1.3 for HPR in the treatments of 4 °C 4 h, 4 °C 12 h, and control. The data revealed that gene expression was enhanced by only short-term (4-h) cold treatment. A ribulose-1, 5-biphosphate carboxylase/oxygenase (Rubisco) activase gene (DQ 486905) was also cloned and analyzed following the same procedure.
The importance of factors controlling species abundance and distribution varies in native and non‐native ranges

How variation in factors controlling species abundance and distribution between native and non-native ranges compares to that within ranges remains poorly understood. We used a globally distributed ruderal, Centaurea solstitialis (Centaurea), to explore the possibility that the importance of those factors exhibits great variation between and within ranges. To test our hypothesis, we established seed addition experiments with soil disturbance (turnover and control) and biocide (fungicides, insecticide, and control) treatments in two regions within native (the Caucasus and south-western Turkey) and non-native (the western United States -US- and central Argentina) distributions. Also, we estimated the rate of vegetation recovery after disturbance (resilience) and related it to Centaurea density in experimental plots. Disturbance strongly increased Centaurea density in all regions. Density was similar between the native Caucasus and non-native Argentina and much greater in those regions than in the native Turkey and non-native US in biocide-free plots. Fungicides had positive effects on density in the US and negative ones in the Caucasus and Argentina, resulting in no differences between those three regions and greater density in the US than Turkey. Insecticide applications promoted Centaurea density in Turkey and Argentina, but inter-regional comparisons of density in treated plots were comparable to those in biocide-free plots. Overall, plants were smaller and less fecund in Turkey than the other regions, except the US. The greatest fungal attack was documented in Turkey, and herbivory was stronger there and in Argentina than in the Caucasus and US. The resilience of the local community explained a large proportion of variation in Centaurea density. These results support our hypothesis, and reveal that the speed at which competition is re-gained after disturbance may influence global variation in Centaurea abundance. Because many ruderals exhibit native and non-native distributions, our results are likely to be generalized to other systems. This article is protected by copyright. All rights reserved.
ROLE OF HAIRY-RELATED (HER) GENES DURING VERTEBRATE RETINAL DEVELOPMENT AND REGENERATION

OF DISSERTATION. ii ACKNOWLEDGEMENTS . vi TABLE OF CONTENTS . 1 LIST OF TABLES . 5 LIST OF FIGURES . 6 CHAPTER 1: Vision, retinal development, and bHLH-O transcription factors . 8 1.
Occurrence of Antibiotic Resistant Bacteria in Raw and Pasteurized Milk Samples of Warangal City, Telangan State

Milk, an essential food for human beings, supports the growth of many microorganisms serving as an ideal medium. Raw milk is an ideal growth medium for several microorganisms especially Lactobacillus, Staphylococcus, and Micrococcus species. Bacterial contamination of raw milk can originate from several sources such as milch animal, air, milking equipment, feed, soil faeces and grass (Pant et al., 2013).
Mitochondrial Metabolism of 3-Mercaptopropionic Acid

The metabolism of 3-mercaptopropionic acid in mitochondria was studied by use of purified mitochondrial enzymes and rat heart mitochondria. Metabolites of 3-mercaptopropionic acid were separated by high performance liquid chromatography and identified by comparing them with chemically synthesized derivatives of 3-mercaptopropionic acid. The initial step in the metabolism of 3-mercaptopropionic acid is its conversion to a CoA thioester, most likely catalyzed by medium-chain acyl-CoA synthetase. The resulting 3mercaptopropionyl-CoA is a poor substrate of acylCoA dehydrogenase but substitutes effectively for CoASH in reactions catalyzed by 3-ketoacyl-CoA thiolase and acetoacetyl-CoA thiolase. S-Acyl-3-mercaptopropionyl-CoA thioesters formed in the thiolase-catalyzed reactions are not at all or only poorly acted upon by acyl-CoA dehydrogenases. However, they are hydrolyzed by thioesterase(s) to CoASH and S-acyl-3mercaptopropionic acid. The hydrolysis of S-acyl-3mercaptopropionyl-CoA thioesters proceeds more rapidly than the hydrolysis of fatty acyl-CoA thioesters of comparable chain lengths. Free CoASH is also regenerated from S-acetyl-3-mercaptopropionyl-CoA and more rapidly from 3-mercaptopropionyl-CoA as a result of their reactions with carnitine catalyzed by carnitine acetyltransferase. These findings lead to the suggestion that the major mitochondrial CoA-containing metabolites of 3-mercaptopropionic acid are Sacyl-3-mercaptopropionyl-CoA thioesters.
IN THE MOSQUITO CULEX PIPIENS

To determine the outcome of the combined effects of gene flow, genetic drift, and selection on the evolution of insecticide-resistance genes in the mosquito Culex pipiens, samples were collected along three transects crossing treated and nontreated areas in northern Spain and southern France. Electrophoretic polymorphisms of five presumably neutral genes disclosed that differentiation among samples was low, and that both Wright F-statistics and Slatkin private-alleles methods provided a high estimate for Nm. In contrast, there was a strong differentiation in the distribution of resistance genes closely associated with insecticide treatments. These divergent situations are explained in relation to both the very recent origin of some resistance genes that are still localized geographically (A2-B2 and Cl), and the high fitness cost of the older and ubiquitous ones in nontreated areas (Al, A4-B4, and AceR).
A Drosophila mir-282 mikroRNS gén szerkezeti és funkcionális jellemzése

A sejtek dinamikusan valtozo genkifejeződesi mintazatainak kialakitasaban a szabalyozo feherjek szerepe mar regota ismert. Az utobbi bő egy evtizedben azonban RNS alapu regulator komplexeket azonositottak, melyek szinten reszt vesznek a genaktivitas szabalyozasaban. A mikroRNS-ek (miRNS) endogen, egyszalu szabalyzo RNS-ek, melyek hajtű alaku atmeneti transzkriptumbol keletkeznek. Az erett, korulbelul 22 nukleotid hosszu miRNS-ek nehany feherjevel komplexet alkotva poszt-transzkripcionalis szinten fejtik ki negativ szabalyozo hatasukat. PhD dolgozatom a bioinformatikai modszerekkel előrejelzett mir-282 nevű Drosophila melanogaster miRNS gen molekularis es fenotipusos jellemzesevel foglalkozik. A Drosophila melanogaster mir-282 genjenek bizonyitottuk transzkripcios aktivitasat, kifejeződesenek es elsődleges szerkezetenek leirasaval alatamasztottuk a korabbi gen előrejelzest. Ujonnan indukalt mir-282-re specifikus delecio vizsgalataval bizonyitottuk, hogy a mir-282 lokusz funkcionalis transzkriptumot kodol, mely befolyasolja az elethosszt, az eletkepesseget es a petehozamot.Megvizsgaltuk a mir-282 potencialis celgenjeit is, es a mir-282 negativ genszabalyozo funkciojat a rutabaga gen eseteben kiserletesen bizonyitottuk.
In Silico Technologies in Drug Target Identification and Validation

In Silico Technologies in Drug Target Identification and Validation-Darryl Leon 2006-06-13 The pharmaceutical industry relies on numerous well-designed experiments involving high-throughput techniques and in silico approaches to analyze potential drug targets. These in silico methods are often predictive, yielding faster and less expensive analyses than traditional in vivo or in vitro procedures. In Silico Technologies in Drug Target Identification and Validation addresses the challenge of testing a growing number of new potential targets and reviews currently available in silico approaches for identifying and validating these targets. The book emphasizes computational tools, public and commercial databases, mathematical methods, and software for interpreting complex experimental data. The book describes how these tools are used to visualize a target structure, identify binding sites, and predict behavior. World-renowned researchers cover many topics not typically found in most informatics books, including functional annotation, siRNA design, pathways, text mining, ontologies, systems biology, database management, data pipelining, and pharmacogenomics. Covering issues that range from prescreening target selection to genetic modeling and valuable data integration, In Silico Technologies in Drug Target Identification and Validation is a self-contained and practical guide to the various computational tools that can accelerate the identification and validation stages of drug target discovery and determine the biological functionality of potential targets more effectively. Daniel E. Levy, editor of the Drug Discovery Series, is the founder of DEL BioPharma, a consulting service for drug discovery programs. He also maintains a blog that explores organic chemistry.
Coexpression of MYC and BCL-2 Predicts Inferior Survival in Pgi-DLBCL Treated with CHOP-like Regimen/Rituximab

MYC protein expression has been identified to be associated with inferior overall survival (OS) and progression-free survival (PFS) when coexpressed with BCL-2 protein in patients with diffuse large B cell lymphoma (DLBCL). But the concurrent expression of MYC and BCL-2 proteins in primary gastrointestinal (PGI)-DLBCL has not been clearly understood. Here, we investigated whether this coexpression has prognostic significance in PGI-DLBCL patients and explored its associations with patients’ clinical parameters. We enrolled 60 PGI-DLBCL patients and 30 age- and sex-matched healthy controls. Expression levels of MYC and BCL-2 were detected from both protein and mRNA levels by immunohistochemistry and real-time RT-PCR. Positive expression levels of MYC and BCL-2 proteins were detected in 35% and 45% of patients, respectively. MYC+/BCL-2+ protein was present in 30% of patients. MYC and BCL-2 protein were correlated with high MYC and BCL-2 mRNA expression, respectively (both p<0.05). We found that patients with advanced-stage disease (at IIE-IV) having higher MYC and BCL-2 coexpression levels (p<0.05). In addition, MYC+/BCL-2+ patients had more difficulty achieving complete remission than others (p<0.05). Presence of MYC protein expression only affected OS and PFS when BCL-2 protein was coexpressed. The adverse prognostic impact of MYC+/BCL-2+ protein on PFS remained significant (p<0.05) even after adjusting for age, Lugano stage, IPI, and BCL-2 protein expression in a multivariable model. MYC+/BCL-2+ patients have poorer chemotherapy response and poorer prognosis than patients who only express one of the two proteins, suggesting that assessment of MYC and BCL-2 expression by immunohistochemistry has clinical significance in predicting prognosis of PGI-DLBCL patients. Disclosures No relevant conflicts of interest to declare.
Lengths of Haploid and Diploid Spermatozoa of the Honeybee and the Question of the Production of Triploid Workers

SummaryAltogether the whole lengths of 3575 spermatozoa from 59 diploid and 84 haploid drones, and the lengths of the nuclei of 450 diploid and haploid spermatozoa, were compared.The shortest diploid spermatozoa were 15 μm longer than the longest haploid ones produced by drones originating from the same queen. The average length of diploid spermatozoa was 313 μm and that of haploid spermatozoa 242 μm. The head length of diploid spermatozoa averaged 7·4 μm and of haploids 4·8 μm. Thus length may be used to distinguish haploid from diploid spermatozoa, and consequently haploid from diploid drones.Reports of production of triploid worker bees are considered questionable.