Miracle-dz/UniFAR-FTUs huggingface dataset:
Enrichment-free High-throughput Liquid Chromatography–Multiple-Reaction Monitoring Quantification of Cytochrome P450 Proteins in Plated Human Hepatocytes Direct from 96-Well Plates Enables Routine Protein Induction Measurements

Despite the availability of liquid chromatography (LC)–mass spectrometry (MS) methods for quantifying cytochrome P450 (P450) proteins, incorporation of P450 protein quantification into induction study workflows has not been widely adopted. To more readily enable P450 protein quantification in induction study workflows, DMPK research groups need a simple, robust, cost-effective, high-throughput method compatible with 96-well–plated human hepatocyte formats. Here, we provide such a methodology. Our method bypasses both microsomal enrichment and antibody-based enrichment to go directly from the plate to LC-MS/MS analysis. We use this “plate-to-peaks” approach for quantifying CYP3A4, CYP2B6, and CYP1A2, the major inducible hepatic P450s representative of pregnane X receptor–, constitutive androstane receptor–, and aryl hydrocarbon receptor–mediated induction, respectively. We leveraged our induction study-aligned assay format to assess induction across mRNA, protein, and enzyme activity using known induction control compounds. As expected, results from the three methods using model inducers were broadly concordant, but the magnitude of the induction response differed. Induction of CYP3A4 using 10 µM rifampicin was 12-fold for RNA, eightfold for protein, and threefold for activity; for CYP1A2 with 50 µM omeprazole, induction was 30-fold for RNA, 13-fold for protein, and 17-fold for activity; for CYP2B6 with 50 µM phenytoin, induction was 23-fold for RNA, twofold for protein, and fivefold for activity. Most importantly, we anticipate the relative ease of this method will enable researchers to routinely adopt P450 protein quantification as part of nonclinical evaluation of P450 induction. SIGNIFICANCE STATEMENT Current methodologies for quantifying P450 proteins by liquid chromatography (LC)–tandem mass spectrometry are either cumbersome, too costly, or both to be widely adopted into induction study workflows by the ADME research community. We present a simplified LC-MS/MS methodology for quantifying P450 proteins directly from human hepatocytes, without any form of enrichment, in 96-well induction assay plate format that should be readily adoptable by any ADME laboratory with LC–multiple-reaction monitoring capabilities.
Plant Community Composition and Structure of Chenab Valley in a Part of Nanda Devi Biosphere Reserve

The present paper deals with the vegetation communities and their diversity patterns in Chenab valley, the buffer zone of Nanda Devi Biosphere Reserve (NDBR) in Chamoli District of Uttarakhand, India. A total of 42 sites were selected randomly based on the landform heterogeneity of the area. Eight forest communities with overlap among vegetation types and also various plant associations were noticed through Principal Component Analysis (PCA) following PAST program and two shrub communities identified separately were, Berberis and bamboo. The range of density in various forest communities was from 203-545 trees ha -1 and total basal area from 17.5-71.7 m 2 ha -1 . The range of species richness of tree layer, shrub layer and herb layer was from 2-14, 1-10 and 4-14 and diversity from 0.693-2.304, 0.5142. 052 and 1.202-2.583, respectively. The distribution pattern of trees, shrubs and herbs shows that the species were evenly distributed in most of the sites and the s-diversity of the present study area is 7.4. Rhododendron and Taxus , the undercanopy species facilitated the regeneration of Chimnobambusa falcata, while the conversion of lower girth class individuals to higher girth class individuals is steady and progressive. Though, evergreen and deciduous species had good population of seedlings and saplings, but the conversion to next girth class was very poor due to the high anthropogenic pressure. The present study reveals that the forest vegetation in Chenab valley is better than that of other parts of Nanda Devi Biosphere Reserve, for which conservation strategies have been discussed in the paper.
Effect of growth retardants on flowering and yield of African marigold ( Tagetes erecta L.) cv. 'DOUBLE ORANGE' under South Gujarat conditions

The vigorous growth of African marigold cv. ‘DOUBLE ORANGE’ plant in terms of plant height was recorded maximum when plant sprayed at 35 days after transplanting in treatment (S 3 ) while, number of branches and plant spread were noted maximum under treatment S 1 i.e. spraying at 15 days after transplanting. Same treatment (S 1 ) induced early flowering and took minimum days for 50 per cent flowering. The plants gave the highest flower diameter, flower weight, more longevity and vase life of flower in treatment (S 1 ). The yield of flowers was also noted maximum in treatment (S 1 ). The plant height was noticed highest in the plants treated with PBZ 50 mg l -1 treatment (C 5 ) while, the number of branches per plant and plant spread were recorded maximum under plants receiving CCC 750 mg l -1 treatment (C 2 ). Consequently these plants produced early flowers and took minimum days for 50 per cent flowering with maximum flower diameter, flower weight, flower longevity as well as vase life of flower. The yield of flowers was also produced maximum in these plants. See end of the article for authors’ affiliations Correspondence to :
Species concepts and biodiversity in Trichoderma and Hypocrea：from aggregate species to species clusters？

Trichoderma/Hypocrea is a genus of soil-borne or wood-decaying fungi containing members important to mankind as producers of industrial enzymes and biocontrol agents against plant pathogens, but also as opportunistic pathogens of immunocompromised humans. Species identification, while essential in view of the controversial properties of taxa ofthis genus, has been problematic by traditional methods. Here we will present a critical survey of the various identification methods in use. In addition,we will present an update on the taxonomy and phylogeny of the 88 taxa (which occur as 14 holomorphs, 49 teleomorphs and 25 anamorphs in nature) of Trichoderma/Hypocrea that have been confirmed by a combination of morphological, physiological and genetic approaches.
ESTUDO DA PREVALÊNCIA DE OTITES CLÍNICAS POR Rhabditis sp. EM BOVINOS DA RAÇA GIR NO ESTADO DE GOIÁS

The prevalence of clinical otitis causal by Rhabditis sp. in Gir cattle was studied in 12 farms from 11 municipal districts in the Goias State-Brazil, from July to December 1997. During this, work temperature, relative humidity air and pluviometric precipitation were registered in order to check correlation between prevalence and climatic parameters. Samples of ear discharges were collected by swabs in 255 bovines. The frequency varied from 30% to 95%. The prevalence for clinical otitis by Rhabditis sp. was 78.43%, although the seasonal influence over prevalence was not shown clearly. KEY-WORDS: Bovine; Rhabditis ; otitis; prevalence.
Development and Calibration of the Polar Organic Chemical Integrative Sampler (POCIS) for Neonicotinoid Pesticides

Neonicotinoid pesticides are highly hydrophilic systemic insecticides that have been extensively used worldwide. To evaluate their environmental risks, the concentrations of these pesticides in the aquatic environment must be monitored. Although the polar organic chemical integrative sampler (POCIS) has proved to be a suitable passive sampler for many highly hydrophilic compounds, Oasis HLB (Waters) POCIS has shown limitations for the monitoring of neonicotinoid pesticides, such as short linear uptake ranges. In the present study we optimized POCIS for neonicotinoid pesticides by selecting suitable adsorbents and filters. The ENVI‐Carb (Supelco) nonporous carbon‐based adsorbent demonstrated a good balance between strong sorption and high recovery. Static renewal experiments showed that the our POCIS device using ENVI‐Carb with a polyethersulfone membrane filter had a 3 d (dinotefuran) to 28 d (clothianidin, imidacloprid, acetamiprid, and thiacloprid) linear range, which is longer than that of HLB POCIS (≤1 [dinotefuran] to 14 d). The POCIS using ENVI‐Carb with a polytetrafluoroethylene membrane had higher sampling rates (0.270 L/d [clothianidin] to 0.686 [imidacloprid] L/d) than those of the HLB POCIS for short‐term deployment. The time‐weighted average concentrations in actual river water measured by the new POCIS were in good agreement with those obtained by repeated grab sampling, within 30%. Moreover, POCIS detected 2 neonicotinoid pesticides that were not detected by grab sampling. Thus, the proposed POCIS is a promising tool for the monitoring of neonicotinoid pesticides. Environ Toxicol Chem 2020;39:1325–1333. © 2020 SETAC
Effect of Particulate Matter Exposure on Respiratory Health of e-Waste Workers at Agbogbloshie, Accra, Ghana

Background: Direct and continuous exposure to particulate matter (PM), especially in occupational settings is known to impact negatively on respiratory health and lung function. Objective: To determine the association between concentrations of PM (2.5, 2.5–10 and 10 µm) in breathing zone and lung function of informal e-waste workers at Agbogbloshie. Methods: To evaluate lung function responses to PM (2.5, 2.5–10 and 10 µm), we conducted a longitudinal cohort study with three repeated measures among 207 participants comprising 142 healthy e-waste workers from Agbogbloshie scrapyard and 65 control participants from Madina-Zongo in Accra, Ghana from 2017–2018. Lung function parameters (FVC, FEV1, FEV1/FVC, PEF, and FEF 25-75) and PM (2.5, 2.5–10 and 10 µm) concentrations were measured, corresponding to prevailing seasonal variations. Socio-demographic data, respiratory exposures and lifestyle habits were determined using questionnaires. Random effects models were then used to examine the effects of PM (2.5, 2.5–10 and 10 µm) on lung function. Results: The median concentrations of PM (2.5, 2.5–10 and 10 µm) were all consistently above the WHO ambient air standards across the study waves. Small effect estimates per IQR of PM (2.5, 2.5–10 and 10 µm) on lung function parameters were observed even after adjustment for potential confounders. However, a 10 µg increase in PM (2.5, 2.5–10 and 10 µm) was associated with decreases in PEF and FEF 25–75 by 13.3% % [β = −3.133; 95% CI: −0.243, −0.022) and 26.6% [β = −0.266; 95% CI: −0.437, 0.094]. E-waste burning and a history of asthma significantly predicted a decrease in PEF by 14.2% [β = −0.142; 95% CI: −0.278, −0.008) and FEV1 by 35.8% [β = −0.358; 95% CI: −0.590, 0.125] among e-waste burners. Conclusions: Direct exposure of e-waste workers to PM predisposes to decline in lung function and risk for small airway diseases such as asthma and COPD.
Isolated intracranial myeloid sarcoma: report of a case and review of the literature

Abstract Myeloid sarcoma is a rare malignant tumor of primitive myeloid cell origin often associated with hematologic disorders. The central nervous system is rarely involved and differentiating between myeloid sarcoma and other tumors is not possible on imaging. Here we present the rare case of an isolated intracranial myeloid sarcoma, initially misdiagnosed radiologically as a meningioma, treated with surgical total resection and subsequent chemotherapy, with no signs of any hematological disorder at follow up. Differential diagnosis and management strategies, as well as follow-up implications are discussed along with literature review, which pointed out that only five cases with no further signs of hematological disorders at follow up have been described in the literature so far and this case has the longest follow up of them at 9 years.
The two paralogous kiwellin proteins KWL1 and KWL1-b from maize are structurally related and have overlapping functions in plant defense

Many plant-pathogenic bacteria and fungi deploy effector proteins that down-regulate plant defense responses and reprogram plant metabolism for colonization and survival in planta. Kiwellin (KWL) proteins are a widespread family of plant-defense proteins that target these microbial effectors. The KWL1 protein from maize (corn, Zea mays) specifically inhibits the enzymatic activity of the secreted chorismate mutase Cmu1, a virulence-promoting effector of the smut fungus Ustilago maydis. In addition to KWL1, 19 additional KWL paralogs have been identified in maize. Here, we investigated the structure and mechanism of the closest KWL1 homolog, KWL1-b (ZEAMA_GRMZM2G305329). We solved the Cmu1–KWL1-b complex to 2.75 Å resolution, revealing a highly symmetric Cmu1–KWL1-b heterotetramer in which each KWL1-b monomer interacts with a monomer of the Cmu1 homodimer. The structure also revealed that the overall architecture of the heterotetramer is highly similar to that of the previously reported Cmu1–KWL1 complex. We found that upon U. maydis infection of Z. mays, KWL1-b is expressed at significantly lower levels than KWL1 and exhibits differential tissue-specific expression patterns. We also show that KWL1-b inhibits Cmu1 activity similarly to KWL1. We conclude that KWL1 and KWL1-b are part of a redundant defense system that tissue-specifically targets Cmu1. This notion was supported by the observation that both KWL proteins are carbohydrate-binding proteins with distinct and likely tissue-related specificities. Moreover, binding by Cmu1 modulated the carbohydrate-binding properties of both KWLs. These findings indicate that KWL proteins are part of a spatiotemporally coordinated, plant-wide defense response comprising proteins with overlapping activities.
Coalescing traditions—Coalescing people: Community formation in Pannonia after the decline of the Roman Empire

The decline of the Roman rule caused significant political instability and led to the emergence of various ‘Barbarian’ powers. While the names of the involved groups appeared in written sources, it is largely unknown how these changes affected the daily lives of the people during the 5th century AD. Did late Roman traditions persist, did new customs emerge, and did both amalgamate into new cultural expressions? A prime area to investigate these population and settlement historical changes is the Carpathian Basin (Hungary). Particularly, we studied archaeological and anthropological evidence, as well as radiogenic and stable isotope ratios of strontium, carbon, and nitrogen of human remains from 96 graves at the cemetery of Mözs-Icsei dűlő. Integrated data analysis suggests that most members of the founder generation at the site exhibited burial practises of late Antique traditions, even though they were heterogeneous regarding their places of origin and dietary habits. Furthermore, the isotope data disclosed a nonlocal group of people with similar dietary habits. According to the archaeological evidence, they joined the community a few decades after the founder generation and followed mainly foreign traditions with artificial skull modification as their most prominent characteristic. Moreover, individuals with modified skulls and late Antique grave attributes attest to deliberate cultural amalgamation, whereas burials of largely different isotope ratios underline the recipient habitus of the community. The integration of archaeological and bioarchaeological information at the individual level discloses the complex coalescence of people and traditions during the 5th century.
First record of anaxyelid woodwasps (Hymenoptera: Anaxyelidae) in Lower Cretaceous Spanish amber

A new species of the family Anaxyelidae (Eosyntexis parva n. sp.) is described. This is the first record of the family from Lower Cretaceous Spanish amber. The specimen is mostly well preserved, except for dorsally. This makes it possible to identify several important details rarely or never observed in compression fossils. Eosyntexis spp. and the closely related genus Cretosyntexis are confined to the Eurasian Lower Cretaceous, whereas the extant monotypic genus Syntexis is restricted to western North America. The morphology of this new species suggests xylophagous habitus, and its relation with Syntexis libocedrii implies a possible relationship with burned wood, apparently a frequently available resource in northern Spanish forests of the Lower Cretaceous.
Hyposalivation as a potential risk for SARS‐CoV‐2 infection: Inhibitory role of saliva

Human saliva is an inquisitively complex fluid and has an imperative role for prevention and protection from viral infection, particularly through innate immune system, which is a prominent first-line defense against viral infection (Malamud et al., 2011; Dawes et al., 2015). Despite the clear role of saliva in the continuous cleansing of oral cavity, we focus on proteins that illustrate antiviral activity, particularly against corona viruses.
Use of Probiotics for the Management of Acute Gastroenteritis in Children. An Update.

Since the publication of the 2014 ESPGHAN Working Group (WG) on Probiotics & Prebiotics guidelines on probiotics for management of acute gastroenteritis (AGE), new evidence concerning the efficacy of probiotics has become available. This document provides updated recommendations on the use of probiotics for the treatment of AGE in previously presumed healthy infants and children. A systematic literature search was performed. All pooled analyses were explicitly performed for the current report. The WG graded the recommendations and assessed the certainty of the supporting evidence using the Grading of Recommendations, Assessment Development, and Evaluations (GRADE) tool. The recommendations were formulated if at least two randomized controlled trials (RCTs) that used a given probiotic were available. Despite the large number of identified trials, the WG could not identify two RCTs of high quality for any strain that provided benefit when used for treating AGE. The WG made weak recommendations for (in descending order in terms of the number of trials evaluating any given strain): Saccharomyces boulardii (low to very low certainty of evidence); Lactobacillus rhamnosus GG (very low certainty of evidence); L reuteri DSM 17938 (low to very low certainty of evidence); and L rhamnosus 19070-2 & L reuteri DSM 12246 (very low certainty of evidence). The WG made a strong recommendation against L helveticus R0052 & L rhamnosus R0011 (moderate certainty of evidence) and a weak recommendation against Bacillus clausii strains O/C, SIN, N/R, and T (very low certainty of evidence).
Variation in Cell Surface Hydrophobicity among Cryptococcus neoformans Strains Influences Interactions with Amoebas

The interaction of a microbial cell with its environment is influenced by the biophysical properties of a cell. The affinity of the cell surface for water, defined by the cell surface hydrophobicity (CSH), is a biophysical parameter that varies among different strains of Cryptococcus neoformans. The CSH influences the phagocytosis of the yeast by its natural predator in the soil, the amoeba. Studying variation in biophysical properties like CSH gives us insight into the dynamic host-predator interaction and host-pathogen interaction in a damage-response framework. ABSTRACT Cryptococcus neoformans and Cryptococcus gattii are pathogenic fungi that cause significant morbidity and mortality. Cell surface hydrophobicity (CSH) is a biophysical parameter that influences the adhesion of fungal cells or spores to biotic and abiotic surfaces. C. neoformans is encased by polysaccharide capsule that is highly hydrophilic and is a critical determinant of virulence. In this study, we report large differences in the CSH of some C. neoformans and C. gattii strains. The capsular polysaccharides of C. neoformans strains differ in repeating motifs and therefore vary in the number of hydroxyl groups, which, along with higher-order structure of the capsule, may contribute to the variation in hydrophobicity that we observed. We found that cell wall composition, in the context of chitin-chitosan content, does not influence CSH. For C. neoformans, CSH correlated with phagocytosis by natural soil predator Acanthamoeba castellanii. Furthermore, capsular binding of the protective antibody (18B7), but not the nonprotective antibody (13F1), altered the CSH of C. neoformans strains. Variability in CSH could be an important characteristic in comparing the biological properties of cryptococcal strains. IMPORTANCE The interaction of a microbial cell with its environment is influenced by the biophysical properties of a cell. The affinity of the cell surface for water, defined by the cell surface hydrophobicity (CSH), is a biophysical parameter that varies among different strains of Cryptococcus neoformans. The CSH influences the phagocytosis of the yeast by its natural predator in the soil, the amoeba. Studying variation in biophysical properties like CSH gives us insight into the dynamic host-predator interaction and host-pathogen interaction in a damage-response framework.
Cardiovascular Complications of Systemic Therapy in Non-Small-Cell Lung Cancer

Cardiovascular diseases may determine therapy outcomes of non-small-cell lung cancer (NSCLC). The evidence for how iatrogenic cardiovascular complications contribute to ceasing anticancer treatment, decreasing the quality of life or even premature death, is unclear. Older patients and smokers are at risk of atherosclerosis and arterial thromboembolic events (TE), such as myocardial infarction or stroke. Venous TE can be observed in up to 15% of NSCLC patients, but the risk increases three to five times in ALK (anaplastic lymphoma kinase)-rearranged NSCLC. ALK inhibitors are associated with electrophysiological disorders. Cytotoxic agents and anti-VEGF inhibitors mainly cause vascular complications, including venous or arterial TE. Cardiac dysfunction and arrhythmias seem to be less frequent. Chemotherapy is often administered in two-drug regimens. Clinical events can be triggered by different mechanisms. Among epidermal growth factor inhibitors, erlotinib and gefitinib can lead to coronary artery events; however, afatinib and osimertinib can be associated with the development of heart failure. During anti-PD1/anti-PDL1 therapy, myocarditis is possible, which must be differentiated from acute coronary syndrome and heart failure. Awareness of all possible cardiovascular complications in NSCLC encourages vigilance in early diagnostics and treatment.
Reproductive performance of otters Lutra lutra (Linnaeus, 1758) in Eastern Germany: low reproduction in a long-term strategy

The reproductive status of female otters (Lutra lutra) was determined from an examination of 518 carcasses collected from Eastern Germany between 1950 and 2001. In Germany otters mate throughout the year. Significant seasonal differences are evident with a distinct peak in summer. Females were in breeding condition between the ages of three and 15 years, with the majority between six and nine years. The mean litter size at birth was 2.36, which was the lowest when compared with other inland populations. There were no significant differences in litter size for regions, seasons or age. Prenatal losses account for 26.31%. The mortality between birth and first appearance of cubs following their mother is about 29%. An effective reproduction rate of 78.4% was deduced from the known age structure of the sample and the proportion of breeding females. Reproductively active females show a significantly higher body condition than non-reproductive females. Following these investigations into breeding status, suggestions on reproductive output and the life history of the otter are discussed. © 2002 The Linnean Society of London, Biological Journal of the Linnean Society, 2002, 77, 329–340.