Miracle-dz/UniFAR-FTUs huggingface dataset:
Fully human anti-CD39 antibody potently inhibits ATPase activity in cancer cells via uncompetitive allosteric mechanism

ABSTRACT The extracellular ATP/adenosine axis in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), otherwise known as CD39, is highly expressed in the TME, both on infiltrating immune cells and tumor cells across a broad set of cancer indications. CD39 processes pro-inflammatory extracellular ATP to ADP and AMP, which is then processed by Ecto-5ʹ-nucleotidase/CD73 to immunosuppressive adenosine. Directly inhibiting the enzymatic function of CD39 via an antibody has the potential to unleash an immune-mediated anti-tumor response via two mechanisms: 1) increasing the availability of immunostimulatory extracellular ATP released by damaged and/or dying cells, and 2) reducing the generation and accumulation of suppressive adenosine within the TME. Tizona Therapeutics has engineered a novel first-in-class fully human anti-CD39 antibody, TTX-030, that directly inhibits CD39 ATPase enzymatic function with sub-nanomolar potency. Further characterization of the mechanism of inhibition by TTX-030 using CD39+ human melanoma cell line SK-MEL-28 revealed an uncompetitive allosteric mechanism (α < 1). The uncompetitive mechanism of action enables TTX-030 to inhibit CD39 at the elevated ATP concentrations reported in the TME. Maximal inhibition of cellular CD39 ATPase velocity was 85%, which compares favorably to results reported for antibody inhibitors to other enzyme targets. The allosteric mechanism of TTX-030 was confirmed via mapping the epitope to a region of CD39 distant from its active site, which suggests possible models for how potent inhibition is achieved. In summary, TTX-030 is a potent allosteric inhibitor of CD39 ATPase activity that is currently being evaluated in clinical trials for cancer therapy.
Diversity of Acyl Homoserine Lactone Molecules in Anaerobic Membrane Bioreactors Treating Sewage at Psychrophilic Temperatures

This study explores the types of acyl homoserine lactone (AHL) and their concentrations in different compartments of different conventional anaerobic bioreactors: (i) an upflow anaerobic membrane bioreactor (UAnMBR, biofilm/mixed liquor (sludge)); (ii) an anaerobic membrane bioreactor (AnMBR, biofilm/mixed liquor (sludge)); and (iii) an upflow sludge blanket (UASB, sludge only), all operating at 15 °C. Ten types of the AHL, namely C4-HSL, 3-oxo-C4-HSL, C6-HSL, 3-oxo-C6-HSL, C8-HSL, 3-oxo-C8-HSL, C10-HSL, 3-oxo-C10-HSL, C12-HSL, and 3-oxo-C12-HSL, which were investigated in this study, were found in UAnMBR and UASB, whilst only six of them (C4-HSL, 3-oxo-C4-HSL, C8-HSL, C10-HSL, 3-oxo-C10-HSL, and C12-HSL) were found in AnMBR. Concentrations of total AHL were generally higher in the biofilm than the sludge for both membrane bioreactors trialed. C10-HSL was the predominant AHL found in all reactors (biofilm and sludge) followed by C4-HSL and C8-HSL. Overall, the UAnMBR biofilm and sludge had 10-fold higher concentrations of AHL compared to the AnMBR. C10-HSL was only correlated with bacteria (p < 0.05), whilst other types of AHL were correlated with both bacteria and archaea. This study improves our understanding of AHL-mediated Quorum Sensing (QS) in the biofilms/sludge of UAnMBR and AnMBR, and provides new information that could contribute to the development of quorum quenching anti-fouling strategies in such systems.
Structural Insight on Functional Regulation of Human MINERVA Protein

MINERVA (melanoma invasion by ERK), also known as FAM129B, is a member of the FAM129 protein family, which is only present in vertebrates. MINERVA is involved in key signaling pathways regulating cell survival, proliferation and apoptosis and found upregulated in many types of cancer promoting invasion. However, the exact function of the protein remains elusive. X-ray crystallographic methods were implemented to determine the crystal structure of MINERVAΔC, lacking C-terminal flexible region. Trypsin digestion was required before crystallization to obtain diffraction-quality crystals. While the N-terminal pleckstrin homology (PH) domain exhibits the typical fold of PH domains, lipid binding assay indicates specific affinity towards phosphatidic acid and inositol 3-phosphate. A helix-rich domain that constitutes the rest of the molecule demonstrates a novel L-shaped fold that encompasses the PH domain. The overall structure of MINERVAΔC with binding assays and cell-based experiments suggest plasma membrane association of MINERVA and its function seem to be tightly regulated by various motifs within the C-terminal flexible region. Elucidation of MINERVAΔC structure presents a novel fold for an α-helix bundle domain that would provide a binding platform for interacting partners.
Cytoplasmic mRNPs revisited: Singletons and condensates

Cytoplasmic messenger ribonucleoprotein particles (mRNPs) represent the cellular transcriptome, and recent data have challenged our current understanding of their architecture, transport, and complexity before translation. Pre‐translational mRNPs are composed of a single transcript, whereas P‐bodies and stress granules are condensates. Both pre‐translational mRNPs and actively translating mRNPs seem to adopt a linear rather than a closed‐loop configuration. Moreover, assembly of pre‐translational mRNPs in physical RNA regulons is an unlikely event, and co‐regulated translation may occur locally following extracellular cues. We envisage a stochastic mRNP transport mechanism where translational repression of single mRNPs—in combination with microtubule‐mediated cytoplasmic streaming and docking events—are prerequisites for local translation, rather than direct transport.
Record of Carineta Amyot and Audinet-Serville, 1843 (Hemiptera: Cicadidae: Cicadettinae: Carinetini) in Goiás State, Brazil

Cicadas (Hemiptera: Cicadidae) são insetos caracterizados principalmente pelo som que emitem, o que torna sua presença evidente em áreas naturais e urbanas. Além disso, sabemos pouco sobre as espécies que ocorrem na região neotropical, inclusive no Brasil. Este é o primeiro relato de espécies de Carineta no estado de Goiás, Brasil. As coletas foram feitas com armadilhas luminosas em duas localidades próximas na área central do bioma Cerrado. Foram amostradas as espécies Carineta durantoni Boulard, 1986, C. gemella Boulard, 1986, C. rufescens (Fabricius, 1803) e C. spoliata (Walker, 1858). Imagens dessas espécies e sua distribuição atual são apresentadas aqui.
Implementation Monitoring of a Promotora-Led, Home-Based Obesity Prevention Pilot Study With Latino Preschool Children and Their Mothers

Background Latino preschool children have higher rates of obesity than children from other racial/ethnic backgrounds. Few effective, culturally-tailored obesity prevention interventions exist that have focused on Latino preschool children, and even fewer have published results of the process evaluation. The purpose of this paper was to monitor reach, fidelity, and completeness of implementation to determine whether ANDALE, a promising promotora-led, home-based pilot study to prevent obesity in Latino preschool children, was implemented as planned. Methods Guided by a logic model, we assessed reach, implementation fidelity and completeness through descriptive analyses of multiple data sources. Reach was assessed through attendance records. Fidelity was assessed via observation checklist and completeness was assessed via survey with both parents and promotoras in a subsample of 12 families. Results Promotoras recruited participants primarily through their own social networks and delivered the intervention to 50 families (mother-child dyads); the majority were of Mexican-origin, low-acculturation, dual-parent households. Nearly all (98%) families completed the whole 10-week intervention. Results demonstrated completeness and fidelity of implementation were acceptable in a subsample of 12 families. In sum, 75% of families in the subsample met the criteria (≥75%) for overall implementation of essential program elements (i.e., reach, completeness, and fidelity). Conclusion Evidence suggests that ANDALE was delivered with high levels of completeness and fidelity in this sample of Latino families with preschool-aged children. These results support implementation of ANDALE in a large, randomized trial.
Heterotrimeric G-proteins in unfolded protein response mediate plant growth-defense tradeoffs upstream of steroid and immune signaling

Plants prioritize growth over defense to gain a competitive advantage for limited resources, but change priorities to successfully fight infection and herbivory. Despite the importance of growth-defense tradeoffs in optimizing plant productivity in natural and agricultural populations, the molecular mechanisms that link growth and immunity remain unclear. Here, we demonstrate that growth-defense tradeoffs between pathways activated by BRI1, a steroid receptor, and FLS2, an innate immune receptor, are uncoupled in an Arabidopsis mutant (agg1 agg2) lacking two redundant heterotrimeric G-protein gamma subunits that form stable heterodimers with the Gβ subunit AGB1 to control one arm of the unfolded protein response (UPR) independently of ER stress. Growth inhibition from induced immunity in wild-type plants is likely caused by AGB1-AGG1/2 dimers interacting with nascent BRI1 and FLS2 proteins on the endoplasmic reticulum (ER) membrane and repressing an UPR response that is hardwired to promote BRI1 protein biogenesis and FLS2 protein degradation via autophagy. The ability to unlock and fine-tune growth-defense tradeoffs through UPR signaling provides a novel strategy to increase the natural defenses of crops while maintaining optimal plant productivity.
Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen

The aim of this retrospective study was to assess the rate of full donor chimerism (F‐DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE‐ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre‐HSCT (31% vs 59%), had more frequently intermediate‐2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre‐HSCT (26% vs 7%). The proportion of patients with F‐DC on day +30, in the TBF vs the ONE‐ALK group, was respectively 87% vs 45% (P < .001). The 5‐year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE‐ALK group (P < .001). The 5‐year actuarial disease‐free survival was 63% for TBF and 38% for the ONE‐ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.
Validation of the DAPT score in large-scale consecutive and contemporary patients population in the real world

Abstract Dual antiplatelet therapy (DAPT) score emerged as a tool for quantification of ischemia and bleeding risks. However, there was discrepancy of the prediction ability of DAPT score in previous studies. We aimed to assess the utility of DAPT score in a large-scale cohort of consecutive percutaneous coronary intervention (PCI) patients. This study enrolled 9,114 patients who had undergone PCI at Fuwai Hospital in 2013, adhered to DAPT and were event-free within the first 12 months following PCI. The endpoints included primary ischemic endpoints (major adverse cardiovascular and cerebrovascular events, and myocardial infarction and/or stent thrombosis), and bleeding endpoint from 12 through 24 months after PCI. Patients were classified into low (score <2, n = 3,989) and high (score ≥2, n = 5,125) DAPT score groups. The incidence rates of primary ischemic endpoints and bleeding endpoint were similar between the two groups. Multivariable analysis demonstrated DAPT score not to be an independent predictor of primary ischemic endpoints or bleeding endpoint. Based on receiver operating characteristic curves analysis, the C-statistic of DAPT score for primary ischemic endpoints or bleeding endpoint did not achieve a significant extent. In this large-scale cohort of PCI patients, DAPT score did not discriminate the risks of ischemic and bleeding events.
DNA Methylation in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a widespread hepatic disorder in the United States and other Westernized countries. Nonalcoholic steatohepatitis (NASH), an advanced stage of NAFLD, can progress to end-stage liver disease, including cirrhosis and liver cancer. Poor understanding of mechanisms underlying NAFLD progression from simple steatosis to NASH has limited the development of effective therapies and biomarkers. An accumulating body of studies has suggested the importance of DNA methylation, which plays pivotal roles in NAFLD pathogenesis. DNA methylation signatures that can affect gene expression are influenced by environmental and lifestyle experiences such as diet, obesity, and physical activity and are reversible. Hence, DNA methylation signatures and modifiers in NAFLD may provide the basis for developing biomarkers indicating the onset and progression of NAFLD and therapeutics for NAFLD. Herein, we review an update on the recent findings in DNA methylation signatures and their roles in the pathogenesis of NAFLD and broaden people’s perspectives on potential DNA methylation-related treatments and biomarkers for NAFLD.
Circular RNA expression profiles in umbilical cord blood exosomes from normal and gestational diabetes mellitus patients

Abstract Circular RNA (circRNA) is a novel member of endogenous noncoding RNAs with widespread distribution and diverse cellular functions. Recently, circRNAs have been identified for their enrichment and stability in exosomes. However, the roles of circRNAs from umbilical cord blood exosomes in gestational diabetes mellitus (GDM) occurrence and fetus growth remains poorly understood. In the present study, we used microarray technology to construct a comparative circRNA profiling of umbilical cord blood exosomes between GDM patients and controls. We found the exosome particle size was larger, and the exosome concentration was higher in the GDM patients. A total of 88,371 circRNAs in umbilical cord blood exosomes from two groups were evaluated. Of these, 229 circRNAs were significantly up-regulated and 278 circRNAs were significantly down-regulated in the GDM patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses demonstrated that circRNA parental genes involved in the regulation of metabolic process, growth and development were significantly enriched, which are important in GDM development and fetus growth. Further circRNA/miRNA interactions analysis showed that most of the exosomal circRNAs harbored miRNA binding sites, and some miRNAs were associated with GDM. Collectively, these results lay a foundation for extensive studies on the role of exosomal circRNAs in GDM development and fetus growth.
An Architectural Multi-Agent System for a Pavement Monitoring System with Pothole Recognition in UAV Images

In recent years, maintenance work on public transport routes has drastically decreased in many countries due to difficult economic situations. The various studies that have been conducted by groups of drivers and groups related to road safety concluded that accidents are increasing due to the poor conditions of road surfaces, even affecting the condition of vehicles through costly breakdowns. Currently, the processes of detecting any type of damage to a road are carried out manually or are based on the use of a road vehicle, which incurs a high labor cost. To solve this problem, many research centers are investigating image processing techniques to identify poor-condition road areas using deep learning algorithms. The main objective of this work is to design of a distributed platform that allows the detection of damage to transport routes using drones and to provide the results of the most important classifiers. A case study is presented using a multi-agent system based on PANGEA that coordinates the different parts of the architecture using techniques based on ubiquitous computing. The results obtained by means of the customization of the You Only Look Once (YOLO) v4 classifier are promising, reaching an accuracy of more than 95%. The images used have been published in a dataset for use by the scientific community.
Transcriptional Analysis of Carotenoids Accumulation and Metabolism in a Pink-Fleshed Lemon Mutant

Pink lemon is a spontaneous bud mutation of lemon (Citrus limon, L. Burm. f) characterized by the production of pink-fleshed fruits due to an unusual accumulation of lycopene. To elucidate the genetic determinism of the altered pigmentation, comparative carotenoid profiling and transcriptional analysis of both the genes involved in carotenoid precursors and metabolism, and the proteins related to carotenoid-sequestering structures were performed in pink-fleshed lemon and its wild-type. The carotenoid profile of pink lemon pulp is characterized by an increased accumulation of linear carotenoids, such as lycopene, phytoene and phytofluene, from the early stages of development, reaching their maximum in mature green fruits. The distinctive phenotype of pink lemon is associated with an up-regulation and down-regulation of the genes upstream and downstream the lycopene cyclase, respectively. In particular, 9-cis epoxycarotenoid dioxygenase genes were overexpressed in pink lemon compared with the wild-type, suggesting an altered regulation of abscisic acid biosynthesis. Similarly, during early development of the fruits, genes of the carotenoid-associated proteins heat shock protein 21, fibrillin 1 and 2 and orange gene were overexpressed in the pulp of the pink-fleshed lemon compared to the wild-type, indicating its increased capacity for sequestration, stabilization or accumulation of carotenes. Altogether, the results highlighted significant differences at the transcriptomic level between the pink-fleshed lemon and its wild-type, in terms of carotenoid metabolism and the capacity of stabilization in storage structures between the two accessions. Such changes may be either responsible for the altered carotenoid accumulation or in contrast, a metabolic consequence.
State-of-the-Art Technologies for Understanding Brassinosteroid Signaling Networks

Brassinosteroids, the steroid hormones of plants, control physiological and developmental processes through its signaling pathway. The major brassinosteroid signaling network components, from the receptor to transcription factors, have been identified in the past two decades. The development of biotechnologies has driven the identification of novel brassinosteroid signaling components, even revealing several crosstalks between brassinosteroid and other plant signaling pathways. Herein, we would like to summarize the identification and improvement of several representative brassinosteroid signaling components through the development of new technologies, including brassinosteroid-insensitive 1 (BRI1), BRI1-associated kinase 1 (BAK1), BR-insensitive 2 (BIN2), BRI1 kinase inhibitor 1 (BKI1), BRI1-suppressor 1 (BSU1), BR signaling kinases (BSKs), BRI1 ethyl methanesulfonate suppressor 1 (BES1), and brassinazole resistant 1 (BZR1). Furthermore, improvement of BR signaling knowledge, such as the function of BKI1, BES1 and its homologous through clustered regularly interspaced short palindromic repeats (CRISPR), the regulation of BIN2 through single-molecule methods, and the new in vivo interactors of BIN2 identified by proximity labeling are described. Among these technologies, recent advanced methods proximity labeling and single-molecule methods will be reviewed in detail to provide insights to brassinosteroid and other phytohormone signaling pathway studies.
Heat stress impairs egg production in commercial laying hens infected by fowl typhoid

ABSTRACT Salmonella Gallinarum (SG) is an avian-restricted pathogen that causes fowl typhoid in poultry. Although it has been reported frequently over many decades in poultry flocks worldwide, the microorganism is more commonly associated with poultry in developing countries, particularly those with high ambient temperatures, where the acute form of the disease results in considerable economic losses. A more detailed investigation of environmental factors that affect the course of disease may assist in identifying effective prevention and control measures. Heat stress is known to impair the immunological response to a variety of pathogens and clearly may be an important contributory factor in the prevalence of disease in countries with warm or hot climates. Thus, the objective of the present study was to evaluate the effects of heat stress on chickens infected with SG. For this, light and semi-heavy commercial laying hens were distributed randomly within four groups as follows: infected and non-infected groups in rooms held at ambient temperature, and infected and non-infected groups under heat stress. Clinical signs, egg production, and mortality were recorded daily. Bacteriological counts in liver and spleen samples were estimated at 2, 5, 7, and 14 days post-infection. The results showed that both SG infection and heat stress had similar effects on egg production and a synergistic effect of the two stressors was observed. The data show an interaction between disease and heat stress which could point towards environmental and biosecurity approaches to resolving the possible 30% fall in production observed in such countries.
Seasonal Patterns of Dominant Microbes Involved in Central Nutrient Cycles in the Subsurface

Microbial communities play a key role for central biogeochemical cycles in the subsurface. Little is known about whether short-term seasonal drought and rewetting events influence the dominant microbes involved in C- and N-cycles. Here, we applied metaproteomics at different subsurface sites in winter, summer and autumn from surface litter layer, seepage water at increasing subsoil depths and remote located groundwater from two wells within the Hainich Critical Zone Exploratory, Germany. We observed changes in the dominance of microbial families at subsurface sampling sites with increasing distances, i.e., Microcoleaceae dominated in topsoil seepage, while Candidatus Brocadiaceae dominated at deeper and more distant groundwater wells. Nitrifying bacteria showed a shift in dominance from drought to rewetting events from summer by Nitrosomandaceae to autumn by Candidatus Brocadiaceae. We further observed that the reductive pentose phosphate pathway was a prominent CO2-fixation strategy, dominated by Woeseiaceae in wet early winter, which decreased under drought conditions and changed to a dominance of Sphingobacteriaceae under rewetting conditions. This study shows that increasing subsurface sites and rewetting event after drought alter the dominances of key subsurface microbes. This helps to predict the consequences of annual seasonal dynamics on the nutrient cycling microbes that contribute to ecosystem functioning.