Miracle-dz/UniFAR-FTUs huggingface dataset:
METTL5, an 18S rRNA-specific m6A methyltransferase, modulates expression of stress response genes

RNA N6-methyladenosine (m6A) modification is present in different RNA molecules, including protein-coding mRNAs and non-coding RNAs such as ribosomal RNAs (rRNAs). Previous studies identified m6A in both the 18S and 28S rRNAs, but the roles of these methylation events are poorly understood due to the lack of knowledge of the responsible methyltransferases. Here, we report that mammalian METTL5, a member of a highly conserved methyltransferase family, specifically methylates adenosine 1832 (A1832) in the 18S rRNA in vivo and in vitro. We identify TRMT112 as a near stoichiometric partner of METTL5 important for the enzymatic activity of METTL5. By mapping the positions of translating ribosomes (Ribo-seq), we found translation of multiple stress response-related mRNAs, including Atf4 mRNA, is selectively reduced in the Mettl5 knockout (KO) mouse B16 melanoma cells. Atf4 is a key transcription factor that mediates the Integrated Stress Response (ISR), as exemplified by the Endoplasmic Reticulum (ER) stress. Consistently, transcription of ISR effector genes is reduced in Mettl5 KO cells during ER stress, suggesting a compromised ISR. Our findings reveal a new mechanism that regulates expression of stress response genes and suggest that chemical modifications of ribosomal RNAs may play a key role in selectively impacting translation and possibly ISR.
Low-Molecular-Weight Heparin Reduces Ventilation-Induced Lung Injury through Hypoxia Inducible Factor-1α in a Murine Endotoxemia Model

Patients with sepsis frequently require mechanical ventilation (MV) to survive. However, MV has been shown to induce the production of proinflammatory cytokines, causing ventilator-induced lung injury (VILI). It has been demonstrated that hypoxia-inducible factor (HIF)-1α plays a crucial role in inducing both apoptotic and inflammatory processes. Low-molecular-weight heparin (LMWH) has been shown to have anti-inflammatory activities. However, the effects of HIF-1α and LMWH on sepsis-related acute lung injury (ALI) have not been fully delineated. We hypothesized that LMWH would reduce lung injury, production of free radicals and epithelial apoptosis through the HIF-1α pathway. Male C57BL/6 mice were exposed to 6-mL/kg or 30-mL/kg MV for 5 h. Enoxaparin, 4 mg/kg, was administered subcutaneously 30 min before MV. We observed that MV with endotoxemia induced microvascular permeability; interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2 and vascular endothelial growth factor protein production; neutrophil infiltration; oxidative loads; HIF-1α mRNA activation; HIF-1α expression; bronchial epithelial apoptosis; and decreased respiratory function in mice (p < 0.05). Endotoxin-induced augmentation of VILI and epithelial apoptosis were reduced in the HIF-1α-deficient mice and in the wild-type mice following enoxaparin administration (p < 0.05). Our data suggest that enoxaparin reduces endotoxin-augmented MV-induced ALI, partially by inhibiting the HIF-1α pathway.
The role of multiple reproductive barriers: Strong post-pollination interactions govern cytotype isolation in a tetraploid-octoploid contact zone.

BACKGROUND AND AIMS Polyploidy is an important contributor to sympatric speciation and assortative mating is a key mechanism driving cytotype interactions at contact zones. While strong reproductive barriers can mediate the coexistence of different cytotypes in sympatry, positive frequency-dependent mating disadvantage ultimately drives the transition to single-ploidy populations. However, comprehensive estimates of reproductive isolation among cytotypes and across multiple barriers are rare. We quantify the strength of isolation across multiple reproductive stages in a tetraploid-octoploid contact zone to understand the potential for coexistence. METHODS Assortative mating due to flowering asynchrony, pollinator behaviour, morphological overlap, self-fertilization and gametic competition between tetraploid and octoploid Gladiolus communis in a contact zone in Western Iberian Peninsula were assessed in natural and experimental populations to quantify reproductive isolation (RI) between cytotypes. KEY RESULTS Tetraploids and octoploids have a high degree of overlap in flowering time, similar floral morphology, and are visited by generalist insects without cytotype foraging preferences, resulting in weak pre-pollination reproductive isolation (RI from 0.00 to 0.21). In contrast, post-pollination isolation resulting from gametic selection was a strong barrier to inter-cytotype mating, with ploidy composition in stigmatic pollen loads determining the levels of RI (RI from 0.54 to 1.00). Between-cytotype cross-incompatibility was relatively high (RI from 0.54 to 0.63) as was isolation acquired through self-pollination (RI of 0.59 in tetraploids and 0.39 in octoploids). CONCLUSIONS Total RI was high for both tetraploids (RI from 0.90 to 1.00) and octoploids (RI from 0.78 to 0.98). Such high rates of assortative mating will enable cytotype coexistence in mixed-ploidy populations by weakening the impacts of minority cytotype exclusion. This study reveals the key role of gametic selection in cytotype siring success and highlights the importance of comprehensive estimates across multiple reproductive barriers to understand cytotype interactions at contact zones.
BK Virus RNA in Renal Allograft Biopsies

BK polyomavirus–associated nephropathy (BKpyVAN) remains a cause of graft loss in kidney transplant recipients on immunosuppressive therapy. Its diagnosis relies on the identification of BK virus (BKV) in the renal allograft biopsy by positive immunohistochemical (IHC) stain for the viral SV40 large T antigen, although in situ hybridization (ISH) for viral DNA is used in some centers. We examined tissue detection of BKV RNA by RNAscope, a novel, automated ISH test, in 61 allograft biopsies from 56 patients with BKpyVAN. We found good correlation between the estimate of BKV tissue load by RNAscope ISH and SV40 IHC (R2 = 0.65, p<0.0001). RNAscope ISH showed 88% sensitivity and 79% specificity and, as an alternative test, could confirm the presence of BKV tissue in presumed BKpyVAN and rule out BKV as the causative agent in JC virus nephropathy. We also used tissue BK viral load estimates by both RNAscope ISH and SV40 IHC to examine the relation between tissue and plasma BK levels and found significant correlation only between BK viremia and tissue BK measured by RNAscope ISH. Our findings suggest that the RNAscope ISH assay could be a reliable test for BKV detection in allograft biopsies.
Ras Inhibitor CAPRI Enables Neutrophils to Chemotax Through a Higher-Concentration Range of Gradients

Neutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that, in human neutrophils, Calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI (caprikd) exhibit chemoattractant-induced non-adaptive Ras activation; significantly increased phosphorylation of AKT, GSK3α/3β, and cofilin; and excessive actin polymerization. caprikd cells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher concentration range of chemoattractant gradients. Significance Statement Neutrophils provide first-line host defense by migrating through chemoattractant gradients to the sites of inflammation. Inappropriate recruitment and mis-regulated activation of neutrophils contribute to tissue damage and cause autoimmune and inflammatory disease. One fascinating feature of chemotactic neutrophils is their ability to migrate through an enormous concentration range of chemoattractant gradients (10−9 ∼ 10−5 M) through “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. Our study reveals, for the first time, that the inhibitory component, CAPRI, is essential for both the sensitivity and the GPCR-mediated adaptation of human neutrophils.
Blocking gephyrin phosphorylation or microglia BDNF signaling prevents synapse loss and reduces infarct volume after ischemia

Microglia interact with neurons to facilitate synapse plasticity; however, signal transducers between microglia and neuron remain unknown. Here, using in vitro organotypic hippocampal slice cultures and transient MCAO in genetically-engineered mice in vivo, we report that at 24 h post-ischemia microglia release BDNF to downregulate glutamatergic and GABAergic synapses within the peri-infarct area. Analysis of the CA1 hippocampal formation in vitro shows that proBDNF and mBDNF downregulate glutamatergic dendritic spines and gephyrin scaffold stability through p75NTR and TrkB receptors respectively. Post-MCAO, we report that in the peri- infarct area and in the corresponding contralateral hemisphere similar neuroplasticity occur through microglia activation and gephyrin phosphorylation at Ser268, Ser270 in vivo. Targeted deletion of the Bdnf gene in microglia or GphnS268A/S270A (phospho-null) point-mutations protect against ischemic brain damage, neuroinflamation and synapse downregulation normally seen post-MCAO. Collectively, we report that gephyrin phosphorylation and microglia derived BDNF faciliate synapse plasticity after transient ischemia.
Research Review: Conflicts of Interest (COIs) in autism early intervention research - a meta-analysis of COI influences on intervention effects.

BACKGROUND The presence, types, disclosure rates, and effects of conflicts of interest (COIs) on autism early intervention research have not previously been studied. The purpose of this study was to examine these issues. METHODS This study is a secondary analysis of a comprehensive meta-analysis of all group-design, nonpharmacological early intervention autism research conducted between 1970 and 2018. We coded reports for the presence/absence of COI statements, the types of COIs that were disclosed, and for 8 types of COIs, including (a) the author developed the intervention, (b) the author is affiliated with a clinical provider, (c) the author is employed by a clinical provider, (d) the author is affiliated with an institution that trains others to use the intervention, (e) the author receives payment or royalties related to the intervention, (f) the study was funded by an intervention provider, (g) the study used a commercially available measure developed by the author, and (h) proceeds of the intervention fund the author's research. Frequencies and proportions were calculated to determine prevalence of COIs and COI disclosures. Meta-analysis was used to estimate summary effects by COI type and to determine if they were larger than for reports with no coded COIs. RESULTS Seventy percent of reports were coded for ≥ 1 COI, but only ~ 6% of reports contained COI statements fully accounting for all coded COIs. Metaregressions did not detect significant influences of any COI type on summary effects; however, point estimates for each COI type were larger than for reports with no coded COIs. CONCLUSIONS Conflicts of interest are prevalent but under-reported in autism early intervention research. Improved reporting practices are necessary for researcher transparency and would enable more robust examination of the effects of COIs on research outcomes.
Somatomotor cortical representations are predicted by levels of short-interval intracortical inhibition

Transcranial magnetic stimulation (TMS) can be used to probe for the location of cortical somatomotor representations in humans. These somatomotor representations are dynamic and are perturbed following motor training, systematic intervention, and in disease. Evidence suggests that these representations are maintained by the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA). In the current study, we quantified the location, outline, and variability of the first dorsal interosseous (FDI) hand muscle somatomotor representation using a novel rapid-acquisition TMS method in 14 healthy young volunteers. In addition, resting motor thresholds were measured using established protocols. TMS was also used to examine short-interval intracortical inhibition (SICI), which is thought to measure transiently activated cortical gamma-Aminobutyric acid (GABA) interneurons. Using stepwise regression, our results showed that the level of intracortical inhibition was a significant predictor of the FDI somatomotor representation suggesting that greater excitability of the hand area representation is possibly governed by greater activation of transient GABA interneurons.
Genome Sequence Resources of Colletotrichum truncatum, C. plurivorum, C. musicola and C. sojae: Four Species Pathogenic to Soybean (Glycine max).

Colletotrichum is a large genus of plant pathogenic fungi comprising more than 200 species. In this work we present the genome sequences of four Colletotrichum species pathogenic to soybean: C. truncatum, C. plurivorum, C. musicola and C. sojae. While C. truncatum is globally considered the most important pathogen the other three species have been described and associated with soybean only recently. The genome sequences will provide insights into factors that contribute to pathogenicity towards soybean and will be useful for further research into the evolution of Colletotrichum.
Naphthoquinones as Covalent Reversible Inhibitors of Cysteine Proteases—Studies on Inhibition Mechanism and Kinetics

The facile synthesis and detailed investigation of a class of highly potent protease inhibitors based on 1,4-naphthoquinones with a dipeptidic recognition motif (HN-l-Phe-l-Leu-OR) in the 2-position and an electron-withdrawing group (EWG) in the 3-position is presented. One of the compound representatives, namely the acid with EWG = CN and with R = H proved to be a highly potent rhodesain inhibitor with nanomolar affinity. The respective benzyl ester (R = Bn) was found to be hydrolyzed by the target enzyme itself yielding the free acid. Detailed kinetic and mass spectrometry studies revealed a reversible covalent binding mode. Theoretical calculations with different density functionals (DFT) as well as wavefunction-based approaches were performed to elucidate the mode of action.
Compositional Safety of DAS-68416-4 (AAD-12) Herbicide-Tolerant Soybean

The composition of transgenic DAS-68416-4 soybean seed and forage was compared with that of non-transgenic soybean. DAS-68416-4 soybean expresses the aryloxyalkanoate dioxygenase-12 enzyme from the soil bacterium, Delftia acidovorans, which detoxifies 2,4-dichlorophenoxyacetic acid (2,4-D), conferring tolerance to this herbicide. DAS-68416-4 also expresses the phosphinothricin acetyltransferase enzyme from Streptomyces viridochromogenes which confers tolerance to glufosinate-ammonium herbicides. As expected for an input trait, results indicate that DAS-68416 soybean is compositionally equivalent to non-transgenic soybean.
Review on Credit Card Fraud Detection using Data Mining Classification Techniques & Machine Learning Algorithms

Data mining (DM) involves a core algorithm that enables data deeper than basic insights and knowledge. In fact, data mining is more part of knowledge discovery process. Credit card (CC) providers provide multiple cards to their customers. All credit card users must be genuine and sincere. Giving a card to any kind of mistake can lead to a financial crisis. Due to the rapid growth in cashless transactions, it is unlikely, Fake transactions can also be increased. A fraudulent transaction can be identified by studying credit cards of various behaviors as a previous transaction history data set. If there is any deviation from the available cost pattern, it is a bogus transaction. DM &amp; machine learning techniques (MLT) are widely applied in credit card fraud detection (CCFD). In this survey paper we show an indication of various widely available DM &amp; MLT for detecting credit card fraud.
Identification of genes involved in the onset of female puberty of rat

Onset of female puberty follows a series of prepubertal cellular and molecular events including changes of synaptic plasticity, synthetic and releasing activity and gene expression. Dramatic increase of gonadal steroid level is one of the most prominent changes before the onset of puberty. Based on the importance of steroid feedback upon the hypothalamus, we adopted an estrogen sterilized rat (ESR) model where 100 ng of 17p‐estradiol were administered into neonatal pubs for 7 days after birth. To identify genes involved in the onset of female puberty, we applied PCR differential display using RNA samples derived from ESR and control rat hypothalami. About 100 out of more than 1000 RNA species examined displayed differential expression patterns between a 60‐day old control rat and ESR. Sequence analysis of differentially amplified PCR products showed homology with genes such as mouse kinesin superfamily‐associated protein 3 (KAP3) and several cDNAs previously described by others in mouse and human tissues.
Analysis of Detection Models for Disaster-Related Tweets

Social media is perceived as a rich resource for disaster management and relief e � orts, but the high class imbalance between disaster-related and non-disaster-related messages challenges a reliable detection. We analyze and compare the e � ectiveness of three state-of-the-art machine learning models for detecting disaster-related tweets. In this regard we introduce the Disaster Tweet Corpus 2020, an extended compilation of existing resources, which comprises a total of 123,166 tweets from 46 disasters covering 9 disaster types. Our ﬁndings from a large experiments series include: detection models work equally well over a broad range of disaster types when being trained for the respective type, a domain transfer across disaster types leads to unacceptable performance drops, or, similarly, type-agnostic classiﬁcation models behave more robust at a lower e � ectiveness level. Altogether, the average misclassiﬁcation rate of 3,8% on performance-optimized detection models indicates e � ective classiﬁcation knowledge but comes at the price of insu � cient generalizability.
Towards Integrated 3D Reconstruction and Semantic Interpretation of Urban Scenes

: We describe recent progress made towards automated extraction of semantically annotated 3D city models from aerial imagery. The idea of semantic 3D reconstruction is to reconstruct the 3D geometry of an observed scene while at the same time also interpreting the scene in terms of semantic object classes (such as buildings, vegetation etc.) - similar to a human operator, who also interprets the image content while making measurements. The advantage of jointly reasoning about shape and object class is that one can exploit class-specific a-priori knowledge about the geometry: on the one hand the type of object provides information about its shape, e.g. walls are likely to be vertical, whereas streets are not; on the other hand, 3D geometry is also an important cue for classification, e.g. in our example vertical surfaces are more likely to be walls than streets. Recent work has developed computational models that allow one to jointly infer geometry and class. For simple priors, such as preferred surface orientations, these models even have favourable mathematical properties like convexity of the optimisation. However, they rely on a dense, volumetric discretisation of 3D space, therefore the computation is memory-hungry and slow. We have developed an adaptive, hierarchical formulation of semantic 3D reconstruction, which makes it possible to process scenes of much larger, realistic size. The intuition is that both high spatial resolution and high numerical precision are only required in regions that are likely to contain a surface. Technically, our scheme amounts to repeatedly solving a constrained, convex optimisation problem, while iteratively removing low-confidence constraints. In our experiments the adaptive reconstruction incurs no loss in accuracy, but offers up to 98% lower memory consumption and up to 95% shorter computation time.
Pangenome Analytics Reveal Two-Component Systems as Conserved Targets in ESKAPEE Pathogens

The ESKAPEE pathogens are the leading cause of health care-associated infections worldwide. Two-component systems (TCSs) can be used as effective targets against pathogenic bacteria since they are ubiquitous and manage various vital functions such as antibiotic resistance, virulence, biofilms, quorum sensing, and pH balance, among others. ABSTRACT The two-component system (TCS) helps bacteria sense and respond to environmental stimuli through histidine kinases and response regulators. TCSs are the largest family of multistep signal transduction processes, and they are involved in many important cellular processes such as antibiotic resistance, pathogenicity, quorum sensing, osmotic stress, and biofilms. Here, we perform the first comprehensive study to highlight the role of TCSs as potential drug targets against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) pathogens through annotation, mapping, pangenomic status, gene orientation, and sequence variation analysis. The distribution of the TCSs is group specific with regard to Gram-positive and Gram-negative bacteria, except for KdpDE. The TCSs among ESKAPEE pathogens form closed pangenomes, except for Pseudomonas aeruginosa. Furthermore, their conserved nature due to closed pangenomes might make them good drug targets. Fitness score analysis suggests that any mutation in some TCSs such as BaeSR, ArcBA, EvgSA, and AtoSC, etc., might be lethal to the cell. Taken together, the results of this pangenomic assessment of TCSs reveal a range of strategies deployed by the ESKAPEE pathogens to manifest pathogenicity and antibiotic resistance. This study further suggests that the conserved features of TCSs might make them an attractive group of potential targets with which to address antibiotic resistance. IMPORTANCE The ESKAPEE pathogens are the leading cause of health care-associated infections worldwide. Two-component systems (TCSs) can be used as effective targets against pathogenic bacteria since they are ubiquitous and manage various vital functions such as antibiotic resistance, virulence, biofilms, quorum sensing, and pH balance, among others. This study provides a comprehensive overview of the pangenomic status of the TCSs among ESKAPEE pathogens. The annotation and pangenomic analysis of TCSs show that they are significantly distributed and conserved among the pathogens, as most of them form closed pangenomes. Furthermore, our analysis also reveals that the removal of the TCSs significantly affects the fitness of the cell. Hence, they may be used as promising drug targets against bacteria.