Miracle-dz/UniFAR-FTUs huggingface dataset:
The catheterized bladder environment promotes Efg1- and Als1-dependent Candida albicans infection

Catheter-associated urinary tract infections (CAUTIs) account for 40% of all hospital-acquired infections. Given that 20-50% of all hospitalized patients receive a catheter, CAUTIs are one of the most common hospital-acquired infections and a significant medical complication as they result in increased morbidity, mortality, and an estimated annual cost of $340-370 million. Candida spp. – specifically Candida albicans – are a major causative agent of CAUTIs (17.8%), making it the second most common CAUTI uropathogen. Despite this frequent occurrence, the cellular and molecular details of C. albicans infection in the CAUTI microenvironment are poorly understood. Here, we characterize fungal virulence mechanisms and fungal biofilm formation during CAUTI for the first time. We found that the catheterized bladder environment triggers Candida virulence programs and robust biofilm formation through Efg1-dependent hyphal morphogenesis and Als1, an Efg1-downstream effector. Additionally, we show that the adhesin Als1 is necessary for in vitro and in vivo C. albicans biofilm formation dependent on the presence of fibrinogen (Fg), a coagulation factor released in the bladder due to the mechanical damage caused by urinary catheterization. Furthermore, in the presence of Fg, overexpression of ALS1 in C. albicans led to enhanced colonization and dissemination, while deletion of ALS1 reduced both outcomes during CAUTIs. Our study ultimately unveils the mechanism that contributes to fungal CAUTI, which may provide more effective targets for future therapies to prevent these infections.
SynBOLD-DisCo: Synthetic BOLD images for distortion correction of fMRI without additional calibration scans

The blood oxygen level dependent (BOLD) signal from functional magnetic resonance imaging (fMRI) is a noninvasive technique that has been widely used in research to study brain function. However, fMRI suffers from susceptibility-induced off resonance fields which may cause geometric distortions and mismatches with anatomical images. State-of-the-art correction methods require acquiring reverse phase encoded images or additional field maps to enable distortion correction. However, not all imaging protocols include these additional scans and thus cannot take advantage of these susceptibility correction capabilities. As such, in this study we aim to enable state-of-the-art distortion correction with FSL’s topup algorithm of historical and/or limited fMRI data that include only a structural image and single phase encoded fMRI. To do this, we use 3D U-net models to synthesize undistorted fMRI BOLD contrast images from the structural image and use this undistorted synthetic image as an anatomical target for distortion correction with topup. We evaluate the efficacy of this approach, named SynBOLD-DisCo (synthetic BOLD images for distortion correction), and show that BOLD images corrected using our approach are geometrically more similar to structural images than the distorted BOLD data and are practically equivalent to state-of-the-art correction methods which require reverse phase encoded data. Future directions include additional validation studies, integration with other preprocessing operations, retraining with broader pathologies, and investigating the effects of spin echo versus gradient echo images for training and distortion correction. In summary, we demonstrate SynBOLD-DisCo corrects distortion of fMRI when reverse phase encoding scans or field maps are not available.
Diversification of the ruminant skull along an evolutionary line of least resistance

Morphological integration is relevant to evolutionary biology and paleontology because the structure of variation within populations determines the ways in which a population can respond to selective pressures. However, understanding the macroevolutionary consequences of morphological integration is elusive because the adaptive landscape is dynamic and population-level constraints themselves evolve. By analyzing a previously published dataset of 2859 ruminant crania with 3D geometric morphometrics and phylogenetic comparative methods, we find that variation within and between ruminant species is biased by a highly conserved mammalian-wide allometric pattern, CREA, where larger species have proportionally longer faces. More tightly integrated species and species more biased towards CREA have diverged farther from their ancestors, and Ruminantia as a clade diversified farther than expected in the direction anticipated by CREA. Our analyses indicate that CREA acts as an evolutionary ‘line of least resistance’ and facilitates morphological diversification due to its alignment with the browser-grazer continuum. These results demonstrate that biological processes constraining variation at the microevolutionary level can produce highly directional phenotypic evolution over macroevolutionary timescales.
Reduced coenzyme Q synthesis confers non-target site resistance to the herbicide thaxtomin A

Herbicide resistance in weeds is a growing threat to global crop production. Non-target site resistance is problematic because a single resistance allele can confer tolerance to many herbicides (cross resistance), and it is often a polygenic trait so it can be difficult to identify the molecular mechanisms involved. Most characterized molecular mechanisms of non-target site resistance are caused by gain-of-function mutations in genes from a few key gene families – the mechanisms of resistance caused by loss-of-function mutations remain unclear. In this study, we first show that the mechanism of non-target site resistance to the herbicide thaxtomin A conferred by loss-of-function of the gene PAM16 is conserved in Marchantia polymorpha, validating its use as a model species with which to study non-target site resistance. To identify mechanisms of non-target site resistance caused by loss-of-function mutations, we generated 107 UV-B mutagenized M. polymorpha spores and screened for resistance to the herbicide thaxtomin A. We isolated 13 thaxtomin A-resistant mutants and found that 3 mutants carried candidate resistance-conferring SNPs in the MpRTN4IP1L gene. Mprtn4ip1l mutants are defective in coenzyme Q biosynthesis and accumulate higher levels of reactive oxygen species (ROS) than wild-type plants. Mutants are also defective in thaxtomin A metabolism, consistent with the hypothesis that loss of MpRTN4IP1L function confers non-target site resistance. We conclude that loss of MpRTN4IP1L function is a novel mechanism of non-target site herbicide resistance, and propose that other mutations which increase ROS levels or decrease thaxtomin A metabolism could confer thaxtomin A resistance in the field. AUTHOR SUMMARY Modern agriculture relies on herbicides to control weed populations. However, herbicide resistance in weeds threatens the efficacy of herbicides and global crop production, similar to how antibiotic resistance poses a global health threat. Understanding the molecular mechanisms behind herbicide resistance helps to prevent resistance from evolving and to better manage herbicide resistant weeds in the field. Here, we use a forward genetic approach in the model species Marchantia polymorpha to discover novel mechanisms of herbicide resistance. We report the discovery of a novel mechanism of herbicide resistance caused by loss-of-function mutations in the MpRTN4IP1L gene. We find that Mprtn4ip1l mutants are resistant to the herbicides thaxtomin A and isoxaben, accumulate higher levels of reactive oxygen species than wild type plants, and are defective in thaxtomin A metabolism. We predict that loss-of-function mutations or treatments that increase reactive oxygen species production could contribute to thaxtomin A tolerance.
A novel insertional allele of CG18135 gene is associated with severe mutant phenotypes in Drosophila melanogaster

Drosophila melanogaster has been at the forefront of genetic studies and biochemical modelling for over a century. Yet, the functions of many genes are still unknown mainly because no phenotypic data are available. Herein, we present first evidence data regarding the particular molecular and other quantifiable phenotypes, such as viability and anatomical anomalies, induced by a novel P{lacW} insertional mutant allele of CG18135 gene. So far, the CG18135 functions have only been theorized based on electronic annotation and presumptive associations inferred upon high-throughput proteomics or RNA sequencing experiments. The descendants of individuals harboring the CG18135P{lacW}CG18135 allele were scored in order to assess mutant embryos, larvae and pupae viability versus Canton Special. Our results revealed that the homozygous CG18135P{lacW}CG18135/CG18135P{lacW}CG18135 genotype determines significant lethality both at the inception of larval stage and during pupal development. Few imago escapers that breach the puparium and even more rarely fully exit from it exhibit specific eye depigmentation, wing abnormal unfolding and strong locomotor impairment with apparent spasmodic legs movements. Their maximum lifespan is shorter than two days. When using the quantitative Real-Time PCR (qRT-PCR) method to confirm that CG18135 is indeed upregulated in males compared to females an unexpected gene upregulation was also detected in heterozygous mutants comparative to wild-type flies, probably because of regulatory perturbations induced by P{lacW} transposon. Our work provides the first phenotypic evidence for the essential role of CG18135, a scenario in accordance with the putative role of this gene in the carbohydrate binding processes.
SPRAY-INDUCED GENE SILENCING IDENTIFIES PATHOGEN PROCESSES CONTRIBUTING TO POWDERY MILDEW PROLIFERATION

Spray-induced gene silencing (SIGS) is an emerging tool for crop pest protection. It utilizes exogenously applied double stranded RNA to specifically reduce pest target gene expression using endogenous RNA interference machinery. Powdery mildews, widespread obligate biotrophic fungi infect agricultural crops including wheat, barley, cucurbits, grapevine, and ornamentals such as roses. In this study, SIGS methods were developed and optimized for powdery mildews using the known azole-fungicide target CYP51 and the Golovinomyces orontii-Arabidopsis thaliana pathosystem. Additional screening resulted in the identification of conserved gene targets and processes important to powdery mildew proliferation: apoptosis-antagonizing transcription factor in essential cellular metabolism and stress response; lipase a, lipase 1, and acetyl-CoA oxidase in lipid catabolism; 9-cis-epoxycarotenoid dioxygenase, xanthoxin dehydrogenase, and a putative abscisic acid G-protein coupled receptor predicted to function in manipulation of the plant hormone abscisic acid; and the secreted effector EC2. Powdery mildew is the dominant disease impacting grapes and extensive powdery mildew resistance to applied fungicides has been reported. Therefore, we developed SIGS for the Erysiphe necator-Vitis vinifera system and tested six successful targets identified using the G. orontii-A. thaliana system. For all targets tested, a similar reduction in powdery mildew disease was observed between systems. This indicates screening of broadly conserved targets in the G. orontii-A. thaliana pathosystem identifies targets and processes for the successful control of other powdery mildews. The flexibility, specificity, reduced environmental and health risks, and rapid transition from the bench to the field make SIGS an exciting prospect for commercial powdery mildew control.
The intrinsically disordered protein glue of myelin: Linking AlphaFold2 predictions to experimental data

Numerous human proteins are either partially or fully classified as intrinsically disordered proteins (IDPs). Due to their properties, high-resolution structural information about IDPs is generally lacking. On the other hand, IDPs are known to adopt local ordered structures upon interactions with ligands, which could be e.g. other proteins or lipid membrane surfaces. While recent developments in protein structure prediction have been revolutionary, their impact on IDP research at high resolution remains limited. We took a specific example of two myelin-specific IDPs, the myelin basic protein (MBP) and the cytoplasmic domain of myelin protein zero (P0ct). Both of these IDPs are known to be crucial for normal nervous system development and function, and while they are disordered in solution, upon membrane binding, they partially fold into helices, being embedded into the lipid membrane. We carried out AlphaFold2 predictions of both proteins and analysed the models in light of previously published data related to solution structure and molecular interactions. We observe that the predicted models have helical segments that closely correspond to the characterised membrane-binding sites on both proteins. We furthermore analyse the fits of the models to SAXS data from the same IDPs. Artificial intelligence-based models of IDPs appear to be able to provide detailed information on the ligand-bound state of these proteins, instead of the form dominating free in solution. We further discuss the implications of the predictions for normal mammalian nervous system myelination and their relevance to understanding disease aspects of these IDPs.
Activity-dependent post-translational regulation of palmitoylating and depalmitoylating enzymes in the hippocampus

Activity-induced changes in protein palmitoylation can regulate the plasticity of synaptic connections, critically impacting learning and memory. Palmitoylation is a reversible post-translational modification regulated by both palmitoyl-acyl transferases that mediate palmitoylation and palmitoyl thioesterases that depalmitoylate proteins. However, it is not clear how fluctuations in synaptic activity can mediate the dynamic palmitoylation of neuronal proteins. Using primary hippocampal cultures, we demonstrate that synaptic activity does not impact the transcription of palmitoylating / depalmitoylating enzymes, changes in thioesterase activity, nor post-translational modification of the depalmitoylating enzymes, ABHD17 and APT2. In contrast, synaptic activity does mediate post-translational modification of the palmitoylating enzymes ZDHHC2, ZDHHC5, and ZDHHC9 (but not ZDHHC8) to influence protein-protein interaction, enzyme stability and enzyme function. Post-translational modifications of ZDHHC enzymes were also observed in the hippocampus following fear conditioning. Together, our findings demonstrate that signaling events activated by synaptic activity largely impact activity of the ZDHHC family of palmitoyl-acyl transferases with less influence on the activity of palmitoyl thioesterases.
Body mass change over winter is consistently sex-specific across roe deer populations

In polygynous vertebrates, males must allocate energy to growing the secondary sexual characteristics, such as ornaments or weapons, that they require to attract and defend potential mates, impacting body condition and potentially entailing fitness costs. We investigated sex differences in over winter body mass change across five intensively monitored populations of roe deer with markedly contrasting environmental conditions. At winter onset, males weighed, on average, 8.5% (from 4.5% in the most northerly population to 12.3% in the most southerly one) more than females. However, across all populations, males fared worse over the winter than females, losing more (Sweden) or gaining less (France) mass, so that sexual mass dimorphism was virtually absent prior to the onset of spring. Our findings reveal that the direction of over-winter change in mass of roe deer depends on winter severity, but that males are consistently more sensitive to this environmental constraint than females. As a result of this sex-specific change in body mass, sexual mass dimorphism is lowest at the onset of the territorial season. We suggest that allocation to antler growth and territory establishment drives this pattern, providing a likely explanation to account for the lower rates of male adult survival that are consistently reported in this weakly dimorphic species.
Pbp1 stabilizes and promotes the translation of Puf3-target mRNAs involved in mitochondrial biogenesis

Pbp1 (poly(A)-binding protein - binding protein 1) is a cytoplasmic stress granule marker that is capable of forming condensates that function in the negative regulation of TORC1 signaling under respiratory conditions. How mutations in its mammalian ortholog ataxin-2 are linked to neurodegenerative conditions remains unclear. Here, we show that loss of Pbp1 leads to decreases in amounts of mitochondrial proteins whose encoding mRNAs are targets of Puf3, a member of the PUF (Pumilio and FBF) family of RNA-binding proteins. We found that Pbp1 stabilizes and promotes the translation of Puf3-target mRNAs in respiratory conditions, such as those involved in the assembly of cytochrome c oxidase. We further show that Pbp1 and Puf3 interact through their respective low complexity domains, which is required for Puf3-target mRNA stabilization and translation. Our findings reveal a key role for Pbp1-containing assemblies in enabling the translation of mRNAs critical for mitochondrial biogenesis and respiration. They may further begin to explain prior associations of Pbp1/ataxin-2 with RNA, stress granule biology, mitochondrial function, and neuronal health.
High-resolution imaging of the osteogenic and angiogenic interface at the site of murine cranial bone defect repair via multiphoton microscopy

The spatiotemporal blood vessel formation and specification at the osteogenic and angiogenic interface of cranial bone defect repair were examined utilizing a high-resolution multiphoton-based imaging platform in conjunction with advanced optical techniques that allow interrogation of the oxygen microenvironment and cellular energy metabolism in living animals. Our study demonstrates the dynamic changes of vessel types, i.e. arterial, venous and capillary vessel networks at the superior and dura periosteum of cranial bone defect, suggesting a differential coupling of the vessel type with osteoblast expansion and bone tissue deposition/remodeling during repair. Employing transgenic reporter mouse models that label distinct types of vessels at the site of repair, we further show that oxygen distributions in capillary vessels at the healing site are heterogeneous as well as time and location-dependent. The endothelial cells coupling to osteoblasts prefer glycolysis and are less sensitive to microenvironmental oxygen changes than osteoblasts. In comparison, osteoblasts utilize relatively more OxPhos and potentially consume more oxygen at the site of repair. Taken together, our study highlights the dynamics and functional significance of blood vessel types at the site of defect repair, opening up opportunities for further delineating the oxygen and metabolic microenvironment at the interface of bone tissue regeneration.
A Study of Emotional Intelligence of the Sons of Army and Civil Personnel: A Comparative Study

This study is mainly originated to understand how emotional intelligence is affecting the lives of the children of army and civil personnel. It has been conducted to compare the emotional intelligence scores of army children who are facing different emotional breakdowns and deployments throughout their lives with the children belonging to civil background who deal with totally different situations.The purpose is to define Emotional intelligence in different dimensions in the lives of the children of army and civil personnel. In the present research the main objective is to compare the emotional intelligence scores of the children (Sons) of army and civil personnel. There are three hypothesis formed by the researcher which are tested in this study. This is a descriptive research and researcher used questionnaire as the tool of data collection. The sample of 200 students has been taken which contains 100 male students of secondary level and 100 of senior secondary level by purposive sampling method. The study has been limited to KVS and ARMY schools of Bareilly region only. A tool developed by A.K. Singh and Shruti Narain has been used for this study. The study found that there is no significant difference found in the Emotional intelligence of students (sons) of army and civil personnel.
IS GREED REWARDED? DEVELOPING HEURISTICS FOR GREEDY INVESTORS USING UPPER PARTIAL MOMENTS

Rules of thumb play an important role in making investment decisions. This study gives the rule of a thumb/heuristic known as “Pleonexia rule” based on the trait of greed of an investor. The heuristic in the paper is developed using the Upper partial moment (UPM) ratio, which is based on upside risk only, non-restrictive to normal distribution and risk-taking and risk-neutral investors can be accommodated. Portfolios are formed by using the monthly prices taken from Pakistan Stock Exchange for the period from Dec 1999 to June 2018. Two staged methodology is proposed for the development and empirical testing of the Pleonexia rule. At first stage forecasted the probabilities to know whether it is possible to develop such type of rule or not. At second stage the Pleonexia rule is developed and tested by using the probabilities. The results reveal that on average there are above 90% chances that the investors get minimum returns or gains by meeting the benchmark which is PSX-100 index. Moreover, greed is not rewarded because there is less probability of getting gains higher than the optimal level. These results are better for the developing countries like Pakistan.
PCR4ALL: A Comprehensive Evaluation Benchmark for Pronoun Coreference Resolution in English

Pronoun Coreference Resolution (PCR) is the task of resolving pronominal expressions to all mentions they refer to. The correct resolution of pronouns typically involves the complex inference over both linguistic knowledge and general world knowledge. Recently, with the help of pre-trained language representation models, the community has made significant progress on various PCR tasks. However, as most existing works focus on developing PCR models for specific datasets and measuring the accuracy or F1 alone, it is still unclear whether current PCR systems are reliable in real applications. Motivated by this, we propose PCR4ALL, a new benchmark and a toolbox that evaluates and analyzes the performance of PCR systems from different perspectives (i.e., knowledge source, domain, data size, frequency, relevance, and polarity). Experiments demonstrate notable performance differences when the models are examined from different angles. We hope that PCR4ALL can motivate the community to pay more attention to solving the overall PCR problem and understand the performance comprehensively. All data and codes are available at: https://github.com/HKUST-KnowComp/PCR4ALL.
Numerical Model for Sugarcane Base Cutting Modelo numérico

In the present work, a numerical model is developed for sugarcane base cutting from experimental data obtained in five varieties of cane evaluated in the Physics and Resistance of Materials Laboratories of Ciego de Ávila University. The performance of the BONEM and BUSSOLA base-cutter blade was analyzed in relation to process parameters such as stresses, cutting force and cutting moment. It was shown that BUSSOLA cutter blade had a better performance than BONEM for each of the varieties tested. In the analysis of a model with average magnitudes of the physical-mechanical properties of the stems of the varieties examined, the behavior graphs of the cutting forces over time and the Force - Displacement graphs for both segments were obtained. The main results show that there are no representative differences in relation to the magnitude of the stresses generated in the stems of each of the sugarcane varieties when they are cut with the different cutter blades. In addition, it was shown that the magnitudes of cutting force and cutting moment generated with the use of BONEM cutter-blade are significantly higher than those generated with BUSSOLA cutter-blade.