Miracle-dz/UniFAR-FTUs huggingface dataset:
Quasi-essentiality of RNase Y in Bacillus subtilis is caused by its critical role in the control of mRNA homeostasis

RNA turnover is essential in all domains of life. The endonuclease RNase Y (rny) is one of the key components involved in RNA metabolism of the model organism Bacillus subtilis. Essentiality of RNase Y has been a matter of discussion, since deletion of the rny gene is possible, but leads to severe phenotypic effects. In this work, we demonstrate that the rny mutant strain rapidly evolves suppressor mutations to at least partially alleviate these defects. All suppressor mutants had acquired a duplication of an about 60 kb long genomic region encompassing genes for all three core subunits of the RNA polymerase – α, β, β′. When the duplication of the RNA polymerase genes was prevented by relocation of the rpoA gene in the B. subtilis genome, all suppressor mutants carried distinct single point mutations in evolutionary conserved regions of genes coding either for the β or β’ subunits of the RNA polymerase that were not tolerated by wild type bacteria. In vitro transcription assays with the mutated polymerase variants showed massive decreases in transcription efficiency. Altogether, our results suggest a tight cooperation between RNase Y and the RNA polymerase to establish an optimal RNA homeostasis in B. subtilis cells.
The role of intolerance of uncertainty in the acquisition and extinction of reward

Individuals, who score high in self-reported intolerance of uncertainty (IU), tend to find uncertainty anxiety-provoking. IU has been reliably associated with disrupted threat extinction. However, it remains unclear whether IU would be related to disrupted extinction to other arousing stimuli that are not threatening (i.e., rewarding). We addressed this question by conducting a reward associative learning task with acquisition and extinction training phases (n = 58). Throughout the associative learning task, we recorded valence ratings (i.e. liking), skin conductance response (SCR) (i.e. sweating), and corrugator supercilii activity (i.e. brow muscle indicative or negative and positive affect) to learned reward and neutral cues. During acquisition training with partial reward reinforcement, higher IU was associated with greater corrugator supercilii activity to neutral compared to reward cues. IU was not related to valence ratings or SCR’s during the acquisition or extinction training phases. These preliminary results suggest that IU-related deficits during extinction may be limited to situations with threat. The findings further our conceptual understanding of IU’s role in the associative learning and extinction of reward, and in relation to the processing of threat and reward more generally.
Alk1 mutant endothelial cells undergo clonal expansion in mouse brain arteriovenous malformations

Rationale Mutation in human arteriovenous malformation (AVM) causative genes in a fraction of endothelial cells (ECs) causes AVMs in mice. It is unclear how a small number of mutant ECs can lead to AVM formation. Objective To understand how a fraction of mutant ECs causes AVM, we tested the following hypotheses: (1) activin receptor-like kinase 1 (Alk1 or Acvlr1) mutant brain ECs undergo clonal expansion upon angiogenic stimulation, (2) Alk1 mutant ECs display growth advantage, (3) the burden of Alk1 mutant ECs correlates with AVM severity, and (4) Alk1 mutant bone marrow (BM) derived ECs alone is sufficient to cause AVM. Methods and Results We used PdgfbiCreER;Alk1f/f;confetti+/− mice which express an EC-specific tamoxifen (TM)-inducible Cre recombinase, a Cre-regulated confetti transgene, and Alk1 floxed alleles. Brain AVMs were induced by direct brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) followed with intra-peritoneal injection of TM two weeks later. Color-predominance of confetti reporter in AVMs compared to control brain ECs suggested that clonal expansion was associated with AVM development. We treated PdgfbiCreER;Alk1f/f with different doses of TM to create a mosaic of wild-type (WT) and mutant ECs and found that equal numbers of Alk1+ and Alk1− ECs were proliferating. Increase of TM dose increased the number of Alk1− ECs, the abnormal vessels in brain AVMs, the number of arteriovenous shunts in the intestines, and mouse mortality. To test if mutation of Alk1 in BM-derived ECs can cause brain AVM, we transplanted WT mice with BM of PdgfbiCreER;Alk1f/f mice. After AAV-VEGF and TM treatment, these mice developed AVMs in their brains and arteriovenous shunts in their intestines. Conclusion Clonal expansion of Alk1 mutant ECs could partly explain why a fraction of mutant ECs causes AVM. Mutation of AVM causal genes in BM-derived ECs is sufficient to cause AVM formation.
Current and Projected Distributions of Aedes aegypti and Ae. albopictus in Canada and the U.S.

Background: Aedes aegypti and Ae. albopictus are mosquito vectors of more than 22 arboviruses that infect humans. Objectives: Our objective was to develop regional ecological niche models for Ae. aegypti and Ae. albopictus in the conterminous United States and Canada with current observed and simulated climate and land-use data using boosted regression trees (BRTs). Methods: We used BRTs to assess climatic suitability for Ae. albopictus and Ae. aegypti mosquitoes in Canada and the United States under current and future projected climates. Results: Models for both species were mostly influenced by minimum daily temperature and demonstrated high accuracy for predicting their geographic ranges under the current climate. The northward range expansion of suitable niches for both species was projected under future climate models. Much of the United States and parts of southern Canada are projected to be suitable for both species by 2100, with Ae. albopictus projected to expand its range north earlier this century and further north than Ae. aegypti. Discussion: Our projections suggest that the suitable ecological niche for Aedes will expand with climate change in Canada and the United States, thus increasing the risk of Aedes-transmitted arboviruses. Increased surveillance for these vectors and the pathogens they carry would be prudent. https://doi.org/10.1289/EHP5899
FINE STRUCTURE OF THE OVIDUCT OF THE LAYING HEN

24 hours, the substance for the coverings of the egg. The material was obtained from eight laying birds, one with no egg in the oviduct ; four with an egg in the magnum ; one with an egg in the isthmus ; and two with an egg in the shell gland. The hens were perfused with I p. 100 Gluteraldehyde before obtaining samples of the mucous membrane from the different regions of the duct for preparation. The pattern of folds of the mucous membrane varies throughout the duct. The innermost epithelial lining has two cell types, ― ciliated and glandular, with a cha-
Influence of sward defoliation and soil disturbance on seedling emergence and survival in the Southern Tall Grassveld

Development of vegetation from seed requires a seed bank, germination, emergence and subsequent seedling survival. Reports on the influence of a number of practicably feasible treatments to the vegetation and soil on emergence and survival of grass seedlings in the Southern Tall Grassveld of Natal. Illustrates with graphs and tables. Keywords: defoliation; disturbance; emergence; fire; grassveld; seedling survival; soil; South Africa; Southern Tall Grassveld; survivorship; sward defoliation; tillage; University of Natal Research Farm African Journal of Range & Forage Science , Vol. 13, Iss 3
Serological Biomarkers for Early Detection of Hepatocellular Carcinoma: A Focus on Autoantibodies against Tumor-Associated Antigens Encoded by Cancer Driver Genes

Substantial evidence manifests the occurrence of autoantibodies to tumor-associated antigens (TAAs) in the early stage of hepatocellular carcinoma (HCC), and previous studies have mainly focused on known TAAs. In the present study, protein microarrays based on cancer driver genes were customized to screen TAAs. Subsequently, autoantibodies against selected TAAs in sera were tested by enzyme-linked immunosorbent assays (ELISA) in 1175 subjects of three independent datasets (verification dataset, training dataset, and validation dataset). The verification dataset was used to verify the results from the microarrays. A logistic regression model was constructed within the training dataset; seven TAAs were included in the model and yielded an area under the receiver operating characteristic curve (AUC) of 0.831. The validation dataset further evaluated the model, exhibiting an AUC of 0.789. Remarkably, as the aggravation of HCC increased, the prediction probability (PP) of the model tended to decrease, the trend of which was contrary to alpha-fetoprotein (AFP). For AFP-negative HCC patients, the positive rate of this model reached 67.3% in the training dataset and 50.9% in the validation dataset. Screening TAAs with protein microarrays based on cancer driver genes is the latest, fast, and effective method for finding indicators of HCC. The identified anti-TAA autoantibodies can be potential biomarkers in the early detection of HCC.
FETAL ANDROGEN EXPOSURE INHIBITS FETAL RAT LUNG FIBROBLAST LIPID UPTAKE AND RELEASE

Fetal lung fibroblasts provide lipid substrate for type II cell surfactant phospholipid synthesis. This process is developmental and glucocorticoid dependent. Previous studies in our laboratory demonstrating sex differences in several aspects of lung maturation suggest that these differences may be due to effects of fetal androgens. Based on these studies, we hypothesized that fetal lung fibroblast triglyceride metabolism is determined by opposing effects of fetal androgens and glucocorticoids. To model the effects of androgens on fetal lung fibroblast triglyceride metabolism, pregnant rats were treated with dihydrotestosterone (DHT) 1 mg/kg/day from the days 15 to 20 of gestation, and changes in triglyceride content of freshly isolated fetal rat lung fibroblasts (FRLF) and rates of uptake and prostaglandin E2(PGE2)-mediated release by cultured FRLFin response to glucocorticoids in the presence or absence of DHT in vitro were measured. During lung development, the triglyceride content and rate of uptake of female-derived FRLF increased 3.5- and 4.8-fold, respectively, between days 18 and 20 of gestation. From days 19 to 22, male FRLF trigyclyceride content and rate of uptake were lower than the content and uptake by female FRLF. Maternal DHT treatment inhibited the normal developmental increase in fibroblast triglyceride content and rate of uptake between days 19 and 22 by both male and female FRLF. In the absence of maternal DHT, in vitro dexamethasone stimulated triglyceride uptake 3-fold by day 21 in FRLF. This effect was blocked by maternal pretreatment with DHT. Maternal DHT exposure prevented stimulation of triglyceride release by PGE2. Although in vitro dexamethasone stimulated triglyceride release by maternal DHT-exposed fibroblasts, it did not enhance the response to PGE2. These data suggest that in utero exposure to androgens (1) delay the developmental increase in triglyceride content and (2) oppose the effects of glucocorticoid on cultured FRLF triglyceride uptake and PGE2-mediated release.
A singleton NLR of recent origin causes hybrid necrosis in Arabidopsis thaliana

Hybrid necrosis in plants arises from conflict between divergent alleles of immunity genes contributed by different parents, resulting in autoimmunity. We investigate a severe hybrid necrosis case in Arabidopsis thaliana, where the hybrid does not develop past the cotyledon stage and dies three weeks after sowing. Massive transcriptional changes take place in the hybrid, including the upregulation of most NLR disease resistance genes. This is due to an incompatible interaction between the singleton TIR-NLR gene DANGEROUS MIX 10 (DM10), which was recently relocated from a larger NLR cluster, and an unlinked locus, DANGEROUS MIX 11 (DM11). There are multiple DM10 allelic variants in the global A. thaliana population, several of which have premature stop codons. One of these, which has a truncated LRR domain, corresponds to the DM10 risk allele. The DM10 locus and the adjacent genomic region in the risk allele carriers are highly differentiated from those in the non-risk carriers in the global A. thaliana population, suggesting that this allele became geographically widespread only relatively recently. The DM11 risk allele is much rarer and found only in two accessions from southwestern Spain – a region from which the DM10 risk haplotype is absent – indicating that the ranges of DM10 and DM11 risk alleles may be non-overlapping.
Enumeration of microorganisms from deep-sea hydrothermal chimney samples

Enumerating microorganisms from particle-laden environmental samples can often prove difficult. Procedures involving the separation of the cells from the particles are required, as well as an evaluation of the extraction efficiency. Here we present for the first time a method enabling direct counts to be performed on environmental samples of deep-sea hydrothermal vent sulfide chimney samples. This method involves a separation of cells from the metallic sulfide particles by detergent and ultrasound treatments, followed by an estimation of the extraction efficiency by the Leslie regression method. Successful counts were obtained from the outer portions of two active chimneys from the Mid-Atlantic Ridge, and from the East Pacific Rise. The outer crust of these chimneys contained up to ca. 1010 cells g−1 of chimney (dry weight).
Within tree distribution of a gall-inducing Eurytoma (Hymenoptera, Eurytomidae) on Caryocar brasiliense (Caryocaraceae)

For the first time, we identified the insect herbivore that induces one of the most conspicuous galls on the leaves of Caryocar brasiliense Camb. (Caryocaraceae), a widespread, typical cerrado woody plant of large economic importance. The gall inducing organism is a new and undescribed species of Eurytoma sp. (Hymenoptera, Eurytomidae). Furthermore, we recorded its spatial distribution within C. brasiliense trees. More Eurytoma galls were found on the eastern tree slope, followed the southern and northern slopes. More galls were found in the interior of the tree crown, i.e., on the proximal portion of the stems compared to the terminal portion. At the leaf level, more galls were found on the median region compared to the distal or proximal, perhaps due to the lower trichome density found in there. Leaf colonization by Eurytoma sp. may initiate at the leaf margin but after colonization reaches 50% the central portion starts to be colonized.
Spontaneous variability in gamma dynamics described by a linear harmonic oscillator driven by noise

Circuits of excitatory and inhibitory neurons can generate rhythmic activity in the gamma frequency-range (30-80Hz). Individual gamma-cycles show spontaneous variability in amplitude and duration. The mechanisms underlying this variability are not fully understood. We recorded local-field-potentials (LFPs) and spikes from awake macaque V1, and developed a noise-robust method to detect gamma-cycle amplitudes and durations. Amplitudes and durations showed a weak but positive correlation. This correlation, and the joint amplitude-duration distribution, is well reproduced by a dampened harmonic oscillator driven by stochastic noise. We show that this model accurately fits LFP power spectra and is equivalent to a linear PING (Pyramidal Interneuron Network Gamma) circuit. The model recapitulates two additional features of V1 gamma: (1) Amplitude-duration correlations decrease with oscillation strength; (2) Amplitudes and durations exhibit strong and weak autocorrelations, respectively, depending on oscillation strength. Finally, longer gamma-cycles are associated with stronger spike-synchrony, but lower spike-rates in both (putative) excitatory and inhibitory neurons. In sum, V1 gamma-dynamics are well described by the simplest possible model of gamma: A linear harmonic oscillator driven by noise.
In silico molecular target prediction unveils mebendazole as a potent MAPK14 inhibitor

The concept of polypharmacology involves the interaction of drug molecules with multiple molecular targets. It provides a unique opportunity for the repurposing of already-approved drugs to target key factors involved in human diseases. Herein, we used an in silico target prediction algorithm to investigate the mechanism of action of mebendazole, an anti-helminthic drug, currently repurposed in the treatment of brain tumors. First, we confirmed that mebendazole decreased the viability of glioblastoma cells in vitro. Our in silico approach unveiled 21 putative molecular targets for mebendazole, including 12 proteins significantly up-regulated at the gene level in glioblastoma as compared to normal brain tissue. Validation experiments were performed on three major kinases involved in cancer biology: ABL1, MAPK1/ERK2 and MAPK14/p38α. Mebendazole could inhibit the activity of these kinases in vitro in a dose-dependent manner, with a high potency against MAPK14. Its direct binding to MAPK14 was further validated in vitro and inhibition of MAPK14 kinase activity was confirmed in live glioblastoma cells. Consistent with biophysical data, molecular modeling suggested that mebendazole was able to bind to the catalytic site of MAPK14. Finally, gene silencing demonstrated that MAPK14 is involved in glioblastoma tumor spheroid growth and response to mebendazole treatment. This study thus highlighted the role of MAPK14 in the anticancer mechanism of action of mebendazole and provides further rationale for the pharmacological targeting of MAPK14 in brain tumors. It also opens new avenues for the development of novel MAPK14/p38α inhibitors to treat human diseases. Significance Statement This study provides a framework to investigate drug polypharmacology by rapidly identifying novel molecular targets of already-approved drugs. It unveils a new mechanism involved in the anticancer activity of anti-helminthic drug, mebendazole, which is currently being repurposed for the treatment of brain tumors. By helping to decipher the mechanism(s) of action of repurposed drugs in their new indications, this approach could contribute to the development of safer and more effective therapeutic strategies in oncology and beyond.
RdRp mutations are associated with SARS-CoV-2 genome evolution

COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.
Dual-Purpose Inoculants and Their Effects on Corn Silage

This study was conducted to screen dual-purpose lactic acid bacteria (LAB) from uncontrolled farm-scale silage, and then we confirmed their effects on corn silage. The LAB were isolated from eight farm-scale corn silages, and then we screened the antifungal activity against Fusarium graminearum and the carboxylesterase activity using spectrophotometer with p-nitrophenyl octanoate as substrate and McIlvane solution as buffer. From a total of 25 isolates, 5M2 and 6M1 isolates were selected as silage inoculants because presented both activities of antifungal and carboxylesterase. According 16S rRNA gene sequencing method, 5M2 isolate had 100.0% similarity with Lactobacillus brevis, and 6M1 isolate had 99.7% similarity with L. buchneri. Corn forage was ensiled in bale silo (500 kg) for 72 d without inoculant (CON) or with mixture of selected isolates at 1:1 ratio (INO). The INO silage had higher nutrient digestibility in the rumen than CON silage. Acetate was higher and yeasts were lower in INO silage than in CON silage on the day of silo opening. In all days of aerobic exposure, yeasts were lower in INO silage than CON silage. The present study concluded that Lactobacillus brevis 5M2 and L. buchneri 6M1 confirmed antifungal and carboxylesterase activities on farm-scale corn silage.
Effects of age on pre-stimulus neural activity predictive of successful memory encoding: an fMRI study

Pre-stimulus subsequent memory effects (SMEs) – differences in neural activity preceding the onset of study items that are predictive of later memory performance – have consistently been reported in young adults. The present fMRI experiment investigated potential age-related differences in pre-stimulus SMEs. During study, healthy young and older participants made one of two semantic judgments on images, with the judgment signaled by a preceding cue. In the test phase, participants first made an item recognition judgment and, for each item judged old, a source memory judgment. Age-invariant pre-stimulus SMEs were observed in left dorsomedial prefrontal cortex, left hippocampus, and right subgenual cortex. In each case, the effects reflected lower BOLD signal for later recognized items, regardless of source accuracy, than unrecognized items. A similar age-invariant pattern was observed in left orbitofrontal cortex, but the effect in this region was specific to items attracting a correct source response compared to unrecognized items. In contrast, the left angular gyrus and fusiform cortex demonstrated negative pre-stimulus SMEs that were exclusive to young participants. The findings indicate that age differences in pre-stimulus SMEs are regionally specific and suggest that pre-stimulus SMEs reflect multiple cognitive processes, only some of which are vulnerable to advancing age.
Diet, fecundity and egg size in some polyphagous predatory carabid beetles

Egg size was measured at different rates of egg laying in three polyphagous carabid species, known to be useful predators of cereal aphids; the small Bembidion lampros Herbst and the medium‐sized Pterostichus cupreus L. and P. melanarius Illiger. Variations in fecundity, as well as the ability of the medium‐sized species to also build up fat reserves, were obtained when beetles were subjected to different dietary regimes consisting of aphids, or foods with a lower or higher protein content. Egg size was found to be dependent on the rate of egg laying within a species. A diet of cereal aphids appeared to be adequate for egg production in these polyphagous carabids, but female P. cupreus were unable to build up fat reserves when they ingested aphids contaminated with the aphicide pirimicarb. Beetles were able to devote resources to more and larger eggs (B. lampros), or to larger eggs and/or fat reserves (P. melanarius/P. cupreus) when given access to a carbohydrate‐rich food with low protein content. The highest rate of egg laying was obtained when female P. cupreus and P. melanarius were given a more varied diet at frequent intervals; including regular shifts between unsprayed aphids, carbohydrate‐rich food and protein‐rich maggots. Within the varied diet treatment a negative relationship was obtained between egg size and egg number among similar‐sized individuals of P. cupreus and P. melanarius; females producing the largest number also laid the smallest eggs. Egg size affected larval survival, since first instars hatching from large eggs were found to survive longer than those hatching from small eggs. The influence of differences in food intake on reproduction, maintenance metabolism, and survival of field‐inhabiting carabids is discussed.