Miracle-dz/UniFAR-FTUs huggingface dataset:
Machine Learning Models Combined with Virtual Screening and Molecular Docking to Predict Human Topoisomerase I Inhibitors

In this work, random forest (RF), support vector machine, k-nearest neighbor and C4.5 decision tree, were used to establish classification models for predicting whether an unknown molecule is an inhibitor of human topoisomerase I (Top1) protein. All these models have achieved satisfactory results, with total prediction accuracies from 89.70% to 97.12%. Through comparative analysis, it can be found that the RF model has the best forecasting effect. The parameters were further optimized to generate the best-performing RF model. At the same time, features selection was implemented to choose properties most relevant to the inhibition of Top1 from 189 molecular descriptors through a special RF procedure. Subsequently, a ligand-based virtual screening was performed from the Maybridge database by the optimal RF model and 596 hits were picked out. Then, 67 molecules with relative probability scores over 0.7 were selected based on the screening results. Next, the 67 molecules above were docked to Top1 using AutoDock Vina. Finally, six top-ranked molecules with binding energies less than −10.0 kcal/mol were screened out and a common backbone, which is entirely different from that of existing Top1 inhibitors reported in the literature, was found.
Development of Risk-Taking, Perspective-Taking, and Inhibitory Control During Adolescence

ABSTRACT Structural and functional brain development is thought to lead to different developmental progressions of cognitive control, risk/reward processing, and social cognition during adolescence. We compared these abilities in a cross-sectional sample of 90 adolescents aged 12, 15, or 17 years old, using computerized measures of inhibitory control (Go/No-Go task), risk-taking (Balloon Analogue Risk task), and social perspective–taking (Director task). Fifteen-year-olds exhibited better inhibitory control than 12-year-olds, while 17-year-olds exhibited greater perspective-taking than younger adolescents. Risk-taking was greater in older adolescents than 12-year-olds when controlling for inhibitory control. These findings are consistent with earlier findings obtained in separate samples.
Examining Cumulative Inequality in the Association Between Childhood SES and BMI from Midlife to Old Age.

OBJECTIVES Socioeconomic status (SES) is among the strongest determinants of body mass index (BMI), particularly for women. For older populations, selection bias due to attrition is a large barrier to assessing the accumulation of inequality. Under multiple missing data mechanisms, we investigated the extent to which childhood and midlife SES affects BMI from midlife to old age and gender differences in the association. METHODS Data come from a longitudinal national study of 2,345 U.S. adults aged 40-54 at baseline. We used latent growth models to estimate BMI trajectory over a period of 20 years. We examined results under different missing data patterns and applied methods that account for nonrandom-selection bias. RESULTS Compared to individuals who had higher childhood SES, individuals who had lower childhood SES have higher BMI in midlife and experience a faster increase in BMI between midlife and old age. The observed associations remain significant even after controlling for midlife SES. After addressing nonrandom selection, the gap in BMI between high and low childhood SES widens from midlife to old age for women. DISCUSSION The findings provide new evidence of cumulative inequality among older adults, documenting increasing BMI inequality from midlife to old age, particularly for women from low SES families.
Monophyly, Taxon Sampling, and the Nature of Ranks in the Classification of Orb-weaving Spiders (Araneae: Araneoidea).

We address some of the taxonomic and classification changes proposed by Kuntner et al. (in press) in a comparative study on the evolution of sexual size dimorphism in nephiline spiders. Their proposal to re-circumscribe araneids and to rank the subfamily Nephilinae is fundamentally flawed as it renders the family Araneidae paraphyletic. We discuss the importance of monophyly, outgroup selection and taxon sampling, the subjectivity of ranks, and the implications of the age of origin criterion to assign categorical ranks in biological classifications. We explore the outcome of applying the approach of Kuntner et al. (in press) to the classification of spiders with emphasis on the ecribellate orb-weavers (Araneoidea) using a recently published dated phylogeny. We discuss the implications of including the putative sister group of Nephilinae (the sexually dimorphic genus Paraplectanoides) and the putative sister group of Araneidae (the miniature, monomorphic family Theridiosomatidae). We propose continuation of the phylogenetic classification put forth by Dimitrov et al. (2017) and we formally rank Nephilinae and Phonognathinae as subfamilies of Araneidae. Our classification better reflects the understanding of the phylogenetic placement and evolutionary history of nephilines and phonognathines while maintaining the diagnosability of Nephilinae. It also fulfills the fundamental requirement that taxa must be monophyletic, and thus avoids the paraphyly of Araneidae implied by Kuntner et al. (in press).
Core temperature after birth in babies with neonatal encephalopathy in a sub‐Saharan African hospital setting

Therapeutic hypothermia (HT) to 33.0–34.0°C for 72 h provides optimal therapy for infants with neonatal encephalopathy (NE) in high‐resource settings. HT is not universally implemented in low‐ and middle‐income countries as a result of both limited resources and evidence. Facilitated passive cooling, comprising infants being allowed to passively lower their body temperature in the days after birth, is an emerging practice in some West African neonatal units. In this observational study, we demonstrate that infants undergoing facilitated passive cooling in a neonatal unit in Accra, Ghana, achieve temperatures within the HT target range ∼20% of the 72 h. Depth of HT fluctuates and can be excessive, as well as not maintained, especially after 24 h. Sustained and deeper passive cooling was evident for severe NE and for those that died. It is important to prevent excessive cooling, to understand that severe NE babies cool more and to be aware of facilitated passive cooling with respect to the design of clinical trials in low‐ and mid‐resource settings.
Outcome and Prognostic Factors of High-Risk Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

Background Allogeneic transplantation remains one of the best therapies for high-risk acute myeloid leukemia (HR-AML). Material/Methods This study retrospectively analyzed 126 patients with HR-AML after allogeneic hematopoietic stem cell transplantation (allo-HCST). Results The disease-free survival (DFS) rates of 1 year and 3 years were 58.83% (95%CI: 50.75–68.20%) and 53.09% (95%CI: 44.59–63.22%) respectively. The cumulative relapse rates of 1 year and 3 years were 21.1% (95%CI: 14.4–28.8%) and 25.9% (95%CI: 18.1–34.5%) respectively. The cumulative incidences of III to IV acute graft-versus-host disease (aGVHD) for 100 days was 8.70% (95%CI: 4.6–14.5%). The cumulative rate of extensive chronic graft-versus-host disease (cGVHD) for 1-year was 4.1% (95%CI: 1.5–8.7%). The cumulative transplantation related mortality rate of 1 year and 3 years were 20.1% (95%CI: 13.6–27.6%) and 21.0% (95%CI: 14.3–28.6%) respectively. Univariate analysis revealed that lower overall survival was correlated with age, bacterial or fungal infection, disease status at transplantation, III–IV aGVHD, post-transplantation lymphoproliferative disorders (PTLD), white blood cell engraftment, and extramedullary involvement (P<0.05). The results of multivariate analysis were that the aforementioned factors were also related to lower overall survival except for PTLD (P<0.05). The results of univariate and multivariate analysis were that extramedullary involvement, III–IV aGVHD, and status pre-transplantation influenced DFS (P<0.05). The risk factors for relapse were status pre-transplantation and extramedullary involvement by univariate and multivariate analysis (P<0.05). Conclusions HR-AML has inferior prognosis. Our study indicated the necessity of achieving remission status prior to hematopoietic stem cell transplantation, and administration of preventive treatments on high-risk patients after hematopoietic stem cell transplantation. In addition, adequate prevention and treatment of complications are needed.
Survey of image-based representations and compression techniques

We survey the techniques for image-based rendering (IBR) and for compressing image-based representations. Unlike traditional three-dimensional (3-D) computer graphics, in which 3-D geometry of the scene is known, IBR techniques render novel views directly from input images. IBR techniques can be classified into three categories according to how much geometric information is used: rendering without geometry, rendering with implicit geometry (i.e., correspondence), and rendering with explicit geometry (either with approximate or accurate geometry). We discuss the characteristics of these categories and their representative techniques. IBR techniques demonstrate a surprising diverse range in their extent of use of images and geometry in representing 3-D scenes. We explore the issues in trading off the use of images and geometry by revisiting plenoptic-sampling analysis and the notions of view dependency and geometric proxies. Finally, we highlight compression techniques specifically designed for image-based representations. Such compression techniques are important in making IBR techniques practical.
The molecular genetics of nitrate assimilation in fungi and plants.

NITRATE ASSIMILATION IN FUNGI . 116 Structural Genes . 116 The Molybdenum Cofactor 117 Gene Regulation 117 NITRATE ASSIMILATION IN PLANTS . 128 Nitrate Reduction . 128 Nitrite Reduction 133 Nitrate Uptake . 134 Nitrate Assimilatory Genes as Genetic Tools . 136
Combining next‐generation sequencing and progeny testing for rapid identification of induced recessive and dominant mutations in maize M2 individuals

Summary Molecular identification of mutant alleles responsible for certain phenotypic alterations is a central goal of genetic analyses. In this study we describe a rapid procedure suitable for the identification of induced recessive and dominant mutations applied to two Zea mays mutants expressing a dwarf and a pale green phenotype, respectively, which were obtained through pollen ethyl methanesulfonate (EMS) mutagenesis. First, without prior backcrossing, induced mutations (single nucleotide polymorphisms, SNPs) segregating in a (M2) family derived from a heterozygous (M1) parent were identified using whole‐genome shotgun (WGS) sequencing of a small number of (M2) individuals with mutant and wild‐type phenotypes. Second, the state of zygosity of the mutation causing the phenotype was determined for each sequenced individual by phenotypic segregation analysis of the self‐pollinated (M3) offspring. Finally, we filtered for segregating EMS‐induced SNPs whose state of zygosity matched the determined state of zygosity of the mutant locus in each sequenced (M2) individuals. Through this procedure, combining sequencing of individuals and Mendelian inheritance, three and four SNPs in linkage passed our zygosity filter for the homozygous dwarf and heterozygous pale green mutation, respectively. The dwarf mutation was found to be allelic to the an1 locus and caused by an insertion in the largest exon of the AN1 gene. The pale green mutation affected the nuclear W2 gene and was caused by a non‐synonymous amino acid exchange in encoded chloroplast DNA polymerase with a predicted deleterious effect. This coincided with lower cpDNA levels in pale green plants.
Effects of alpha‐cyclodextrin on cholesterol control and Compound K on glycaemic control in people with pre‐diabetes: Protocol for a Phase III randomized controlled trial

The prevalence of pre‐diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre‐diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha‐cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti‐hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12‐month randomized controlled trial to investigate the metabolic effects of these two products in people with pre‐diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow‐up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre‐diabetes to help reduce the risk of progression to type 2 diabetes.
Cyclin-dependent kinase–mediated phosphorylation of the exocyst subunit Exo84 in late G1 phase suppresses exocytic secretion and cell growth in yeast

In eukaryotic cells, the growth rate is strictly regulated for proper progression of the cell cycle. In the budding yeast Saccharomyces cerevisiae, it was previously shown that cell growth dramatically slows down when the cells start budding at the G1/S transition. However, the molecular mechanism for this G1/S-associated growth arrest is unclear. In this study, using exocytic secretion, cyclin-dependent kinase (CDK) assay, immunoprecipitation, and microscopy, we demonstrate that the exocyst subunit Exo84, which is known to be phosphorylated in mitosis, can also be phosphorylated directly by Cdk1 in the late G1 phase. Of note, we found that the Cdk1-mediated Exo84 phosphorylation impairs exocytic secretion in the late G1 phase. Using conditional cdc mutants and phosphodeficient and phosphomimetic exo84 mutants, we further observed that Cdk1-phosphoryated Exo84 inhibits the exocyst complex assembly, exocytic secretion, and cell growth, which may be important for proper execution of the G1/S-phase transition before commitment to a complete cell cycle. Our results suggest that the direct Cdk1-mediated regulation of the exocyst complex critically contributes to the coordination of cell growth and cell cycle progression.
Draft Genome Sequences of Antibiotic-Resistant Escherichia coli Isolates from U.S. Wastewater Treatment Plants

The spread of antibiotic-resistant microorganisms is a major public health concern. Here, we report the draft genome sequences of three Escherichia coli isolates from primary effluent collected from geographically dispersed U.S. ABSTRACT The spread of antibiotic-resistant microorganisms is a major public health concern. Here, we report the draft genome sequences of three Escherichia coli isolates from primary effluent collected from geographically dispersed U.S. wastewater treatment plants (WWTPs). Genomic analysis confirms the presence of genes encoding resistance to a broad spectrum of antibiotics.
Systems Properties of the Haemophilus influenzaeRd Metabolic Genotype*

Haemophilus influenzae Rd was the first free-living organism for which the complete genomic sequence was established. The annotated sequence and known biochemical information was used to define the H. influenzae Rd metabolic genotype. This genotype contains 488 metabolic reactions operating on 343 metabolites. The stoichiometric matrix was used to determine the systems characteristics of the metabolic genotype and to assess the metabolic capabilities of H. influenzae. The need to balance cofactor and biosynthetic precursor production during growth on mixed substrates led to the definition of six different optimal metabolic phenotypes arising from the same metabolic genotype, each with different constraining features. The effects of variations in the metabolic genotype were also studied, and it was shown that theH. influenzae Rd metabolic genotype contains redundant functions under defined conditions. We thus show that the synthesis ofin silico metabolic genotypes from annotated genome sequences is possible and that systems analysis methods are available that can be used to analyze and interpret phenotypic behavior of such genotypes.
Histone deacetylase 4 downregulation elicits post-traumatic psychiatric disorders through impairment of neurogenesis.

An enduring deficit in neurogenesis largely contributes to the development of severe posttraumatic psychiatric disorders such as anxiety, depression, and memory impairment following Traumatic brain injury (TBI); however, the mechanism remains obscure. Here we have shown that an imbalance in the generation of GABAergic and glutamatergic neurons due to aberrant induction of vGlut1 positive glutamatergic cells is responsible for impaired neuronal differentiation in the hippocampus following TBI. To elucidate the molecular mechanism, we found that TBI activates a transcription factor Pax3 by increasing its acetylation status and subsequently induces Ngn2 transcription. This event, in turn, augments the vGlut1 expressing glutamatergic neurons and accumulation of excess glutamate in the hippocampus that can affect neuronal differentiation. The acetylation of Pax3 was increased due to loss of its interaction with a deacetylase HDAC4, which was downregulated after TBI. TBI induced activation of GSK3 was responsible for the degradation of HDAC4. We also showed that overexpression of HDAC4 before TBI reduces Pax3 acetylation by restoring an interaction between HDAC4 and Pax3 in the hippocampus. This event prevents the aberrant induction of vGlut1 positive glutamatergic neurons by decreasing Ngn2 level and subsequently reinforces the balance between GABAergic and glutamatergic neurons following TBI. Furthermore, we found that overexpression of HDAC4 in the hippocampus improves in anxiety and depressive-like behavior and memory functions following TBI.
Proximal Lck Promoter–Driven Cre Function Is Limited in Neonatal and Ineffective in Adult γδ T Cell Development

Key Points pLckCre inefficiently deletes floxed genes in γδ T cells generated in the adult. pLckCre expression mainly effects γδ T cells developing early in ontogeny. Endogenous Lck expression is diminished in developing γδ compared with αβ T cells. Visual Abstract During T cell development, Lck gene expression is temporally controlled by its proximal and distal promoters. The pLckCre transgenic mouse available from The Jackson Laboratory, in which the proximal promoter of Lck drives Cre expression, is a commonly used Cre driver line to recombine genes flanked by loxP sites in T cells. pLckCre drives recombination early in thymocyte development and is frequently used to delete genes in αβ and γδ T cells. We found that pLckCre failed to efficiently delete floxed genes in γδ T cells in contrast to a complete deletion in conventional as well as unconventional αβ T cells. Mechanistically, γδ T cells inefficiently transcribed the endogenous proximal Lck promoter compared with αβ T cells during adult thymic development. A small population of γδ T cells that had activated pLckCre was detected, many of which were located in nonlymphoid organs as well as precommitted IL-17– or IFN-γ–producing γδ T effector cells. In newborn thymi, both pLckCre and endogenous Lck proximal promoter expression were substantially enhanced, giving rise to an elevated fraction of γδ T cells with recombined floxed genes that were increased in unique γδ T subsets, such as the IL-17–producing γδ T cells. Our data point out striking differences in Lck transcription between perinatal and adult γδ T cell development. Taken together, the data presented in this study shed new light on γδ T cell development and stimulate a reanalysis of data generated using the pLckCre transgenic mice.
Evaluation of Two-dimensional Differential Gel Electrophoresis for Proteomic Expression Analysis of a Model Breast Cancer Cell System*

The technique of fluorescent two-dimensional (2D) difference gel electrophoresis for differential protein expression analysis has been evaluated using a model breast cancer cell system of ErbB-2 overexpression. Labeling of paired cell lysate samples with N-hydroxy succinimidyl ester-derivatives of fluorescent Cy3 and Cy5 dyes for separation on the same 2D gel enabled quantitative, sensitive, and reproducible differential expression analysis of the cell lines. SyproRuby staining was shown to be a highly sensitive and 2D difference gel electrophoresis-compatible method for post-electrophoretic visualization of proteins, which could then be picked and identified by matrix-assisted laser-desorption ionization mass spectroscopy. Indeed, from these experiments, we have identified multiple proteins that are likely to be involved in ErbB-2-mediated transformation. A triple dye labeling methodology was used to identify proteins differentially expressed in the cell system over a time course of growth factor stimulation. A Cy2-labeled pool of samples was used as a standard with all Cy3- and Cy5-labeled sample pairs to facilitate cross-gel quantitative analysis. DeCyder (Amersham Biosciences, Inc.) software was used to distinguish clear statistical differences in protein expression over time and between the cell lines.
Throwing Shade at Cyrus: Willingness to Censor Teen Homosexuality in Disney’s Andi Mack

ABSTRACT The inclusion of a gay 13-year-old main character (Cyrus Goodman) on the Disney television series Andi Mack prompted social conservatives to call for the show’s cancellation due to the alleged negative impact that Cyrus would have on the show’s child audience. The present study explored individuals’ support for the censorship of television portrayals of teen homosexuality in a sample of 232 United States residents who viewed clips from the series detailing Cyrus’ storyline. Results found that censorship support was explained by homonegativity, conservative ideology, and authoritarianism, as well as perceptions that such depictions have a negative impact on the self and others. Response surface modeling also found evidence for a severity third-person effect (others more negatively impacted than the self) being related to increased censorship support. Directions for future research on the role of authoritarianism and sexual orientation beliefs in willingness to censor depictions of homosexuality are discussed.