Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Potential Key Genes for Pathogenesis and Prognosis in Prostate Cancer by Integrated Analysis of Gene Expression Profiles and the Cancer Genome Atlas

Background: Prostate cancer (PCa)is a malignancy of the urinary system with a high incidence, which is the second most common male cancer in the world. There are still huge challenges in the treatment of prostate cancer. It is urgent to screen out potential key biomarkers for the pathogenesis and prognosis of PCa. Methods: Multiple gene differential expression profile datasets of PCa tissues and normal prostate tissues were integrated analysis by R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the overlapping Differentially Expressed Genes (DEG) were performed. The STRING online database was used in conjunction with Cytospace software for protein-protein interaction (PPI) network analysis to define hub genes. The relative mRNA expression of hub genes was detected in Gene Expression Profiling Interactive Analysis (GEPIA) database. A prognostic gene signature was identified by Univariate and multivariate Cox regression analysis. Results: Three hundred twelve up-regulated genes and 85 down-regulated genes were identified from three gene expression profiles (GSE69223, GSE3325, GSE55945) and The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset. Seven hub genes (FGF2, FLNA, FLNC, VCL, CAV1, ACTC1, and MYLK) further were detected, which related to the pathogenesis of PCa. Seven prognostic genes (BCO1, BAIAP2L2, C7, AP000844.2, ASB9, MKI67P1, and TMEM272) were screened to construct a prognostic gene signature, which shows good predictive power for survival by the ROC curve analysis. Conclusions: We identified a robust set of new potential key genes in PCa, which would provide reliable biomarkers for early diagnosis and prognosis and would promote molecular targeting therapy for PCa.
Effects of Vessel Activity on the Near-Shore Ecology of Kittlitz's Murrelets (Brachyramphus Brevirostris) in Glacier Bay, Alaska

Abstract Summer breeding populations of Kittlitz's Murrelets (Brachyramphus brevirostris) have declined by 80–90% in southeastern Alaska during the past 25 years. Boating activities overlap considerably in space and time with Kittlitz's Murrelets in Glacier Bay, and disturbance could affect individuals by causing them to fly away from preferred foraging sites, thereby disrupting foraging bouts or resting periods. We observed the effects of vessel activity on Kittlitz's Murrelets at sea for each of three response variables (density, group size, and behaviors) in Glacier Bay. Response variables were characterized at three time-scales of inference: immediate (instantaneous response to vessel passage), short-term (response that persisted 30 min after vessel passage), and daily (response on days with different vessel traffic rates). Group size was not affected by vessel activity. By contrast, near-shore densities were suppressed temporarily by vessel passage but recovered within the day. Density effects did not persist at the daily time-scale and, therefore, did not result in persistent loss of foraging habitat for Kittlitz's Murrelets. Also, behavior was affected at both the immediate and daily time-scales, but not at the short-term time-scale, and may have affected Kittlitz's Murrelets by increasing the amount of time spent flying, which is energetically costly. Vessel passage caused a 30-fold increase in flight behavior (from 0% to 30%). Large and fast-moving vessels caused the greatest disturbance to Kittlitz's Murrelets, which has implications for management of vessel activity.
Role of Low‐Molecular‐Weight Ciliostatic Toxins in Vibriosis of Bivalve Mollusks

Abstract Toxins play a major role in bacillary necrosis of hatchery-reared bivalve larvae. Two principal types of toxin of Vibrio spp. have been identified: A proteinase (molecular weight = 40,000) that degrades connective tissue and at least one ciliostatic toxin (molecular weight = 500–1,000). The ciliostatic toxin is stable at 100°C for 10 min and probably accounts for the cessation of feeding and swimming in the early stages of bacillary necrosis. Ciliostatic toxins were produced by 17 of 20 Vibrio spp. that are pathogenic to fish or that were isolated from diseased mollusks and included Vibrio tubiashii, V. anguillarum, and V. alginolyticus. Of 53 Vibrio and Aeromonas isolates not associated with bivalve infections, only 15 produced a ciliostatic toxin.
Association of water use efficiency and nitrogen use efficiency with photosynthetic characteristics of two wheat cultivars

We examined if higher plant water use efficiency is related to a higher investment of nitrogen in compon- ents of the photosynthetic apparatus and if this is associated with a less efficient use of nitrogen for photosynthesis or for growth. We also assessed the influence of a reduced supply of water and nitrogen on these relationships. For this purpose we used two Triticum aestivum cultivars, differing in whole plant water use efficiency. Differences in leaf water use efficiency (A/E) between cultivars or treatments were associated with differences in Rubisco activity or rate of electron transport and, in general, with differences in plant water use efficiency. They were not invariably related to a low photosynthetic nitrogen use efficiency (PNUE). A high A/E was associated with a low PNUE, e.g. when we compared cultivars at high irradiance. In this case, a high A/E and a high leaf nitrogen concentration were associated with a low stomatal conductance and an equal rate of photosynthesis. A high A/E was not associated with a low PNUE when differences in A/E were mainly caused by higher rates of photosynthesis associated with higher nitrogen concentrations, e.g. when we compared cultivars at low irradiance and high water and nitrogen supply. An increase in the proportion of total leaf nitrogen associated with the photosynthetic apparatus at low soil-nitrogen increased PNUE, without affecting A/E in the opposite way. We conclude that whole plant nitrogen use efficiency was low for the cultivars with a high plant water use efficiency.
Extracellular proteinases from the mycelium of the cultivated mushroom Agaricus bisporus

The edible mushroom, Agaricus bisporus, when cultivated commercially derives its nitrogen from the proteins present in compost, much of which is firmly bound to the lignin-humic complex. The proteinases involved in mobilization of nitrogen were studied in both the filtrates of liquid culture and mushroom compost. Proteinase activities were detected in liquid culture filtrates with a range of substrate specificities. One activity with chymotrypsin-like specificity was found by Western blotting to be the 27 kDa serine proteinase previously purified from senescent sporophores. Serine proteinase activity and level in the filtrates rapidly increased during mycelial growth on liquid medium containing humic fraction (extracted from mushroom compost) as sole nitrogen source. Activity and level remained low in filtrates of cultures grown on glutamate or casein. Non-denaturing gel analysis revealed the serine proteinase to be the most prominent proteolytic activity in compost filtrates. Regulation of the activity in compost was indicated by a doubling during the early stages of sporophore growth.
In silico analysis of SNPs in human phosphofructokinase, Muscle (PFKM) gene: An apparent therapeutic target of aerobic glycolysis and cancer

Phosphofructokinase, muscle (PFKM), a key glycolytic regulatory enzyme is a potential target for cancer therapeutic studies accredited to the employed inefficient phenomenon known as Warburg effect. PFKM is encoded by PFKM gene located at chromosome 12q13.11. Single nucleotide polymorphisms (SNPs) are known to profoundly affect gene expression and protein function. Therefore, the first attempt was made to computationally identify putative functional PFKM variants. These SNPs were further explored to find their probable association with different cancer types. A total of 9694 SNPs were retrieved from dbSNP database. Of which, only 85 validated SNPs with ≥10% minor allele frequency (MAF) were subjected to analysis by softwares including Ensembl Genome browser, FuncPred (SNPinfo), regulomeDB (v 2.0), SIFT and PolyPhen-2. The relative analysis of output obtained classified the selected-SNPs into 11 highly prioritized (HP), 20 moderately prioritized and 54 not/poorly prioritized SNPs. The 11 HP-SNPs were found to have the highest likelihood of being functionally important, evidenced by previous association of rs2269935, rs11168417, rs11609399 and rs2228500 HP-SNPs with cachexia, lung and breast cancer. The study warrants further experiments to confirm the predictive role of prioritized SNPs in cancer etiology and also provides directions to fellow researchers.
Far-red light enhances soluble sugar levels and Botrytis cinerea disease development in tomato leaves in a jasmonate-dependent manner

Plants lacking phytochrome photoreceptors display elevated soluble sugar levels in leaves. Although pathogens principally feed on sugars supplied by the plant, the link between increased plant sugar levels upon phytochrome inactivation and disease development has not been considered. Tomato plants were exposed to control white LED (WL) or a combination of white and far-red LED (WL+FR) light, to inactivate phytochrome signaling and modulate soluble sugar levels. We also experimentally manipulated internal sugar levels by either supplementing glucose or inhibiting photosynthesis in tomato leaflets prior to performing soluble sugar quantifications or bioassays with pathogens. Tomato plants exposed to WL+FR or lacking phytochrome B (phyB1phyB2 double mutants) show enhanced levels of soluble sugars, especially glucose and fructose, in their leaves. The jasmonic acid biosynthesis mutant def1 also has elevated soluble sugar levels, which could be rescued by exogenous methyl-jasmonate application. This indicates an interplay between JA signaling and primary metabolism. The increase in soluble sugar levels in tomato leaves upon phytochrome inactivation is regulated in a JA-dependent manner. Our data stress the importance of primary metabolism in the FR-induced susceptibility in tomato that could contribute to promote plant resistance when grown at high density.
CRISPR Knockdown of Kcnq3 Attenuates the M-current in NPY/AgRP Neurons

Arcuate nucleus Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons drive ingestive behavior in response to the internal and external environment of an organism. NPY/AgRP neurons are adjacent to the median eminence, a circumventricular organ, and circulating metabolic factors and hormones communicate the energy state of the animal via these neurons by altering the excitability of NPY/AgRP neurons, which produces an appropriate change in behavior to maintain homeostasis. One example of this plasticity is seen in the M-current, a subthreshold, non-inactivating K+ current that acts to modulate excitability. Fasting decreases while estradiol increases the M-current through regulation of subunit mRNA expression of Kcnq 2, 3, & 5. KCNQ2/3 heteromers are thought to mediate the majority of the M-current. Here we used a recently developed single adeno-associated viral (AAV) vector containing a recombinase-dependent Staphylococcus aureus Cas9 (SaCas9) and a single guide RNA against Kcnq3 to selectively delete Kcnq3 in NPY/AgRP neurons to produce a loss of function in the M-current. We found that this virus was effective at knocking down Kcnq3 but not Kcnq2 expression. With the reduced KCNQ3 channel expression NPY/AgRP neurons were more depolarized, exhibited a higher input resistance, and the rheobase current needed to induce firing was significantly reduced, indicative of increased excitability. Although the resulting decrease in the M-current did not overtly alter ingestive behavior, it did significantly reduce the locomotor activity as measured in open field testing. Therefore, the SaCas9-sgKcnq3 is efficient to knock down Kcnq3 expression thereby reducing the M-current and increasing the excitability of NPY/AgRP neurons.
Acid- and Enzyme-Mediated Solubilization of Cell-Wall β-1.3,β-1.4-d-Glucan in Maize Coleoptiles : Implications for Auxin-Mediated Growth

The release of soluble carbohydrates from isolated cell wall of maize (Zea mays L.) was investigated in the range of pH 1 to 8.5. The pH profile demonstrated two peaks, a broad peak at pH 6 due to enzymatic breakdown of β-glucan to monosaccharides (wall autolysis) and a sharp peak at pH 2.5 due to acid-mediated, nonenzymatic liberation of macromolecular β-glucan from the wall. The pH dependence of acid-induced growth and cell-wall extensibility of coleoptile segments closely agrees with the pH dependence of acid-mediated β-glucan solubilization in the isolated wall. However, there is no evidence that enzymatic or nonenzymatic β-glucan solubilization is involved in the mechanism of auxin-mediated growth.
Seasonal and Spatial Occurrence of Aphid Natural Enemies in Organic Brassica Fields: Diversity, Phenology, and Reproduction

A pest monitoring dataset collected for organic Brassica fields in south coastal British Columbia, Canada, was examined to test three possible scenarios explaining poor aphid control by natural enemy insects: the lack of diversity within the enemy guild, slow colonization of fields by enemies, and poor natural enemy reproduction. Both parasitoids and predators were detected, but the predator guild was composed primarily of syrphid larvae and very few coccinellids. We detected a lag in the colonization of fields by enemies: aphids were detected in >20% of samples, but enemies in <5% within 3 weeks of transplanting. Within the first week of transplanting, aphids exceeded the spray action threshold of 10% colonized plants. Although we predicted that Brassica plants located next to field margins would have more parasitism and syrphid oviposition, because of their proximity to floral resources (pollen and nectar) in weeds and shrubs of field margins, the levels of parasitism were equal in both interior and edge plants, and the highest levels of syrphid oviposition activity were observed in plants within fields. These findings suggest that solutions for enhancing biological control of aphids in organic Brassica fields should focus on earlier establishment of enemies within fields, and that aphid control could be enhanced by increasing the diversity of the predator guild, focusing especially on highly mobile predators that are aphidophagous as adults. One possible strategy would be to introduce ladybird beetles on host plants to fields prior to transplanting the crop.
mbkmeans: Fast clustering for single cell data using mini-batch k-means

Single-cell RNA-Sequencing (scRNA-seq) is the most widely used high-throughput technology to measure genome-wide gene expression at the single-cell level. One of the most common analyses of scRNA-seq data detects distinct subpopulations of cells through the use of unsupervised clustering algorithms. However, recent advances in scRNA-seq technologies result in current datasets ranging from thousands to millions of cells. Popular clustering algorithms, such as k-means, typically require the data to be loaded entirely into memory and therefore can be slow or impossible to run with large datasets. To address this problem, we developed the mbkmeans R/Bioconductor package, an open-source implementation of the mini-batch k-means algorithm. Our package allows for on-disk data representations, such as the common HDF5 file format widely used for single-cell data, that do not require all the data to be loaded into memory at one time. We demonstrate the performance of the mbkmeans package using large datasets, including one with 1.3 million cells. We also highlight and compare the computing performance of mbkmeans against the standard implementation of k - means. Our software package is available in Bioconductor at https://bioconductor.org/packages/mbkmeans.
Universal Nature of Drug Treatment Responses in Drug-Tissue-Wide Model-Animal Experiments Using Tensor Decomposition-Based Unsupervised Feature Extraction

Gene expression profiles of tissues treated with drugs have recently been used to infer clinical outcomes. Although this method is often successful from the application point of view, gene expression altered by drugs is rarely analyzed in detail, because of the extremely large number of genes involved. Here, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to the gene expression profiles of 24 mouse tissues treated with 15 drugs. TD-based unsupervised FE enabled identification of the common effects of 15 drugs including an interesting universal feature: these drugs affect genes in a gene-group-wide manner and were dependent on three tissue types (neuronal, muscular, and gastroenterological). For each tissue group, TD-based unsupervised FE enabled identification of a few tens to a few hundreds of genes affected by the drug treatment. These genes are distinctly expressed between drug treatments and controls as well as between tissues in individual tissue groups and other tissues. We also validated the assignment of genes to individual tissue groups using multiple enrichment analyses. We conclude that TD-based unsupervised FE is a promising method for integrated analysis of gene expression profiles from multiple tissues treated with multiple drugs in a completely unsupervised manner.
Further Observations on Nonsymbiotic Germination of Orchid Seeds

In an earlier paper (5) on the nonsymbiotic germination of orchid seeds, a method was described for germinating seeds under pure culture conditions, and the successful germination of orchid seeds by the use of certain sugars was noted. The practical value of this method was indicated, and certain aspects of the problem respecting the relation of the fungus to germination were considered. It was suggested that germination is dependent upon a supply of organic substances. If the germinating orchid seed is dependent on an available supply of organic matter, then the method should be applicable to seeds of orchids other than those used in the previous experiments. The seeds successfully germinated by the use of sugar were those of Cattleya, Laelia, and Epidendron. No other seeds were available at that time. RAMSBOTTOM (7), reviewing this work of the writer, states that while the method may be useful in the germination of Cattleya and related forms, it will not prove successful for the seeds of Odontoglossum and related genera. He states, furthermore, that there is not much difficulty in germinating seeds of Cattleya, but the fact remains that under pure culture conditions Cattleya has not been germinated as yet in the absence of organic matter. Seeds of Cattleya and probably seeds of most orchids are unusual in that germination does not occur except when an outside source of carbon is available. In order to discover whether the method is applicable to other seeds, experiments were made with seeds of various genera, and that germination is possible is shown in the experiments here described. Certain other aspects of the problem are also considered. The methods used were essentially those previously described (5). Solution B or Pfeffer's solution was used throughout, although
Scorepochs: A Computer-Aided Scoring Tool for Resting-State M/EEG Epochs

M/EEG resting-state analysis often requires the definition of the epoch length and the criteria to select which epochs to include in the subsequent steps. However, the effects of epoch selection remain scarcely investigated and the procedure used to (visually) inspect, label, and remove bad epochs is often not documented, thus hindering the reproducibility of the reported results. In this study, we present Scorepochs, a simple and freely available tool for the automatic scoring of resting-state M/EEG epochs that aims to provide an objective method to aid M/EEG experts during epoch selection procedure. We tested our approach on a freely available EEG dataset containing recordings from 109 subjects using the BCI2000 64-channel system.
Essential amnion signals for primate primitive streak formation resolved by scRNA map

The signaling network governing the formation of the primitive streak is well understood in mice, but largely unexplored in primates. Advances in single-cell technology and in vitro embryo culture have enabled to characterize the major cell populations involved. However, a detailed map of this process and insights into its regulatory networks are lacking. Herein, we generated a serial single cell atlas of over 30,000 cells spanning peri-implantation to early primitive streak stages in non-human primates (NHP) describing the emergence of the primitive streak, extraembryonic mesenchyme and amnion. We discovered that ISL1, a gene with a well-established role in cardiogenesis, controls a gene regulatory network in primate amniotic cells. Strikingly, CRISPR/Cas9-targeting of ISL1 resulted in NHP embryos failing to form primitive streak. BMP4 was identified as a key signaling pathway in this process. This was confirmed in human embryonic stem cell lines, suggesting a conserved function in humans. Notably, no viable ISL1 hypomorphic NHP mutant embryos could be recovered after embryo transfer confirming the essential requirement of ISL1. This highlights the importance of the amnion as a signaling center during primate embryogenesis and demonstrates the potential of in vitro primate model systems to investigate the genetics of early human development.
Real-space quantum-based refinement for cryo-EM: Q|R#3

Electron cryo-microscopy (cryo-EM) is fast becoming a major competitor to X-ray crystallography especially for large structures that are difficult or impossible to crystallize. While recent spectacular technology improvements are leading to significantly higher resolution of three-dimensional reconstructions, the average quality of cryo-EM maps is still on the low-resolution end of the range compared to crystallography. A long-standing challenge for atomic model refinement has been the production of stereochemically meaningful models for this resolution regime. Here we demonstrate how including accurate model geometry restraints derived from ab initio quantum-chemical calculations (HF-D3/6-31G) can improve the refinements of an example structure (chain A of 3j63). The robustness of the procedure is tested for additional structures with up to 7k atoms (3a5x, and chain C of 5fn5) by means of the less expensive semi-empirical (GFN1-xTB) model. Necessary algorithms enabling real-space quantum refinement are implemented in the latest version of qr.refine and are described herein. Synopsis The implementation of quantum-based real-space refinement in qr.refine is described.