Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental Stroke Induces Chronic Gut Dysbiosis and Neuroinflammation in Male Mice

Recent literature implicates gut epithelia mucosa and intestinal microbiota as important players in post-stroke morbidity and mortality. As most studies have focused on the acute effects of stroke on gut dysbiosis, our study objective was to measure chronic, longitudinal changes in the gut microbiota and intestinal pathology following ischemic stroke. We hypothesized that mice with experimental ischemic stroke would exhibit chronic gut dysbiosis and intestinal pathology up to 36 days post-stroke compared to sham controls. Male C57BL/6J mice were subjected to 60 minutes of transient middle cerebral artery occlusion (tMCAO) or sham surgery. To determine the long-term effects of tMCAO on gut dysbiosis, fecal boli were collected pre- and post-tMCAO on days 0, 3, 14, and 28. Bioinformatics analysis demonstrate significant differences in abundance among Firmicutes and Bacteroidetes taxa at the phylum, family, and species levels in tMCAO compared to sham mice that persisted up to one month post-stroke. The most persistent changes in post-stroke microbial abundance were a decrease in bacteria family S24-7 and significant increases in Ruminococcaceae. Overall, these changes resulted in a persistently increased Firmicutes:Bacteroidetes ratio in stroke animals. Intestinal histopathology showed evidence of chronic intestinal inflammation that included marked increases in immune cell infiltration with mild-moderate epithelial hyperplasia and villous blunting. Increased astrocyte and microglial activity were also detected one-month post-stroke. These results demonstrate that acute, post-stroke disruption of the gut-brain-microbiota axis progresses to chronic gut dysbiosis, intestinal inflammation, and chronic neuroinflammation. Clinical Perspectives The microbiota-gut-brain axis, recently implicated in several neurological disorders, remains largely unexplored at chronic time points post-tMCAO. Our results demonstrate chronic gut dysbiosis, prolonged behavioral deficits, and persistent cerebral and intestinal inflammation post-tMCAO in male C57BL/6J mice. These results suggest that manipulation of microbiota may help reduce poor outcomes after stroke and lead to improved post-stroke functional recovery.
Role of combined cell membrane and wall mechanical properties regulated by polarity signals in cell budding

Budding yeast, Saccharomyces cerevisiae, serves as a prime biological model to study mechanisms underlying asymmetric growth. Previous studies have shown that prior to bud emergence, polarization of a conserved small GTPase Cdc42 must be established on the cell membrane of a budding yeast. Additionally, such polarization contributes to the delivery of cell wall remodeling enzymes and hydrolase from cytosol through the membrane, to change the mechanical properties of the cell wall. This leads to the hypothesis that Cdc42 and its associated proteins at least indirectly regulate cell surface mechanical properties. However, how the surface mechanical properties in the emerging bud are changed and whether such change is important are not well understood. To test several hypothesised mechanisms, a novel three-dimensional coarse-grained particle-based model has been developed which describes inhomogeneous mechanical properties of the cell surface. Model simulations predict alternation of the levels of stretching and bending stiffness of the cell surface in the bud region by the polarized Cdc42 signals is essential for initiating bud formation. Model simulations also suggest that bud shape depends strongly on the distribution of the polarized signaling molecules while the neck width of the emerging bud is strongly impacted by the mechanical properties of the chitin and septin rings. Moreover, the temporal change of the bud mechanical properties is shown to affect the symmetry of the bud shape. The 3D model of asymmetric cell growth can also be used for studying viral budding and other vegetative reproduction processes performed via budding, as well as detailed studies of cell growth.
Prediction and characterization of transcription factors involved in drought stress response

Transcription factors (TFs) play a central role in regulating molecular level responses of plants to external stresses such as water limiting conditions, but identification of such TFs in the genome remains a challenge. Here, we describe a network-based supervised machine learning framework that accurately predicts and ranks all TFs in the genome according to their potential association with drought tolerance. We show that top ranked regulators fall mainly into two ‘age’ groups; genes that appeared first in land plants and genes that emerged later in the Oryza clade. TFs predicted to be high in the ranking belong to specific gene families, have relatively simple intron/exon and protein structures, and functionally converge to regulate primary and secondary metabolism pathways. Repeated trials of nested cross-validation tests showed that models trained only on regulatory network patterns, inferred from large transcriptome datasets, outperform models trained on heterogenous genomic features in the prediction of known drought response regulators. A new R/Shiny based web application, called the DroughtApp, provides a primer for generation of new testable hypotheses related to regulation of drought stress response. Furthermore, to test the system we experimentally validated predictions on the functional role of the rice transcription factor OsbHLH148, using RNA sequencing of knockout mutants in response to drought stress and protein-DNA interaction assays. Our study exemplifies the integration of domain knowledge for prioritization of regulatory genes in biological pathways of well-studied agricultural traits. One Sentence Summary Network-based supervised machine learning accurately predicts transcription factors involved in drought tolerance.
Concurrent stem- and lineage-affiliated chromatin programs precede hematopoietic lineage restriction

The emerging notion of hematopoietic stem- and progenitor cells (HSPCs) as a low-primed cloud without sharply demarcated gene expression programs raises the question on how cellular fate options emerge, and at which stem-like stage lineage priming is initiated. Here we investigated single-cell chromatin accessibility of Lineage−, cKit+, Sca1+ (LSK) HSPCs spanning the early differentiation landscape. Application of a signal-processing algorithm to detect transition points corresponding to massive alterations in accessibility of 571 transcription factor-motifs revealed a population of LSK FMS-like tyrosine kinase 3(Flt3)intCD9high cells that concurrently display stem-like and lineage-affiliated chromatin signatures pointing to a simultaneous gain of both Lympho-Myeloid and Megakaryocyte-Erythroid programs. Molecularly and functionally, these cells position between stem cells and committed progenitors, display multi-lineage capacity in vitro and in vivo, but lack self-renewal activity. This integrative molecular analysis resolves the heterogeneity of cells along hematopoietic differentiation and permits investigation of chromatin-mediated transition between multipotency and lineage restriction.
Production of Intergeneric Hybrids between the C3-C4 Intermediate Species Diplotaxis tenuifolia (L.) DC. and Raphanus sativus L.

In intergeneric crossings between Diplotaxis tenuifolia (2n = 22, DtDt) and five cultivars of Raphanus sativus (2n = 18, RR), an intergeneric F1 hybrid was produced from the crossing of D. tenuifolia × R. sativus cv. ‘4-season leaf’ through ovary culture followed by embryo culture. The induced amphidiploid (2n = 40, DtDtRR) showed well-regulated meiotic features at PMCs and a high pollen fertility (75 %). Three BC1 hybrids with DtRR (2n = 29) or DtDtR (2n = 31) genome constitutions were obtained by the same embryo rescue procedure in the crossings of amphidiploid × R. sativus and D. tenuifolia × amphidiploid, respectively. In the successive backcrossings of two BC1 hybrids (DtRR, 2n = 29) to R. sativus, 102 BC2 hybrids were obtained by conventional pollination. In the reciprocal crossing of R. sativus × BC1 hybrids, 12 reciprocal BC2 hybrids were also produced without embryo rescue. The somatic chromosome number of 89 BC2 hybrids with D. tenuifolia cytoplasm and 12 reciprocal BC2 hybrids with R. sativus cytoplasm ranged from 2n = 18 to 2n = 23 that were estimated to carry 2n = 18 chromosomes of R. sativus and zero to five chromosomes of D. tenuifolia. Among them, 24.7 % of the BC2 hybrids and 41.6 % of the reciprocal BC2 hybrids were assumed to be monosomic addition lines (MALs, 2n = 19). The novel intergeneric hybrids obtained in this study could become useful materials for investigating the genetic effects on C3-C 4 intermediate traits at the genomic and chromosomal levels, as well as for estimating the performance of genetic improvement in Brassicaceae.
Selection of soybean mutants with increased concentrations of seed methionine and cysteine

Soybean [Glycine max. (L.) Merr. ] protein, which is deficient in the sulfur amino acids, especially methionine, is consumed world-wide by both humans and other animals. Methionine deficiency is caused by an abundance of the β-chain of β-conglycinin, a seed storage protein that lacks methionine, De noyo synthesis of the β-chain is inhibited by an elevated concentration of methionine. The objectives of our investigations were to mutagenize soybean seeds, characterize a methionine over-producing phenotype, and select several methionine over-producing genetic lines, Mutant lines with a methionine over-producing phenotype were isolated and crossed. Seeds from a cross, designated H82 × 20a 2 , contained a normal seed nitrogen concentration and an 18% increase in seed sulfur concentration. The S/N atomic ratio of line H82 × 20a 2 was 16.2% greater than that of the parental line. Amino acid analyses of seeds from the derived and parental lines revealed mole percentages of 1.84 and 1.51, respectively, for methionine and 1.685 and 1.32, respectively, for cysteine. Thus, seed methionine and cysteine concentrations of H82 × 20a 2 were each approximately 20% greater than those of the parental line. Protein produced by the derived lise may fulfill nutritional requirements for methionine and cysteine.
Suicidal Thoughts, Behaviors, and Event-Related Potentials: A Meta-Analysis

Suicidal thoughts and behaviors (STBs) are thought to be the result, at least in part, of abnormalities in various neural systems. Event-related potentials (ERPs) are a useful method for studying neural activity, and can be leveraged to study neural deficits related to STBs, but it is unknown how effective ERPs are at differentiating various STB groups. The present metaanalysis examined how well ERPs can differentiate those with and without suicidal ideation (SI), suicide attempts (SA), and those determined to be at different levels of suicide risk, or suicidality. Our meta-analysis included 192 effect sizes from 24 studies. We used a random effects meta-analysis and found a small-to-moderate relationship between ERPs and STBs. However, we also found evidence that the literature may be suffering from small sample publication bias. Our results suggest that ERPs may compliment other approaches, such as fMRI, in the study of the neurobiology of individuals with STBs. However, the clinical utility of ERPs to predict STBs remains to be tested, and larger samples are needed to confirm the results of the present meta-analysis.
Quantifying the impact of polyphagous invertebrate predators in controlling cereal aphids and in preventing wheat yield and quality reductions

Summary Exclusion barriers were used to manipulate numbers of polyphagous invertebrate predators so that their impact on cereal aphids and consequently wheat yield and quality could be examined. Experiments were conducted within the framework of the LINK Integrated Farming Systems Project which allowed comparisons to be made between the integrated and conventional farming systems under examination on a study farm in Hampshire, UK. Only in 1995 were the numbers of aphids per tiller, the aphid peak and rate of increase to the peak significantly greater in the exclusion areas where the density of polyphagous predators had been reduced. The maximum increase in aphids as a result of excluding polyphagous predators was 31%, which was equivalent to 130 aphid days. However, the polyphagous predators did not reduce the number of tillers infested. The relatively low impact of polyphagous predators was attributed to the aphid population phenology and greater effects may have been found had aphids infested the crops earlier in their development. Sowing date was shown to govern the time over which a crop may be susceptible to yield loss from aphids, with later-drilled crops being more susceptible to late-summer aphid infestations. Aphid numbers rarely affected grain yield but were found to be related to some grain quality parameters, but reducing polyphagous predators had no direct impact on grain yield or quality even where the aphid burden increased. The peak period of activity and density differed between the species of Carabidae, Staphylinidae and Araneae consequently influencing their relationship with the aphids. Some negative correlations were found between these groups of polyphagous predators and aphids. Species composition and abundance differed between fields thereby influencing the level of aphid predation. The exclusion barriers were most effective at reducing numbers of Carabidae although numbers of Staphylinidae and Araneae were also reduced. The consequences for Integrated Crop Management are discussed.
Conservative and liberal attitudes drive polarized neural responses to political content

Significance Partisan biases in processing political information contribute to rising divisions in society. How do such biases arise in the brain? We measured the neural activity of participants watching videos related to immigration policy. Despite watching the same videos, conservative and liberal participants exhibited divergent neural responses. This “neural polarization” between groups occurred in a brain area associated with the interpretation of narrative content and intensified in response to language associated with risk, emotion, and morality. Furthermore, polarized neural responses predicted attitude change in response to the videos. These findings suggest that biased processing in the brain drives divergent interpretations of political information and subsequent attitude polarization. People tend to interpret political information in a manner that confirms their prior beliefs, a cognitive bias that contributes to rising political polarization. In this study, we combined functional magnetic resonance imaging with semantic content analyses to investigate the neural mechanisms that underlie the biased processing of real-world political content. We scanned American participants with conservative-leaning or liberal-leaning immigration attitudes while they watched news clips, campaign ads, and public speeches related to immigration policy. We searched for evidence of “neural polarization”: activity in the brain that diverges between people who hold liberal versus conservative political attitudes. Neural polarization was observed in the dorsomedial prefrontal cortex (DMPFC), a brain region associated with the interpretation of narrative content. Neural polarization in the DMPFC intensified during moments in the videos that included risk-related and moral-emotional language, highlighting content features most likely to drive divergent interpretations between conservatives and liberals. Finally, participants whose DMPFC activity closely matched that of the average conservative or the average liberal participant were more likely to change their attitudes in the direction of that group’s position. Our work introduces a multimethod approach to study the neural basis of political cognition in naturalistic settings. Using this approach, we characterize how political attitudes biased information processing in the brain, the language most likely to drive polarized neural responses, and the consequences of biased processing for attitude change. Together, these results shed light on the psychological and neural underpinnings of how identical information is interpreted differently by conservatives and liberals.
Impact of integrated management systems on jointed goatgrass (Aegilops cylindrica) populations

Abstract Research during the past several decades on jointed goatgrass management has focused on individual cultural practices rather than on multi- or interdisciplinary components. Field studies were conducted at Hays, KS, from 1997 to 2003 to evaluate the interaction of crop rotation, fallow weed management, and winter wheat variety on jointed goatgrass density. Extending a wheat–fallow (W–F) rotation to include grain sorghum or grain sorghum and sunflower reduced jointed goatgrass populations more than other cultural practices tested. Fallow treatments were equal in most years, but mechanical fallow resulted in increased jointed goatgrass emergence compared with chemical fallow under drought conditions. Winter wheat cultivars had little effect on jointed goatgrass populations. However, taller, more competitive varieties are favorable for jointed goatgrass control in an integrated management program. No specific combination of crop rotation, fallow weed management, and wheat variety consistently reduced jointed goatgrass density more than other combinations during multiple years. Nomenclature: Jointed goatgrass, Aegilops cylindrica Host AEGCY; grain sorghum, Sorghum bicolor (L.) Moench ‘DK-35’; sunflower, Helianthus annuus L. ‘Triumph 562’; winter wheat, Triticum aestivum L. ‘Ike’, ‘TAM 107’, ‘Jagger’, ‘Vista’.
Knock-Down of Hippocampal DISC1 in Immune-Challenged Mice Impairs the Prefrontal–Hippocampal Coupling and the Cognitive Performance Throughout Development

Disrupted-in-Schizophrenia 1 (DISC1) gene represents an intracellular hub of developmental processes and has been related to cognitive dysfunction in psychiatric disorders. Mice with whole-brain DISC1 knock-down show memory and executive deficits as result of impaired prefrontal-hippocampal communication throughout development, especially when combined with early environmental stressors, such as maternal immune activation (MIA). While synaptic dysfunction of layer 2/3 pyramidal neurons in neonatal prefrontal cortex (PFC) has been recently identified as one source of abnormal long-range coupling in these mice, it is still unclear whether the hippocampus (HP) is also compromised during development. Here we aim to fill this knowledge gap by combining in vivo electrophysiology and optogenetics with morphological and behavioral assessment of immune-challenged mice with DISC1 knock-down either in the whole brain (GE) or restricted to pyramidal neurons in CA1 area of intermediate/ventral HP (i/vHP) (GHPE). Both groups of mice show abnormal network activity, sharp-waves (SPWs) and neuronal firing in CA1 area. Moreover, optogenetic stimulation of CA1 pyramidal neurons fails to activate the local circuits in the neonatal PFC. These deficits that persist until pre-juvenile development are due to dendrite sparsification and loss of spines of CA1 pyramidal neurons. As a long-term consequence, DISC1 knock-down in immune-challenged mice leads to poorer recognition memory at pre-juvenile age. Thus, besides PFC, hippocampal CA1 area has a critical role for the developmental miswiring and long-lasting cognitive impairment related to mental illness. Significance Statement Developmental miswiring within prefrontal-hippocampal networks has been proposed to account for cognitive impairment in mental disorders. Indeed, during development, long before the emergence of cognitive deficits, the functional coupling within these networks is reduced in mouse models of disease. However, the cellular mechanisms of dysfunction are largely unknown. Here we combine in vivo electrophysiology and optogenetics with behavioral assessment in immune-challenged mice with hippocampus-confined DISC1 knock-down and show that pyramidal neurons in CA1 area are critical for the developmental dysfunction of prefrontal-hippocampal communication and cognitive impairment.
Low-pass sequencing increases the power of GWAS and decreases measurement error of polygenic risk scores compared to genotyping arrays

Low-pass sequencing (sequencing a genome to an average depth less than 1x coverage) combined with genotype imputation has been proposed as an alternative to genotyping arrays for trait mapping and calculation of polygenic scores; however, the current literature is largely limited to simulation- and downsampling-based approaches. To empirically assess the relative performance of these technologies for different applications, we performed low-pass sequencing (targeting coverage levels of 0.5x and 1x) and array genotyping (using the Illumina Global Screening Array) on 120 DNA samples derived from African and European-ancestry individuals that are part of the 1000 Genomes Project. We then imputed both the sequencing data and the genotyping array data to the 1000 Genomes Phase 3 haplotype reference panel using a leave-one-out design. First, we evaluated overall imputation accuracy from these different assays as measured by genotype concordance; we introduce the concept of effective coverage that accounts for evenness of sequencing and show that this metric is a better predictor of imputation accuracy than nominal mapped coverage for low-pass sequencing data. Next, we evaluated overall power for genome-wide association studies (GWAS) as measured by the squared correlation between imputed and true genotypes. In the African individuals, at common variants (> 5% minor allele frequency), imputation r2 averaged 0.83 for the array data and ranged from 0.89 to 0.95 for the low-pass sequencing data, corresponding to an effective 7 – 15% increase in GWAS discovery power. For the same variants in the European individuals, imputation r2 averaged 0.91 for the array data and ranged from 0.92-0.96 for the low-pass sequencing data, corresponding to an effective 1-6% increase in GWAS discovery power. Finally, we computed polygenic risk scores for breast cancer and coronary artery disease from the different assays. We observed consistently lower measurement error for risk scores computed from low-pass sequencing data above an effective coverage of ∼ 0.5x. The mean squared error of the array-based estimates was three to four times that of the estimates from samples sequenced at an effective coverage of ∼ 1.2x for coronary artery disease, with qualitatively similar results for breast cancer. We conclude that low-pass sequencing plus imputation, in addition to providing a substantial increase in statistical power for genome wide association studies, provides increased accuracy for polygenic risk prediction at effective coverages of ∼ 0.5x and higher.
Vegetative compatibility groups among nonpathogenic root-colonizing strains of Fusarium oxysporum

A total of 110 isolates of Fusarium oxysporum were collected from apparently healthy celery roots from the major celery production areas of California. All isolates used in this study were nonpathogenic on celery. Nitrate-nonutilizing mutants (nit mutants) were used to test for vegetative compatibility among the isolates. Twenty-eight isolates were randomly selected from the collection and used as tester isolates. Complementary nit mutants, arbitrarily designated nitA and nitB, were recovered from each of the 28 tester isolates and paired in all combinations to test for vegetative compatibility among the isolates. Fourteen distinct vegetative compatibility groups, designated VCG2001 through VCG2014, were recovered. The remaining 82 isolates were then tested for vegetative compatibility with these 14 vegetative compatibility groups. Fifty of the 110 isolates belong to one of the 14 vegetative compatibility groups. Two vegetative compatibility groups, VCG2001 and VCG2002, were found in the highest frequency.