Miracle-dz/UniFAR-FTUs huggingface dataset:
The Structures of SctK and SctD from Pseudomonas aeruginosa Reveal the Interface of the Type III Secretion System Basal Body and Sorting Platform

Many Gram-negative bacterial pathogens use type III secretion systems (T3SS) to inject effector proteins into eukaryotic cells to subvert normal cellular functions. The T3SS apparatus (injectisome) shares a common overall architecture in all systems studied thus far, comprising three major components – the cytoplasmic sorting platform, the envelope-spanning basal body and the external needle with controlling tip complex. The sorting platform consists of an ATPase (SctN) connected to “pods” (SctQ) having six-fold symmetry via radial spokes (SctL). These pods interface with the 24-fold symmetric SctD inner membrane ring (IR) via an adaptor protein (SctK). Here we report the first high-resolution structure of a SctK protein family member, PscK from Pseudomonas aeruginosa, as well as the structure of its interacting partner, the cytoplasmic domain of PscD (SctD). The cytoplasmic domain of PscD forms a forkhead-associated (FHA) fold, like that of its homologues from other T3SS. PscK, on the other hand, forms a helix-rich structure that does not resemble any known protein fold. Based on these structural findings, we present the first model for an interaction between proteins from the sorting platform and the IR. We also test the importance of the PscD residues predicted to mediate this electrostatic interaction using a two-hybrid analysis. The functional need for Arg96 in vivo was then confirmed by monitoring secretion of the effector ExoU. These structures will contribute to the development of atomic-resolution models of the entire sorting platform and to our understanding of the mechanistic interface between the sorting platform and the basal body of the injectisome. Highlights The structures of Pseudomonas aeruginosa PscD (SctD) and PscK (SctK) were solved The interface between the T3SS basal body and sorting platform was modeled The crystal structure of PscK is the first for any SctK family member PscK represents a novel protein fold Site-directed mutagenesis supports a computational model of the PscD-PscK interface Graphical abstract. The first reported structure for a T3SS SctK protein family member was solved for PscK from Pseudomonas aeruginosa and this allowed for modeling of the interface between this sorting platform protein and the cytoplasmic domain of PscD (a SctD protein family member). This allowed for identification of amino acid residues that may play a role in the interaction between these proteins. The interface appears to be dominated by electrostatic interactions and mutagenesis confirmed the importance of key residues in driving their interaction based on two-hybrid analysis.
Host phylogeny and host ecology structure the mammalian gut microbiota at different taxonomic scales

The gut microbiota is critical for host function. Among mammals, host phylogenetic relatedness and diet are strong drivers of gut microbiota structure, but one factor may be more influential than the other. Here, we used 16S rRNA gene sequencing to determine the relative contributions of host phylogeny and host diet in structuring the gut microbiotas of 11 herbivore species from 5 families living sympatrically in southwest Kenya. Herbivore species were classified as grazers, browsers, or mixed-feeders and dietary data (% C4 grasses in diet) were compiled from previously published sources. We found that herbivore gut microbiotas were highly species-specific, and that host taxonomy accounted for more variation in the gut microbiota (30%) than did host dietary guild (10%) or sample month (8%). Overall, similarity in the gut microbiota increased with host phylogenetic relatedness ( r = 0.74) across the 11 species of herbivores, but among 7 closely related Bovid species, dietary %C4 grass values more strongly predicted gut microbiota structure ( r = 0.64). Additionally, within bovids, host dietary guild explained more of the variation in the gut microbiota (17%) than did host species (12%). Lastly, while we found that the gut microbiotas of herbivores residing in southwest Kenya converge with those of distinct populations of conspecifics from central Kenya, fine-scale differences in the abundances of bacterial amplicon sequence variants (ASVs) between individuals from the two regions were also observed. Overall, our findings suggest that host phylogeny and taxonomy strongly structure the gut microbiota across broad host taxonomic scales, but these gut microbiotas can be further modified by host ecology (i.e., diet, geography), especially among closely related host species.
Ex vivo Demonstration of Functional Deficiencies in Popliteal Lymphatic Vessels from TNF-Tg Mice with Inflammatory Arthritis

Background Rheumatoid arthritis (RA) is a progressive immune-mediated inflammatory disease characterized by intermittent episodes of pain and inflammation in affected joints, or flares. Recent studies demonstrated lymphangiogenesis and expansion of draining lymph nodes during chronic inflammatory arthritis, and lymphatic dysfunction associated with collapse of draining lymph nodes in RA patients and TNF-transgenic (TNF-Tg) mice experiencing arthritic flare. As the intrinsic differences between lymphatic vessels afferent to healthy, expanding, and collapsed draining lymph nodes are unknown, we characterized the ex vivo behavior of popliteal lymphatic vessels (PLVs) from WT and TNF-Tg mice. We also interrogated the mechanisms of lymphatic dysfunction through inhibition of nitric oxide synthase (NOS). Methods Popliteal lymph nodes (PLNs) in TNF-Tg mice were phenotyped as Expanding or Collapsed by in vivo ultrasound and age-matched to WT littermate controls. The PLVs were harvested and cannulated for ex vivo functional analysis over a relatively wide range of hydrostatic pressures (0.5 to 10 cmH2O) to quantify the end diastolic diameter (EDD), tone, amplitude (AMP), ejection fraction (EF), contraction frequency (FREQ) and fractional pump flow (FPF) with or without NOS inhibitors Data was analyzed using repeated measures two-way ANOVA with Bonferroni’s post hoc test. Results Real time videos of the cannulated PLVs demonstrated the predicted phenotypes of robust versus weak contractions of the WT versus TNF-Tg PLV, respectively. Quantitative analyses confirmed that TNF-Tg PLVs had significantly decreased AMP, EF and FPF versus WT (p<0.05). EF and FPF were recovered by NOS inhibition, while the reduction in AMP was NOS independent. No differences in EDD, tone, or FREQ were observed between WT and TNF-Tg PLVs, nor between Expanding versus Collapsed PLVs. Conclusion These findings support the concept that chronic inflammatory arthritis leads to NOS dependent and independent draining lymphatic vessel dysfunction that exacerbates disease, and may trigger arthritic flare due to decreased egress of inflammatory cells and soluble factors from affected joints.
Mother's curse is pervasive across a large mitonuclear Drosophila panel

The maternal inheritance of mitochondrial genomes entails a sex-specific selective sieve, whereby mutations in mitochondrial DNA can only respond to selection acting directly on females. In theory, this enables male-harming mutations to accumulate in mitochondrial genomes if they are neutral, beneficial, or only slightly deleterious to females. Ultimately, this bias could drive the evolution of male-specific mitochondrial mutation loads, an idea known as mother’s curse. Earlier work on this hypothesis has mainly used small Drosophila panels, in which naturally-sourced mitochondrial genomes were coupled to an isogenic nuclear background. However, the lack of nuclear genetic variation has precluded robust generalization. Here we test the predictions of mother’s curse using a large Drosophila mito-nuclear genetic panel, comprising 9 isogenic nuclear genomes coupled to 9 mitochondrial haplotypes, giving a total of 81 different mito-nuclear genotypes. This enables systematic testing of both mito-nuclear interactions and mitochondrial genetic variance. Following a predictive framework, we performed a screen for wing centroid size, as this trait is highly sexually dimorphic and depends on metabolic function. We confirmed that the trait is sexually dimorphic, and show high levels of mito-nuclear epistasis. Importantly, we report that mitochondrial genetic variance has a greater impact on male versus female Drosophila, in 8 out of the 9 nuclear genetic backgrounds. These results demonstrate that the maternal inheritance of mitochondrial DNA does indeed modulate male life-history traits in a more generalisable way than previously envisaged.
Altered Visual Function in a Larval Zebrafish Knockout of Neurodevelopmental Risk Gene pdzk1

The human PDZK1 gene is located in a genomic susceptibility region for neurodevelopmental disorders. A genome-wide association study (GWAS) identified links between PDZK1 polymorphisms and altered visual contrast sensitivity, an endophenotype for schizophrenia and autism spectrum disorder. The PDZK1 protein is implicated in neurological functioning, interacting with synaptic molecules including post-synaptic density 95 (PSD-95), N-methyl-D-aspartate receptors (NMDAR), corticotropin-releasing factor receptor 1 (CRFR1) and serotonin 2A receptors. To elucidate the role of PDZK1, we generated pdzk1-knockout (pdzk1-KO) zebrafish using CRISPR/Cas-9 genome editing. Visual function of 7-day-old fish was assessed at behavioural and functional levels using the optomotor response (OMR) and scotopic electroretinogram (ERG). We also quantified retinal morphology and densities of PSD-95, NMDAR1, CRFR1 and serotonin in the synaptic inner plexiform layer at 7 days, 4 weeks and 8 weeks of age. Relative to wild-type, pdzk1-KO larvae showed spatial-frequency tuning functions with increased amplitude (likely due to abnormal gain control) and reduced ERG b-waves (suggestive of inner retinal dysfunction). However, these functional differences were not associated with gross synaptic or morphological retinal phenotypes. The findings corroborate a role for pdzk1 in visual function, and our model system provides a platform for investigating other genes associated with abnormal visual behaviour.
The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer’s disease mutations

Amyloid fibrils are associated with many human diseases but how mutations alter the propensity of proteins to form fibrils has not been comprehensively investigated and is not well understood. Alzheimer’s Disease (AD) is the most common form of dementia with amyloid plaques of the amyloid beta (Aß) peptide a pathological hallmark of the disease. Mutations in Aß also cause familial forms of AD (fAD). Here we use deep mutational scanning to quantify the effects of >14,000 mutations on the aggregation of Aß. The resulting genetic landscape reveals fundamental mechanistic insights into fibril nucleation, including the importance of charge and gatekeeper residues in the disordered region outside of the amyloid core in preventing nucleation. Strikingly, unlike computational predictors and previous measurements, the in vivo nucleation scores accurately identify all known dominant fAD mutations, validating this simple cell-based assay as highly relevant to the human genetic disease and suggesting accelerated fibril nucleation is the ultimate cause of fAD. Our results provide the first comprehensive map of how mutations alter the formation of any amyloid fibril and a validated resource for the interpretation of genetic variation in Aß. Highlights First comprehensive map of how mutations alter the propensity of a protein to form amyloid fibrils. Charge and gatekeeper residues in the disordered N-terminus of amyloid beta prevent fibril nucleation. Rates of nucleation in a cell-based assay accurately identify the mutations that cause dominant familial Alzheimer’s disease. The combination of deep mutational scanning and human genetics provides a general strategy to quantify the disease-relevance of in vitro and in vivo assays.
NS-Forest: A machine learning method for the objective identification of minimum marker gene combinations for cell type determination from single cell RNA sequencing

Single cell genomics is rapidly advancing our knowledge of cell phenotypic types and states. Driven by single cell/nucleus RNA sequencing (scRNA-seq) data, comprehensive atlas projects covering a wide range of organisms and tissues are currently underway. As a result, it is critical that the cell transcriptional phenotypes discovered are defined and disseminated in a consistent and concise manner. Molecular biomarkers have historically played an important role in biological research, from defining immune cell-types by surface protein expression to defining diseases by molecular drivers. Here we describe a machine learning-based marker gene selection algorithm, NS-Forest version 2.0, which leverages the non-linear attributes of random forest feature selection and a binary expression scoring approach to discover the minimal marker gene expression combinations that precisely captures the cell type identity represented in the complete scRNA-seq transcriptional profiles. The marker genes selected provide a barcode of the necessary and sufficient characteristics for semantic cell type definition and serve as useful tools for downstream biological investigation. The use of NS-Forest to identify marker genes for human brain middle temporal gyrus cell types reveals the importance of cell signaling and non-coding RNAs in neuronal cell type identity.
Expression study of soybean germin-like gene family reveals a role of GLP7 gene in various abiotic stress tolerances

Abstract Germin-like proteins (GLPs) are ubiquitous plant glycoproteins (belonging to the cupin super family) that play diverse roles, including abiotic stress resistance in many plant species. To identify the molecular functions underlying abiotic stress responses, the expression of germin-like protein encoding genes of soybean GmGLPs was analyzed. qRT-PCR analyses of 21 GmGLPs transcripts abundances were conducted in soybean leave tissues. The results showed that GmGLPs transcripts were highly abundant upon treatments with high salinity, PEG6000, abscisic acid (ABA) and methyl viologen (MV). The peaks of transcript copiousness induced by PEG6000 and NaCl were mostly observed after 18 h, while some genes expressed earlier than 4 h after abiotic stress treatment. A specific GmGLP7 gene, that was highly abundant under salinity, drought, ABA and MV conditions, was further characterized. The ectopic overexpression of GmGLP7 (Glyma.08G226800.1) in transgenic Arabidopsis enhanced drought, salt, and oxidative tolerance and resulted in hypersensitive phenotypes toward ABA-mediated seed germination and primary root elongation, compared to the wild-type. Taken together, these results suggest that GmGLP7 positively confers abiotic tolerance in plants.
A numeric index based on spatial frequency for the tortuosity of retinal vessels and its application to plus disease in retinopathy of prematurity.

BACKGROUND In retinopathy of prematurity (ROP), tortuosity of vessels near the posterior pole of the fundus is an important clinical sign, yet clinicians have difficulty estimating how tortuous the vessels are. METHODS The authors have devised an objective, numeric index of retinal blood vessel tortuosity that is especially sensitive to the structural changes in vessels that occur in ROP, but it is not particularly sensitive to non-ROP changes. Computer software is used to calculate the index from fundus images; the quality of these images is typical of photographs or video-cassette frames that the authors record in the premature nursery. RESULTS The index reliably segregates tortuous vessels from nontortuous ones and separates eyes that reach ROP treatment threshold from eyes that do not. CONCLUSIONS The index forms an objective measure of the ROP disease state. Its calculation requires only segments of vessels and thus, is potentially adaptable to imaging systems that automatically extract vessel portions from fundus images.
When pull turns to shove: A continuous-time model for opinion dynamics

Accurate modeling of opinion dynamics has the potential to help us understand polarization and what makes effective political discourse possible or impossible. Here, we use physics-based methods to model the evolution of political opinions within a continuously distributed population. We utilize a network-free system of determining political influence and a local-attraction, distal-repulsion dynamic for reaction to perceived content. Our approach allows for the incorporation of intergroup bias such that messages from trusted in-group sources enjoy greater leeway than out-group ones. We are able to extrapolate these nonlinear microscopic dynamics to macroscopic population distributions by using probabilistic functions representing biased environments. The framework we put forward can reproduce real-world political distributions and experimentally observed dynamics, and is amenable to further refinement as more data becomes available.
Thermoelectric generation of orbital magnetization in metals

We propose an orbital magnetothermal effect wherein a temperature gradient generates an orbital magnetization (OM) for Bloch electrons, and we present a unified theory for electrically and thermally induced OM, valid for both metals and insulators. We reveal that there exists an intrinsic response of OM, for which the susceptibilities are completely determined by the band geometric quantities such as interband Berry connections, interband orbital moments, and the quantum metric. The theory can be readily combined with first-principles calculations to study real materials. As an example, we calculate the OM response in CrI$_{3}$ bilayers, where the intrinsic contribution dominates. The temperature scaling of intrinsic and extrinsic responses, the effect of phonon drag, and the phonon angular momentum contribution to OM are discussed.
Adjustment in assessment scores and their usage: A taxonomy and evaluation methods.

Methods of adjusting group differences in assessment and test scores are described, classified, and evaluated. The adjustments are classified on the basis of (a) the type of adjusted difference, (b) the method of adjustment, and (c) the purpose of the adjustment. Adjustments used to improve the social fairness of outcomes either could not be fully evaluated or were inconsistent with the underlying fairness model. Adjustments designed to reduce score bias, in the technical sense, could be meaningful and internally consistent only if the observed group difference could be related to constructs targeted by the assessment procedure
The Source of Carbon for Proline Synthesis in Osmotically Stressed Artichoke Tuber Slices

When thin slices of tubers of Helianthus tuberosus L. are plasmolysed in mannitol solutions, the initially large pool of free arginine decreases within 24 h and then, during the next 72 h, a several- fold increase in the concentration of free proline occurs. Radioactivity from DL-ornithine, L-arginine and L-glutamate was shown to label proline in plasmolysed discs of tubers. The percentage conversion to proline of each of the precursors was 20 to 50 times greater in discs plasmolysed for 24 h than in freshly plasmolysed discs. By comparing the transfer of radioactivity from L-[U-14C]arginine and L-[5-3H]arginine to proline, metabolism of arginine directly to proline without passage through a glutamate pool was established. It is concluded from this and other evidence that pathways from arginine and glutamate to proline operate independently. Calculations based on the specific activity of precursors, the pool sizes of free arginine and glutamate, and the transfer rates of radioactivity to proline indicate that arginine is quantitatively the more important precursor for proline synthesis in this tissue.
Effects of temperature and sunlight on mycosis (Beauveria bassiana) (Hyphomycetes: Sympodulosporae) of grasshoppers under field conditions

The influence of environmental conditions on mycosis of grasshoppers caused by Beauveria bassiana (Balsamo) Vuillemin, was investigated. Despite the deposition of considerable quantities of conidia onto grasshoppers (6.7 x 10 3 colony-forming units [CFU] per nymph), B. bassiana did not significantly reduce field populations nor did it affect specific grasshopper taxa. Conditions were warm and sunny during the trial, and slopes of conidial persistence were equally poor on both grasshoppers and grass leaves. Small numbers of conidia (<2 CFU per grasshopper) were recovered from surface-sterilized grasshoppers 5-15 d after application indicating that if infection occurred, B. bassiana did not proliferate in the hemocoel. Considerable mycosis was observed in grasshoppers placed in cages in the greenhouse, but not in grasshoppers confined in cages adjacent to the field plots. Furthermore, the prevalence of disease in the greenhouse cages decreased with the sampling date but the onset of mycosis always occurred 3-4 d after collection, suggesting that environmental conditions in the greenhouse were responsible for the increased susceptibility of grasshoppers. Higher prevalence and more rapid development of disease were observed in grasshoppers placed in shaded cages (83-89%) than in cages exposed to full sunlight (0-15%) or protected from UVB radiation (1-43%); conidial survival was equally enhanced in the shaded and UVB-protected environments. Our results indicate that the poor efficacy of B. bassiana against rangeland grasshoppers was a result of conditions of temperature and light exposure (reduced grasshopper thermoregulation), and not the result of inadequate host targeting or pathogen virulence.
The Ramsey number of a long cycle and complete graphs.

In this paper, we prove that the multicolored Ramsey number $R(G_1,\dots,G_n,K_{n_1},\dots,K_{n_r})$ is at least $(\gamma-1)(\kappa-1)+1$ for arbitrary connected graphs $G_1,\dots,G_n$ and $n_1,\dots,n_r\in\mathbb{N}$, where $\gamma=R(G_1,\dots,G_n)$ and $\kappa=R(K_{n_1},\dots,K_{n_r})$. Erd\H os at al. conjectured that $R(C_n,K_l)=(n-1)(l-1)+1$ for every $n\geq l\geq 3$ except for $n=l=3$. Nikiforov proved this conjecture for $n\geq 4l+2$. Using the above bound, we derive the following generalization of this result. $R(C_n,K_{n_1},\dots,K_{n_r})=(n-1)(\kappa-1)+1$, where $\kappa=R(K_{n_1},\dots,K_{n_r})$ and $n\geq 4\kappa+2$.
Cross-lingual Supervision Improves Unsupervised Neural Machine Translation

We propose to improve unsupervised neural machine translation with cross-lingual supervision (), which utilizes supervision signals from high resource language pairs to improve the translation of zero-source languages. Specifically, for training En-Ro system without parallel corpus, we can leverage the corpus from En-Fr and En-De to collectively train the translation from one language into many languages under one model. % is based on multilingual models which require no changes to the standard unsupervised NMT. Simple and effective, significantly improves the translation quality with a big margin in the benchmark unsupervised translation tasks, and even achieves comparable performance to supervised NMT. In particular, on WMT’14 -tasks achieves 37.6 and 35.18 BLEU score, which is very close to the large scale supervised setting and on WMT’16 -tasks achieves 35.09 BLEU score which is even better than the supervised Transformer baseline.