Miracle-dz/UniFAR-FTUs huggingface dataset:
The centromere/kinetochore is assembled through CENP-C oligomerization

The kinetochore is an essential protein complex for accurate chromosome segregation. The constitutive centromere-associated network (CCAN), a subcomplex of the kinetochore, associates with centromeric chromatin providing a platform for the kinetochore assembly. A CCAN protein, CENP-C, is thought to be a central hub for the centromere/kinetochore organization. However, the crucial role of CENP-C in centromeres remains to be elucidated. Here, we demonstrated that both the CCAN-binding domain and C-terminal Cupin domain of CENP-C are necessary and sufficient for chicken CENP-C function. Our structural and biochemical analyses revealed that the Cupin domain of chicken and human CENP-C is self-oligomerization domain, which is crucial for centromeric chromatin organization. CENP-C mutants lacking the oligomerization interface cause mislocalization of CCAN and cell death. Based on these results, we conclude that the CENP-C oligomerization plays a crucial role in centromere function via providing the robust centromeric chromatin in vertebrate cells.
A conserved HOTAIRM1-HOXA1 regulatory axis coordinates early neuronal differentiation

HOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 is required for proper progression through the early stages of neuronal differentiation. We found that it associates with the HOXA1 transcription factor and participates in its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis controlling the transition from a pluripotent to a differentiated neuronal state.
Prophage-encoded small protein YqaH counteracts the activities of the replication initiator DnaA in Bacillus subtilis

Bacterial genomes harbor cryptic prophages that are mostly transcriptionally silent with many unannotated genes. Still, cryptic prophages may contribute to their host fitness and phenotypes. In B. subtilis, the yqaF-yqaN operon belongs to the prophage element skin, and is tightly repressed by the Xre-like repressor sknR. This operon contains several short open reading frames (smORFs) potentially encoding small-sized proteins. The smORF-encoded peptide YqaH was previously reported to bind to the replication initiator DnaA. Here, using a yeast two-hybrid assay, we found that YqaH binds to the DNA binding domain IV of DnaA and interacts with Spo0A, a master regulator of sporulation. We isolated single amino acid substitutions in YqaH that abolished interaction with DnaA but not with Spo0A. Then, we studied in B. subtilis the phenotypes associated with the specific loss-of-interaction with DnaA (DnaA-LOI). We found that expression of yqaH carrying DnaA-LOI mutations abolished the deleterious effects of yqaH WT expression on chromosome segregation, replication initiation and DnaA-regulated transcription. When YqaH was induced after vegetative growth, DnaA-LOI mutations abolished the deleterious effects of YqaH WT on sporulation and biofilm formation. Thus, YqaH inhibits replication, sporulation and biofilm formation mainly by antagonizing DnaA in a manner that is independent of the cell cycle checkpoint Sda.
Conduction velocity along a key white matter tract is associated with autobiographical memory recall ability

Conduction velocity is the speed at which electrical signals travel along axons and is a crucial determinant of neural communication. Inferences about conduction velocity can now be made in vivo in humans using a measure called the magnetic resonance (MR) g-ratio. This is the ratio of the inner axon diameter relative to that of the axon plus the myelin sheath that encases it. Here, in the first application to cognition, we found that variations in MR g-ratio, and by inference conduction velocity, of the parahippocampal cingulum bundle were associated with autobiographical memory recall ability in 217 healthy adults. This tract connects the hippocampus with a range of other brain areas. We further observed that the association seemed to be with inner axon diameter rather than myelin content. The extent to which neurites were coherently organised within the parahippocampal cingulum bundle was also linked with autobiographical memory recall ability. Moreover, these findings were specific to autobiographical memory recall, and were not apparent for laboratory-based memory tests. Our results offer a new perspective on individual differences in autobiographical memory recall ability, highlighting the possible influence of specific features of white matter microstructure when recalling detailed memories of our real-life past experiences.
A Syntenin Inhibitor Blocks Endosomal Entry of SARS-CoV-2 and a Panel of RNA Viruses

Viruses are dependent on interactions with host factors in order to efficiently establish an infection and replicate. Targeting such interactions provides an attractive strategy to develop novel antivirals. Syntenin is a protein known to regulate the architecture of cellular membranes by its involvement in protein trafficking, and has previously been shown to be important for HPV infection. Here we show that a highly potent and metabolically stable peptide inhibitor that binds to the PDZ1 domain of syntenin inhibits SARS-CoV-2 infection by blocking the endosomal entry of the virus. Furthermore, we found that the inhibitor also hampered chikungunya infection, and strongly reduced flavivirus infection, which are completely dependent on receptor mediated endocytosis for their entry. In conclusion, we have identified a novel pan-viral inhibitor that efficiently target a broad range of RNA viruses.
Recurrent mutation in the ancestry of a rare variant

Recurrent mutation produces multiple copies of the same allele which may be co-segregating in a population. Yet most analyses of allele-frequency or site-frequency spectra assume that all observed copies of an allele trace back to a single mutation. We develop a sampling theory for the number of latent mutations in the ancestry of a rare variant, specifically a variant observed in relatively small count in a large sample. Our results follow from the statistical independence of low-count mutations, which we show to hold for the standard neutral coalescent or diffusion model of population genetics as well as for more general coalescent trees. For populations of constant size, these counts are given by the Ewens sampling formula. We develop a Poisson sampling model for populations of varying size, and illustrate it using new results for site-frequency spectra in an exponentially growing population. We apply our model to a large data set of human SNPs and use it to explain dramatic differences in site-frequency spectra across the range of mutation rates in the human genome.
Tunable tension for gesture animation

Variation in muscular tension has important expressive impacts on agent motion; however, it is difficult to tune simulations to achieve particular effects. With a focus on gesture animation, we introduce mass trackers, a lightweight approach that employs proportional derivative control to track point masses that define the position of each wrist. The restriction to point masses allows the derivation of response functions that support straightforward tuning of system behavior. Using the point mass as an end-effector for an inverse kinematics rig allows easy control of both loose and high tension arm motion. Examples illustrate the expressive variation that can be achieved with this tension modulation. Two perceptual studies confirm that these changes impact the overall level of tension perceived in the motion of a gesturing character and further explore the parameter space. Practical guidelines on tuning are discussed.
Cooperative Trajectory Planning for Haptic Shared Control Between Driver and Automation in Highway Driving

This paper addresses the driver–automation shared driving control for lane keeping and obstacle avoidance of automated vehicles in highway traffic. The proposed shared control framework is established from a novel cooperative trajectory planning algorithm and a fuzzy steering controller. Based on polynomial functions, the cooperative trajectory planning is formulated by judiciously exploiting the information on the maneuver decision, the conflict management, and the driver monitoring. As a result, the planned trajectory of the vehicle is continuously adapted according to the driver's actions and intentions. By means of Lyapunov stability arguments, sufficient conditions in terms of linear matrix inequalities are given to design a Takagi–Sugeno fuzzy model-based controller. This robust steering controller provides a necessary assistive torque to track the planned vehicle trajectory. The new shared driving control framework allows reducing effectively the driver–automation conflict issue while offering the driver more freedom to swerve within a predefined lane. The advantages of the proposed approach are evaluated using both objective and subjective results, experimentally obtained from several human drivers and an advanced interactive dynamic driving simulator.
Analysis of nonlinear large signal intrinsic elements for InGaP/GaAs HBT based on Gummel‐Poon model

A large signal analysis method based on Gummel‐Poon model is proposed to predict nonlinear behavior of InGaP/GaAs HBT. A 2 × 20 μm2 transistor is fabricated with InGaP/GaAs HBT technology. The large signal transconductance Gm, conductance Gbe, and capacitance CBE, CBC are calculated based on the proposed method and measured using a RF testing probe. The calculated and measured results show good consistency up to nonlinear power level. The proposed method is applied to analyze variations of nonlinear large signal intrinsic elements of this transistor with increasing power under different bias conditions, in order to raise benefit of nonlinear consideration for power amplifiers.
Fast Markov Localization using Angle-Histogram

Localization is one of the most important issues for mobile robots since all tasks are commanded to a mobile robot based on the assumption that the mobile robot knows its position. Even though non-probabilistic techniques are faster than probabilistic approaches, those are sensitive to measurement errors and a mobile robot may lose its position in complex environments. On the contrary, probabilistic approaches have many advantages since those can cope with sensor noises and can globally localize a mobile robot. However, those probabilistic approaches are time-consuming techniques because of the heavy computational loads due to huge comparative data. In this paper, we propose a probabilistic localization method including global localization by remodeling raw laser sensory data using angle histogram to reduce computational loads for localization. Furthermore, exact heading angle of a mobile robot is determined in a fast manner. The algorithm is experimented successfully by using a mobile robot named KARA.
Transcriptional dynamics of Chitinophaga sp. strain R-73072-mediated alkannin/shikonin biosynthesis in Lithospermum officinale

Plants are colonized by a wide range of bacteria, several of which are known to confer benefits to their hosts such as enhancing plant growth and the biosynthesis of secondary metabolites (SMs). Recently, it has been shown that Chitinophaga sp. strain R-73072 enhances the production of alkannin/shikonin, SMs of pharmaceutical and ecological importance. However, the mechanisms by which this bacterial strain increases these SMs in plants are not yet understood. To gain insight into these mechanisms, we analyzed the molecular responses of Lithospermum officinale, an alkannin/shikonin producing member of Boraginaceae, to inoculation with R-73072 in a gnotobiotic system using comparative transcriptomics and targeted metabolite profiling of root samples. We found that R-73072 modulated the expression of 1,328 genes, of which the majority appeared to be involved in plant defense and SMs biosynthesis including alkannin/shikonin derivatives. Importantly, bacterial inoculation induced the expression of genes that predominately participate in jasmonate and ethylene biosynthesis and signaling, suggesting an important role of these phytohormones in R-73072-mediated alkannin/shikonin biosynthesis. A detached leaf bioassay further showed that R-73072 confers systemic protection against Botrytis cinerea. Finally, R-73072-mediated coregulation of genes involved in plant defense and the enhanced production of alkannin/shikonin esters further suggest that these SMs could be important components of the plant defense machinery in alkannin/shikonin producing species.
Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention

Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
Expression, correlation, and prognostic significance of different nicotinic acetylcholine receptors, programed death ligand 1, and dopamine receptor D2 in lung adenocarcinoma

Objective The objective of this study is to evaluate the expression of different nicotinic acetylcholine receptors (nAChRs), programmed death ligand-1 (PD-L1), and dopamine receptor D2 (DRD2) as prognostic factors in lung cancer and any correlation among them. Since all of the above genes are typically upregulated in response to smoking, we hypothesized that a correlation might exist between DRD2, PD-L1, and nAChR expression in NSCLC patients with a smoking history and a prediction model may be developed to assess the clinical outcome. Methods We retrospectively analyzed samples from 46 patients with primary lung adenocarcinoma who underwent surgical resection at Mayo Clinic Rochester from June 2000 to October 2008. The expression of PD-L1, DRD2, CHRNA5, CHRNA7, and CHRNA9 were analyzed by quantitative PCR and correlated amongst themselves and with age, stage and grade, smoking status, overall survival (OS), and relapse-free survival (RFS). Results Only PD-L1 showed a statistically significant increase in expression in patients older than 65. All the above genes showed higher expression in stage IIIB than IIIA, but none reached statistical significance. Interestingly, we did not observe significant differences among never, former, and current smokers, but patients with pack years greater than 30 showed significantly higher expression of CHRNA9. We observed a strong positive correlation between PD-L1/DRD2, PD-L1/CHRNA5, and CHRNA5/CHRNA7 and a weak positive correlation between DRD2/CHRNA5 and DRD2/CHRNA7. Older age was independently associated with poor OS, whereas lower CHRNA7 expression was independently associated with better OS. Conclusions We observed strong positive correlations among PD-L1, DRD2, and some of the nAChRs. We investigated their prognostic significance in lung cancer patients and found CHRNA7 to be an independent prognostic factor. Overall, the results obtained from this preliminary study warrant a large cohort-based analysis that may ultimately lead to potential patient-specific stratification biomarkers predicting cancer-treatment outcomes.
Aberrant signaling of immune cells in Sjögren’s syndrome patient subgroups upon interferon stimulation

Background Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, characterized by mononuclear cell infiltrates in the salivary and lacrimal glands, leading to glandular atrophy and dryness. Patient heterogeneity and lack of knowledge regarding its pathogenesis makes pSS a difficult disease to manage. Methods An exploratory analysis using mass cytometry was conducted of MAPK/ERK and JAK/STAT signaling pathways in peripheral blood mononuclear cells (PBMC) from 16 female medication free pSS patients (8 anti-Sjögren’s syndrome-related antigen A negative/SSA- and 8 SSA+) and 8 female age-matched healthy donors after stimulation with interferons (IFNs). Results We found significant differences in the frequencies of memory B cells, CD8+ T central and effector memory cells and terminally differentiated CD4+ T cells among the healthy donors and patient subgroups. In addition, we observed an upregulation of HLA-DR and CD38 in many cell subsets in the patients. Upon IFNα2b stimulation, slightly increased signaling through pSTAT1 Y701 was observed in most cell types in pSS patients compared to controls, while phosphorylation of STAT3 Y705 and STAT5 Y694 were slightly reduced. IFNγ stimulation resulted in significantly increased pSTAT1 Y701 induction in conventional dendritic cells (cDCs) and classical and non-classical monocytes in the patients. Most of the observed differences were more prominent in the SSA+ subgroup, indicating greater disease severity in them. Conclusions Augmented activation status of certain cell types along with potentiated pSTAT1 Y701 signaling and reduced pSTAT3 Y705 and pSTAT5 Y694 induction may predispose pSS patients, especially the SSA+ subgroup, to upregulated expression of IFN-induced genes and production of autoantibodies. These patients may benefit from therapies targeting these pathways.
Biosynthesis of silver nanoparticles with antibacterial, antioxidant, anti-inflammatory properties and their burn wound healing efficacy

The current study aims to develop a novel burn wound ointment consisting of sheep’s tail ointment loaded with AgNP. The AgNP in the ointment serves as an antibacterial, antioxidant and anti-inflammatory agent. The AgNP was developed via the biological method with the assistance of the medicinal plant Rhodiola rosea. The characterization of AgNP was assessed using UV-Vis spectroscopy, FTIR, Zeta Potential, XRD, PCCS, SEM, and EDX techniques. The formation of AgNP was confirmed by UV-Vis spectrum at the absorbance of ∼430 nm, and the biomolecules responsible for reducing and capping the AgNP were characterized by FTIR analysis. The stability of AgNP was determined with Zeta potential, which revealed a highly stable colloidal solution with a surface charge of −68.38 ± 3.4 mV. The synthesized AgNP had a face-centered cubic structure with a crystallite size of 23 nm and average grain size of 67.5 nm. The SEM image showed a fairly monodisperse 20 nm-sized spherical-shaped AgNP. The synthesized AgNP contained high purity of the silver, and a low concentration of AgNP inhibited both Gram-positive and Gram-negative bacteria. Moreover, the scavenging activity of AgNP was investigated using DPPH and H2O2 scavenging assay, and the results revealed a dose-dependent antioxidant activity with the highest activity at a concentration of 450 μg/ml. Finally, the burn wound healing effect was evaluated by applying the AgNP-loaded ointment to the wound site of BALB/c mice. The in-vivo studies confirmed that AgNP-loaded ointment reduced the wound size, decreased the epidermis layer, and lowered mast cell migration compared to untreated burn wounds. And the synthesized AgNP regulated both pro-inflammatory and anti-inflammatory gene expression, thereby promoting burn wound closure on BALB/c mice. The developed AgNP-loaded ointment has the potential to be applied in the biomedical field.
Primary cilium in kidney development, function and disease

The primary cilium is a hair-like, microtubule-based organelle that is covered by the cell membrane and extends from the surface of most vertebrate cells. It detects and translates extracellular signals to direct various cellular signaling pathways to maintain homeostasis. It is mainly distributed in the proximal and distal tubules and collecting ducts in the kidney. Specific signaling transduction proteins localize to primary cilia. Defects in cilia structure and function lead to a class of diseases termed ciliopathies. The proper functioning of primary cilia is essential to kidney organogenesis and the maintenance of epithelial cell differentiation and proliferation. Persistent cilia dysfunction has a role in the early stages and progression of renal diseases, such as cystogenesis and acute tubular necrosis (ATN). In this review, we focus on the central role of cilia in kidney development and illustrate how defects in cilia are associated with renal disease progression.
Drinking natural water unchangeably is associated with reduced all-cause mortality in elderly people: A longitudinal prospective study from China

Objective Because of rapid economic growth and followed urban expansion in China, many people drinking natural water had to change their water sources to tap water. We aimed to test the unknown association that whether continued use of natural water for drinking is different from switching to tap water in all-cause mortality risks in elderly people. Methods In total, based on Chinese Longitudinal Healthy Longevity Survey, 26,688 elderly participants drinking natural water from childhood to young-old were included in the final analyses. Associations between whether changing drinking water sources or not and all-cause mortality risk were then estimated by Cox regression models with the use of multiple propensity score methods, and the primary analysis used propensity score matching, with other propensity score methods confirming the robustness of the results. Results Baseline characteristics were fairly well balanced by the three post-randomization methods. During a median follow-up period of 3.00 (IQR: 1.52, 5.73) years, 21,379 deaths were recorded. The primary analysis showed people using natural water unchangeably was associated with a lower risk of all-cause mortality than those switching to tap water in later life (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001). Other propensity score methods, as well as Cox regression analysis without using propensity score methods, showed similar results. Conclusions Among elderly people depending on natural water for drinking from their childhood to young-old in China, continued use of natural water was associated with a lower all-cause mortality risk than conversion to tap water later. Further studies in different countries and populations are needed to verify our conclusions.