Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Novel Genetic Regulatory Region for Proprotein Convertase FURIN and Interferon Gamma in T Cells

The proprotein convertase enzyme FURIN promotes the proteolytic maturation of pro-proteins and thereby it serves as an important factor for maintaining cellular homeostasis. In T cells, FURIN is critical for maintaining the T regulatory cell dependent peripheral immune tolerance and intact T helper cell polarization. The enzymatic activity of FURIN is directly associated with its expression levels, but genetic determinants for cell-type specific Furin gene regulation have remained elusive. By exploring the histone acetyltransferase p300 binding patterns in T helper cells, a putative regulatory region at ca. 20kB upstream of Furin gene was identified. When this region was deleted with CRISPR/Cas9 the production of Furin mRNA was significantly reduced in activated mouse T cells. Genome-wide RNA profiling by sequencing revealed that the novel Furin regulator region also impacted the expression of several genes that have previously been associated with the Th1 type hall mark cytokine IFNγ regulation or function. Finally, Furin genetic regulatory region was found to specifically promote the secretion of IFNγ by activated T cells. In sum, our data unravels the presence of Furin expression regulatory region in T cells that has characteristics of a super-enhancer for Th1 cell fate.
Optimal Approach for Signal Detection in Steady-State Visual Evoked Potentials in Humans Using Single-Channel EEG and Stereoscopic Stimuli

In EEG studies, one of the most common ways to detect a weak periodic signal in the steady-state visual evoked potential (SSVEP) is spectral evaluation, a process that detects peaks of power present at notable temporal frequencies. However, the presence of noise decreases the signal-to-noise ratio (SNR), which in turn lowers the probability of successful detection of these spectral peaks. In this paper, using a single EEG channel, we compare the detection performance of four different metrics to analyse the SSVEP: two metrics that use spectral power density, and two other metrics that use phase coherency. We employ these metrics find weak signals with a known temporal frequency hidden in the SSVEP, using both simulation and real data from a stereoscopic apparent depth movement perception task. We demonstrate that out of these metrics, the phase coherency analysis is the most sensitive way to find weak signals in the SSVEP, provided that the phase information of the stimulus eliciting the SSVEP is preserved.
Region-Specific Effects of 10-Hz Transcranial Alternate Current Stimulation Over the Left Posterior Parietal Cortex and Primary Somatosensory Area on Tactile Two-Point Discrimination Threshold

Changes in α-band cortical oscillatory activity (8–13 Hz) affect perception; however, how these changes in the left posterior parietal cortex (PPC) and primary somatosensory cortex (S1), which play different roles in determining the two-point discrimination (TPD) threshold, affect TPD threshold remains unelucidated. Therefore, to determine TPD threshold, we aimed to investigate the function of the left PPC and S1 by applying α-band transcranial alternating current stimulation (α-tACS; 10 Hz). TPD threshold was examined at the pad of the right index finger, contralateral to the stimulation site, in 17 healthy adults using a custom-made, computer-controlled, two-point tactile stimulation device, with random application of either active or sham α-tACS over the left PPC (Experiment 1) and left S1 (Experiment 2). Then, 50% TPD threshold was obtained in the active and sham conditions via logistic regression analysis. Afterward, we compared the difference between the active and sham conditions at 50% TPD threshold in each region and found that α-tACS reduced TPD threshold when applied over the left PPC (P = 0.010); however, its effect was insignificant when applied over the left S1 (P = 0.74). Moreover, a comparison of the change in 50% TPD threshold among the regions revealed that α-tACS applied over the left PPC significantly reduced TPD threshold compared with that applied over the left S1 (P = 0.003). Although we did not reveal the actual changes in cortical activity induced by α-tACS, this is the first empirical evidence that α-tACS applied over the left PPC and left S1 exerts region-specific effects on determining TPD threshold assessed in the contralateral index finger pad by stimulation.
The Arabidopsis thaliana Class II Formin FH13 Modulates Pollen Tube Growth

Formins are a large, evolutionarily conserved family of actin-nucleating proteins with additional roles in regulating microfilament, microtubule, and membrane dynamics. Angiosperm formins, expressed in both sporophytic and gametophytic tissues, can be divided into two subfamilies, Class I and Class II, each often exhibiting characteristic domain organization. Gametophytically expressed Class I formins have been documented to mediate plasma membrane-based actin assembly in pollen grains and pollen tubes, contributing to proper pollen germination and pollen tube tip growth, and a rice Class II formin, FH5/RMD, has been proposed to act as a positive regulator of pollen tube growth based on mutant phenotype and overexpression data. Here we report functional characterization of the Arabidopsis thaliana pollen-expressed typical Class II formin FH13 (At5g58160). Consistent with published transcriptome data, live-cell imaging in transgenic plants expressing fluorescent protein-tagged FH13 under the control of the FH13 promoter revealed expression in pollen and pollen tubes with non-homogeneous signal distribution in pollen tube cytoplasm, suggesting that this formin functions in the male gametophyte. Surprisingly, fh13 loss of function mutations do not affect plant fertility but result in stimulation of in vitro pollen tube growth, while tagged FH13 overexpression inhibits pollen tube elongation. Pollen tubes of mutants expressing a fluorescent actin marker exhibited possible minor alterations of actin organization. Our results thus indicate that FH13 controls or limits pollen tube growth, or, more generally, that typical Class II formins should be understood as modulators of pollen tube elongation rather than merely components of the molecular apparatus executing tip growth.
Inflammation and Antiviral Immune Response Associated With Severe Progression of COVID-19

Coronavirus disease-2019 (COVID-19) is a novel respiratory disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It remains poorly understood how the host immune system responds to the infection during disease progression. We applied microarray analysis of the whole genome transcriptome to peripheral blood mononuclear cells (PBMCs) taken from severe and mild COVID-19 patients as well as healthy controls. Functional enrichment analysis of genes associated with COVID-19 severity indicated that disease progression is featured by overactivation of myeloid cells and deficient T cell function. The upregulation of TLR6 and MMP9, which promote the neutrophils-mediated inflammatory response, and the downregulation of SKAP1 and LAG3, which regulate T cells function, were associated with disease severity. Importantly, the regulation of these four genes was absent in patients with influenza A (H1N1). And compared with stimulation with hemagglutinin (HA) of H1N1 virus, the regulation pattern of these genes was unique in PBMCs response to Spike protein of SARS-CoV-2 ex vivo. Our data also suggested that severe SARS-CoV-2 infection largely silenced the response of type I interferons (IFNs) and altered the proportion of immune cells, providing a potential mechanism for the hypercytokinemia. This study indicates that SARS-CoV-2 infection impairs inflammatory and immune signatures in patients, especially those at severe stage. The potential mechanisms underpinning severe COVID-19 progression include overactive myeloid cells, impaired function of T cells, and inadequate induction of type I IFNs signaling.
Amplitude of Low-Frequency Fluctuations and Resting-State Functional Connectivity in Trait Positive Empathy: A Resting-State fMRI Study

Positive empathy is the ability to share and understand the positive emotions of others. In recent years, although positive empathy has received more and more attention, trait positive empathy (TPE)-related spontaneous brain activity during the resting state has not been extensively explored. We used the amplitude of low-frequency fluctuations (ALFFs) and resting-state functional connectivity (RSFC) of the resting-state functional magnetic resonance imaging signal to explore TPE-associated brain regions. We found that higher TPE was associated with higher ALFFs in the right insula and lower ALFFs in the right subgenual cingulate (SGC), right dorsomedial prefrontal cortex (dmPFC), and right precuneus. RSFC analyses showed that higher functional connectivity between the right insula and left parahippocampal gyrus, left inferior parietal lobule and left middle temporal gyrus were related to higher TPE. Moreover, the connection between the right dmPFC and the left medial orbitofrontal cortex, left middle occipital gyrus and left posterior cingulate cortex were positively related to TPE. Meanwhile, the strength of functional connectivity between the right SGC and left supplementary motor area was positively associated with TPE. These findings may indicate that TPE is linked to emotional (especially the experience of more positive emotions and better negative emotion regulation) and self-referential processing.
Insight Into the Strengthening Mechanism of the Al-Induced Cross-Linked Calcium Aluminosilicate Hydrate Gel: A Molecular Dynamics Study

Understanding and controlling the mechanical properties of calcium aluminosilicate hydrate (C-A-S-H) gel is essential to the performance improvement of cementing materials. This study characterizes the mechanical properties and failure mechanism of cross-linked C-A-S-H that have Al/Si ratios ranging from 0 to 0.20 by employing the reactive molecular dynamics simulation. In these constructed C-A-S-H models, the Al-induced cross-linking effect on the aluminosilicate chains is well reproduced. With the incorporation of aluminate species, layered C-S-H structure gradually transforms into three-dimensional C-A-S-H. The uniaxial tensile tests show that Al-induced cross-links significantly increase the cohesive force and stiffness of C-A-S-H along both y - and z -directions. In the C-A-S-H model with the Al/Si ratio equal to 0.2, in which all the bridging sites are cross-linked, the toughness along y-direction significantly improves the interlayer mechanical properties compared to those within the layers. The deformation mechanism of the C-A-S-H structure is also studied. Results show that the depolymerization of the calcium aluminosilicate skeleton is the main route to uptake the loading energy. Both the increase of y - and z -directional strength of the structure can be related to the increasing polymerization of aluminosilicate chains along that direction. This demonstrates the important role of aluminosilicate chains in resisting the external tensile loading. Besides, during the failure process in C-A-S-H elongation, the hydrolysis reactions of calcium silicate skeleton are caused by the coupling effect of loading and interlayer water “attack. ” While the Al-O-Si bond breakage results from the protonation of bridging oxygen atom, the hydrolytic reaction of Si-O-Si is initiated by five-coordinate silicon formation. Both pathways weaken the bridging bond and thus result in the breakage of T-O-Si, where T is Al or Si.
Establishment and Application of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry for Detection of Shewanella Genus

Shewanella species are widely distributed in the aquatic environment and aquatic organisms. They are opportunistic human pathogens with increasing clinical infections reported in recent years. However, there is a lack of a rapid and accurate method to identify Shewanella species. We evaluated here matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid identification of Shewanella. A peptide mass reference spectra (PMRS) database was constructed for the type strains of 36 Shewanella species. The main spectrum projection (MSP) cluster dendrogram showed that the type strains of Shewanella species can be effectively distinguished according to the different MS fingerprinting. The PMRS database was validated using 125 Shewanella test strains isolated from various sources and periods; 92.8% (n = 116) of the strains were correctly identified at the species level, compared with the results of multilocus sequence analysis (MLSA), which was previously shown to be a method for identifying Shewanella at the species level. The misidentified strains (n = 9) by MALDI-TOF MS involved five species of two groups, i.e., Shewanella algae–Shewanella chilikensis–Shewanella indica and Shewanella seohaensis–Shewanella xiamenensis. We then identified and defined species-specific biomarker peaks of the 36 species using the type strains and validated these selected biomarkers using 125 test strains. Our study demonstrated that MALDI-TOF MS was a reliable and powerful tool for the rapid identification of Shewanella strains at the species level.
Low-Latency Spiking Neural Networks Using Pre-Charged Membrane Potential and Delayed Evaluation

Spiking neural networks (SNNs) have attracted many researchers’ interests due to its biological plausibility and event-driven characteristic. In particular, recently, many studies on high-performance SNNs comparable to the conventional analog-valued neural networks (ANNs) have been reported by converting weights trained from ANNs into SNNs. However, unlike ANNs, SNNs have an inherent latency that is required to reach the best performance because of differences in operations of neuron. In SNNs, not only spatial integration but also temporal integration exists, and the information is encoded by spike trains rather than values in ANNs. Therefore, it takes time to achieve a steady-state of the performance in SNNs. The latency is worse in deep networks and required to be reduced for the practical applications. In this work, we propose a pre-charged membrane potential (PCMP) for the latency reduction in SNN. A variety of neural network applications (e.g., classification, autoencoder using MNIST and CIFAR-10 datasets) are trained and converted to SNNs to demonstrate the effect of the proposed approach. The latency of SNNs is successfully reduced without accuracy loss. In addition, we propose a delayed evaluation method (DE), by which the errors during the initial transient are discarded. The error spikes occurring in the initial transient is removed by DE, resulting in the further latency reduction. DE can be used in combination with PCMP for further latency reduction. Finally, we also show the advantages of the proposed methods in improving the number of spikes required to reach a steady-state of the performance in SNNs for energy-efficient computing.
Immunoreactivity of Vesicular Glutamate Transporter 2 Corresponds to Cytochrome Oxidase-Rich Subcompartments in the Visual Cortex of Squirrel Monkeys

Cytochrome oxidase (CO) histochemistry has been used to reveal the cytoarchitecture of the primate brain, including blobs/puffs/patches in the striate cortex (V1), and thick, thin and pale stripes in the middle layer of the secondary visual cortex (V2). It has been suggested that CO activity is coupled with the spiking activity of neurons, implying that neurons in these CO-rich subcompartments are more active than surrounding regions. However, we have discussed possibility that CO histochemistry represents the distribution of thalamo-cortical afferent terminals that generally use vesicular glutamate transporter 2 (VGLUT2) as their main glutamate transporter, and not the activity of cortical neurons. In this study, we systematically compared the labeling patterns observed between CO histochemistry and immunohistochemistry (IHC) for VGLUT2 from the system to microarchitecture levels in the visual cortex of squirrel monkeys. The two staining patterns bore striking similarities at all levels of the visual cortex, including the honeycomb structure of V1 layer 3Bβ (Brodmann's layer 4A), the patchy architecture in the deep layers of V1, the superficial blobs of V1, and the V2 stripes. The microarchitecture was more evident in VGLUT2 IHC, as expected. VGLUT2 protein expression that produced specific IHC labeling is thought to originate from the thalamus since the lateral geniculate nucleus (LGN) and the pulvinar complex both show high expression levels of VGLUT2 mRNA, but cortical neurons do not. These observations support our theory that the subcompartments revealed by CO histochemistry represent the distribution of thalamo-cortical afferent terminals in the primate visual cortex.
Brain Ultrastructure: Putting the Pieces Together

Unraveling the fine structure of the brain is important to provide a better understanding of its normal and abnormal functioning. Application of high-resolution electron microscopic techniques gives us an unprecedented opportunity to discern details of the brain parenchyma at nanoscale resolution, although identifying different cell types and their unique features in two-dimensional, or three-dimensional images, remains a challenge even to experts in the field. This article provides insights into how to identify the different cell types in the central nervous system, based on nuclear and cytoplasmic features, amongst other unique characteristics. From the basic distinction between neurons and their supporting cells, the glia, to differences in their subcellular compartments, organelles and their interactions, ultrastructural analyses can provide unique insights into the changes in brain function during aging and disease conditions, such as stroke, neurodegeneration, infection and trauma. Brain parenchyma is composed of a dense mixture of neuronal and glial cell bodies, together with their intertwined processes. Intracellular components that vary between cells, and can become altered with aging or disease, relate to the cytoplasmic and nucleoplasmic density, nuclear heterochromatin pattern, mitochondria, endoplasmic reticulum and Golgi complex, lysosomes, neurosecretory vesicles, and cytoskeletal elements (actin, intermediate filaments, and microtubules). Applying immunolabeling techniques to visualize membrane-bound or intracellular proteins in neurons and glial cells gives an even better appreciation of the subtle differences unique to these cells across contexts of health and disease. Together, our observations reveal how simple ultrastructural features can be used to identify specific changes in cell types, their health status, and functional relationships in the brain.
An Experimental Investigation and Performance Evaluation of 1.5 TR Window Air-Conditioner by Using R22, R407C and R410A by Varying the Capillary Pitch

Due to ecological problems like Ozone depletion and Global warming certain refrigerants like R-22 have to be replaced. HCFC's (Hydro Chloro fluoro carbon) have been identified as the prime foremost cause of Ozone depletion. Driven by 1992 amendment to the Montreal-Protocol that calls for the phase out of HCFC's. HFC's (Hydro fluoro carbon) are substantially less damaging to the Ozone layer than HCFC's. Several refrigerants have emerged as substitutes to replace R-22, the most widely used Fluoro carbon refrigerant in the world. These include the environmentally friendly hydro carbon refrigerants such as R134a, R410A, R407A and R407C. In this present work problem of R-22 phase out in air conditioning application is addressed. The main objective of the project is Performance analysis of an window air conditioning system by using three refrigerants like R-22, R407C and R410A with different capillary pitches. In view of this it is proposed to carry out a number of experiments on window air conditioner of capacity 1.5 TR using R22, R407C and R410A by varying the capillary pitch. Further it is proposed to make a detailed analysis and comparison of the performance of these refrigerants at various pitches for an window air conditioner. From the results it is evident that the refrigerant with R410A with a capillary pitch of 18mm gave the best Coefficient of performance to retrofit an window air conditioner working on R22.
Case Report: De novo Variants of KMT2E Cause O'Donnell-Luria-Rodan Syndrome: Additional Cases and Literature Review

Introduction: O'Donnell-Luria-Rodan syndrome was recently identified as an autosomal dominant systemic disorder caused by variants in KMT2E. It is characterized by global developmental delay, some patients also exhibit autism, seizures, hypotonia, and/or feeding difficulties. Methods: Whole-exome sequencing of family trios were performed for two independent children with unexplained recurrent seizures and developmental delay. Both cases were identified as having de novo variants in KMT2E. We also collected and summarized the clinical data and diagnosed them with O'Donnell-Luria-Rodan syndrome. Structural-prediction programs were used to draw the variants' locations. Results: A 186 G>A synonymous variant [NM_182931. 3:exon4: c.186G>A (p.Ala62=)] was found in one family, resulting in alternative splicing acid. A 5417 C>T transition variant [NM_182931. 3:exon27: c.5417C>T (p.Pro1806Leu)] was found in another family, resulting in 1806 Pro-to-Leu substitution. Both variants were classified as likely pathogenic according to the ACMG (American College of Medical Genetics and Genomics) guidelines and verified by Sanger sequencing. Conclusion: To date, three studies of O'Donnell-Luria-Rodan syndrome have been reported with heterogeneous clinical manifestations. As a newly recognized inherited systemic disorder, O'Donnell-Luria-Rodan syndrome needs to be paid more attention, especially in gene testing.
Bryophyllum pinnatum Compounds Inhibit Oxytocin-Induced Signaling Pathways in Human Myometrial Cells

Bryophyllum pinnatum has been used in the treatment of premature labor, first in anthroposophic hospitals and, recently, in conventional settings as an add-on medication. In vitro work with hTERT human myometrial cells showed that B. pinnatum leaf press juice inhibits the increase of intracellular free calcium concentration induced by oxytocin, a hormone known to play a role in labor. Our aim was to identify fractions/compounds in B. pinnatum press juice that contribute to this inhibitory effect, and to investigate their effect on oxytocin-driven activation of the MAPK cascade. Several fractions/compounds from B. pinnatum press juice led to a concentration-dependent decrease of oxytocin-induced increase of intracellular free calcium concentration, but none of them was as strong as B. pinnatum press juice. However, the combination of a bufadienolide and a flavonoid-enriched fraction was as effective as B. pinnatum press juice, and their combination had a synergistic effect. B. pinnatum press juice inhibited oxytocin-driven activation of MAPKs SAPK/JNK and ERK1/2, an effect also exerted by the bufadienolide-enriched fraction. The effect of B. pinnatum press juice on oxytocin-induced signaling pathways was comparable to that of the oxytocin-receptor antagonist and tocolytic agent atosiban. Our findings further substantiate the use of B. pinnatum press juice preparations in the treatment of preterm labor.