Miracle-dz/UniFAR-FTUs huggingface dataset:
Tanshinone IIA Suppresses Proliferation and Inflammatory Cytokine Production of Synovial Fibroblasts from Rheumatoid Arthritis Patients Induced by TNF-α and Attenuates the Inflammatory Response in AIA Mice

Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease in which activated RA fibroblast-1ike synoviocytes (RA-FLSs) are one of the main factors responsible for inducing morbidity. Previous reports have shown that RA-FLSs have proliferative features similar to cancer cells, in addition to causing cartilage erosion that eventually causes joint damage. Thus, new therapeutic strategies and drugs that can effectively contain the abnormal hyperplasia of RA-FLSs and restrain RA development are necessary for the treatment of RA. Tanshinone IIA (Tan IIA), one of the main phytochemicals isolated from Salvia miltiorrhiza Bunge, is capable of promoting RA-FLS apoptosis and inhibiting arthritis in an AIA mouse model. In addition, RA patients treated at our clinic with Tan IIA showed significant improvements in their clinical symptoms. However, the details of the molecular mechanism by which Tan IIA effects RA are unknown. To clarify this mechanism, we evaluated the antiproliferative and inhibitory effects of proinflammatory factor production caused by Tan IIA to RA-FLSs. We demonstrated that Tan IIA can restrict the proliferation, migration, and invasion of RA-FLSs in a time- and dose-dependent manner. Moreover, Tan IIA effectively suppressed the increase in mRNA expression of some matrix metalloproteinases and proinflammatory factors induced by TNF-α in RA-FLSs, resulting in inflammatory reactivity inhibition and blocking the destruction of the knee joint. Through the integration of network pharmacology analyses with the experimental data obtained, it is revealed that the effects of Tan IIA on RA can be attributed to its influence on different signaling pathways, including MAPK, AKT/mTOR, HIF-1, and NF-kB. Taken together, these data suggest that the compound Tan IIA has great therapeutic potential for RA treatment.
Disparity Sensitivity and Binocular Integration in Mouse Visual Cortex Areas

Binocular disparity, the difference between the two eyes' images, is a powerful cue to generate the 3D depth percept known as stereopsis. In primates, binocular disparity is processed in multiple areas of the visual cortex, with distinct contributions of higher areas to specific aspects of depth perception. Binocular disparity, the difference between the two eyes' images, is a powerful cue to generate the 3D depth percept known as stereopsis. In primates, binocular disparity is processed in multiple areas of the visual cortex, with distinct contributions of higher areas to specific aspects of depth perception. Mice, too, can perceive stereoscopic depth, and neurons in primary visual cortex (V1) and higher-order, lateromedial (LM) and rostrolateral (RL) areas were found to be sensitive to binocular disparity. A detailed characterization of disparity tuning across mouse visual areas is lacking, however, and acquiring such data might help clarifying the role of higher areas for disparity processing and establishing putative functional correspondences to primate areas. We used two-photon calcium imaging in female mice to characterize the disparity tuning properties of neurons in visual areas V1, LM, and RL in response to dichoptically presented binocular gratings, as well as random dot correlograms (RDC). In all three areas, many neurons were tuned to disparity, showing strong response facilitation or suppression at optimal or null disparity, respectively, even in neurons classified as monocular by conventional ocular dominance (OD) measurements. Neurons in higher areas exhibited broader and more asymmetric disparity tuning curves compared with V1, as observed in primate visual cortex. Finally, we probed neurons' sensitivity to true stereo correspondence by comparing responses to correlated RDC (cRDC) and anticorrelated RDC (aRDC). Area LM, akin to primate ventral visual stream areas, showed higher selectivity for correlated stimuli and reduced anticorrelated responses, indicating higher-level disparity processing in LM compared with V1 and RL. SIGNIFICANCE STATEMENT A major cue for inferring 3D depth is disparity between the two eyes' images. Investigating how binocular disparity is processed in the mouse visual system will not only help delineating the role of mouse higher areas for visual processing, but also shed light on how the mammalian brain computes stereopsis. We found that binocular integration is a prominent feature of mouse visual cortex, as many neurons are selectively and strongly modulated by binocular disparity. Comparison of responses to correlated and anticorrelated random dot correlograms (RDC) revealed that lateromedial area (LM) is more selective to correlated stimuli, while less sensitive to anticorrelated stimuli compared with primary visual cortex (V1) and rostrolateral area (RL), suggesting higher-level disparity processing in LM, resembling primate ventral visual stream areas.
Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase to ensure proper centriole duplication cycle

Centrioles duplicate in the interphase only once per cell cycle. Newly formed centrioles remain associated with their mother centrioles. The two centrioles disengage at the end of mitosis, which licenses centriole duplication in the next cell cycle. Therefore, timely centriole disengagement is critical for the proper centriole duplication cycle. However, the mechanisms underlying centriole engagement during interphase are poorly understood. Here, we show that Cep57 and Cep57L1 cooperatively maintain centriole engagement during interphase. Co-depletion of Cep57 and Cep57L1 induces precocious centriole disengagement in the interphase without compromising cell cycle progression. The disengaged daughter centrioles convert into centrosomes during interphase in a Plk1-dependent manner. Furthermore, the centrioles reduplicate and the centriole number increases, which results in chromosome segregation errors. Overall, these findings demonstrate that the maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for the tight control of centriole copy number and thus for proper chromosome segregation.
Reverse regression increases power for detecting trans-eQTLs

Trans-acting expression quantitative trait loci (trans-eQTLs) are genetic variants affecting the expression of distant genes. They account for ≥70% expression heritability and could therefore facilitate uncovering mechansisms underlying the origination of complex diseases. However, unlike cis-eQTLs, identifying trans-eQTLs is challenging because of small effect sizes, tissue-specificity, and the severe multiple-testing burden. Trans-eQTLs affect multiple target genes, but aggregating evidence over individual SNP-gene associations is hampered by strong gene expression correlations resulting in correlated p-values. Our method Tejaas predicts trans-eQTLs by performing L2-regularized ‘reverse’ multiple regression of each SNP on all genes, aggregating evidence from many small trans-effects while being unaffected by the strong expression correlations. Combined with a novel non-linear, unsupervised k-nearest-neighbor method to remove confounders, Tejaas predicted 18851 unique trans-eQTLs across 49 tissues from GTEx. They are enriched in open chromatin, enhancers and other regulatory regions. Many overlap with disease-associated SNPs, pointing to tissue-specific transcriptional regulation mechanisms. Tejaas is available under GPL at https://github.com/soedinglab/tejaas.
VviMYB41 orthologs contribute to the water deficit induced suberization of grapevine fine roots

The permeability of roots to water and nutrients is controlled through a variety of mechanisms and one of the most conspicuous is the presence of structures such as the Casparian strips and suberin lamellae. Roots actively regulate the creation of these structures developmentally, along the length of the root, and in response to the environment, including abiotic stresses such as drought. In the current study, we characterized the suberin composition along the length of grapevine fine roots during development and in response to water deficit. In parallel samples we quantified changes in expression of suberin biosynthesis- and deposition-related gene families (via RNAseq) allowing the identification of drought-responsive suberin-related genes. Grapevine suberin composition did not differ between primary and lateral roots, and was similar to that of other species. Under water deficit there was a global upregulation of suberin biosynthesis which resulted in an increase of suberin specific monomers, but without changes in their relative abundances, and this upregulation took place across all the developmental stages of fine roots. These changes corresponded to the upregulation of numerous suberin biosynthesis- and deposition-related genes which included orthologs of the previously characterized AtMYB41 transcriptional factor. Functional validation of two grapevine MYB41 orthologs, VviMYB41 and VviMYB41-like, confirmed their ability to globally upregulate suberin biosynthesis and deposition. This study provides a detailed characterization of the developmental and water deficit induced suberization of grapevine fine roots and identifies important orthologs responsible for suberin biosynthesis, deposition, and its regulation in grape. One sentence summary Our study details the biochemical changes and molecular regulation of how grapevines decrease their root permeability during drought.
Virulence of Aeromonas salmonicida: Lack of Relationship with Phenotypic Characteristics

Abstract The pathogenicity of 28 Aeromonas salmonicida isolates was investigated by intraperitoneal injection into juvenile brook trout Salvelinus fontinalis. Ten isolates were found to be virulent, killing 100% or 87–100% of experimental animals following injections of 1 × 106 or 1 × 103 colony-forming units (CFU)/fish, respectively. All virulent isolates possessed an A layer, autoaggregated in liquid culture, and were positive on Coomassie brilliant blue and Congo red (CR) media. Nine isolates, which were negative for all of the above characteristics, were avirulent in fish and caused no mortality following an injection of 1 × 106 CFU/fish. The last group of nine isolates was also avirulent (no mortality after an injection of 1 × 106 CFU/fish) and are referred to as A+ avirulent strains because they possess the same in vitro characteristics as the virulent strains described above. For all isolates, the following cell-surface-related properties were then investigated: Cell-surface hydrophobicity, presenc.
The Impact of Isolation Measures Due to COVID-19 on Energy Intake and Physical Activity Levels in Australian University Students

Background: The pandemic inflicted by coronavirus disease 2019 (COVID-19) resulted in physical isolation measures in many parts of the world. In Australia, nationwide restrictions included staying at home, unless seeking medical care, providing care, purchasing food, undertaking exercise, or attending work in an essential service. All undergraduate university classes transitioned to online, mostly home-based learning. This disruption to daily life may have consequences for eating and physical activity patterns. Methods: In this observational study, we examined the effect of isolation measures, during the early phase of the COVID-19 pandemic in Australia (March/April), on diet (24-hour diet recall, ASA-24) and physical activity (Active Australia Survey) patterns among third-year biomedical students in Brisbane, Australia. Findings were compared to students enrolled in the same course in the previous two years. Results: In females, energy intake was ~20% greater in 2020 compared with 2018 and 2019, and the frequency of snacking and energy density of consumed snacks were also increased. In males, there was no difference in energy intake or snacking behaviour. Physical activity was impacted for both sexes, whereby fewer students undertook any walking activity and, of those that did, time spent doing so was less compared with 2018 and 2019. The proportion of students reporting any vigorous activity was not different for males or females but, among males who participated in this level of activity, the duration was less in 2020 compared with previous years. The proportion of male and female students achieving sufficient levels of activity, defined by at least 150 mins over at least 5 sessions, was ~30% less in 2020. Indeed, the majority of students reported as having undertaken less physical activity than usual. Conclusions: Increased energy intake for females and reduced physical activity for males and females demonstrate impacts of isolation measures that may have deleterious consequences for physical and mental wellbeing, with the potential to affect long-term nutrition and activity patterns.
Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder: The roles of BDNF and APOE polymorphisms

Objective. To assess the utility of the modulation of motor cortex (M1) excitability by continuous theta-burst stimulation (cTBS) as a physiologic biomarker for adults with autism spectrum disorder (ASD), and to evaluate the influences of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms on cTBS aftereffects. Methods. 44 neurotypical individuals (NT; age 21-65, 34 males) and 19 age-matched adults with high-functioning ASD (age 21-58, 17 males) underwent M1 cTBS. Cortico-motor reactivity was assessed before cTBS and thereafter every 5-10 minutes for 60 minutes (T5-T60). Results. Logistic regressions found cTBS-induced change in amplitude of motor evoked potentials ({Delta}MEP) at T15 was a significant predictor of ASD diagnosis (p=0.04). {Delta}MEP at T15 remained a significant predictor of diagnosis among BDNF Met+ subjects and APOE{varepsilon}4- subjects (p-values < 0.05) but not BDNF Met- subjects. {Delta}MEP at T30 was the best predictor of diagnosis among APOE{varepsilon}4+ subjects (p = 0.08). Conclusions. We confirm previous findings on the utility of cTBS measures of plasticity for adults with ASD, and we find the diagnostic utility of cTBS is modulated by BDNF and APOE SNPs. Significance. It is important to control for BDNF and APOE polymorphisms when comparing TBS aftereffects in ASD and NT individuals.
Isolation of Eyespots of Green Algae and Analyses of Pigments

Eyespot granules were isolated from cells of Pyramimonas parkeae Norris et Pearson (Prasinophyceae) and their morphology and pigment composition were analyzed. Isolated eyespot granules were fixed with osmium tetroxide and examined by scanning and transmission electron microscopy. The isolated eyespot granules were 0.15-0.20 μιη in diameter, and were associated with several kinds of structures, e. g. membranes. Eyespot pigments were analyzed by high performance liquid chromatography (HPLC). The major components were α-, β-, and γ-carotene, other pigments were virtually absent. The ratio of aand -carotenes was l : 6. Eyespots of Mesostigma viride Lauterborn (Prasinophyceae) and female gametes of Bryopsis maxima Okamura (Ulvophyceae) were also isolated, and their pigments were investigated. The major pigment of isolated eyespots of M. viride was carotene, that of B. maxima was α-carotene.
Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation

Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation.
Ibex-Associated Malignant Catarrhal Fever in Duikers (Cephalophus Spp)

Eight duikers, representing 3 different species cohoused in a single zoological collection, died in a 10-month period. Black, red-flanked, and yellow-backed duikers were affected, appearing clinically with a combination of anorexia, diarrhea, ataxia, tremors, and/or stupor, followed by death within 72 hours of onset of clinical signs. Consistent gross findings were pulmonary ecchymoses (8/8), generalized lymphadenomegaly (6/8), ascites (5/8), and pleural effusion (4/8). Dense lymphocyte infiltrates and arteritis affected numerous tissues in most animals. Ibex-associated malignant catarrhal fever (MCF) viral DNA was detected in all cases by polymerase chain reaction and in situ hybridization. Identical ibex-MCF virus sequence was detected in spleen of a clinically healthy ibex (Capra ibex) housed in a separate enclosure 35 meters away from the duikers.
UbcH5 interacts with substrates to participate in lysine selection with the E3 ubiquitin ligase CHIP.

The E3 ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) plays a critical role in regulating the ubiquitin-dependent degradation of misfolded proteins. CHIP mediates the ubiquitination of the alpha-amino terminus of substrates with the E2 Ube2w and facilitates the ubiquitination of lysine residues with the E2 UbcH5. While it is known that Ube2w directly interacts with disordered regions at the N-terminus of its substrates, it is unclear how CHIP and UbcH5 mediate substrate lysine selection. Here, we have decoupled the contributions of the E2, UbcH5, and the E3, CHIP, in ubiquitin transfer. We show that UbcH5 selects substrate lysine residues independent of CHIP, and CHIP participates in lysine selection by fine-tuning the subset of substrate lysines that are ubiquitinated. We also identify lysine 128 near the C-terminus of UbcH5 as a critical residue for efficient ubiquitin transfer by UbcH5 in both the presence and absence of CHIP. Together, these data demonstrate an important role for UbcH5/substrate interactions in mediating efficient ubiquitin transfer by the CHIP/UbcH5 complex.
CRISPR-Cas12a–assisted PCR tagging of mammalian genes

Fueller et al. describe a simple one-step procedure for quick and scalable chromosomal tagging of genes in mammalian cells using PCR products that contain all elements necessary for Cas12a tagging: homology arms and a guide RNA gene for chromosomal insertion, the tag (such as GFP), and a selection marker.
Genetic diversity of Pseudomonas syringae pv. syringae causing leaf blight of litchi in Bangladesh

Leaf blight of caused by Pseudomonas syringae pv . syringae is a severe disease of litchi saplings, which is considered as a threat for raising healthy sapling of the fruit in Bangladesh. A survey was conducted to find out incidence and severity of the disease in five regions of Bangladesh namely Rajshahi, Dinajpur, Mymensingh, Barishal and Khagrachari. The highest disease incidence was recorded in Dinajpur and Kagrachari regions and the lowest in Mymensingh region. On the other hand, the highest disease severity was found in Dinajpur and Kagrachari regions and the lowest in Mymensingh region. Another experiment was conducted to determine genetic diversity of the causal bacterium following molecular study. Twenty five diseased samples of bacterial leaf blight of litchi were collected from 25 locations in five regions and one isolate of P. syringae pv . syringae was isolated from each sample. The values of pair-wise comparisons of Neis (1972) genetic distance among5 different locations of P. syringae pv . syringae were computed. From the UPGMA dendrogram drawn on the basis of Neis (1972) genetic distances and comparatively the highest genetic distance (0.9163) was observed in Khajrachari vs Barishal, Mymensingh vs Barishal and Rajshahi vs Mymensingh but Dinajpur was close to the Barishal with the least genetic distance (0.3567). Thus, the results indicate that remarkable genetic diversity exists among the isolates of P. syringae pv. syringae from different origins Bangladesh. DOI: http://dx.doi. org/10.3329/sja.v12i1. 21121 SAARC J. Agri. , 12(1): 150-161 (2014)
Development and initial validation of the Queer People of Color Identity Affirmation Scale.

Despite growing literature on sexual minority (SM; e.g., lesbian, gay, bisexual, queer, asexual) people of Color (PoC), there is a dearth of research examining positive aspects of SM-PoC identity. This article presents the development and initial validation of the Queer People of Color Identity Affirmation Scale (QPIAS). First, items were developed through interviews with SM-PoC (N = 10) and then pilot-tested (N = 293). We then administered the scale to a second sample of SM-PoC (N = 703), which was randomly divided for exploratory and confirmatory factor analyses. The final QPIAS consists of 12 items and 2 subscales: Identity-Based Growth and Identity Cohesion. Participant performance on the final QPIAS was compared to other constructs of identity and psychosocial wellbeing to assess convergent validity. As predicted, the QPIAS was significantly positively associated with resilience, empowerment, sexual identity affirmation, and ethnoracial identity affirmation, and negatively associated with depression and sexual and ethnoracial identity conflict. Results also suggest that this scale may be useful in predicting resilience and empowerment beyond existing measures of sexual and ethnoracial identity affirmation. Use of this scale may provide new information on factors contributing to wellbeing in this population and be a beneficial tool in multiculturally competent assessment. (PsycInfo Database Record (c) 2020 APA, all rights reserved).