Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Diversity and Population Structure of Asian and European Common Wheat Accessions Based on Genotyping-By-Sequencing

Obtaining information on the genetic diversity and population structure of germplasm facilitates its use in wheat breeding programs. Recently, with the development of next-generation sequencing technology, genotyping-by-sequencing (GBS) has been used as a high-throughput and cost-effective molecular tool for examination of the genetic diversity of wheat breeding lines. In this study, GBS was used to characterize a population of 180 accessions of common wheat originating from Asia and Europe between the latitudes 30° and 45°N. In total, 24,767 high-quality single-nucleotide polymorphism (SNP) markers were used for analysis of genetic diversity and population structure. The B genome contained the highest number of SNPs, followed by the A and D genomes. The polymorphism information content was in the range of 0.1 to 0.4, with a mean of 0.26. The distribution of SNPs markers on the 21 chromosomes ranged from 243 on chromosome 4D to 2,337 on chromosome 3B. Structure and cluster analyses divided the panel of accessions into two subgroups (G1 and G2). G1 principally consisted of European and partial Asian accessions, and G2 comprised mainly accessions from the Middle East and partial Asia. Molecular analysis of variance showed that the genetic variation was greater within groups (99%) than between groups (1%). Comparison of the two subgroups indicated that G1 and G2 contained a high level of genetic diversity. The genetic diversity of G2 was slightly higher as indicated by the observed heterozygosity (Ho) = 0.23, and unbiased diversity index (uh) = 0.34. The present results will not only help breeders to understand the genetic diversity of wheat germplasm on the Eurasian continent between the latitudes of 30° and 45°N, but also provide valuable information for wheat genetic improvement through introgression of novel genetic variation in this region.
Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection

The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans, from asymptomatic or mild disease to severe disease that can require mechanical ventilation. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from indiviuals that go on to become infected with SARS-CoV-2. Here, we utilized data from a screen of genetically diverse mice from the Collaborative Cross (CC) infected with SARS-CoV to determine whether circulating baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Further, early control of virus in the lung correlates with an increased abundance of activated CD4 and CD8 T cells and regulatory T cells prior to infections across strains. A basal propensity of T cells to express IFNg and IL17 over TNFa also correlated with early viral control. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. While future studies of human samples prior to infection with SARS-CoV-2 are required, our studies in mice with SARS-CoV serve as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease. Summary We used a screen of genetically diverse mice from the Collaborative Cross infected with mouse-adapted SARS-CoV in combination with comprehensive pre-infection immunophenotyping to identify baseline circulating immune correlates of severe virologic and clinical outcomes upon SARS-CoV infection.
Determining the inherent reaction-diffusion properties of actin-binding proteins in cells by incorporating genetic engineering to FRAP-based framework

Proteins in cells undergo repeated association to other molecules, thereby reducing the apparent extent of their intracellular diffusion. While much effort has been made to analytically decouple these combined effects of pure diffusion and chemical reaction, it is difficult to attribute the measured quantities to the nature of specific domains of the probed proteins particularly if, as is often the case, the protein has multiple domains to independently interact with the same types but different molecules. Motivated by the common goal in cell signaling research aimed at identifying the protein domains responsible for particular intermolecular interactions, here we describe a new approach to determining the domain-level reaction and pure diffusion properties. To validate this methodology, we apply it to transgelin-2, an actin-binding protein whose intracellular dynamics remains elusive. We develop a fluorescence recovery after photobleaching (FRAP)-based framework, in which comprehensive combinations of domain-deletion mutants are created with genetic engineering, and the difference among the mutants in FRAP response is analyzed. We demonstrate that transgelin-2 in cells interacts with F-actin via two separate domains, and the chemical equilibrium constant of the interaction is determined at the individual domain levels. Its pure diffusion properties independent of the association to F-actin is also obtained. This approach requires some effort to construct the mutants, but instead enables in situ domain-level determination of the physicochemical properties, which will be useful, as specifically shown here for transgelin-2, in addressing the signaling mechanism of cellular proteins.
SARS-CoV-2 Nsp1 suppresses host but not viral translation through a bipartite mechanism

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly contagious virus that underlies the current COVID-19 pandemic. SARS-CoV-2 is thought to disable various features of host immunity and cellular defense. The SARS-CoV-2 nonstructural protein 1 (Nsp1) is known to inhibit host protein translation and could be a target for antiviral therapy against COVID-19. However, how SARS-CoV-2 circumvents this translational blockage for the production of its own proteins is an open question. Here, we report a bipartite mechanism of SARS-CoV-2 Nsp1 which operates by: (1) hijacking the host ribosome via direct interaction of its C-terminal domain (CT) with the 40S ribosomal subunit and (2) specifically lifting this inhibition for SARS-CoV-2 via a direct interaction of its N-terminal domain (NT) with the 5’ untranslated region (5’ UTR) of SARS-CoV-2 mRNA. We show that while Nsp1-CT is sufficient for binding to 40S and inhibition of host protein translation, the 5’ UTR of SARS-CoV-2 mRNA removes this inhibition by binding to Nsp1-NT, suggesting that the Nsp1-NT-UTR interaction is incompatible with the Nsp1-CT-40S interaction. Indeed, lengthening the linker between Nsp1-NT and Nsp1-CT of Nsp1 progressively reduced the ability of SARS-CoV-2 5’ UTR to escape the translational inhibition, supporting that the incompatibility is likely steric in nature. The short SL1 region of the 5’ UTR is required for viral mRNA translation in the presence of Nsp1. Thus, our data provide a comprehensive view on how Nsp1 switches infected cells from host mRNA translation to SARS-CoV-2 mRNA translation, and that Nsp1 and 5’ UTR may be targeted for anti-COVID-19 therapeutics.
Telmisartan Potentiates Insulin Secretion via Ion Channels, Independent of the AT1 Receptor and PPARγ

Angiotensin II type 1 receptor blockers (ARBs), as antihypertensive drugs, have drawn attention for their benefits to individuals with diabetes and prediabetes. However, the effects of ARBs on insulin secretion remain unclear. Here, we investigated the insulinotropic effects of ARBs (telmisartan, valsartan, and irbesartan) and the underlying electrophysiological mechanism in rat islets. We found that only telmisartan among the three ARBs exhibited an insulin secretagogue role. Distinct from other ARBs, telmisartan exerted effects on ion channels including voltage-gated potassium (Kv) channels and voltage-gated Ca2+ channels to promote extracellular Ca2+ influx, thereby potentiating insulin secretion in a glucose-dependent manner. We observed that the peroxisome proliferator-activated receptor γ pathway was not involved in these telmisartan-induced effects. Furthermore, we identified that telmisartan at least directly inhibited Kv2.1 channel through construction of a Chinese hamster ovary cell line with Kv2.1 channel overexpression. Acute exposure of type 2 diabetes model (db/db) mice to a telmisartan dose equivalent to therapeutic doses in humans resulted in lower blood glucose and increased plasma insulin concentration in the oral glucose tolerance test. We further observed the telmisartan-induced insulinotropic and electrophysiological effects on pathological pancreatic islets isolated from db/db mice. Collectively, our results establish an important function of telmisartan distinct from other ARBs in the treatment of diabetes.
Antimetabolic cooperativity with the clinically approved kidrolase and tyrosine kinase inhibitors to eradicate cml stem cells

Long-term treatment with tyrosine kinase inhibitors (TKI) represents an effective treatment for chronic myeloid leukemia (CML) and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells indicate that new therapeutic strategies are needed to prevent molecular relapses. We investigated the metabolic pathways responsible for CML surviving to Imatinib exposure and its potential therapeutic utility to improve the efficiency of TKI against CML stem cells. Using complementary cell-based techniques, we demonstrated that TKI suppressed glycolysis in a large panel of BCR-ABL1 + cell lines as well as in primary CD34+ stem-like cells from CML patients. However, compensatory glutamine-dependent mitochondrial oxidation supported ATP synthesis and CML cell survival. Glutamine metabolism was inhibited by L-asparaginases such as Kidrolase without inducing predominant CML cell death. Clinically relevant concentrations of TKI render CML progenitors and stem cells susceptible to Kidrolase. The combination of TKI with L-asparaginase reactivated the intinsic apoptotic pathway leading to efficient CML cell death. Thus, targeting glutamine metabolism with the clinically-approved drug Kidrolase, in combination with TKI that suppress glycolysis represents an effective and widely applicable therapeutic strategy for eradicating CML stem cells.
Variability in the diet diversity of catfish highlighted through DNA barcoding

Identification and quantification of fish diet diversity was the first step in understanding the food web dynamics and ecosystem energetics, where the contribution of DNA barcoding technique has been important. We used DNA barcoding to identify the stomach contents of a euryhaline, benthophagous catfish Ariius maculatus. From 40 catfish stomach items sampled in two different seasons, we barcoded 67 prey items of chordates and macro-invertebrates identified as belonging to 13 species in 4 major phyla (viz., Chordate, Arthropod, Annelida and Mollusca). It is important to note that the mollusc taxa (Meritrix meritrix and Perna viridis) and the species of fish (Stolephorus indicus) could not be found among the gut contents of A. maculatus sampled during the pre- and post-monsoon season, respectively. Among the chordate diets of A. maculatus, Eubleekeria splendens (23.5%) and Stolephorus indicus (23.5%) were the major prey taxa during pre-monsoon season. The hermit crabs forms the major constituents of both pre- and post-monsoon seasons, among invertebrate taxa. Polychaete, Capitella capitata (25.92%) was abundantly consumed invertebrates next to hermit crabs. We noticed that in pre-monsoon A. maculatus was more piscivorous than post-monsoon. As revealed through Kimura-2 parametric pair-wise distance analysis, the diet diversity was relatively higher in post-monsoon. The accumulation curve estimated 57 haplotypes within 14 barcoded species (including the host A. maculatus). Majority of haplotypes were found in Chordates (47.36%) followed by Arthropods (28.07%), Annelids (14.03%) and Mollusca (10.52%), respectively. This study also highlights that there is a growing concern about A. maculatus’s aggressive predation on commercially important stocks of fish and invertebrates. We will continue to expand the coverage of species barcoded in the reference database, which will become more significant as meta- and environmental DNA barcoding techniques become cheaper and prevalent.
Cold Storage of Oranges as a Disinfestation Treatment Against the Fruit Flies Dacus tryoni (Froggau) and Ceratitis capitata (Wiedemann) (Diptera: Tephritidae)

The presence in Australia of the Queensland fruit fly, Dacus tryoni (Froggatt), and Mediterranean fruit fly, Ceratitis capitata (Wiedemann), restricts access for Australian oranges to some world markets because of plant quarantine regulations. Oranges infested with eggs, young larvae, or old larvae of these insects were stored for various periods at 1 or 1.5°C. For both insects, eggs were the stage most susceptible to cold in oranges, and no significant difference in cold tolerance was seen between young and old larvae. D. tryoni larvae were generally less cold-tolerant than those of C. capitata . The effectiveness of 16 d storage at 1.0°C (±0.5°C) against both insects was demonstrated by 100%mortality on treating more than 90,000 D. tryoni larvae and more than 40,000 C. capitata larvae in oranges.
Metabolic Reprogramming of Sulfur in Hepatocellular Carcinoma and Sulfane Sulfur-Triggered Anti-Cancer Strategy

Metabolic reprogramming is a cancer hallmark. Although the reprogramming of central carbon has been well documented, the role of sulfur metabolism has been largely overlooked. Additionally, the effects of sulfur are sometimes contradictory in tumorigenesis. In this study, we aimed to investigate the gene expression profile in hepatocellular carcinoma (HCC) and the effects of reactive sulfur species (RSS) on HCC tumor cells. Furthermore, the cell imaging technology was applied to discover some potential anti-cancer compounds. Gene Set Enrichment Analysis (GSEA) of Gene Expression Omnibus (GEO) dataset (GSE102083) revealed that sulfur amino acid-related metabolism and vitamin B6 binding activity in HCC tissues were downregulated. Calculation of the interaction network identified nine hub genes, among which eight were validated by differential expression and survival analysis in the TCGA_LIHC cohort, and two (CSE and CBS) had the highest enrichment degree. The metabolomics analysis suggested that the hub genes were associated with RSS metabolism including H2S, H2S2, cystine, cysteine, homocysteine, cystathionine, and methionine. The cell viability assay demonstrated that H2S2 had significant anti-cancer effects in HCC SNU398 tumor cells. The cell imaging assay showed that treatment with H2S2 remarkably increased intracellular sulfane sulfur content. On this basis, the anti-cancer activity of some other sulfane sulfur compounds, such as DATS and DADS, was further verified. Lastly, according to the fact that HCC tumor cells preferentially take in cystine due to high expression of SLC7A11 (a cystine/glutamate transporter), persulfided cysteine precursor (PSCP) was tested for its sulfane sulfur release capability and found to selectively inhibit HCC tumor cell viability. Collectively, this study uncovered sulfur metabolism in HCC was reprogrammed, and provided a potential therapeutic strategy for HCC by donating sulfane sulfur.
Placebo Analgesia, Nocebo Hyperalgesia, and the Cardiovascular System: A Qualitative Systematic Review

Background: Placebo/nocebo effects involve the autonomic nervous system, including cardiac activity, but studies have reported inconsistent findings on how cardiac activity is modulated following a placebo/nocebo effect. However, no systematic review has been conducted to provide a clear picture of cardiac placebo responses. Objective: The main goal of the present study is to review the effects of placebo analgesia and nocebo hyperalgesia on cardiac activity as measured by blood pressure, heart rate, and heart rate variability. Methods: Using several Boolean keyword combinations, the PubMed, EMBASE, PsycINFO, Cochrane Review Library, and ISI Web of Knowledge databases were searched until January 5, 2020, to find studies that analyzed blood pressure, heart rate, or heart rate variability indexes following a placebo analgesic/nocebo hyperalgesic effect. Results: Nineteen studies were found, with some reporting more than one index of cardiac activity; eight studies were on blood pressure, 14 studies on heart rate, and six on heart rate variability. No reliable association between placebo/nocebo effects and blood pressure or heart rate was found. However, placebo effects reduced, and nocebo effects increased low-frequency heart rate variability, and heart rate variability significantly predicted placebo effects in two studies. Conclusion: Placebo/nocebo effects can have reliable effects on heart rate variability, but not on heart rate and blood pressure.
The Effect of Ni-ZSM-5 Catalysts on Catalytic Pyrolysis and Hydro-Pyrolysis of Biomass

With the demand of energy and re-utilization of wastes, the renewable lignocellulosic biomass, has attracted increasing and significant attention for alleviating the growing energy crisis and environment problems. As main components of lignocellulosic biomass, lignin, cellulose, and hemicellulose are connected by hydrogen bond to form a compact skeleton structure, resulting the trenchant condition of biomass pyrolysis. Also, pyrolysis products of above three main constituents contain a large amount of oxygenates that cause low heating value, high corrosiveness, high viscosity, and instability. Meanwhile, zeolites are of considerable significance to the conversion of lignocellulosic biomass to desirable chemical products on account of fine shape selectivity and moderate acid sites and strength. Among numerous zeolites, ZSM-5-based catalysts have been most extensively studied, and the acidity and porosity of ZSM-5 can be tuned by changing the content of Si or Al in zeolite. Beyond that, doping of other metal elements, such as Mn, Co, Ni, Ga, Ce, Pt, into ZSM-5 is also an efficient way to regulate the strength and density of acid sites in zeolite precisely. This review focused on the recent investigation of Ni-modified microporous ZSM-5 used in catalytic pyrolysis of lignin and cellulose. The application of metal-modified hierarchical ZSM-5 is also covered.
Psychological Well-Being and Youth Autonomy: Comparative Analysis of Spain and Colombia

The construct of autonomy appears in literature associated with individual psychological wellbeing. In Ryff’s model, autonomy is presented as one of the dimensions of wellbeing, along with self-acceptance, positive relationships with others, environmental mastery, purpose in life, and personal growth. The present study compared the levels of autonomy and psychological wellbeing between Spanish and Colombian young people. Ryff’s Scale of Psychological Wellbeing and the Transition to Adulthood Autonomy (EDATVA) scales were used on a sample of 1,146 young people aged between 16 and 21; 506 Spaniards and 640 Colombians. Results showed differences in autonomy and in two of the four dimensions proposed by the EDATVA: self-organization and critical thinking. Similarly, important differences were observed in the subscales of positive relations and purpose in life. The importance of contextual factors in the development of psychological well-being and autonomy in young people in transition to adulthood is discussed.
Effectiveness of Surgical Face Masks in Reducing Acute Respiratory Infections in Non-Healthcare Settings: A Systematic Review and Meta-Analysis

Background: Acute respiratory illnesses (ARIs) are the most common respiratory infectious diseases among humans globally. Surgical mask (SM) wearing has been shown to be effective in reducing ARI among healthcare workers. However, the effectiveness of SM in reducing ARI in the non-healthcare settings remains unclear. This review aims to summarize and assess the association between SM wearing and ARI incidence, from existing interventional and observational studies conducted in non-healthcare settings. Methods: Systematic literature searches conducted in PubMed, Cochrane Library, and Embase databases identified 503 unique studies. After screening, 15 studies (5 randomized controlled trials and 10 observational studies) were assessed for reporting and methodological qualities. Proportions of ARI episodes in each group and adjusted summary statistics with their relevant 95% CIs were extracted. Data from 10 observational studies were pooled using the generic inverse variance method. Results: A total of 23,892 participants between 7 and 89 years old involved across 15 studies from 11 countries were involved. Key settings identified were Hajj, schools, and in-flight settings. A modest but non-significant protective effect of SM on ARI incidence was observed (pooled OR 0.96, 95% CI 0.8–1.15). Subgroup analysis according to age group, outcome ascertainment and different non-healthcare settings also revealed no significant associations between SM use and ARI incidence. Conclusion: Surgical mask wearing among individuals in non-healthcare settings is not significantly associated with reduction in ARI incidence in this meta-review.
Triggering Receptor Expressed on Myeloid Cell 2 R47H Exacerbates Immune Response in Alzheimer’s Disease Brain

The R47H variant in the microglial triggering receptor expressed on myeloid cell 2 (TREM2) receptor is a strong risk factor for Alzheimer’s disease (AD). To characterize processes affected by R47H, we performed an integrative network analysis of genes expressed in brains of AD patients with R47H, sporadic AD without the variant, and patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), systemic disease with early-onset dementia caused by loss-of-function mutations in TREM2 or its adaptor TYRO protein tyrosine kinase-binding protein (TYROBP). Although sporadic AD had few perturbed microglial and immune genes, TREM2 R47H AD demonstrated upregulation of interferon type I response and pro-inflammatory cytokines accompanied by induction of NKG2D stress ligands. In contrast, PLOSL had distinct sets of highly perturbed immune and microglial genes that included inflammatory mediators, immune signaling, cell adhesion, and phagocytosis. TREM2 knockout (KO) in THP1, a human myeloid cell line that constitutively expresses the TREM2- TYROBP receptor, inhibited response to the viral RNA mimetic poly(I:C) and phagocytosis of amyloid-beta oligomers; overexpression of ectopic TREM2 restored these functions. Compared with wild-type protein, R47H TREM2 had a higher stimulatory effect on the interferon type I response signature. Our findings point to a role of the TREM2 receptor in the control of the interferon type I response in myeloid cells and provide insight regarding the contribution of R47H TREM2 to AD pathology.