Miracle-dz/UniFAR-FTUs huggingface dataset:
Rice stripe virus suppresses jasmonic acid-mediated resistance by hijacking brassinosteroid signaling pathway in rice

Rice stripe virus (RSV) is one of the most destructive viral diseases affecting rice production. However, so far, only one RSV resistance gene has been cloned, the molecular mechanisms underlying host-RSV interaction are still poorly understood. Here, we show that increasing levels or signaling of brassinosteroids (BR) and jasmonic acid (JA) can significantly enhance the resistance against RSV. On the contrary, plants impaired in BR or JA signaling are more susceptible to RSV. Moreover, the enhancement of RSV resistance conferred by BR is impaired in OsMYC2 (a key positive regulator of JA response) knockout plants, suggesting that BR-mediated RSV resistance requires active JA pathway. In addition, we found that RSV infection suppresses the endogenous BR levels to increase the accumulation of OsGSK2, a key negative regulator of BR signaling. OsGSK2 physically interacts with OsMYC2, resulting in the degradation of OsMYC2 by phosphorylation and reduces JA-mediated defense to facilitate virus infection. These findings not only reveal a novel molecular mechanism mediating the crosstalk between BR and JA in response to virus infection and deepen our understanding about the interaction of virus and plants, but also suggest new effective means of breeding RSV resistant crops using genetic engineering.
An update on the pathophysiology of immune thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder mediated by antiplatelet autoantibodies and antigen-specific T cells that either destroy platelets peripherally in the spleen or impair platelet production in the bone marrow. There have been a plethora of publications relating to the pathophysiology of ITP and since January of 2019, at least 50 papers have been published on ITP pathophysiology. Purpose of review To summarize the literature relating to the pathophysiology of ITP including the working mechanisms of therapies, T-cell and B-cell physiology, protein/RNA/DNA biochemistry, and animal models in an attempt to unify the perceived abnormal immune processes. Recent findings The most recent pathophysiologic irregularities associated with ITP relate to abnormal T-cell responses, particularly, defective T regulatory cell activity and how therapeutics can restore these responses. The robust literature on T cells in ITP points to the notion that ITP is a disease initiated by faulty self-tolerance mechanisms very much like that of other organ-specific autoimmune diseases. There is also a large literature on new and existing animal models of ITP and these will be discussed. It appears that understanding how to specifically modulate T cells in patients with ITP will undoubtedly lead to effective antigen-specific therapeutics. Conclusions ITP is predominately a T cell disorder which leads to a breakdown in self tolerance mechanisms and allows for the generation of anti-platelet autoantibodies and T cells. Novel therapeutics that target T cells may be the most effective way to perhaps cure this disorder.
Studies on structure / function relationship in the delta70 subunit of RNA polymerase and on scrP, an erstwhile candidate minor sigma gene of Esherichia coli

ix Abbreviations . I . INTRODUCTION . 1 1.1. Sigma subunit of RNA polymerase. 2 1.1.1. Transcription initiation by bacterial RNA polymerase.2 1.1.2. Conservation among members of o70 family.6 1.1. 3. Amino acids in a subunits involved in promoter recognition and opening . 8 1.1. 4. Possible roles of region 3 in transcription initiation.13 1.1. 5. Use of cysteine residues and modification producing free radicals in structural and functional studies of a 70 14 1.1. 6. The region of 070 between the conserved regions 1.2 and 2.1.16 1.2. scrP, an erstwhile candidate minor sigma gene of E. coli. 19 1.2.1. Discovery and early studies of ScrP.19 1.2. 2. Characterisation of scrP by gene disruption . 22 1.2. 3. ScrP protein.23 1.2. 4. Polypeptides with sequence similarities to ScrP.24 1.2. 5. Environment of the scrP gene on the bacterial chromosome . 26 1.2. 6. The mtgA gene and its product.27
Angiogenic and anti-inflammatory properties of azadirachtin A improve random skin flap survival in rats

Random skin flaps are widely used to repair tissue defects. However, the distal flap regions are prone to ischemic necrosis, limiting clinical applications. Azadirachtin A, a fruit extract from the neem, improves tissue blood supply and metabolism, reduces cell swelling, promotes tissue healing, and prevents venous thrombosis. We explored whether it enhances random skin flap survival. Fifty-four Sprague-Dawley rats were divided into control, low-dose, and high-dose Azadirachtin A-treated groups using a random number table. We used an improved version of the McFarlane technique to create flaps. On day 2, superoxide dismutase and malondialdehyde levels were measured. Tissue slices prepared on day 7 were stained with hematoxylin and eosin. The expression levels of vascular endothelial growth factor (VEGF), toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-kB), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were immunohistochemically assayed. Microcirculatory blood flow was measured via laser Doppler blood flowmetry. Flap angiography was performed using the lead-oxide gelatin injection technique. And the azadirachtin A groups exhibited a greater mean flap survival area, an improved mean blood vessel density, a greater blood flow, and higher superoxide dismutase and VEGF levels, especially at the high dose. Azadirachtin A markedly reduced the levels of TNF-α, IL-6, IL-1β, TLR4, and NF-kB. These findings suggest that azadirachtin A promotes random skin flap survival by improving the blood supply, reducing tissue inflammation, and inhibiting flap ischemia reperfusion injury.
Natural environment and childhood obesity: A systematic review

The associations between built and food environments and childhood obesity have been studied extensively. However, the association between the natural environment and childhood obesity has received too little scholarly attention. This study reviewed the literature published before 1 January 2019, which described associations between a full range of natural environmental factors (e.g., rainfall, temperature, sunlight, natural disasters, flood and drought) and weight‐related behaviours and childhood obesity. Five cross‐sectional studies and one longitudinal study were identified. Measures of natural environmental factors varied across six included studies, falling into five broad categories: weather conditions, altitude, natural disaster risk, air quality and day length. It was found that temperature was a significant weather indicator in most included studies and was associated with a reduction of daily physical activity. Children living in high‐altitude areas were more likely to be shorter and heavier than their counterparts in low‐altitude areas. Findings of this study will contribute to helping multiple stakeholders, including policy makers and urban planners, and formulate health policies and interventions to mitigate the detrimental impact of the natural environment on childhood obesity. More longitudinal studies should be designed to confirm these effects and explore the potential health effects of more natural environmental factors.
Molecular interactions and functions of IL‐32

IL‐32 is a multifaceted cytokine associated with several diseases and inflammatory conditions. Its expression is induced in response to cellular stress such as hypoxia, infections, and pro‐inflammatory cytokines. IL‐32 can be secreted from cells and can induce the production of pro‐inflammatory cytokines from several cell types but are also described to have anti‐inflammatory functions. The intracellular form of IL‐32 is shown to play an important role in various cellular processes, including the defense against intracellular bacteria and viruses and in modulation of cell metabolism. In this review, we discuss current literature on molecular interactions of IL‐32 with other proteins. We also review data on the role of intracellular IL‐32 as a metabolic regulator and its role in antimicrobial host defense.
Race, Ancestry and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis.

CONTEXT A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases. OBJECTIVE Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. DESIGN, SETTING, PARTICIPANTS In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N=1,759), White (N=2,507), Chinese (N=788) and Hispanic (N=1,411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. RESULTS Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. CONCLUSIONS Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production and be attributable, at least partly, to genetic ancestry.
Gastric emptying in humans : carbohydrate ingestion, gastrointestinal hormones and genetic variation

The prevalence of overweight and obesity continues to rise substantially across the world. It is the leading preventable cause of death worldwide and is associated with a large number of comorbidities that present a perpetual burden on healthcare costs. Much of the recent work to understand and address the problem of obesity has focused on the role of gastrointestinal hormones on the regulation of appetite, satiety, and food intake, and how interventions such as physical activity and exercise can affect the secretion of these hormones. However, the gastrointestinal system and the role of gastric emptying are often overlooked. The aim of this thesis was to enhance understanding of the physiology and regulation of gastric emptying and its interactions with carbohydrates. This will help in the development of novel non-pharmacological dietary interventions or foods that can modulate appetite and energy intake. A series of studies on human volunteers are presented in this thesis. Firstly, the gastric emptying rate of different 6% simple sugar solutions (water control, fructose, glucose, sucrose, 50:50 fructose and glucose) and gut hormone responses of circulating acylated ghrelin, active glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic polypeptide (GIP) and insulin were investigated. Hepatic metabolism and function in response to the different simple sugar solutions were also examined. The time of maximal gastric emptying rate (Tlag) differed significantly between between sucrose and glucose solutions. Differences in insulin and GIP responses between fructose containing solutions and glucose only solutions were also seen. No differences in hepatic metabolism measures or function were observed following the intake of 36 g of the various test sugars. However, lactate production was significantly greater for fructose containing solutions. Following on from these results, the effect of increased dietary fructose intake on gastric emptying rate of glucose and fructose was investigated. Three days supplementation with 120g/d fructose resulted in acceleration of gastric emptying rate of a fructose but not a glucose solution. No significant differences in the circulating concentration of gastrointestinal hormones, but subtle differences in responses over time were suggested which may explain the specific monosaccharide adaptations of gastric emptying. Further work is required to confirm this and to investigate the longevity and reversibility of the gastrointestinal adaptation and the mechanism involved. Lastly, several tagging single nucleotide polymorphisms (SNP) of the GLP-1 receptor gene were associated with gastric emptying rate. Further work is required on the regions identified to pinpoint the exact SNP or SNPs responsible.
Rates of prescription orders for United States active duty service members diagnosed with alcohol use disorder

Background Alcohol-use disorders (AUD) pose a significant challenge for the United States (US) military. The US Department of Defense has strongly recommended several medications for use in the treatment of patients with diagnosed AUD. This study assessed the prescription of medications for active duty service members (ADSMs) diagnosed with AUD in the US Military Health System (MHS). Methods Rates of prescription orders were retrospectively examined from 2010 to 2017 among ADSMs with an incident diagnosis of moderate-to-severe AUD. The rate of prescription orders was defined as the proportion of ADSMs with an ICD-9 or ICD-10 diagnosis code of alcohol dependence who received an order for acamprosate, disulfiram, naltrexone, and/or topiramate at a military treatment facility in the year following their incident diagnosis. Results ADSMs receiving an order for at least one medication in the year following their incident AUD diagnosis increased from 8.8% in 2010 to 16.2% in 2017 (RR = 1.84, 95% CI, 1.76, 1.93). Oral naltrexone was ordered most frequently among this patient population, while injectable naltrexone, a medication option meant to ease and improve adherence, was ordered for a smaller proportion of patients. Conclusions Most ADSMs who might benefit from prescriptions for AUD are not receiving them as part of their treatment despite strong clinical evidence and Department of Defense policy support for their use among this cohort.
Denosumab for Effective Tumor Size Reduction in Patients With Giant Cell Tumors of the Bone: A Systematic Review and Meta-Analysis

Background: Denosumab is a human monoclonal antibody that has been used successfully in the treatment of giant cell tumors of bone. These tumors are rare and, in principle, benign, but they are highly aggressive, locally advanced, osteolytic bone tumors that can metastasize to the lungs. Denosumab is an effective treatment when these tumors cannot be surgically removed or when surgical resection is likely to lead to severe morbidity (eg, loss of limbs or joints). The aim of this systematic review and meta-analysis was to investigate patients with giant cell tumors of bone who experienced tumor progression during treatment with denosumab and to compare them with patients who experienced reduction of their giant cell tumors of bone during treatment with denosumab. Methods: Embase, Cochrane Library, and MEDLINE/PubMed databases were searched for trials submitted by January 7, 2020, that reported the efficacy and safety of denosumab in patients with giant cell tumors of bone. Results: Sixty studies were reviewed, involving a total of 1074 patients who had giant cell tumors of bone and were treated with denosumab. Of the 60 studies, 58% of the patients were from case series studies, 39% from open-label phase II studies, and 3% from case reports. The response rate for denosumab as a treatment for giant cell tumors of bone was 97.5%, with statistical significance (P < .0001). Pain in the limbs was statistically the most common adverse event for denosumab treatment in case series studies (P < .0001). No treatment-related deaths occurred in the reviewed studies. Conclusion: Cumulative evidence supports the addition of surgery to optimal medical therapy with denosumab to reduce tumor size, clinical symptoms, and mortality among patients with giant cell tumors of bone.
Concentrations of Acute-Phase Proteins in Milk from Cows with Clinical Mastitis Caused by Different Pathogens

Among the new diagnostic methods for mastitis detection under development, milk acute-phase proteins (APPs) are receiving special attention. The study aimed to compare the profile of milk APPs from cows with natural clinical mastitis caused by distinct pathogens. The concentrations of haptoglobin (Hp), serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP), and C-reactive protein (CRP) were measured by Spatial Proximity Analyte Reagent Capture Luminescence (SPARCL). Each APP was compared across the pathogens causing mastitis. The APPs differed statistically (p < 0.05) among the pathogens causing udder infection. There were significant and positive correlations among the concentration profile, for each pathogen, in three of four APPs studied. It can be concluded that the pathogen causing mastitis could modify the profile of release of the APPs in milk. The profile of Hp, AGP, and CRP demonstrated significant correlation, indicating that the three APPs are suggested as biomarkers, in milk, for bovine mastitis.
Lake-type-specific seasonal patterns of nutrient limitation in German lakes, with target nitrogen and phosphorus concentrations for good ecological status

Summary Eutrophication is a global environmental problem that leaves many lakes with impaired ecological status. Human activity has increased the total concentrations of both nitrogen and phosphorus in aquatic systems, but their relative influence on phytoplankton biomass is uncertain. Their action as alternative limiting resources complicates assessment of their relative influence and disagreement may be in part due to seasonal shifts and lake-type-specific differences in the prevalence of limitation by nitrogen versus phosphorus. Debate continues as to whether measures to reduce nitrogen would be beneficial in addition to controls placed on phosphorus. We used a piecewise model to test whether total nitrogen (TN) concentrations, in addition to total phosphorus (TP), influence phytoplankton biomass in 369 lowland German lakes. The piecewise model predicts biomass from TN for low N : P ratio lakes, and from TP for high N : P ratio lakes. We tested three N : P mass ratios to divide lakes: dissolved inorganic nitrogen to TP (DIN : TP), DIN to dissolved reactive phosphorus (DIN : DIP) and TN : TP. TN was a better predictor of biomass than TP when either the DIN : TP ratio was below 1.6, DIN : DIP was below 8.4, or TN : TP below 29; predictions were most accurate when using the DIN : TP ratio. To investigate seasonal and lake-type-specific patterns of N and P limitation, we used the DIN : TP ratio, together with absolute concentrations of DIN and DIP, to predict the limiting nutrient at each lake in each month of the vegetation period. N limitation was much more common in polymictic than stratified lakes. While a high proportion of both stratified and polymictic lakes were P limited in early spring (60–70%), for polymictic lakes, we found a strong shift from P limitation to N limitation in summer: more than 50% of polymictic lakes were N limited between June and September and only 15–30% were P limited. To obtain lake-type-specific nutrient targets we estimated the average TN and TP concentrations at which lakes of different types achieved good ecological status according to EU water framework directive criteria. Stratified lakes achieved good ecological status at concentrations of 400–500 μg L−1 TN or 20–35 μg L−1 TP, while for polymictic lakes values of 500–1000 μg L−1 TN, or 35–75 μg L−1 TP were required. We estimate that nitrogen has an important influence on phytoplankton biovolume, and thus ecological status, for many polymictic lakes in Germany. While there is some uncertainty in the nutrient targets required to achieve good ecological status, this uncertainty is small compared with the range of concentrations currently observed, and lakes with moderate or worse status have concentrations of both TN and TP that are far above these current target estimates.
Gait Phase Recognition Using Deep Convolutional Neural Network with Inertial Measurement Units

Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user’s current gait phase must first be identified accurately. Gait phase recognition can potentially be achieved through input from wearable sensors. Deep convolutional neural networks (DCNN) is a machine learning approach that is widely used in image recognition. User kinematics, measured from inertial measurement unit (IMU) output, can be considered as an ‘image’ since it exhibits some local ‘spatial’ pattern when the sensor data is arranged in sequence. We propose a specialized DCNN to distinguish five phases in a gait cycle, based on IMU data and classified with foot switch information. The DCNN showed approximately 97% accuracy during an offline evaluation of gait phase recognition. Accuracy was highest in the swing phase and lowest in terminal stance.
A randomized, double-blind, dose-ranging, pilot trial of piperine with resveratrol on the effects on serum levels of resveratrol.

Resveratrol (3,4,5-trihydroxystilbene) is a naturally occurring phytoalexin with purported health-promoting effects, but with limited oral bioavailability. Our prior murine modeling research observed enhanced resveratrol bioavailability with piperine co-administration. In this study, single-dose pharmacokinetics of resveratrol with or without piperine and the associated toxicities were studied on a cohort of healthy volunteers. We performed a double-blind, randomized, three-arm pilot study. Participants were randomized to receive a single dose of resveratrol 2.5 g, with piperine in 0 mg, 5 mg, or 25 mg dose. An improved liquid chromatography/mass spectrometry assay was used to determine serum levels of resveratrol and resveratrol-glucuronide. Baseline through 24 h post-study drug serum analyses were performed and adverse events were followed for 30 days. Twenty-four participants were enroled. No significant relationship between dose and pharmacokinetic values were found. In the sex stratified analysis, Cmax for resveratrol in women showed a trend (P = 0.057) toward an increase with piperine. Pharmacokinetic values for resveratrol were: Cmax - 18.5 ± 16 ng/mL resveratrol alone, 29 ± 29 resveratrol + 5 mg piperine, 16 ± 13 resveratrol + 25 mg piperine; area under the concentration × time curve - 1270 ± 852 ng/h/mL resveratrol alone, 2083 ± 2284 resveratrol + 5 mg piperine, 1132 ± 222 resveratrol + 25 mg piperine. All subjects tolerated their protocol therapy with minimal to no toxicity and no evidence of differences between the three groups. The co-administration of resveratrol with piperine at 5 and 25 mg doses did not sufficiently alter the pharmacokinetics of resveratrol or resveratrol-glucuronide to demonstrate the significant enhancement observed in murine modeling.