Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulatory effect of resveratrol and melatonin on natural killer cell activity and adrenomedullin in diabetic rats

Background/aim Epidemiological evidence suggests that diabetes poses a high risk for many chronic diseases, especially cardiovascular diseases, and cancer by stimulating many inflammatory and immunological pathogenic mediators and affecting natural killer (NK)-cell activity. In this study, the effects of melatonin and resveratrol on IL-6, TNF-alpha, oxidant/antioxidant capacity, NK-cell activity, and mid-regional proadrenomedullin (MR-proADM) levels of diabetic rats were investigated. Materials and methods In the study, 28 Sprague Dawley rats were randomly divided into the control group (group I) and 3 streptozotocin-induced diabetes mellitus (DM) groups (group II, III, and IV), each group consisting of 7 rats. Five mg/kg/day melatonin to group III and 5 mg/kg/day resveratrol (intraperitoneal) to group IV was given. At the end of 3 weeks, NK-cell activity, total antioxidant/oxidant capacity, MR-proADM, IL-6, and TNF-alpha levels were measured in intracardiac blood taken under anesthesia. Results NK-cell activity of group II was found lower than group I, group III, and group IV (7.4 ± 2.0 vs. 22.5 ± 11.9, 30.6 ± 22.5 and 20.4 ± 9.1 pg/mL; p = 0.0018, respectively). The difference was more prominent in diabetic rats receiving melatonin (p < 0.01). TNF-alpha levels of group II were higher than the group I (p < 0.05). The MR-proADM levels of group II were found to be lower than the group I and group III (6.4 ± 3.6 vs. 14.4 ± 3.2 and 14.0 ± 4.2 ng/L; p < 0.05, respectively). In addition, NK-cell activity was moderately correlated with MR-proADM (r = 0.5618, p = 0.0019). Conclusion Resveratrol and, more effectively, melatonin modulate by reversing the adverse effects of diabetes on NK-cell activity, which has a protective function in inflammatory and immunological processes. In this modulation, melatonin also acts through adrenomedullin.
Delayed introduction of sirolimus in paediatric intestinal transplant recipients: indications and long‐term benefits

To review our experience using sirolimus in a single centre paediatric intestinal transplantation cohort. Intestinal transplant patients with more than 3 months follow‐up were divided into two groups according to their immunosuppression regimen: tacrolimus, (TAC group, n = 45 grafts) or sirolimus (SRL group, n = 38 grafts), which included those partially or completely converted from tacrolimus to sirolimus. The indications to switch were tacrolimus side effects and immunological complications. Survival and complications were retrospectively analysed comparing both groups. SRL was introduced 9 months (0 months–16.9 years) after transplant. The main cause for conversion was worsening renal function (45%), followed by haemolytic anaemia (21%) and graft‐versus‐host‐disease (16%). Both groups showed a similar overall patient/graft survival (P = 0.76/0.08) and occurrence of rejection (24%/17%, P = 0.36). Immunological complications did not recur after conversion. Renal function significantly improved in most SRL patients. After a median follow‐up of 65.17 months, 28/46 survivors were on SRL, 26 with monotherapy, with good graft function. Over one‐third of our patients eventually required SRL conversion that allowed to improve their kidney function and immunological events, without entailing additional complications or survival impairment. Further trials are warranted to clarify the potential improvement of the standard tacrolimus maintenance by sirolimus conversion or addition.
VHUT-cryo-FIB, a method to fabricate frozen-hydrated lamella of tissue specimen for in situ cryo-electron tomography

Cryo-electron tomography (cryo-ET) provides a promising technique to study high resolution structures of macromolecules in situ, opening a new era of structural biology. One major bottleneck of this technique is to prepare suitable cryo-lamellas of cell/tissue samples. The emergence of cryo-focused ion beam (cryo-FIB) milling technique provides a good solution of this bottleneck. However, there are still large limitations of using cryo-FIB to prepare cryo-lamella of tissue specimen because the thickness of tissue increases the difficulty of specimen freezing and cryo-FIB milling. Here we report a new workflow, VHUT-cryo-FIB (Vibratome - High pressure freezing - Ultramicrotome Trimming – cryo-FIB), aiming for efficient preparation of frozen hydrated tissue lamella for subsequent cryo-ET data collection. This workflow includes tissue slicing using vibratome, high pressure freezing, ultramicrotome cryo-trimming, cryo-FIB milling and the subsequent cryo-electron microscopy (cryo-EM). The modification of equipment in this workflow is highly eliminated. We developed two strategies with a special cryo-holder tip or carrier for loading cryo-lamella into side entry cryo-holder or Autoloader catridge. We tested this workflow using the tissue sample of rat skeleton muscle and spinach leaf and collected high quality cryo-ET tilt series, which enabled us to obtain an in situ structure of spinach ribosome by sub-tomogram averaging.
Single‐cell RNA‐Seq reveals a highly coordinated transcriptional program in mouse germ cells during primordial follicle formation

The assembly of primordial follicles in mammals represents one of the most critical processes in ovarian biology. It directly affects the number of oocytes available to a female throughout her reproductive life. Premature depletion of primordial follicles contributes to the ovarian pathology primary ovarian insufficiency (POI). To delineate the developmental trajectory and regulatory mechanisms of oocytes during the process, we performed RNA‐seq on single germ cells from newborn (P0.5) ovaries. Three cell clusters were classified which corresponded to three cell states (germ cell cyst, cyst breakdown, and follicle) in the newborn ovary. By Monocle analysis, a uniform trajectory of oocyte development was built with a series of genes showed dynamic changes along the pseudo‐timeline. Gene Ontology term enrichment revealed a significant decrease in meiosis‐related genes and a dramatic increase in oocyte‐specific genes which marked the transition from a germ cell to a functional oocyte. We then established a network of regulons by using single‐cell regulatory network inference and clustering (SCENIC) algorithm and identified possible candidate transcription factors that may maintain transcription programs during follicle formation. Following functional studies further revealed the differential regulation of the identified regulon Id2 and its family member Id1, on the establishment of primordial follicle pool by using siRNA knockdown and genetic modified mouse models. In summary, our study systematically reconstructed molecular cascades in oocytes and identified a series of genes and molecular pathways in follicle formation and development.
Black-box Fuzzing Approaches to Secure Web Applications: Survey

Web applications are increasingly important tools in our modern daily lives, such as in education, business transactions, and social media. Because of their prevalence, they are becoming more susceptible to different types of attacks that exploit security vulnerabilities. Exploiting these vulnerabilities may cause damage to the web applications as well as the endusers. Thus, web apps’ developers should identify vulnerabilities and fix them before an attacker exploits them. Using blackbox fuzzing techniques for vulnerability identification is very popular during the web apps’ development life cycle. These techniques pledge to find vulnerabilities in web applications by constructing attacks without accessing their source codes. This survey explores the research that has been done in the black-box vulnerability finding and exploits construction in web applications and proposes future directions. Keywords—Black-box fuzzing; web application security; vulnerability scanning; automatic web app testing; vulnerability detection; survey
Response of Physic Nut Trees to Liming of Acidic Soils

ABSTRACT The physic nut tree (Jatropha curcas) is an oilseed species with potential for biodiesel production. We evaluated the effect of soil acidity indices on nutrient uptake for optimal growth in physic nut plants grown on acidic soils under greenhouse conditions. Two soils were used in the experiment. Maximum growth was obtained with the application of 1.05 g lime kg-1 for both soils. Maximum growth of the physic nut plants occurred under the following conditions: pH of water = 6.1, calcium (Ca2+) = 17.0 mmolc kg−1, magnesium (Mg2+) = 5.7 mmolc kg−1, acidity saturation = 10.3%, base saturation = 52.3%, Ca saturation = 36.0%, Mg saturation = 12.0% and potassium (K) saturation = 3.8%. Furthermore, the nitrogen (N) requirement of physic nut trees was shown to be high, and to a lesser degree, Ca and Mg requirements were also high, suggesting that liming is very important in crop cultivation of this species.
Invited Review Stability of Lead(II) Arsenates

Summary. Predictions of lead arsenate solubility and thermodynamic stability have been based on the value of the solubility constant for a precipitate with the general composition Pb3(AsO4)2. The solubility of this precipitate is high and lead arsenate is considered to be unsuitable for lead and arsenic control in the environment. Standard Gibbs energy of formation for bayldonite, duftite, mimetite, philipsbornite, and schultenite can be found in the literature from solubility studies. From these data, stability diagrams were established for the environmentally relevant lead containing solid phases – anglesite, cerussite, schultenite, and mimetite. The diagrams lead to the conclusion that mimetite is a lead arsenate that can be used for remediation techniques.
Shear Induced Phase Boundary Shift in the Critical and Off-Critical Regions for a Polybutadiene/Polyisoprene Blend

The rheology of near- and off-critical elastomeric blends of polybutadiene (PB)/ low vinyl content polyisoprene (LPI) has been studied as a function of temperature, heating rate, and shear frequency. Depending on the composition, near or far away from the critical point, blends showed different behaviors in several aspects: temperature ramp curves, shift of the apparent binodal and spinodal points under oscillatory shear at the given frequency and strain amplitude. The composition dependent rheological responses are interpreted by the differences in the amplitude of the critical fluctuation near the phase boundary and in the shear induced mixing mechanisms between near- and off-critical blends. For near-critical blends, the critical fluctuation is large enough to induce a considerable extra stress when the blend is still in the miscible state. As a result, a heating rate independent upturn of G′ can be observed and the apparent spinodal point can be greatly shifted through the strong suppression of the la.
Silence of crowdworkers—reasons and implications for work conditions and quality

Abstract Microtasks accomplished by humans are used in many corners of the Internet. They help to make decisions where it is not possible to rely on algorithms (yet) like insult detection or fake reviews. People conducting crowdwork, crowdworkers, are often recruited via platforms where employers have more power than crowdworkers. This is sometimes misused by offering poor work conditions, which can lead to poor work quality. Online feedback systems (OFS) can discipline employers to improve work conditions and subsequently work quality. Unfortunately, the majority of crowdworkers do not contribute to an OFS and remain silent. We develop and test a model based on self-determination theory with PLS-SEM to explain their silence. Perceived cost and perceived non-relevance are deterrents to contributions. However, satisfaction in helping others and the wish to belong to the community are significant motivational factors, which could be used in the design of an OFS to foster crowdworkers’ contributions.
Evaluating Pre-silicon Treatment to Alleviate Drought Stress and Increases Antioxidative Activity in Zoysia japonica

This study was performed to determine the effects of silicon on zoysiagrass after the application of drought stress. The daily amount of water or scilicon solution was 150 ml per a pot. For 14 days, plants were treated with 0.1 and 1.0 mM silicon (Si) and with distilled water for control and the drought only-treatment. Afterward, the plants in Si and drought treatment were exposed to a 21-day under drought stress condition but the plants in control received water. The results indicated that the growth and the moisture and chlorophyll contents decreased in the drought only-treatment and 0.1 mM Si compared to the control. However, 1.0 mM Si showed an increase in the growth with a significant increase of water and chlorophyll contents. The MDA and H₂O₂ concentrations and electrolyte leakage decreased, while the radical scavenging capacity increased in 1.0 mM Si. 1.0 mM Si showed little to no differences in the growth and no differences in water and chlorophyll contents, electrolyte leakage, MDA and H₂O₂ concentrations and antioxidant capacity compared to the control. These results suggested that application of silicon is useful for drought tolerance improvement of zoysiagrass under drought that is occurring in turf fields.
Exploring BCI Control in Smart Environments

The brain–computer interface (BCI) control technology that utilizes motor imagery to perform the desired action instead of manual operation will be widely used in smart environments. However, most of the research lacks robust feature representation of multi-channel EEG series, resulting in low intention recognition accuracy. This article proposes an EEG2Image based Denoised-ConvNets (called EID) to enhance feature representation of the intention recognition task. Specifically, we perform signal decomposition, slicing, and image mapping to decrease the noise from the irrelevant frequency bands. After that, we construct the Denoised-ConvNets structure to learn the colorspace and spatial variations of image objects without cropping new training images precisely. Toward further utilizing the color and spatial transformation layers, the colorspace and colored area of image objects have been enhanced and enlarged, respectively. In the multi-classification scenario, extensive experiments on publicly available EEG datasets confirm that the proposed method has better performance than state-of-the-art methods.
Niche partitioning of bacterial communities along the stratified water column in the Black Sea

The Black Sea is the largest semi‐closed permanently anoxic basin on our planet with long‐term stratification. The study aimed at describing the Black Sea microbial community taxonomic and functional composition within the range of depths spanning across oxic/anoxic interface, and to uncover the factors behind both their vertical and regional differentiation. 16S rRNA gene MiSeq sequencing was applied to get the data on microbial community taxonomy, and the PICRUSt pipeline was used to infer their functional profile. The normoxic zone was mainly inhabited by primary producers and heterotrophic prokaryotes (e.g., Flavobacteriaceae, Rhodobacteraceae, Synechococcaceae) whereas the euxinic zone—by heterotrophic and chemoautotrophic taxa (e.g., MSBL2, Piscirickettsiaceae, and Desulfarculaceae). Assimilatory sulfate reduction and oxygenic photosynthesis were prevailing within the normoxic zone, while the role of nitrification, dissimilatory sulfate reduction, and anoxygenic photosynthesis increased in the oxygen‐depleted water column part. Regional differentiation of microbial communities between the Ukrainian shelf and offshore zone was detected as well, yet it was significantly less pronounced than the vertical one. It is suggested that regional differentiation within a well‐oxygenated zone is driven by the difference in phytoplankton communities providing various substrates for the prokaryotes, whereas redox stratification is the main driving force behind microbial community vertical structure.
Lipid and Nucleocapsid N-Protein Accumulation in COVID-19 Patient Lung and Infected Cells

Visualization of the subcellular localization of SARS-CoV-2 proteins in lung patient material of COVID-19 patients is important for the understanding of this new virus. We detected viral proteins in the context of the ultrastructure of infected cells and tissues and discovered that some viral proteins accumulate in novel, lipid-filled compartments. ABSTRACT The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global outbreak and prompted an enormous research effort. Still, the subcellular localization of the coronavirus in lungs of COVID-19 patients is not well understood. Here, the localization of the SARS-CoV-2 proteins is studied in postmortem lung material of COVID-19 patients and in SARS-CoV-2-infected Vero cells, processed identically. Correlative light and electron microscopy on semithick cryo-sections demonstrated induction of electron-lucent, lipid-filled compartments after SARS-CoV-2 infection in both lung and cell cultures. In lung tissue, the nonstructural protein 4 and the stable nucleocapsid N-protein were detected on these novel lipid-filled compartments. The induction of such lipid-filled compartments and the localization of the viral proteins in lung of patients with fatal COVID-19 may explain the extensive inflammatory response and provide a new hallmark for SARS-CoV-2 infection at the final, fatal stage of infection. IMPORTANCE Visualization of the subcellular localization of SARS-CoV-2 proteins in lung patient material of COVID-19 patients is important for the understanding of this new virus. We detected viral proteins in the context of the ultrastructure of infected cells and tissues and discovered that some viral proteins accumulate in novel, lipid-filled compartments. These structures are induced in Vero cells but, more importantly, also in lung of patients with COVID-19. We have characterized these lipid-filled compartments and determined that this is a novel, virus-induced structure. Immunogold labeling demonstrated that cellular markers, such as CD63 and lipid droplet marker PLIN-2, are absent. Colocalization of lipid-filled compartments with the stable N-protein and nonstructural protein 4 in lung of the last stages of COVID-19 indicates that these compartments play a key role in the devastating immune response that SARS-CoV-2 infections provoke.
SARS-CoV-2 Variants are Selecting for Spike Protein Mutations that Increase Protein Stability

The emergence of SARS-CoV-2 in 2019 has caused severe disruption and a huge number of human deaths across the globe. As the pandemic spreads, a natural result is the emergence of variants with a variety of amino acid mutations. Variants of SARS-CoV-2 with mutations in their spike protein may result in an increased infectivity, increased lethality, or immune escape, and whilst many of these properties can be explained through changes to binding affinity or changes to post-translational modification, many mutations have no known biophysical impact on the structure of protein. The Gibbs free energy of a protein represents a measure of protein stability, with an increased stability resulting in a protein that is more thermodynamically stable, and more robust to changes in external environment. Here we show that mutations in the spike proteins of SARS-CoV-2 are selecting for amino acid changes that result in a more stable protein than expected by chance. We calculate all possible mutations in the SARS-CoV-2 spike protein, and show that many variants are more stable than expected when compared to the background, indicating that protein stability is an important consideration for the understanding of SARS-CoV-2 evolution. Variants exhibit a range of stabilities, and we further suggest that some stabilising mutations may be acting as a “counterbalance” to destabilising mutations that have other properties, such as increasing binding site affinity for the human ACE2 receptor. We suggest that protein folding calculations offer a useful tool for early identification of advantageous mutations.
Protection of the prodomain α1-helix correlates with latency in the transforming growth factor-β family

The 33 members of the transforming growth factor beta (TGF-β) family are fundamentally important for organismal development and homeostasis. Family members are synthesized and secreted as pro-complexes of prodomains that are non-covalently bound to the growth factor (GF). The pro-complexes of some members are latent and require activation steps to release the GF for signaling. Why some members are latent while others are non-latent is incompletely understood, but crystal structures and hydrogen-deuterium exchange (HDX) of four family members have begun to unravel how latency is regulated. Here, we extend this understanding by comparing pro-complex conformation in negative stain EM (nsEM) and HDX of ActA, BMP7, BMP9, BMP10, GDF8, TGF-β1, and TGF-β2. nsEM revealed that family members varied in either adopting cross-armed, open-armed, or V-armed configurations. Latency was achieved in both cross-armed and V-armed but not open-armed conformations. HDX revealed remarkably varying patterns of exchange between family members, consistent with large prodomain sequence divergence. We observed a strong correlation between latency and protection of the prodomain α1-helix from exchange, which in latent members coincided with greater buried surface area of the α1-helix and more hydrogen and cation-pi bonds from the prodomain fastener and GF to the α1-helix. Strong sequence conservation of the α1-helix and fastener only in latent members suggests that similar interactions are conserved and sufficient to confer latency. Moreover, most members exhibited rapid exchange in the unstructured “association region” at the prodomain N-terminus, highlighting their availability for interacting with factors that may regulate latency and extracellular storage.
Phylogenetic network analysis revealed the recombinant origin of the SARS-CoV-2 VOC202012/01 (B.1.1.7) variant first discovered in U.K.

The emergence of new variants of the SARS-CoV-2 virus poses serious problems to the control of the current COVID-19 pandemic. Understanding how the variants originate is critical for effective control of the spread of the virus and the global pandemic. The study of the virus evolution so far has been dominated by phylogenetic tree analysis, which however is inappropriate for a few important reasons. Here we used phylogenetic network approach to study the origin of the VOC202012/01 (Alpha) or so-called UK variant (PANGO Lineage B.1.1.7). The multiple network analyses using different methods consistently revealed that the VOC202012/01 variant was a result of recombination, in contrast to the common assumption that the variant evolved from step-wise mutations in a linear order. The study provides an example for the power and application of phylogenetic network analysis in studying virus evolution, which can be applied to study the evolutionary processes leading to the emergence of other variants of the SARS-CoV-2 virus as well as many other viruses. Significance The emergence of new variants of the SARS-CoV-2 virus, including the Alpha variant first found in U.K., poses serious challenges to the control of the current COVID-19 pandemic. Understanding how new variant originated is paramount to end the pandemic as effectively and quickly as possible. The dominant phylogenetic tree approach to study virus evolution has been inadequate and even misleading. Here we used a phylogenetic network approach to study the origin of the VOC202012/01 (Alpha) variant which was first reported in U.K. last year but has soon spread into many other countries, leading to dramatic increase in infection and death. Multiple analyses consistently revealed that the variant originated through recombination of pre-existing virus strains, highlighting an important but largely ignored mechanism in the evolution of the SARS-CoV-2 virus so far.