Miracle-dz/UniFAR-FTUs huggingface dataset:
1061-1070 Shirian S.pmd

There are little information about Th17 cells and cutaneous Leishmaniasis (CL), due to an important effect of Th17 cells on immune response, it is worth to explore the role of Th17 on CL. The purpose of this study was to assess Th17 population in patients with acute vs. chronic CL lesions in comparison with skin samples collected from healthy volunteers in an endemic region of Old World CL. A total of 49 patients with clinical manifestations of chronic (n=16) and acute (n=33) CL lesions were recruited. The clinical diagnosis of CL was confirmed by direct smear or PCR. Biopsy specimens from prelesional skin of non-infectious lesions of 30 healthy individuals were used as control. Tissue sections of 3μm thickness were prepared and used for immunohistochemistry (IHC) analysis with primary antibody specific for Th17 associated antigen (CD161). For IHC, Envision+ (DakoCytomation) system was used and developed by using diaminobenzidine (DakoCytomation). The mean age of 33 patients with acute CL and the mean age of 16 patients with chronic CL were accordingly 45.24±16.43 and 33.56±15.87. In acute and chronic CL the mean (±standard deviation) and median (±interquartile range) were accordingly 2.92±2.21, 2.56±2.9 and 2.1±1.99, 1.54±2.81. In healthy controls the mean (±standard deviation) and median (±interquartile range) were 0.72±0.41 and 0.61±0.58 respectively. With pairwise comparison of acute, chronic and control groups, there were significant difference between acute and control (P value < 0.001), chronic and control (P value = 0.043). The results showed that there was an increasing cellular response of Th17 in both acute and chronic CL patients. Th17 was significantly higher in patients with acute and chronic CL lesions in comparison with healthy control group. However, there was no significant difference between acute and chronic infection concerning to Th17 cells.
Massive Ni-Cu-(PGE) Sulfide Remobilization: Processes, Products, and Implications for Exploration

Archean komatiite-hosted, Ni-Cu-(PGE) deposits are undeniably the product of primary magmatic processes. In such a situation, Ni-rich sulfides accumulate near the base of crystallizing high-temperature, low-viscosity, ultramafic magmas that intruded countryrocks or erupted as a lava. A common consequence of these primary processes is the concentration of massive sulfides and their overlying disseminated sulfides along the stratigraphic footwall margin of komatiite units (e.g., Ni deposits of Kambalda, AgnewWiluna belt, Superior craton). ISSUE 9, SEPTEMBER 2009
The Medical Triazole Voriconazole Can Select for Tandem Repeat Variations in Azole-Resistant Aspergillus Fumigatus Harboring TR34/L98H Via Asexual Reproduction

Azole-resistant Aspergillus fumigatus isolates recovered at high frequency from patients, harbor mutations that are associated with variation of promoter length in the cyp51A gene. Following the discovery of the TR34/L98H genotype, new variations in tandem repeat (TR) length and number of repeats were identified, as well as additional single nucleotide polymorphisms (SNPs) in the cyp51A gene, indicating that the diversity of resistance mutations in A. fumigatus is likely to continue to increase. Investigating the development routes of TR variants is critical to be able to design preventive interventions. In this study, we tested the potential effects of azole exposure on the selection of TR variations, while allowing haploid A. fumigatus to undergo asexual reproduction. Through experimental evolution involving voriconazole (VOR) exposure, an isolate harboring TR343/L98H evolved from a clinical TR34/L98H ancestor isolate, confirmed by whole genome sequencing. TR343/L98H was associated with increased cyp51A expression and high VOR and posaconazole MICs, although additional acquired SNPs could also have contributed to the highly azole-resistant phenotype. Exposure to medical azoles was found to select for TR343, thus supporting the possibility of in-host selection of TR34 variants.
Complex sensory environments alter mate choice outcomes

ABSTRACT Noise is a common problem in animal communication. We know little, however, about how animals communicate in the presence of noise using multimodal signals. Multimodal signals are hypothesised to be favoured by evolution because they increase the efficacy of detection and discrimination in noisy environments. We tested the hypothesis that female túngara frogs’ responses to attractive male advertisement calls are improved in noise when a visual signal component is added to the available choices. We tested this at two levels of decision complexity (two and three choices). In a two-choice test, the presence of noise did not reduce female preferences for attractive calls. The visual component of a calling male, associated with an unattractive call, also did not reduce preference for attractive calls in the absence of noise. In the presence of noise, however, females were more likely to choose an unattractive call coupled with the visual component. In three-choice tests, the presence of noise alone reduced female responses to attractive calls and this was not strongly affected by the presence or absence of visual components. The responses in these experiments fail to support the multimodal signal efficacy hypothesis. Instead, the data suggest that audio-visual perception and cognitive processing, related to mate choice decisions, are dependent on the complexity of the sensory scene. Summary: Audio-visual perception and cognitive processing, related to mate choice decisions, are dependent on the complexity of the sensory scene.
FBW7 Inhibits Myeloid Differentiation in Acute Myeloid Leukemia via GSK3-Dependent Ubiquitination of PU.1

Glycogen synthase kinase 3β (GSK3β), an ubiquitously expressed serine/threonine kinase is reported to be overexpressed and hyperactivated in cancers including acute myeloid leukemia (AML) where it promotes self-renewal, growth, and survival of AML cells. Therefore, GSK3β inhibition results in AML cell growth inhibition and myeloid differentiation. Here we identified master transcription factor PU.1 of monocyte–macrophage differentiation pathway as potential GSK3β target. We demonstrate that GSK3β phosphorylates PU.1 at Ser41 and Ser140 leading to its recognition and subsequent ubiquitin-mediated degradation by E3 ubiquitin ligase FBW7. This GSK3-dependent degradation of PU.1 by FBW7 inhibited monocyte–macrophage differentiation. We further showed that a phospho-deficient PU.1 mutant (PU.1-S41, S140A) neither bound to FBW7 nor was degraded by it. Consequently, PU.1-S41, S140A retained its transactivation, DNA-binding ability and promoted monocyte–macrophage differentiation of U937 cells even without phorbol 12-myristate 13-acetate (PMA) treatment. We further showed that FBW7 overexpression inhibited both PMA as well as M-CSF–induced macrophage differentiation of myeloid cell lines and peripheral blood mononuclear cells (PBMC) from healthy volunteers, respectively. Contrarily, FBW7 depletion promoted differentiation of these cells even without any inducer suggesting for a robust role of GSK3β–FBW7 axis in negatively regulating myeloid differentiation. Furthermore, we also recapitulated these findings in PBMCs isolated from patients with leukemia where FBW7 overexpression markedly inhibited endogenous PU.1 protein levels. In addition, PBMCs also showed enhanced differentiation when treated with M-CSF and GSK3 inhibitor (SB216763) together compared with M-CSF treatment alone. Implications: Our data demonstrate a plausible mechanism behind PU.1 restoration and induction of myeloid differentiation upon GSK3β inhibition and further substantiates potential of GSK3β as a therapeutic target in AML.
Determining the Molecular Mechanisms of Huntington’s Disease through Multi-Scale Modeling

OF THE DISSERTATION Determining the Molecular Mechanisms of Huntington’s Disease through Multi-Scale Modeling by Kiersten M. Ruff Doctor of Philosophy in Biology and Biomedical Sciences Computational and Systems Biology Washington University in St. Louis, 2017 Professor Rohit V. Pappu, Chair Huntington’s disease (HD) is associated with a mutational CAG repeat expansion within exon 1 of the huntingtin (Htt) gene. Post-transcriptional processing leads to the generation of N-terminal Htt protein fragments (Htt-NTFs), including those that encompass exon 1 (Httex1). Within Httex1, the CAG-repeat encoded polyglutamine (polyQ) tract is flanked N-terminally by a 17-residue amphipathic stretch (N17) and C-terminally by a 50-residue proline rich (PR) domain. Htt-NTFs, including Httex1, are among the smallest fragments that recapitulate HD pathology in mouse models. However, the direct link between Htt-NTFs with polyQ expansions and neurodegeneration that leads to HD remains unresolved. Despite being a monogenic disease, the onset and progression of HD are governed by an array of complex factors. Like other neurodegenerative diseases, HD too is characterized by deleterious changes across multiple length scales. These include, the length of the polyQ tract, the presence/absence of flanking sequences, the network of endogenous HttNTF interaction partners, the engagement of specific sub-cellular processes such as autophagy, and the cell-to-cell transfer of Htt-NTF aggregates. In this work, I have focused on uncovering the
Find and fuse: Unsolved mysteries in sperm–egg recognition

Sexual reproduction is such a successful way of creating progeny with subtle genetic variations that the vast majority of eukaryotic species use it. In mammals, it involves the formation of highly specialised cells: the sperm in males and the egg in females, each carrying the genetic inheritance of an individual. The interaction of sperm and egg culminates with the fusion of their cell membranes, triggering the molecular events that result in the formation of a new genetically distinct organism. Although we have a good cellular description of fertilisation in mammals, many of the molecules involved remain unknown, and especially the identity and role of cell surface proteins that are responsible for sperm–egg recognition, binding, and fusion. Here, we will highlight and discuss these gaps in our knowledge and how the role of some recently discovered sperm cell surface and secreted proteins contribute to our understanding of this fundamental process.
Predictors of Staying at Home during the COVID-19 Pandemic and Social Lockdown based on Protection Motivation Theory: A Cross-Sectional Study in Japan

During the COVID-19 pandemic, a social lockdown should be put in place and individuals should stay at home. Behavioral change is the only way to prevent the pandemic and overwhelmed healthcare systems until vaccines are available. We aimed to examine the psychological factors that predict staying at home during the COVID-19 pandemic and social lockdown. A total of 1980 participants in Japan completed a survey for this study from 9 to 11 May 2020, when the state of emergency covered all prefectures in the country. Self-reported behavior in terms of staying at home, the perceived severity of the pandemic, vulnerability to the pandemic, response efficacy, and self-efficacy based on protection motivation theory were assessed. Multiple regression analysis showed that perceived severity (standardized β = 0.11, p < 0.001) and self-efficacy (standardized β = 0.32, p < 0.001) significantly predicted greater levels of staying at home, after controlling for socio-demographics. However, perceived vulnerability and response efficacy did not. To encourage people to stay at home during the pandemic and social lockdown, increasing the perceived severity of infection by COVID-19 and self-efficacy in terms of exercising restraint with respect to going out may consequently encourage people to stay at home.
Effects of Soil Amendments on Heavy Metal Immobilization and Accumulation by Maize Grown in a Multiple-Metal-Contaminated Soil and Their Potential for Safe Crop Production

Soil amendments have been proposed for immobilizing metallic contaminants, thus reducing their uptake by plants. For the safe production of crops in contaminated soil, there is a need to select suitable amendments that can mitigate heavy metal uptake and enhance crop yield. The present experiment compared the effects of three amendments, hydroxyapatite (HAP), organic manure (OM), and biochar (BC), on plant growth and heavy metal accumulation by maize in an acidic soil contaminated with Cd, Pb, and Zn, and their potential for safe crop production. Toxicity characteristic leaching procedure (TCLP) tests, energy dispersive X-ray spectroscopy (EDS) analysis, and X-ray diffraction (XRD) analysis were used to evaluate the effectiveness and mechanisms of heavy metal immobilization by the amendments. The results showed that shoot and root biomass was significantly increased by HAP and 1% OM, with an order of 1% HAP > 0.1% HAP > 1% OM, but not changed by 0.1% OM and BC (0.1% and 1%). HAP significantly decreased Cd, Pb, and Zn concentrations in both shoots and roots, and the effects were more pronounced at the higher doses. OM decreased the shoot Cd and Pb concentrations and root Zn concentrations, but only 1% OM decreased the shoot Zn and root Pb concentrations. BC decreased the shoot Cd and Pb concentrations, but decreased the shoot Zn and root Pb concentrations only at 1%. HAP decreased the translocation factors (TFs) of Cd, Pb, and Zn (except at the 0.1% dose). OM and BC decreased the TFs of Cd and Zn, respectively, at the 1% dose but showed no significant effects in other cases. Overall, plant P, K, Fe, and Cu nutrition was improved by HAP and 1% OM, but not by 0.1 OM and BC. Soil pH was significantly increased by HAP, 1% OM, and 1% BC, following an order of 1% HAP > 1% OM > 0.1% HAP > 1% BC. The TCLP levels for Cd, Pb, and Zn were significantly reduced by HAP, which can be partly attributed to its liming effects and the formation of sparingly soluble Cd-, Pb-, and Zn-P-containing minerals in the HAP-amended soils. To some extent, all the amendments positively influenced plant and soil traits, but HAP was the optimal one for stabilizing heavy metals, reducing heavy metal uptake, and promoting plant growth in the contaminated soil, suggesting its potential for safe crop production.
Microbially induced carbonate precipitation via methanogenesis pathway by a microbial consortium enriched from activated anaerobic sludge

Various applications of microbially induced carbonate precipitation (MICP) has been proposed. However, most studies use cultured pure strains to obtain MICP, ignoring advantages of microbial consortia. The aims of this study were to: (i) test the feasibility of a microbial consortium to produce MICP; (ii) identify functional micro‐organisms and their relationship; (iii) explain the MICP mechanism; (iv) propose a way of applying the MICP technique to soil media.
Regulation of renal pendrin activity by aldosterone

Purpose of review Pendrin resides on the luminal membrane of type B intercalated cells in the renal collecting tubule system mediating the absorption of chloride in exchange for bicarbonate. In mice or humans lacking pendrin, blood pressure is lower, and pendrin knockout mice are resistant to aldosterone-induced hypertension. Here we discuss recent findings on the regulation of pendrin. Recent findings Pendrin activity is stimulated during alkalosis partly mediated by secretin. Also, angiotensin II and aldosterone stimulate pendrin activity requiring the mineralocorticoid receptor in intercalated cells. Angiotensin II induces dephosphorylation of the mineralocorticoid receptor rendering the receptor susceptible for aldosterone binding. In the absence of the mineralocorticoid receptor in intercalated cells, angiotensin II does not stimulate pendrin. The effect of aldosterone on pendrin expression is in part mediated by the development of hypokalemic alkalosis and blunted by K+-supplements or amiloride. Part of the blood pressure-increasing effect of pendrin is also mediated by its stimulatory effect on the epithelial Na+-channel in neighbouring principal cells. Summary These findings identify pendrin as a critical regulator of renal salt handling and blood pressure along with acid--base balance. A regulatory network of hormones fine-tuning activity is emerging. Drugs blocking pendrin are being developed.
Characterization of a Macro- and Micro-Textured Titanium Grade 5 Alloy Surface Obtained by Etching Only without Sandblasting

Our purpose was to physically characterize the surface, and the subsurface, of a macro- and micro-textured titanium grade 5 dental implant surface obtained by etching only, without sandblasting. The topography, surface roughness, as well as the surface structure and subsurface distribution of elements, were determined by scanning electronic microscopy (SEM), non-contact profilometry, X-ray diffraction (XRD), and a concentration profile performed by Auger electron spectroscopy (AES). The hydrogen concentration in the implants was measured; the ability to generate nanostructures when stored in deionized water was also investigated. Under SEM, the surface resembled a sandblasted and etched titanium surface with its typical macro- and micro-texture; roughness was moderate with average roughness (Sa) 1.29 µm. No titanium hydride was found at the implant surface and no enrichment of any alloying element was identified at the surface and subsurface. Hydrogen concentration was 79 ppm, within the normative tolerance (<130 ppm). After storage in water for 6 months, densely packed finger-like nanostructures were observed. The clinical advantage of this textured titanium alloy surface is that it displays the typical macro- and micro-features of a moderately rough sandblasted and etched (SLA) titanium surface without leaving behind any foreign sandblasting material.
Adjuvant therapy of operable nonsmall cell lung cancer: an update

Purpose of review The current status of postoperative adjuvant therapy for nonsmall cell lung cancer (NSCLC) is reviewed. Recent findings Cisplatin-based postoperative chemotherapy is a current standard of care for patients with stage II–III NSCLC who underwent complete resection. However, its benefit is limited. In these 20 years, the introduction of targeted therapies and immune checkpoint inhibitors has dramatically changed the treatment of metastatic lung cancer. The accumulated knowledge is now being applied in the adjuvant setting and many clinical trials are underway. Recently, postoperative osimertinib was shown to greatly prolong disease-free survival of patients with resected, stage II/IIIA NSCLC with EGFR mutation with an unprecedented hazard ratio of 0.17 in ADAURA study. Furthermore, initial results of adjuvant studies of immune checkpoint inhibitors are expected to be reported shortly. Summary As lung cancer is inherently prone to metastasize even though it looks in its earlier stage, it is essential to develop a newer generation of adjuvant therapies to improve patient outcomes. To this end, international and multidisciplinary collaboration is key to establish a new standard of care. It is anticipated that the treatment algorithm of early-stage lung cancer will be completely revised in 5 years using a more individualized approach.
The Role of Electronic Noses in Phenotyping Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common progressive disorder of the respiratory system which is currently the third leading cause of death worldwide. Exhaled breath analysis is a non-invasive method to study lung diseases, and electronic noses have been extensively used in breath research. Studies with electronic noses have proved that the pattern of exhaled volatile organic compounds is different in COPD. More recent investigations have reported that electronic noses could potentially distinguish different endotypes (i.e., neutrophilic vs. eosinophilic) and are able to detect microorganisms in the airways responsible for exacerbations. This article will review the published literature on electronic noses and COPD and help in identifying methodological, physiological, and disease-related factors which could affect the results.
Self-Controlled Choice Arises from Dynamic Prefrontal Signals That Enable Future Anticipation

Self-control allows humans the patience necessary to maximize reward attainment in the future. Yet it remains elusive when and how the preference to self-controlled choice is formed. We measured brain activity while female and male humans performed an intertemporal choice task in which they first received delayed real liquid rewards (forced-choice trial), and then made a choice between the reward options based on the experiences (free-choice trial). We found that, while subjects were awaiting an upcoming reward in the forced-choice trial, the anterior prefrontal cortex (aPFC) tracked a dynamic signal reflecting the pleasure of anticipating the future reward. Importantly, this prefrontal signal was specifically observed in self-controlled individuals, and moreover, interregional negative coupling between the prefrontal region and the ventral striatum (VS) became stronger in those individuals. During consumption of the liquid rewards, reduced ventral striatal activity predicted self-controlled choices in the subsequent free-choice trials. These results suggest that a well-coordinated prefrontal-striatal mechanism during the reward experience shapes preferences regarding the future self-controlled choice. SIGNIFICANCE STATEMENT Anticipating future desirable events is a critical mental function that guides self-controlled behavior in humans. When and how are the self-controlled choices formed in the brain? We monitored brain activity while humans awaited a real liquid reward that became available in tens of seconds. We found that the frontal polar cortex tracked temporally evolving signals reflecting the pleasure of anticipating the future reward, which was enhanced in self-controlled individuals. Our results highlight the contribution of the fronto-polar cortex to the formation of self-controlled preferences, and further suggest that future prospect in the prefrontal cortex (PFC) plays an important role in shaping future choice behavior.
Buffering negative effects of immigration on cognitive, social, and educational development: A multinational meta-analysis of child and adolescent prevention programmes.

Growing up in migrant families is a well-known distal risk factor related to poorer outcomes in child and adolescent health, academic, socioemotional and behavioural development. This article reviews the effects of various prevention measures such as early education programmes, cognitive and language training or parent and teacher training on child and adolescent developmental outcomes in immigration samples. Using several comprehensive literature searches, we found 138 research reports with 141 studies and 175 comparisons on preventing negative effects of immigration. Overall, programmes yielded an effect size of d = 0.26 at post-test using the random effect model. These effects decreased over time while still differing significantly from zero. A cross-tabulation of prevention approach/programme type by different outcome domains revealed several important results such as high effects of child cognitive and language training programmes on child academic and language outcomes and relatively low effects of all programmes on child socioemotional outcomes. In addition, individualised and culturally tailored programmes seems to be more effective. However, generalised effects on more distal educational outcomes (e.g., school degrees) were generally weak. Hence, it remains questionable whether individual psychosocial and educational programmes are able to counterbalance the multifaceted risks of immigration.