Miracle-dz/UniFAR-FTUs huggingface dataset:
Gα-cAMP/PKA pathway positively regulates pigmentation, chaetoglobosin A biosynthesis and sexual development in Chaetomium globosum

Sensing the environmental signals, the canonical Gα-cAMP/PKA pathway modulates mycelial growth and development, and negatively regulates some secondary metabolism in filamentous fungi, e.g. aflatoxin in Aspergillus nidulans. Here we report the characterization of this signaling pathway in Chaetomium globosum, a widely spread fungus known for synthesizing abundant secondary metabolites, e.g. chaetoglobosin A (ChA). RNAi-mediated knockdown of a putative Gα-encoding gene gna-1, led to plural changes in phenotype, e.g. albino mycelium, significant restriction on perithecium development and decreased production of ChA. RNA-seq profiling and qRT-PCR verified significantly fall in expression of corresponding genes, e.g. pks-1 and CgcheA. These defects could be restored by simultaneous knock-down of the pkaR gene encoding a regulatory subunit of cAMP-dependent protein kinase A (PKA), suggesting that pkaR had a negative effect on the above mentioned traits. Confirmatively, the intracellular level of cAMP in wild-type strain was about 3.4-fold to that in gna-1 silenced mutant pG14, and addition of a cAMP analog, 8-Br-cAMP, restored the same defects, e.g., the expression of CgcheA. Furthermore, the intracellular cAMP in gna-1 and pkaR double silenced mutant was approaching the normal level. The following activity inhibition experiment proved that the expression of CgcheA was indeed regulated by PKA. Down-regulation of LaeA/VeA/SptJ expression in gna-1 mutant was also observed, implying that Gα signaling may crosstalk to other regulatory pathways. Taken together, this study proposes that the heterotrimeric Gα protein-cAMP/PKA signaling pathway positively mediates the sexual development, melanin biosynthesis, and secondary metabolism in C. globosum.
Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study

Objectives Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD. Design Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention. Setting 135 primary care practices in South London, UK. Participants 1742 adults, 49–74 years, 86% male at high (≥20%) risk of developing CVD in the next 10 years as defined via QRISK2 score. Outcome measures The main explanatory variable was depressive symptoms measured via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and weekend days. Results The median daily step count of the total sample was 6151 (IQR 3510) with significant differences (P<0.001) in mean daily step count between participants with low (PHQ-9 score: 0–4), mild (PHQ-9 score: 5–9) and moderate to severe depressive symptoms (PHQ-9 score: ≥10). Controlling for age, gender, ethnicity, education level, body mass index (BMI), smoking, consumption of alcohol, day of the week and season, individuals with mild depressive symptoms and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8% to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals, respectively. Furthermore, male gender, white ethnicity, higher education level, lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were independently associated with higher step count. Conclusions People at high risk of CVD with depressive symptoms have lower levels of PA. Trial registration ISRCTN84864870; Pre-results.
Urinary cytokines and mRNA expression as biomarkers of disease activity in lupus nephritis

Introduction Renal involvement is one of the most serious manifestations of systemic lupus erythematosus, but non-invasive assessment of inflammatory response in kidneys is challenging. In this study we aimed to validate markers of active lupus nephritis (LN) using urine immune profiling. Methods Urine and serum cytokines (17-plex array) and urine mRNA expression (∼40 immune and glomerular injury genes) were measured in LN patients with active disease (n = 17) during remission (n = 16) and in healthy subjects (n = 18). Results Urine and serum levels of CCL2, CCL5 and CXCL10 were elevated in active LN as compared with disease remission (best discrimination for urine CXCL10 and CCL2) and correlated with LN activity. In the active disease, urinary cell transcriptome showed marked upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), and type-1 immunity-related genes (e.g. CD3G, CD4, TBX21, IFNG). An active pattern of gene expression was also observed in four patients in remission, who had moderately increased urinary leucocyte count. Two patients from this group developed renal exacerbation during the following 3 months. Markers of type-17 immune axis (e.g. IL-17A) were not significantly increased in active LN. Conclusions Active LN patients were characterized by marked increase of proinflammatory mediators in the urine. Urine cytokines (CCL2 and CXCL10) and type-1 T-cell-related gene markers in the urine sediment had similar diagnostic performance in detection of active LN.
Polymorphisms in LEPR, PPARG and APM1 genes: associations with energy intake and metabolic traits in young children.

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) in five genes - leptin, leptin receptor (LEPR), adiponectin (APM1), peroxisome proliferator-activated receptor gamma (PPARG) and uncoupling protein 1 - with anthropometric, metabolic, and dietary parameters in a Southern Brazilian cohort of 325 children followed up from birth to 4 years old. MATERIALS AND METHODS SNPs were analyzed using polymerase chain reaction-based procedures, and their association with phenotypes was evaluated by t-test, analysis of variance, and general linear models. RESULTS LEPR223Arg allele (rs1137101) was associated with higher daily energy intake at 4 years of age (P = 0.002; Pcorrected = 0.024). PPARG 12Ala-carriers (rs1801282) presented higher glucose levels than Pro/Pro homozygotes (P = 0.007; Pcorrected = 0.042). CONCLUSIONS Two of the six studied SNPs presented consistent associations, showing that it is already possible to detect the influences of genetic variants on susceptibility to overweight in 4-year-old children.
Carrot Juice Fermentations as Man-Made Microbial Ecosystems Dominated by Lactic Acid Bacteria

ABSTRACT Spontaneous vegetable fermentations, with their rich flavors and postulated health benefits, are regaining popularity. However, their microbiology is still poorly understood, therefore raising concerns about food safety. In addition, such spontaneous fermentations form interesting cases of man-made microbial ecosystems. Here, samples from 38 carrot juice fermentations were collected through a citizen science initiative, in addition to three laboratory fermentations. Culturing showed that Enterobacteriaceae were outcompeted by lactic acid bacteria (LAB) between 3 and 13 days of fermentation. Metabolite-target analysis showed that lactic acid and mannitol were highly produced, as well as the biogenic amine cadaverine. High-throughput 16S rRNA gene sequencing revealed that mainly species of Leuconostoc and Lactobacillus (as identified by 8 and 20 amplicon sequence variants [ASVs], respectively) mediated the fermentations in subsequent order. The analyses at the DNA level still detected a high number of Enterobacteriaceae, but their relative abundance was low when RNA-based sequencing was performed to detect presumptive metabolically active bacterial cells. In addition, this method greatly reduced host read contamination. Phylogenetic placement indicated a high LAB diversity, with ASVs from nine different phylogenetic groups of the Lactobacillus genus complex. However, fermentation experiments with isolates showed that only strains belonging to the most prevalent phylogenetic groups preserved the fermentation dynamics. The carrot juice fermentation thus forms a robust man-made microbial ecosystem suitable for studies on LAB diversity and niche specificity. IMPORTANCE The usage of fermented food products by professional chefs is steadily growing worldwide. Meanwhile, this interest has also increased at the household level. However, many of these artisanal food products remain understudied. Here, an extensive microbial analysis was performed of spontaneous fermented carrot juices which are used as nonalcoholic alternatives for wine in a Belgian Michelin star restaurant. Samples were collected through an active citizen science approach with 38 participants, in addition to three laboratory fermentations. Identification of the main microbial players revealed that mainly species of Leuconostoc and Lactobacillus mediated the fermentations in subsequent order. In addition, a high diversity of lactic acid bacteria was found; however, fermentation experiments with isolates showed that only strains belonging to the most prevalent lactic acid bacteria preserved the fermentation dynamics. Finally, this study showed that the usage of RNA-based 16S rRNA amplicon sequencing greatly reduces host read contamination.
Investigating Aerobic, Anaerobic Combine Technical Trainings' Effects on Performance in Tennis Players

The aim of this study is to investigate eight-week aerobic, anaerobic combine technical trainings' effects on developments of performance. 21 athletes of tennis proficiency students from Sports Sciences Department were joined to the study voluntarily. Participated in the research athletes' ages' mean was 22,2±0,3 year, lengths' mean was 177,3±1,4 cm, weights' mean was 69,5±1,4 kg. Trainings were planned as 8 week and 3 days a week, in each unit training 90 minutes. In the research flexibility, vertical jump, standing long jump, right-left hand-grip strength, back and leg strength, anaerobic power, 20 meters shuttle run test, 5 and 10 meters sprint run, 1 maximal strength and ITN technical tests were applied. For analyzing handled data statistically, SPSS programme was used. Paired Samples t Test was applied as statistical process. Comparing before and after training groups' Flexibility, Strength, 5 and 10 m. Sprint run, Anaerobic Power, 20 m. Shuttle Run Test and ITN Technical Test values; there were statistically found to be different in all measurements(p<0,05). As a result of this study found that, aerobic, anaerobic combine technical trainings affect positively biomotoric, physiologic and technical features.
MTHFR C 677 T genotype influences the isotopic enrichment of one-carbon metabolites in folate-compromised men consuming d 9-choline 1 – 3

Background: Homozygosity for the variant 677T allele in the methylenetetrahydrofolate reductase (MTHFR) gene increases the requirement for folate and may alter the metabolic use of choline. The choline adequate intake is 550 mg/d for men, although the metabolic consequences of consuming extra choline are unclear. Objective: Deuterium-labeled choline (d9-choline) as tracer was used to determine the differential effects of the MTHFR C677T genotype and the effect of various choline intakes on the isotopic enrichment of choline derivatives in folate-compromised men. Design: Mexican American men with the MTHFR 677CC or 677TT genotype consumed a diet providing 300 mg choline/d plus supplemental choline chloride for total choline intakes of 550 (n = 11; 4 with 677CC and 7 with 677TT) or 1100 (n = 12; 4 with 677CC and 8 with 677TT ) mg/d for 12 wk. During the last 3 wk, 15% of the total choline intake was provided as d9-choline. Results: Low but measurable enrichments of the choline metabolites were achieved, including that of d3-phosphatidylcholine (d3-PtdCho) —a metabolite produced in the de novo pathway via choline-derived methyl groups. Men with the MTHFR 677TT genotype had a higher urinary enrichment ratio of betaine to choline (P = 0.041), a higher urinary enrichment of sarcosine (P = 0.041), and a greater plasma enrichment ratio of d9-betaine to d9-PtdCho with the 1100 mg choline/d
Postfledging Survival of Grasshopper Sparrows in Grasslands Managed with Fire and Grazing

Abstract. More accurate estimates of survival after nestlings fledge are needed for population models to be parameterized and population dynamics to be understood during this vulnerable life stage. The period after fledging is the time when chicks learn to fly, forage, and hide from predators. We monitored postfledging survival, causespecific mortality, and movements of Grasshopper Sparrows (Ammodramus savannarum) in grassland managed with fire and grazing. In 2009, we attached radio transmitters to 50 nestlings from 50 different broods and modeled their survival in response to climatic, biological, and ecological variables. There was no effect of treatment on survival. The factor most influencing postfledging survival was age; no other variable was significant. The majority of chicks (74%) died within 3 days of radio-transmitter attachment. We attributed most mortality to mesopredators (48%) and exposure (28%). Fledglings' movements increased rapidly for the first 4 days after they left the nest and were relatively stable for the remaining 10 days we tracked them. On average, fledglings took flight for the first time 4 days after fledging and flew ≥10 m 9 days after fledging. Our data show that the Grasshopper Sparrow's survival rates may be less than most models relying on nest-success estimates predict, and we emphasize the importance of incorporating estimates of survival during the postfledging period in demographic models.
Introduction of Genetically Modified CD3ζ Improves Proliferation and Persistence of Antigen-Specific CTLs

It may be safer to improve adoptive T-cell therapy through increased signaling rather than increased antigen affinity of the TCRs. Modifying intracellular signaling enhanced the proliferation and persistence of CTLs while improving antitumor efficacy. The clinical efficacy of T-cell therapies based on T cells transduced with genes encoding tumor-specific T-cell receptors (TCR-T) is related to the in vivo persistence of the T cells. To improve persistence without modifying TCR affinity, we instead modified intracellular signaling, using artificial T cell–activating adapter molecules (ATAM), generated by inserting the intracellular domain (ICD) of activating T-cell signaling moieties into CD3ζ. ATAMs with the ICD of either CD28 or 4-1BB were generated, assembled into the TCR complex as a part of CD3ζ, and enhanced downstream signaling from the supramolecular activation cluster. ATAMs were retrovirally introduced into human CMV-specific or NY-ESO-1–specific TCR-transduced CD8+ T lymphocytes, and downstream functionality was then examined. ATAM-transduced NY-ESO-1 TCR-T cells were also investigated using the U266-xenograft mouse model. ATAMs were successfully transduced and localized to the cell membrane. ATAM-transduced CMV-specific T cells retained their cytotoxic activity and cytokine production against peptide-pulsed target cells without altering antigen-specificity and showed resistance to activation-induced cell death. Upon both single and repeated stimulation, CD3ζ/4-1BB–transduced T cells had superior proliferation to the CD3ζ-transduced T cells in both the CMV-specific and the NY-ESO-1 TCR-T models and significantly improved antitumor activity compared with untransduced T cells both in vitro and in a mouse xenograft model. ATAM-transduced TCR-T cells demonstrated improved proliferation and persistence in vitro and in vivo. This strategy to control the intracellular signaling of TCR-T cells by ATAM transduction in combination with various tumor-specific TCRs may improve the efficacy of TCR-T therapy. Cancer Immunol Res; 6(6); 733–44. ©2018 AACR.
RHIC and LHC phenomena with an unified parton transport

We discuss recent applications of the partonic pQCD based cascade model BAMPS with focus on heavy-ion phenomeneology in hard and soft momentum range. The nuclear modification factor as well as elliptic flow are calculated in BAMPS for RHIC end LHC energies. These observables are also discussed within the same framework for charm and bottom quarks. Contributing to the recent jet-quenching investigations we present first preliminary results on application of jet reconstruction algorithms in BAMPS. Finally, collective effects induced by jets are investigated: we demonstrate the development of Mach cones in ideal matter as well in the highly viscous regime.
Methyl balance and transmethylation fluxes in humans 1 4 S

Various questions have been raised about labile methyl balance and total transmethylation fluxes, and further discussion has been encouraged. This report reviews and discusses some of the relevant evidence now available. The fact that, if needed, labile methyl balance is maintained by methylneogenesis appears to be established, but several aspects of transmethylation remain uncertain: definitive measurements of the rate of total transmethylation in humans of both sexes on various diets and at various ages; the extent to which synthesis of phosphatidylcholine has been underestimated; and the relative contributions of the 2 pathways for the formation of sarcosine (ie, N-methylglycine). The available evidence indicates that the quantitatively most important pathways for S-adenosylmethionine–dependent transmethylation in mammals are the syntheses of creatine by guanidinoacetate methyltransferase, of phosphatidylcholine by phosphatidylethanolamine methyltransferase, and of sarcosine by glycine N-methyltransferase. Data presented in this report show that S-adenosylmethionine and methionine accumulate abnormally in the plasma of humans with glycine N-methyltransferase deficiency but not of those with guanidinoacetate N-methyltransferase deficiency or in the plasma or livers of mice devoid of phosphatidylethanolamine N-methyltransferase activity. The absence of such accumulations in the latter 2 conditions may be due to removal of S-adenosylmethionine by synthesis of sarcosine. Steps that may help clarify the remaining issues include the determination of the relative rates of synthesis of sarcosine, creatine, and phosphatidylcholine by rapid measurement of the rates of radiolabel incorporation into these compounds from L-[methyl-H]methionine administered intraportally to an experimental animal; clarification of the intracellular hepatic isotope enrichment value during stable-isotope infusion studies to enhance the certainty of methyl flux estimates during such studies; and definitive measurement of the dietary betaine intake from various diets. Am J Clin Nutr 2007;85:19–25.
The semantics of similarity in geographic information retrieval

Similarity measures have a long tradition in fields such as information retrieval, artificial intelligence, and cognitive science. Within the last years, these measures have been extended and reused to measure semantic similarity; i.e., for comparing meanings rather than syntactic differences. Various measures for spatial applications have been de- veloped, but a solid foundation for answering what they measure; how they are best ap- plied in information retrieval; which role contextual information plays; and how similarity values or rankings should be interpreted is still missing. It is therefore difficult to decide which measure should be used for a particular application or to compare results from dif- ferent similarity theories. Based on a review of existing similarity measures, we introduce a framework to specify the semantics of similarity. We discuss similarity-based information retrieval paradigms as well as their implementation in web-based user interfaces for geo- graphic information retrieval to demonstrate the applicability of the framework. Finally, we formulate open challenges for similarity research.
Leukocyte Telomere Length in Major Depression: Correlations with Chronicity, Inflammation and Oxidative Stress - Preliminary Findings

Background Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of “accelerated aging” in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. Methodology Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex. Principal Findings The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of “accelerated cell aging. ” Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05). Conclusions These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure.
Geochemical and Hydrological Observations for Earthquake Prediction in Japan

Several research groups have made efforts to accumulate reliable data on various geochemical and hydrological parameters for periods longer than 10 years. The data accumulation has enabled them to characterize background fluctuations in the data and consequently to examine their relation to earthquake occurrences without prejudice. As a result, a number of earthquake-related anomalies have consistently been identified in various geochemical and hydrological observations, suggesting that they are sensitive indicators of earthquake occurrence. Comprehensive monitoring based on multicomponent and multi-station observations has begun to result in the detection of more reliable precursory phenomena which appeared simultaneously in two or different kinds of observations at several stations.
Reciprocal relationships and the importance of feedback in patient and public involvement: A mixed methods study

Reciprocal relationships between researchers and patient and public involvement (PPI) contributors can enable successful PPI in research. However, research and anecdotal evidence suggest that researchers do not commonly provide feedback to PPI contributors thus preventing them from knowing whether, how or where their contributions were useful to researchers and research overall.