Miracle-dz/UniFAR-FTUs huggingface dataset:
A contribution of budding yeast to unravel aging. Entry into quiescence relies on the transceptor Mtl1 by sensing nutrients and regulation of signaling pathways

Saccharomyces cerevisiae is a premier model system to study ageing in post mitotic cells. In this study, we show that Mtl1, member of the Cell Wall Integrity pathway (CWI), plays a positive role in Chronological Life Span (CLS). The absence of Mtl1 shortens CLS whereas its overexpression extends it. In mtl1 cells, we observe mitochondrial dysfunction during diauxic shift that is reflected in i) increase in uncoupled respiration associated to low oxygen consumption; ii) significant increase in mitochondrial membrane potential; iii) ROS (Reactive Oxygen Species) accumulation and as well as iv) a descent in aconitase activity. We demonstrate that this mitochondrial dysfunction observed in mtl1 mutant is a consequence of improper regulation of key signaling pathwaysrequired for entry in quiescence. TOR1/SCH9 deletion and less effectively PKA (Protein Kinase A) inactivation in mtl1 not only suppressed the mitochondrial defects but also increased the CLS. Mtl1 links mitochondrial dysfunction with TOR (Target of Rapamycin) and PKA pathways in quiescence. In the absence of Mtl1, the stability of the inhibitory subunit of PKA, Bcy1 is severely reduced, mainly as a consequence of a high PKA activity. Mtl1 regulates PKA inactivation through Bcy1 phosphorylation, both in diauxic conditions and mainly in response to glucose depletion. In these conditions, Mtl1 negatively regulates Tor1/Sch9 function to phosphorylate Bcy1 and thus to inhibit PKA through phosphorylation of Bcy1 by Slt2 MAPK, although additional kinases might be also involved in this signal. We also show that Mtl1 function in CLS does not totally depend on CWI pathway since mtl1slt2 double mutant presents synthetic lethality. Mtl1 acts as a glucose sensor thereby it regulates both NCR (Nitrogen Catabolite Repression) and RTG (Retrograde Response Mitochondrial- Nucleus) pathways through Snf1 kinase upon glucose depletion, although independent of TORC1 and PKA functions. Again, additional targets are not completely ruled out. In conclusion, Mtl1 is an efficient transceptor involved in sensing and signaling nutrient availability in quiescence, mainly glucose, and in regulating multiple pathways involved in life extension.
Impact and consequences of intensive chemotherapy on intestinal barrier and microbiota in acute myeloid leukemia: the role of mucosal strengthening

ABSTRACT Induction chemotherapy (7 + 3 regimen) remains the gold standard for patients with acute myeloid leukemia (AML) but is responsible for gut damage leading to several complications such as bloodstream infection (BSI). We aimed to investigate the impact of induction chemotherapy on the intestinal barrier of patients with AML and in wild-type mice. Next, we assessed the potential benefit of strengthening the mucosal barrier in transgenic mice releasing a recombinant protein able to reinforce the mucus layer (Tg222). In patients, we observed a decrease of plasma citrulline, which is a marker of the functional enterocyte mass, of short-chain fatty acids and of fecal bacterial load, except for Escherichia coli and Enterococcus spp. , which became dominant. Both the α and β-diversities of fecal microbiota decreased. In wild-type mice, citrulline levels decreased under chemotherapy along with an increase of E. coli and Enterococcus spp load associated with concomitant histologic impairment. By comparison with wild-type mice, Tg222 mice, 3 days after completing chemotherapy, had higher citrulline levels, a faster healing epithelium, and preserved α-diversity of their intestinal microbiota. This was associated with reduced bacterial translocations. Our results highlight the intestinal damage and the dysbiosis induced by the 7 + 3 regimen. As a proof of concept, our transgenic model suggests that strengthening the intestinal barrier is a promising approach to limit BSI and improve AML patients’ outcome.
Prediction of individual differences in circadian adaptation to night work among older adults: application of a mathematical model using individual sleep-wake and light exposure data

ABSTRACT Circadian misalignment remains a distinct challenge for night shift workers. Variability in individual sleep-wake/light-dark patterns might contribute to individual differences in circadian alignment in night shift workers. In this simulation study, we compared the predicted phase shift from a mathematical model of the effect of light on the human circadian pacemaker to the observed melatonin phase shift among individuals who completed one of four interventions during simulated night shift work. Two inputs to the model were used to simulate circadian phase: sleep-wake/light-dark patterns measured from a wrist monitor (Simulation 1) and sleep-wake/light-dark patterns measured from a wrist monitor enhanced by known light levels measured at the level of the eye during simulated night shifts (Simulation 2). The estimated phase shift from the model was within 2 hours of the observed phase shift in ~80% of night shift workers for both simulations; none of the model-predicted phase shifts was more than ~3 hours from the observed phase shift. Overall, the root-mean-square error between observed and predicted phase shifts was better for Simulation 1. The light input from the wrist monitor informed by actual light level measured at the eye performed better in the sub-group exposed to bright light during their night shifts. The findings from this simulation study suggest that using a mathematical model combined with sleep-wake and light exposure data from a wrist monitor can facilitate the design of shift work schedules to enhance circadian alignment, which is expected to improve sleep, alertness, and performance.
Developmental onset of enduring long‐term potentiation in mouse hippocampus

Analysis of long‐term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L‐LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in the stratum radiatum of rat hippocampal area CA1. The goal here was to determine the developmental profile of synaptic plasticity leading to L‐LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6J and Fmr1−/y on the C57BL/6J background, and 129SVE and Hevin−/− (Sparcl1−/−) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse‐induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10‐P35 in the expression of short‐term potentiation (STP), lasting ≤1 hr. In the 129SVE mice, L‐LTP onset (>25% of slices) occurred by 3 weeks, reliable L‐LTP (>50% slices) was achieved by 4 weeks, and Hevin−/− advanced this profile by 1 week. In the C57BL/6J mice, L‐LTP onset occurred significantly later, over 3–4 weeks, and reliability was not achieved until 5 weeks. Although some of the Fmr1−/y mice showed L‐LTP before 3 weeks, reliable L‐LTP also was not achieved until 5 weeks. L‐LTP onset was not advanced in any of the mouse genotypes by multiple bouts of theta‐burst stimulation at 90 or 180 min intervals. These findings show important species differences in the onset of STP and L‐LTP, which occur at the same age in rats but are sequentially acquired in mice.
Blood transfusion following major orthopaedic surgery in cerebral palsy: a retrospective analysis

Progressive musculoskeletal pathology is ubiquitous among children with cerebral palsy (CP). Corrective surgery places them at risk of major blood loss and red blood cell (RBC) transfusion. Significant variability exists in uptake of perioperative patient blood management (PBM) strategies. This study aimed to examine factors contributing to RBC transfusion and assist in future development of care pathways.
HIV serostatus, inflammatory biomarkers and the frailty phenotype among older people in rural KwaZulu-Natal, South Africa

Objective: We compared the prevalence of frailty by HIV serostatus and related biomarkers to the modified frailty phenotype among older individuals in a rural population in South Africa. Methods: Questionnaire data were from a cohort of people living with HIV (PWH) on antiretroviral therapy (ART) and HIV-uninfected people aged 50 years and older sampled from the Africa Health Research Institute Demographic Health and Surveillance area in northern KwaZulu-Natal. The prevalence of frailty was compared using five categories: (1) physical activity; (2) mobility; (3) fatigue; (4) gait speed; and (5) grip strength, and assessed for demographic, clinical, and inflammatory correlates of frailty. Results: Among 614 individuals in the study, 384 (62.5%) were women. The median age at study enrolment was 64 years [Interquartile range (IQR) (58.6–72.0)]. 292 (47.6%) were PWH. 499 (81%) were classified as either pre-frail or frail. 43 (7%) were frail and HIV positive, 185 (30%) were pre-frail and HIV positive, 57 were frail and HIV negative and 214 (35%) were pre-frail and HIV negative. Frailty was similar for HIV negative and PWH (17.7% vs 14.7%, p = 0.72). Women were more likely to be frail (18.3% vs 13.04%, p = 0.16). The prevalence of frailty increased with age for both HIV groups. In the multivariable analysis, the odds of being frail were higher in those aged 70 years and above than those aged between 50 and 59 years (p < 0.001). Females were less likely to be pre-frail than males (p < 0.001). There was no association between any of the inflammatory biomarkers and frailty and pre-frailty. Conclusion: In this population, the prevalence of frailty is similar for PWH and people without HIV, but higher for women than men. These data suggest that the odds of developing frailty is similar for PWH over the age of 50 years, who survive into older age, as for people without HIV.
Fate of Enterohemorrhagic Escherichia coli O157: H7 in Commercial Mayonnaise.

The fate of enterohemorrhagic Escherichia coli O157:H7 was determined in three different lots of commercial mayonnaise, including four different samples from a lot implicated in an outbreak of E. coli O157:H7 infection. The initial pH of the products ranged from 3.6 to 3.9. Products were inoculated with 6.5 × 103 E. coli O157:H7/g and incubated at 5 or 20°C. Escherichia coli O157:H7 did not grow at either temperature but survived for 34 to 55 days at 5°C and for 8 to 21 days at 20°C, depending on the lot. Survival was greatest in real mayonnaise purchased at retail among six mayonnaise samples which included a reduced calorie mayonnaise. Escherichia coli O157:H7 populations decreased between 2- and 100-fold by 3 weeks at 5°C, and between 10- and 1,000-fold by 7 days at 20°C. There was little or no change in pH (<0.1 unit), aerobic plate count, mold and yeast count or Lactobacillus count (< 1 log10 CFU/g) for the duration of the study. Commercial mayonnaise manufactured under good manufacturing practices is not a public health concern. Abusive handling of mayonnaise resulting in cross-contamination with E. coli O157:H7-contaminated food or contamination by an infected foodhandler is the principal basis for concern.
Omega‐3 fatty acids and neurocognitive ability in young people at ultra‐high risk for psychosis

Neurocognitive impairments are core early features of psychosis and are observed in those at ultra‐high risk (UHR) for psychosis. The aim of the present study was to explore whether neurocognition is associated with polyunsaturated fatty acids (PUFAs), as has been observed in other clinical populations.
Metabolic syndrome and its components in people with intellectual disability: a meta-analysis.

BACKGROUND People with intellectual disability have an increased risk for cardiovascular diseases and associated premature mortality. Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The aim of this meta-analysis was to describe the pooled prevalence of MetS and its components in people with intellectual disability taking into account variations in demographic, clinical and treatment-related variables. METHODS Pubmed, Embase and CINAHL were searched until 5 August 2020 for studies reporting cross-sectional data on prevalences of MetS and its components in people with intellectual disability. Two independent reviewers extracted data. Random effects meta-analyses with subgroup and meta-regression analyses were employed. RESULTS The pooled MetS prevalence after adjusting for publication bias was 22.5% [95% confidence interval (CI) = 16.8%-29.6%; N studies = 10; n participants = 2443, median age at study level = 38.5 years; 52% male]. Abdominal obesity was observed in 52.0% (95% CI = 42.0%-61.9%; I2 = 86.5; N = 5; n = 844), hypertension in 36.7% (95% CI = 26.1%-48.7%; N = 6; n = 926), hypertriglyceridaemia in 23.5% (95% CI = 18.8%-28.9%; N = 5; n = 845), low high-density-lipoprotein-cholesterol in 23.4% (95% CI = 19.3%-28.0%; N = 6; n = 917), and hyperglycaemia in 10.2% (95% CI = 7.6%-13.3%; N = 5; n = 845). Meta-regression revealed that a higher MetS frequency was moderated by older age (coefficient = 0.03; standard error = 0.01, 95% CI = 0.008 to 0.055; N = 19; n = 2443) and a higher proportion of people on antidepressants in the study (coefficient = 7.24; standard error = 0.90, 95% CI = 5.48-9.00; N = 4; n = 546). There were insufficient data comparing MetS in people with intellectual disability with age-matched and gender-matched controls. CONCLUSIONS Considering that more than one fifth of people with intellectual disability have MetS, routine screening and multidisciplinary management of metabolic abnormalities in people with intellectual disability is needed. Attention should be given to older people and those on antidepressants.
A role for the tubular Na+-H+-exchanger NHE3 in the natriuretic effect of the SGLT2 inhibitor empagliflozin.

Inhibitors of the proximal tubular sodium glucose cotransporter SGLT2 are natriuretic and they lower blood pressure. There are reports that the activities of SGLT2 and the Na+-H+-exchanger, NHE3, are coordinated. If so, then part of the natriuretic response to an SGLT2 inhibitor is mediated by suppressing NHE3. To examine this further, we compared the effects of the SGLT2 inhibitor, empagliflozin, on urine composition and systolic blood pressure (SBP) in non-diabetic mice with tubule-specific NHE3 knock-down (NHE3-ko) and wild-type littermates (WT). A single dose of empagliflozin, titrated to cause minimal glucosuria, increased urinary excretion of Na+ and bicarbonate, and raised urine pH in WT, but not in NHE3-ko. Chronic empagliflozin treatment tended to lower SBP despite higher renal renin mRNA expression, and lowered the ratio of SBP to renin mRNA, indicating volume loss. This effect of empagliflozin depended on tubular NHE3. In diabetic Akita mice, chronic empagliflozin enhanced phosphorylation of NHE3 (S552/S605), changes previously linked to lesser NHE3-mediated reabsorption. Chronic empagliflozin also increased expression of genes involved with renal gluconeogenesis, bicarbonate regeneration, and ammonium formation. While this could reflect compensatory responses to acidification of proximal tubular cells resulting from reduced NHE3 activity, these effects were at least in part independent of tubular NHE3 and potentially indicated metabolic adaptations to urinary glucose loss. Moreover, empagliflozin increased luminal α-ketoglutarate, which may serve to stimulate compensatory distal NaCl reabsorption, while co-generated and excreted ammonium balances urine losses of this "potential bicarbonate". The data implicate NHE3 as a determinant of the natriuretic effect of empagliflozin.
Impact of nutrients and water level changes on submerged macrophytes along a temperature gradient: A pan‐European mesocosm experiment

Submerged macrophytes are of key importance for the structure and functioning of shallow lakes and can be decisive for maintaining them in a clear water state. The ongoing climate change affects the macrophytes through changes in temperature and precipitation, causing variations in nutrient load, water level and light availability. To investigate how these factors jointly determine macrophyte dominance and growth, we conducted a highly standardized pan‐European experiment involving the installation of mesocosms in lakes. The experimental design consisted of mesotrophic and eutrophic nutrient conditions at 1 m (shallow) and 2 m (deep) depth along a latitudinal temperature gradient with average water temperatures ranging from 14.9 to 23.9°C (Sweden to Greece) and a natural drop in water levels in the warmest countries (Greece and Turkey). We determined percent plant volume inhabited (PVI) of submerged macrophytes on a monthly basis for 5 months and dry weight at the end of the experiment. Over the temperature gradient, PVI was highest in the shallow mesotrophic mesocosms followed by intermediate levels in the shallow eutrophic and deep mesotrophic mesocosms, and lowest levels in the deep eutrophic mesocosms. We identified three pathways along which water temperature likely affected PVI, exhibiting (a) a direct positive effect if light was not limiting; (b) an indirect positive effect due to an evaporation‐driven water level reduction, causing a nonlinear increase in mean available light; and (c) an indirect negative effect through algal growth and, thus, high light attenuation under eutrophic conditions. We conclude that high temperatures combined with a temperature‐mediated water level decrease can counterbalance the negative effects of eutrophic conditions on macrophytes by enhancing the light availability. While a water level reduction can promote macrophyte dominance, an extreme reduction will likely decrease macrophyte biomass and, consequently, their capacity to function as a carbon store and food source.
The Trapping Effect of Aggregation Pheromone for the Red Palm Weevil(Rhynchorus ferrugineus(Olivier)) and Its Traps Development

The development and use of aggregation pheromone traps and the trapping effect of pheromone for the red palm weevil in the field were introduced and studied in this paper.The results showed that the average population was 21.21 head per month for each trap,with 1∶0.90 ratio of female to male.The average trapped population per trap was the highest(34.25 head) in July.The climate conditions had an obvious influence on the trapping effect of pheromone for the red palm weevil.The trapping population was significantly reduced in the conditions of rain and low temperature.
Comparison of culture method and real-time PCR for detection of putative periodontopathogenic bacteria in deep periodontal pockets

The goal of this study was to compare the diagnostic potential of microbiological culture and real-time polymerase chain reaction (PCR) identification, regarding patients with severe chronic periodontitis. Sixty patients were enrolled in this study and 300 microbiological samples were obtained from pockets with probing depth >7 mm. The presence of nine periodontal pathogens was evaluated with both culture analysis and real-time PCR identification. The comparison of both methods revealed a better diagnostic capability of the real-time PCR for all of the investigated pathogens, with statistically significant higher detection levels of 100% for Treponema denticola, Tanerella forsythia, Peptostreptococcus micros and Capnocytophaga gingivalis, 93.33% for Porphyromonas gingivalis, 80% for Prevotella intermedia, 76.67% for Fusobacterium nucleatum and Eubacterium nodatum, and 30% for Aggregatibacter actinomycetemcomitans. Only three pathogens were detected by using culture analysis – P. gingivalis and P. intermedia in 33.33% of the patients, and T. forsythia in 43.33% of the patients. The real-time PCR quantitative determination presented 65.82% prevalence of the red complex. Better sensitivity of the real-time PCR, when compared to the microbiological culture method, was demonstrated, in regards to the detection of the periodontal pathogens. These discrepancies may be explained by the lower detection levels of the cultivation methods, when compared to the real-time PCR and the problems of keeping pathogenic bacteria viable, which is required for the standard cultivation.
Effect of different media and temperature on growth of Fusarium moniliforme causing foot rot of basmati rice and its survival

Investigations were conducted to find the suitable media, effect of temperature on growth of Fusarium moniliforme and its survival under different conditions. Potato Dextrose Agar was found to be best medium for growth and sporulation of F. moniliforme followed by Nutrient Glucose Agar and Richard Agar. Growth was significantly influenced at different temperatures and maximum radial growth of 81 mm was recorded at a temperature of 30±2oC followed by 78 mm at 25±2 oC. Studies on the survival of pathogen revealed that it can survive for longer period of time both at room temperature and in refrigerator. However, percentage of survival greatly reduced with time in both the cases. Survival of F. moniliforme in soil reduced with passage of time. The total survival period of the fungus was for five to six months in soil. It was found that in the infected grains and straw bits collected in November, 2009 after harvesting, survival percentage was > 90% up to the month of March, 2010. It further reduced to 5.55–16.10% under different conditions till January, 2011.
Involvement of cGMP in cellular melatonin responses *

Melatonin can enhance and suppress constitutive protein secretion from murine melanoma M2R cells in vitro in a cholera‐toxin (CTX) sensitive process. In a number of tissues melatonin has been shown to modulate cGMP levels. The involvement of cGMP in melatonin responses in the melanoma cells was investigated. The effects of melatonin on melanoma cells cGMP and cGMP‐phosphodiesterase activity and the effects of cGMP analogs on the melatonin‐mediated modulation of protein secretion were studied. Melatonin reduced cGMP levels in the melanoma cells. CTX treatment had a similar and non‐additive effect. The effects of melatonin on protein secretion were abrogated by activation of cGMP‐dependent protein kinases. In addition, melatonin inhibited cGMP phosphodiesterase activity in these cells. The data presented indicate that inhibition of cGMP via a CTX sensitive G protein may be a major signal transduction pathway used by melatonin in melanoma cells.
Study on the roles of HLA-A gene polymorphism in the susceptibility and symptom of SARS-Coronavirus infection

Objective:To study the association between HLA-A gene polymorphism and the susceptibility and symptom of SARS-Coronavirus infection in Northern Chinese Han ethnics.Methods:HLA-A were typed in 53 SARS cases,44 high risks and 77 controls using PCR-SBT methods in two case-control studies.Data were analyzed using SPSS version 11.5 and chi squares and OR were used to show the differences and association.Results:The frequency of HLA-A*2453 allele in SARS patients was markedly higher than that of the high risk care workers(P=0.039,OR=4.479,95%CI 0.955-21.015). However,the frequency of HLA-A*2444 allele in SARS patients was lower than that of the health control(P=0.029). There was no significant difference of the distribution of HLA-A allele frequency in mild cases and severe cases.Conclusion:Genotype of HLA-A*2453 may be one risk factor for infection of SARS-Cov,however,HLA-A*2444 may be protect factor for it infection.The severity of SARS may not relate with the genotype of HLA-A.