EARLY FLOWERING3 sub-nuclear localization responds to changes in ambient temperature.
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ABSTRACT:
SUBMITTER: Ronald J
PROVIDER: S-EPMC8644450 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:TonEBP is a Rel domain-containing transcription factor implicated in adaptive immunity, viral replication, and cancer. In the mammalian kidney, TonEBP is a central regulator of water homeostasis. Animals deficient in TonEBP suffer from life-threatening dehydration due to renal water loss. Ambient tonicity (effective osmolality) is the prominent signal for TonEBP in a bidirectional manner; TonEBP activity decreases in hypotonicity, whereas it increases in hypertonicity. Here we found that TonEBP displayed nuclear export in response to hypotonicity and nuclear import in response to hypertonicity. The nuclear export of TonEBP was not mediated by the nuclear export receptor CRM1 or discrete nuclear export signal. In contrast, a dominant nuclear localization signal (NLS) was found in a small region of 16 amino acid residues. When short peptides containing the NLS were fused to constitutively cytoplasmic proteins, the fusion proteins displayed tonicity-dependent nucleocytoplasmic trafficking like TonEBP. Thus, tonicity-dependent activation of the NLS is crucial in the nucleocytoplasmic trafficking of TonEBP. The novel NLS is present only in the vertebrates, indicating that it developed late in evolution.
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Project description:BackgroundExtreme temperature is associated with adverse birth outcomes but it is unclear whether it increases early delivery risk.ObjectivesWe aimed to determine the association between ambient temperature and early delivery.MethodsMedical records from 223,375 singleton deliveries from 12 U.S. sites were linked to local ambient temperature. Exposure to hot (> 90th percentile) or cold (< 10th percentile) using site-specific and window-specific temperature distributions were defined for 3-months preconception, 7-week periods during the first two trimesters, 1 week preceding delivery, and whole pregnancy. Poisson regression with generalized estimating equations calculated the relative risk (RR) and 95% confidence interval for early deliveries associated with hot/cold exposures, adjusting for conception month, humidity, site, sex, maternal demographics, parity, insurance, prepregnancy body mass index, pregnancy complications, and smoking or drinking during pregnancy. Acute temperature associations were estimated separately for warm (May-September) and cold season (October-April) in a case-crossover analysis using conditional logistic regression.ResultsCompared with mild temperature (10-90th percentile), exposure to hot or cold during weeks 1-7 increased risk for early preterm (< 34 weeks) [RRhot: 1.11 (95% CI: 1.01, 1.21); RRcold: 1.20 (95% CI: 1.11, 1.30)], late preterm (34-36 weeks) [RRcold: 1.09 (95% CI: 1.04, 1.15)], and early term (37-38 weeks) [RRhot: 1.04 (95% CI: 1.02, 1.07); RRcold: 1.03 (95% CI: 1.00, 1.05)] delivery. Findings were similar for hot exposures during weeks 15-21. Examining deliveries at each week from 23 through 38, whole-pregnancy hot exposures increased delivery risk by 6-21% at weeks 34 and 36-38. In the case-crossover analysis, a 5°F increase during the week preceding delivery was associated with 12-16% higher and 4-5% lower early delivery risk during warm and cold season, respectively.ConclusionsBoth acute and chronic ambient temperature extremes may affect early delivery risk. Citation: Ha S, Liu D, Zhu Y, Kim SS, Sherman S, Mendola P. 2017. Ambient temperature and early delivery of singleton pregnancies. Environ Health Perspect 125:453-459;?http://dx.doi.org/10.1289/EHP97.
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Project description:BackgroundSub-nuclear structures or locations are associated with various nuclear processes. Proteins localized in these substructures are important to understand the interior nuclear mechanisms. Despite advances in high-throughput methods, experimental protein annotations remain limited. Predictions of cellular compartments have become very accurate, largely at the expense of leaving out substructures inside the nucleus making a fine-grained analysis impossible.ResultsHere, we present a new method (LocNuclei) that predicts nuclear substructures from sequence alone. LocNuclei used a string-based Profile Kernel with Support Vector Machines (SVMs). It distinguishes sub-nuclear localization in 13 distinct substructures and distinguishes between nuclear proteins confined to the nucleus and those that are also native to other compartments (traveler proteins). High performance was achieved by implicitly leveraging a large biological knowledge-base in creating predictions by homology-based inference through BLAST. Using this approach, the performance reached AUC = 0.70-0.74 and Q13 = 59-65%. Travelling proteins (nucleus and other) were identified at Q2 = 70-74%. A Gene Ontology (GO) analysis of the enrichment of biological processes revealed that the predicted sub-nuclear compartments matched the expected functionality. Analysis of protein-protein interactions (PPI) show that formation of compartments and functionality of proteins in these compartments highly rely on interactions between proteins. This suggested that the LocNuclei predictions carry important information about function. The source code and data sets are available through GitHub: https://github.com/Rostlab/LocNuclei .ConclusionsLocNuclei predicts subnuclear compartments and traveler proteins accurately. These predictions carry important information about functionality and PPIs.
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Project description:BackgroundBoth increases and decreases in ambient temperature have been associated with increased cardiovascular mortality and morbidity. However, the mechanism(s) remain unclear.ObjectivesWe examined associations between biomarkers of pathways thought to, in part, explain these associations and changes in ambient temperature in a panel of predominantly post-myocardial infarction or post-stent patients.MethodsWe studied 76 subjects who had a recent coronary event and were participating in a cardiac rehabilitation program. In these patients, we measured heart rate variability, repolarization, and baroreflex sensitivity parameters using Holter ECG recordings before and during supervised, graded, twice weekly, exercise sessions. Hourly temperature measurements were made at a monitoring site near the rehabilitation center.ResultsUsing linear mixed models, we observed decreases in rMSSD (square root of the mean of the sum of the squared differences between adjacent NN intervals) and deceleration capacity, associated with increases in ambient temperature in the previous four days. Additionally, decreased rMSSD was associated with both increasing temperature (mean in previous 6 hours) in the summer and decreasing temperature (mean in the previous 3 weeks) in the winter.ConclusionsIn a panel of cardiac rehabilitation patients, changes in ambient temperature were associated with decreases in markers of heart rate variability and baroreflex sensitivity, which may lead to increased risk of arrhythmic events and sudden death in post-infarction patients.
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Project description:Zinc transporters have been characterized to further understand the absorption and metabolism of dietary zinc. Our goal was to characterize zinc transporter Slc39a11 (ZIP11) expression and its subcellular localization within cells of the murine gastrointestinal tract of mice and to determine if dietary zinc regulates ZIP11. The greatest ZIP11 expression was in the stomach, cecum, and colon. Both Zip11 mRNA and ZIP11 protein were shown to be downregulated during dietary zinc restriction (<1 mg Zn/kg) in the murine stomach tissue but were unaffected in the colon. Acute repletion with zinc did not restore Zip11 mRNA levels in the stomach. Immunohistochemistry (IHC) revealed high ZIP11 levels in the lower regions of gastric glands and parietal cells of the stomach. IHC analysis of the colon showed a marked ZIP11 abundance within the cytoplasm of the colonic epithelial cells. IHC also showed an increase in ZIP11 expression in the colon during zinc restriction. There is a robust abundance of ZIP11 in the nuclei of cells of both stomach and colon. Our experiments suggest that when dietary zinc intake is compromised, the colon may increase zinc transporter expression to improve the efficiency for absorption via increased expression of specific zinc transporters, including ZIP11 and also zinc transporter Slc39a4. In conclusion, ZIP11 is highly expressed within the murine stomach and colon and appears to be partially regulated by dietary zinc intake within these tissues. ZIP11 may play a specialized role in zinc homeostasis within these tissues, helping to maintain mucosal integrity and function.
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Project description:BackgroundClimate change is increasing global average temperatures, as well as the frequency of extreme weather events. Both low and high ambient temperatures have been associated with elevated mortality; however, little is known about the cardiovascular impacts of hourly temperature.MethodsWe assessed the association between hourly ambient temperature and risk of myocardial infarction (MI) across adult residents of New York State (NYS). We identified cases across NYS hospitals from 2000 to 2015 in the New York Department of Health Statewide Planning and Research Cooperative System dataset, using ICD codes. Hourly ambient temperature was assessed at each patient's residential ZIP code, up to 48 hours prior to MI. We employed a time-stratified case-crossover study design matching case to control periods on hour of day, day of week, month and year.ResultsOf the 791,695 primary MI hospital admissions, 45% were female, the mean (standard deviation; SD) age was 70 (15) years, and 49% of cases occurred among New York City residents. The observed temperature range was -29 °C to 39 °C, with a mean of 10.8 °C (10.5 °C). Temperature in the 6 h preceding the MI was positively associated with risk of MI, across the range of observed temperatures, with null or nearly null associations for earlier hours. We estimated a cumulative percent increase in hourly myocardial infarction rate of 7.9% (95% confidence interval [CI]: 5.2%, 10.6%) for an 11 °C (median) to 27 °C (95th percentile) temperature increase for lag hours 0-5. Men, Medicare-ineligible individuals (age < 65), and those experiencing their first MI were most sensitive.ConclusionOur study provides evidence that increases in hourly ambient temperature can trigger myocardial infarction. Health-based definitions of extreme heat events may better capture the deleterious effects of heat by accounting for hourly temperature. Our findings can inform the design of more effective preparedness strategies for the increasingly frequent extreme heat events.
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Project description:Changes in ambient temperature influence crop fertility and production. Understanding of how crops sense and respond to temperature is thus crucial for sustainable agriculture. The thermosensitive genic male-sterile (TGMS) lines are widely used for hybrid rice breeding and also provide a good system to investigate the mechanisms underlying temperature sensing and responses in crops. Here, we show that OsMS1 is a histone binding protein, and its natural allele OsMS1wenmin1 confers thermosensitive male sterility in rice. OsMS1 is primarily localized in nuclei, while OsMS1wenmin1 is localized in nuclei and cytoplasm. Temperature regulates the abundances of OsMS1 and OsMS1wenmin1 proteins. The high temperature causes more reduction of OsMS1wenmin1 than OsMS1 in nuclei. OsMS1 associates with the transcription factor TDR to regulate expression of downstream genes in a temperature-dependent manner. Thus, our findings uncover a thermosensitive mechanism that could be useful for hybrid crop breeding.
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Project description:BackgroundPreterm birth is a major determinant of adverse health consequences, and early term births are also associated with increased risk of various outcomes. In light of climate change, the effect of ambient temperature on earlier delivery is an important factor to consider. Several studies have focused on associations of ambient air temperature (Ta) on preterm birth, but few have examined associations with early term births.AimsTo investigate the association of prenatal exposure to Ta with preterm birth (<37 completed gestation weeks) and with early-term birth (<39 completed gestation weeks) in a semi-arid climate.MethodsAll singleton deliveries at the Soroka Medical Center from the Southern district of Israel, with estimated conception dates between May 1, 2004 and March 31, 2013 (N = 62,547) were linked to prenatal Ta estimates from a spatiotemporally resolved model, with daily 1 km resolution. We used time-dependent Cox regression models with weekly mean Ta throughout gestation, adjusted for calendar month and year of conception, ethnicity, census-level socio-economic status and population density.ResultsTa was positively associated with late preterm birth (31 + 0/7 - 36 + 6/7 weeks), with increased risk in the upper Ta quintile as compared to the third quintile, hazard ratio (HR) = 1.31, 95% confidence interval (CI) = 1.11-1.56. Ta also associated with early term birth (37 + 0/6 - 38 + 6/7), with increased risk in the upper Ta quintile as compared to the third quintile, HR = 1.24, 95% CI = 1.13-1.36.ConclusionExposure to high ambient temperature during pregnancy is associated with a higher risk of preterm and early term birth in southern Israel.
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Project description:Staphylococcus aureus is an opportunistic pathogen that colonizes the anterior nares of 30 to 50% of the population. Colonization is most often asymptomatic; however, self-inoculation can give rise to potentially fatal infections of the deeper tissues and blood. Like all bacteria, S. aureus can sense and respond to environmental cues and modify gene expression to adapt to specific environmental conditions. The transition of S. aureus from the nares to the deeper tissues and blood is accompanied by changes in environmental conditions, such as nutrient availability, pH, and temperature. In this study, we perform transcriptomics and proteomics on S. aureus cultures growing at three physiologically relevant temperatures, 34°C (nares), 37°C (body), and 40°C (pyrexia), to determine if small scale, biologically meaningful alterations in temperature impact S. aureus gene expression. Results show that small but definite temperature changes elicit a large-scale restructuring of the S. aureus transcriptome and proteome in a manner that, most often, inversely correlates with increasing temperature. We also provide evidence that a large majority of these changes are modulated at the posttranscriptional level, possibly by sRNA regulatory elements. Phenotypic analyses were also performed to demonstrate that these changes have physiological relevance. Finally, we investigate the impact of temperature-dependent alterations in gene expression on S. aureus pathogenesis and demonstrate decreased intracellular invasion of S. aureus grown at 34°C. Collectively, our results demonstrate that small but biologically meaningful alterations in temperature influence S. aureus gene expression, a process that is likely a major contributor to the transition from a commensal to pathogen.IMPORTANCE Enteric bacterial pathogens, like Escherichia coli, are known to experience large temperature differences as they are transmitted through the fecal oral route. This change in temperature has been demonstrated to influence bacterial gene expression and facilitate infection. Staphylococcus aureus is a human-associated pathogen that can live as a commensal on the skin and nares or cause invasive infections of the deeper tissues and blood. Factors influencing S. aureus nasal colonization are not fully understood; however, individuals colonized with S. aureus are at increased risk of invasive infections through self-inoculation. The transition of S. aureus from the nose (colonization) to the body (infection) is accompanied by a modest but definite temperature increase, from 34°C to 37°C. In this study, we investigate whether these host-associated small temperature changes can influence S. aureus gene expression. Results show widespread changes in the bacterial transcriptome and proteome at three physiologically relevant temperatures (34°C, 37°C, and 40°C).
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