Mosquitoes must feed on vertebrate blood for egg development. As a consequence, some mosquito species are vectors for pathogens that cause devastating diseases in humans. Hence, understanding the ...mechanisms that control egg developmental cycles is important for developing novel approaches for the control of mosquito‐borne diseases. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum (ER) stress. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the ER. Massive proteins have been shown to be produced during egg development, and it is obvious that unfolded or misfolded proteins may arise during vitellogenesis. It has been shown that autophagy in the mosquito fat body plays a central role in the progression of gonadotrophic cycles in the mosquito Aedes aegypti. However, the molecular mechanisms underlying the induction of UPR and the correlation between UPR and autophagy remain unclear. Here, we demonstrate that autophagy is activated during vitellogenesis and that the activation of autophagy is correlated with the UPR. We also show that the expressions of UPR and autophagy can be induced in an in vitro fat body culture system through an amino acid treatment. In addition, the expressions of UPR, autophagy‐specific markers and vitellogenin were also induced during dithiothreitol treatment. Interestingly, the silencing of UPR‐related genes significantly reduced the expression of autophagy‐specific markers and inhibited mosquito fecundity. Taken together, we conclude that autophagy‐mediated egg production in the mosquito A. aegypti is regulated by UPR.
Unfolded protein response (UPR) is responsible for the activation of autophagy during mosquito vitellogenesis.
The expressions of UPR and autophagy can be induced in an in vitro fat body culture system.
Silencing of UPR‐related genes significantly reduced the expression of autophagy‐specific markers and inhibited mosquito fecundity.
Objectives
We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD).
Design
Retrospective observational ...cohort.
Setting and Participants
At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center.
Measurements
Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function.
Results
Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25–75% of FVC (FEF25–75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors.
Conclusion
Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.
Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV-level electron-positron colliders. Current staging schemes ...feed subsequent laser pulses into stages using plasma mirrors while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize the simultaneous coupling of the electron beam and the laser pulse into a second stage. A partly curved channel, integrating a straight acceleration stage with a curved transition segment, is used to guide a fresh laser pulse into a subsequent straight channel, while the electrons continue straight. This scheme benefits from a shorter coupling distance and continuous guiding of the electrons in plasma while suppressing transverse beam dispersion. Particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration while maintaining high capture efficiency, stability, and beam quality.
The ERK pathway not only upregulates growth-promoting genes, but also downregulates anti-proliferative and tumor-suppressive genes. In particular, ERK signaling contributes to repression of the ...E-cadherin gene during epithelial-mesenchymal transition (EMT). The CtBP transcriptional co-repressor is also involved in gene silencing of E-cadherin. However, the functional relationship between ERK signaling and CtBP is unknown. Here, we identified an ERK substrate, designated MCRIP1, which bridges ERK signaling and CtBP-mediated gene silencing. CtBP is recruited to promoter elements of target genes by interacting with the DNA-binding transcriptional repressor ZEB1. We found that MCRIP1 binds to CtBP, thereby competitively inhibiting CtBP-ZEB1 interaction. When phosphorylated by ERK, MCRIP1 dissociates from CtBP, allowing CtBP to interact with ZEB1. In this manner, the CtBP co-repressor complex is recruited to, and silences, the E-cadherin promoter by inducing chromatin modifications. Our findings reveal a molecular mechanism underlying ERK-induced epigenetic gene silencing during EMT and its dysregulation in cancer.
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•A previously uncharacterized protein, MCRIP1, was identified as an ERK substrate•Unphosphorylated MCRIP1 binds to and inhibits the transcriptional co-repressor CtBP•When phosphorylated by ERK, MCRIP1 releases CtBP to induce chromatin modifications•ERK-induced MCRIP1 phosphorylation is critical for E-cadherin gene silencing and EMT
The ERK pathway not only upregulates growth-related genes, but also downregulates tumor-suppressive genes, although the latter mechanism remains ill-defined. Ichikawa et al. demonstrate that MCRIP1, an ERK substrate, mediates crosstalk between ERK signaling and the transcriptional co-repressor CtBP, and functions in ERK-induced epigenetic gene silencing of E-cadherin during epithelial-mesenchymal transition.
Preliminary studies suggest that maternal heat stress (HS) during late gestation exerts carryover effects on a calf’s insulin response after weaning, but a comprehensive evaluation of how maternal HS ...affects calf intake, growth, and metabolic response from birth to weaning is lacking. Our objective was to evaluate the effects of maternal HS during the dry period on dry matter intake, growth, and metabolism from birth to weaning. After birth, 20 heifers born to either HS (n=10) or cooled (CL, n=10) dry cows were immediately separated from their dams and fed 3.8 L of colostrum from a common pool within 4h of birth. All heifers were managed identically and weaned at 49 d of age (DOA). Calf starter intake was recorded daily, and body weight was assessed at birth and every 2 wk from birth to 56 DOA. Blood samples were collected twice a week until 56 DOA to assess hematocrit and concentrations of insulin and metabolites. To evaluate metabolic responses to maternal HS, a glucose tolerance test, insulin, and epinephrine challenge were performed on 3 consecutive days for all heifers at 8, 29, and 57 DOA. Maternal HS during the dry period did not affect heifer birth weight. Compared with HS, CL calves consumed more starter (0.53 vs. 0.34kg/d) from birth to 56 DOA and were heavier (71.7 vs. 61.4kg) at 56 DOA. Relative to HS calves, CL calves tended to have higher hematocrit (27.4 vs. 24.7%). No differences were found between treatments in plasma concentrations of insulin and glucose, but HS calves had higher nonesterified fatty acids and β-hydroxybutyrate concentrations after 32 DOA. Compared with CL, HS calves had a faster glucose clearance after a glucose tolerance test and a slower insulin clearance after an insulin challenge. In conclusion, maternal HS during late gestation reduces calf starter intake and growth, alters blood metabolite profile, and increases noninsulin-dependent glucose uptake.
Aims
To reveal the relationship of the bacterial communities in shrimp intestine and surrounding environments.
Methods and Results
We examined bacterial communities in the intestine of pacific white ...shrimp, Litopenaeus vannamei, the surrounding water and sediment by high‐throughput sequencing analysis. Sequences were clustered into operational taxonomic units (OTUs) at 97% similarity levels, which ranged from 4956 to 5976 in each sample. All OTUs were affiliated with at least 64 phyla. The 10 most abundant phyla were Proteobacteria, Cyanobacteria, Bacteroidetes, Chloroflexi, Firmicutes, Acidobacteria, Actinobacteria, Planctomycetes, Gemmatimonadetes and Verrucomicrobia. The relationship of bacterial communities in the intestine and the surroundings was also investigated. A total of 1395 OTUs shared in the three habitats, accounting for 80, 65 and 77% in the intestine, the surrounding water and sediment respectively. There were 352, 891, 833 unique OTUs in intestine, surrounding water and sediment. Welch's t‐test analysis showed that the abundances of some taxa were significantly different between the shrimp intestine and surroundings. Unweighted pair‐group method with arithmetic mean analysis revealed that there was a generally similar bacterial community composition in three environments.
Conclusions
These results showed that the bacterial compositions are mostly the same in shrimp intestine, water and sediment, but with different relative abundances of the bacterial communities.
Significance and Impact of the Study
This study provided valuable findings on the relationship of the bacterial communities in shrimp intestine, the surrounding water and sediment, which can expand our knowledge of the broad trend on bacterial community in shrimp cultural ecosystems.
Objective
To investigate the risks of attempted and completed suicide in women who experienced a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally and compare this risk ...with that in women who experienced a live birth.
Design
A nested case–control study.
Setting
Linking three nationwide population‐based data sets in Taiwan: the National Health Insurance Research Database, the National Birth Registry and the National Death Registry.
Sample
In all, 485 and 350 cases of attempted and completed suicide, respectively, were identified during 2001–11; for each case, ten controls were randomly selected and matched to the cases according to the age and year of delivery.
Methods
Conditional logistic regression.
Main outcome measures
Attempted and completed suicidal statuses were determined.
Results
The rates of attempted suicide increased in the women who experienced fetal loss. The risk of completed suicide was higher in women who experienced a stillbirth adjusted odds ratio (aOR) 5.2; 95% CI 1.77–15.32, miscarriage (aOR 3.81; 95% CI 2.81–5.15), or termination of pregnancy (aOR 3.12; 95% CI 1.77–5.5) than in those who had a live birth. Furthermore, the risk of attempted suicide was significantly higher in women who experienced a miscarriage (aOR 2.1; 95% CI 1.66–2.65) or termination of pregnancy (aOR 2.5; 95% CI 1.63–3.82). In addition to marital and educational statuses, psychological illness increased the risk of suicidal behaviour.
Conclusions
The risk of suicide might increase in women who experience fetal loss within 1 year postnatally. Healthcare professionals and family members should enhance their sensitivity to care for possible mental distress, particularly for women who have experienced a stillbirth.
Tweetable
Suicide risk increased in women who had a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally.
Tweetable
Suicide risk increased in women who had a stillbirth or abortion within 1 year postnatally.
The goal of this open-label trial was to examine the efficacy and safety of a 12-week omega-3 fatty acids supplementation among children suffering with Autism Spectrum Disorders (ASD). A total of 41 ...children and adolescents aged 7-18 years (36 boys, 5 girls; mean age = 11.66, s.d. = 3.05) diagnosed with ASD participated in the study. At post-treatment, participants showed significant improvements on all subscales of the Social Responsiveness Scale (P < 0.01) and the Social and Attention Problems syndrome scales of the Child Behavior Checklist (P < 0.05). Blood fatty acid levels were significantly correlated with changes in the core symptoms of ASD. Baseline levels of blood fatty acid levels were also predictive of response to the omega-3 treatment. Omega-3 fatty acids supplementation was well-tolerated and did not cause any serious side effects. Our findings lend some preliminary support for the use of omega-3 fatty acids supplementation in addressing ASD. Future randomized controlled trials of omega-3 fatty acids in ASD with blood fatty acid measurements with a larger sample and longer follow-up period is warranted.
ABSTRACT
In 2011 December, PSR B054−69 experienced a spin-down rate transition (SRT), after which the spin-down power of the pulsar increased by $\sim 36{{\ \rm per\ cent}}$. About 1000 d after the ...SRT, the X-ray luminosity of the associated pulsar wind nebula (PWN) was found to brighten by $32\pm 8{{\ \rm per\ cent}}$. After the SRT, the braking index n of PSR B0540−69 changes from n = 2.12 to 0.03 and then keeps this value for about five years before rising to n = 0.9 in the following years. We find that most of the current models have difficulties in explaining the measured braking index. One exceptive model of the braking index evolution is the increasing dipole magnetic field of PSR B0540−69. We suggest that the field increase may result from some instabilities within the pulsar core that enhance the poloidal component at the price of toroidal component of the magnetic field. The increasing dipole magnetic field will result in the X-ray brightening of the PWN. We fit the PWN X-ray light curve by two models: one assumes a constant magnetic field within the PWN during the brightening and the other assumes an enhanced magnetic field proportional to the energy density of the PWN. It appears that the two models fit the data well, though the later model seems to fit the data a bit better. This provides marginal observational evidence that magnetic field in the PWN is generated by the termination shock. Future high-quality and high-cadence data are required to draw a solid conclusion.
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