Stem cells reside in a niche, a local environment whose cellular and molecular complexity is still being elucidated. In
ovaries, germline stem cells depend on cap cells for self-renewing signals and ...physical attachment. Germline stem cells also contact the anterior escort cells, and here we report that anterior escort cells are absolutely required for germline stem cell maintenance. When escort cells die from impaired Wnt signaling or
expression, the loss of anterior escort cells causes loss of germline stem cells. Anterior escort cells function as an integral niche component by promoting DE-cadherin anchorage and by transiently expressing the Dpp ligand to promote full-strength BMP signaling in germline stem cells. Anterior escort cells are maintained by Wnt6 ligands produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving vacancies in the niche, leading to loss of germline stem cells. Our data identify anterior escort cells as constituents of the germline stem cell niche, maintained by a cap cell-produced Wnt6 survival signal.
Ligand-based signaling can potentiate communication between neighboring cells and between cells separated by large distances. In the Drosophila melanogaster ovary, Wingless (Wg) promotes ...proliferation of follicle stem cells located ~50 µm or five cell diameters away from the Wg source. How Wg traverses this distance is unclear. We find that this long-range signaling requires Division abnormally delayed (Dally)-like (Dlp), a glypican known to extend the range of Wg ligand in the wing disc by binding Wg. Dlp-mediated spreading of Wg to follicle stem cells is opposed by the extracellular protease Mmp2, which cleaved Dlp in cell culture, triggering its relocalization such that Dlp no longer contacted Wg protein. Mmp2-deficient ovaries displayed increased Wg distribution, activity, and stem cell proliferation. Mmp2 protein is expressed in the same cells that produce Wg; thus, niche cells produce both a long-range stem cell proliferation factor and a negative regulator of its spreading. This system could allow for spatial control of Wg signaling to targets at different distances from the source.
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral ...RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo-electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.
Huntington disease (HD) is a progressive neurodegenerative disorder caused by dominant polyglutamine (polyQ) expansion within the N terminus of huntingtin (Htt) protein. Abnormal metal accumulation ...in the striatum of HD patients has been reported for many years, but a causative relationship has not yet been established. Furthermore, if metal is indeed involved in HD, the underlying mechanism needs to be explored. Here using a Drosophila model of HD, wherein Htt exon1 with expanded polyQ (Htt exon1-polyQ) is introduced, we show that altered expression of genes involved in copper metabolism significantly modulates the HD progression. Intervention of dietary copper levels also modifies HD phenotypes in the fly. Copper reduction to a large extent decreases the level of oligomerized and aggregated Htt. Strikingly, substitution of two potential copper-binding residues of Htt, Met8 and His82, completely dissociates the copper-intensifying toxicity of Htt exon1-polyQ. Our results therefore indicate HD entails two levels of toxicity: the copper-facilitated protein aggregation as conferred by a direct copper binding in the exon1 and the copper-independent polyQ toxicity. The existence of these two parallel pathways converging into Htt toxicity also suggests that an ideal HD therapy would be a multipronged approach that takes both these actions into consideration.
Various portions of pork fat in Harbin sausage were replaced by a camellia oil gelled emulsion during the process, and the subsequent effects were studied in order to improve their quality ...characteristics and fatty acid composition. Percentages of pork back fat replacement were 10%, 20%, 30%, 40% and 50%. Proximate composition, instrumental color and texture, pH, TBARS and fatty acid composition of the sausages were studied after substituting portion of the pork fat with camellia oil gelled emulsion. The replacement of pork back fat by camellia oil gels did not affect the cohesiveness, resilience, springiness and protein content, while it increased moisture content, lightness and yellowness. TBARS values was significantly (P < 0.05) decreased by the pork back fat substitution. Addition of camellia oil gels significantly (P < 0.05) affected the fatty acid profile. The study suggests that a substantial reduction in SFA can be achieved by incorporating camellia oil gels in Harbin sausage without clearly affecting the studied sausage properties.
•The use of camellia oil to replace pork back fat in Harbin sausage was studied, which had not been reported before.•Using camellia oil gelled emulsion did not affect the texture properties and protein content in Harbin sausage.•Camellia oil emulsion achieved a shift in the fatty acid profiles towards a greater unsaturation.•The replacement of pork back-fat with camellia oil gels decreased the TBARS value of Harbin sausage significantly.
Cropland is a main source of global nitrogen pollution
. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of ...farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers
. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (10
g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.
The COVID-19 pandemic caused by nonstop infections of SARS-CoV-2 has continued to ravage many countries worldwide. Here we report that suramin, a 100-year-old drug, is a potent inhibitor of the ...SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and acts by blocking the binding of RNA to the enzyme. In biochemical assays, suramin and its derivatives are at least 20-fold more potent than remdesivir, the currently approved nucleotide drug for treatment of COVID-19. The 2.6 Å cryo-electron microscopy structure of the viral RdRp bound to suramin reveals two binding sites. One site directly blocks the binding of the RNA template strand and the other site clashes with the RNA primer strand near the RdRp catalytic site, thus inhibiting RdRp activity. Suramin blocks viral replication in Vero E6 cells, although the reasons underlying this effect are likely various. Our results provide a structural mechanism for a nonnucleotide inhibitor of the SARS-CoV-2 RdRp.
The psychological distress of medical students has been widely acknowledged. However, few studies focused on positive well-being among medical students. The purpose of this study was to investigate ...related demographic factors of life satisfaction among Chinese medical students, to examine the relationship between stress and life satisfaction among this group of people, and to explore the mediating role of resilience in this relationship.
This multicenter cross-sectional study was carried out in June 2014. Self-reported questionnaires consisting of Perceived Stress Scale (PSS), Wagnild and Young Resilience Scale (RS-14), Satisfaction with Life Scale (SWLS), as well as demographic section were distributed to students at four medical colleges and universities in Liaoning province, China. A total of 2925 students (effective response rate: 83.6%) became our subjects. Hierarchical linear regression models were used to explore the mediating role of resilience.
Among the demographic factors, life satisfaction was significantly different in gender (P = 0.001) and study programs (P < 0.001). Stress was negatively correlated with life satisfaction (r = -0.35, P < 0.01). After adjusting for the demographic factors, stress accounted for 12% of the variance in life satisfaction (β = -0.34, P < 0.001) while resilience explained an additional 18% of the variance (β = 0.46, P < 0.001). Resilience functioned as a partial mediator in the relationship between stress and life satisfaction among Chinese medical students.
Both stress and resilience played a big role in life satisfaction among Chinese medical students. Besides reducing perceived stress, the university authorities should adopt evidence-based intervention strategies to enhance their resilience in order to promote life satisfaction among the students.
Cancer-related fatigue (CRF) is considered one of the most prevalent and distressing symptoms among cancer patients and may vary among patients with different cancer types. However, few studies have ...explored the influence of physical and psychological symptoms on CRF among esophageal cancer (EC) patients without esophagectomy. Therefore, this study aimed to examine the effects of physical and psychological symptoms on CRF among EC patients without esophagectomy.
In the present study, a cross-sectional study was conducted from February 2021 to March 2022 in Liaoning Province, China. Among the 112 included participants, 97 completed our investigation. The questionnaires used consisted of the Brief Fatigue Inventory (BFI), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and demographic and clinical information. Multivariate linear regression was conducted to test the relationships between physical and psychological symptoms and CRF.
Of the 97 EC patients, 60.8% reported CRF (BFI ≥ 4). The mean age of the participants was 64.92 years (SD = 8.67). According to the regression model, all the variables explained 74.5% of the variance in CRF. Regression analysis indicated that physical symptoms, including constipation, diarrhoea, and difficulty swallowing, contributed to CRF. On the other hand, depressive symptoms increased the level of CRF among EC patients without esophagectomy.
Given the high prevalence of CRF among EC patients without esophagectomy, it is urgent to emphasize the importance of fatigue management interventions based on physical and psychological symptoms to alleviate CRF in EC patients.
A better understanding of the relationship between land surface temperature (LST) and its influencing factors is important to the livable, healthy, and sustainable development of cities. In this ...study, we focused on the potential effect of human daily activities on LST from a short-term perspective. Beijing was selected as a case city, and Weibo check-in data were employed to measure the intensity of human daily activities. MODIS data were analyzed and used for urban LST measurement. We adopted spatial autocorrelation analysis, Pearson correlation analysis, and spatial autoregressive model to explore the influence mechanism of LST, and the study was performed at both the pixel scale and subdistrict scale. The results show that there is a significant and positive spatial autocorrelation between LSTs, and urban landscape components are strong explainers of LST. A significant and positive effect of human daily activities on LST is captured at night, and this effect can last and accumulate over a few hours. The variables of land use functions and building forms show varying impacts on LST from daytime to nighttime. Moreover, the comparison between results at different scales indicates that the relationships between LST and some explainers are sensitive to the study scale. The current study enriches the literature on LST and offers meaningful and practical suggestions for the monitoring, early warning, and management of urban thermal environment with remote sensing technology and spatial big data sources.
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