Extracellular vesicles (EVs) play important roles in cell-cell communication. In budding yeast (Saccharomyces cerevisiae), EVs function as carriers to transport cargo proteins into the periplasm for ...storage during glucose starvation. However, intracellular organelles that synthesize these EV-associated cargo proteins have not been identified. Here, we investigated whether cytoplasmic organelles—called intracellular vesicle clusters (IVCs)—serve as sites for the synthesis of proteins targeted for secretion as EV-associated proteins. Using proteomics, we identified 377 IVC-associated proteins in yeast cells grown under steady-state low-glucose conditions, with the largest group being involved in protein translation. Isolated IVCs exhibited protein synthesis activities that required initiation and elongation factors. We have also identified 431 newly synthesized proteins on isolated IVCs. Expression of 103Q-GFP, a foreign protein with a long polyglutamine extension, resulted in distribution of this protein as large puncta that co-localized with IVC markers, including fructose-1,6-bisphosphatase (FBPase) and the vacuole import and degradation protein Vid24p. We did not observe this pattern in cycloheximide-treated cells or in cells lacking VID genes, required for IVC formation. The induction of 103Q-GFP on IVCs adversely affected total protein synthesis in intact cells and on isolated IVCs. This expression also decreased levels of EV-associated cargo proteins in the extracellular fraction without affecting the number of secreted EVs. Our results provide important insights into the functions of IVCs as sites for the synthesis of EV-associated proteins targeted for secretion to the periplasm.
The economic risk of solar plant projects due to the inter-annual solar resource variability is usually quantified by the exceedance probabilities. The estimation of these probabilities depends on ...the datasets used for the study; actually, the uncertainty associated to these datasets affects the viability study of the project. Due to this dependence, in this work two different types of datasets are used in the estimation of the exceedance probabilities and their uncertainties: synthetic datasets and satellite-derived datasets.
Besides, the intra-annual variability of the irradiation variations (intermittency) can affect the production rate of the solar plant. Thus, the knowledge of this variability allows us to foresee the discontinuities in the production rate of the solar plants and to plan the needs for high or low storage capacity according to different temporal periods. In order to quantify the effect of the intra-annual variability in the viability study, a Viability Index based on Discontinuity in the production rate, VID, is proposed, which estimates viability from the exceedance probabilities of the variations. The inclusion of this analysis can provide us with important information about the viability assessment of the projects.
•We propose exceedance probability of variations as a tool to assess project viability•Exceedance probability uncertainty is higher for satellite than for synthetic datasets•Seasonal and inter-annual viability analysis can give opposite results•Costs of intermittency and quantity of irradiation must be balanced•We propose a Viability Index based on Discontinuity in the production rate
Abstract
While prior research has demonstrated a relationship between sleep and cognitive performance, how sleep relates to underlying genetic and environmental etiologies contributing to cognitive ...functioning, regardless of the level of cognitive function, is unclear. The present study assessed whether the importance of genetic and environmental contributions to cognition vary depending on an individual’s aging-related sleep characteristics. The large sample consisted of twins from six studies within the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium spanning mid- to late-life (Average age Mage = 57.6, range = 27–91 years, N = 7052, Female = 43.70%, 1525 complete monozygotic MZ pairs, 2001 complete dizygotic DZ pairs). Quantitative genetic twin models considered sleep duration as a primary moderator of genetic and environmental contributions to cognitive performance in four cognitive abilities (Semantic Fluency, Spatial-Visual Reasoning, Processing Speed, and Episodic Memory), while accounting for age moderation. Results suggested genetic and both shared and nonshared environmental contributions for Semantic Fluency and genetic and shared environmental contributions for Episodic Memory vary by sleep duration, while no significant moderation was observed for Spatial-Visual Reasoning or Processing Speed. Results for Semantic Fluency and Episodic Memory illustrated patterns of higher genetic influences on cognitive function at shorter sleep durations (i.e. 4 hours) and higher shared environmental contributions to cognitive function at longer sleep durations (i.e. 10 hours). Overall, these findings may align with associations of upregulation of neuroinflammatory processes and ineffective beta-amyloid clearance in short sleep contexts and common reporting of mental fatigue in long sleep contexts, both associated with poorer cognitive functioning.
We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data ...from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
Antecedentes: El biocontrol de las enfermedades fúngicas de la madera de la vid (EMV), es una alternativa amigable frente al control químico causante de resistencia y/o contaminación del ecosistema. ...Objetivo: aislar microorganismos nativos de raíz y rizósfera de vid con potencial de biocontrol de hongos de la madera de la vid. Metodología: Se estudió la “competencia por sustrato” (CS) con la escala de Bell, “el tiempo de contacto” (TC) entre antagonista-patógeno” (días) y la antibiosis por el porcentaje de inhibición del crecimiento (PIC). Resultados: Se aislaron e identificaron: siete-cepas de Trichoderma spp. (raíz: Tr-1, Tr-2, Tr3, Tr-6; y rizósfera: Tr-4, Tr-5, Tr-7); seis-Bacillus spp. (raíz: Bac-4, Bac-5, Bac-6; y rizósfera: Bac-1, Bac-2, Bac-3); y dos-Streptomyces sp. (rizósfera: Act-1, Act-2). Los resultados de la CS evaluados con la escala de Bell demostraron a Tr-1, Tr-7, T.atv (Trichoderma atroviride) y T-22 (Trichoderma harzianum) se ubicaron en la clase 1 frente a Lasiodiplodia theobromae y, todos los aislados se ubicaron en la clase 1 frente a Campylocarpon pseudofasciculare y Phaeoacremonium parasiticum. El TC de Trichoderma fue 2 días (L. theobromae) y 3 días (C. pseudofasciculare y P. parasiticum). En la antibiosis Tr-5 (Trichoderma) y Bac-3 (Bacillus) tuvieron el mayor PIC (>50%) frente a los patógenos. El aislado Act-2 (Streptomyces sp.) presentó PIC, >70% (L. theobromae), >40% (C. pseudofasciculare) y >30% (P. parasiticum). Implicaciones: El uso del control biológico en el manejo de enfermedades de la madera de la vid es una herramienta eficaz, y puede integrarse en una estrategia de manejo integrado de estas patologías. Conclusiones: Los aislados nativos Bac-3 (Bacillus spp.), Tr-5 (Trichoderma spp.), Act-2 (Streptomyces sp.) demostraron control in vitro frente a los patógenos L. theobromae, C. pseudofasciculare y P. parasiticum, patógenos asociados a enfermedades de la madera de la vid.
Aims
There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 ...diabetes, diagnosed before age 18, and long‐term morbidity and mortality, and to investigate whether cognitive ability plays a role in long‐term morbidity and mortality risk.
Methods
In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan‐Meier analyses with log‐rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated.
Results
Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56–5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27–9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79–5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes.
Conclusions
In this historical cohort study with 60 years of follow‐up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes.
People with impaired hearing or deafness often perceive communication barriers when and participating in their daily lives, such as when contacting primary healthcare, leading to a risk of them using ...emergency services for less urgent conditions. Therefore, the aim of the present study was to describe the perceptions of individuals with hearing impairments and deafness in relation to the treatment and communication they received from primary healthcare professionals. The study employed a mixed-methods design, and the data comprised questionnaire responses from 101 individuals with hearing impairments or deafness, including 11 open-ended questions, analyzed with conventional content analysis. The study was evaluated using the COREQ checklist and the GRAMMS guidelines to further improve the transparency of the research. The results indicate that healthcare professionals who are responsive, considerate, and respectful regarding communication were perceived among people with hearing impairments or deafness to be professionals. The ideal healthcare encounter for people with hearing impairments or deafness would be where the healthcare professionals could perform sign language, which would allow the healthcare professional to communicate freely. Healthcare professionals need more knowledge about how they can best meet, care for, and communicate with individuals with hearing impairments or deafness.
This paper presents a 60 GHz, 16% tuning range VCO, and a 40 GHz, 18 bits, 14% tuning range DCO incorporating variable inductor (VID) techniques. The variable inductor, consisting of a transformer ...and a variable resistor, is tunable by adjusting its resistor. By employing the proposed frequency tuning scheme, wide-tuning range as well as multi-band operation are achieved without sacrificing their operating frequencies. To verify the operation principles, the VCO and DCO are both fabricated in 90 nm CMOS technology. The tuning range of VCO is from 52.2 GHz to 61.3 GHz. The measured phase noise from a 61.3-GHz carrier is about - 118.75 dBc/Hz at 10-MHz offset, and the output power is -6.6 dBm. It dissipates 8.7 mW from a 0.7-V supply, and the chip size is 0.28×0.36mm 2 . On the other hand, the DCO is capable of covering frequency range from 37.6 GHz to 43.4 GHz. The measured phase noise from a 43 GHz carrier is about -109 dBc/Hz at 10-MHz offset, and the output power is -11 dBm. The DCO core dissipates 19 mW from a 1.2-V supply. Chip size is 0.5×0.15mm 2 .
Communicating a terminal prognosis is challenging for patients, families and healthcare professionals. However, positive effects have been reported when children are told about their diagnosis and ...prognosis, including fewer symptoms of anxiety and depression and enhanced adherence to treatment (1). When research about prognostic communication was first published in the 1950s and 1960s, it recommended protecting children from bad news. By the late 1960s, a more open approach was recommended and by the late 1980s the advice was to always tell children. There has been a growing awareness of the complexity of prognostic disclosure and the need to balance often competing factors, such as hope and patient and family considerations, on a case-to-case basis (2).
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