BDNF Val66Met and DRD2 Taq1A polymorphisms interact to influence PTSD symptom severity: A preliminary investigation in a South African population

BACKGROUND: We evaluated the role that selected variants in serotonin transporter (5-HTT), dopamine receptor 2 (DRD2) and brain-derived neurotrophic factor (BDNF) genes play in PTSD symptom severity in an at-risk population. We also investigated the interaction between the genetic variants to determine whether these variables and the interactions between the variables influenced the severity of PTSD symptoms. METHODS: PTSD symptoms were quantitatively assessed using the Davidson Trauma Scale (DTS) in 150 participants from an at-risk South African population. All participants were genotyped for the 5-HTTLPR, DRD2 Taq1A and BDNF Val66Met polymorphisms. Gene–gene interactions were investigated using various linear models. All analyses were adjusted for age, gender, major depressive disorder diagnosis, level of resilience, level of social support and alcohol dependence. RESULTS: A significant interaction effect between DRD2 Taq1A and BDNF Val66Met variants on DTS score was observed. On the background of the BDNF Val66Val genotype, DTS score increased significantly with the addition of a DRD2 Taq1A A1 allele. However, on the BDNF Met66 allele background, the addition of an A1 allele was found to reduce total DTS score. CONCLUSIONS: This study provides preliminary evidence for an epistatic interaction between BDNF Val66Met and DRD2 Taq1A polymorphisms on the severity of PTSD symptoms, where both too little and too much dopamine can result in increased PTSD symptom severity.Web of Scienc

A genetic chronology for the Indian Subcontinent points to heavily sex-biased dispersals

Background India is a patchwork of tribal and non-tribal populations that speak many different languages from various language families. Indo-European, spoken across northern and central India, and also in Pakistan and Bangladesh, has been frequently connected to the so-called “Indo-Aryan invasions” from Central Asia ~3.5 ka and the establishment of the caste system, but the extent of immigration at this time remains extremely controversial. South India, on the other hand, is dominated by Dravidian languages. India displays a high level of endogamy due to its strict social boundaries, and high genetic drift as a result of long-term isolation which, together with a very complex history, makes the genetic study of Indian populations challenging. Results We have combined a detailed, high-resolution mitogenome analysis with summaries of autosomal data and Y-chromosome lineages to establish a settlement chronology for the Indian Subcontinent. Maternal lineages document the earliest settlement ~55–65 ka (thousand years ago), and major population shifts in the later Pleistocene that explain previous dating discrepancies and neutrality violation. Whilst current genome-wide analyses conflate all dispersals from Southwest and Central Asia, we were able to tease out from the mitogenome data distinct dispersal episodes dating from between the Last Glacial Maximum to the Bronze Age. Moreover, we found an extremely marked sex bias by comparing the different genetic systems. Conclusions Maternal lineages primarily reflect earlier, pre-Holocene processes, and paternal lineages predominantly episodes within the last 10 ka. In particular, genetic influx from Central Asia in the Bronze Age was strongly male-driven, consistent with the patriarchal, patrilocal and patrilineal social structure attributed to the inferred pastoralist early Indo-European society. This was part of a much wider process of Indo-European expansion, with an ultimate source in the Pontic-Caspian region, which carried closely related Y-chromosome lineages, a smaller fraction of autosomal genome-wide variation and an even smaller fraction of mitogenomes across a vast swathe of Eurasia between 5 and 3.5 ka

Ultrahigh speed endoscopic swept source optical coherence tomography using a VCSEL light source and micromotor catheter

We developed an ultrahigh speed endoscopic swept source optical coherence tomography (OCT) system for clinical gastroenterology using a vertical-cavity surface-emitting laser (VCSEL) and micromotor based imaging catheter, which provided an imaging speed of 600 kHz axial scan rate and 8 μm axial resolution in tissue. The micromotor catheter was 3.2 mm in diameter and could be introduced through the 3.7 mm accessory port of an endoscope. Imaging was performed at 400 frames per second with an 8 μm spot size using a pullback to generate volumetric data over 16 mm with a pixel spacing of 5 μm in the longitudinal direction. Three-dimensional OCT (3D-OCT) imaging was performed in patients with a cross section of pathologies undergoing standard upper and lower endoscopy at the Veterans Affairs Boston Healthcare System (VABHS). Patients with Barrett’s esophagus, dysplasia, and inflammatory bowel disease were imaged. The use of distally actuated imaging catheters allowed OCT imaging with more flexibility such as volumetric imaging in the terminal ileum and the assessment of the hiatal hernia using retroflex imaging. The high rotational stability of the micromotor enabled 3D volumetric imaging with micron scale volumetric accuracy for both en face and cross-sectional imaging. The ability to perform 3D OCT imaging in the GI tract with microscopic accuracy should enable a wide range of studies to investigate the ability of OCT to detect pathology as well as assess treatment response.National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (R01-CA75289-17)National Institutes of Health (U.S.) (R44-CA101067-06)National Institutes of Health (U.S.) ( R01-EY011289-27)National Institutes of Health (U.S.) (R01-HL095717-04)National Institutes of Health (U.S.) (R01-NS057476-05)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)United States. Air Force Office of Scientific Research. Medical Free Electron Laser Program (FA9550-10-1-0551)German Research Foundation (DFG-GSC80-SAOT)German Research Foundation (DFG-HO-1791/11-1)Center for Integration of Medicine and Innovative Technolog

High thyrotropin is critical for cardiac electrical remodeling and arrhythmia vulnerability in hypothyroidism

Background: Hypothyroidism, the most common endocrine disease, induces cardiac electrical remodeling that creates a substrate for ventricular arrhythmias. Recent studies report that high thyrotropin (TSH) levels are related to cardiac electrical abnormalities and increased mortality rates. The aim of the present work was to investigate the direct effects of TSH on the heart and its possible causative role in the increased incidence of arrhythmia in hypothyroidism. Methods: A new rat model of central hypothyroidism (low TSH levels) was created and characterized together with the classical propylthiouracil-induced primary hypothyroidism model (high TSH levels). Electrocardiograms were recorded in vivo, and ionic currents were recorded from isolated ventricular myocytes in vitro by the patch-clamp technique. Protein and mRNA were measured by Western blot and quantitative reverse transcription polymerase chain reaction in rat and human cardiac myocytes. Adult human action potentials were simulated in silico to incorporate the experimentally observed changes. Results: Both primary and central hypothyroidism models increased the L-type Ca2+ current (ICa-L) and decreased the ultra-rapid delayed rectifier K+ current (IKur) densities. However, only primary but not central hypothyroidism showed electrocardiographic repolarization abnormalities and increased ventricular arrhythmia incidence during caffeine/dobutamine challenge. These changes were paralleled by a decrease in the density of the transient outward K+ current (Ito) in cardiomyocytes from animals with primary but not central hypothyroidism. In vitro treatment with TSH for 24 hours enhanced isoproterenol-induced spontaneous activity in control ventricular cells and diminished Ito density in cardiomyocytes from control and central but not primary hypothyroidism animals. In human myocytes, TSH decreased the expression of KCND3 and KCNQ1, Ito, and the delayed rectifier K+ current (IKs) encoding proteins in a protein kinase A–dependent way. Transposing the changes produced by hypothyroidism and TSH to a computer model of human ventricular action potential resulted in enhanced occurrence of early afterdepolarizations and arrhythmia mostly in primary hypothyroidism, especially under b-adrenergic stimulation. Conclusions: The results suggest that suppression of repolarizing K+ currents by TSH underlies most of the electrical remodeling observed in hypothyroidism. This work demonstrates that the activation of the TSHreceptor/protein kinase A pathway in the heart is responsible for the cardiac electrical remodeling and arrhythmia generation seen in hypothyroidism.Fil: Fernandez Ruocco, Maria Julieta. Universidade Federal do Rio de Janeiro; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Gallego, Monica. Universidad del País Vasco; EspañaFil: Rodriguez de Yurre, Ainhoa. Universidade Federal do Rio de Janeiro; Brasil. Universidad del País Vasco; EspañaFil: Zayas Arrabal, Julian. Universidad del País Vasco; EspañaFil: Echeazarra, Leyre. Universidade Federal do Rio de Janeiro; BrasilFil: Alquiza, Amaia. Universidad del País Vasco; EspañaFil: Fernández López, Victor. Universidad del País Vasco; EspañaFil: Rodriguez Robledo, Juan M.. Universidad del País Vasco; EspañaFil: Brito, Oscar. Instituto Nacional de Cardiologia; BrasilFil: Schleier, Ygor. Universidade Federal do Rio de Janeiro; BrasilFil: Sepúlveda, Marisa Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Oshiyama, Natalia F.. University of Campinas. Center for Biomedical Engineering; BrasilFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Bassani, Rosana A.. University of Campinas. Center for Biomedical Engineering; BrasilFil: Medei, Emiliano H.. Universidade Federal do Rio de Janeiro; BrasilFil: Casis, Oscar. Universidad del País Vasco; Españ

17-a-estradiol late in life extends lifespan in aging UM-HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex.

In genetically heterogeneous mice produced by the CByB6F1 x C3D2F1 cross, the non-feminizing estrogen, 17-α-estradiol (17aE2), extended median male lifespan by 19% (p \u3c 0.0001, log-rank test) and 11% (p = 0.007) when fed at 14.4 ppm starting at 16 and 20 months, respectively. 90th percentile lifespans were extended 7% (p = 0.004, Wang-Allison test) and 5% (p = 0.17). Body weights were reduced about 20% after starting the 17aE2 diets. Four other interventions were tested in males and females: nicotinamide riboside, candesartan cilexetil, geranylgeranylacetone, and MIF098. Despite some data suggesting that nicotinamide riboside would be effective, neither it nor the other three increased lifespans significantly at the doses tested. The 17aE2 results confirm and extend our original reports, with very similar results when started at 16 months compared with mice started at 10 months of age in a prior study. The consistently large lifespan benefit in males, even when treatment is started late in life, may provide information on sex-specific aspects of aging

Spatial and temporal variability of personal environmental exposure to radio frequency electromagnetic fields in children in Europe

Exposure to radiofrequency electromagnetic fields (RF-EMF) has rapidly increased and little is known about exposure levels in children. This study describes personal RF-EMF environmental exposure levels from handheld devices and fixed site transmitters in European children, the determinants of this, and the day-to-day and year-to-year repeatability of these exposure levels.; Personal environmental RF-EMF exposure (μW/m; 2; , power flux density) was measured in 529 children (ages 8-18 years) in Denmark, the Netherlands, Slovenia, Switzerland, and Spain using personal portable exposure meters for a period of up to three days between 2014 and 2016, and repeated in a subsample of 28 children one year later. The meters captured 16 frequency bands every 4 s and incorporated a GPS. Activity diaries and questionnaires were used to collect children's location, use of handheld devices, and presence of indoor RF-EMF sources. Six general frequency bands were defined: total, digital enhanced cordless telecommunications (DECT), television and radio antennas (broadcast), mobile phones (uplink), mobile phone base stations (downlink), and Wireless Fidelity (WiFi). We used adjusted mixed effects models with region random effects to estimate associations of handheld device use habits and indoor RF-EMF sources with personal RF-EMF exposure. Day-to-day and year-to-year repeatability of personal RF-EMF exposure were calculated through intraclass correlations (ICC).; Median total personal RF-EMF exposure was 75.5 μW/m; 2; . Downlink was the largest contributor to total exposure (median: 27.2 μW/m; 2; ) followed by broadcast (9.9 μW/m; 2; ). Exposure from uplink (4.7 μW/m; 2; ) was lower. WiFi and DECT contributed very little to exposure levels. Exposure was higher during day (94.2 μW/m; 2; ) than night (23.0 μW/m; 2; ), and slightly higher during weekends than weekdays, although varying across regions. Median exposures were highest while children were outside (157.0 μW/m; 2; ) or traveling (171.3 μW/m; 2; ), and much lower at home (33.0 μW/m; 2; ) or in school (35.1 μW/m; 2; ). Children living in urban environments had higher exposure than children in rural environments. Older children and users of mobile phones had higher uplink exposure but not total exposure, compared to younger children and those that did not use mobile phones. Day-to-day repeatability was moderate to high for most of the general frequency bands (ICCs between 0.43 and 0.85), as well as for total, broadcast, and downlink for the year-to-year repeatability (ICCs between 0.49 and 0.80) in a small subsample.; The largest contributors to total personal environmental RF-EMF exposure were downlink and broadcast, and these exposures showed high repeatability. Urbanicity was the most important determinant of total exposure and mobile phone use was the most important determinant of uplink exposure. It is important to continue evaluating RF-EMF exposure in children as device use habits, exposure levels, and main contributing sources may change

Стилистический эффект разговорной речи и его составляющие

В обучении русскому языку как иностранному на современном этапе большое внимание уделяется особенностям русской разговорной речи. Это обусловлено целым рядом причин, среди которых, на наш взгляд, можно выделить следующие: во-первых, разговорная речь всегда отличается активностью проникновения во все сферы жизнедеятельности людей и функционирует как в повседневном общении, так и в различных сферах (литературе, кино, политике и т.д.). Во-вторых, разговорная речь носит многожанровый характер, что зачастую затрудняет ее понимание иностранными студентами. В-третьих, в разговорную речь помимо слов нейтрального стиля все активнее стала проникать арготическая лексика. Именно в связи с этим особый интерес у нас вызывает разговорный стиль речи в преломлении на инофонную аудиторию

Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice.

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding

Massively distributed authorship of academic papers

Wiki-like or crowdsourcing models of collaboration can provide a number of benefits to academic work. These techniques may engage expertise from different disciplines, and potentially increase productivity. This paper presents a model of massively distributed collaborative authorship of academic papers. This model, developed by a collective of thirty authors, identifies key tools and techniques that would be necessary or useful to the writing process. The process of collaboratively writing this paper was used to discover, negotiate, and document issues in massively authored scholarship. Our work provides the first extensive discussion of the experiential aspects of large-scale collaborative research.Peer ReviewedPostprint (author's final draft