103 research outputs found
Identification of a Functional Non-coding Variant in the GABA
GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of GABRA2 brain protein and mRNA in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair deletion located in an intron adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR-Cas9-mediated gene editing on a B6J genetic background completely restored brain levels of GABRA2 protein and mRNA. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the Gabra2 gene is of critical importance to molecular genetic studies in neurobiological research because this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by GABRA2 function
Association of physical function with predialysis blood pressure in patients on hemodialysis
BACKGROUND: New information from various clinical settings suggests that tight blood pressure control may not reduce mortality and may be associated with more side effects. METHODS: We performed cross-sectional multivariable ordered logistic regression to examine the association between predialysis blood pressure and the short physical performance battery (SPPB) in a cohort of 749 prevalent hemodialysis patients in the San Francisco and Atlanta areas recruited from July 2009 to August 2011 to study the relationship between systolic blood pressure and objective measures of physical function. Mean blood pressure for three hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110-129 mmHg (reference), 130-159 mmHg, and ≥160 mmHg. SPPB includes three components: timed repeated chair stands, timed 15-ft walk, and balance tests. SPPB was categorized into ordinal groups (≤6, 7-9, 10-12) based on prior literature. RESULTS: Patients with blood pressure 130-159 mmHg had lower odds (OR 0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose blood pressure was between 110 and 129 mmHg, while those with blood pressure ≥160 mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when compared with blood pressure 110-129 mmHg. When individual components were examined, blood pressure was significantly associated with chair stand (130-159 mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (≥160 mmHg: OR 0.59, 95% CI 0.35-0.98). Blood pressure ≥160 mmHg was not associated with substantially higher SPPB score compared with 130-159 mmHg. CONCLUSIONS: Patients with systolic blood pressure at or above 130 mmHg had better physical performance than patients with lower blood pressure in the normotensive range. The risk-benefit tradeoff of aggressive blood pressure control, particularly in low-functioning patients, should be reexamined
Influence of gestational age at initiation of antihypertensive therapy: secondary analysis of CHIPS trial data (control of hypertension in pregnancy study)
For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight 48 hours (Pinteraction=0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks (Pinteraction=0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes
Identification of a Functional Non-coding Variant in the GABAA Receptor α2 Subunit of the C57BL/6J Mouse Reference Genome: Major Implications for Neuroscience Research
GABA type-A (GABA-A) receptors containing the α2 subunit (GABRA2) are expressed in most brain regions and are critical in modulating inhibitory synaptic function. Genetic variation at the GABRA2 locus has been implicated in epilepsy, affective and psychiatric disorders, alcoholism and drug abuse. Gabra2 expression varies as a function of genotype and is modulated by sequence variants in several brain structures and populations, including F2 crosses originating from C57BL/6J (B6J) and the BXD recombinant inbred family derived from B6J and DBA/2J. Here we demonstrate a global reduction of GABRA2 brain protein and mRNA in the B6J strain relative to other inbred strains, and identify and validate the causal mutation in B6J. The mutation is a single base pair deletion located in an intron adjacent to a splice acceptor site that only occurs in the B6J reference genome. The deletion became fixed in B6J between 1976 and 1991 and is now pervasive in many engineered lines, BXD strains generated after 1991, the Collaborative Cross, and the majority of consomic lines. Repair of the deletion using CRISPR-Cas9-mediated gene editing on a B6J genetic background completely restored brain levels of GABRA2 protein and mRNA. Comparison of transcript expression in hippocampus, cortex, and striatum between B6J and repaired genotypes revealed alterations in GABA-A receptor subunit expression, especially in striatum. These results suggest that naturally occurring variation in GABRA2 levels between B6J and other substrains or inbred strains may also explain strain differences in anxiety-like or alcohol and drug response traits related to striatal function. Characterization of the B6J private mutation in the Gabra2 gene is of critical importance to molecular genetic studies in neurobiological research because this strain is widely used to generate genetically engineered mice and murine genetic populations, and is the most widely utilized strain for evaluation of anxiety-like, depression-like, pain, epilepsy, and drug response traits that may be partly modulated by GABRA2 function
Revisiting Proxima with ESPRESSO
We aim to confirm the presence of Proxima b using independent measurements
obtained with the new ESPRESSO spectrograph, and refine the planetary
parameters taking advantage of its improved precision. We analysed 63
spectroscopic ESPRESSO observations of Proxima taken during 2019. We obtained
radial velocity measurements with a typical radial velocity photon noise of 26
cm/s. We ran a joint MCMC analysis on the time series of the radial velocity
and full-width half maximum of the cross-correlation function to model the
planetary and stellar signals present in the data, applying Gaussian process
regression to deal with stellar activity. We confirm the presence of Proxima b
independently in the ESPRESSO data. The ESPRESSO data on its own shows Proxima
b at a period of 11.218 0.029 days, with a minimum mass of 1.29
0.13 Me. In the combined dataset we measure a period of 11.18427 0.00070
days with a minimum mass of 1.173 0.086 Me. We find no evidence of
stellar activity as a potential cause for the 11.2 days signal. We find some
evidence for the presence of a second short-period signal, at 5.15 days with a
semi-amplitude of merely 40 cm/s. If caused by a planetary companion, it would
correspond to a minimum mass of 0.29 0.08 Me. We find that the FWHM of
the CCF can be used as a proxy for the brightness changes and that its gradient
with time can be used to successfully detrend the radial velocity data from
part of the influence of stellar activity. The activity-induced radial velocity
signal in the ESPRESSO data shows a trend in amplitude towards redder
wavelengths. Velocities measured using the red end of the spectrograph are less
affected by activity, suggesting that the stellar activity is spot-dominated.
The data collected excludes the presence of extra companions with masses above
0.6 Me at periods shorter than 50 days.Comment: 25 pages, 26 figure
Interactions between marine megafauna and plastic pollution in Southeast Asia
Southeast (SE) Asia is a highly biodiverse region, yet it is also estimated to cumulatively contribute a third of the total global marine plastic pollution. This threat is known to have adverse impacts on marine megafauna, however, understanding of its impacts has recently been highlighted as a priority for research in the region. To address this knowledge gap, a structured literature review was conducted for species of cartilaginous fishes, marine mammals, marine reptiles, and seabirds present in SE Asia, collating cases on a global scale to allow for comparison, coupled with a regional expert elicitation to gather additional published and grey literature cases which would have been omitted during the structured literature review. Of the 380 marine megafauna species present in SE Asia, but also studied elsewhere, we found that 9.1 % and 4.5 % of all publications documenting plastic entanglement (n = 55) and ingestion (n = 291) were conducted in SE Asian countries. At the species level, published cases of entanglement from SE Asian countries were available for 10 % or less of species within each taxonomic group. Additionally, published ingestion cases were available primarily for marine mammals and were lacking entirely for seabirds in the region. The regional expert elicitation led to entanglement and ingestion cases from SE Asian countries being documented in 10 and 15 additional species respectively, highlighting the utility of a broader approach to data synthesis. While the scale of the plastic pollution in SE Asia is of particular concern for marine ecosystems, knowledge of its interactions and impacts on marine megafauna lags behind other areas of the world, even after the inclusion of a regional expert elicitation. Additional funding to help collate baseline data are critically needed to inform policy and solutions towards limiting the interactions of marine megafauna and plastic pollution in SE Asia
Anti-lymphangiogenic properties of mTOR inhibitors in head and neck squamous cell carcinoma experimental models
Caracterización de aislamientos de Trichoderma spp. como promotores de crecimiento vegetal y agentes de control biológico de enfermedades en arroz.
First report of zonate leaf spot in sorghum caused by Microdochium sorghi in Uruguay. (Comunicación breve). [Primer reporte de mancha zonada de la hoja del sorgo causada por Microdochium sorghi en Uruguay].
ABSTRACT.Sorghum leaves with concentric lesions, alternating purple to red and beige to cinnamon, were observed for the first time inJanuary 2017. The same symptoms were observed later in 29 % of sorghum cultivars in official Evaluación Nacional deCultivares INASE-INIA trials. The pathogen was identified as Microdochium sorghi (syn. Gloeocercospora sorghi) oncepathogenicity trials, morphological and molecular descriptions were done. This is the first report of this pathogen affectingsorghum in Uruguay.RESUMEN.En enero de 2017 se observaron por primera vez hojas de sorgo con lesiones formando manchas concéntricas,alternando color púrpura o rojo con bandas beige o canela. La misma sintomatología fue observada posteriormente en el29 % de los materiales de los ensayos de sorgo de Evaluación Nacional de Cultivares INASE-INIA. Una vez realizada laprueba de patogenicidad, descripción morfológica y molecular, se identificó al patógeno como Microdochium sorghi (sin.Gloeocercospora sorghi). Este es el primer reporte de este patógeno afectando sorgo en Uruguay
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