282 research outputs found
Theoretical calculation of the pressure distribution, span loading, and rolling moment due to sideslip at supersonic speeds for thin sweptback tapered wings with supersonic trailing edges and wing tips parallel to the axis of wing symmetry
Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms
To Vax or Not to Vax: Predictors of Anti-Vax Attitudes and COVID-19 Vaccine Hesitancy Prior to Widespread Vaccine Availability
The novel coronavirus (COVID-19) is a highly contagious disease responsible for millions of deaths worldwide. Effective vaccines against COVID-19 are now available, however, an extreme form of vaccine hesitancy known as anti-vax attitudes challenge vaccine acceptance and distribution efforts. To understand these anti-vax attitudes and their associated psychological characteristics, we examined several predictors of vaccine hesitancy for COVID-19 and anti-vax attitudes generally. We surveyed 1004 adults (M = 47.0 years, SD = 17.1 years, range 18–98 years) in September-October 2020 across the United States (51% female, 49% male; 76.5% White, 23.5% non-White), prior to widespread availability of the COVID-19 vaccines. Attitudes toward vaccinations were influenced by a variety of factors, especially political attitudes. We should therefore anticipate and attempt to mitigate these challenges to achieving widespread vaccination to reduce the spread of COVID-19 and other communicable diseases
A next generation sequencing-based protocol for screening of variants of concern in autism spectrum disorder
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic influences. There is an increasing demand for ASD genetic testing beyond the traditionally recommended microarray and syndromic autism testing; however, the current whole genome sequencing (WGS) and whole exome sequencing (WES) methods are lacking an academic standard for WGS variant annotation, reporting, and interpretation, tailored towards patients with ASD and offer very limited interpretation for clinical significance. Using WGS data from six family trios, we demonstrate the clinical feasibility and technical implementation of an evidence-based, fully transparent bioinformatics pipeline and report framework for an ASD-focused WGS genetic report. We confirmed a portion of the key variants with Sanger sequencing and provided interpretation with consideration of patients\u27 clinical symptoms and detailed literature review. Furthermore, we showed that identification of the genetic contributions of ASD core symptoms and comorbidities may promote a better understanding of the ASD pathophysiology, lead to early detection of associated comorbidities, and facilitate pharmacologic intervention based on pathological pathways inferred from the genetic information. We will make the bioinformatics pipeline and interpretation framework publicly available, in an easily accessible format, after validation with a larger cohort. We hope that the present proposed protocol can serve as a starting point to invite discourse and debate to further improve approaches in WGS-based genetic consultation for patients with ASD
The Embryonic Transcriptome Of The Red-Eared Slider Turtle (Trachemys Scripta)
The bony shell of the turtle is an evolutionary novelty not found in any other group of animals, however, research into its formation has suggested that it has evolved through modification of conserved developmental mechanisms. Although these mechanisms have been extensively characterized in model organisms, the tools for characterizing them in non-model organisms such as turtles have been limited by a lack of genomic resources. We have used a next generation sequencing approach to generate and assemble a transcriptome from stage 14 and 17 Trachemys scripta embryos, stages during which important events in shell development are known to take place. The transcriptome consists of 231,876 sequences with an N-50 of 1,166 bp. GO terms and EC codes were assigned to the 61,643 unique predicted proteins identified in the transcriptome sequences. All major GO categories and metabolic pathways are represented in the transcriptome. Transcriptome sequences were used to amplify several cDNA fragments designed for use as RNA in situ probes. One of these, BMP5, was hybridized to a T. scripta embryo and exhibits both conserved and novel expression patterns. The transcriptome sequences should be of broad use for understanding the evolution and development of the turtle shell and for annotating any future T. scripta genome sequences
Supplementary data on virus-like particles in the brainstem of Parkinson's disease patients and controls [version 2; peer review: 2 approved]
In this study, we present 84 transmission electron microscopy (TEM) images of human brainstem tissue from 11 cases of late onset Parkinson's disease (PD). The tissues were fixed, embedded, sectioned, and stained for TEM application. In addition, we present 14 images from autopsy specimens of 1 case of human poliomyelitis infection as positive controls and 14 images from 8 cases of autopsy specimens of other conditions as negative controls. In the TEM images of the PD cases there were cytoplasmic inclusion bodies consisting of virus-like particles (VLP) 30 nm in diameter that were associated with endoplasmic reticulum membranes. In the nuclei of the PD neurons there were VLP ranging from 40 nm to 50 nm in diameter. In the poliomyelitis cases, similar particles as were observed in PD which were interpreted to be poliomyelitis virus particles. In the negative controls one case was identified which showed similar VLP (Figure 1, controls). A Lewy body was found in this "control" case (Figure 10) suggesting that this was an undiagnosed case of PD. Cytoplasmic ribosomes measuring approximately 17 nm were observed in the control neurons
Cell-Cycle Protein Expression in a Population-Based Study of Ovarian and Endometrial Cancers
Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, p27) and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were available for ovarian cancer patients and examined using Kaplan-Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n=175), positive p21 expression was associated with endometrioid tumors (OR=12.22, 95% CI=1.45-102.78) and higher overall survival (log-rank p=0.002). In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio=0.65, 95% CI=0.42-1.05). Among endometrial cancer patients (n=289), positive p21 expression was inversely associated with age (OR ≥ 65 years of age=0.25, 95% CI=0.07-0.84) and current smoking status (OR: 0.33, 95% CI 0.15, 0.72) compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted
Necessary fictions: indigenous claims and the humanity of rights
Indigenous right insistently challenges the surpassing arrogations of sovereign right. In so doing, it affirms dimensions of being-together denied or stunted in sovereign modes of political formation. This force of Indigenous right is amplified here through legal and literary instantiations. These, in turn, uncover the continuously created and fictional quality of rights, revealing them to be necessary fictions
Biological control of the vernal population increase of Calanus finmarchicus on Georges Bank
Author Posting. © Elsevier B.V., 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 53 (2006): 2632-2655, doi:10.1016/j.dsr2.2006.08.011.An adjoint data assimilation approach was used to quantify the physical and biological controls on Calanus finmarchicus N3 to C stages on Georges Bank and its nearby environs. The mean seasonal cycle of vertically-averaged distributions, from 5 years of the GLOBEC Georges Bank Broad-Scale Surveys between January and June, was assimilated into a physical-biological model based on the climatological circulation. Large seasonal and spatial variability is present in the inferred supply sources, mortality rates, computed molting fluxes, and physical transports. Estimated mortalities fall within the range of observed rates, and exhibit stage structure that is consistent with earlier findings. Inferred off-bank initial conditions indicate that the deep basins in the Gulf of Maine are source regions of early-stage nauplii and late-stage copepodids in January. However, the population increase on Georges Bank from January to April is controlled mostly by local biological processes. Magnitudes of the physical transport terms are nearly as large as the mortality and molting fluxes, but their bank-wide averages are small in comparison to the biological terms. The hypothesis of local biological control is tested in a sensitivity experiment in which upstream sources are set to zero. In that solution, the lack of upstream sources is compensated by a decrease in mortality that is much smaller than the uncertainty in observational estimates.This work was supported by the US GLOBEC Georges Bank program: Integration and Synthesis of Georges Bank Broad-Scale Survey Results, sponsored by NSF (OCE-0233800) and NOAA (NA17RJ1223)
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