Previously unidentified single nucleotide polymorphisms in HIV/AIDS cases associate with clinical parameters and disease progression

© 2016 Vladimir V. Anokhin et al.The genetic background of an individual plays an important role in the progression of HIV infection to AIDS. Identifying previously unknown or uncharacterized single nucleotide polymorphisms (SNPs) that associate with disease progression may reveal important therapeutic targets and provide a greater understanding of disease pathogenesis. In the present study, we employed ultra-high multiplex PCR on an Ion Torrent next-generation sequencing platform to sequence 23 innate immune genes from 94 individuals with HIV/AIDS. This data was used to identify potential associations of SNPs with clinical parameters and disease progression. SNPs that associated with an increased viral load were identified in the genes for the interleukin 15 receptor (IL15RA), toll-like receptor 7 (TLR7), tripartite motif-containing protein 5 (TRIM5), and two killer-cell immunoglobulin-like receptors (KIR2DL1 and KIR2DL3). Additionally, SNPs that associated with progression from HIV infection to AIDS were identified in two 2′-5′-oligoadenylate synthetase genes (OAS2 and OAS3). In contrast, other SNPs identified in OAS2 and OAS3 genes, as well as in the TRIM5 and KIR2DS4 genes, were associated with a slower progression of disease. Taken together, our data demonstrates the utility of ultra-high multiplex PCR in identifying polymorphisms of potential clinical significance and further,identifies SNPs that may play a role in HIV pathogenesis

MLP: a MATLAB toolbox for rapid and reliable auditory threshold estimation

In this paper, we present MLP, a MATLAB toolbox enabling auditory thresholds estimation via the adaptive Maximum Likelihood procedure proposed by David Green (1990, 1993). This adaptive procedure is particularly appealing for those psychologists that need to estimate thresholds with a good degree of accuracy and in a short time. Together with a description of the toolbox, the current text provides an introduction to the threshold estimation theory and a theoretical explanation of the maximum likelihood adaptive procedure. MLP comes with a graphical interface and it is provided with several built-in, classic psychoacoustics experiments ready to use at a mouse click

Abstract sounds and their applications in audio and perception research

International audienceRecognition of sound sources and events is an important pro- cess in sound perception and has been studied in many research domains. Conversely sounds that cannot be recognized are not often studied except by electroacoustic music composers. Besides, considerations on recogni- tion of sources might help to address the problem of stimulus selection and categorization of sounds in the context of perception research. This paper introduces what we call abstract sounds with the existing musical background and shows their relevance for different applications

Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity

© 2016 The Author(s)Myalgic encephalomyelitis (ME) is a complex, heterogeneous illness of unknown etiology. The search for biomarkers that can delineate cases from controls is one of the most active areas of ME research; however, little progress has been made in achieving this goal. In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process. Although these proteins might be unknown, it is possible to detect antibodies that react to these proteins using random peptide arrays. In the present study, we probe a custom 125,000 random 12-mer peptide microarray with sera from 21 ME cases and 21 controls from the USA and Europe and used these data to develop a diagnostic signature. We further used these peptide sequences to potentially uncover the naturally occurring candidate antigens to which these antibodies may specifically react with in vivo. Our analysis revealed a subset of 25 peptides that distinguished cases and controls with high specificity and sensitivity. Additionally, Basic Local Alignment Search Tool (BLAST) searches suggest that these peptides primarily represent human self-antigens and endogenous retroviral sequences and, to a minor extent, viral and bacterial pathogens

Pyogenic spinal infections warrant a total spine MRI

Study design: retrospective case series. Objective: the presenting clinical symptoms of spinal infections are often nonspecific and a delay in diagnosis can lead to adverse patient outcomes. The morbidity and mortality of patients with multifocal spinal infections is significantly higher compared to unifocal infections. The purpose of the current study was to analyse the risk factors for multifocal spinal infections. Methods: we conducted a retrospective review of all pyogenic non-tuberculous spinal infections treated surgically at a single tertiary care medical center from 2006–2020. The medical records, imaging studies, and laboratory data of 43 patients during this time period were reviewed and analysed after receiving Institutional Review Board approval. Univariate and multivariate analyses were performed to identify factors associated with a multifocal spinal infection. Results: 15 patients (35 %) had multifocal infections. In univariate analysis, there was a significant association with chronic kidney disease (p=0.040), gender (p=0.003), a white blood cell count (p=0.011), and cervical (p&lt;0.001) or thoracic (p&lt;0.001) involvement. In multivariate analysis, both cervical and thoracic involvement remained statistically significant (p=0.001 and p&lt;0.001, respectively). Conclusions: patients with infections in the thoracic or cervical region are more likely to have a multifocal infection. Multifocal pyogenic spinal infections remain a common entity and a total spine MRI should be performed to aid in prompt diagnosis.</p

Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease

© 2016 - IOS Press and the authors. All rights reserved.Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD

An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action

Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin

Insights on the Neuromagnetic Representation of Temporal Asymmetry in Human Auditory Cortex.

Communication sounds are typically asymmetric in time and human listeners are highly sensitive to this short-term temporal asymmetry. Nevertheless, causal neurophysiological correlates of auditory perceptual asymmetry remain largely elusive to our current analyses and models. Auditory modelling and animal electrophysiological recordings suggest that perceptual asymmetry results from the presence of multiple time scales of temporal integration, central to the auditory periphery. To test this hypothesis we recorded auditory evoked fields (AEF) elicited by asymmetric sounds in humans. We found a strong correlation between perceived tonal salience of ramped and damped sinusoids and the AEFs, as quantified by the amplitude of the N100m dynamics. The N100m amplitude increased with stimulus half-life time, showing a maximum difference between the ramped and damped stimulus for a modulation half-life time of 4 ms which is greatly reduced at 0.5 ms and 32 ms. This behaviour of the N100m closely parallels psychophysical data in a manner that: i) longer half-life times are associated with a stronger tonal percept, and ii) perceptual differences between damped and ramped are maximal at 4 ms half-life time. Interestingly, differences in evoked fields were significantly stronger in the right hemisphere, indicating some degree of hemispheric specialisation. Furthermore, the N100m magnitude was successfully explained by a pitch perception model using multiple scales of temporal integration of auditory nerve activity patterns. This striking correlation between AEFs, perception, and model predictions suggests that the physiological mechanisms involved in the processing of pitch evoked by temporal asymmetric sounds are reflected in the N100m