Biology subjects

Schmid, P.

Publications and source records attributed to Schmid, P..

7 recordsLinked to original sources

bioRxiv2025

Interdependent Dynamics of mRNA Expression and HIV-1 Viral Load: Insights from Transcriptomics and Mendelian Randomization

The interaction between HIV-1 and the host immune system plays a crucial role in the natural control and progression of the infection. Previous studies have identified APOBEC3G, Tetherin, SAMHD1, and SERINC5 as HIV-1 host restriction factors, which are counteracted by the viral proteins Vif, Vpu, and Nef, respectively. The blood expression levels of some of these host proteins are correlated with HIV load, suggesting that interindividual differences in the spontaneous control of HIV infection might lead to the identification of novel HIV restriction factors. Our study enrolled 150 participants from the Swiss HIV Cohort Study with human genome-wide genotyping data, pre-antiretroviral treatment peripheral blood mononuclear cells (PBMC) aliquots and HIV load measurements. Using BrB-seq, we quantified mRNA expression of all protein-coding genes and found significant associations between 792 genes and HIV load. Pathway analysis revealed that higher viral load associated with the upregulation of innate immune response, proteasome complex, mitochondrial and cell-cycle related activity, and with the downregulation of ribosomal transcripts and genes involved in cytokine-cytokine receptor interaction, including IL4R, IL7R, and TCF7. Mendelian Randomization confirmed the viral restriction activity of TRABD2A and identified new candidates as potential restriction factors. These findings provide novel insights into the host-virus interplay and suggest additional genes that may contribute to the natural control of HIV-1 infection.

immunology↗

bioRxiv2024

Temporal kinetics of brain state effects on visual perception

We investigated the effects of brain states on human perception and early visual response comparing focused wakefulness (ON state) to external inattention (OFF state). In two experiments, we investigated the temporal kinetics of brain states changes during stimulus processing and assessed fluctuations across extended periods of time. We used a classifier to distinguish between these states on a single trial level using theta activity in MEG sensors. We found that participants shifted from an ON to an OFF state as rapidly as two seconds. Visual target discrimination was comparable in both states, but reaction times were slower and more variable during the OFF state. Broad band high-frequency activity (BHA) recorded in MEG sensors covering the occipital cortex tracked target grating orientation. BHA was reduced during the OFF state but participants were still able to distinguish sensory information highlighting the role of BHA in visual perception across cognitive brain states.

neuroscience↗

bioRxiv2024

Physical Exercise Improves Working Memory through Ripple-Spindle Coupling

Spindle-ripple coupling enhances memory consolidation during sleep. Ripples, representing the compressed reactivation of environmental information, provide a mechanism for retaining memory information in chronological order and are also crucial for working memory (WM) during wakefulness. Brief sessions of physical exercise (PE) are proposed to boost WM. In concurrent EEG/MEG sessions, we investigated the role of PE in WM performance and high-frequency-ripple to spindle coupling. Ripples, identified in MEG sensors covering the medial temporal lobe (MTL) region, predicted individual WM performance. Ripples were locked to robust oscillatory patterns in the EEG defined spindle band. Spindle activity and ripples decrease during initial stimulus presentation and rebound after 1 sec. Behaviorally, PE enhanced WM performance. Neurophysiologically, PE scaled the ripple rate with the number of items to be kept in WM and strengthened the coupling between ripple events and spindle oscillations. These findings reveal that PE enhances WM by coordinating ripple-spindle interaction.

neuroscience↗

bioRxiv2023

The Benchtop mesoSPIM: a next-generation open-source light-sheet microscope for large cleared samples

In 2015, we launched the mesoSPIM initiative (www.mesospim.org), an open-source project for making light-sheet microscopy of large cleared tissues more accessible. Meanwhile, the demand for imaging larger samples at higher speed and resolution has increased, requiring major improvements in the capabilities of light-sheet microscopy. Here, we introduce the next-generation mesoSPIM ("Benchtop") with significantly increased field of view, improved resolution, higher throughput, more affordable cost and simpler assembly compared to the original version. We developed a new method for testing objectives, enabling us to select detection objectives optimal for light-sheet imaging with large-sensor sCMOS cameras. The new mesoSPIM achieves high spatial resolution (1.5 {micro}m laterally, 3.3 {micro}m axially) across the entire field of view, a magnification up to 20x, and supports sample sizes ranging from sub-mm up to several centimetres, while being compatible with multiple clearing techniques. The new microscope serves a broad range of applications in neuroscience, developmental biology, and even physics.

neuroscience↗

bioRxiv2021

New fossils of Australopithecus sediba reveal a nearly complete lower back

Adaptations of the lower back to bipedalism are frequently discussed but infrequently demonstrated in early fossil hominins. Newly discovered lumbar vertebrae contribute to a near-complete lower back of Malapa Hominin 2 (MH2), offering additional insights into posture and locomotion in Australopithecus sediba. We show that MH2 demonstrates a lower back consistent with human-like lumbar lordosis and other adaptations to bipedalism, including an increase in the width of intervertebral articular facets from the upper to lower lumbar column ("pyramidal configuration"). This contrasts with recent work on lordosis in fossil hominins, where MH2 was argued to demonstrate no appreciable lordosis ("hypolordosis") similar to Neandertals. Our three-dimensional geometric morphometric (3D GM) analyses show that MH2s nearly complete middle lumbar vertebra is human-like in shape but bears large, cranially-directed transverse processes, implying powerful trunk musculature. We interpret this combination of features to indicate that A. sediba used its lower back in both human-like bipedalism and ape-like arboreal positional behaviors, as previously suggested based on multiple lines of evidence from other parts of the skeleton and reconstructed paleobiology of A. sediba.

paleontology↗

bioRxiv2019

Cardiorespiratory fitness predicts greater hippocampal volume and rate of episodic associative learning in older adults

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate in the Episodic Associative Learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show that higher CRF was associated with larger hippocampal volume and faster learning rate. Larger hippocampal volume was also associated with faster learning rate, and hippocampal volume partially mediated the relationship between CRF and learning rate. Further, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found that EAL learning rate was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time we show that higher CRF in healthy older adults is related to enhanced rate of relational memory acquisition, in part mediated by benefits on the hippocampus.

neuroscience↗

bioRxiv2017

Dissecting HIV Virulence: Heritability Of Setpoint Viral Load, CD4+ T Cell Decline And Per-Parasite Pathogenicity

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as \"per-parasite pathogenicity\". Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence -- measured as the rate of decline of CD4+ T cells -- and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%-30%), and that of the per-parasite pathogenicity is 17% (4%-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.

evolutionary biology↗