Biology subjects

Wassenaar, T.

Publications and source records attributed to Wassenaar, T..

5 recordsLinked to original sources

bioRxiv2021

Molecular architecture of SARS-CoV-2 envelope by integrative modeling

Despite tremendous efforts by the research community during the COVID-19 pandemic, the exact structure of SARS-CoV-2 and related betacoronaviruses remains elusive. Being a key structural component of the SARS-CoV-2 virion, the envelope encapsulates viral RNA and is composed of three structural proteins, spike (S), membrane (M), and envelope (E), which interact with each other and with the lipids acquired from the host membranes. Here, we developed and applied an integrative multiscale computational approach to model the envelope structure of SARS-CoV-2 with near atomistic detail, focusing on studying the dynamic nature and molecular interactions of its most abundant, but largely understudied, M protein. The molecular dynamics simulations allowed us to test the envelope stability under different configurations and revealed that the M dimers agglomerated into large, filament-like, macromolecular assemblies with distinct molecular patterns formed by Ms transmembrane and intravirion (endo) domains. These results are in good agreement with current experimental data, demonstrating a generic and versatile integrative approach to model the structure of a virus de novo. We anticipate our work to provide insights into critical roles of structural proteins in the viral assembly and integration, proposing new targets for the antiviral therapies.

biophysics↗

bioRxiv2020

Multimodal imaging brain markers in early adolescence are linked with a physically active lifestyle

The World Health Organization (WHO) promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and brain development are not fully understood. Here, we asked whether a brain - physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7-days physical activity, body-mass index, heart rate, and blood pressure. Using canonical correlation analysis we unravel a latent mode of brain - physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater grey matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity, covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence. Significance statementAn active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain - body relationships in an effort to foster brain health at this crucial stage in development.

neuroscience↗

bioRxiv2020

Very high extinction risk for Welwitschia mirabilis in the northern Namib Desert

One of the most recognisable icon of the Namib Desert is the endemic gymnosperm Welwitschia mirabilis. Recent studies indicated that climate change may seriously affect populations in the northern Namibia subrange (Kunene region) but their extinction risk has not yet been assessed. In this study, we apply IUCN criteria to define the extinction risk of welwitschia populations in northern Namibia and assign them to a red list category. We collected field data in the field to estimate relevant parameters for this assessment. We observed 1330 plants clustered in 12 small and isolated stands. The extent of occurrence has a surface of 214.2 km2 (i.e. < 5000 km2) and the area of occupancy a surface of 56.0 km2 (i.e. < 500 km2). The quality of habitat is expected to face a reduction of 69.47 % (i.e. > 50 %) as a consequence of climate change predicted in the area. These data indicate a very high extinction risk for welwitschia in northern Kunene and classify these populations as endangered (EN) according to IUCN criteria. Similar assessments for other subranges are prevented by the lack of relevant data, an issue that deserves further research attention. Our results advocate the necessity of a management plan for the species, including measures for mitigating the impact of climate change on isolated populations across its fragmented range.

ecology↗

bioRxiv2020

Evidence of climate change impacts on the iconic Welwitschia mirabilis in the Namib Desert

Climate change represents an important threat to global biodiversity and African ecosystems are particularly vulnerable. Recent studies predicted substantial variations of climatic suitability for Welwitschia mirabilis under future conditions. Latitudinal/altitudinal range shifts are well-known responses to climate change but not coherent patterns were documented. This study aims to verify whether welwitschia populations are responding to climate change and if the assumption of a latitudinal/altitudinal shift is applicable. We collected field data on welwitschia distribution, health condition, reproductive status, and plant size in northern Namibia. We used ecological niche models to predict the expected geographic shift of climatic suitability under future scenarios. For each variable, we compared the observed pattern with the expected responses. Finally, we tested the presence of simple geographical gradients in the observed patterns. The realized thermal niche of welwitschia will be almost completely unavailable in the next 30 years in northern Namibia. Expected reductions of climatic suitability in the stand sites are strongly associated with indicators of negative population conditions. The same population conditions does not fit any simple latitudinal or altitudinal gradient. The observed pattern of population conditions mirrors the expected pattern of climate change effect but no simple geographical gradient was relieved. Overall, we observed negative population conditions in areas with stronger reductions of suitability. This makes welwitschia a suitable sentinel for climate change effect in the Namib Desert ecosystems. Our approach to detect population responses to climate change could be extensively adopted for selecting sentinel species in other regions and ecosystems.

ecology↗

bioRxiv2017

Lipid-protein interactions are unique fingerprints for membrane proteins

Cell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.

biophysics↗