| 1. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 2. |
- Engqvist, Martin, 1983, et al.
(författare)
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Directed evolution of gloeobacter violaceus rhodopsin spectral properties
- 2015
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 427:1, s. 205-220
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Tidskriftsartikel (refereegranskat)abstract
- Proton-pumping rhodopsins (PPRs) are photoactive retinal-binding proteins that transport ions across biological membranes in response to light. These proteins are interesting for light-harvesting applications in bioenergy production, in optogenetics applications in neuroscience, and as fluorescent sensors of membrane potential. Little is known, however, about how the protein sequence determines the considerable variation in spectral properties of PPRs from different biological niches or how to engineer these properties in a given PPR. Here we report a comprehensive study of amino acid substitutions in the retinal-binding pocket of Gloeobacter violaceus rhodopsin (GR) that tune its spectral properties. Directed evolution generated 70 GR variants with absorption maxima shifted by up to ± 80 nm, extending the protein's light absorption significantly beyond the range of known natural PPRs. While proton-pumping activity was disrupted in many of the spectrally shifted variants, we identified single tuning mutations that incurred blue and red shifts of 42 nm and 22 nm, respectively, that did not disrupt proton pumping. Blue-shifting mutations were distributed evenly along the retinal molecule while red-shifting mutations were clustered near the residue K257, which forms a covalent bond with retinal through a Schiff base linkage. Thirty eight of the identified tuning mutations are not found in known microbial rhodopsins. We discovered a subset of red-shifted GRs that exhibit high levels of fluorescence relative to the WT (wild-type) protein.
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| 3. |
- Kronfeld-Schor, N, et al.
(författare)
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Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19
- 2021
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Ingår i: Journal of biological rhythms. - : SAGE Publications. - 1552-4531 .- 0748-7304. ; 36:1, s. 35-54
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Tidskriftsartikel (refereegranskat)abstract
- Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.
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| 4. |
- Priebe, Stefan, et al.
(författare)
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Good practice in mental health care for socially marginalized groups in Europe : a qualitative study in 14 countries
- 2012
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; :12, s. 248-
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Tidskriftsartikel (refereegranskat)abstract
- Background:Socially marginalised groups tend to have higher rates of mental disorders than the general populationand can be difficult to engage in health care. Providing mental health care for these groups represents a particularchallenge, and evidence on good practice is required. Thisstudy explored the experiences and views of experts in 14European countries regarding mental health care for six socially marginalised groups: long-term unemployed; street sexworkers; homeless; refugees/asylum seekers; irregular migrants and members of the travelling communities.Methods:Two highly deprived areas were selected in the capital cities of 14 countries, and experts were interviewed foreach of the six marginalised groups. Semi-structured interviews with case vignettes were conducted to exploreexperiences of good practice and analysed using thematic analysis.Results:In a total of 154 interviews, four components of good practice were identified across all six groups: a) establishingoutreach programmes to identify and engage with individuals with mental disorders; b) facilitating access to services thatprovide different aspects of health care, including mental health care, and thus reducing the need for further referrals; c)strengthening the collaboration and co-ordination betweendifferent services; and d) disseminating information onservices both to marginalised groups and to practitioners in the area.Conclusions:Experts across Europe hold similar views on what constitutes good practice in mental health care formarginalised groups. Care may be improved through better service organisation, coordination and information.
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