Penny C Sparkes, Mufuliat Toyin Famodimu, Eduardo Alves, Eric Springer, Jude Przyborski, Michael J Delves
{"title":"Mitochondrial ATP synthesis is essential for efficient gametogenesis in Plasmodium falciparum.","authors":"Penny C Sparkes, Mufuliat Toyin Famodimu, Eduardo Alves, Eric Springer, Jude Przyborski, Michael J Delves","doi":"10.1038/s42003-024-07240-z","DOIUrl":"10.1038/s42003-024-07240-z","url":null,"abstract":"<p><p>Plasmodium male and female gametocytes are the gatekeepers of human-to-mosquito transmission, therefore essential for propagation of malaria within a population. Whilst dormant in humans, their divergent roles during transmission become apparent soon after mosquito feeding with a rapid transformation into gametes - males forming eight motile sperm-like cells aiming to fertilise a single female gamete. Little is known about how the parasite fuels this abrupt change, and the potential role played by their large and elaborate cristate mitochondrion. Using a sex-specific antibody and functional mitochondrial labelling, we show that the male gametocyte mitochondrion is less active than that of female gametocytes and more sensitive to antimalarials targeting mitochondrial energy metabolism. Rather than a vestigial organelle discarded during male gametogenesis, we demonstrate that mitochondrial ATP synthesis is essential for its completion. Additionally, using a genetically encoded ratiometric ATP sensor, we show that gametocytes can maintain cytoplasmic ATP homeostasis in the absence of mitochondrial respiration, indicating the essentiality of the gametocyte mitochondrion for transmission alone. Together, this reveals how gametocytes responsively balance the conflicting demands of a dormant and active lifestyle, highlighting the mitochondria as a rich source of transmission-blocking targets for future drug development.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1525"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valentina Hopl, Adéla Tiffner, Armin Wutscher, Matthias Sallinger, Herwig Grabmayr, Magdalena Prantl, Maximilian Fröhlich, Julia Söllner, Sarah Weiß, Hadil Najjar, Yuliia Nazarenko, Selina Harant, Natalia Kriško, Marc Fahrner, Christina Humer, Carmen Höglinger, Heinrich Krobath, Daniel Bonhenry, Isabella Derler
{"title":"Water in peripheral TM-interfaces of Orai1-channels triggers pore opening.","authors":"Valentina Hopl, Adéla Tiffner, Armin Wutscher, Matthias Sallinger, Herwig Grabmayr, Magdalena Prantl, Maximilian Fröhlich, Julia Söllner, Sarah Weiß, Hadil Najjar, Yuliia Nazarenko, Selina Harant, Natalia Kriško, Marc Fahrner, Christina Humer, Carmen Höglinger, Heinrich Krobath, Daniel Bonhenry, Isabella Derler","doi":"10.1038/s42003-024-07174-6","DOIUrl":"10.1038/s42003-024-07174-6","url":null,"abstract":"<p><p>The activation of the Ca<sup>2+</sup>-channel Orai1 via the physiological activator stromal interaction molecule 1 (STIM1) requires structural rearrangements within the entire channel complex involving a series of gating checkpoints. Focusing on the gating mechanism operating along the peripheral transmembrane domain (TM) 3/TM4-interface, we report here that some charged substitutions close to the center of TM3 or TM4 lead to constitutively active Orai1 variants triggering nuclear factor of activated T-cell (NFAT) translocation into the nucleus. Molecular dynamics simulations unveil that this gain-of-function correlates with enhanced hydration at peripheral TM-interfaces, leading to increased local structural flexibility of the channel periphery and global conformational changes permitting pore opening. Our findings indicate that efficient dehydration of the peripheral TM-interfaces driven by the hydrophobic effect is critical for maintaining the closed state of Orai1. We conclude that a charge close to the center of TM3 or TM4 facilitates concomitant hydration and widening of peripheral TM interfaces to trigger constitutive Orai1 pore opening to a level comparable to or exceeding that of native activated Orai1.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1522"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Demeter Túrós, Jelica Vasiljevic, Kerstin Hahn, Sven Rottenberg, Alberto Valdeolivas
{"title":"Chrysalis: decoding tissue compartments in spatial transcriptomics with archetypal analysis.","authors":"Demeter Túrós, Jelica Vasiljevic, Kerstin Hahn, Sven Rottenberg, Alberto Valdeolivas","doi":"10.1038/s42003-024-07165-7","DOIUrl":"10.1038/s42003-024-07165-7","url":null,"abstract":"<p><p>Dissecting tissue compartments in spatial transcriptomics (ST) remains challenging due to limited spatial resolution and dependence on single-cell reference data. We present Chrysalis, a computational method that rapidly uncovers tissue compartments through spatially variable gene (SVG) detection and archetypal analysis without requiring external reference data. Additionally, it offers a unique visualisation approach for swift tissue characterisation and provides access to the underlying gene expression signatures, enabling the identification of spatially and functionally distinct cellular niches. Chrysalis was evaluated through various benchmarks and validated against deconvolution, independently obtained cell type abundance data, and histopathological annotations, demonstrating superior performance compared to other algorithms on both in silico and real-world test examples. Furthermore, we showcased its versatility across different technologies, such as Visium, Visium HD, Slide-seq, and Stereo-seq.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1520"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"NuSAP4 regulates chromosome segregation in Trypanosoma brucei by promoting bipolar spindle assembly.","authors":"Qing Zhou, Ziyin Li","doi":"10.1038/s42003-024-07248-5","DOIUrl":"10.1038/s42003-024-07248-5","url":null,"abstract":"<p><p>Faithful chromosome segregation in eukaryotes requires the assembly of a bipolar spindle and the faithful attachment of kinetochores to spindle microtubules, which are regulated by various spindle-associated proteins (SAPs) that play distinct functions in regulating spindle dynamics and microtubule-kinetochore attachment. The protozoan parasite Trypanosoma brucei employs evolutionarily conserved and kinetoplastid-specific proteins, including some kinetoplastid-specific nucleus- and spindle-associated proteins (NuSAPs), to regulate chromosome segregation. Here, we characterized NuSAP4 and its functional interplay with diverse SAPs in promoting chromosome segregation in T. brucei. NuSAP4 associates with the spindle during mitosis and concentrates at spindle poles where it interacts with SPB1 and MAP103. Knockdown of NuSAP4 impairs chromosome segregation by disrupting bipolar spindle assembly and spindle pole protein localization. These results uncover the mechanistic role of NuSAP4 in regulating chromosome segregation by promoting bipolar spindle assembly, and highlight the unusual features of mitotic regulation by spindle-associated proteins in this early divergent microbial eukaryote.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1524"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Uncovering disease-related multicellular pathway modules on large-scale single-cell transcriptomes with scPAFA.","authors":"Zhuoli Huang, Yuhui Zheng, Weikai Wang, Wenwen Zhou, Yanbo Zhang, Chen Wei, Xiuqing Zhang, Xin Jin, Jianhua Yin","doi":"10.1038/s42003-024-07238-7","DOIUrl":"10.1038/s42003-024-07238-7","url":null,"abstract":"<p><p>Pathway analysis is a crucial analytical phase in disease research on single-cell RNA sequencing (scRNA-seq) data, offering biological interpretations based on prior knowledge. However, currently available tools for generating cell-level pathway activity scores (PAS) exhibit computational inefficacy in large-scale scRNA-seq datasets. Additionally, disease-related pathways are often identified through cross-condition comparisons within specific cell types, overlooking potential patterns that involve multiple cell types. Here, we present single-cell pathway activity factor analysis (scPAFA), a Python library designed for large-scale single-cell datasets allowing rapid PAS computation and uncovering biologically interpretable disease-related multicellular pathway modules, which are low-dimensional representations of disease-related PAS alterations in multiple cell types. Application on colorectal cancer (CRC) datasets and large-scale lupus atlas over 1.2 million cells demonstrated that scPAFA can achieve over 40-fold reductions in the runtime of PAS computation and further identified reliable and interpretable multicellular pathway modules that capture the heterogeneity of CRC and transcriptional abnormalities in lupus patients, respectively. Overall, scPAFA presents a valuable addition to existing research tools in disease research, with the potential to reveal complex disease mechanisms and support biomarker discovery at the pathway level.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1523"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thanumol Abdul Khader, Waqar Ahmad, Shaima Akhlaq, Neena Gopinathan Panicker, Bushra Gull, Jasmin Baby, Tahir A Rizvi, Farah Mustafa
{"title":"Transactivation of the novel 5' cis-acting element of mouse mammary tumor virus (MMTV) by human retroviral transactivators Tat and Tax.","authors":"Thanumol Abdul Khader, Waqar Ahmad, Shaima Akhlaq, Neena Gopinathan Panicker, Bushra Gull, Jasmin Baby, Tahir A Rizvi, Farah Mustafa","doi":"10.1038/s42003-024-07139-9","DOIUrl":"10.1038/s42003-024-07139-9","url":null,"abstract":"<p><p>The mouse mammary tumor virus (MMTV) encodes a 5' element crucial for transcription of its genome along with the Rem/Rem-responsive element (RmRE) responsible for nuclear export of this unspliced RNA. Whether the 5' element is Rem-responsive or has any functional interaction with host/viral factors to facilitate MMTV gene expression was tested in this study. Our results reveal that the 5' element is non-responsive to Rem, but can be transactivated by both HIV Tat and HTLV-1 Tax activators. Reciprocally, MMTV could transactivate not only HIV TAR (similar to HTLV Tax), but also its 5' element. Furthermore, we reveal involvement of pTEFb, a general elongation factor associated with transactivation by Tat/Tax. This makes MMTV the first betaretrovirus to encode both Rem/RRE and Tat/TAR-Tax/TRE-like transcription regulatory systems. This study should enhance not only our understanding of retrovirus replication and virally-induced cancers/immunodeficiency syndromes, but also development of improved retroviral vectors for human gene therapy.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1521"},"PeriodicalIF":5.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annika Haessler, Michael Candlish, Jasmin K. Hefendehl, Nathalie Jung, Maike Windbergs
{"title":"Mapping cellular stress and lipid dysregulation in Alzheimer-related progressive neurodegeneration using label-free Raman microscopy","authors":"Annika Haessler, Michael Candlish, Jasmin K. Hefendehl, Nathalie Jung, Maike Windbergs","doi":"10.1038/s42003-024-07182-6","DOIUrl":"10.1038/s42003-024-07182-6","url":null,"abstract":"Aβ plaques are a main feature of Alzheimer’s disease, and pathological alterations especially in their microenvironment have recently come into focus. However, a holistic imaging approach unveiling these changes and their biochemical nature is still lacking. In this context, we leverage confocal Raman microscopy as unbiased tool for non-destructive, label-free differentiation of progressive biomolecular changes in the Aβ plaque microenvironment in brain tissue of a murine model of cerebral amyloidosis. By developing a detailed approach, overcoming many challenges of chemical imaging, we identify spatially-resolved molecular signatures of disease-associated structures. Specifically, our study reveals nuclear condensation, indicating cellular degeneration, and increased levels of cytochrome c, showing mitochondrial dysfunction, in the vicinity of Aβ plaques. Further, we observe severe accumulation of especially unsaturated lipids. Thus, our study contributes to a comprehensive understanding of disease progression in the Aβ plaque microenvironment, underscoring the prospective of Raman imaging in neurodegenerative disorder research. Multivariate analysis of hyperspectral Raman imaging data unveils severe cellular toxicity and lipid dysregulation in the chemically complex Aβ plaque microenvironment.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-11"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42003-024-07182-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hang Zhou, Viola Neudecker, Jose F. Perez-Zoghbi, Ansgar M. Brambrink, Guang Yang
{"title":"Age-dependent cerebral vasodilation induced by volatile anesthetics is mediated by NG2+ vascular mural cells","authors":"Hang Zhou, Viola Neudecker, Jose F. Perez-Zoghbi, Ansgar M. Brambrink, Guang Yang","doi":"10.1038/s42003-024-07200-7","DOIUrl":"10.1038/s42003-024-07200-7","url":null,"abstract":"Anesthesia can influence cerebral blood flow by altering vessel diameter. Using in vivo two-photon imaging, we examined the effects of volatile anesthetics, sevoflurane and isoflurane, on vessel diameter in young and adult mice. Our results show that these anesthetics induce robust dilation of cortical arterioles and arteriole-proximate capillaries in adult mice, with milder effects in juveniles and no dilation in infants. This anesthesia-induced vasodilation correlates with decreased cytosolic Ca2+ levels in NG2+ vascular mural cells. Optogenetic manipulation of these cells bidirectionally regulates vessel diameter, and their ablation abolishes the vasodilatory response to anesthetics. In immature brains, NG2+ mural cells are fewer in number and express lower levels of Kir6.1, a subunit of ATP-sensitive potassium channels. This likely contributes to the age-dependent differences in vasodilation, as Kir6.1 activation promotes, while its inhibition reduces, anesthesia-induced vasodilation. These findings highlight the essential role of NG2+ mural cells in mediating anesthesia-induced cerebral vasodilation. Live animal imaging reveals age-dependent cerebral vasodilatory responses to volatile anesthetics, pronounced in adult mice and diminished or absent in developing brains. These effects are mediated by NG2+ mural cells and Kir6.1 signaling.","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":" ","pages":"1-16"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tobias Richter, Lisa Geres, Sebastian König, Kristin H Braziunas, Cornelius Senf, Dominik Thom, Claus Bässler, Jörg Müller, Rupert Seidl, Sebastian Seibold
{"title":"Effects of climate and forest development on habitat specialization and biodiversity in Central European mountain forests.","authors":"Tobias Richter, Lisa Geres, Sebastian König, Kristin H Braziunas, Cornelius Senf, Dominik Thom, Claus Bässler, Jörg Müller, Rupert Seidl, Sebastian Seibold","doi":"10.1038/s42003-024-07239-6","DOIUrl":"10.1038/s42003-024-07239-6","url":null,"abstract":"<p><p>Mountain forests are biodiversity hotspots with competing hypotheses proposed to explain elevational trends in habitat specialization and species richness. The altitudinal-niche-breadth hypothesis suggests decreasing specialization with elevation, which could lead to decreasing species richness and weaker differences in species richness and beta diversity among habitat types with increasing elevation. Testing these predictions for bacteria, fungi, plants, arthropods, and vertebrates, we found decreasing habitat specialization (represented by forest developmental stages) with elevation in mountain forests of the Northern Alps - supporting the altitudinal-niche-breadth hypothesis. Species richness decreased with elevation only for arthropods, whereas changes in beta diversity varied among taxa. Along the forest developmental gradient, species richness mainly followed a U-shaped pattern which remained stable along elevation. This highlights the importance of early and late developmental stages for biodiversity and indicates that climate change may alter community composition not only through distributional shifts along elevation but also across forest developmental stages.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1518"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Feeding postures as indicators of mutable collagenous tissue in extinct echinoderms.","authors":"Johnny A Waters, Jan Bohatý, D Bradford Macurda","doi":"10.1038/s42003-024-07232-z","DOIUrl":"10.1038/s42003-024-07232-z","url":null,"abstract":"<p><p>Echinoderms are a diverse phylum with a rich fossil record. The five extant classes of echinoderms are characterised by a pentameral (or pseudo-pentameral) symmetry, a water vascular system, a mesodermal skeleton of calcite stereom, and Mutable Collagenous Tissue (MCT), a unique type of connective tissue. Difficulties in tracing the geologic history of these traits complicates phylogenetic analyses of echinoderms. We present evidence herein of MCT in an extinct class of echinoderms, the Blastoidea. Blastoids have composite hair-like structures, brachioles, which formed a feeding filtration fan. Rare specimens from the Devonian of Germany demonstrate the presence of MCT by preserving brachioles as long rigid structures making a feeding fan with MCT in a rigid state. Specimens show brachioles in different configurations in the same specimen, which may indicate nervous control of MCT in individual brachioles. Other specimens appear to indicate the transition of MCT from a rigid to a compliant state as rigid brachioles begin to curve. Still other specimens show a majority of brachioles as limp hair-like structures swept by currents while a minority of brachioles remain rigid. These remarkable specimens could capture MCT transitioning from its rigid to compliant states in individual specimens indicating rapid burial and preservation.</p>","PeriodicalId":10552,"journal":{"name":"Communications Biology","volume":"7 1","pages":"1516"},"PeriodicalIF":5.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}