Communications Biology最新文献

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.

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.

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.

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.

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.

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.

Current tests of hearing fail to diagnose pathologies in ~10% of patients seeking help for hearing difficulties. Neural ensemble responses to perceptually relevant cues in the amplitude envelope, termed envelope following responses (EFR), hold promise as an objective diagnostic tool to probe these 'hidden' hearing difficulties. But clinical translation is impeded by current measurement approaches involving static amplitude modulated (AM) tones, which are time-consuming and lack optimal spectrotemporal resolution. Here we develop a framework to rapidly measure EFRs using dynamically varying AMs combined with spectrally specific analyses. These analyses offer 5x improvement in time and 30x improvement in spectrotemporal resolution, and more generally, are optimal for analyzing time-varying signals with known spectral trajectories of interest. We validate this approach across several mammalian species, including humans, and demonstrate robust responses that are highly correlated with traditional static EFRs. Our analytic technique facilitates rapid and objective neural assessment of temporal processing throughout the brain that can be applied to track auditory neurodegeneration using EFRs, as well as tracking recovery after therapeutic interventions.