Biology subjects

Wood, C.

Publications and source records attributed to Wood, C..

7 recordsLinked to original sources

bioRxiv2018

Nanoscale organization of rotavirus replication machineries

Rotavirus genome replication and assembly take place in cytoplasmic electron dense inclusions termed viro-plasms (VPs). Previous conventional optical microscopy studies observing the intracellular distribution of rotavirus proteins and their organization in VPs have lacked molecular-scale spatial resolution, due to inherent spatial resolution constraints. In this work we employed super-resolution microscopy to reveal the nanometric-scale organization of VPs formed during rotavirus infection, and quantitatively describe the structural organization of seven viral proteins and viral dsRNA within and around the VPs. The observed viral components are spatially organized as 6 concentric layers, in which NSP5 localizes at the center of the VPs, surrounded by a layer of NSP2 and NSP4 proteins, followed by an intermediate zone comprised of the VP1, VP2, VP6 proteins and the dsRNA. In the outermost zone, we observed a ring of VP4 and finally a layer of VP7. These findings show that rotavirus VPs are highly organized organelles.

microbiology↗

bioRxiv2018

SOCIAL STRESS AS A PRIMING MECHANISM FOR THERMAL TOLERANCE DURING A POLEWARD RANGE SHIFT

Cold tolerance plays a critical role in determining species geographical range limits. Previous studies have found that range shifts in response to climate warming are facilitated by cold acclimation capacities, due to increasingly colder and variable weather at high latitudes, and that cold tolerance can also be influenced by social factors. In this study we combined experiments and field studies to investigate the climatic and social factors affecting cold tolerances in range-shifting populations of the female-polymorphic damselfly Ischnura elegans in northeast Scotland. In the field, we observed both environmental (measured via habitat suitability) and social (sex ratio and density) effects on cold tolerance (CTmin). Androchrome females (male-like females) were less susceptible to beneficial social effects on cold tolerance than gynochromes (female-like females), and correspondingly, gynochrome frequency increased at colder, environmentally-limiting sites towards the range margin. Our manipulations of density in the laboratory further provide novel, experimental evidence that social interactions directly impact cold tolerance n this species. These results suggest that reciprocal effects of social environments on thermal acclimation may be an important but commonly overlooked aspect of allee effects which contribute to the formation of range margins. Moreover, our results point to a wider need to consider the role of population and social dynamics to shape both the thermal physiology of individuals and the thermal niches of species.

evolutionary biology↗

bioRxiv2018

The Relationship Between the Cervical Microbiome, HIV Status, and Pre-Cancerous Lesions

Nearly all cervical cancers are causally associated with Human Papillomavirus (HPV). The burden of HPV-associated dysplasias in Sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep-sequenced. Alpha diversity metrics; Chao1, PD whole tree, and operational taxonomic Unit (OTU) estimates, displayed significantly higher bacterial richness in HIV positive patients (P = 0.01) than in HIV negative patients. Within HIV positive patients, there was higher bacterial richness in patients with high grade squamous intraepithelial lesions (HSIL; P = 0.13) than those without lesions. The most abundant OTUs associated with high-grade squamous intraepitheilal lesions (HSIL) were Mycoplasmatales, Pseudomonadales, and Staphylococcus. We suggest that a chronic mycoplasma infection of the cervix can contribute to HPV-dependent dysplasia by sustained inflammatory signals.

cancer biology↗

bioRxiv2018

Conserved Roles of C. elegans and Human MANFs in Sulfatide Binding and Cytoprotection

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) is an endoplasmic reticulum (ER) protein that can be secreted and protect dopamine neurons and cardiomyocytes from ER stress and apoptosis. The mechanism of action of extracellular MANF has long been elusive. From a genetic screen for mutants with abnormal ER stress response, we identified the gene Y54G2A.23 as the evolutionarily conserved C. elegans MANF orthologue. We find that MANF binds to the lipid sulfatide, also known as 3-O-sulfogalactosylceramide present in serum and outer-cell membrane leaflets, directly in isolated forms and in reconstituted lipid micelles. Sulfatide binding promotes cellular MANF uptake and cytoprotection from hypoxia-induced cell death. Heightened ER stress responses of MANF-null C. elegans mutants and mammalian cells are alleviated by human MANF in a sulfatide-dependent manner. Our results demonstrate conserved roles of MANF in sulfatide binding and ER stress response, supporting sulfatide as a long-sought lipid mediator of MANFs cytoprotection.

cell biology↗

bioRxiv2017

Sperm chemotaxis is driven by the slope of the chemoattractant concentration field

Spermatozoa of marine invertebrates are attracted to their conspecific female gamete by diffusive molecules, called chemoattractants, released from the egg investments in a process known as chemotaxis. The information from the egg chemoattractant concentration field is decoded into intracellular Ca2+ concentration ([Ca2+]i) changes that regulate the internal motors that shape the flagellum as it beats. By studying sea urchin species-specific differences in sperm chemoattractant-receptor characteristics we show that receptor density constrains the steepness of the chemoattractant concentration gradient detectable by spermatozoa. Through analyzing different chemoattractant gradient forms, we demonstrate for the first time that Strongylocentrotus purpuratus sperm are chemotactic and this response is consistent with frequency entrainment of two coupled physiological oscillators: i) the stimulus function and ii) the [Ca2+]i changes. We demonstrate that the slope of the chemoattractant gradients provides the coupling force between both oscillators, arising as a fundamental requirement for sperm chemotaxis.

biophysics↗

bioRxiv2017

De novo assembly of microbial genomes from human gut metagenomes using barcoded short read sequences

Although shotgun short-read sequencing has facilitated the study of strain-level architecture within complex microbial communities, existing metagenomic approaches often cannot capture structural differences between closely related co-occurring strains. Recent methods, which employ read cloud sequencing and specialized assembly techniques, provide significantly improved genome drafts and show potential to capture these strain-level differences. Here, we apply this read cloud metagenomic approach to longitudinal stool samples from a patient undergoing hematopoietic cell transplantation. The patients microbiome is profoundly disrupted and is eventually dominated by Bacteroides caccae. Comparative analysis of B. caccae genomes obtained using read cloud sequencing together with metagenomic RNA sequencing allows us to predict that particular mobile element integrations result in increased antibiotic resistance, which we further support using in vitro antibiotic susceptibility testing. Thus, we find read cloud sequencing to be useful in identifying strain-level differences that underlie differential fitness.

bioinformatics↗

bioRxiv2017

Geographically structured genetic variation in the Medicago lupulina-Ensifer mutualism

Mutualisms are interspecific interactions affecting the ecology and evolution of species. Patterns of geographic variation in interacting species may play an important role in understanding how variation is maintained in mutualisms, particularly in introduced ranges. One agriculturally and ecologically important mutualism is the partnership between legume plants and rhizobia. Through characterizing and comparing the population genomic structure of the legume Medicago lupulina and two rhizobial species (Ensifer medicae and E. meliloti), we explored the spatial scale of population differentiation between interacting partners in their introduced range in North America. We found high proportions of E. meliloti in southeastern populations and high proportions of E. medicae in northwestern populations. Medicago lupulina and the Ensifer genus showed similar patterns of spatial genetic structure (isolation by distance). However, we detected no evidence of isolation by distance or population structure within either species of bacteria. Genome-wide nucleotide diversity within each of the two Ensifer species was low, suggesting limited introduction of strains, founder events, or severe bottlenecks. Our results suggest that there is potential for geographically structured coevolution between M. lupulina and the Ensifer genus, but not between M. lupulina and either Ensifer species.

evolutionary biology↗