Biology subjects

Carey, C.

Publications and source records attributed to Carey, C..

5 recordsLinked to original sources

bioRxiv2025

Muscle Strength and Size Relationships with Unilateral Progressive Resistance Training

PurposeThis study defines correlative and causal relationships between muscle strength and size before and after unilateral resistance training (RT) in a large cohort of healthy adults, focusing on sex differences within these relationships. MethodsResults from 1233 participants (504 males and 729 females) in a retrospective analysis were included. Maximal voluntary isometric contraction strength (MVC), one-repetition maximum strength (1RM), biceps cross-sectional area (CSA) and elbow flexor volume (VOL) measures of the non-dominant and dominant arm were evaluated from baseline and after 12-wk RT twice per week. Correlations of MVC and VOL and 1RM and VOL were calculated in the whole cohort and within each sex independently. Causal analysis modeling was used to infer mechanistic relationships among variables. ResultsAbsolute muscle strength and size related to one another both at baseline and following training, however correlation strength in each sex were weak. After RT, MVC relative change and VOL relative change correlations were correlated for the whole cohort (r=0.16; p<0.001) and females (r=0.18; p<0.001), but not in males (r=0.11; p=0.07). No significant correlations for relative change in 1RM and VOL were observed for the whole cohort or within sex. Causal discovery determined that change in VOL caused significant change in 1RM (but not MVC) and age was identified as a potential cause. ConclusionsSex differences occur in muscle size and strength relationship adaptations following resistance training, most notably the absence of significant relationships between relative size and strength changes in men. Simpsons paradox bias, where assessing the combined data of males and females (also affecting overall sample size) affects identifies patterns differently than assessing relationships within each sex, may partially explain our findings.

physiology↗

bioRxiv2020

Poised cell circuits in human skin are activated in disease

The human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid cells and macrophages in developing skin in contrast to T cells and migratory dendritic cells in adult skin. We demonstrate dual keratinocyte differentiation trajectories and activated cellular circuits comprising vascular endothelial cells mediating immune cell trafficking, disease-specific clonally expanded IL13/IL22 and IL17A/F-expressing lymphocytes, epidermal IL23-expressing dendritic cells and inflammatory keratinocytes in disease. Our findings provide key insights into the dynamic cellular landscape of human skin in health and disease. One Sentence SummarySingle cell atlas of human skin reveals cell circuits which are quantitatively and qualitatively reconfigured in inflammatory skin disease.

immunology↗

bioRxiv2020

Evaluation of the bacterial and fungal microbiome on the skin of Anaxyrus boreas, Rhinella marina, and Xenopus laevis and implications related to Batrachochytrium dendrobatidis susceptibility

The skin and its microbiome are the first lines of defense against environmental stressors and pathogens. The symbiotic relationships between the host and the microbiome and within the microbiome are critical to host health. In frogs, this research area is lacking especially in the context of their skin infection with Batrachochytrium dendrobatidis. B. dendrobatidis is a major fungal skin pathogen to amphibians that has caused the extinction of hundreds of amphibian species populations. While some frog species are known susceptible to B. dendrobatidis infections, and others are resistant, we hypothesized that the skin microbiome of frogs plays a role in the prevention of B. dendrobatidis infections that is yet unknown. Therefore, in this work we have examined the bacterial and fungal skin microbiome of one species that is sensitive to B. dendrobatidis infections, Anaxyrus boreas (formerly: Bufo boreas), and the resistant species, Xenopus laevis and Rhinella marina (formerly: Bufo marinus). This was accomplished using tag-encoded FLX amplicon pyrosequencing (bTEFAP) of the 16S rRNA and ITS DNA regions. Our results showed that the bacterial and fungal skin microbiome of A. boreas and R. marina were more similar than to that of X. laevis. We found distinct patterns between the skin microbiome of B. dendrobatidis sensitive and resistant frog species. For the bacterial microbiome, the most abundant bacterial genus observed in all frog samples was Microbacterium. The resistant species had higher abundance in the genera Pseudomonas, Sphingobium, Pedobacter, Variovorax, Morganella, Sphingomonas, Giesbergeria, and Agromyces. In contrast, they had lower abundance of Elizabethkingia (formerly: Flavobacterium), Enterobacter, Ochrobactrum, Arthobacter, Stenotrophomonas, Shinella, Klebsiella, Aeromonas, Comomonas, Chitinophaga, and Rhodococcus. Regarding the fungal microbiome, the resistant species showed higher abundance in the genera Aspergillus, Cladosporium, Elaphomyces, Monascus, Tritirachium, Ceratostomella, and Claviceps, while Asterotremella, Trichosporon, and Malasezzia genera were less represented in resistant species. We have also observed that in the resistant species, the skin microbiome had higher diversity in the fungal microbiota, but not in the bacterial microbiota. We speculate that those observed differences have implications in B. dendrobatidis susceptibility that are yet to be determined, possibly through competition for nutrients or the production of specific anti-fungal molecules. GRAPHICAL ABSTRACT O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2020

Genetic analyses identify widespread sex-differential participation bias

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of this participation bias is challenging as it requires the genotypes of unseen individuals. However, we demonstrate that it is possible to estimate comparative biases by performing GWAS contrasting one subgroup versus another. For example, we show that sex exhibits autosomal heritability in the presence of sex-differential participation bias. By performing a GWAS of sex in ~3.3 million males and females, we identify over 158 autosomal loci significantly associated with sex and highlight complex traits underpinning differences in study participation between sexes. For example, the body mass index (BMI) increasing allele at the FTO locus was observed at higher frequency in males compared to females (OR 1.02 [1.02-1.03], P=4.4x10-36). Finally, we demonstrate how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

genetics↗

bioRxiv2019

Pathognomonic and epistatic genetic alterations in B-cell non-Hodgkin lymphoma

B-cell non-Hodgkins lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL such as diffuse large B-cell lymphoma (DLBCL) have been comprehensively interrogated at the genomic level. But rarer subtypes such as mantle cell lymphoma (MCL) remain sparsely characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth; including DLBCL, MCL, follicular lymphoma (FL), and Burkitt lymphoma (BL). We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumor from each subtype, including the frequent genetic deregulation of the ubiquitin proteasome system (UPS). In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis.

genomics↗