by Kory P. Luedke, Jiro Yoshino, Chang Yin, Nan Jiang, Jessica M. Huang, Kevin Huynh, Jay Z. Parrish An animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila ..read more

by Darius Camp, Bhavya Venkatesh, Veronika Solianova, Lorena Varela, Benjamin T. Goult, Guy Tanentzapf Cell adhesion requires linkage of transmembrane receptors to the cytoskeleton through intermediary linker proteins. Integrin-based adhesion to the extracellular matrix (ECM) involves large adhesion complexes that contain multiple cytoskeletal adapters that connect to the actin cytoskeleton. Many of these adapters, including the essential cytoskeletal linker Talin, have been shown to contain multiple actin-binding sites (ABSs) within a single protein. To investigate the possible role of having ..read more

by Callan O’Connor, Gregory R. Keele, Whitney Martin, Timothy Stodola, Daniel Gatti, Brian R. Hoffman, Ron Korstanje, Gary A. Churchill, Laura G. Reinholdt The health risks that arise from environmental exposures vary widely within and across human populations, and these differences are largely determined by genetic variation and gene-by-environment (gene–environment) interactions. However, risk assessment in laboratory mice typically involves isogenic strains and therefore, does not account for these known genetic effects. In this context, genetically heterogenous cell lines from laboratory m ..read more

by Boxi Lin, Andrew D. Paterson, Lei Sun Genetic effects can be sex-specific, particularly for traits such as testosterone, a sex hormone. While sex-stratified analysis provides easily interpretable sex-specific effect size estimates, the presence of sex-differences in SNP effect implies a SNP×sex interaction. This suggests the usage of the often overlooked joint test, testing for an SNP’s main and SNP×sex interaction effects simultaneously. Notably, even without individual-level data, the joint test statistic can be derived from sex-stratified summary statistics through an omnibus meta-analys ..read more

by Liu Xu, Yibing Chen, Lingling Liu, Xinyu Hu, Chengsi He, Yuan Zhou, Xinyi Ding, Minhua Luo, Jiajing Yan, Quentin Liu, Hongsheng Li, Dongming Lai, Zhengzhi Zou Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were ..read more

by Peiyao Wang, Zhaotong Lin, Haoran Xue, Wei Pan Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects ..read more

by Iain R. Timmins, The PRACTICAL Consortium , Frank Dudbridge Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of ..read more

by Paris Veltsos, John K. Kelly Gene expression can be influenced by genetic variants that are closely linked to the expressed gene (cis eQTLs) and variants in other parts of the genome (trans eQTLs). We created a multiparental mapping population by sampling genotypes from a single natural population of Mimulus guttatus and scored gene expression in the leaves of 1,588 plants. We find that nearly every measured gene exhibits cis regulatory variation (91% have FDR ..read more

by Beth L. Dumont, Daniel M. Gatti, Mallory A. Ballinger, Dana Lin, Megan Phifer-Rixey, Michael J. Sheehan, Taichi A. Suzuki, Lydia K. Wooldridge, Hilda Opoku Frempong, Raman Akinyanju Lawal, Gary A. Churchill, Cathleen Lutz, Nadia Rosenthal, Jacqueline K. White, Michael W. Nachman The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenot ..read more

by Manuela Alvarado Obando, Diego Rey-Varela, Felipe Cava, Tobias Dörr Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and a series of PG modifications are required to allow expansion of the sacculus. Endopeptidases (EPs), for example, cleave the crosslinks between adjacent PG strands to allow the incorporation of newly synthesized PG. EPs are collectively essential for bacterial growth and must ..read more