A functional bacteria-derived restriction modification system in the mitochondrion of a heterotrophic protist

The overarching trend in mitochondrial genome evolution is functional streamlining coupled with gene loss; therefore, gene acquisition by mitochondria is considered to be exceedingly rare. Selfish elements in the form of self-splicing introns occur in many organellar genomes, but the wider diversity of selfish elements, and how they persist in the DNA of organelles, has not been explored. In the mitochondrial genome of a marine heterotrophic katablepharid protist, we identify a functional type II restriction modification (RM) system originating from a horizontal gene transfer (HGT) event involving bacteria related to flavobacteria. This RM system consists of an HpaII-like endonuclease and a cognate cytosine methyltransferase (CM). We demonstrate that these proteins are functional by heterologous expression in both bacterial and eukaryotic cells. These results suggest that a mitochondrial-encoded RM system can function as a toxin-antitoxin selfish element and that such elements could be co-opted by eukaryotic genomes to drive biased organellar inheritance.Peer reviewe

Comparative- and Network-based Proteomic Analysis of Bacterial Chondronecrosis with Osteomyelitis Lesions in Broiler\u27s Proximal Tibiae Identifies New Molecular Signatures of Lameness

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a specific cause of lameness in commercial fast-growing broiler (meat-type) chickens and represents significant economic, health, and wellbeing burdens. However, the molecular mechanisms underlying the pathogenesis remain poorly understood. This study represents the first comprehensive characterization of the proximal tibia proteome from healthy and BCO chickens. Among a total of 547 proteins identified, 222 were differentially expressed (DE) with 158 up- and 64 down-regulated proteins in tibia of BCO vs. normal chickens. Biological function analysis using Ingenuity Pathways showed that the DE proteins were associated with a variety of diseases including cell death, organismal injury, skeletal and muscular disorder, immunological and inflammatory diseases. Canonical pathway and protein–protein interaction network analysis indicated that these DE proteins were involved in stress response, unfolded protein response, ribosomal protein dysfunction, and actin cytoskeleton signaling. Further, we identified proteins involved in bone resorption (osteoclast-stimulating factor 1, OSFT1) and bone structural integrity (collagen alpha-2 (I) chain, COL2A1), as potential key proteins involved in bone attrition. These results provide new insights by identifying key protein candidates involved in BCO and will have significant impact in understanding BCO pathogenesis

Endocrine responses to sport-related brain injury in female athletes: a narrative review and a call for action

Sport-related brain injury (SRBI) occurs when a blow to the head causes the brain to move back and forth in the skull, and can lead to neuroendocrine dysfunction. Research has shown that males and females experience and recover from SRBI differently, yet most of what is known regarding diagnosis, treatment, and recovery of SRBI is based on male normative data even though females meet or exceed incidence numbers of SRBIs compared to those of males. Females also have been known to have worse outcomes and a greater number of symptoms following SRBI than males. Research is limited as to why females have worse outcomes, but sex hormones have been suggested as a potential reason. SRBI may cause a dysregulation of the hypothalamic–pituitary–gonadal (HPG) axis, which is responsible for regulating the sex hormones estrogen and progesterone. Initial research has shown that SRBI may suppress estrogen and progesterone, and the concentration of these sex hormones could be indicative of injury severity and recovery trajectory. This review discusses the sex-specific differences in SRBI and also the future direction of research that is needed in order to identify the repercussions of SRBIs for female athletes, which will eventually lead to better clinical treatment, sideline care, and recovery profiles

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Comparative genomic analysis of the ‘pseudofungus’ Hyphochytrium catenoides

Eukaryotic microbes have three primary mechanisms for obtaining nutrients and energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the latter two functions arose independently multiple times in the eukaryotes. The Fungi successfully coupled osmotrophy with filamentous growth, and similar traits are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both the Fungi and the Pseudofungi encompass a diversity of plant and animal parasites. Genome-sequencing efforts have focused on host-associated microbes (mutualistic symbionts or parasites), providing limited comparisons with free-living relatives. Here we report the first draft genome sequence of a hyphochytriomycete ‘pseudofungus’; Hyphochytrium catenoides. Using phylogenomic approaches, we identify genes of recent viral ancestry, with related viral derived genes also present on the genomes of oomycetes, suggesting a complex history of viral coevolution and integration across the Pseudofungi. H. catenoides has a complex life cycle involving diverse filamentous structures and a flagellated zoospore with a single anterior tinselate flagellum. We use genome comparisons, drug sensitivity analysis and high-throughput culture arrays to investigate the ancestry of oomycete/pseudofungal characteristics, demonstrating that many of the genetic features associated with parasitic traits evolved specifically within the oomycete radiation. Comparative genomics also identified differences in the repertoire of genes associated with filamentous growth between the Fungi and the Pseudofungi, including differences in vesicle trafficking systems, cell-wall synthesis pathways and motor protein repertoire, demonstrating that unique cellular systems underpinned the convergent evolution of filamentous osmotrophic growth in these two eukaryotic groups

Adverse childhood experience and adult persistent pain and disability: protocol for a systematic review and meta-analysis

A growing body of research highlights the pervasive harms of adverse childhood experiences (ACEs) on health throughout the life-course. However, findings from prior reviews and recent longitudinal studies investigating the association between types of ACEs and persistent pain have yielded inconsistent findings in the strength and direction of associations. The purpose of this review is to appraise and summarize evidence on the relationship between ACEs and persistent pain and disability outcomes in adulthood. The specific aims are (1) to determine whether there is a relationship between exposure to ACE and persistent pain and disability in adults and (2) to determine whether unique and cumulative ACEs exposures (number and type) increase the risk of developing persistent pain and disability in adulthood

Energy allocation and behaviour in the growing broiler chicken

Broiler chickens are increasingly at the forefront of global meat production but the consequences of fast growth and selection for an increase in body mass on bird health are an ongoing concern for industry and consumers. To better understand the implications of selection we evaluated energetics and behaviour over the 6-week hatch-to-slaughter developmental period in a commercial broiler. The effect of posture on resting metabolic rate becomes increasingly significant as broilers grow, as standing became more energetically expensive than sitting. The proportion of overall metabolic rate accounted for by locomotor behaviour decreased over development, corresponding to declining activity levels, mean and peak walking speeds. These data are consistent with the inference that broilers allocate energy to activity within a constrained metabolic budget and that there is a reducing metabolic scope for exercise throughout their development. Comparison with similarly sized galliforms reveals that locomotion is relatively energetically expensive in broilers