Revising the Freshwater Thelohania to Astathelohania gen. et comb. nov., and Description of Two New Species

Crayfish are common hosts of microsporidian parasites, prominently from the genus Thelohania. Thelohania is a polyphyletic genus, with multiple genetically distinct lineages found from freshwater and marine environments. Researchers have been calling for a revision of this group for over a decade. We provide evidence that crayfish-infecting freshwater Thelohania are genetically and phylogenetically distinct from the marine Thelohania (Clade V/Glugeida), whilst also describing two new species that give further support to the taxonomic revision. We propose that the freshwater Thelohania should be transferred to their own genus, Astathelohania gen. et comb. nov., in a new family (Astathelohaniidae n. fam.). This results in the revision of Thelohania contejeani (Astathelohania contejeani), Thelohania montirivulorum (Astathelohania montirivulorum), and Thelohania parastaci (Astathelohania parastaci). We also describe two novel muscle-infecting Astathelohania species, A. virili n. sp. and A. rusti n. sp., from North American crayfishes (Faxonius sp.). We used histological, molecular, and ultrastructural data to formally describe the novel isolates. Our data suggest that the Astathelohania are genetically distinct from other known microsporidian genera, outside any described family, and that their SSU rRNA gene sequence diversity follows their host species and native geographic location. The range of this genus currently includes North America, Europe, and Australia

Alternosema astaquatica n. sp. (Microsporidia: Enterocytozoonida), a systemic parasite of the crayfish Faxonius virilis

Crayfish have strong ecological impacts in freshwater systems, yet our knowledge of their parasites is limited. This study describes the first systemic microsporidium (infects multiple tissue types) Alternosema astaquatica n. sp. (Enterocytozoonida) isolated from a crayfish host, Faxonius virilis, using histopathology, transmission electron microscopy, gene sequencing, and phylogenetics. The parasite develops in direct contact with the host cell cytoplasm producing mature spores that are monokaryotic and ellipsoid in shape. Spores have 9–10 coils of the polar filament and measure 3.07 ± 0.26 µm (SD) in length and 0.93 ± 0.08 µm (SD) in width. Our novel isolate has high genetic similarity to Alternosema bostrichidis isolated from terrestrial beetles; however, genetic data from this parasite is restricted to a small fragment (396 bp) of the SSU gene. Additional data related to spore morphology and development, host, environment, and ecology indicate that our novel isolate is distinct from A. bostrichidis, which supports a new species description. Alternosema astaquatica n. sp. represents a novel member of the Orthosomella-like group which appears to be a set of opportunists within the Enterocytozoonida. The presence of this microsporidium in F. virilis could be relevant for freshwater ecosystems across this crayfish's broad geographic range in North America and may affect interactions between F. virilis and invasive rusty crayfish Faxonius rusticus in the Midwest USA.</p

Cambaraspora faxoni n. sp. (Microsporidia: Glugeida) from native and invasive crayfish in the USA and a novel host of Cambaraspora floridanus

Crayfishes are among the most widely introduced freshwater taxa and can have extensive ecological impacts. Knowledge of the parasites crayfish harbor is limited, yet co-invasion of parasites is a significant risk associated with invasions. In this study, we describe a novel microsporidium, Cambaraspora faxoni n. sp. (Glugeida: Tuzetiidae), from two crayfish hosts in the Midwest USA, Faxonius virilis and Faxonius rusticus. We also expand the known host range of Cambaraspora floridanus to include Procambarus spiculifer. Cambaraspora faxoni infects muscle and heart tissue of F. rusticus and develops within a sporophorous vesicle. The mature spore measures 3.22 ± 0.14 μm in length and 1.45 ± 0.13 μm in width, with 8–9 turns of the polar filament. SSU sequencing indicates the isolates from F. virilis and F. rusticus were identical (100%) and 93.49% similar to C. floridanus, supporting the erection of a new species within the Cambaraspora genus. The novel parasite was discovered within the native range of F. rusticus (Ohio, USA) and within a native congeneric (F. virilis) in the invasive range of F. rusticus (Wisconsin, USA). Faxonius virilis is invasive in other regions. This new parasite could have been introduced to Wisconsin with F. rusticus or it may be a generalist species with a broad distribution. In either case, this parasite infects two crayfish species that have been widely introduced to new drainages throughout North America and could have future effects on invasion dynamics or impacts.</p

North American crayfish harbour diverse members of the Nudiviridae

Three novel crayfish-infecting nudiviruses from crayfish in North America represent the first genomic confirmation of nudiviruses in crayfish: Faxonius propinquus nudivirus (FpNV), Faxonius rusticus nudivirus (FrNV),and Faxonius virilis nudivirus (FvNV). Histopathology and electron microscopy revealed nuclear infections,including nuclear hypertrophy in hepatopancreatic epithelial cells and the presence of membrane-bound bacilliform virions. Metagenomic sequencing resulted in complete circular genome assembly, and phylogenetic analyses (based on nudivirus core genes) placed these viruses within the unofficial Epsilonnudivirus genus. One ofthe nudiviruses was detected in the antennal gland of its host, and another is correlated with invasive crayfishdecline in one infected lake ecosystem - suggesting a potential route for viral transmission through water, andpossible population level impact. This study highlights the importance of genomic and ecological data inelucidating the diversity and evolutionary relationships of the Nudiviridae, while expanding their known diversityand range of host species

Motion analysis of match-play in elite U12 to U16 age-group soccer players

The aim of this study was to quantify the motion demands of match-play in elite U12 to U16 age-group soccer players. Altogether, 112 players from two professional soccer clubs at five age-group levels (U12–U16) were monitored during competitive matches (n=14) using a 5 Hz non-differential global positioning system (NdGPS). Velocity thresholds were normalized for each age-group using the mean squad times for a flying 10 m sprint test as a reference point. Match performance was reported as total distance, high-intensity distance, very high-intensity distance, and sprint distance. Data were reported both in absolute (m) and relative (m min-1) terms due to a rolling substitute policy. The U15 (1.35±0.09 s) and U16 (1.31±0.06 s) players were significantly quicker than the U12 (1.58±0.10 s), U13 (1.52±0.07 s), and U14 (1.51±0.08 s) players in the flying 10 m sprint test (P U12, U13, U14), high-intensity distance (U16 > U12, U13, U14, U15), very high-intensity distance (U16 4 U12, U13), and sprint distance (U16 > U12, U13) than their younger counterparts (P<0.05). When the data are considered relative to match exposure, few differences are apparent. Training prescription for youth soccer players should consider the specific demands of competitive match-play in each age-group

Genomic evidence supports a clonal diaspora model for metastases of esophageal adenocarcinoma.

The poor outcomes in esophageal adenocarcinoma (EAC) prompted us to interrogate the pattern and timing of metastatic spread. Whole-genome sequencing and phylogenetic analysis of 388 samples across 18 individuals with EAC showed, in 90% of patients, that multiple subclones from the primary tumor spread very rapidly from the primary site to form multiple metastases, including lymph nodes and distant tissues-a mode of dissemination that we term 'clonal diaspora'. Metastatic subclones at autopsy were present in tissue and blood samples from earlier time points. These findings have implications for our understanding and clinical evaluation of EAC.MRC core grant (RG84369), an NIHR Research Professorship (RG67258) and Cancer Research UK (RG66287)

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters.

Funder: All funders per study are acknowledged in the Supplementary FileA new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo