A deep Chandra observation of the Groth Strip. I. The X-ray data

We present the results of a 200 ks Chandra observation of part of the Groth Strip region, using the ACIS-I instrument. We present a relatively simple method for the detection of point-sources and calculation of limiting sensitivities, which we argue is at least as sensitive and more self-consistent than previous methods presented in the literature. 158 distinct X-ray sources are included in our point-source catalogue in the ACIS-I area. The number counts show a relative dearth of X-ray sources in this region. For example at a flux limit of 1E-15 (cgs) around 20 per cent more soft band sources are detected in the HDF-N and almost 50 per cent more in the ELAIS-N1 field, which we have analysed by the same method for comparison. We find, however, that these differences are consistent with Poisson variations at 2 sigma significance, and therefore there is no evidence for cosmic variance based on these number counts alone. We determine the average spectra of the objects and find a marked difference between the soft-band selected sources, which have Gamma=1.9 typical of unobscured AGN, and the hard-band selected sources, which have Gamma=1.0. Reassuringly, the sample as a whole has a mean spectrum of Gamma=1.4\pm 0.1, the same as the X-ray background. Nonetheless, our results imply that the fraction of sources with significant obscuration is only ~25 per cent, much less than predicted by standard AGN population synthesis models. This is confirmed by direct spectral fitting, with only a handful of objects showing evidence for absorption. After accounting for absorption, all objects are consistent with mean intrinsic spectrum of Gamma=1.76 \pm 0.08, very similar to local Seyferts (abridged).Comment: 17 pages, 4 figures, MNRAS, in pres

Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design

BACKGROUND: The ITPR1 gene encodes the inositol 1,4,5-trisphosphate (IP3 ) receptor type 1 (IP3 R1), a critical player in cerebellar intracellular calcium signaling. Pathogenic missense variants in ITPR1 cause congenital spinocerebellar ataxia type 29 (SCA29), Gillespie syndrome (GLSP), and severe pontine/cerebellar hypoplasia. The pathophysiological basis of the different phenotypes is poorly understood. OBJECTIVES: We aimed to identify novel SCA29 and GLSP cases to define core phenotypes, describe the spectrum of missense variation across ITPR1, standardize the ITPR1 variant nomenclature, and investigate disease progression in relation to cerebellar atrophy. METHODS: Cases were identified using next-generation sequencing through the Deciphering Developmental Disorders study, the 100,000 Genomes project, and clinical collaborations. ITPR1 alternative splicing in the human cerebellum was investigated by quantitative polymerase chain reaction. RESULTS: We report the largest, multinational case series of 46 patients with 28 unique ITPR1 missense variants. Variants clustered in functional domains of the protein, especially in the N-terminal IP3 -binding domain, the carbonic anhydrase 8 (CA8)-binding region, and the C-terminal transmembrane channel domain. Variants outside these domains were of questionable clinical significance. Standardized transcript annotation, based on our ITPR1 transcript expression data, greatly facilitated analysis. Genotype-phenotype associations were highly variable. Importantly, while cerebellar atrophy was common, cerebellar volume loss did not correlate with symptom progression. CONCLUSIONS: This dataset represents the largest cohort of patients with ITPR1 missense variants, expanding the clinical spectrum of SCA29 and GLSP. Standardized transcript annotation is essential for future reporting. Our findings will aid in diagnostic interpretation in the clinic and guide selection of variants for preclinical studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Genetic Population Structure in the Antarctic Benthos: Insights from the Widespread Amphipod, Orchomenella franklini

Currently there is very limited understanding of genetic population structure in the Antarctic benthos. We conducted one of the first studies of microsatellite variation in an Antarctic benthic invertebrate, using the ubiquitous amphipod Orchomenella franklini (Walker, 1903). Seven microsatellite loci were used to assess genetic structure on three spatial scales: sites (100 s of metres), locations (1–10 kilometres) and regions (1000 s of kilometres) sampled in East Antarctica at Casey and Davis stations. Considerable genetic diversity was revealed, which varied between the two regions and also between polluted and unpolluted sites. Genetic differentiation among all populations was highly significant (FST = 0.086, RST = 0.139, p<0.001) consistent with the brooding mode of development in O. franklini. Hierarchical AMOVA revealed that the majority of the genetic subdivision occurred across the largest geographical scale, with Nem≈1 suggesting insufficient gene flow to prevent independent evolution of the two regions, i.e., Casey and Davis are effectively isolated. Isolation by distance was detected at smaller scales and indicates that gene flow in O. franklini occurs primarily through stepping-stone dispersal. Three of the microsatellite loci showed signs of selection, providing evidence that localised adaptation may occur within the Antarctic benthos. These results provide insights into processes of speciation in Antarctic brooders, and will help inform the design of spatial management initiatives recently endorsed for the Antarctic benthos

Infrared spectral histopathology using haematoxylin and eosin (H&amp;E) stained glass slides: a major step forward towards clinical translation

Infrared spectral histopathology has shown great promise as an important diagnostic tool, with the potential to complement current pathological methods.</p

Screening for footrot resistant gene markers and white blood cell types in Katahdin and Katahdin crossbred sheep

Footrot is the most costly and impacting animal welfare disease in small ruminants. The putative gene group with variation from highly resistance to highly susceptible allele has been identified and a DNA marker (DQA2) is being developed for marker assisted selection in sheep. Katahdin and Katahdin crossbred sheep were screened for footrot resistant gene markers. A value for a pair of alleles was derived and animals were classed into five categorical groups (1, 2, 3, 4, and 5) from highest to lowest resistance to footrot. White blood cell types were analyzed in the progeny groups. Both allelic and genotypic distributions were significantly (P < 0.01) different in the five gene marker score groups. There was no difference (P > 0.05) in white blood cell types by marker score groups, but a significant difference for hematocrits (P < 0.05) between breeds