We present an extensible software model for the genotype and phenotype community, XGAP. Readers can download a standard XGAP (http://www.xgap.org) or auto-generate a custom version using MOLGENIS ...with programming interfaces to R-software and web-services or user interfaces for biologists. XGAP has simple load formats for any type of genotype, epigenotype, transcript, protein, metabolite or other phenotype data. Current functionality includes tools ranging from eQTL analysis in mouse to genome-wide association studies in humans.
Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its ...pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid. Recovered only hours after falling, the composition of the Winchcombe meteorite is largely unmodified by the terrestrial environment. It contains abundant hydrated silicates formed during fluid-rock reactions, and carbon- and nitrogen-bearing organic matter including soluble protein amino acids. The near-pristine hydrogen isotopic composition of the Winchcombe meteorite is comparable to the terrestrial hydrosphere, providing further evidence that volatile-rich carbonaceous asteroids played an important role in the origin of Earth's water.
Twilight is characterised by changes in both quantity ("irradiance") and quality ("colour") of light. Animals use the variation in irradiance to adjust their internal circadian clocks, aligning their ...behaviour and physiology with the solar cycle. However, it is currently unknown whether changes in colour also contribute to this entrainment process. Using environmental measurements, we show here that mammalian blue-yellow colour discrimination provides a more reliable method of tracking twilight progression than simply measuring irradiance. We next use electrophysiological recordings to demonstrate that neurons in the mouse suprachiasmatic circadian clock display the cone-dependent spectral opponency required to make use of this information. Thus, our data show that some clock neurons are highly sensitive to changes in spectral composition occurring over twilight and that this input dictates their response to changes in irradiance. Finally, using mice housed under photoperiods with simulated dawn/dusk transitions, we confirm that spectral changes occurring during twilight are required for appropriate circadian alignment under natural conditions. Together, these data reveal a new sensory mechanism for telling time of day that would be available to any mammalian species capable of chromatic vision.
The Exomiser was launched by Robinson et al. in 2014 1 as a freely available Java program to annotate, filter and prioritise variants from next-generation sequencing (NGS) projects for disease gene ...discovery or differential diagnostics of Mendelian disease. The software requires i) a variant call format (VCF) file with the called variants of a rare disease patient and ii) a set of patient’s phenotypes encoded using the Human Phenotype Ontology (HPO) 2. A range of user-defined variant filtering criteria can be applied based on JANNOVAR functional annotation 3, frequency and expected inheritance pattern. The filtered variants are then prioritised according to their rarity and algorithm-predicted pathogenicity, combined with the phenotypic similarity between the patient’s HPO terms and those used to annotate genes in known human diseases, mouse/zebrafish model organisms and/or relevant proteinprotein interactions. The Exomiser was able to prioritise causative variants as top candidates in 97% of simulated whole-exomes 4. Here, we present the latest Exomiser version 9.0.1 with a number of new features, including the use of additional publicly available datasets (e.g., gnomAD), the choice of Ensembl, UCSC or RefSeq gene transcript definitions, and the analysis of non-coding 5 and mitochondrial variants. We assessed the software performance using a set of 132 whole-exomes from patients with a range of different rare retinal diseases and a confirmed molecular diagnosis. The causative variant(s) were ranked first/up to 5th/up to 10th in 74%/87%/89% of the patients’s exomes. The Exomiser is an effective variant prioritization tool for the integrative analysis of Mendelian HPO-encoded clinical diagnoses and NGS data.
On February 28, 2021, a fireball dropped \(\sim0.6\) kg of recovered CM2 carbonaceous chondrite meteorites in South-West England near the town of Winchcombe. We reconstruct the fireball's atmospheric ...trajectory, light curve, fragmentation behaviour, and pre-atmospheric orbit from optical records contributed by five networks. The progenitor meteoroid was three orders of magnitude less massive (\(\sim13\) kg) than any previously observed carbonaceous fall. The Winchcombe meteorite survived entry because it was exposed to a very low peak atmospheric dynamic pressure (\(\sim0.6\) MPa) due to a fortuitous combination of entry parameters, notably low velocity (13.9 km/s). A near-catastrophic fragmentation at \(\sim0.07\) MPa points to the body's fragility. Low entry speeds which cause low peak dynamic pressures are likely necessary conditions for a small carbonaceous meteoroid to survive atmospheric entry, strongly constraining the radiant direction to the general antapex direction. Orbital integrations show that the meteoroid was injected into the near-Earth region \(\sim0.08\) Myr ago and it never had a perihelion distance smaller than \(\sim0.7\) AU, while other CM2 meteorites with known orbits approached the Sun closer (\(\sim0.5\) AU) and were heated to at least 100 K higher temperatures.
We present PATICE, a GIS database of Patagonian glacial geomorphology and recalibrated chronological data. PATICE includes 58,823 landforms and 1,669 geochronological ages, and extends from 38°S to ...55°S in southern South America. We use these data to generate new empirical reconstructions of the Patagonian Ice Sheet (PIS) and subsequent ice masses and ice-dammed palaeolakes at 35 ka, 30 ka, 25 ka, 20 ka, 15 ka, 13 ka (synchronous with the Antarctic Cold Reversal), 10 ka, 5 ka, 0.2 ka and 2011 AD. At 35 ka, the PIS covered of 492.6 x103 km2, had a sea level equivalent of ~1,496 mm, was 350 km wide and 2090 km long, and was grounded on the Pacific continental shelf edge. Outlet glacier lobes remained topographically confined and the largest generated the suites of subglacial streamlined bedforms characteristic of ice streams. The PIS reached its maximum extent by 33 – 28 ka from 38°S to 48°S, and earlier, around 47 ka from 48°S southwards. Net retreat from maximum positions began by 25 ka, with ice-marginal stabilisation then at 21 – 18 ka, which was then followed by rapid, irreversible deglaciation. By 15 ka, the PIS had separated into disparate ice masses, draining into large ice-dammed lakes along the eastern margin, which strongly influenced rates of recession. Glacial readvances or stabilisations occurred at least at 14 – 13 ka, 11 ka, 6 – 5 ka, 2 – 1 ka, and 0.5 – 0.2 ka. We suggest that 20th century glacial recession (% a-1) is occurring faster than at any time documented during the Holocene.
Display omitted
This paper describes the PROMOTE UV Record, which aims to provide a global long-term record of the surface UV radiation. The algorithm developed takes as input cloud information from the ...International Satellite Cloud Climatology Project (ISCCP) and a recently developed multisensor assimilated record of the total ozone column. Aerosols and surface albedo are based on climatologies. Here, first validation results of the PROMOTE UV Record are presented through comparison against ground-based measurements of daily erythemal UV doses at eight European stations. The validation shows that the method is working reasonably, although there is a clear tendency toward overestimation. Typically, the median bias as compared to measurements is 3%-10% and 56%-68% of the daily doses are within plusmn20% from the ground-based reference. The prototype version of the PROMOTE UV Record included in this paper covers the period from July 2002 to June 2005. The time series will later be extended to start in 1983.
Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the ...significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.
Liver disease is a significant contributor to morbidity and mortality in HIV-infected individuals, even during successful viral suppression with combination antiretroviral therapy (cART). Similar to ...HIV infection, SIV infection of rhesus macaques is associated with gut microbiome dysbiosis and microbial translocation that can be detected systemically in the blood. As microbes leaving the intestines must first pass through the liver
the portal vein, we evaluated the livers of both SIV-infected (SIV+) and SIV-infected cART treated (SIV+cART) rhesus macaques for evidence of microbial changes compared to uninfected macaques. Dysbiosis was observed in both the SIV+ and SIV+cART macaques, encompassing changes in the relative abundance of several genera, including a reduction in the levels of
and
. Most strikingly, we found an increase in the relative abundance and absolute quantity of bacteria within the
genus in both SIV+ and SIV+cART macaques. Multi-gene sequencing identified a species of atypical mycobacteria similar to the opportunistic pathogen
. Phosphatidyl inositol lipoarabinomannan (PILAM) (a glycolipid cell wall component found in atypical mycobacteria) stimulation in primary human hepatocytes resulted in an upregulation of inflammatory transcriptional responses, including an increase in the chemokines associated with neutrophil recruitment (CXCL1, CXCL5, and CXCL6). These studies provide key insights into SIV associated changes in hepatic microbial composition and indicate a link between microbial components and immune cell recruitment in SIV+ and SIV+cART treated macaques.
PDF
