263 research outputs found

    Compulsory Medical Treatment - A Moral Evaluation

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    Compulsory Medical Treatment - A Moral Evaluation

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    Bats of St. Vincent, Lesser Antilles

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    The chiropteran fauna of the island of Saint Vincent, represented by 12 species, is among the most complex in the Lesser Antilles, being represented by four families including Noctilionidae (1 species), Mormoopidae (1), Phyllostomidae (8), and Molossidae (2). This fauna includes four trophic guilds as represented by Noctilio leporinus (piscivore/insectivore); Glossophaga longirostris and Monophyllus plethodon (nectarivore/pollenivore); Artibeus lituratus, A. schwartzi, Brachyphylla cavernarum, Ardops nichollsi, and Sturnira paulsoni (frugivore); and Pteronotus fuscus, Micronycteris buriri, Molossus molossus, and Tadarida brasiliensis (insectivore). One species—Micronycteris buriri—and two subspecies—Sturnira paulsoni paulsoni and Ardops nichollsi vincentensis—are endemic to the island. Recent advancements in population genomics have led to the discovery of the reticulated evolutionary history of Artibeus schwartzi and it is likely that the formation of the hybrid evolutionary trajectory of this species is linked with classical island biogeography. The bat fauna of St. Vincent is unique in the West Indies, characterized by being a crossroads for species, an outpost for both northern and southern species, the boundary for a multi-island bat fauna as marked by Koopman’s Line, and a site of endemism. Based on our studies, we place the bat fauna of St. Vincent as the southern-most island in the Lesser Antillean Faunal Core

    A Tandem Mass Spectrometry Sequence Database Search Method for Identification of O-Fucosylated Proteins by Mass Spectrometry.

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    Thrombospondin type 1 repeats (TSRs), small adhesive protein domains with a wide range of functions, are usually modified with O-linked fucose, which may be extended to O-fucose-β1,3-glucose. Collision-induced dissociation (CID) spectra of O-fucosylated peptides cannot be sequenced by standard tandem mass spectrometry (MS/MS) sequence database search engines because O-linked glycans are highly labile in the gas phase and are effectively absent from the CID peptide fragment spectra, resulting in a large mass error. Electron transfer dissociation (ETD) preserves O-linked glycans on peptide fragments, but only a subset of tryptic peptides with low m/ z can be reliably sequenced from ETD spectra compared to CID. Accordingly, studies to date that have used MS to identify O-fucosylated TSRs have required manual interpretation of CID mass spectra even when ETD was also employed. In order to facilitate high-throughput, automatic identification of O-fucosylated peptides from CID spectra, we re-engineered the MS/MS sequence database search engine Comet and the MS data analysis suite Trans-Proteomic Pipeline to enable automated sequencing of peptides exhibiting the neutral losses characteristic of labile O-linked glycans. We used our approach to reanalyze published proteomics data from Plasmodium parasites and identified multiple glycoforms of TSR-containing proteins

    Two techniques for the preparation of cell-scaffold constructs suitable for sinus augmentation: steps into clinical application.

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    The objective of this clinical trial was the analysis of 2 methods for engineering of autologous bone grafts for maxillary sinus augmentation with secondary implant placement. Group 1 (8 patients, 12 sinuses): cells of mandibular periosteum were cultured in a good manufacturing practice laboratory (2 weeks) with autologous serum and then transferred onto a collagen matrix. After another week, these composites were transplanted into the sinuses. In group 2A (2 patients, 3 sinuses), cells of maxillary bone were cultivated with autologous serum for 2 weeks, seeded onto natural bone mineral (NBM, diameter [Ø] = 8 mm) blocks, and cultivated for another 1.5 months. These composites were transplanted into the sinuses. Group 2B (control, 3 patients, 5 sinuses) received NBM blocks alone. In the course of implant placement 6 (group 1) and 8 (group 2) months later, core biopsy were taken. Clinical follow-up period was 1 to 2.5 years in group 1 and approximately 7 years in groups 2A and 2B. New vital bone was found in all cases at median densities of 38\% (n = 12) in group 1, 32\% in group 2A (n = 3), and 25\% in group 2B (n = 5). Differences between group 1 and 2B as well as 2A and 2B were statistically significant ( p = 0.025). No adverse effects were seen. All methods described were capable of creating new bone tissue with sufficient stability for successful implant placement

    Comparison of family health history in surveys vs electronic health record data mapped to the observational medical outcomes partnership data model in the All of Us Research Program

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    OBJECTIVE: Family health history is important to clinical care and precision medicine. Prior studies show gaps in data collected from patient surveys and electronic health records (EHRs). The All of Us Research Program collects family history from participants via surveys and EHRs. This Demonstration Project aims to evaluate availability of family health history information within the publicly available data from All of Us and to characterize the data from both sources. MATERIALS AND METHODS: Surveys were completed by participants on an electronic portal. EHR data was mapped to the Observational Medical Outcomes Partnership data model. We used descriptive statistics to perform exploratory analysis of the data, including evaluating a list of medically actionable genetic disorders. We performed a subanalysis on participants who had both survey and EHR data. RESULTS: There were 54 872 participants with family history data. Of those, 26% had EHR data only, 63% had survey only, and 10.5% had data from both sources. There were 35 217 participants with reported family history of a medically actionable genetic disorder (9% from EHR only, 89% from surveys, and 2% from both). In the subanalysis, we found inconsistencies between the surveys and EHRs. More details came from surveys. When both mentioned a similar disease, the source of truth was unclear. CONCLUSIONS: Compiling data from both surveys and EHR can provide a more comprehensive source for family health history, but informatics challenges and opportunities exist. Access to more complete understanding of a person\u27s family health history may provide opportunities for precision medicine

    Biological sex impacts oxidative stress in skeletal muscle in a porcine heat stress model

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    Oxidative stress contributes to heat stress (HS)-mediated alterations in skeletal muscle; however, the extent to which biological sex mediates oxidative stress during HS remains unknown. We hypothesized muscle from males would be more resistant to oxidative stress caused by HS than muscle from females. To address this, male and female pigs were housed in thermoneutral conditions (TN; 20.8 ± 1.6°C; 62.0 ± 4.7% relative humidity; n = 8/sex) or subjected to HS (39.4 ± 0.6°C; 33.7 ± 6.3% relative humidity) for 1 (HS1; n = 8/sex) or 7 days (HS7; n = 8/sex) followed by collection of the oxidative portion of the semitendinosus. Although HS increased muscle temperature, by 7 days, muscle from heat-stressed females was cooler than muscle from heat-stressed males (0.3°C; P < 0.05). Relative protein abundance of 4-hydroxynonenal (4-HNE)-modified proteins increased in HS1 females compared with TN (P = 0.05). Furthermore, malondialdehyde (MDA)-modified proteins and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentration, a DNA damage marker, was increased in HS7 females compared with TN females (P = 0.05). Enzymatic activities of catalase and superoxide dismutase (SOD) remained similar between groups; however, glutathione peroxidase (GPX) activity decreased in HS7 females compared with TN and HS1 females (P ≤ 0.03) and HS7 males (P = 0.02). Notably, HS increased skeletal muscle Ca2+ deposition (P = 0.05) and was greater in HS1 females compared with TN females (P < 0.05). Heat stress increased sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA)2a protein abundance (P < 0.01); however, Ca2+ ATPase activity remained similar between groups. Overall, despite having lower muscle temperature, muscle from heat-stressed females had increased markers of oxidative stress and calcium deposition than muscle from males following identical environmental exposure.This article is published as Rudolph, Tori E., Melissa Roths, Alyssa D. Freestone, Sau Qwan E. Yap, Alyona Michael, Robert P. Rhoads, Sarah White-Springer, Lance H. Baumgard, and Joshua T. Selsby. "Biological sex impacts oxidative stress in skeletal muscle in a porcine heat stress model." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 326 (2024): R578-R587. doi:https://doi.org/10.1152/ajpregu.00268.2023. © 2024 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0

    Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

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    We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

    A Phylogeny and Timescale for the Evolution of Pseudocheiridae (Marsupialia: Diprotodontia) in Australia and New Guinea

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    Pseudocheiridae (Marsupialia: Diprotodontia) is a family of endemic Australasian arboreal folivores, more commonly known as ringtail possums. Seventeen extant species are grouped into six genera (Pseudocheirus, Pseudochirulus, Hemibelideus, Petauroides, Pseudochirops, Petropseudes). Pseudochirops and Pseudochirulus are the only genera with representatives on New Guinea and surrounding western islands. Here, we examine phylogenetic relationships among 13 of the 17 extant pseudocheirid species based on protein-coding portions of the ApoB, BRCA1, ENAM, IRBP, Rag1, and vWF genes. Maximum parsimony, maximum likelihood, and Bayesian methods were used to estimate phylogenetic relationships. Two different relaxed molecular clock methods were used to estimate divergence times. Bayesian and maximum parsimony methods were used to reconstruct ancestral character states for geographic provenance and maximum elevation occupied. We find robust support for the monophyly of Pseudocheirinae (Pseudochirulus + Pseudocheirus), Hemibelidinae (Hemibelideus + Petauroides), and Pseudochiropsinae (Pseudochirops + Petropseudes), respectively, and for an association of Pseudocheirinae and Hemibelidinae to the exclusion of Pseudochiropsinae. Within Pseudochiropsinae, Petropseudes grouped more closely with the New Guinean Pseudochirops spp. than with the Australian Pseudochirops archeri, rendering Pseudochirops paraphyletic. New Guinean species belonging to Pseudochirops are monophyletic, as are New Guinean species belonging to Pseudochirulus. Molecular dates and ancestral reconstructions of geographic provenance combine to suggest that the ancestors of extant New Guinean Pseudochirops spp. and Pseudochirulus spp. dispersed from Australia to New Guinea ∼12.1–6.5 Ma (Pseudochirops) and ∼6.0–2.4 Ma (Pseudochirulus). Ancestral state reconstructions support the hypothesis that occupation of high elevations (>3000 m) is a derived feature that evolved on the terminal branch leading to Pseudochirops cupreus, and either evolved in the ancestor of Pseudochirulus forbesi, Pseudochirulus mayeri, and Pseudochirulus caroli, with subsequent loss in P. caroli, or evolved independently in P. mayeri and P. forbesi. Divergence times within the New Guinean Pseudochirops clade are generally coincident with the uplift of the central cordillera and other highlands. Diversification within New Guinean Pseudochirulus occurred in the Plio-Pleistocene after the establishment of the Central Range and other highlands
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