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Biology subjects

Palmer, S. M.

Publications and source records attributed to Palmer, S. M..

5 recordsLinked to original sources

Soft tissue morphology of the vomeronasal organ in Lontra canadensis and its osteological correlate: Implications for the evolution of the caniform accessory olfactory system

The olfactory system plays a critical role in mammalian environmental perception, with some clades relying on an expanded accessory olfactory (vomeronasal) system (VNS) to detect larger, non-volatile odorants. Mammals make extensive use of this system for social communication between conspecifics. Recent studies have begun to investigate how the VNS changes in response to or as part of ecological transitions. Several studies have identified trends of VNS-associated gene loss or regression in secondarily aquatic mammals. However, continuing discussion on genotype-phenotype correlation within the VNS means that greater effort should be made to investigate the morphology of the VNS in species where it remains poorly understood. Here, we use skeletal and soft-tissue data to demonstrate that the vomeronasal groove, an established osteological correlate for the VNO in bats and primates, is also a valid indicator for its presence in Caniformia. Additionally, we confirm the presence of the VNO in the secondarily aquatic North American river otter (Lontra canadensis) and compare its morphology with that of two close-related species, the semi-aquatic American mink (Neogale vison) and the terrestrial long-tailed weasel (Neogale frenata). This study expands the valid taxonomic scope of the vomeronasal grooves proxy as an osteological correlate, confirms the presence of the VNO in the previously undescribed system of the North American river otter, and highlights the complexity of the mammalian accessory olfactory system.

evolutionary biology↗

The origin and evolution of amphibious hearing in pinnipeds

Seals (pinnipeds) are the only mammals that can hear in both air and water. How and when they achieved the ability to negotiate such contrasting auditory media remains unknown. Here, we apply 3D shape and phylogenetic comparative analyses to a large dataset of caniform carnivorans (119 species, 217 specimens) to study the emergence of amphibious hearing in pinnipeds despite significant evolutionary constraints. We find support for the cavernous tissue as a functional and evolutionary mechanism for amphibious hearing. This tissue, which fills with blood during diving to equalise air pressure in the ear, enables a shift from in-air to underwater hearing by matching the acoustic impedance of the ear to that of the surrounding water. Early diverging freshwater pinnipeds had impaired hearing underwater. The first marine pinnipeds could hear amphibiously but were limited by a functional tradeoff between hearing abilities and the need to prevent damage from loud underwater sounds. Subsequently, otariids (eared seals) and phocids (true seals) independently acquired middle ear adaptations that expanded their underwater hearing range. This iterative evolution likely facilitated the exploration of novel auditory adaptive zones by crown pinnipeds, resulting in rare acoustic abilities like ultrasonic singing, vocal learning, and keeping rhythm.

evolutionary biology↗

Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens inflammation in airway cells.

Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways associated with poor SARS-CoV-2 disease outcomes. Additionally, SNX-5422 interrupted expression of host factors that are crucial for SARS-CoV-2 replication machinery. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.

microbiology↗

Ontology-guided segmentation and object identification for developmental mouse lung immunofluorescent images

BackgroundImmunofluorescent confocal microscopy uses labeled antibodies as probes against specific macromolecules to discriminate between multiple cell types. For images of the developmental mouse lung, these cells are themselves organized into densely packed higher-level anatomical structures. These types of images can be challenging to segment automatically for several reasons, including the relevance of biomedical context, dependence on the specific set of probes used, prohibitive cost of generating labeled training data, as well as the complexity and dense packing of anatomical structures in the image. The use of an application ontology surmounts these challenges by combining image data with its metadata to provide a meaningful biological context, and hence constraining and simplifying the process of segmentation and object identification. ResultsWe propose an innovative approach for the automated analysis of complex and densely packed anatomical structures from immunofluorescent images that utilizes an application ontology to provide a simplified context for image segmentation and object identification. We describe how the logical organization of biological facts in the form of an ontology can provide useful constraints that enhance automatic processing of complex images. We demonstrate the results of ontology-guided segmentation and object identification in mouse developmental lung images from the Bioinformatics REsource ATlas for the Healthy lung (BREATH) database of the Molecular Atlas of Lung Development (LungMAP1) program. ConclusionThe microscopy analysis pipeline library (micap) is available at https://github.com/duke-lungmap-team/microscopy-analysis-pipeline. Code to reproduce our analysis of LungMAP images is also available at https://github.com/duke-lungmap-team/lungmap-pipeline. Finally, the application ontology is available at https://github.com/duke-lungmap-team/lung_ontology and includes example SPARQL queries. ContactAnna Maria Masci email: annamaria.masci@duke.edu

bioinformatics↗

Screening of candidate substrates and coupling ions of transporters by thermostability shift assays

Substrates of most transport proteins have not been identified, limiting our understanding of their role in physiology and disease. Traditional identification methods use transport assays with radioactive compounds, but they are technically challenging and many compounds are unavailable in radioactive form or are prohibitively expensive, precluding large-scale trials. Here, we present a high-throughput screening method that can identify candidate substrates from libraries of unlabeled compounds. The assay is based on the principle that transport proteins recognize substrates through specific interactions, which lead to enhanced stabilization of the transporter population in thermostability shift assays. Representatives of three different transporter (super)families were tested, which differ in structure as well as transport and ion coupling mechanisms. In each case, the substrates were identified correctly from a large set of chemically related compounds, including stereo-isoforms. In some cases, stabilization by substrate binding was enhanced further by ions, providing testable hypotheses on energy coupling mechanisms.

biophysics↗