Biology subjects

Newman, K.

Publications and source records attributed to Newman, K..

4 recordsLinked to original sources

bioRxiv2026

Comparative anatomy of the giraffe distal limb

Giraffe in human care are known to experience significant clinical issues related to their feet. To characterize normal foot anatomy, we analyzed six sets of front and hind feet from wild Angolan giraffe and one calf in human care. We used computed tomography, three-dimensional reconstruction, sagittal sections, and gross dissection to acquire as much gross anatomical detail as possible. Significant anatomical findings include the deep digital flexor tendon that is very gracile as it crosses the fetlock and proximal phalanges but widens significantly before inserting onto the entire palmar/plantar surface of the distal phalanx. Significant subcutaneous abaxial veins were noted at the level of the fetlock in both front and hind feet. The digital cushion was found to be a complex structure consisting of two distinct regions, one underneath the distal phalanx, characterized by multiple transversely oriented small adipose compartments separated by dense connective tissue septa, and a significantly larger portion within the heel bulb, consisting of two sagittally oriented fat bodies encased in a dense connective tissue capsule and divided by a thick septum. The proportion of adipose tissue volume in the heel bulbs compared to the distal phalanx decreases with age. The thickness of the sole was found to be much greater than that of the wall and the sole appears to be the major weight supporting structure of the foot. In particular, the heel is greatly expanded in giraffe relative to other ruminants and was found to consist of softer material than the rest of the sole. Data presented here provide an overview of normal giraffe foot anatomy, which can be compared with data from giraffe in human care to better understand, guide treatment and prevention of abnormal anatomical conditions.

zoology↗

bioRxiv2025

Comparison of oral and gut microbiome highlights role of oral bacteria in systemic inflammation in HIV

BackgroundChronic HIV-1 infection is associated with increased inflammation-related comorbidities, despite effective viral suppression with antiretroviral therapy. While the role of the gut microbiome in inflammation is well-studied, the contribution of the oral microbiome remains less clear. This study investigates the relationship between the oral and gut microbiomes in driving systemic inflammation in persons with HIV. MethodsThis cross-sectional study utilized archived samples from 198 participants (99 with HIV and 99 without HIV). Oral microbiome composition was analyzed via 16S rRNA sequencing and systemic inflammatory biomarkers were measured using multiplex assays. Gut microbiome data from previous studies were integrated for comparative analyses. Bacterial inflammatory potential was assessed through in vitro co-culture and epithelial barrier permeability assays. ResultsThe oral microbiome in HIV was characterized by increased Veillonella, Capnocytophaga, and Megasphaera, and several decreased genera including Fusobacterium. Using PERMANOVA, we found that the oral microbiome was a significant driver of cytokine variation in HIV compared to the gut microbiome, and identified specific associations with oral Veillonella and Megasphaera. We found no differences in anti-Veillonella parvula serum IgG by HIV status, but IgG titers did correlate with microbial translocation markers sCD14 and LBP in HIV. In vitro studies demonstrated that Veillonella parvula increased oral epithelial barrier permeability and induced monocyte activation. ConclusionsThe oral microbiome, particularly Veillonella parvula, may contributes to systemic inflammation in HIV through mechanisms involving epithelial barrier disruption, oral translocation, and monocyte activation.

microbiology↗

bioRxiv2024

Astrocytic RIPK3 exerts protective anti-inflammatory activity during viral encephalitis via induction of serpin protease inhibitors.

Flaviviruses pose a significant threat to public health due to their ability to infect the central nervous system (CNS) and cause severe neurologic disease. Astrocytes play a crucial role in the pathogenesis of flavivirus encephalitis through their maintenance of blood-brain barrier (BBB) integrity and their modulation of immune cell recruitment and activation within the CNS. We have previously shown that receptor interacting protein kinase-3 (RIPK3) is a central coordinator of neuroinflammation during CNS viral infection, a function that occurs independently of its canonical function in inducing necroptotic cell death. To date, however, roles for necroptosis-independent RIPK3 signaling in astrocytes are poorly understood. Here, we use mouse genetic tools to induce astrocyte-specific deletion, overexpression, and chemogenetic activation of RIPK3 to demonstrate an unexpected anti-inflammatory function for astrocytic RIPK3. RIPK3 activation in astrocytes was required for host survival in multiple models of flavivirus encephalitis, where it restricted neuropathogenesis by limiting immune cell recruitment to the CNS. Transcriptomic analysis revealed that, despite inducing a traditional pro-inflammatory transcriptional program, astrocytic RIPK3 paradoxically promoted neuroprotection through the upregulation of serpins, endogenous protease inhibitors with broad immunomodulatory activity. Notably, intracerebroventricular administration of SerpinA3N in infected mice preserved BBB integrity, reduced leukocyte infiltration, and improved survival outcomes in mice lacking astrocytic RIPK3. These findings highlight a previously unappreciated role for astrocytic RIPK3 in suppressing pathologic neuroinflammation and suggests new therapeutic targets for the treatment of flavivirus encephalitis.

immunology↗

bioRxiv2022

Conformational dynamics and putative substrate extrusion pathways of the N-glycosylated outer membrane factor CmeC from Campylobacter jejuni

The outer membrane factor CmeC of the efflux machinery CmeABC plays an important role in conferring antibiotic and bile resistance to Campylobacter jejuni. Curiously, the protein is N-glycosylated, with the glycans playing a key role in the effective function of this system. In this work we have employed atomistic equilibrium molecular dynamics simulations of CmeC in a representative model of the C. jejuni outer membrane to characterise the dynamics of the protein and its associated glycans. We show that the glycans are more conformationally labile than had previously been thought. The extracellular loops of CmeC visit the open and closed states freely suggesting the absence of a gating mechanism on this side, while the narrow periplasmic entrance remains tightly closed, regulated via coordination to solvated cations. We identify several cation binding sites on the interior surface of the protein. Additionally, we used steered molecular dynamics simulations to elucidate translocation pathways for a bile acid and a macrolide antibiotic. These, and additional equilibrium simulations suggest that the anionic bile acid utilises multivalent cations to climb the ladder of acidic residues that line the interior surface of the protein.

biophysics↗