Biology subjects

Brown, M. B.

Publications and source records attributed to Brown, M. B..

5 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↗

bioRxiv2024

Pathogenicity determinant protein E is a Francisella type VI secretion system effector protein that modulates host death

Francisella tularensis is a highly pathogenic Gram-negative intracellular bacterial pathogen and the etiologic agent of tularemia, a fatal zoonotic disease that poses a threat to global public health. F. tularensis virulence is mediated by genes on the Francisella pathogenicity island (FPI), which encodes a unique contractile secretion apparatus with functional and structural similarity to bacterial type VI secretion systems (T6SSs). T6SSs can inject effector proteins into host cells to facilitate invasion, intracellular proliferation, and pathogenesis; however, the identity and function of Francisella effectors are still unclear. In this study, we measured T6SS activity in a series of FPI deletion mutants to identify genes that are required for core apparatus activity. We found that Pathogenicity Determinant Protein E (PdpE) is not required for secretion of T6SS substrates or intramacrophage growth. Instead, PdpE forms a complex with another T6SS-secreted effector, PdpC, and limits death of infected host cells by attenuating the macrophage type I interferon response. Importantly, a {Delta}pdpE mutant more rapidly induces death in an established invertebrate in vivo model for Francisella infection. These data define the role of a previously uncharacterized substrate of the Francisella T6SS and provide new insights into host-Francisella interaction.

microbiology↗

bioRxiv2024

Pangenomic analysis of Helcococcus ovis reveals widespread tetracycline resistance and a novel bacterial species, Helcococcus bovis.

Helcococcus ovis (H. ovis) is an opportunistic bacterial pathogen of a wide range of animal hosts including domestic ruminants, swine, avians, and humans. In this study, we sequenced the genomes of 35 Helcococcus sp. clinical isolates from the uterus of dairy cows and explored their antimicrobial resistance and biochemical phenotypes. Phylogenetic and average nucleotide identity analyses placed four Helcococcus isolates within a cryptic clade-representing an undescribed species, for which we propose the name Helcococcus bovis sp. nov. We applied whole genome comparative analyses to explore the pangenome, resistome, virulome, and taxonomic diversity of the remaining 31 H. ovis isolates. H. ovis was more often isolated from cows with metritis, however, there was no associations between H. ovis gene clusters and uterine infection. The phylogenetic distribution of high-virulence determinants of H. ovis is consistent with convergent gene loss in the species. The majority of H. ovis strains (30/31) contain mobile tetracycline resistance genes, leading to higher minimum inhibitory concentrations of tetracyclines in vitro. In summary, this study showed that the presence of H. ovis is associated with uterine infection in dairy cows, that mobile genetic element-mediated tetracycline resistance is widespread in H. ovis, and that there is evidence of co-occurring virulence factors across clades suggesting convergent gene loss in the species. Finally, we introduced a novel Helcococcus species closely related to H. ovis, called H. bovis sp. nov. HighlightsO_LIThe presence of Helcococcus ovis is associated with uterine infection in dairy cows C_LIO_LIMobile genetic element-mediated tetracycline resistance is widespread in H. ovis C_LIO_LICo-occurring virulence factors across clades suggest convergent gene loss in the species C_LIO_LIHelcococcus bovis is a novel species closely related to Helcococcus ovis C_LI

microbiology↗

bioRxiv2023

Cell based dATP delivery as a therapy for chronic heart failure.

Withdrawal StatementThe authors have withdrawn this manuscript because the senior authors have identified inconsistencies in the data presented in this manuscript, which affect the reliability of the main conclusions. In keeping with our commitment to scientific rigor and transparency, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding authors.

pathology↗

bioRxiv2020

Muscle fiber type differences in nitrate and nitrite storage and nitric oxide signaling in rats

Recent studies have emphasized the importance of the nitric oxide synthase (NOS)-independent, nitrate (NO3-) [->] nitrite (NO2-) [->] nitric oxide (NO) pathway in skeletal muscle. In particular, it has been hypothesized that this pathway is especially active in type II, or fast-twitch, muscle fibers, necessitating greater NO3- and NO2- storage. We therefore measured NO3- and NO2- concentrations in the predominantly fast-twitch vastus lateralis and predominantly slow-twitch soleus muscles of rats. Contrary to the above hypothesis, we found that NO3- and NO2- concentrations were 3.4-fold and 1.8-fold higher, respectively, in the soleus. On the other hand, NO signaling (i.e., cyclic guanosine monophosphate (cGMP) level) was comparable in the two muscles. Although the physiological significance of these observations remains to be determined, we speculate that NO production via the NO3- [->] NO2- [->] NO pathway is normally higher in slow-twitch muscles, thus helping compensate for their inherently lower NOS activity.

physiology↗