Biology subjects

Kennedy, M. W.

Publications and source records attributed to Kennedy, M. W..

8 recordsLinked to original sources

bioRxiv2026

Uterocalin: a protein uniquely specialised to support mobile encapsulated embryos of horses, rhinos and tapirs

Equids are considered unique in having encapsulated embryos that are actively moved between the uteri of mares during the first two and three weeks of pregnancy and do not form a placenta until about 40 days, the longest pre-placentation period known amongst Eutheria. Their embryos are likely supplied through the glycoprotein capsule with selected nutrients by uterocalin, a carrier protein secreted by maternal endometrial glands. Uterocalin binds polyunsaturated fatty acids and retinol (Vitamin A), concentrates in the capsule, and is internalised by the embryo. Here it is shown that the structures of equid uterocalin comprise an excess of metabolism-related essential amino acids, and structural specialisations potentially involved in stabilising the capsule matrix until emergence and engagement with a receptor on the trophoblast surface. The genomes of other perissodactyls (rhinos and tapirs) encode uterocalins with amino acid sequences, excesses of essential amino acids, and predicted structural properties, all closely similar to horse uterocalin. These characteristics are unique to the perissodactyl uterocalins and are not found in similar proteins of other mammal groups. Hence, rhinos and tapirs probably have equid-like reproductive specialisations retained since before the Cretaceous-Paleogene mass extinction and that uterocalin is key to both embryo nutrition and capsule formation.

zoology↗

bioRxiv2025

Sp Transcription Factors Establish the Signaling Environment in the Neuromesodermal Progenitor Niche During Axial Elongation

Neuromesodermal competent progenitors (NMCs) are located in the caudal epiblast near the node and primitive streak and give rise to spinal cord and somitic mesoderm during trunk and tail elongation. Their self-renewal depends on an autoregulatory loop involving Wnt3a and Fgf signaling, and the Tbxt and Cdx transcription factors, but the mechanisms underlying loop formation and the establishment of the niche are poorly understood. Here, we identify the zinc-finger transcription factors Sp5 and Sp8 (Sp5/8) as essential regulators of NMC maintenance. Sp5/8 expression is controlled by Wnt, Fgf and retinoic acid signaling, and they cooperate with Tbxt, Tcf7 and Cdx2 to sustain a robust autoregulatory network that promotes high Wnt/Fgf and low retinoic acid activity in the niche. These factors bind a novel enhancer essential for Wnt3a expression and feedback-loop integrity. Mechanistically, Sp5/8 regulate the dynamic exchange of activating and repressive Tcf complexes at Wnt-responsive enhancers. Our findings define a transcriptional module centered on Sp5/8 that stabilizes niche signaling and transcriptional circuitry essential for NMC fate decisions and trunk development.

developmental biology↗

bioRxiv2025

Transcription factors SP5 and SP8 drive primary cilia formation

While specific transcription factors are known to regulate cell fate decisions, the degree to which they can stimulate formation of specific cell organelles is less clear. We used a multi-omics comparison of the transcriptomes of ciliated and non-ciliated embryonic cells to identify transcription factors upregulated in ciliated cells, and conditional genetics in mouse embryos and stem cells to demonstrate that SP5/8 regulate cilia formation and gene expression. In Sp5/8 mutant embryos primary and motile cilia are shorter than normal and reduced in number across cell types, contributing to situs inversus and hydrocephalus. Moreover, expression of SP8 is sufficient to induce primary cilia in unciliated cells. This work opens new avenues for studying cilia assembly using stem cell models and offers new insights into human ciliopathies.

developmental biology↗

bioRxiv2025

The immunomodulatory p43 secreted protein of Trichuris whipworm parasites is a lipid carrier that binds signalling lipids and precursors

Parasitic helminths such as the Trichuris whipworms contribute to significant disease and morbidity in humans and other animals. They cause prolonged infections despite intact immune systems of their hosts, and their persistence is increasingly attributed to immunomodulatory activities of their secreted products. We examined the p43 (Tm-DLP-1) protein of Trichuris muris that comprises about 95% of the protein secreted by the adult parasite, is known to bind matrix proteoglycans, and have IL-13-neutralising activity. We show here that worm-derived p43 purified from secretions binds fatty acids and retinol, including signalling lipids or precursors thereof. This binding activity might therefore contribute to the parasites modulation of the infection site by delivering or sequestering influential lipids. A recombinant orthologue of p43 from the human whipworm, Trichuris trichiura (p47; Tt-DLP-1), has similar lipid-binding activity, with a similarly highly apolar biding site. From the known molecular structure of p43, we note the existence of extensive surface-accessible cavities with diverse surface charge characteristics which may indicate binding of a range of small molecule types in addition to lipids, and that its internally duplicated subdomains likely possess discrete characteristics. p43 belongs to the "dorylipophorins" that have only been found in Dorylaimia (Clade I) nematodes and appear to be the chief lipid carrier in their pseudocoelomic fluids, replacing the major lipid transporters of other nematode clades. In T. muris, and potentially other trichurids, these molecules appear to have been adapted for both internal physiological and external immunomodulatory activities.

biochemistry↗

bioRxiv2023

A seven-year record of fluctuating core body temperatures of nesting leatherback and hawksbill sea turtles

Sea turtles experience changes in water temperatures during migrations and seasonal movements that will influence their body temperatures. Nothing is known of how sea turtles core body temperatures vary from season to season at nesting sites. Over seven consecutive seasons we measured the surface temperatures of freshly laid eggs as proxies of core temperatures of sea turtles using non-contact infrared thermometers. We measured egg temperatures of two species that have contrasting lifestyles - leatherbacks, the largest, which are adapted to migrate between tropical breeding sites to cold temperate waters, and the smaller hawksbills that are confined to the tropics and sub-tropics. We found considerable year-to-year variations in temperatures in both species (year means 30.4 {degrees}C to 31.5 {degrees}C in leatherbacks), hawksbills the more so (28.1 {degrees}C to 30.3 {degrees}C). These differences will likely be modified by both natural seasonal variations and anthropogenic changes in global ocean temperatures and resulting changes in currents and water temperatures local to nesting beaches. These previously unrecognised diversities in body temperatures of nesting turtles are pertinent to predicting environmental tolerances, reproductive success, and nest site selection by sea turtles, and could contribute to predicting which rookeries may remain viable or not during future ocean warming.

zoology↗

bioRxiv2021

Frog nest foam as a drug delivery system

Foams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from a predators and parasites, to prevent desiccation, to control gaseous exchange, temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time, that nests of the Tungara frog (Engystomops pustulosus) is stable ex situ with useful physiochemical and biocompatible properties and is capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as a topical drug delivery systems (DDS).

bioengineering↗

bioRxiv2017

Rapid changes in Atlantic grey seal milk from birth to desertion

True seals have the shortest lactation periods of any group of placental mammal. Most are capital breeders that undergo short, intense lactations, during which they fast while transferring substantial proportions of their body reserves to their pups, which they then abruptly desert. Milk was collected from Atlantic grey seals (Halichoerus grypus) periodically from birth until near desertion. Milk protein profiles matured within 24 hours or less, indicating the most rapid transition from colostrum to mature phase lactation yet observed. There was an unexpected persistence of immunoglobulin G almost until weaning, potentially indicating prolonged trans-intestinal transfer of IgG. Among components of innate immune protection were found fucosyllactose and siallylactose that are thought to impede colonisation by pathogens and encourage an appropriate gut microbiome. These oligosaccharides decreased from early lactation to almost undetectable levels by weaning. Taurine levels were initially high, then fell, possibly indicative of taurine dependency in seals, and progressive depletion of maternal reserves. Metabolites that could signal changes in the mothers metabolism of fats, such as nicotinamide and derivatives, rose from virtual absence, and acetylcarnitines fell. It is therefore possible that indicators of maternal metabolic strain exist that signal the imminence of desertion.

zoology↗

bioRxiv2016

Pulse of α-2-macroglobulin and lipocalin-1 in the pregnant uterus of European polecats (Mustela putorius) at the time of implantation

Uterine secretory proteins protect the uterus and conceptuses against infection, facilitate implantation, control cellular damage resulting from implantation, and supply embryos with nutrients. The early conceptus of the European polecat (Mustela putorius) grows and develops free in the uterus until implanting at about 12 days after mating. Using a proteomics approach we found that the proteins appearing in the uterus leading up to and including the time of implantation changed dramatically with time. Several of the proteins identified have been found in pregnant uteri of other placental mammals, such as 1-antitrypsin, serum albumin, lactoferrin, cathepsin L1, uteroferrin, and ectonucleotide pyrophosphatase. The broad-spectrum proteinase inhibitor 2-macroglobulin rose from relatively low abundance initially to dominate the protein profile by the time of implantation. Its functions may be to limit damage caused by the release of proteinases during implantation, and to control other processes around the site of implantation. Lipocalin-1 (also known as tear lipocalin) has not previously been recorded as a uterine secretion in pregnancy, and also increased substantially in concentration. If polecat lipocalin-1 has similar biochemical properties to the human form, then it may have a combined function in transporting or scavenging lipids, and antimicrobial activities. The changes in the uterine secretory proteome of Euroepan polecats may be similar in those species of mustelid that engage in embryonic diapause, but possibly only following reactivation of the embryo.

developmental biology↗