Masticatory musculature of the African mole-rats (Rodentia: Bathyergidae)

The Bathyergidae, commonly known as blesmols or African mole-rats, is a family of rodents well-known for their subterranean lifestyle and tunnelling behaviour. Four of the five extant bathyergid genera (Cryptomys, Fukomys, Georychus and Heliophobius) are chisel-tooth diggers, that is they dig through soil with their enlarged incisors, whereas the remaining genus (Bathyergus) is a scratch-digger, only using its forelimbs for burrowing. Heterocephalus glaber, the naked mole-rat, is also a chisel-tooth digger and was until recently included within the Bathyergidae (as the most basally branching genus), but has now been placed by some researchers into its own family, the Heterocephalidae. Given the importance of the masticatory apparatus in habitat construction in this group, knowledge and understanding of the morphology and arrangement of the jaw-closing muscles in Bathyergidae is vital for future functional analyses. Here, we use diffusible iodine-based contrast-enhanced microCT to reveal and describe the muscles of mastication in representative specimens of each genus of bathyergid mole-rat and to compare them to the previously described musculature of the naked mole-rat. In all bathyergids, as in all rodents, the masseter muscle is the most dominant component of the masticatory musculature. However, the temporalis is also a relatively large muscle, a condition normally associated with sciuromorphous rodents. Unlike their hystricomorphous relatives, the bathyergids do not show an extension of the masseter through the infraorbital foramen on to the rostrum (other than a very slight protrusion in Cryptomys and Fukomys). Thus, morphologically, bathyergids are protrogomorphous, although this is thought to be secondarily derived rather than retained from ancestral rodents. Overall, the relative proportions of the jaw-closing muscles were found to be fairly consistent between genera except in Bathyergus, which was found to have an enlarged superficial masseter and relatively smaller pterygoid muscles. It is concluded that these differences may be a reflection of the behaviour of Bathyergus which, uniquely in the family, does not use its incisors for digging

Comparable Overall Survival in Patients with Hepatocellular Carcinoma Diagnosed within and outside a Surveillance Programme:The Potential Impact of Liver Cirrhosis

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death, and its incidence is rising. Mortality from HCC is predicted to increase by 140% by 2035. Surveillance of high-risk patients with cirrhosis or chronic liver disease may be one means of reducing HCC mortality, but the level of supporting evidence for international guidelines is low/moderate. This study explores the real-world experience of HCC surveillance at a tertiary referral centre. Electronic patient records for all new HCCs diagnosed between August 2012 and December 2021 were retrospectively reviewed. Patient and tumour characteristics were evaluated, including the co-existence of chronic liver disease, cancer treatment and survival, and categorised according to HCC diagnosis within or outside a surveillance programme. Patients with HCC who presented through surveillance had smaller tumours diagnosed at an earlier stage, but this did not translate into improved overall survival. All patients in surveillance had chronic liver disease, including 91% (n = 101) with cirrhosis, compared to 45% (n = 29) in the non-surveillance cohort. We propose that the immune dysfunction associated with cirrhosis predisposes patients to a more aggressive tumour biology than the largely non-cirrhotic population in the non-surveillance group

Ageing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species.

BACKGROUND: Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species. RESULTS: A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu. CONCLUSIONS: Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process

Phylogenetic Relationships in Pterodroma Petrels Are Obscured by Recent Secondary Contact and Hybridization

The classification of petrels (Pterodroma spp.) from Round Island, near Mauritius in the Indian Ocean, has confounded researchers since their discovery in 1948. In this study we investigate the relationships between Round Island petrels and their closest relatives using evidence from mitochondrial DNA sequence data and ectoparasites. Far from providing clear delimitation of species boundaries, our results reveal that hybridization among species on Round Island has led to genetic leakage between populations from different ocean basins. The most common species on the island, Pterodroma arminjoniana, appears to be hybridizing with two rarer species (P. heraldica and P. neglecta), subverting the reproductive isolation of all three and allowing gene flow. P. heraldica and P. neglecta breed sympatrically in the Pacific Ocean, where P. arminjoniana is absent, but no record of hybridization between these two exists and they remain phenotypically distinct. The breakdown of species boundaries in Round Island petrels followed environmental change (deforestation and changes in species composition due to hunting) within their overlapping ranges. Such multi-species interactions have implications not only for conservation, but also for our understanding of the processes of evolutionary diversification and speciation

The naked truth:a comprehensive clarification and classification of current 'myths' in naked mole-rat biology

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions

Field evidence for aseasonality of reproduction and colony size in the Afrotropical giant mole-rat Fukomys mechowii (Rodentia: Bathyergidae)

The giant mole-rat, Fukomys mechowii is a cooperatively breeding subterranean mole-rat exhibiting a reproductive division of labour in which usually one, or occasionally two, females are responsible for procreation. In a field study that involved complete excavation of 32 burrow systems, mean colony size was 9.9 individuals (range 7–16). Pregnant reproductive females were found throughout the study period (September 2005 until June 2006), supporting preliminary evidence that reproduction occurs throughout the year. Of the 32 colonies sampled, 10 of 14 in which the reproductive female could be identified as pregnant contained a single reproductive female, while four had two females breeding simultaneously (plural breeding). The population sex ratio was skewed towards females at 1:1.46. Autopsy of pregnant reproductive females (n = 18) revealed that the production of two (10/18 pregnancies) or three (7/18) offspring was the norm, with one case of four embryos being present. These new data increase our fragmentary knowledge of the natural history of this little-studied species.Key words: Fukomys mechowii, Bathyergidae, Cryptomys, colony size, seasonality, reproductive skew

Masticatory musculature of the African mole-rats (Rodentia: Bathyergidae)

The Bathyergidae, commonly known as blesmols or African mole-rats, is a family of rodents well-known for their subterranean lifestyle and tunnelling behaviour. Four of the five extant bathyergid genera (Cryptomys, Fukomys, Georychus and Heliophobius) are chisel-tooth diggers, that is they dig through soil with their enlarged incisors, whereas the remaining genus (Bathyergus) is a scratch-digger, only using its forelimbs for burrowing. Heterocephalus glaber, the naked mole-rat, is also a chisel-tooth digger and was until recently included within the Bathyergidae (as the most basally branching genus), but has now been placed by some researchers into its own family, the Heterocephalidae. Given the importance of the masticatory apparatus in habitat construction in this group, knowledge and understanding of the morphology and arrangement of the jaw-closing muscles in Bathyergidae is vital for future functional analyses. Here, we use diffusible iodine-based contrast-enhanced microCT to reveal and describe the muscles of mastication in representative specimens of each genus of bathyergid mole-rat and to compare them to the previously described musculature of the naked mole-rat. In all bathyergids, as in all rodents, the masseter muscle is the most dominant component of the masticatory musculature. However, the temporalis is also a relatively large muscle, a condition normally associated with sciuromorphous rodents. Unlike their hystricomorphous relatives, the bathyergids do not show an extension of the masseter through the infraorbital foramen on to the rostrum (other than a very slight protrusion in Cryptomys and Fukomys). Thus, morphologically, bathyergids are protrogomorphous, although this is thought to be secondarily derived rather than retained from ancestral rodents. Overall, the relative proportions of the jaw-closing muscles were found to be fairly consistent between genera except in Bathyergus, which was found to have an enlarged superficial masseter and relatively smaller pterygoid muscles. It is concluded that these differences may be a reflection of the behaviour of Bathyergus which, uniquely in the family, does not use its incisors for digging.Supplementary material: Table S1: Specimen information and scanning parameters. Specimen IDs, DOIs and microCT scanning parameters for each specimen used in this analysis.Table S2: Masticatory muscle masses. Absolute masses (in g) of masticatory muscles of African mole-rats. Data for Heterocephalus from Cox & Faulkes (2014).The DST-NRF SARChI Chair (GUN 647560).https://peerj.comhj2020Mammal Research InstituteZoology and Entomolog

Effects of Transplantation-Related Immunosuppression on Co-Existent Neuroendocrine Tumours.

BACKGROUND Here we detail our experience of managing patients found to have a neuroendocrine neoplasm (NEN) whilst on immunosuppression for a transplanted organ. AIM We aimed to quantify the behaviour of NENs under solid-organ transplant-related immunosuppression. DESIGN This was an observational, retrospective case series. METHODS 10 patients were identified from a prospectively kept database. 3 were excluded. RESULTS Four patients received a liver, two a kidney, and one a heart transplant. All but one received calcineurin-based immunosuppression.NENs were found in five patients post-transplant: one had surgery for transverse colonic neuroendocrine carcinoma NEC (pT4N1M0, Ki67 60%), was cancer-free after four years; one had cold biopsy of duodenal NEN (pT1N0M0, Ki67 2%), cancer-free at four months; one 7 mm pancreatic NEN (pT1N0M0), untreated and stable for seven years;; one small bowel NEN with mesenteric metastasis (pTxNxM1), alive four years after diagnosis; and one untreated small-bowel NEN with mesenteric metastasis, stable at 1 year after liver transplantation.Two NENs were discovered pre-transplant, one pancreatic NEN (pT1N0M0, Ki67 5%), remains untreated and stable at three years. One gastric NEN (type 3, pT1bN0M0, Ki67 2%) remains stable without treatment for two years. CONCLUSIONS NENs demonstrate indolent behaviour in the presence of transplant-related immunosuppression