Reexamining echidna physiology: The big picture for Tachyglossus aculeatus acanthion

The early divergence of monotremes and therian mammals has resulted in considerable interest in the comparative physiology of the short-beaked echidna (Tachyglossus aculeatus), the most common and widespread living monotreme. However, there are many and varied interpretations of its physiology, reflecting the many and varied studies, limitations and uncertainties of aspects of some previous studies, and potential differences between the various subspecies. Consequently, we thoroughly examine here the standardized physiology of the most widely distributed subspecies of short-beaked echidna (T. aculeatus acanthion) over a wide range of ambient temperatures to definitively assess its physiology in a comparative context. We conclude that the low and variable body temperature of the short-beaked echidna is physiologically “primitive,” but it also reflects adaptation to its myrmecophagous niche. Other aspects of its physiology are more typically mammalian. A low metabolic rate reflects its low body temperature, and ventilatory variables are matched to accommodate a modest gas exchange requirement. Thermal conductance is typical for a mammal of equivalent mass. In contrast to previous studies, we demonstrate that short-beaked echidnas can enhance evaporative water loss above thermoneutrality, like other mammals, with a similar capacity for evaporative heat loss. Cooling of their nasal blood sinus with nasalmucousmay contribute to this enhanced evaporative cooling. Their capacity to evaporatively cool explains how their distribution can include habitats where ambient temperature, even in shelters, exceeds their supposed critical thermal limit

The personal experience of parenting a child with Juvenile Huntington’s Disease: perceptions across Europe

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington’s disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,. A secondary aim was to see the extent to which the findings from the UK study were repeated across Europe and the degree of commonality or divergence across the different countries. Fourteen parents who were the primary caregiver took part in a semistructured interview. These were analyzed using an established qualitative methodology, interpretative phenomenological analysis. Five analytic themes were derived from the analysis: the early signs of something wrong; parental understanding of juvenile Huntington’s disease; living with the disease; other people’s knowledge and understanding; and need for support. These are discussed in light of the considerable convergence between the experiences of families in the United Kingdom and elsewhere in Europe

Research and theory for nursing and midwifery: Rethinking the nature of evidence

Background and Rationale: The rise in the principles of evidence-based medicine in the 1990s heralded a re-emerging orthodoxy in research methodologies. The view of the randomised controlled trial (RCT) as a “gold standard” for evaluation of medical interventions has extended recently to evaluation of organisational forms and reforms and of change in complex systems—within health care and in other human services. Relatively little attention has been given to the epistemological assumptions underlying such a hierarchy of research evidence. Aims and Methods: Case studies from research in maternity care are used in this article to describe problems and limitations encountered in using RCTs to evaluate some recent policy-driven and consumer-oriented developments. These are discussed in relation to theory of knowledge and the epistemological assumptions, or paradigms, underpinning health services research. The aim in this discussion is not to advocate, or to reject, particular approaches to research but to advocate a more open and critical engagement with questions about the nature of evidence. Findings and Discussion: Experimental approaches are of considerable value in investigating deterministic and probabilistic cause and effect relationships, and in testing often well-established but unevaluated technologies. However, little attention has been paid to contextual and cultural factors in the effects of interventions, in the culturally constructed nature of research questions themselves, or of the data on which much research is based. More complex, and less linear, approaches to methodology are needed to address these issues. A simple hierarchical approach does not represent the complexity of evidence well and should move toward a more cyclical view of knowledge development

The Spatial Distribution of LGR5+ Cells Correlates With Gastric Cancer Progression

In this study we tested the prevalence, histoanatomical distribution and tumour biological significance of the Wnt target protein and cancer stem cell marker LGR5 in tumours of the human gastrointestinal tract. Differential expression of LGR5 was studied on transcriptional (real-time polymerase chain reaction) and translational level (immunohistochemistry) in malignant and corresponding non-malignant tissues of 127 patients comprising six different primary tumour sites, i.e. oesophagus, stomach, liver, pancreas, colon and rectum. The clinico-pathological significance of LGR5 expression was studied in 100 patients with gastric carcinoma (GC). Non-neoplastic tissue usually harboured only very few scattered LGR5+ cells. The corresponding carcinomas of the oesophagus, stomach, liver, pancreas, colon and rectum showed significantly more LGR5+ cells as well as significantly higher levels of LGR5-mRNA compared with the corresponding non-neoplastic tissue. Double staining experiments revealed a coexpression of LGR5 with the putative stem cell markers CD44, Musashi-1 and ADAM17. Next we tested the hypothesis that the sequential changes of gastric carcinogenesis, i.e. chronic atrophic gastritis, intestinal metaplasia and invasive carcinoma, are associated with a reallocation of the LGR5+ cells. Interestingly, the spatial distribution of LGR5 changed: in non-neoplastic stomach mucosa, LGR5+ cells were found predominantly in the mucous neck region; in intestinal metaplasia LGR5+ cells were localized at the crypt base, and in GC LGR5+ cells were present at the luminal surface, the tumour centre and the invasion front. The expression of LGR5 in the tumour centre and invasion front of GC correlated significantly with the local tumour growth (T-category) and the nodal spread (N-category). Furthermore, patients with LGR5+ GCs had a shorter median survival (28.0±8.6 months) than patients with LGR5− GCs (54.5±6.3 months). Our results show that LGR5 is differentially expressed in gastrointestinal cancers and that the spatial histoanatomical distribution of LGR5+ cells has to be considered when their tumour biological significance is sought

A Novel Acyl-CoA Beta-Transaminase Characterized from a Metagenome

BACKGROUND: Bacteria are key components in all ecosystems. However, our knowledge of bacterial metabolism is based solely on the study of cultivated organisms which represent just a tiny fraction of microbial diversity. To access new enzymatic reactions and new or alternative pathways, we investigated bacterial metabolism through analyses of uncultivated bacterial consortia. METHODOLOGY/PRINCIPAL FINDINGS: We applied the gene context approach to assembled sequences of the metagenome of the anaerobic digester of a municipal wastewater treatment plant, and identified a new gene which may participate in an alternative pathway of lysine fermentation. CONCLUSIONS: We characterized a novel, unique aminotransferase that acts exclusively on Coenzyme A (CoA) esters, and proposed a variant route for lysine fermentation. Results suggest that most of the lysine fermenting organisms use this new pathway in the digester. Its presence in organisms representative of two distinct bacterial divisions indicate that it may also be present in other organisms

Domestic Violence and Health Care: Opening Pandora¿s Box ¿ Challenges and Dilemmas

In this article we take a critical stance toward the rational progressive narrative surrounding the integration of domestic violence within health care. Whilst changes in recent UK policy and practice have resulted in several tangible benefits, it is argued that there may be hidden dilemmas and challenges. We suggest that the medical model of care and its discursive practices position women as individually accountable for domestic violence-related symptoms and injuries. This may not only be ineffective in terms of service provision but could also have the potential to reduce the political significance of domestic violence as an issue of concern for all women. Furthermore, it is argued that the use of specific metaphors enables practitioners to distance themselves from interactions that may prove to be less comfortable and provide less than certain outcomes. Our analysis explores the possibilities for change that might currently be available. This would appear to involve a consideration of alternative discourses and the reformulation of power relations and subject positions in health care

Prenatal Hyperandrogenization Induces Metabolic and Endocrine Alterations Which Depend on the Levels of Testosterone Exposure

Prenatal hyperandrogenism is able to induce polycystic ovary syndrome (PCOS) in rats. The aim of the present study was to establish if the levels of prenatal testosterone may determine the extent of metabolic and endocrine alterations during the adult life. Pregnant Sprague Dawley rats were prenatally injected with either 2 or 5 mg free testosterone (groups T2 and T5 respectively) from day 16 to day 19 day of gestation. Female offspring from T2 and T5 displayed different phenotype of PCOS during adult life. Offspring from T2 showed hyperandrogenism, ovarian cysts and ovulatory cycles whereas those from T5 displayed hyperandrogenism, ovarian cysts and anovulatory cycles. Both group showed increased circulating glucose levels after the intraperitoneal glucose tolerance test (IPGTT; an evaluation of insulin resistance). IPGTT was higher in T5 rats and directly correlated with body weight at prepubertal age. However, the decrease in the body weight at prepubertal age was compensated during adult life. Although both groups showed enhanced ovarian steroidogenesis, it appears that the molecular mechanisms involved were different. The higher dose of testosterone enhanced the expression of both the protein that regulates cholesterol availability (the steroidogenic acute regulatory protein (StAR)) and the protein expression of the transcriptional factor: peroxisome proliferator-activated receptor gamma (PPAR gamma). Prenatal hyperandrogenization induced an anti-oxidant response that prevented a possible pro-oxidant status. The higher dose of testosterone induced a pro-inflammatory state in ovarian tissue mediated by increased levels of prostaglandin E (PG) and the protein expression of cyclooxygenase 2 (COX2, the limiting enzyme of PGs synthesis). In summary, our data show that the levels of testosterone prenatally injected modulate the uterine environment and that this, in turn, would be responsible for the endocrine and metabolic abnormalities and the phenotype of PCOS during the adult life

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

Background: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. Methods: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. Results: Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. Conclusion: Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele

Delta1 Expression, Cell Cycle Exit, and Commitment to a Specific Secretory Fate Coincide within a Few Hours in the Mouse Intestinal Stem Cell System

The stem cells of the small intestine are multipotent: they give rise, via transit-amplifying cell divisions, to large numbers of columnar absorptive cells mixed with much smaller numbers of three different classes of secretory cells - mucus-secreting goblet cells, hormone-secreting enteroendocrine cells, and bactericide-secreting Paneth cells. Notch signaling is known to control commitment to a secretory fate, but why are the secretory cells such a small fraction of the population, and how does the diversity of secretory cell types arise? Using the mouse as our model organism, we find that secretory cells, and only secretory cells, pass through a phase of strong expression of the Notch ligand Delta1 (Dll1). Onset of this Dll1 expression coincides with a block to further cell division and is followed in much less than a cell cycle time by expression of Neurog3 – a marker of enteroendocrine fate – or Gfi1 – a marker of goblet or Paneth cell fate. By conditional knock-out of Dll1, we confirm that Delta-Notch signaling controls secretory commitment through lateral inhibition. We infer that cells stop dividing as they become committed to a secretory fate, while their neighbors continue dividing, explaining the final excess of absorptive over secretory cells. Our data rule out schemes in which cells first become committed to be secretory, and then diversify through subsequent cell divisions. A simple mathematical model shows how, instead, Notch signaling may simultaneously govern the commitment to be secretory and the choice between alternative modes of secretory differentiation