Evidence for a vertebrate catapult: elastic energy storage in the plantaris tendon during frog jumping

Anuran jumping is one of the most powerful accelerations in vertebrate locomotion. Several species are hypothesized to use a catapult-like mechanism to store and rapidly release elastic energy, producing power outputs far beyond the capability of muscle. Most evidence for this mechanism comes from measurements of whole-body power output; the decoupling of joint motion and muscle shortening expected in a catapult-like mechanism has not been demonstrated. We used high-speed marker-based biplanar X-ray cinefluoroscopy to quantify plantaris muscle fascicle strain and ankle joint motion in frogs in order to test for two hallmarks of a catapult mechanism: (i) shortening of fascicles prior to joint movement (during tendon stretch), and (ii) rapid joint movement during the jump without rapid muscle-shortening (during tendon recoil). During all jumps, muscle fascicles shortened by an average of 7.8 per cent (54% of total strain) prior to joint movement, stretching the tendon. The subsequent period of initial joint movement and high joint angular acceleration occurred with minimal muscle fascicle length change, consistent with the recoil of the elastic tendon. These data support the plantaris longus tendon as a site of elastic energy storage during frog jumping, and demonstrate that catapult mechanisms may be employed even in sub-maximal jumps.     

Proteomic analyses of intermediate filaments reveals cytokeratin8 is highly acetylated--implications for colorectal epithelial homeostasis.

Butyrate is a critical cancer-preventive element in the colon milieu whose mechanism of action is unclear, but appears to be mediated through inhibition of histone deacetylases (HDACs) and consequent alterations in global protein acetylation. Cytokeratins (CKs) have roles in cytoskeletal function as components of the intermediate filaments (IFs) and this involves CKs in the regulation of tissue homeostasis of high-turnover epithelia such as the colon. We used a 2-D gel/MS analysis to characterise the proteome of IFs, and a novel monitoring-initiated detection and sequencing (MIDAS) approach to identify acetylation sites on principal proteins. We report that CKs are highly acetylated in a colon cancer cell line, with five acetylation sites characterised on CK8 and a further one on CK18. Acetylation of CK8 is responsive to butyrate. HDAC5 is the deacetylase associated with IFs. These data indicate a novel action of butyrate as a cancer preventive agent. Acetylation of CK8 may be associated with IFs stabilisation and thereby provide a candidate mechanism for the appropriate retention or loss of epithelial cells from the flat mucosa.     

Implication of new WHO growth standards on identification of risk factors and estimated prevalence of malnutrition in rural Malawian infants

Background

The World Health Organization (WHO) released new Child Growth Standards in 2006 to replace the current National Center for Health Statistics (NCHS) growth reference. We assessed how switching from the NCHS to the newly released WHO Growth Standards affects the estimated prevalence of wasting, underweight and stunting, and the pattern of risk factors identified.

Methodology/Principal Findings

Data were drawn from a village-informant driven Demographic Surveillance System in Northern Malawi. Children (n = 1328) were visited twice at 0–4 months and 11–15 months. Data were collected on the demographic and socio-economic environment of the child, health history, maternal and child anthropometry and child feeding practices. Weight-for-length, weight-for-age and length-for-age were derived in z-scores using the two growth references. In early infancy, prevalence estimates were 2.9, 6.1, and 8.5 fold higher for stunting, underweight, and wasting respectively using the WHO standards compared to NCHS reference (p<0.001 for all). At one year, prevalence estimates for wasting and stunting did not differ significantly according to reference used, but the prevalence of underweight was half that with the NCHS reference (p<0.001). Patterns of risk factors were similar with the two growth references for all outcomes at one year although the strength of association was higher with WHO standards.

Conclusions/Significance

Differences in prevalence estimates differed in magnitude but not direction from previous studies. The scale of these differences depends on the population''s nutritional status thus it should not be assumed a priori. The increase in estimated prevalence of wasting in early infancy has implications for feeding programs targeting lactating mothers and ante-natal multiple micronutrients supplementation to tackle small birth size. Risk factors identified using WHO standards remain comparable with findings based on the NCHS reference in similar settings. Further research should aim to identify whether the young infants additionally diagnosed as malnourished by this new standard are more appropriate targets for interventions than those identified with the NCHS reference.     

A novel role for PECAM-1 (CD31) in regulating haematopoietic progenitor cell compartmentalization between the peripheral blood and bone marrow

Although the expression of PECAM-1 (CD31) on vascular and haematopoietic cells within the bone marrow microenvironment has been recognized for some time, its physiological role within this niche remains unexplored. In this study we show that PECAM-1 influences steady state hematopoietic stem cell (HSC) progenitor numbers in the peripheral blood but not the bone marrow compartment. PECAM-1(-/-) mice have higher levels of HSC progenitors in the blood compared to their littermate controls. We show that PECAM-1 is required on both progenitors and bone marrow vascular cells in order for efficient transition between the blood and bone marrow to occur. We have identified key roles for PECAM-1 in both the regulation of HSC migration to the chemokine CXCL12, as well as maintaining levels of the matrix degrading enzyme MMP-9 in the bone marrow vascular niche. Using intravital microscopy and adoptive transfer of either wild type (WT) or PECAM-1(-/-) bone marrow precursors, we demonstrate that the increase in HSC progenitors in the blood is due in part to a reduced ability to migrate from blood to the bone marrow vascular niche. These findings suggest a novel role for PECAM-1 as a regulator of resting homeostatic progenitor cell numbers in the blood.     

Horse personality: Variation between breeds

Anecdotal evidence from horse owners and handlers suggests the existence of breed typical behaviour and personality in horses. This is further supported by current research on heritability of personality characteristics in a range of species. The Horse Personality Questionnaire (HPQ) is a 25-item rating method that has previously been shown to be reliable for the assessment of personality in horses. Principal component analysis on HPQ data has identified six underlying personality components in horses. These are Dominance, Anxiousness, Excitability, Protection, Sociability and Inquisitiveness. Using the HPQ a survey of 1223 horses of eight different breeds was completed. Data were analysed to explore any differences in personality between breeds across the six personality components. Breed differences in personality were identified, and it was noted that variability between breeds varied between personality components. Anxiousness and Excitability showed the most variation between breeds, whilst Dominance and Protection showed the least variance. The results identified breed typical personalities that were comparable to results from previous studies as well as anecdotal evidence provided by the popular equine literature. The results are discussed in terms of the potential selection pressures that may have resulted in these differences.     

Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis

Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1–q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor β (OSMRβ), in three families. OSMRβ is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching.     

Novel phenotypes identified by plasma biochemical screening in the mouse

We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.     

Allium ampeloprasum var. babingtonii (Alliaceae): an isoclonal plant found across a range of habitats in S.W. England

Despite the widespread distribution and common habitat dominance of clonal plant species the mechanisms for their ecological success often remain uncertain. Allium ampeloprasum var. babingtonii is a sterile plant that reproduces with physiologically independent asexual propagules. The variety is found mainly in the S.W. of England over a wide habitat range including sea cliffs and open woodlands and displays an autumn-spring phenology in common with its close Mediterranean relatives. The role of population genetic structure in the remarkable habitat distribution of the variety is not known. Genetic variation in A. ampeloprasum var. babingtonii was analysed using RAPD markers in single individuals of var. babingtonii from 16 distinct populations and five further individuals from a single population. This analysis revealed no polymorphism suggesting that all sampled individuals are part of a single clone. We offer the conjecture that in the absence of genetic variation an ecological release, due to temporal separation from competing species, may contribute to the ability of var. babingtonii to exploit heterogeneous environmental conditions.