Left gaze bias in humans, rhesus monkeys and domestic dogs

While viewing faces, human adults often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the viewee’s face is often inspected first and for longer periods. Using a preferential looking paradigm, we demonstrate that this bias is neither uniquely human nor limited to primates, and provide evidence to help elucidate its biological function within a broader social cognitive framework. We observed that 6-month-old infants showed a wider tendency for left gaze preference towards objects and faces of different species and orientation, while in adults the bias appears only towards upright human faces. Rhesus monkeys showed a left gaze bias towards upright human and monkey faces, but not towards inverted faces. Domestic dogs, however, only demonstrated a left gaze bias towards human faces, but not towards monkey or dog faces, nor to inanimate object images. Our findings suggest that face- and species-sensitive gaze asymmetry is more widespread in the animal kingdom than previously recognised, is not constrained by attentional or scanning bias, and could be shaped by experience to develop adaptive behavioural significance

Occupational differences, cardiovascular risk factors and lifestyle habits in South Eastern rural Australia

BACKGROUND: In rural and remote Australia, cardiovascular mortality and morbidity rates are higher than metropolitan rates.This study analysed cardiovascular and other chronic disease risk factors and related health behaviours by occupational status, to determine whether agricultural workers have higher cardiovascular disease (CVD) risk than other rural workers. METHODS: Cross-sectional surveys in three rural regions of South Eastern Australia (2004-2006). A stratified random sample of 1001 men and women aged 25-74 from electoral rolls were categorised by occupation into agricultural workers (men = 214, women = 79), technicians (men = 123), managers (men = 148, women = 272) and 'home duties' (women = 165). Data were collected from self-administered questionnaire, physical measurements and laboratory tests. Cardiovascular disease (CVD) and coronary heart disease (CHD) risk were assessed by Framingham 5 years risk calculation. RESULTS: Amongst men, agricultural workers had higher occupational physical activity levels, healthier more traditional diet, lower alcohol consumption, lower fasting plasma glucose, the lowest proportion of daily smokers and lower age-adjusted 5 year CVD and CHD risk scores.Amongst women, managers were younger with higher HDL cholesterol, lower systolic blood pressure, less hypertension, lower waist circumference, less self-reported diabetes and better 5 year CVD and CHD risk scores.Agricultural workers did not have higher cardiovascular disease risk than other occupational groups. CONCLUSIONS: Previous studies have suggested that farmers have higher risks of cardiovascular disease but this is because the risk has been compared with non-rural populations. In this study, the comparison has been made with other rural occupations. Cardiovascular risk reduction programs are justified for all. Programs tailored only for agricultural workers are unwarranted

Syndromic (phenotypic) diarrhea in early infancy

Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). To date, no epidemiological data are available. The estimated prevalence is approximately 1/300,000–400,000 live births in Western Europe. Ethnic origin does not appear to be associated with SD. Infants are born small for gestational age and present with facial dysmorphism including prominent forehead and cheeks, broad nasal root and hypertelorism. Hairs are woolly, easily removed and poorly pigmented. Severe and persistent diarrhea starts within the first 6 months of life (≤ 1 month in most cases) and is accompanied by severe malabsorption leading to early and relentless protein energy malnutrition with failure to thrive. Liver disease affects about half of patients with extensive fibrosis or cirrhosis. There is currently no specific biochemical profile, though a functional T-cell immune deficiency with defective antibody production was reported. Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. Histopathological analysis of small intestine biopsy shows non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria, and no specific histological abnormalities involving the epithelium. The etiology remains unknown. The frequent association of the disorder with parental consanguinity and/or affected siblings suggests a genetic origin with an autosomal recessive mode of transmission. Early management consists of total PN. Some infants have a rather milder phenotype with partial PN dependency or require only enteral feeding. Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature

Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

<p>Abstract</p> <p>Background</p> <p>Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these <it>Pax6</it>^-/-ES cells died rapidly after neuronal differentiation in vitro.</p> <p>Results</p> <p>Here we report the derivation of new lines of <it>Pax6</it>^-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new <it>Pax6</it>^-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported <it>Pax6</it>^-/-ES cell lines. The new lines of <it>Pax6</it>^-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras in which the mutant cells survived and displayed the same phenotypes as <it>Pax6</it>^-/-cells in <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras made by embryo aggregation.</p> <p>Conclusions</p> <p>We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.</p

Transcriptional Reprogramming in Nonhuman Primate (Rhesus Macaque) Tuberculosis Granulomas

In response to Mtb infection, the host remodels the infection foci into a dense mass of cells known as the granuloma. The key objective of the granuloma is to contain the spread of Mtb into uninfected regions of the lung. However, it appears that Mtb has evolved mechanisms to resist killing in the granuloma. Profiling granuloma transcriptome will identify key immune signaling pathways active during TB infection. Such studies are not possible in human granulomas, due to various confounding factors. Nonhuman Primates (NHPs) infected with Mtb accurately reflect human TB in clinical and pathological contexts.We studied transcriptomics of granuloma lesions in the lungs of NHPs exhibiting active TB, during early and late stages of infection. Early TB lesions were characterized by a highly pro-inflammatory environment, expressing high levels of immune signaling pathways involving IFNgamma, TNFalpha, JAK, STAT and C-C/C-X-C chemokines. Late TB lesions, while morphologically similar to the early ones, exhibited an overwhelming silencing of the inflammatory response. Reprogramming of the granuloma transcriptome was highly significant. The expression of approximately two-thirds of all genes induced in early lesions was later repressed.The transcriptional characteristics of TB granulomas undergo drastic changes during the course of infection. The overwhelming reprogramming of the initial pro-inflammatory surge in late lesions may be a host strategy to limit immunopathology. We propose that these host profiles can predict changes in bacterial replication and physiology, perhaps serving as markers for latency and reactivation

Identification of Host-Dependent Survival Factors for Intracellular Mycobacterium tuberculosis through an siRNA Screen

The stable infection of host macrophages by Mycobacterium tuberculosis (Mtb) involves, and depends on, the attenuation of the diverse microbicidal responses mounted by the host cell. This is primarily achieved through targeted perturbations of the host cellular signaling machinery. Therefore, in view of the dependency of the pathogen on host molecules for its intracellular survival, we wanted to test whether targeting such factors could provide an alternate route for the therapeutic management of tuberculosis. To first identify components of the host signaling machinery that regulate intracellular survival of Mtb, we performed an siRNA screen against all known kinases and phosphatases in murine macrophages infected with the virulent strain, H37Rv. Several validated targets could be identified by this method where silencing led either to a significant decrease, or enhancement in the intracellular mycobacterial load. To further resolve the functional relevance of these targets, we also screened against these identified targets in cells infected with different strains of multiple drug-resistant mycobacteria which differed in terms of their intracellular growth properties. The results obtained subsequently allowed us to filter the core set of host regulatory molecules that functioned independently of the phenotypic variations exhibited by the pathogen. Then, using a combination of both in vitro and in vivo experimentation, we could demonstrate that at least some of these host factors provide attractive targets for anti-TB drug development. These results provide a “proof-of-concept” demonstration that targeting host factors subverted by intracellular Mtb provides an attractive and feasible strategy for the development of anti-tuberculosis drugs. Importantly, our findings also emphasize the advantage of such an approach by establishing its equal applicability to infections with Mtb strains exhibiting a range of phenotypic diversifications, including multiple drug-resistance. Thus the host factors identified here may potentially be exploited for the development of anti-tuberculosis drugs

The p38/MK2/Hsp25 Pathway Is Required for BMP-2-Induced Cell Migration

Background: Bone morphogenetic proteins (BMPs) have been shown to participate in the patterning and specification of several tissues and organs during development and to regulate cell growth, differentiation and migration in different cell types. BMP-mediated cell migration requires activation of the small GTPase Cdc42 and LIMK1 activities. In our earlier report we showed that activation of LIMK1 also requires the activation of PAKs through Cdc42 and PI3K. However, the requirement of additional signaling is not clearly known. Methodology/Principal Findings: Activation of p38 MAPK has been shown to be relevant for a number of BMP-2¿s physiological effects. We report here that BMP-2 regulation of cell migration and actin cytoskeleton remodelling are dependent on p38 activity. BMP-2 treatment of mesenchymal cells results in activation of the p38/MK2/Hsp25 signaling pathway downstream from the BMP receptors. Moreover, chemical inhibition of p38 signaling or genetic ablation of either p38¿ or MK2 blocks the ability to activate the downstream effectors of the pathway and abolishes BMP-2-induction of cell migration. These signaling effects on p38/MK2/Hsp25 do not require the activity of either Cdc42 or PAK, whereas p38/MK2 activities do not significantly modify the BMP-2-dependent activation of LIMK1, measured by either kinase activity or with an antibody raised against phospho-threonine 508 at its activation loop. Finally, phosphorylated Hsp25 colocalizes with the BMP receptor complexes in lamellipodia and overexpression of a phosphorylation mutant form of Hsp25 is able to abolish the migration of cells in response to BMP-2. Conclusions: These results indicate that Cdc42/PAK/LIMK1 and p38/MK2/Hsp25 pathways, acting in parallel and modulating specific actin regulatory proteins, play a critical role in integrating responses during BMP-induced actin reorganization and cell migration

Identification and denitrification characteristics of a salt-tolerant denitrifying bacterium Pannonibacter phragmitetus F1

A salt-tolerant denitrifying bacterium F1 was isolated in this study, which has high nitrite (NO -N) and nitrate (NO -N) removal abilities. The salt tolerance capacity of strain F1 was further verified and the effects of initial pH, initial NaNO concentration and inoculation size on the denitrification capacity of strain F1 under saline conditions were evaluated. Strain F1 was identified as Pannonibacter phragmitetus and named Pannonibacter phragmitetus F1. This strain can tolerate NaCl concentrations up to 70 g/L, and its most efficient denitrification capacity was observed at NaCl concentrations of 0-10 g/L. Under non-saline condition, the removal percentages of NO -N and NO -N by strain Pannonibacter phragmitetus F1 at pH of 10 and inoculation size of 5% were 100% and 83%, respectively, after cultivation for 5 days. Gas generation was observed during the cultivation, indicating that an efficient denitrification performance was achieved. When pH was 10 and the inoculation size was 5%, both the highest removal percentages of NO -N (99%) and NO -N (95%) by strain Pannonibacter phragmitetus F1 were observed at NaCl concentration of 10 g/L. When the NaCl concentration was 10 g/L, strain Pannonibacter phragmitetus F1 can adapt to a wide range of neutral and alkaline environments (pH of 7-10) and is highly tolerant of NaNO concentration (0.4-1.6 g/L). In conclusion, strain Pannonibacter phragmitetus F1 has a great potential to be applied in the treatment of saline wastewater containing high nitrogen concentrations, e.g. coastal aquaculture wastewater