The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict

Summer effects on body mass index (BMI) gain and growth patterns of American Indian children from kindergarten to first grade: a prospective study

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are highly prevalent among American Indian children, especially those living on reservations. There is little scientific evidence about the effects of summer vacation on obesity development in children. The purpose of this study was to investigate the effects of summer vacation between kindergarten and first grade on growth in height, weight, and body mass index (BMI) for a sample of American Indian children.</p> <p>Methods</p> <p>Children had their height and weight measured in four rounds of data collection (yielded three intervals: kindergarten, summer vacation, and first grade) as part of a school-based obesity prevention trial (Bright Start) in a Northern Plains Indian Reservation. Demographic variables were collected at baseline from parent surveys. Growth velocities (Z-score units/year) for BMI, weight, and height were estimated and compared for each interval using generalized linear mixed models.</p> <p>Results</p> <p>The children were taller and heavier than median of same age counterparts. Height Z-scores were positively associated with increasing weight status category. The mean weight velocity during summer was significantly less than during the school year. More rapid growth velocity in height during summer than during school year was observed. Obese children gained less adjusted-BMI in the first grade after gaining more than their counterparts during the previous two intervals. No statistically significant interval effects were found for height and BMI velocities.</p> <p>Conclusions</p> <p>There was no indication of a significant summer effect on children's BMI. Rather than seasonal or school-related patterns, the predominant pattern indicated by weight-Z and BMI-Z velocities might be related to age or maturation.</p> <p>Trial registration</p> <p>Bright Start: Obesity Prevention in American Indian Children Clinical Trial Govt ID# <a href="http://www.clinicaltrials.gov/ct2/show/NCT00123032">NCT00123032</a></p

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF / ) mice and compared outcomes of disease against TNF f/f control and global TNF / mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF / mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF / mice were resistant to infection and presented with a phenotype similar to that in TNF f/f control mice. Impaired immunity in TNF / mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB

Seasonal patterns of suicides over the period of socio-economic transition in Lithuania

BACKGROUND: In Lithuania, suicides are a grave public health problem, requiring more extensive investigation. The aim of the study was to assess the seasonal variations of suicides in Lithuania throughout the years 1993–2002, describing patterns by gender, age and method of suicide. METHODS: The study material consisted of all registered suicides (n = 16,147) committed throughout 1993–2002 in Lithuania. Smoothed trends were inspected. The seasonal effect was explored using monthly ratio statistics and spectral analysis. RESULTS: Suicides in Lithuania have a distinct annual rhythm with peaks in summer and troughs in December. The December frequencies fell by more than 23% in men and 30% in women, while June peak reached nearly 23% in men and July peak exceeded 29% in women, compare with the average levels, (p < 0.05). Hanging was the most common method of suicide both in men and women comprising up to 90% among all suicides in 1998–2002. Among different methods, only hanging suicides showed significant seasonal variations, especially in men. The seasonal amplitude has decreased over time. CONCLUSION: Substantial seasonal variations in suicides were associated with a high proportion of hanging. Extremely high suicide rates in Lithuania require further extensive studies and urgent preventive programs, taking into account the suggestions of this survey

Plastic and Heritable Components of Phenotypic Variation in Nucella lapillus: An Assessment Using Reciprocal Transplant and Common Garden Experiments

Assessment of plastic and heritable components of phenotypic variation is crucial for understanding the evolution of adaptive character traits in heterogeneous environments. We assessed the above in relation to adaptive shell morphology of the rocky intertidal snail Nucella lapillus by reciprocal transplantation of snails between two shores differing in wave action and rearing snails of the same provenance in a common garden. Results were compared with those reported for similar experiments conducted elsewhere. Microsatellite variation indicated limited gene flow between the populations. Intrinsic growth rate was greater in exposed-site than sheltered-site snails, but the reverse was true of absolute growth rate, suggesting heritable compensation for reduced foraging opportunity at the exposed site. Shell morphology of reciprocal transplants partially converged through plasticity toward that of native snails. Shell morphology of F2s in the common garden partially retained characteristics of the P-generation, suggesting genetic control. A maternal effect was revealed by greater resemblance of F1s than F2s to the P-generation. The observed synergistic effects of plastic, maternal and genetic control of shell-shape may be expected to maximise fitness when environmental characteristics become unpredictable through dispersal

Lung epithelial stem cells and their niches : Fgf10 takes center stage

Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)

Modified Vaccinia Virus Ankara Exerts Potent Immune Modulatory Activities in a Murine Model

Background: Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, has been used as vaccine delivery vector in preclinical and clinical studies against infectious diseases and malignancies. Here, we investigated whether an MVA which does not encode any antigen (Ag) could be exploited as adjuvant per se. Methodology/Principal Findings: We showed that dendritic cells infected in vitro with non-recombinant (nr) MVA expressed maturation and activation markers and were able to efficiently present exogenously pulsed Ag to T cells. In contrast to the dominant T helper (Th) 1 biased responses elicited against Ags produced by recombinant MVA vectors, the use of nrMVA as adjuvant for the co-administered soluble Ags resulted in a long lasting mixed Th1/Th2 responses. Conclusions/Significance: These findings open new ways to potentiate and modulate the immune responses to vaccin

Effect of running therapy on depression (EFFORT-D). Design of a randomised controlled trial in adult patients [ISRCTN 1894]

<p>Abstract</p> <p>Background</p> <p>The societal and personal burden of depressive illness is considerable. Despite the developments in treatment strategies, the effectiveness of both medication and psychotherapy is not ideal. Physical activity, including exercise, is a relatively cheap and non-harmful lifestyle intervention which lacks the side-effects of medication and does not require the introspective ability necessary for most psychotherapies. Several cohort studies and randomised controlled trials (RCTs) have been performed to establish the effect of physical activity on prevention and remission of depressive illness. However, recent meta-analysis's of all RCTs in this area showed conflicting results. The objective of the present article is to describe the design of a RCT examining the effect of exercise on depressive patients.</p> <p>Methods/Design</p> <p>The EFFect Of Running Therapy on Depression in adults (EFFORT-D) is a RCT, studying the effectiveness of exercise therapy (running therapy (RT) or Nordic walking (NW)) on depression in adults, in addition to usual care. The study population consists of patients with depressive disorder, Hamilton Rating Scale for Depression (HRSD) ≥ 14, recruited from specialised mental health care. The experimental group receives the exercise intervention besides treatment as usual, the control group receives treatment as usual. The intervention program is a group-based, 1 h session, two times a week for 6 months and of increasing intensity. The control group only performs low intensive non-aerobic exercises. Measurements are performed at inclusion and at 3,6 and 12 months.</p> <p>Primary outcome measure is reduction in depressive symptoms measured by the HRSD. Cardio-respiratory fitness is measured using a sub maximal cycling test, biometric information is gathered and blood samples are collected for metabolic parameters. Also, co-morbidity with pain, anxiety and personality traits is studied, as well as quality of life and cost-effectiveness.</p> <p>Discussion</p> <p>Exercise in depression can be used as a standalone or as an add-on intervention. In specialised mental health care, chronic forms of depression, co-morbid anxiety or physical complaints and treatment resistance are common. An add-on strategy therefore seems the best choice. This is the first high quality large trial into the effectiveness of exercise as an add-on treatment for depression in adult patients in specialised mental health care.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1894">NTR1894</a></p

Genomic Profiling Identifies GATA6 as a Candidate Oncogene Amplified in Pancreatobiliary Cancer

Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46%) primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies