Work-related correlates of occupational sitting in a diverse sample of employees in Midwest metropolitan cities

The worksite serves as an ideal setting to reduce sedentary time. Yet little research has focused on occupational sitting, and few have considered factors beyond the personal or socio-demographic level. The current study i) examined variation in occupational sitting across different occupations, ii) explored whether worksite level factors (e.g., employer size, worksite supports and policies) may be associated with occupational sitting. Between 2012 and 2013, participants residing in four Missouri metropolitan areas were interviewed via telephone and provided information on socio-demographic characteristics, schedule flexibility, occupation, work related factors, and worksite supports and policies. Occupational sitting was self-reported (daily minutes spent sitting at work), and dichotomized. Occupation-stratified analyses were conducted to identify correlates of occupational sitting using multiple logistic regressions. A total of 1668 participants provided completed data. Those employed in business and office/administrative support spent more daily occupational sitting time (median 330 min) compared to service and blue collar employees (median 30 min). Few worksite supports and policies were sitting specific, yet factors such as having a full-time job, larger employer size, schedule flexibility, and stair prompt signage were associated with occupational sitting. For example, larger employer size was associated with higher occupational sitting in health care, education/professional, and service occupations. Work-related factors, worksite supports and policies are associated with occupational sitting. The pattern of association varies among different occupation groups. This exploratory work adds to the body of research on worksite level correlates of occupational sitting. This may provide information on priority venues for targeting highly sedentary occupation groups

Heat shock-induced phosphorylation of TAR DNA-binding protein 43 (TDP-43) by MAPK/ERK kinase regulates TDP-43 function

TAR DNA-binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway. TDP-43 dual phosphorylation by MEK, at threonine 153 and tyrosine 155 (p-T153/Y155), was dramatically increased by the heat shock response (HSR) in human cells. HSR promotes cell survival under proteotoxic conditions by maintaining protein homeostasis and preventing protein misfolding. MEK is activated by HSR and contributes to the regulation of proteome stability. Phosphorylated TDP-43 was not associated with TDP-43 aggregation, and p-T153/Y155 remained soluble under conditions that promote protein misfolding. We found that active MEK significantly alters TDP-43-regulated splicing and that phosphomimetic substitutions at these two residues reduce binding to GU-rich RNA. Cellular imaging using a phospho-specific p-T153/Y155 antibody showed that phosphorylated TDP-43 was specifically recruited to the nucleoli, suggesting that p-T153/Y155 regulates a previously unappreciated function of TDP-43 in the processing of nucleolar-associated RNA. These findings highlight a new mechanism that regulates TDP-43 function and homeostasis through phosphorylation and, therefore, may contribute to the development of strategies to prevent TDP-43 aggregation and to uncover previously unexplored roles of TDP-43 in cell metabolism

Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study.

Although individuals at clinical high risk (CHR) for psychosis exhibit a psychosis-risk syndrome involving attenuated forms of the positive symptoms typical of schizophrenia (SZ), it remains unclear whether their resting-state brain intrinsic functional networks (INs) show attenuated or qualitatively distinct patterns of functional dysconnectivity relative to SZ patients. Based on resting-state functional magnetic imaging data from 70 healthy controls (HCs), 53 CHR individuals (among which 41 subjects were antipsychotic medication-naive), and 58 early illness SZ (ESZ) patients (among which 53 patients took antipsychotic medication) within five years of illness onset, we estimated subject-specific INs using a novel group information guided independent component analysis (GIG-ICA) and investigated group differences in INs. We found that when compared to HCs, both CHR and ESZ groups showed significant differences, primarily in default mode, salience, auditory-related, visuospatial, sensory-motor, and parietal INs. Our findings suggest that widespread INs were diversely impacted. More than 25% of voxels in the identified significant discriminative regions (obtained using all 19 possible changing patterns excepting the no-difference pattern) from six of the 15 interrogated INs exhibited monotonically decreasing Z-scores (in INs) from the HC to CHR to ESZ, and the related regions included the left lingual gyrus of two vision-related networks, the right postcentral cortex of the visuospatial network, the left thalamus region of the salience network, the left calcarine region of the fronto-occipital network and fronto-parieto-occipital network. Compared to HCs and CHR individuals, ESZ patients showed both increasing and decreasing connectivity, mainly hypo-connectivity involving 15% of the altered voxels from four INs. The left supplementary motor area from the sensory-motor network and the right inferior occipital gyrus in the vision-related network showed a common abnormality in CHR and ESZ groups. Some brain regions also showed a CHR-unique alteration (primarily the CHR-increasing connectivity). In summary, CHR individuals generally showed intermediate connectivity between HCs and ESZ patients across multiple INs, suggesting that some dysconnectivity patterns evident in ESZ predate psychosis in attenuated form during the psychosis risk stage. Hence, these connectivity measures may serve as possible biomarkers to predict schizophrenia progression

Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for regulation of foetal development, tissue differentiation and homeostasis, and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease specific bone metastasis

Non-Gaussianity in the Weak Lensing Correlation Function Likelihood -- Implications for Cosmological Parameter Biases

We study the significance of non-Gaussianity in the likelihood of weak lensing shear two-point correlation functions, detecting significantly non-zero skewness and kurtosis in one-dimensional marginal distributions of shear two-point correlation functions in simulated weak lensing data. We examine the implications in the context of future surveys, in particular LSST, with derivations of how the non-Gaussianity scales with survey area. We show that there is no significant bias in one-dimensional posteriors of $\Omega_{\rm m}$ and $\sigma_{\rm 8}$ due to the non-Gaussian likelihood distributions of shear correlations functions using the mock data ($100$ deg$^{2}$). We also present a systematic approach to constructing approximate multivariate likelihoods with one-dimensional parametric functions by assuming independence or more flexible non-parametric multivariate methods after decorrelating the data points using principal component analysis (PCA). While the use of PCA does not modify the non-Gaussianity of the multivariate likelihood, we find empirically that the one-dimensional marginal sampling distributions of the PCA components exhibit less skewness and kurtosis than the original shear correlation functions.Modeling the likelihood with marginal parametric functions based on the assumption of independence between PCA components thus gives a lower limit for the biases. We further demonstrate that the difference in cosmological parameter constraints between the multivariate Gaussian likelihood model and more complex non-Gaussian likelihood models would be even smaller for an LSST-like survey. In addition, the PCA approach automatically serves as a data compression method, enabling the retention of the majority of the cosmological information while reducing the dimensionality of the data vector by a factor of $\sim$5.Comment: 16 pages, 10 figures, published MNRA

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative.

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation

Investigation of ammonium diuranate calcination with high temperature X-ray diffraction

The thermal decomposition of ammonium diuranate (ADU) in air is investigated using in-situ high-temperature x-ray diffraction (HT-XRD), thermogravimetry, and differential thermal analysis (TG/DTA). Data have been collected in the temperature range from 30 to 1000 °C, allowing to observe the sequence of phase transformations and to assess the energy changes involved in the calcination of ADU. The starting material 2UO3•NH3•3H2O undergoes a process involving several endothermic and exothermic reactions. In situ HT-XRD shows that amorphous UO3 is obtained after achieving complete dehydration at 300 °C, and denitration at about 450 °C. After cooling from heat treatment at 600 °C, a crystalline UO3 phase appears, as displayed by ex-situ XRD. The self-reduction of UO3 into orthorhombic U3O8 takes place at about 600 °C, but a long heat treatment or higher temperature is required to stabilize the structure of U3O8 at room temperature. U3O8 remains stable in air up to 850 °C. Above this temperature, oxygen losses lead to the formation of U3O8-x, as demonstrated by subtle changes in the diffraction pattern and by a mass loss recorded by TGA.JRC.E.6-Actinide researc

Female Sex Development and Reproductive Duct Formation Depend on Wnt4a in Zebrafish.

In laboratory strains of zebrafish, sex determination occurs in the absence of a typical sex chromosome and it is not known what regulates the proportion of animals that develop as males or females. Many sex determination and gonad differentiation genes that act downstream of a sex chromosome are well conserved among vertebrates, but studies that test their contribution to this process have mostly been limited to mammalian models. In mammals, WNT4 is a signaling ligand that is essential for ovary and Müllerian duct development, where it antagonizes the male-promoting FGF9 signal. Wnt4 is well conserved across all vertebrates, but it is not known if Wnt4 plays a role in sex determination and/or the differentiation of sex organs in nonmammalian vertebrates. This question is especially interesting in teleosts, such as zebrafish, because they lack an Fgf9 ortholog. Here we show that wnt4a is the ortholog of mammalian Wnt4, and that wnt4b was present in the last common ancestor of humans and zebrafish, but was lost in mammals. We show that wnt4a loss-of-function mutants develop predominantly as males and conclude that wnt4a activity promotes female sex determination and/or differentiation in zebrafish. Additionally, both male and female wnt4a mutants are sterile due to defects in reproductive duct development. Together these results strongly argue that Wnt4a is a conserved regulator of female sex determination and reproductive duct development in mammalian and nonmammalian vertebrates

Constraints on the relationship between stellar mass and halo mass at low and high redshift

We use a statistical approach to determine the relationship between the stellar masses of galaxies and the masses of the dark matter halos in which they reside. We obtain a parameterized stellar-to-halo mass (SHM) relation by populating halos and subhalos in an N-body simulation with galaxies and requiring that the observed stellar mass function be reproduced. We find good agreement with constraints from galaxy-galaxy lensing and predictions of semi-analytic models. Using this mapping, and the positions of the halos and subhalos obtained from the simulation, we find that our model predictions for the galaxy two-point correlation function (CF) as a function of stellar mass are in excellent agreement with the observed clustering properties in the SDSS at z=0. We show that the clustering data do not provide additional strong constraints on the SHM function and conclude that our model can therefore predict clustering as a function of stellar mass. We compute the conditional mass function, which yields the average number of galaxies with stellar masses in the range [m, m+dm] that reside in a halo of mass M. We study the redshift dependence of the SHM relation and show that, for low mass halos, the SHM ratio is lower at higher redshift. The derived SHM relation is used to predict the stellar mass dependent galaxy CF and bias at high redshift. Our model predicts that not only are massive galaxies more biased than low mass ones at all redshifts, but the bias increases more rapidly with increasing redshift for massive galaxies than for low mass ones. We present convenient fitting functions for the SHM relation as a function of redshift, the conditional mass function, and the bias as a function of stellar mass and redshift.Comment: 21 pages, 17 figures, discussion enlarged, one more figure, updated references, accepted for publication in Ap