School-Based Mental Health Services and Programs: A Review of the Literature

In Chapter 1, a rationale, a statement regarding the focus of my paper, and historical backgrounds of both community-based mental health services and the history surrounding school-based mental health (SBMH) services were provided. In Chapter 2, I review 15 studies dated between 2003 and 2017 addressing the results of school-based mental health programs involving either an in-school parental component or services delivered by clinicians in school settings and the implications SBMH presents for the educational system and its personnel. Studies reviewed are summarized in chronological order and include both quantitative data pertaining to changes in behavioral and academic qualities in children and adolescents deemed “at risk” or diagnosed with mental health disorders, as well as qualitative input related to factors contributing to the success of school-based interventions. In the final chapter, I summarize my findings and provide my conclusions and recommendations for future research

Transport activity and presence of ClC-7/Ostm1 complex account for different cellular functions

Loss of the lysosomal ClC-7/Ostm1 2Cl(-)/H(+) exchanger causes lysosomal storage disease and osteopetrosis in humans and additionally changes fur colour in mice. Its conversion into a Cl(-) conductance in Clcn7(unc/unc) mice entails similarly severe lysosomal storage, but less severe osteopetrosis and no change in fur colour. To elucidate the basis for these phenotypical differences, we generated Clcn7(td/td) mice expressing an ion transport-deficient mutant. Their osteopetrosis was as severe as in Clcn7(-/-) mice, suggesting that the electric shunt provided by ClC-7(unc) can partially rescue osteoclast function. The normal coat colour of Clcn7(td/td) mice and their less severe neurodegeneration suggested that the ClC-7 protein, even when lacking measurable ion transport activity, is sufficient for hair pigmentation and that the conductance of ClC-7(unc) is harmful for neurons. Our in vivo structure-function analysis of ClC-7 reveals that both protein-protein interactions and ion transport must be considered in the pathogenesis of ClC-7-related diseases

Differential atom interferometry beyond the standard quantum limit

We analyze methods to go beyond the standard quantum limit for a class of atomic interferometers, where the quantity of interest is the difference of phase shifts obtained by two independent atomic ensembles. An example is given by an atomic Sagnac interferometer, where for two ensembles propagating in opposite directions in the interferometer this phase difference encodes the angular velocity of the experimental setup. We discuss methods of squeezing separately or jointly observables of the two atomic ensembles, and compare in detail advantages and drawbacks of such schemes. In particular we show that the method of joint squeezing may improve the variance by up to a factor of 2. We take into account fluctuations of the number of atoms in both the preparation and the measurement stage, and obtain bounds on the difference of the numbers of atoms in the two ensembles, as well as on the detection efficiency, which have to be fulfilled in order to surpass the standard quantum limit. Under realistic conditions, the performance of both schemes can be improved significantly by reading out the phase difference via a quantum non-demolition (QND) measurement. Finally, we discuss a scheme using macroscopically entangled ensembles.Comment: 10 pages, 5 figures; eq. (3) corrected and other minor change

Cell-specific responses to the cytokine TGFβ are determined by variability in protein levels

The cytokine TGFβ provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFβ are involved in severe human diseases. To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time-resolved measurements of pathway activation at the single-cell level. We established dynamic time warping to quantitatively compare signaling dynamics of thousands of individual cells and described heterogeneous single-cell responses by mathematical modeling. Our combined experimental and theoretical study revealed that the response to a given dose of TGFβ is determined cell specifically by the levels of defined signaling proteins. This heterogeneity in signaling protein expression leads to decomposition of cells into classes with qualitatively distinct signaling dynamics and phenotypic outcome. Negative feedback regulators promote heterogeneous signaling, as a SMAD7 knock-out specifically affected the signal duration in a subpopulation of cells. Taken together, we propose a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity

Contested firm governance, institutions and the undertaking of corporate restructuring practices in Germany

This article investigates the undertaking of corporate restructuring practices (employee downsizing and wage moderation) in Germany from 2008 to 2015. The article presents a political perspective that draws on the insights of the power resources approach and of institutional analyses. The theoretical framework highlights how institutional arrangements structure power relations within companies by empowering, in an asymmetrical manner, different categories of firm stakeholders (employees, managers and shareholders) as well as shaping how they relate to each other in an interactive manner. The article’s empirical findings point to the importance of extensive, but contingent, corporate restructuring in Germany. Companies are more likely to implement ‘defensive’ corporate restructuring practices under conditions of high leverage/debt than when confronted by shareholder value driven investors, thereby reflecting the presence of overlapping interests between employees and managers

Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated Topoisomerase I to promote genome stability

Peer reviewedPublisher PD

A Synthetic Chloride Channel Restores Chloride Conductance in Human Cystic Fibrosis Epithelial Cells

Mutations in the gene-encoding cystic fibrosis transmembrane conductance regulator (CFTR) cause defective transepithelial transport of chloride (Cl−) ions and fluid, thereby becoming responsible for the onset of cystic fibrosis (CF). One strategy to reduce the pathophysiology associated with CF is to increase Cl− transport through alternative pathways. In this paper, we demonstrate that a small synthetic molecule which forms Cl− channels to mediate Cl− transport across lipid bilayer membranes is capable of restoring Cl− permeability in human CF epithelial cells; as a result, it has the potential to become a lead compound for the treatment of human diseases associated with Cl− channel dysfunction

A Cytoplasmic Domain Mutation in ClC-Kb Affects Long-Distance Communication Across the Membrane

BACKGROUND: ClC-Kb and ClC-Ka are homologous chloride channels that facilitate chloride homeostasis in the kidney and inner ear. Disruption of ClC-Kb leads to Bartter's Syndrome, a kidney disease. A point mutation in ClC-Kb, R538P, linked to Bartter's Syndrome and located in the C-terminal cytoplasmic domain was hypothesized to alter electrophysiological properties due to its proximity to an important membrane-embedded helix. METHODOLOGY/PRINCIPAL FINDINGS: Two-electrode voltage clamp experiments were used to examine the electrophysiological properties of the mutation R538P in both ClC-Kb and ClC-Ka. R538P selectively abolishes extracellular calcium activation of ClC-Kb but not ClC-Ka. In attempting to determine the reason for this specificity, we hypothesized that the ClC-Kb C-terminal domain had either a different oligomeric status or dimerization interface than that of ClC-Ka, for which a crystal structure has been published. We purified a recombinant protein corresponding to the ClC-Kb C-terminal domain and used multi-angle light scattering together with a cysteine-crosslinking approach to show that the dimerization interface is conserved between the ClC-Kb and ClC-Ka C-terminal domains, despite the fact that there are several differences in the amino acids that occur at this interface. CONCLUSIONS: The R538P mutation in ClC-Kb, which leads to Bartter's Syndrome, abolishes calcium activation of the channel. This suggests that a significant conformational change--ranging from the cytoplasmic side of the protein to the extracellular side of the protein--is involved in the Ca(2+)-activation process for ClC-Kb, and shows that the cytoplasmic domain is important for the channel's electrophysiological properties. In the highly similar ClC-Ka (90% identical), the R538P mutation does not affect activation by extracellular Ca(2+). This selective outcome indicates that ClC-Ka and ClC-Kb differ in how conformational changes are translated to the extracellular domain, despite the fact that the cytoplasmic domains share the same quaternary structure