The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study

Gating a single-molecule transistor with individual atoms

Transistors, regardless of their size, rely on electrical gates to control the conductance between source and drain contacts. In atomic-scale transistors, this conductance is sensitive to single electrons hopping via individual orbitals1, 2. Single-electron transport in molecular transistors has been previously studied using top-down approaches to gating, such as lithography and break junctions1, 3, 4, 5, 6, 7, 8, 9, 10, 11. But atomically precise control of the gate—which is crucial to transistor action at the smallest size scales—is not possible with these approaches. Here, we used individual charged atoms, manipulated by a scanning tunnelling microscope12, to create the electrical gates for a single-molecule transistor. This degree of control allowed us to tune the molecule into the regime of sequential single-electron tunnelling, albeit with a conductance gap more than one order of magnitude larger than observed previously8, 11, 13, 14. This unexpected behaviour arises from the existence of two different orientational conformations of the molecule, depending on its charge state. Our results show that strong coupling between these charge and conformational degrees of freedom leads to new behaviour beyond the established picture of single-electron transport in atomic-scale transistors

NF-kappaB mediates the survival of human bronchial epithelial cells exposed to cigarette smoke extract

Background: We have previously reported that low concentrations of cigarette smoke extract induce DNA damage without leading to apoptosis or necrosis in human bronchial epithelial cells (HBECs), and that IL-6/STAT3 signaling contributes to the cell survival. Since NF-kappa B is also involved in regulating apoptosis and cell survival, the current study was designed to investigate the role of NF-kappa B in mediating cell survival in response to cigarette smoke exposure in HBECs. Methods: Both the pharmacologic inhibitor of NF-kappa B, curcumin, and RNA interference targeting p65 were used to block NF-kappa B signaling in HBECs. Apoptosis and cell survival were then assessed by various methods including COMET assay, LIVE/DEAD Cytotoxicity/Viability assay and colony formation assay. Results: Cigarette smoke extract (CSE) caused DNA damage and cell cycle arrest in S phase without leading to apoptosis in HBECs as evidenced by TUNEL assay, COMET assay and DNA content assay. CSE stimulated NF-kappa B -DNA binding activity and up-regulated Bcl-XL protein in HBECs. Inhibition of NF-kappa B by the pharmacologic inhibitor curcumin (20 mu M) or suppression of p65 by siRNA resulted in a significant increase in cell death in response to cigarette smoke exposure. Furthermore, cells lacking p65 were incapable of forming cellular colonies when these cells were exposed to CSE, while they behaved normally in the regular culture medium. Conclusion: The current study demonstrates that CSE activates NF-kappa B and up-regulates Bcl-XL through NF-kappa B activation in HBECs, and that CSE induces cell death in cells lacking p65. These results suggest that activation of NF-kappa B regulates cell survival following DNA damage by cigarette smoke in human bronchial epithelial cells.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000260432600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Respiratory SystemSCI(E)28ARTICLEnull

Technology transfer offices as boundary spanners in the pre-spin-off process: the case of a hybrid model

Over the past decades, universities have increasingly become ambidextrous organizations reconciling scientific and commercial missions. In order to manage this ambidexterity, technology transfer offices (TTOs) were established in most universities. This paper studies a specific, often implemented, but rather understudied type of TTO, namely a hybrid TTO model uniting centralized and decentralized levels. Employing a qualitative research design, we examine how and why the two TTO levels engage in diverse boundary spanning activities to help nascent spin-off companies move through the pre-spin-off process. Our research identifies differences in the types of boundary spanning activities that centralized and decentralized TTOs perform and in the parties they engage with. We find geographical, technological and organizational proximity to be important antecedents of the TTOs’ engagement in external and internal boundary spanning activities. These results have important implications for both academics and practitioners interested in university technology transfer through spin-off creation

Results from the implementation of aid effectiveness principles in the health sector in Mali

The international community holds high expectations for aid producing demonstrable results in the health sector, at the global and developing country levels. Yet, measuring the effectiveness of aid presents methodological challenges. Existing evaluation frameworks are not sufficiently geared toward learning whether and how practices have changed. We present a framework for measuring the results of implementing aid effectiveness principles at three levels: implementation process, health system strengthening, and outcomes/impact. We developed this framework in the context of monitoring results on the effectiveness of the aid agenda in the health sector in Mali. Despite some changes in behavior that resulted in increased aid effectiveness and improved results at system and outcome levels, overall, the aid effectiveness principles have not been fully implemented. Thus expectations in terms of health outcomes should be realistic.GRAP-PA Sant

A guideline for the annotation of UTR regulatory elements in the UTRsite collection

Gene expression regulatory elements are scattered in gene promoters and pre-mRNAs. In particular, RNA elements lying in untranslated regions (5' and 3'UTRs) are poorly studied because of their peculiar features (i.e., a combination of primary and secondary structure elements) which also pose remarkable computational challenges. Several years ago, we began collecting experimentally characterized UTR regulatory elements, developing the specialized database UTRsite. This paper describes the detailed guidelines to annotate cis-regulatory elements in 5' and 3' UnTranslated Regions (UTRs) by computational analyses, retracing all main steps used by UTRsite curators