The complex role of the chemokine CX3CL1/Fractalkine in major depressive disorder:A narrative review of preclinical and clinical studies

Evidence suggests that neuroinflammation exhibits a dual role in the pathogenesis of major depressive disorder (MDD), both potentiating the onset of depressive symptoms and developing as a consequence of them. Our narrative review focuses on the role of the chemokine fractalkine (FKN) (also known as CX3CL1), which has gained increasing interest for its ability to induce changes to microglial phenotypes through interaction with its corresponding receptor (CX3CR1) that may impact neurophysiological processes relevant to MDD. Despite this, there is a lack of a clear understanding of the role of FKN in MDD. Overall, our review of the literature shows the involvement of FKN in MDD, both in preclinical models of depression, and in clinical studies of depressed patients. Preclinical studies (N = 8) seem to point towards two alternative hypotheses for FKN's role in MDD: a) FKN may drive pro-inflammatory changes to microglia that contribute towards MDD pathogenesis; or b) FKN may inhibit pro-inflammatory changes to microglia, thereby exerting a protective effect against MDD pathogenesis. Evidence for a) primarily derives from preclinical chronic stress models of depression in mice, whereas for b) from preclinical inflammation models of depression. Whereas, in humans, clinical studies (N = 4) consistently showed a positive association between FKN and presence of MDD, however it is not clear whether FKN is driving or moderating MDD pathogenesis. Future studies should aim for larger and more controlled clinical cohorts, in order to advance our understanding of FKN role both in the context of stress and/or inflammation.</p

Biophysical assay for tethered signaling reactions reveals tether-controlled activity for the phosphatase SHP-1

Tethered enzymatic reactions are ubiquitous in signaling networks but are poorly understood. A previously unreported mathematical analysis is established for tethered signaling reactions in surface plasmon resonance (SPR). Applying the method to the phosphatase SHP-1 interacting with a phosphorylated tether corresponding to an immune receptor cytoplasmic tail provides five biophysical/biochemical constants from a single SPR experiment: two binding rates, two catalytic rates, and a reach parameter. Tether binding increases the activity of SHP-1 by 900-fold through a binding-induced allosteric activation (20-fold) and a more significant increase in local substrate concentration (45-fold). The reach parameter indicates that this local substrate concentration is exquisitely sensitive to receptor clustering. We further show that truncation of the tether leads not only to a lower reach but also to lower binding and catalysis. This work establishes a new framework for studying tethered signaling processes and highlights the tether as a control parameter in clustered receptor signaling

Libri novi

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43281/1/11046_2005_Article_BF02052587.pd

The IntAct molecular interaction database in 2012

IntAct is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. Two levels of curation are now available within the database, with both IMEx-level annotation and less detailed MIMIx-compatible entries currently supported. As from September 2011, IntAct contains approximately 275 000 curated binary interaction evidences from over 5000 publications. The IntAct website has been improved to enhance the search process and in particular the graphical display of the results. New data download formats are also available, which will facilitate the inclusion of IntAct's data in the Semantic Web. IntAct is an active contributor to the IMEx consortium (http://www.imexconsortium.org). IntAct source code and data are freely available at http://www.ebi.ac.uk/intac

Perceptions of the crowded sky as assessed through response to aerial infrastructure

Ever increasing numbers of wind turbines, communication towers, power lines, and aerial vehicles are clear evidence of our growing reliance on infrastructure in the lower aerosphere. As this infrastructure expands, it is important to understand public perceptions of an increasingly crowded sky. To gauge tolerance for aerial crowding, 251 participants from across the US completed a survey where they rated tolerance for a series of aerial infrastructure images (i.e., towers, turbines, and airborne vehicles) in four landscapes with varying degrees of pre-existing ground-level infrastructure that approximated rural, suburban, and urban settings. We predicted lower tolerance for aerial infrastructure 1) in more natural scenes and 2) among rural residents. In general, participants preferred an open aesthetic with relatively little aerial infrastructure across all landscape types. No clear association was found between infrastructure tolerance and natural scenes nor rural residency, with participants slightly less tolerant of infrastructure in the suburban scene. Tolerance scores were generally similar across age, income levels, and political affiliations. Women indicated less crowding tolerance than men, with this effect driven by a disproportionate number of women with zero tolerance for aerial infrastructure. African Americans and Asians had higher tolerance scores than other racial/ethnic groups, but these trends may have been affected by low sample sizes of non-white participants. Our survey revealed fewer differences in crowding tolerance across demographic groups than might be expected given widely reported political and geographic polarization in the U.S. Attitudes toward aerial infrastructure were varied with few associations with demographic parameters suggesting that public opinion has not yet solidified with regard to this issue, making possible opportunities for consensus building with regard to responsible development of aerial infrastructure

A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by theUnited StatesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Perceptions of HIV self-testing promotion in black barbershop businesses: implications for equitable engagement of black-owned small businesses for public health programs

Background: HIV self-testing (HIVST) offers an innovative and promising approach to increasing HIV testing among Black men in the United States, a population disproportionately affected by HIV. However, engaging Black men in traditional HIV prevention programs has been challenging due to stigma, medical mistrust, and limited access to preventive health services. This formative qualitative study aimed to explore the potential of utilizing barbershops as an example of a nontraditional healthcare venue to promote and distribute HIVST. Methods: Four virtual focus group discussions (FGDs) consisting of 19 participants in North Carolina were conducted with Black men, including barbershop business owners, barbers, and their customers, to assess perceptions of HIVST and the acceptability of partnering with barbershop businesses to promote HIVST. FGDs were digitally recorded, transcribed, and analyzed using a deductive coding approach to thematic analysis. Results: Participants reported that the trusting relationship between barbers and their customers, which may not exist between Black men and health care providers, is a facilitator of collaborating with barbershop businesses to reach Black men for HIVST distribution. Participants recommended providing education for barbers on the use of HIVST, as well as how to inform self-testers about linkage to care following HIVST to build the credibility of the barbers in delivering the intervention. Participants also raised the issue of the cost of HIVST to barbershop customers as a potential barrier to implementation, as well as the possibility that the implementation of such interventions could be seen as out of place in a barbershop business venue. Participants also expressed a strong belief that compensation to barbershops and their employees should accompany any intervention. Conclusion: These findings suggest that barbershop business venues may provide an appropriate venue for HIVST promotion and distribution, though factors like cost, training, and incentivization of implementers are necessary to consider in implementation planning. Furthermore, partnerships between public health actors and the business community must be built on equitable engagement to ensure the long-term viability of these critical initiatives

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo