Designer Reagents for Mass Spectrometry-Based Proteomics: Clickable Cross-Linkers for Elucidation of Protein Structures and Interactions

We present novel homobifunctional amine-reactive clickable cross-linkers (CXLs) for investigation of three-dimensional protein structures and protein–protein interactions (PPIs). CXLs afford consolidated advantages not previously available in a simple cross-linker, including (1) their small size and cationic nature at physiological pH, resulting in good water solubility and cell-permeability, (2) an alkyne group for bio-orthogonal conjugation to affinity tags via the click reaction for enrichment of cross-linked peptides, (3) a nucleophilic displacement reaction involving the 1,2,3-triazole ring formed in the click reaction, yielding a lock-mass reporter ion for only clicked peptides, and (4) higher charge states of cross-linked peptides in the gas-phase for augmented electron transfer dissociation (ETD) yields. Ubiquitin, a lysine-abundant protein, is used as a model system to demonstrate structural studies using CXLs. To validate the sensitivity of our approach, biotin-azide labeling and subsequent enrichment of cross-linked peptides are performed for cross-linked ubiquitin digests mixed with yeast cell lysates. Cross-linked peptides are detected and identified by collision induced dissociation (CID) and ETD with linear quadrupole ion trap (LTQ)-Fourier transform ion cyclotron resonance (FTICR) and LTQ-Orbitrap mass spectrometers. The application of CXLs to more complex systems (e.g., in vivo cross-linking) is illustrated by Western blot detection of Cul1 complexes including known binders, Cand1 and Skp2, in HEK 293 cells, confirming good water solubility and cell-permeability

Bullying behaviours and other conduct problems: longitudinal investigation of their independent associations with risk factors and later outcomes

Purpose Bullying behaviours and other conduct problems often co-occur. However, we do not yet know whether bullying behaviours are associated with early factors and later poor outcomes independently of conduct problems. While there are difering, specifc interventions for bullying behaviours and for conduct problems, it is unclear if such specifcity is justifed given parallels between both behaviours. Methods We used prospective data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative sample of 2232 children. Mothers and teachers reported on children’s bullying behaviours and conduct problems at ages 7 and 10. We collected measures of risk factors, including temperament and family factors, when children were age 5. We assessed behavioural, emotional, educational and social problems when participants reached the ages of 12 and 18. Results Bullying behaviours and conduct problems co-occurred in childhood. Our fndings indicated that bullying behaviours and other conduct problems were independently associated with the same risk factors. Furthermore, they were associated with the same poor outcomes at both ages 12 and 18. Despite this, bullying behaviours were uniquely associated with behavioural, emotional, educational and social problems at age 18. Conclusions Our fndings suggest that anti-bullying programmes and interventions aimed at reducing conduct problems could beneft from greater integration. Furthermore, our study highlights the mental health problems children who bully may face in later years and the need to consider those in intervention plans

Estimating evaporation from a wet grassland

International audienceWet grasslands are being restored across the UK and Europe to reinstate their high biodiversity following over 50 years of drainage and conversion to arable agriculture. The water balance of many wet grasslands is dominated by precipitation and evaporation and it is essential to quantify evaporation rates to understand the hydrological functioning of wetlands and the implications for water resources in catchments where wetlands are being restored. This paper considers data from direct measurements of evaporation from the Pevensey Levels wet grassland using the eddy correlation method. Equations are derived to predict actual evaporation using meteorological data on the site or from standard meteorological station observations. It was found that evaporation could be estimated reliably from meteorological variables, such as wind speed, temperature and humidity and by water availability. It was also found that when water availability is high, evaporation is high and may exceed reference evaporation values, raising questions over the deployment of the two-step Penman-Monteith model unless reliable crop coefficients and relative evaporation figures can be determined

The AMSC mobile satellite system

The American Mobile Satellite Consortium (AMSC) Mobile Satellite Service (MSS) system is described. AMSC will use three multi-beam satellites to provide L-band MSS coverage to the United States, Canada and Mexico. The AMSC MSS system will have several noteworthy features, including a priority assignment processor that will ensure preemptive access to emergency services, a flexible SCPC channel scheme that will support a wide diversity of services, enlarged system capacity through frequency and orbit reuse, and high effective satellite transmitted power. Each AMSC satellite will make use of 14 MHz (bi-directional) of L-band spectrum. The Ku-band will be used for feeder links

Mobile satellite service in the United States

Mobile satellite service (MSS) has been under development in the United States for more than two decades. The service will soon be provided on a commercial basis by a consortium of eight U.S. companies called the American Mobile Satellite Consortium (AMSC). AMSC will build a three-satellite MSS system that will offer superior performance, reliability and cost effectiveness for organizations requiring mobile communications across the U.S. The development and operation of MSS in North America is being coordinated with Telesat Canada and Mexico. AMSC expects NASA to provide launch services in exchange for capacity on the first AMSC satellite for MSAT-X activities and for government demonstrations

Domestic violence and mental health: a cross-sectional survey of women seeking help from domestic violence support services

Background : Domestic violence and abuse (DVA) are associated with an increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. Objective : To characterize the demography and mental health of women who access specialist DVA services in the United Kingdom and to investigate associations between severity of abuse and measures of mental health and health state utility, accounting for important confounders and moderators. Design : Baseline data on 260 women enrolled in a randomized controlled trial of a psychological intervention for DVA survivors was analyzed. We report prevalence of and associations between mental health status and severity of abuse at the time of recruitment. We used logistic and normal regression models for binary and continuous outcomes, respectively. Mental health measures used were: Clinical Outcomes in Routine Evaluation–Outcome Measure (CORE-OM), Patient Health Questionnaire, Generalized Anxiety Disorder Assessment, and the Posttraumatic Diagnostic Scale (PDS) to measure posttraumatic stress disorder. The Composite Abuse Scale (CAS) measured abuse. Results : Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70–81%). Depression and anxiety levels were high, with means close to clinical thresholds, and all respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA. Conclusions : Women DVA survivors who seek support from DVA services have recently experienced high levels of abuse, depression, anxiety, and especially PTSD. Clinicians need to be aware that patients presenting with mental health conditions or symptoms of depression or anxiety may be experiencing or may have experienced DVA. The high psychological morbidity in this population means that trauma-informed psychological support is needed for survivors who seek support from DVA services. Keywords : domestic violence and abuse; intimate partner violence; mental health; posttraumatic stress disorder; anxiety; CORE-OM; depression; women; advocacy (Published: 15 October 2014) Citation : Glob Health Action 2014,  7 : 25519 -  http://dx.doi.org/10.3402/gha.v7.25519 SPECIAL ISSUE : This paper is part of the Special Issue:  Intimate Partner Violence and Mental Health . More papers from this issue can be found at  http://www.globalhealthaction.net SUPPLEMENTARY MATERIAL : To access the supplementary material for this article, please see  Supplementary files  under Article Tool

Uterine Mast Cells and Immunoglobulin-E Antibody Responses During Clearance of \u3ci\u3eTritrichomonas foetus\u3c/i\u3e

We showed earlier that Tritrichomonas foetus–specific bovine immunoglobulin (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with clearance of this sexually transmitted infection. Eosinophils have been noted in previous studies of bovine trichomoniasis but the role of mast cells and IgE responses have not been reported. The hypothesis that IgE and mast cell degranulation play a role in clearance was tested in 25 virgin heifers inseminated experimentally and infected intravaginally with T. foetus strain D1 at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks, when tissues were fixed and secretions were collected for culture and antibody analysis. Immunohistochemistry using a monoclonal antibody to a soluble lipophosphoglycan (LPG)–containing surface antigen (TF1.17) demonstrated antigen uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen-positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and IgE T. foetus–specific antibodies increased in uterine secretions at weeks 6 and 9 after infection. This was inversely proportional to subepithelial mast cells numbers and most animals cleared the infection by the sampling time after the lowest mast cell count. Furthermore, soluble antigen was found in uterine epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast cells by antigen and perhaps LPG triggering appears to have resulted in degranulation. Released cytokines may account for production of predominantly Th2 (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the infection

Do elephants feel pain and if so, how do we know this?

The objective of this document is to identify the behavior of the academic international production in urban history, from the bibliographical records index-linked in Scopus between 1973 and 2010. We use bibliometric indicators from SCImago Group, applying them to the production in the field of arts and humanities. Afterward, we corroborate the results obtained with the indicators calculated exclusively for 1.098 records of urban history. A geographical concentration is observed in the mechanisms of diffusion, authors and institutional affiliation. Likewise, we identify that over 50% of the works published between 1973 and 2010 have not been used by other authors to create new knowledge.El propósito de este documento es identificar el comportamiento de la producción académica internacional en historia urbana, a partir de los registros bibliográficos indizados en Scopus entre 1973 y 2010. Para ello se emplean indicadores bibliométricos obtenidos de SCImago Group y aplicados a la producción en el área de artes y humanidades. Posteriormente, se contrastan los resultados obtenidos con los indicadores calculados exclusivamente para 1.098 registros de historia urbana. Se evidencia una concentración geográfica en los medios de difusión de los productos del área, los autores y su filiación. Se identifica también que más del 50% de los trabajos realizados entre 1973 y 2010 no ha sido empleado por otro autor para crear nuevo conocimientoO propósito deste documento é identificar o comportamento da produção acadêmica internacional em história urbana, a partir dos registros bibliográficos indexados em Scopus entre 1973 e 2010. Para isso, empregam-se indicadores bibliométricos obtidos de SCImago Group e aplicados à produção na área de artes e humanidades. Posteriormente, se contrastam os resultados obtidos com os indicadores calculados exclusivamente para 1,098 registros de historia urbana. Evidencia-se uma concentração geográfica nos meios de difusão dos produtos da área, os autores e sua filiação. Identifica-se também que mais do 50% dos trabalhos realizados entre 1973 e 2010 não tem sido empregados por outro autor para criar conhecimento novo