Potentiating effect of heparin in the activation of procollagenase by a low-Mr angiogenesis factor

AbstractA low-Mr freely dialysable endothelial cell-stimulating angiogenesis factor (ESAF) from conditioned medium of a mouse lymphoma cell line has previously been shown to activate latent skin fibroblast procollagenase. Activation comparable with the maximum that can be achieved with trypsin is obtained with chemically undetectable amounts of the factor. We now show that when even smaller amounts of ESAF are used heparin is able to potentiate its action in this system. The relationship between this activity and the mechanism of angiogenesis, which is itself potentiated by heparin, is discussed

Genome-wide Linkage Scan to Identify Loci for Age at First Cigarette in Dutch Sibling Pairs

Most smokers begin smoking during adolescence and early age of smoking initiation is related to more frequent current smoking, daily smoking and more dependent smoking (Everret et al., 1999; Lando et al.

Measuring Resilience in Adult Women Using the 10-Items Connor-Davidson Resilience Scale (CD-RISC). Role of Trauma Exposure and Anxiety Disorders

International audiencePURPOSE: Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience. METHODS: We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory). RESULTS: Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21-0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44-7.01]). CONCLUSION: Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a "vaccination" effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations

Phenotypic Consequences of Copy Number Variation: Insights from Smith-Magenis and Potocki-Lupski Syndrome Mouse Models

The characterization of mice with different number of copies of the same genomic segment shows that structural changes influence the phenotypic outcome independently of gene dosage

Eyes wide open: perceived exploitation and its consequences

Drawing on the array of literature on exploitation from several social science disciplines, we propose a new way of seeing employer-employee relationships by introducing the concept of perceived exploitative employee-organization relationships, distinguish it from related concepts, and conduct five studies to develop a scale and test our theoretical model of the effects of such employee perceptions. Contributing to the Employee-Organization Relationships and workplace emotions literatures, perceived exploitation is defined as employees’ perceptions that they have been purposefully taken advantage of in their relationship with the organization, to the benefit of the organization itself. We propose and find that such perceptions are associated with both outward-focused emotions of anger and hostility toward the organization and inward-focused ones of shame and guilt at remaining in an exploitative job. In two studies including construction workers and a time-lagged study of medical residents, we find that the emotions of anger and hostility partially mediate the effects of perceived exploitation on employee engagement, revenge against the organization, organizational commitment, and turnover intentions, whereas the emotions of shame and guilt partially mediate the effects of perceived exploitation on employee burnout, silence, and psychological withdrawal

SAMSN1 is a tumor suppressor gene in multiple myeloma

Multiple myeloma (MM), a hematological malignancy characterized by the clonal growth of malignant plasma cells (PCs) in the bone marrow, is preceded by the benign asymptomatic condition, monoclonal gammopathy of undetermined significance (MGUS). Several genetic abnormalities have been identified as critical for the development of MM; however, a number of these abnormalities are also found in patients with MGUS, indicating that there are other, as yet unidentified, factors that contribute to the onset ofMMdisease. In this study, we identify a Samsn1 gene deletion in the 5TGM1/C57BL/KaLwRij murine model of myeloma. In addition, SAMSN1 expression is reduced in the malignant CD138+ PCs of patients with MM and this reduced expression correlates to total PC burden. We identify promoter methylation as a potential mechanismthrough which SAMSN1 expression is modulated in human myeloma cell lines.Notably, re-expression of Samsn1 in the 5TGM1murinePCline resulted in complete inhibition ofMMdisease development in vivo and decreased proliferation in stromal cell–PC co-cultures in vitro. This is the first study to identify deletion of a key gene in the C57BL/KaLwRij mice that also displays reduced gene expression in patients withMMand is therefore likely to play an integral role in MM disease development.Jacqueline E. Noll, Duncan R. Hewett, Sharon A. Williams, Kate Vandyke, Chung Kok, Luen B. To, and Andrew C.W. Zannettin

Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe