Morc1 knockout evokes a depression-like phenotype in mice

Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress

Toward informatics-enabled preparedness for natural hazards to minimize health impacts of climate change

Natural hazards (NHs) associated with climate change have been increasing in frequency and intensity. These acute events impact humans both directly and through their effects on social and environmental determinants of health. Rather than relying on a fully reactive incident response disposition, it is crucial to ramp up preparedness initiatives for worsening case scenarios. In this perspective, we review the landscape of NH effects for human health and explore the potential of health informatics to address associated challenges, specifically from a preparedness angle. We outline important components in a health informatics agenda for hazard preparedness involving hazard-disease associations, social determinants of health, and hazard forecasting models, and call for novel methods to integrate them toward projecting healthcare needs in the wake of a hazard. We describe potential gaps and barriers in implementing these components and propose some high-level ideas to address them

Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

Mutations of the recombinase Activating Genes 1 and 2 (RAG1, RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment, however high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/- NK cells have a mature phenotype, reduced fitness and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56bright CD16-/int CD57- cells, yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT

Valuing Insect Pollination Services with Cost of Replacement

Value estimates of ecosystem goods and services are useful to justify the allocation of resources towards conservation, but inconclusive estimates risk unsustainable resource allocations. Here we present replacement costs as a more accurate value estimate of insect pollination as an ecosystem service, although this method could also be applied to other services. The importance of insect pollination to agriculture is unequivocal. However, whether this service is largely provided by wild pollinators (genuine ecosystem service) or managed pollinators (commercial service), and which of these requires immediate action amidst reports of pollinator decline, remains contested. If crop pollination is used to argue for biodiversity conservation, clear distinction should be made between values of managed- and wild pollination services. Current methods either under-estimate or over-estimate the pollination service value, and make use of criticised general insect and managed pollinator dependence factors. We apply the theoretical concept of ascribing a value to a service by calculating the cost to replace it, as a novel way of valuing wild and managed pollination services. Adjusted insect and managed pollinator dependence factors were used to estimate the cost of replacing insect- and managed pollination services for the Western Cape deciduous fruit industry of South Africa. Using pollen dusting and hand pollination as suitable replacements, we value pollination services significantly higher than current market prices for commercial pollination, although lower than traditional proportional estimates. The complexity associated with inclusive value estimation of pollination services required several defendable assumptions, but made estimates more inclusive than previous attempts. Consequently this study provides the basis for continued improvement in context specific pollination service value estimates

Einleitung.

L'introduzione offre una panoramica sugli sviluppi del rapporto tra letteratura e musica nel Novecento tedesco

Iron mobilization from crocidolite as enhancer of collagen content in rat lung fibroblasts

Asbestos exposure causes pulmonary fibrosis by mechanisms that remain uncertain. There is increasing evidence that iron from asbestos is responsible for many of its effects. In this paper, we investigated the effect of iron mobilized from crocidolite asbestos on collagen content in rat lung fibroblast cultures under serum-free conditions. Crocidolite (2, 4, 6 microg/cm2 well) increased collagen content in a dose-dependent manner (+42 +/- 8, +92 +/- 10, and +129 +/- 13% vs controls). This effect was specific for collagen, since it did not alter total protein content and was inhibited by the iron chelator deferoxamine (DFO). Preincubation of crocidolite with citrate (1 mM) for 48 hr resulted in iron mobilization (51 microM) and increased collagen production (>3-fold) in treated cells. These effects occurred without the intervention of serum factors. The absence of cell damage, proliferation or lipid peroxidation leads to the supposition that iron from crocidolite per se may act as a profibrogenic agent. Although the in vivo participation of other cells and factors cannot be excluded, we conclude that iron released from crocidolite plays a role in collagen increase occurring during asbestosis

An elastolytic proteinase from rabbit leukocytes: purification and partial characterization.

A proteinase with elastolytic activity was isolated from granules of rabbit bloodstream leukocytes, and purified to apparent homogeneity by a multi-step procedure consisting of ammonium sulfate precipitation, batch fractionation on DEAE-Sephadex A-50, and finally by preparative isoelectric focusing (IEF) on Sephadex G-75 Superfine. The molecule weight of the enzyme, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 28,500. This enzyme shows an isoelectric point at pH 9.0. The proteinase is active against natural elastins as well as toward Suc-(Ala)3-NA, Methoxy-Suc-(Ala)2-Pro-Val-NA, and (to a lesser extent) against Suc-(Ala)2-Pro-Leu-NA and Boc-Ala-ONp. The inhibition profile of the isolated enzyme indicates that rabbit granulocyte elastase belongs to the group of serine proteinases. Inhibition by some natural proteinase inhibitors is also observed. Unlike other mammalian elastases, it is insensitive to elastatinal

Collagen breakdown products and lung collagen metabolism: an in vitro study on fibroblast cultures.

In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connective tissue components, including collagen. It has therefore been hypothesised that products of collagen degradation may have a role in the promotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degradation products in experimental animals stimulated collagen synthesis leading to increased collagen deposition and diffuse interstitial lung disease. Rabbit and human fibroblast cultures from lung and skin were used as an in vitro model to study the responses of these cells to rabbit collagen degradation products. The effects of an acute exposure to collagen degradation products on synthesis of collagen and noncollagenous protein have been studied in confluent cultures by [3H]-proline incorporation. The effects of collagen degradation products on fibroblast proliferation and production of genetic types of collagen have also been investigated. The acute exposure of rabbit lung fibroblast cultures to collagen degradation products significantly increased collagen synthesis without affecting non-collagenous protein synthesis. This effect was dose related, specific for lung fibroblasts, and species specific. Collagen degradation products altered the rate of synthesis of genetic types of collagen with a consequent decrease of type III/I+III collagen ratio (0.26 (0.04) treated with collagen degradation products; 0.45 (0.02) controls). These effects occurred without the intervention of serum factors. In addition, collagen degradation products neither affected fibroblast proliferation nor selected specific clones emphasising one type of collagen. These results suggest that collagen degradation products can influence lung collagen metabolism by stimulating collagen synthesis. The regulation of collagen mass by collagen degradation products may be of importance in lung collagen homeostasis in vivo

Collagen breakdown products and lung collagen metabolism: an in vitro study on fibroblast cultures.

BACKGROUND--In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connective tissue components, including collagen. It has therefore been hypothesised that products of collagen degradation may have a role in the promotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degradation products in experimental animals stimulated collagen synthesis leading to increased collagen deposition and diffuse interstitial lung disease. METHODS--Rabbit and human fibroblast cultures from lung and skin were used as an in vitro model to study the responses of these cells to rabbit collagen degradation products. The effects of an acute exposure to collagen degradation products on synthesis of collagen and noncollagenous protein have been studied in confluent cultures by [3H]-proline incorporation. The effects of collagen degradation products on fibroblast proliferation and production of genetic types of collagen have also been investigated. RESULTS--The acute exposure of rabbit lung fibroblast cultures to collagen degradation products significantly increased collagen synthesis without affecting non-collagenous protein synthesis. This effect was dose related, specific for lung fibroblasts, and species specific. Collagen degradation products altered the rate of synthesis of genetic types of collagen with a consequent decrease of type III/I+III collagen ratio (0.26 (0.04) treated with collagen degradation products; 0.45 (0.02) controls). These effects occurred without the intervention of serum factors. In addition, collagen degradation products neither affected fibroblast proliferation nor selected specific clones emphasising one type of collagen. CONCLUSIONS--These results suggest that collagen degradation products can influence lung collagen metabolism by stimulating collagen synthesis. The regulation of collagen mass by collagen degradation products may be of importance in lung collagen homeostasis in vivo