Postpartum administration of Citalopram reverses gestational stress-induced depressive-like behavior and structural modifications in the reward pathway

Postpartum depression (PPD) is a common complication following childbirth experienced by approximately 20% of new mothers. We have previously shown that chronic gestational stress, a risk factor for PPD, induces depressive-like behavior in postpartum rats and impairs maternal care, a rewarding, motivated behavior. These behavioral consequences of gestational stress are accompanied by structural changes on neurons in the nucleus accumbens (NAc), a key brain region in the reward pathway which is involved in maternal care and which has been implicated in PPD. Here, we extended our previous work in two experiments. First, we examined the effects of gestational stress on other reward-related behaviors known to be altered in mothers with postpartum depression including anhedonia (as assessed with the sucrose preference test) and maternal motivation (as assessed with the conditioned place preference paradigm). Second, because mothers diagnosed with PPD are often prescribed selective serotonin reuptake inhibitors (SSRI) antidepressants to ameliorate mood and other deleterious effects of PPD, we investigated the extent to which the SSRI Citalopram could reverse stress-induced depressive-like behavior and morphological changes in the NAc. Our results show that along with increased depressive-like behavior, postpartum females exposed to chronic stress during pregnancy (from GD7-GD20) exhibited anhedonia, deficits in maternal motivation as well as structural modifications in the NAc. We also found that postpartum administration of Citalopram was able to reverse the depressive-like behavior and the structural modifications in the NAc of gestationally stressed mothers. Overall, our results demonstrate that gestational stress induces numerous behavioral symptoms found in depressed mothers and that depressive-like behavior in gestationally stressed mothers is responsive to antidepressant treatment. In doing so, these results expand the validity of our gestational stress model and suggest that structural plasticity in the NAc pathway may play a critical role in mediating depressive-like behavior in PPD.No embargoAcademic Major: Neuroscienc

Exposure to hypoxia rapidly induces mitochondrial channel activity within a living synapse

Author Posting. © American Society for Biochemistry and Molecular Biology, 2005. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 280 (2005): 4491-4497, doi:10.1074/jbc.M410661200.One of the earliest effects of hypoxia on neuronal function is to produce a run-down of synaptic transmission, and more prolonged hypoxia results in neuronal death. An increase in the permeability of the outer mitochondrial membrane, controlled by BCL-2 family proteins, occurs in response to stimuli that trigger cell death. By patch clamping mitochondrial membranes inside the presynaptic terminal of a squid giant synapse, we have now found that several minutes of hypoxia trigger the opening of large multiconductance channels. The channel activity is induced concurrently with the attenuation of synaptic responses that occurs under hypoxic conditions. Hypoxia-induced channels are inhibited by NADH, an agent that inhibits large conductance channels produced by a pro-apoptotic fragment of BCL-xL in these synaptic mitochondria. The appearance of hypoxia-induced channels was also prevented by the caspase/cysteine protease inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone (Z-VAD-fmk), which inhibits proteolysis of BCL-xL during hypoxia. Both NADH and Z-VAD-fmk reduced significantly the rate of decline of synaptic responses during hypoxia. Our results indicate that an increase in outer mitochondrial channel activity is a very early event in the response of neurons to hypoxia and suggest that this increase in activity may contribute to the decline in synaptic function during hypoxia.This work was supported by Grants NS18496 (to L.K.K.), NS37402 (to J.M.H.), and NS45876 (to E.A.J.) from the National Institutes of Health and by an American Heart Association Established Investigator Award (to E.A.J.)

Managing Partners and Management Professionals: Institutional Work Dyads in Professional Partnerships

This study presents an empirical analysis of the micro-dynamics of institutional work. Examining the ‘corporatization’ of large international law firm partnerships, the study identifies the dyadic relationship that develops between two different types of professionals, the managing partner and management professional, and demonstrates how their relationship becomes a key mechanism for institutional work. The study shows how, by working together, these individuals take advantage of differences in their relative social positions: specifically their formal authority, specialist expertise, and social capital. The study identifies seven forms of institutional work in which they engage and demonstrates how these multiple forms simultaneously encompass the creation, maintenance, and disruption of the institution of partnership. The study argues that this simultaneous occurrence helps to account for the phenomenon of sedimentation, whereby the gradually emerging institutional logic of the corporatized partnership is being integrated into the traditional partnership form

Servitization, digitization and supply chain interdependency

This study draws on literature at the intersection of servitization, digital business models and supply chain management. Work empirically explores how digital disruption has affected Business-to-Business (B2B) interdependencies. Dematerialization of physical products is transforming the way firms are positioned in the supply chain due to a reduction in production and transport costs and the different ways business engage with customers. Specifically, we propose that these new market conditions can empower downstream firms. We further propose that upstream firms can still capture additional value through digital service if their servitized offer includes difficult to imitate elements. The context of the analysis is the publishing industry. The Payment Card method employed is used to test UK and US consumer’s perceptions of digital formats (eBooks) and assess their willingness to pay in relation to printed formats. The method undertaken enables us to elicit aggregated consumer demand for eBooks which in turn identifies optimal pricing strategies for the digital services. Analysis demonstrates that during digital servitization upstream firms should seek to deploy unique resources to ensure their strategic position in the supply chain is not diminished

Recommendations for the management of the haematological and onco-haematological aspects of Gaucher disease1

Current knowledge of the haematological and onco-haematological complications of type 1 Gaucher disease has been reviewed with the aim of identifying best clinical practice for treatment and disease management. It was concluded that: (i) Awareness of typical patterns of cytopenia can help clinicians distinguish haematological co-morbidities. (ii) Red blood cell studies and complete iron metabolism evaluation at baseline are recommended. (iii) Haemoglobin levels defining anaemia should be raised and used in Gaucher disease treatment and monitoring. (iv) Surgeons should be aware of potential bleeding complications during surgery in Gaucher patients. The higher incidence of multiple myeloma in Gaucher disease suggests that Gaucher patients should have their immunoglobulin profile determined at diagnosis and monitored every 2 years (patients <50 years) or every year (patients >50 years). If monoclonal gammopathy of undetermined significance (MGUS) is found, general MGUS guidelines should be followed. Future studies should focus on the utility of early treatment to prevent immunoglobulin abnormalities and multiple myeloma

Virus Movements on the Plasma Membrane Support Infection and Transmission between Cells

How viruses are transmitted across the mucosal epithelia of the respiratory, digestive, or excretory tracts, and how they spread from cell to cell and cause systemic infections, is incompletely understood. Recent advances from single virus tracking experiments have revealed conserved patterns of virus movements on the plasma membrane, including diffusive motions, drifting motions depending on retrograde flow of actin filaments or actin tail formation by polymerization, and confinement to submicrometer areas. Here, we discuss how viruses take advantage of cellular mechanisms that normally drive the movements of proteins and lipids on the cell surface. A concept emerges where short periods of fast diffusive motions allow viruses to rapidly move over several micrometers. Coupling to actin flow supports directional transport of virus particles during entry and cell-cell transmission, and local confinement coincides with either nonproductive stalling or infectious endocytic uptake. These conserved features of virus–host interactions upstream of infectious entry offer new perspectives for anti-viral interference

Concordant Signaling Pathways Produced by Pesticide Exposure in Mice Correspond to Pathways Identified in Human Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disease in which the etiology of 90 percent of the patients is unknown. Pesticide exposure is a major risk factor for PD, and paraquat (PQ), pyridaben (PY) and maneb (MN) are amongst the most widely used pesticides. We studied mRNA expression using transcriptome sequencing (RNA-Seq) in the ventral midbrain (VMB) and striatum (STR) of PQ, PY and paraquat+maneb (MNPQ) treated mice, followed by pathway analysis. We found concordance of signaling pathways between the three pesticide models in both the VMB and STR as well as concordance in these two brain areas. The concordant signaling pathways with relevance to PD pathogenesis were e.g. axonal guidance signaling, Wnt/β-catenin signaling, as well as pathways not previously linked to PD, e.g. basal cell carcinoma, human embryonic stem cell pluripotency and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Human PD pathways previously identified by expression analysis, concordant with VMB pathways identified in our study were axonal guidance signaling, Wnt/β-catenin signaling, IL-6 signaling, ephrin receptor signaling, TGF-β signaling, PPAR signaling and G-protein coupled receptor signaling. Human PD pathways concordant with the STR pathways in our study were Wnt/β-catenin signaling, axonal guidance signaling and G-protein coupled receptor signaling. Peroxisome proliferator activated receptor delta (Ppard) and G-Protein Coupled Receptors (GPCRs) were common genes in VMB and STR identified by network analysis. In conclusion, the pesticides PQ, PY and MNPQ elicit common signaling pathways in the VMB and STR in mice, which are concordant with known signaling pathways identified in human PD, suggesting that these pathways contribute to the pathogenesis of idiopathic PD. The analysis of these networks and pathways may therefore lead to improved understanding of disease pathogenesis, and potential novel therapeutic targets

Recent developments in the production of liquid fuels via catalytic conversion of microalgae: experiments and simulations

Due to continuing high demand, depletion of non-renewable resources and increasing concerns about climate change, the use of fossil fuel-derived transportation fuels faces relentless challenges both from a world markets and an environmental perspective. The production of renewable transportation fuel from microalgae continues to attract much attention because of its potential for fast growth rates, high oil content, ability to grow in unconventional scenarios, and inherent carbon neutrality. Moreover, the use of microalgae would minimize ‘‘food versus fuel’’ concerns associated with several biomass strategies, as microalgae do not compete with food crops in the food chain. This paper reviews the progress of recent research on the production of transportation fuels via homogeneous and heterogeneous catalytic conversions of microalgae. This review also describes the development of tools that may allow for a more fundamental understanding of catalyst selection and conversion processes using computational modelling. The catalytic conversion reaction pathways that have been investigated are fully discussed based on both experimental and theoretical approaches. Finally, this work makes several projections for the potential of various thermocatalytic pathways to produce alternative transportation fuels from algae, and identifies key areas where the authors feel that computational modelling should be directed to elucidate key information to optimize the process

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates