A physiologically inspired model for global remapping in the hippocampus

Europe PMC is an archive of life sciences journal literature., A physiologically inspired model for global remapping in the hippocampus

Symptoms associated with the DSM IV diagnosis of depression in pregnancy and post partum

Pregnancy and the postpartum may affect symptoms of depression. However it has not yet been tested how the symptoms used for the DSM IV diagnosis of depression discriminate depressed from non depressed women perinatally. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all associated DSM IV symptoms of depression with depressed and non depressed women in pregnancy and the postpartum period. Loss of appetite was not associated with depression either ante or postnatally. The antenatal symptom pattern was different from the postnatal. The sensitivity of the symptoms ranged from 0.7% to 51.6%, and specificity from 61.3% to 99.1%. The best discriminating symptoms were motor retardation/agitation and concentration antenatally, and motor retardation/agitation, concentration and fatigue postnatally. Depression in pregnancy and postpartum depression show significantly different symptom profiles. Appetite is not suitable for the diagnosis of depression in the perinatal perio

The DSM IV diagnoses of melancholic and atypical depression in pregnancy

Atypical and melancholic subtypes of depression based on the Diagnostic and Statistical Manual (DSM) IV are important concepts, especially for biological psychiatry. The aim of this study was to determine whether the symptoms used for the diagnoses of atypical and melancholic depression can distinguish these subtypes during pregnancy. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all DSM IV symptoms of melancholic and atypical depression with depressed and non-depressed women in pregnancy. A Swiss cohort of 449 women was interviewed. Four diagnostic groups were compared: women with melancholic, atypical or non specified depression, and those without depression. Seventeen per cent of the cohort met SCID criteria for a depressive episode of depression at least once in pregnancy, with melancholic depression 2.4%, atypical depression 4.4% and non specified depression 10.2%. Many of the symptoms used to distinguish atypical and melancholic depression did not discriminate between these groups during pregnancy. However some, such as mood reactivity, distinct quality of mood and sleep pattern, did discriminate. Differential diagnosis between melancholic and atypical depression in pregnancy needs to be based on pregnancy specific definitions. The possible therapeutic consequences and the neurobiological basis for these findings warrant further researc

Perinatal mental health service provision in Switzerland and the UK

Questions under study: The epidemiology of maternal perinatal-psychiatric disorders as well as their effect on the baby is well recognised. Increasingly well researched specialised treatment methods can reduce maternal morbidity, positively affect mother-baby bonding and empower women’s confidence as a mother. Here, we aimed to compare guidelines and the structure of perinatal-psychiatric service delivery in the United Kingdom and in Switzerland from the government’s perspective. Methods: Swiss cantons provided information regarding guidelines and structure of service delivery in 2000. A subsequent survey using the same questionnaire was carried out in 2007. In the UK, similar information was accessed through published reports from 2000-2012. Results: Guidelines for perinatal psychiatry exist in the UK, whereas in Switzerland in 2000 none of the 26 cantons had guidelines, and in 2007 only one canton did. Joint mother-baby admissions on general psychiatric wards were offered by 92% of the Swiss cantons. In the UK, pregnant women and joint mother-baby admissions are only advised onto specialised perinatal-psychiatric units. In Switzerland, in 2007, three specialised units (max. 24 beds) were in place corresponding to 1 unit per 2.5 million people, while in the UK there were 22 mother-baby units (168 beds) in 2012 (1 unit per 2.8 million). In the UK, less than 50% of trusts provided specialised perinatal-psychiatric health care. Conclusions: The main difference between the UK and Switzerland was the absence of guidelines, regular assessment and plans for future development of perinatal psychiatry in Switzerland. There are still geographical differences in the provision of perinatal-psychiatric services in the UK

A new duplex qPCR-based method to quantify Mycoplasma mycoides in complex cell culture systems and host tissues.

Bacterial pathogen-host interactions are a complex process starting with adherence and colonization followed by a variety of interactions such as invasion or cytotoxicity on one hand and pathogen recognition, secretion of proinflammatory/antibacterial substances and enhancing the barrier function of epithelial layers on the other hand. Therefore, a variety of in vitro, ex vivo and in vivo models have been established to investigate these interactions. Some in vitro models are composed of different cell types and extracellular matrices such as tissue explants or precision cut lung slices. These complex in vitro models mimic the in vivo situation more realistically, however, they often require new and more sophisticated methods for quantification of experimental results. Here we describe a multiplex qPCR-based method to quantify the number of bacteria of Mycoplasma (M.) mycoides interacting with their hosts in an absolute manner as well as normalized to the number of host cells. We choose the adenylate kinase (adk) gene from the pathogen and the Carcinoembryonic antigen-related cell adhesion molecule 18 (CEACAM18) gene from the host to determine cell numbers by a TaqMan-based assay system. Absolute copy numbers of the genes are calculated according to a standard containing a defined number of plasmids containing the sequence which is amplified by the qPCR. The new multiplex qPCR therefore allows the quantification of M. mycoides interacting with host cells in suspension, monolayer, 3D cell culture systems as well as in host tissues

Natural selection supports escape from concerted evolution of a recently duplicated CEACAM1 paralog in the ruminant CEA gene family

Concerted evolution is often observed in multigene families such as the CEA gene family. As a result, sequence similarity of paralogous genes is significantly higher than expected from their evolutionary distance. Gene conversion, a "copy paste" DNA repair mechanism that transfers sequences from one gene to another and homologous recombination are drivers of concerted evolution. Nevertheless, some gene family members escape concerted evolution and acquire sufficient sequence differences that orthologous genes can be assigned in descendant species. Reasons why some gene family members can escape while others are captured by concerted evolution are poorly understood. By analyzing the entire CEA gene family in cattle (Bos taurus) we identified a member (CEACAM32) that was created by gene duplication and cooption of a unique transmembrane domain exon in the most recent ancestor of ruminants. CEACAM32 shows a unique, testis-specific expression pattern. Phylogenetic analysis indicated that CEACAM32 is not involved in concerted evolution of CEACAM1 paralogs in ruminants. However, analysis of gene conversion events revealed that CEACAM32 is subject to gene conversion but remarkably, these events are found in the leader exon and intron sequences but not in exons coding for the Ig-like domains. These findings suggest that natural selection hinders gene conversion affecting protein sequences of the mature protein and thereby support escape of CEACAM32 from concerted evolution

Immunization with GP1 but Not Core-like Particles Displaying Isolated Receptor-Binding Epitopes Elicits Virus-Neutralizing Antibodies against Junín Virus

New World arenaviruses are rodent-transmitted viruses and include a number of pathogens that are responsible for causing severe human disease. This includes Junín virus (JUNV), which is the causative agent of Argentine hemorrhagic fever. The wild nature and mobility of the rodent reservoir host makes it difficult to control the disease, and currently passive immunization with high-titer neutralizing antibody-containing plasma from convalescent patients is the only specific therapy. However, dwindling supplies of naturally available convalescent plasma, and challenges in developing similar resources for other closely related viruses, have made the development of alternative antibody-based therapeutic approaches of critical importance. In this study, we sought to induce a neutralizing antibody response in rabbits against the receptor-binding subunit of the viral glycoprotein, GP1, and the specific peptide sequences in GP1 involved in cellular receptor contacts. While these specific receptor-interacting peptides did not efficiently induce the production of neutralizing antibodies when delivered as a particulate antigen (as part of hepatitis B virus core-like particles), we showed that recombinant JUNV GP1 purified from transfected mammalian cells induced virus-neutralizing antibodies at high titers in rabbits. Further, neutralization was observed across a range of unrelated JUNV strains, a feature that is critical for effectiveness in the field. These results underscore the potential of GP1 alone to induce a potent neutralizing antibody response and highlight the importance of epitope presentation. In addition, effective virus neutralization by rabbit antibodies supports the potential applicability of this species for the future development of immunotherapeutics (e.g., based on humanized monoclonal antibodies). Such information can be applied in the design of vaccines and immunogens for both prevention and specific therapies against this and likely also other closely related pathogenic New World arenaviruses.Fil: Roman Sosa, Gleyder. Ulm University Hospital; AlemaniaFil: Leske, Anne. Friedrich-Loeffler-Institut; AlemaniaFil: Ficht, Xenia. Ulm University Hospital; AlemaniaFil: Dau, Tung Huy. Friedrich-Loeffler-Institut; AlemaniaFil: Holzerland, Julia. Friedrich-Loeffler-Institut; AlemaniaFil: Hoenen, Thomas. Friedrich-Loeffler-Institut; AlemaniaFil: Beer, Martin. Friedrich-Loeffler-Institut; AlemaniaFil: Kammerer, Robert. Friedrich-Loeffler-Institut; AlemaniaFil: Schirmbeck, Reinhold. Friedrich-Loeffler-Institut; AlemaniaFil: Rey, Felix A.. Friedrich-Loeffler-Institut; AlemaniaFil: Cordo, Sandra Myriam. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Groseth, Allison. Friedrich-Loeffler-Institut; Alemani

Recent expansion and adaptive evolution of the carcinoembryonic antigen family in bats of the Yangochiroptera subgroup

Background: Expansions of gene families are predictive for ongoing genetic adaptation to environmental cues. We describe such an expansion of the carcinoembryonic antigen (CEA) gene family in certain bat families. Members of the CEA family in humans and mice are exploited as cellular receptors by a number of pathogens, possibly due to their function in immunity and reproduction. The CEA family is composed of CEA-related cell adhesion molecules (CEACAMs) and secreted pregnancy-specific glycoproteins (PSGs). PSGs are almost exclusively expressed by trophoblast cells at the maternal-fetal interface. The reason why PSGs exist only in a minority of mammals is still unknown. Results: Analysis of the CEA gene family in bats revealed that in certain bat families, belonging to the subgroup Yangochiroptera but not the Yinpterochiroptera subgroup an expansion of the CEA gene family took place, resulting in approximately one hundred CEA family genes in some species of the Vespertilionidae. The majority of these genes encode secreted PSG-like proteins (further referred to as PSG). Remarkably, we found strong evidence that the ligand-binding domain (IgV-like domain) of PSG is under diversifying positive selection indicating that bat PSGs may interact with structurally highly variable ligands. Such ligands might represent bacterial or viral pathogen adhesins. We have identified two distinct clusters of PSGs in three Myotis species. The two PSG cluster differ in the amino acids under positive selection. One cluster was only expanded in members of the Vespertilionidae while the other was found to be expanded in addition in members of the Miniopteridae and Mormoopidae. Thus one round of PSG expansion may have occurred in an ancestry of all three families and a second only in Vespertilionidae. Although maternal ligands of PSGs may exist selective challenges by two distinct pathogens seem to be likely responsible for the expansion of PSGs in Vespertilionidae. Conclusions: The rapid expansion of PSGs in certain bat species together with selection for diversification suggest that bat PSGs could be part of a pathogen defense system by serving as decoy receptors and/or regulators of feto-maternal interactions

A Flagellar A-Kinase Anchoring Protein with Two Amphipathic Helices Forms a Structural Scaffold in the Radial Spoke Complex

A-kinase anchoring proteins (AKAPs) contain an amphipathic helix (AH) that binds the dimerization and docking (D/D) domain, RIIa, in cAMP-dependent protein kinase A (PKA). Many AKAPs were discovered solely based on the AH–RIIa interaction in vitro. An RIIa or a similar Dpy-30 domain is also present in numerous diverged molecules that are implicated in critical processes as diverse as flagellar beating, membrane trafficking, histone methylation, and stem cell differentiation, yet these molecules remain poorly characterized. Here we demonstrate that an AKAP, RSP3, forms a dimeric structural scaffold in the flagellar radial spoke complex, anchoring through two distinct AHs, the RIIa and Dpy-30 domains, in four non-PKA spoke proteins involved in the assembly and modulation of the complex. Interestingly, one AH can bind both RIIa and Dpy-30 domains in vitro. Thus, AHs and D/D domains constitute a versatile yet potentially promiscuous system for localizing various effector mechanisms. These results greatly expand the current concept about anchoring mechanisms and AKAPs

KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients

Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3 using survival analysis. In a total of > 1000 breast cancer patients of two independent data sets we showed a) that KCNJ3 expression is upregulated in tumor tissue compared to corresponding normal tissue (p < 0.001), b) that KCNJ3 expression is associated with estrogen receptor (ER) positive tumors (p < 0.001), but that KCNJ3 expression is variable within this group, and c) that ER positive patients with high KCNJ3 levels have worse overall (p < 0.05) and disease free survival probabilities (p < 0.01), whereby KCNJ3 is an independent prognostic factor (p <0.05). In conclusion, our data suggest that patients with ER positive breast cancer might be stratified into high risk and low risk groups based on the KCNJ3 levels in the tumor