A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.

Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear. We now find that inactivation of NHE9 in mice reproduces behavioral features of ASD including impaired social interaction, repetitive behaviors, and altered sensory processing. Physiological characterization reveals hyperacidic endosomes, a cell-autonomous defect in glutamate receptor expression and impaired neurotransmitter release due to a defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle acidification rescues release but without affecting the primary defect due to loss of NHE9

Sero-epidemiological status and risk factors of toxoplasmosis in pregnant women in Northern Vietnam

Background: In Vietnam, few studies have determined the epidemiological status of toxoplasmosis in pregnant women and no routine prenatal screening is in place. This study was conducted to evaluate the seroprevalence of this zoonotic parasitic infection in pregnant women in Northern Vietnam and to assess the association with awareness, risk factors and congenital toxoplasmosis. Methods: Approximately 800 pregnant women were included in the study from two hospitals, one in Hanoi and one in Thai Binh province, which is known to have a dense cat population. Serological immunoglobulin G (IgG) and immunoglobulin M (IgM) detection was performed to estimate the seroprevalence of toxoplasmosis and sero-incidence of maternal and congenital toxoplasmosis. In addition, a survey was conducted about awareness, clinical history, presentation of signs and symptoms relating to toxoplasmosis and to detect biologically plausible and socio-demographic risk factors associated with toxoplasmosis. Associations with seroprevalence were assessed using univariable and multivariable analysis. Results: The mean IgG seroprevalence after the full diagnostic process was 4.5% (95% confidence interval(CI): 2.7–7.0) and 5.8% (95% CI: 3.7–8.6) in Hanoi and Thai Binh hospital, respectively, and included one seroconversion diagnosed in Thai Binh hospital. Only 2.0% of the pregnant women in Hanoi hospital and 3.3% in Thai Binh hospital had heard about toxoplasmosis before this study. Conclusion: Since the percentage of seronegative, and thus susceptible, pregnant women was high and the awareness was low, we suggest to distribute information about toxoplasmosis and its prevention among women of child bearing age. Furthermore, future studies are recommended to investigate why such a low seroprevalence was seen in pregnant women in Northern Vietnam compared to other countries in South East Asia and globally

Epidemiology of Non-small Cell Lung Cancer in Asian Americans: Incidence Patterns Among Six Subgroups by Nativity

BackgroundDifferences in the epidemiology of lung cancer between Asians and non-Hispanic whites have brought to light the relative influences of genetic and environmental factors on lung cancer risk. We set out to describe the epidemiology of non-small cell lung cancer (NSCLC) among Asians living in California, and to explore the effects of acculturation on lung cancer risk by comparing lung cancer rates between U.S.-born and foreign-born Asians.MethodsAge-adjusted incidence rates of NSCLC were calculated for Chinese, Filipino, Japanese, Korean, Vietnamese, and South Asians in California between 1988 and 2003 using data from the California Cancer Registry. Incidence rates were calculated and stratified by sex and nativity. We analyzed population-based tobacco smoking prevalence data to determine whether differences in rates were associated with prevalence of tobacco smoking.ResultsAsians have overall lower incidence rates of NSCLC compared with whites (29.8 and 57.7 per 100,000, respectively). South Asians have markedly low rates of NSCLC (12.0 per 100,000). Foreign-born Asian men and women have an approximately 35% higher rate of NSCLC than U.S.-born Asian men and women. The incidence pattern by nativity is consistent with the population prevalence of smoking among Asian men; however, among women, the prevalence of smoking is higher among U.S.-born, which is counter to their incidence patterns.ConclusionsForeign-born Asians have a higher rate of NSCLC than U.S.-born Asians, which may be due to environmental tobacco smoke or nontobacco exposures among women. South Asians have a remarkably low rate of NSCLC that approaches white levels among the U.S.-born. More studies with individual-level survey data are needed to identify the specific environmental factors associated with differential lung cancer risk occurring with acculturation among Asians

A Checklist to Publish Collections as Data in GLAM Institutions

Large-scale digitization in Galleries, Libraries, Archives and Museums (GLAM) created the conditions for providing access to collections as data. It opened new opportunities to explore, use and reuse digital collections. Strong proponents of collections as data are the Innovation Labs which provided numerous examples of publishing datasets under open licenses in order to reuse digital content in novel and creative ways. Within the current transition to the emerging data spaces, clouds for cultural heritage and open science, the need to identify practices which support more GLAM institutions to offer datasets becomes a priority, especially within the smaller and medium-sized institutions. This paper answers the need to support GLAM institutions in facilitating the transition into publishing their digital content and to introduce collections as data services; this will also help their future efficient contribution to data spaces and cultural heritage clouds. It offers a checklist that can be used for both creating and evaluating digital collections suitable for computational use. The main contributions of this paper are i) a methodology for devising a checklist to create and assess digital collections for computational use; ii) a checklist to create and assess digital collections suitable for use with computational methods; iii) the assessment of the checklist against the practice of institutions innovating in the Collections as data field; and iv) the results obtained after the application and recommendations for the use of the checklist in GLAM institutions

Contrasting Management Techniques and Soil Types Affect Network Connections between Soil Properties and the Tulip Microbiome

Conventional agriculture relies on high inputs of chemical fertilisers and pesticides, leading to extensive soil damage. As a result, there has been a shift towards organic cultivation to ameliorate these negative effects. However, knowledge gaps remain concerning how different agricultural management regimes can alter soil properties, root-associated biota and relationships between them. We sampled soils and bulbs from clay and sand tulip fields with conventional, organic and hybrid (i.e., intermediate between conventional and organic) management regimes to determine effects on abiotic and biotic soil properties, tulip bulb microbiomes/biota and network connectivity between them. We found that soil abiotic properties were not driven by management. However, soil microbial community composition was determined by interactions between soil type and management. Specifically, conventional management created more heterogeneous and homogenous bacterial and fungal soil communities, respectively, across soil types, while organic and hybrid soil communities differed between soil types. A partial least squares path model revealed that across all fields, soil properties determined the composition of tulip bulb biota (i.e., microorganisms, nematodes), while management techniques did not play a significant role, neither directly nor indirectly. Network analyses revealed more modular (i.e., independent) nodes of association in fields with sandy soils. Specifically, management techniques (i.e., chemical usage, ploughing depth, diminished crop rotation) formed a cluster that was independent from most soil (abiotic and biotic) and bulb biotic properties, while clay field networks showed the opposite. Our results indicate that conventional agriculture can homogenise soil microbial communities, with potential impacts on soil function and buffering capacity to stress. Increased modularity between soil properties, management techniques and tulip bulb biota in sand fields could mean increased resistance to disturbance and abiotic and biotic stress as a result of higher functional redundancy. Interactions between agricultural management regime and soil type must be taken into consideration when determining long-term influences on crop microbiome/biota associations and the potential effects on soil health and productivity

A checklist to publish collections as data in GLAM institutions

Purpose The purpose of this study is to offer a checklist that can be used for both creating and evaluating digital collections, which are also sometimes referred to as data sets as part of the collections as data movement, suitable for computational use. Design/methodology/approach The checklist was built by synthesising and analysing the results of relevant research literature, articles and studies and the issues and needs obtained in an observational study. The checklist was tested and applied both as a tool for assessing a selection of digital collections made available by galleries, libraries, archives and museums (GLAM) institutions as proof of concept and as a supporting tool for creating collections as data. Findings Over the past few years, there has been a growing interest in making available digital collections published by GLAM organisations for computational use. Based on previous work, the authors defined a methodology to build a checklist for the publication of Collections as data. The authors’ evaluation showed several examples of applications that can be useful to encourage other institutions to publish their digital collections for computational use. Originality/value While some work on making available digital collections suitable for computational use exists, giving particular attention to data quality, planning and experimentation, to the best of the authors’ knowledge, none of the work to date provides an easy-to-follow and robust checklist to publish collection data sets in GLAM institutions. This checklist intends to encourage small- and medium-sized institutions to adopt the collection as data principles in daily workflows following best practices and guidelines

NFATc1 affects mouse splenic B cell function by controlling the calcineurin–NFAT signaling network

Mouse B cells lacking NFATc1 exhibit defective proliferation, survival, isotype class switching, cytokine production, and T cell help

Protocol for the ROSE sustainment (ROSES) study, a sequential multiple assignment randomized trial to determine the minimum necessary intervention to maintain a postpartum depression prevention program in prenatal clinics serving low-income women

Background: More research on sustainment of interventions is needed, especially return on investment (ROI) studies to determine cost-benefit trade-offs for effort required to sustain and how much is gained when effective programs are sustained. The ROSE sustainment (ROSES) study uses a sequential multiple assignment randomized (SMART) design to evaluate the effectiveness and cost-effectiveness of a stepwise approach to sustainment of the ROSE postpartum depression prevention program in 90 outpatient clinics providing prenatal care to pregnant women on public assistance. Postpartum depression (PPD) is common and can have lasting consequences. Outpatient clinics offering prenatal care are an opportune place to provide PPD prevention because most women visit while pregnant. The ROSE (Reach Out, Stay Strong, Essentials for mothers of newborns) program is a group educational intervention to prevent PPD, delivered during pregnancy. ROSE has been found to reduce cases of PPD in community prenatal settings serving low-income pregnant women. Methods: All 90 prenatal clinics will receive enhanced implementation as usual (EIAU; initial training + tools for sustainment). At the first time at which a clinic is determined to be at risk for failure to sustain (i.e., at 3, 6, 9, 12, and 15 months), that clinic will be randomized to receive either (1) no additional implementation support (i.e., EIAU only), or (2) low-intensity coaching and feedback (LICF). If clinics receiving LICF are still at risk at subsequent assessments, they will be randomized to either (1) EIAU + LICF only, or (2) high-intensity coaching and feedback (HICF). Additional follow-up interviews will occur at 18, 24, and 30 months, but no implementation intervention will occur after 18 months. Outcomes include (1) percent sustainment of core program elements at each time point, (2) health impact (PPD rates over time at each clinic) and reach, and (3) ROI (costs and cost-effectiveness) of each sustainment step. Hypothesized mechanisms include sustainment of capacity to deliver core elements and engagement/ownership. Discussion: This study is the first randomized trial evaluating the ROI of a stepped approach to sustainment, a critical unanswered question in implementation science. It will also advance knowledge of implementation mechanisms and clinical care for an at-risk population

Decidual-Secreted Factors Alter Invasive Trophoblast Membrane and Secreted Proteins Implying a Role for Decidual Cell Regulation of Placentation

Inadequate or inappropriate implantation and placentation during the establishment of human pregnancy is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. To create the placental blood supply, specialized cells, the ‘extravillous trophoblast’ (EVT) invade through the differentiated uterine endometrium (the decidua) to engraft and remodel uterine spiral arteries. We hypothesized that decidual factors would regulate EVT function by altering the production of EVT membrane and secreted factors. We used a proteomics approach to identify EVT membrane and secreted proteins regulated by decidual cell factors. Human endometrial stromal cells were decidualized in vitro by treatment with estradiol (10−8 M), medroxyprogesterone acetate (10−7 M) and cAMP (0.5 mM) for 14 days. Conditioned media (CM) was collected on day 2 (non-decidualized CM) and 14 (decidualized CM) of treatment. Isolated primary EVT cultured on Matrigel™ were treated with media control, non-decidualized or decidualized CM for 16 h. EVT CM was fractionated for proteins <30 kDa using size-exclusion affinity nanoparticles (SEAN) before trypsin digestion and HPLC-MS/MS. 43 proteins produced by EVT were identified; 14 not previously known to be expressed in the placenta and 12 which had previously been associated with diseases of pregnancy including preeclampsia. Profilin 1, lysosome associated membrane glycoprotein 1 (LAMP1), dipeptidyl peptidase 1 (DPP1/cathepsin C) and annexin A2 expression by interstitial EVT in vivo was validated by immunhistochemistry. Decidual CM regulation in vitro was validated by western blotting: decidualized CM upregulated profilin 1 in EVT CM and non-decidualized CM upregulated annexin A2 in EVT CM and pro-DPP1 in EVT cell lysate. Here, non-decidualized factors induced protease expression by EVT suggesting that non-decidualized factors may induce a pro-inflammatory cascade. Preeclampsia is a pro-inflammatory condition. Overall, we have demonstrated the potential of a proteomics approach to identify novel proteins expressed by EVT and to uncover the mechanisms leading to disease states