Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells.

Related Articles

Cross-Generational Reproductive Fitness Enforced by Microchimeric Maternal Cells.

Cell. 2015 Jul 22;

Authors: Kinder JM, Jiang TT, Ertelt JM, Xin L, Strong BS, Shaaban AF, Way SS

Abstract

Exposure to maternal tissue during in utero development imprints tolerance to immunologically foreign non-inherited maternal antigens (NIMA) that persists into adulthood. The biological advantage of this tolerance, conserved across mammalian species, remains unclear. Here, we show maternal cells that establish microchimerism in female offspring during development promote systemic accumulation of immune suppressive regulatory T cells (Tregs) with NIMA specificity. NIMA-specific Tregs expand during pregnancies sired by males expressing alloantigens with overlapping NIMA specificity, thereby averting fetal wastage triggered by prenatal infection and non-infectious disruptions of fetal tolerance. Therefore, exposure to NIMA selectively enhances reproductive success in second-generation females carrying embryos with overlapping paternally inherited antigens. These findings demonstrate that genetic fitness, canonically thought to be restricted to Mendelian inheritance, is enhanced in female placental mammals through vertically transferred maternal cells that promote conservation of NIMA and enforce cross-generational reproductive benefits.

PMID: 26213383 [PubMed - as supplied by publisher]

β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling.

Related Articles

β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling.

Cell. 2015 Jul 22;

Authors: Anderson GR, Aoto J, Tabuchi K, Földy C, Covy J, Yee AX, Wu D, Lee SJ, Chen L, Malenka RC, Südhof TC

Abstract

α- and β-neurexins are presynaptic cell-adhesion molecules implicated in autism and schizophrenia. We find that, although β-neurexins are expressed at much lower levels than α-neurexins, conditional knockout of β-neurexins with continued expression of α-neurexins dramatically decreased neurotransmitter release at excitatory synapses in cultured cortical neurons. The β-neurexin knockout phenotype was attenuated by CB1-receptor inhibition, which blocks presynaptic endocannabinoid signaling, or by 2-arachidonoylglycerol synthesis inhibition, which impairs postsynaptic endocannabinoid release. In synapses formed by CA1-region pyramidal neurons onto burst-firing subiculum neurons, presynaptic in vivo knockout of β-neurexins aggravated endocannabinoid-mediated inhibition of synaptic transmission and blocked LTP; presynaptic CB1-receptor antagonists or postsynaptic 2-arachidonoylglycerol synthesis inhibition again reversed this block. Moreover, conditional knockout of β-neurexins in CA1-region neurons impaired contextual fear memories. Thus, our data suggest that presynaptic β-neurexins control synaptic strength in excitatory synapses by regulating postsynaptic 2-arachidonoylglycerol synthesis, revealing an unexpected role for β-neurexins in the endocannabinoid-dependent regulation of neural circuits.

PMID: 26213384 [PubMed - as supplied by publisher]

ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole.

Related Articles

ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole.

Cell. 2015 Jul 22;

Authors: Madarampalli B, Yuan Y, Liu D, Lengel K, Xu Y, Li G, Yang J, Liu X, Lu Z, Liu DX

Abstract

Although it is known that the centrioles play instructive roles in pericentriolar material (PCM) assembly and that the PCM is essential for proper centriole formation, the mechanism that governs centriole-PCM interaction is poorly understood. Here, we show that ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the PCM outfitting the proximal end of the mother centriole. ATF5 controls the centriole-PCM interaction in a cell-cycle- and centriole-age-dependent manner. Interaction of ATF5 with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM renders ATF5 as a required molecule in mother centriole-directed PCM accumulation and in PCM-dependent centriole formation. ATF5 depletion blocks PCM accumulation at the centrosome and causes fragmentation of centrioles, leading to the formation of multi-polar mitotic spindles and genomic instability. These data show that ATF5 is an essential structural protein that is required for the interaction between the mother centriole and the PCM.

PMID: 26213385 [PubMed - as supplied by publisher]

Predicting Soluble Nickel in Soils Using Soil Properties and Total Nickel

by Xiaoqing Zhang, Jumei Li, Dongpu Wei, Bo Li, Yibing Ma

Soil soluble nickel (Ni) concentration is very important for determining soil Ni toxicity. In the present study, the relationships between soil properties, total and soluble Ni concentrations in soils were developed in a wide range of soils with different properties and climate characteristics. The multiple regressions showed that soil pH and total soil Ni concentrations were the most significant parameters in predicting soluble Ni concentrations with the adjusted determination coefficients (Radj2) values of 0.75 and 0.68 for soils spiked with soluble Ni salt and the spiked soils leached with artificial rainwater to mimic field conditions, respectively. However, when the soils were divided into three categories (pH < 7, 7–8 and > 8), they obtained better predictions with Radj2 values of 0.78–0.90 and 0.79–0.94 for leached and unleached soils, respectively. Meanwhile, the other soil properties, such as amorphous Fe and Al oxides and clay, were also found to be important for determining soluble Ni concentrations, indicating that they were also presented as active adsorbent surfaces. Additionally, the whole soil speciation including bulk soil properties and total soils Ni concentrations were analyzed by mechanistic speciation models WHAM VI and Visual MINTEQ3.0. It was found that WHAM VI provided the best predictions for the soils with pH < 7, was relatively reasonable for pH 7 to 8, and gave an overestimation for pH > 8. The Visual MINTEQ3.0 could provide better estimation for pH < 8 and meanwhile quite reasonable results for pH > 8. These results indicated the possibility and applicability of these models to predict soil soluble Ni concentration by soil properties.

A Time Series Study of Lophelia pertusa and Reef Megafauna Responses to Drill Cuttings Exposure on the Norwegian Margin

by Autun Purser

As hotspots of local biodiversity in the deep sea, preservation of cold-water coral reef communities is of great importance. In European waters the most extensive reefs are found at depths of 300 – 500 m on the continental margin. In Norwegian waters many of these reefs are located in areas of interest for oil and gas exploration and production. In this study drilling was carried out in the Morvin drill field in proximity to a number of small Lophelia pertusa coral reefs (closest reefs 100 m upstream and 350 m downstream of point of waste drill material release). In a novel monitoring study, ROV video surveys of 9 reefs were conducted prior, during, immediately after and >1 year after drilling operations. Behavior of coral polyps inhabiting reefs exposed to differing concentrations of drill cuttings and drilling fluids (waste drilling material) were compared. Levels of expected exposure to these waste materials were determined for each reef by modelling drill cutting transport following release, using accurate in-situ hydrodynamic data collected during the drilling period and drill cutting discharge data as parameters of a dispersal model. The presence / absence of associate reef species (Acesta excavata, Paragorgia arborea and Primnoa resedaeformis) were also determined from each survey video. There were no significant differences in Lophelia pertusa polyp behavior in corals modelled to have been exposed to pulses of >25 ppm drill cutting material and those modelled to be exposed to negligible concentrations of material. From the video data collected, there were no observed degradations of reef structure over time, nor reductions of associate fauna abundance, regardless of modelled exposure concentration at any of the surveyed reefs. This study focused exclusively on adult fauna, and did not assess the potential hazard posed by waste drilling material to coral or other larvae. Video data was collected by various ROV’s, using different camera and lighting setups throughout the survey campaign, making comparison of observations prior, during and post drilling problematic. A standardization of video monitoring in future monitoring campaigns is recommended.

Clinical Specimen-Direct LAMP: A Useful Tool for the Surveillance of blaOXA-23-Positive Carbapenem-Resistant Acinetobacter baumannii

by Norihisa Yamamoto, Shigeto Hamaguchi, Yukihiro Akeda, Pitak Santanirand, Anusak Kerdsin, Masafumi Seki, Yoshikazu Ishii, Wantana Paveenkittiporn, Robert A. Bonomo, Kazunori Oishi, Kumthorn Malathum, Kazunori Tomono

Healthcare-associated infections are a leading cause of morbidity and mortality worldwide. Treatment is increasingly complicated by the escalating incidence of antimicrobial resistance. Among drug-resistant pathogens, carbapenem-resistant Acinetobacter baumannii (CRAb) is of increasing concern because of the limited applicable therapies and its expanding global distribution in developed countries and newly industrialized countries. Therefore, a rapid detection method that can be used even in resource-poor countries is urgently required to control this global public health threat. Conventional techniques, such as bacterial culture and polymerase chain reaction (PCR), are insufficient to combat this threat because they are time-consuming and laborious. In this study, we developed a loop-mediated isothermal amplification (LAMP) method for detecting blaOXA-23-positive CRAb, the most prevalent form of CRAb in Asia, especially in Thailand, and confirmed its efficacy as a surveillance tool in a clinical setting. Clinical samples of sputum and rectal swabs were collected from patients in a hospital in Bangkok and used for LAMP assays. After boiling and centrifugation, the supernatants were used directly in the assay. In parallel, a culture method was used for comparison purposes to evaluate the specificity and sensitivity of LAMP. As a first step, a total of 120 sputum samples were collected. The sensitivity of LAMP was 88.6% (39/44), and its specificity was 92.1% (70/76) using the culture method as the “gold standard”. When surveillance samples including sputum and rectal swabs were analyzed with the LAMP assay, its sensitivity was 100.0%. This method enables the direct analysis of clinical specimens and provides results within 40 minutes of sample collection, making it a useful tool for surveillance even in resource-poor countries.

Perceptions of Community Members and Healthcare Workers on Male Involvement in Prevention of Mother-To-Child Transmission Services in Khayelitsha, Cape Town, South Africa

by Alice Norah Ladur, Christopher J. Colvin, Kathryn Stinson

Involving male partners of pregnant women accessing PMTCT programs has the potential to improve health outcomes for women and children. This study explored community members’ (men and women) and healthcare workers’ perceptions of male involvement in the prevention of mother-to-child transmission of HIV in Khayelitsha, South Africa. Two focus group discussions were held with 25 men of unknown HIV status and one focus group discussion held with 12 HIV-positive women in the community. In depth interviews were conducted with four HIV-positive couples and five service providers purposely sampled from the community and a health facility, respectively. Both men and women interviewed in this study were receptive towards male involvement in PMTCT. However, men were reluctant to engage with health services due to stigma and negative attitudes from nurses. This study also found HIV testing, disclosure and direct health worker engagement with men increases male involvement in PMTCT. Using men in the media and community to reach out to fellow men with prevention messages tailored to suit specific audiences may reduce perceptions of antenatal care as being a woman`s domain.

How to Break the Cycle of Low Workforce Diversity: A Model for Change

by Katherine R. O’Brien, Marten Scheffer, Egbert H. van Nes, Romy van der Lee

Social justice concerns but also perceived business advantage are behind a widespread drive to increase workplace diversity. However, dominance in terms of ethnicity, gender or other aspects of diversity has been resistant to change in many sectors. The different factors which contribute to low diversity are often hotly contested and difficult to untangle. We propose that many of the barriers to change arise from self-reinforcing feedbacks between low group diversity and inclusivity. Using a dynamic model, we demonstrate how bias in employee appointment and departure can trap organizations in a state with much lower diversity than the applicant pool: a workforce diversity “poverty trap”. Our results also illustrate that if turnover rate is low, employee diversity takes a very long time to change, even in the absence of any bias. The predicted rate of change in workforce composition depends on the rate at which employees enter and leave the organization, and on three measures of inclusion: applicant diversity, appointment bias and departure bias. Quantifying these three inclusion measures is the basis of a new, practical framework to identify barriers and opportunities to increasing workforce diversity. Because we used a systems approach to investigate underlying feedback mechanisms rather than context-specific causes of low workforce diversity, our results are applicable across a wide range of settings.

An Analysis of Organizational Performance Based on Hospital Specialization Level and Strategy Type

by Han-Sung Kim, Young-Hoon Kim, Jung-Sik Woo, Sook-Jung Hyun

Introduction

Hospitals are studying the focused factory concept and attempting to increase their power in a competitive industry by becoming more specialized.

Methodology

This study uses the information theory index (ITI) and the Herfindahl-Hirschman index (HHI) to analyze the extent of specialization by Korean hospitals that receive national health insurance reimbursements. Hierarchical regression analysis is used to assess the impact of hospital specialization on the following four aspects of operational performance: productivity, profitability, efficiency and quality of care.

Study Results

The results show that a focused strategy (high HHI) improves the income and adjusted number of patients per specialist through the efficient utilization of human resources. However, a diversified strategy (high ITI) improves the hospital utilization ratio, income per bed and adjusted number of patients per bed (controlling for material resources such as beds). In addition, as the concentration index increases, case-mix mortality rates and referral rates decrease, indicating that specialization has a positive relationship with quality of care.

Ewes Direct Most Maternal Attention towards Lambs that Show the Greatest Pain-Related Behavioural Responses

by Agnieszka Futro, Katarzyna Masłowska, Cathy M. Dwyer

Although neonatal farm animals are frequently subjected to painful management procedures, the role of maternal behaviour in pain coping, has not been much studied. We investigated whether ewes were able to distinguish between lambs in pain and those that were not, and whether their behaviour altered depending on the severity of lamb pain. Eighty male lambs were allocated to one of 4 pain treatments within 24 hours of birth. Lambs were either handled only (C), bilaterally castrated with tight rubber rings (RR), as for RR but with the application of a Burdizzo clamp immediately proximal to the ring (Combined) or subjected to short scrotum castration (SSC) where the testicles were retained within the abdomen and only the scrotum removed. The behaviour of the ewe, treated lamb and untreated sibling where present (n = 54) were recorded for 30 minutes after treatment. Castration treatment increased the expression of abnormal standing and lying postures, specific pain-related behaviours (head-turning, stamping/kicking, easing quarters, tail wagging) and composite pain scores (P<0.001 for all). The greatest expression of pain-related behaviours was shown by lambs in the RR group, which were the only group to show rolling responses indicative of severe pain, followed by the SSC group. Ewes expressed more licking/sniffing responses to the RR and SSC lambs than towards the Combined and C lambs (P<0.05), and oriented most to RR lambs and least to C lambs (P<0.001). Ewes with two lambs also directed more attention towards the treated than the untreated lamb (P<0.001). The quantity of maternal care directed towards the lamb was positively correlated with the expression of active pain behaviours. The data demonstrate that ewes are able to discriminate between lambs in pain and those that are not, and that their response is increased with a greater severity of pain.