Prenatal maternal depression alters amygdala functional connectivity in 6-month-old infants

10.1038/tp.2015.3Translational Psychiatry52GUSTO (Growing up towards Healthy Outcomes

Intraoperative device closure of perimembranous ventricular septal defects in the young children under transthoracic echocardiographic guidance; initial experience

<p>Abstract</p> <p>Objectives</p> <p>This study aimed to assess the safety and feasibility of intraoperative device closure of perimembranous ventricular septal defects (VSD) in young children guided by transthoracic echocardiography (TTE).</p> <p>Methods</p> <p>We enrolled 18 patients from our hospital to participate in the study from June 2011 to September 2011. A minimal inferior median incision was performed after full evaluation of the perimembranous VSD by real-time TTE, and a domestically made device was inserted to occlude the perimembranous VSD. The proper size of the device was determined by means of transthoracic echocardiographic analysis.</p> <p>Results</p> <p>Implantation was ultimately successful in 16 patients using TTE guidance. In these cases, the complete closure rate immediately following the operation and on subsequent follow-up was 100%. Symmetric devices were used in 14 patients, and asymmetric devices were used in two patients. Two patient were transformed to surgical treatment, one for significant residual shunting, and the other for unsuccessful wire penetration of the VSD. The follow-up periods were less than nine months, and only one patient had mild aortic regurgitation. There were no instances of residual shunt, noticeable aortic regurgitation, significant arrhythmia, thrombosis, or device failure.</p> <p>Conclusions</p> <p>Minimally invasive transthoracic device closure of perimembranous VSDs is safe and feasible, using a domestically made device under transthoracic echocardiographic guidance, without the need for cardiopulmonary bypass. This technique should be considered an acceptable alternative to surgery or device closure guided by transesophageal echocardiography in selected young children. However, a long-term evaluation of outcomes is necessary.</p

Etk/Bmx Regulates Proteinase-Activated-Receptor1 (PAR1) in Breast Cancer Invasion: Signaling Partners, Hierarchy and Physiological Significance

BACKGROUND: While protease-activated-receptor 1 (PAR(1)) plays a central role in tumor progression, little is known about the cell signaling involved. METHODOLOGY/PRINCIPAL FINDINGS: We show here the impact of PAR(1) cellular activities using both an orthotopic mouse mammary xenograft and a colorectal-liver metastasis model in vivo, with biochemical analyses in vitro. Large and highly vascularized tumors were generated by cells over-expressing wt hPar1, Y397Z hPar1, with persistent signaling, or Y381A hPar1 mutant constructs. In contrast, cells over-expressing the truncated form of hPar1, which lacks the cytoplasmic tail, developed small or no tumors, similar to cells expressing empty vector or control untreated cells. Antibody array membranes revealed essential hPar1 partners including Etk/Bmx and Shc. PAR(1) activation induces Etk/Bmx and Shc binding to the receptor C-tail to form a complex. Y/A mutations in the PAR(1) C-tail did not prevent Shc-PAR(1) association, but enhanced the number of liver metastases compared with the already increased metastases obtained with wt hPar1. We found that Etk/Bmx first binds via the PH domain to a region of seven residues, located between C378-S384 in PAR(1) C-tail, enabling subsequent Shc association. Importantly, expression of the hPar1-7A mutant form (substituted A, residues 378-384), which is incapable of binding Etk/Bmx, resulted in inhibition of invasion through Matrigel-coated membranes. Similarly, knocking down Etk/Bmx inhibited PAR(1)-induced MDA-MB-435 cell migration. In addition, intact spheroid morphogenesis of MCF10A cells is markedly disrupted by the ectopic expression of wt hPar1. In contrast, the forced expression of the hPar1-7A mutant results in normal ball-shaped spheroids. Thus, by preventing binding of Etk/Bmx to PAR(1) -C-tail, hPar1 oncogenic properties are abrogated. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that a cytoplasmic portion of the PAR(1) C-tail functions as a scaffold site. We identify here essential signaling partners, determine the hierarchy of binding and provide a platform for therapeutic vehicles via definition of the critical PAR(1)-associating region in the breast cancer signaling niche

Purification and Characterization of Enterovirus 71 Viral Particles Produced from Vero Cells Grown in a Serum-Free Microcarrier Bioreactor System

[[abstract]]Background: Enterovirus 71 (EV71) infections manifest most commonly as a childhood exanthema known as hand-foot-and-mouth disease (HFMD) and can cause neurological disease during acute infection. Principal Finding: In this study, we describe the production, purification and characterization of EV71 virus produced from Vero cells grown in a five-liter serum-free bioreactor system containing 5 g/L Cytodex 1 microcarrier. The viral titer was >106 TCID50/mL by 6 days post infection when a MOI of 10?5 was used at the initial infection. Two EV71 virus fractions were separated and detected when the harvested EV71 virus concentrate was purified by sucrose gradient zonal ultracentrifugation. The EV71 viral particles detected in the 24–28% sucrose fractions had an icosahedral structure 30–31 nm in diameter and had low viral infectivity and RNA content. Three major viral proteins (VP0, VP1 and VP3) were observed by SDS-PAGE. The EV71 viral particles detected in the fractions containing 35–38% sucrose were 33–35 nm in size, had high viral infectivity and RNA content, and were composed of four viral proteins (VP1, VP2, VP3 and VP4), as shown by SDS-PAGE analyses. The two virus fractions were formalin-inactivated and induced high virus neutralizing antibody responses in mouse immunogenicity studies. Both mouse antisera recognized the immunodominant linear neutralization epitope of VP1 (residues 211–225). Conclusion:These results provide important information for cell-based EV71 vaccine development, particularly for the preparation of working standards for viral antigen quantification

Entanglement-enhanced testing of multiple quantum hypotheses

Quantum hypothesis testing has been greatly advanced for the binary discrimination of two states, or two channels. In this setting, we already know that quantum entanglement can be used to enhance the discrimination of two bosonic channels. Here, we remove the restriction of binary hypotheses and show that entangled photons can remarkably boost the discrimination of multiple bosonic channels. More precisely, we formulate a general problem of channel-position finding where the goal is to determine the position of a target channel among many background channels. We prove that, using entangled photons at the input and a generalized form of conditional nulling receiver at the output, we may outperform any classical strategy. Our results can be applied to enhance a range of technological tasks, including the optical readout of sparse classical data, the spectroscopic analysis of a frequency spectrum, and the determination of the direction of a target at fixed range

Gene-Expression Signature Predicts Postoperative Recurrence in Stage I Non-Small Cell Lung Cancer Patients

About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. The purpose of this study is to develop and validate a novel gene-expression signature that can predict tumor recurrence of stage I NSCLC patients. Cox proportional hazards regression analysis was performed to identify recurrence-related genes and a partial Cox regression model was used to generate a gene signature of recurrence in the training dataset −142 stage I lung adenocarcinomas without adjunctive therapy from the Director's Challenge Consortium. Four independent validation datasets, including GSE5843, GSE8894, and two other datasets provided by Mayo Clinic and Washington University, were used to assess the prediction accuracy by calculating the correlation between risk score estimated from gene expression and real recurrence-free survival time and AUC of time-dependent ROC analysis. Pathway-based survival analyses were also performed. 104 probesets correlated with recurrence in the training dataset. They are enriched in cell adhesion, apoptosis and regulation of cell proliferation. A 51-gene expression signature was identified to distinguish patients likely to develop tumor recurrence (Dxy = −0.83, P<1e-16) and this signature was validated in four independent datasets with AUC >85%. Multiple pathways including leukocyte transendothelial migration and cell adhesion were highly correlated with recurrence-free survival. The gene signature is highly predictive of recurrence in stage I NSCLC patients, which has important prognostic and therapeutic implications for the future management of these patients

Phonon-assisted carrier transport through a lattice-mismatched interface

We showed the distinctive unconventional junction effect of MoS2 junctions: a lattice mismatched MoS2. It is unique to observe the difference originated from the atomic interrelation at the interface. The results revealed the dominant scattering source at the conventional naturally stepwise junction, while the misorientationally stacked layer exhibited effectively decoupled behavior and a significantly smaller junction resistance via phonon assist carrier. Therefore, our finding in this paper clearly shows the different mechanisms in carrier transport at both junction interface of MoS2

Prokineticin 2 Regulates the Electrical Activity of Rat Suprachiasmatic Nuclei Neurons

Neuropeptide signaling plays roles in coordinating cellular activities and maintaining robust oscillations within the mammalian suprachiasmatic nucleus (SCN). Prokineticin2 (PK2) is a signaling molecule from the SCN and involves in the generation of circadian locomotor activity. Prokineticin receptor 2 (PKR2), a receptor for PK2, has been shown to be expressed in the SCN. However, very little is known about the cellular action of PK2 within the SCN. In the present study, we investigated the effect of PK2 on spontaneous firing and miniature inhibitory postsynaptic currents (mIPSCs) using whole cell patch-clamp recording in the SCN slices. PK2 dose-dependently increased spontaneous firing rates in most neurons from the dorsal SCN. PK2 acted postsynaptically to reduce γ-aminobutyric acid (GABA)-ergic function within the SCN, and PK2 reduced the amplitude but not frequency of mIPSCs. Furthermore, PK2 also suppressed exogenous GABA-induced currents. And the inhibitory effect of PK2 required PKC activation in the postsynaptic cells. Our data suggest that PK2 could alter cellular activities within the SCN and may influence behavioral and physiological rhythms

Xenograft models of head and neck cancers

Head and neck cancers are among the most prevalent tumors in the world. Despite advances in the treatment of head and neck tumors, the survival of patients with these cancers has not markedly improved over the past several decades because of our inability to control and our poor understanding of the regional and distant spread of this disease. One of the factors contributing to our poor understanding may be the lack of reliable animal models of head and neck cancer metastasis. The earliest xenograft models in which human tumor cells were grown in immunosuppressed mice involved subcutaneous implantation of human head and neck cancer cell lines. Subcutaneous xenograft models have been popular because they are easy to establish, easy to manage, and lend themselves to ready quantitation of the tumor burden. More recently, orthotopic xenograft models, in which the tumor cells are implanted in the tumor site of origin, have been used with greater frequency in animal studies of head and neck cancers. Orthotopic xenograft models are advantageous for their ability to mimic local tumor growth and recapitulate the pathways of metastasis seen in human head and neck cancers. In addition, recent innovations in cell labeling techniques and small-animal imaging have enabled investigators to monitor the metastatic process and quantitate the growth and spread of orthopically implanted tumors. This review summarizes the progress in the development of murine xenograft models of head and neck cancers. We then discuss the advantages and disadvantages of each type of xenograft model. We also discuss the potential for these models to help elucidate the mechanisms of regional and distant metastasis, which could improve our ability to treat head and neck cancers