Genome-wide identification of transcriptional enhancers during human placental development and association with function, differentiation, and disease†.

The placenta is a dynamic organ that must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier protection. Proper placenta development and function are critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown.

The human placenta project: Funded studies, imaging technologies, and future directions.

The placenta plays a critical role in fetal development. It serves as a multi-functional organ that protects and nurtures the fetus during pregnancy. However, despite its importance, the intricacies of placental structure and function in normal and diseased states have remained largely unexplored.

Longitudinal assessment of placental perfusion in normal and hypertensive pregnancies using pseudo-continuous arterial spin-labeled MRI: preliminary experience.

Objectives: To evaluate longitudinal placental perfusion using pseudo-continuous arterial spin-labeled (pCASL) MRI in normal pregnancies and in pregnancies affected by chronic hypertension (cHTN), who are at the greatest risk for placental-mediated disease conditions.

Methods: Eighteen normal and 23 pregnant subjects with cHTN requiring antihypertensive therapy were scanned at 3 T using free-breathing pCASL-MRI at 16-20 and 24-28 weeks of gestational age.

Results: Mean placental perfusion was 103.

Loss of Selenoprotein Iodothyronine Deiodinase 3 Expression Correlates with Progression of Complete Hydatidiform Mole to Gestational Trophoblastic Neoplasia.

To investigate if differences in imprinting at tropho-microRNA (miRNA) genomic clusters can distinguish between pre-gestational trophoblastic neoplasia cases (pre-GTN) and benign complete hydatidiform mole (CHM) cases at the time of initial uterine evacuation. miRNA sequencing was performed on frozen tissue from 39 CHM cases including 9 GTN cases. DIO3, DLK1, RTL1, and MEG 3 mRNA levels were assessed by qRT-PCR.

Prosecuting child abusers, respecting victims: a contrast of approaches in the UK, Tajikistan and Tanzania.

This article summarises child abuse as a global problem of increasing breadth and complexity. It reviews the development of procedures for prosecuting alleged abusers and treating complainants appropriately in the course of investigations, medical examinations and court hearings. It contrasts the diverse environments of the UK, Tajikistan and Tanzania.

Multiple effects of silymarin on the hepatitis C virus lifecycle.

Unlabelled: Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro and in vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had antiviral effects against hepatitis C virus cell culture (HCVcc) infection that included inhibition of virus entry, RNA and protein expression, and infectious virus production.

Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor.

Hepatitis C virus (HCV) infection is a major cause of liver disease. HCV associates with host apolipoproteins and enters hepatocytes through complex processes involving some combination of CD81, claudin-1, occludin, and scavenger receptor BI. Here we show that infectious HCV resembles very low density lipoprotein (VLDL) and that entry involves co-receptor function of the low-density lipoprotein receptor (LDL-R).

Fighting the flu with inflammasome signaling.

A wide variety of stimuli induce the inflammasome, but little is known about its role in immune protection against viruses. In this issue of Immunity, Allen et al. (2009) and Thomas et al.

Evasion and disruption of innate immune signalling by hepatitis C and West Nile viruses.

Signalling pathways leading to type I interferon production are the first line of defence employed by the host to combat viruses, and represent a barrier that an invading virus must overcome in order to establish infection. In this review we highlight the ability of two members of the Flaviviridae, a globally distributed family of RNA viruses that represent a significant public health concern, to disrupt and evade these defences. Hepatitis C virus is a hepatotropic virus, infecting greater than 170 million people worldwide, while West Nile virus is a neurotropic virus that causes encephalitis in humans and horses.

Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA.

Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase.

Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients.

Unlabelled: Interferon regulatory factor-3 (IRF-3) activation directs alpha/beta interferon production and interferon-stimulated gene (ISG) expression, which limits virus infection. Here, we examined the distribution of hepatitis C virus (HCV) nonstructural 3 protein, the status of IRF-3 activation, and expression of IRF-3 target genes and ISGs during asynchronous HCV infection in vitro and in liver biopsies from patients with chronic HCV infection, using confocal microscopy and functional genomics approaches. In general, asynchronous infection with HCV stimulated a low-frequency and transient IRF-3 activation within responsive cells in vitro that was associated with cell-to-cell virus spread.

Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins.

Hepatitis C virus (HCV) and triglyceride-rich very low-density lipoproteins (VLDLs) both are secreted uniquely by hepatocytes and circulate in blood in a complex. Here, we isolated from human hepatoma cells the membrane vesicles in which HCV replicates. These vesicles, which contain the HCV replication complex, are highly enriched in proteins required for VLDL assembly, including apolipoprotein B (apoB), apoE, and microsomal triglyceride transfer protein.

Functional and therapeutic analysis of hepatitis C virus NS3.4A protease control of antiviral immune defense.

Chronic hepatitis C virus (HCV) infection is a major global public health problem. HCV infection is supported by viral strategies to evade the innate antiviral response wherein the viral NS3.4A protease complex targets and cleaves the interferon promoter stimulator-1 (IPS-1) adaptor protein to ablate signaling of interferon alpha/beta immune defenses.

Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection.

Viral signaling through retinoic acid-inducible gene-I (RIG-I) and its adaptor protein, IFN promoter-stimulator 1 (IPS-1), activates IFN regulatory factor-3 (IRF-3) and the host IFN-alpha/beta response that limits virus infection. The hepatitis C virus (HCV) NS3/4A protease cleaves IPS-1 to block RIG-I signaling, but how this regulation controls the host response to HCV is not known. Moreover, endogenous IPS-1 cleavage has not been demonstrated in the context of HCV infection in vitro or in vivo.