Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in São Paulo state, Brazil. We show that different viral genotypes entered São Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in São Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.     

Hypocotyl of seedlings of the large-seeded species Araucaria angustifolia: an important underground sink of the seed reserves

Araucaria angustifolia exhibits cryptogeal germination, where the root–hypocotyl axis emerges first and penetrates into the soil. In Araucaria bidwillii, the whole process of transferring reserves from the seed to the seedling takes place before shoot emergence, and there is a major storage of these reserves in the underground hypocotyl, which assumes a tuberous form. In A. angustifolia, the shoot emerges before seed reserves are depleted. Though it does not grow like a tuber, the hypocotyl of A. angustifolia grows thicker than the adjacent taproot during initial growth, and we hypothesize that it may act as a major sink for seed reserves during this stage. The study tests this hypothesis by evaluating changes in the mass of different plant parts during initial growth. Four harvests were conducted during a ~6-month period to compare the dry mass of different fractions (attached seed, seedling, its shoot and root and the hypocotyl) of seedlings growing under darkness and high light. While seed reserves were still being depleted, the hypocotyl mass showed an initial increase and then a reduction. This was more abrupt when light was available. After seed mass had stabilized, the mass of the hypocotyl continued to decrease in the dark-grown seedlings, but showed a second increase in the light-grown ones. Results confirm the hypothesis that the hypocotyl represents a major sink for the seed reserves of A. angustifolia, acting as an underground storage structure for the growing seedling. Its reserves seem to be important for sustaining initial shoot growth and might also act as a storage sink for photosynthates.     

On Hepatitis C Virus Evolution: The Interaction between Virus and Host towards Treatment Outcome

Background

Hepatitis C is a disease spread throughout the world. Hepatitis C virus (HCV), the etiological agent of this disease, is a single-stranded positive RNA virus. Its genome encodes a single precursor protein that yields ten proteins after processing. NS5A, one of the non-structural viral proteins, is most associated with interferon-based therapy response, the approved treatment for hepatitis C in Brazil. HCV has a high mutation rate and therefore high variability, which may be important for evading the immune system and response to therapy. The aim of this study was to analyze the evolution of NS5A quasispecies before, during, and after treatment in patients infected with HCV genotype 3a who presented different therapy responses.

Methods

Viral RNA was extracted, cDNA was synthesized, the NS5A region was amplified and cloned, and 15 clones from each time-point were sequenced. The sequences were analyzed for evolutionary history, genetic diversity and selection.

Results

This analysis shows that the viral population that persists after treatment for most non-responder patients is present in before-treatment samples, suggesting it is adapted to evade treatment. In contrast, the population found in before treatment samples from most end-of-treatment responder patients either are selected out or appears in low frequency after relapse, therefore changing the population structure. The exceptions illustrate the uniqueness of the evolutionary process, and therefore the treatment resistance process, in each patient.

Conclusion

Although evolutionary behavior throughout treatment showed that each patient presented different population dynamics unrelated to therapy outcome, it seems that the viral population from non-responders that resists the treatment already had strains that could evade therapy before it started.     

Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells

Introduction

We reported that ryanodine receptors are expressed in two different types of mammalian peripheral taste receptor cells: Type II and Type III cells. Type II cells lack voltage-gated calcium channels (VGCCs) and chemical synapses. In these cells, ryanodine receptors contribute to the taste-evoked calcium signals that are initiated by opening inositol trisphosphate receptors located on internal calcium stores. In Type III cells that do have VGCCs and chemical synapses, ryanodine receptors contribute to the depolarization-dependent calcium influx.

Methodology/Principal Findings

The goal of this study was to establish if there was selectivity in the type of VGCC that is associated with the ryanodine receptor in the Type III taste cells or if the ryanodine receptor opens irrespective of the calcium channels involved. We also wished to determine if the ryanodine receptors and VGCCs require a physical linkage to interact or are simply functionally associated with each other. Using calcium imaging and pharmacological inhibitors, we found that ryanodine receptors are selectively associated with L type VGCCs but likely not through a physical linkage.

Conclusions/Significance

Taste cells are able to undergo calcium induced calcium release through ryanodine receptors to increase the initial calcium influx signal and provide a larger calcium response than would otherwise occur when L type channels are activated in Type III taste cells.     

An Exploration of Cultural Identity Patterns and the Family Context among Arab Muslim Young Adults in America

While many studies have explored cultural adaptation and development and its correlates among adult Arab immigrants to the United States (U.S.), little empirical work has focused on Arab youth who were raised in the U.S., particularly Arab Muslim young adults. The present study explores cultural identity patterns and the sociodemographic and family contexts of 150 Arab Muslim American young adults ages 18–25 who completed an Internet study. The participants fell into three cultural identity groups: High Bicultural, Moderate Bicultural, and High Arab Cultural. Although all three groups demonstrated positive general family functioning, the Moderate Bicultural group was distinct in that they were less likely to be engaged or married, and they experienced less family support and more family acculturative stressors. The results highlight the importance of the family context in contributing to a stronger sense of cultural identity for young adults who fall at the intersection of Arab and American culture and Muslim faith.     

Full-length genomic sequence of hepatitis B virus genotype C2 isolated from a native Brazilian patient

The hepatitis B virus (HBV) is among the leading causes of chronic hepatitis, cirrhosis and hepatocellular carcinoma. In Brazil, genotype A is the most frequent, followed by genotypes D and F. Genotypes B and C are found in Brazil exclusively among Asian patients and their descendants. The aim of this study was to sequence the entire HBV genome of a Caucasian patient infected with HBV/C2 and to infer the origin of the virus based on sequencing analysis. The sequence of this Brazilian isolate was grouped with four other sequences described in China. The sequence of this patient is the first complete genome of HBV/C2 reported in Brazil.