Alcohol Impairs Predation Risk Response and Communication in Zebrafish

The effects of ethanol exposure on Danio rerio have been studied from the perspectives of developmental biology and behavior. However, little is known about the effects of ethanol on the prey-predator relationship and chemical communication of predation risk. Here, we showed that visual contact with a predator triggers stress axis activation in zebrafish. We also observed a typical stress response in zebrafish receiving water from these conspecifics, indicating that these fish chemically communicate predation risk. Our work is the first to demonstrate how alcohol effects this prey-predator interaction. We showed for the first time that alcohol exposure completely blocks stress axis activation in both fish seeing the predator and in fish that come in indirect contact with a predator by receiving water from these conspecifics. Together with other research results and with the translational relevance of this fish species, our data points to zebrafish as a promising animal model to study human alcoholism.     

Predictors of Attrition and Immunological Failure in HIV-1 Patients on Highly Active Antiretroviral Therapy from Different Healthcare Settings in Mozambique

In Mozambique, the evaluation of retention in HIV care and ART programmes is limited. To assess rate and predictors of attrition (no retention in care) and HAART effectiveness in HIV-1 infected patients who pay for medication and laboratory testing in Mozambique, we conducted a multicenter survey of HIV-1-infected patients who started HAART during 2002–2006. Cox proportional hazard models were used to assess risk of attrition and of therapy failure. Overall, 142 patients from 16 healthcare centers located in the capital city Maputo were followed-up for 22.2 months (12.1–46.7). The retention rate was 75%, 48% and 37% after one, two and three years, respectively. Risk of attrition was lower in patients with higher baseline CD4 count (P = 0.022) and attending healthcare center 1 (HCC1) (P = 0.013). The proportion of individuals with CD4 count ≤200 cells/µL was 55% (78/142) at baseline and decreased to 6% (3/52) at 36 months. Among the patients with available VL, 86% (64/74) achieved undetectable VL levels. The rate of immunologic failure was 17.2% (95% CI: 12.6–22.9) per 100 person-years. Risk of failure was associated to higher baseline CD4 count (P = 0.002), likely reflecting low adherence levels, and decreased with baseline VL ≥10,000 copies/mL (P = 0.033). These results suggest that HAART can be effective in HIV-1 infected patients from Mozambique that pay for their medication and laboratory testing. Further studies are required to identify the causes for low retention rates in patients with low CD4 counts and to better understand the association between healthcare setting and attrition rate.     

Evaluating the Impact of Different Sequence Databases on Metaproteome Analysis: Insights from a Lab-Assembled Microbial Mixture

Metaproteomics enables the investigation of the protein repertoire expressed by complex microbial communities. However, to unleash its full potential, refinements in bioinformatic approaches for data analysis are still needed. In this context, sequence databases selection represents a major challenge.This work assessed the impact of different databases in metaproteomic investigations by using a mock microbial mixture including nine diverse bacterial and eukaryotic species, which was subjected to shotgun metaproteomic analysis. Then, both the microbial mixture and the single microorganisms were subjected to next generation sequencing to obtain experimental metagenomic- and genomic-derived databases, which were used along with public databases (namely, NCBI, UniProtKB/SwissProt and UniProtKB/TrEMBL, parsed at different taxonomic levels) to analyze the metaproteomic dataset. First, a quantitative comparison in terms of number and overlap of peptide identifications was carried out among all databases. As a result, only 35% of peptides were common to all database classes; moreover, genus/species-specific databases provided up to 17% more identifications compared to databases with generic taxonomy, while the metagenomic database enabled a slight increment in respect to public databases. Then, database behavior in terms of false discovery rate and peptide degeneracy was critically evaluated. Public databases with generic taxonomy exhibited a markedly different trend compared to the counterparts. Finally, the reliability of taxonomic attribution according to the lowest common ancestor approach (using MEGAN and Unipept software) was assessed. The level of misassignments varied among the different databases, and specific thresholds based on the number of taxon-specific peptides were established to minimize false positives. This study confirms that database selection has a significant impact in metaproteomics, and provides critical indications for improving depth and reliability of metaproteomic results. Specifically, the use of iterative searches and of suitable filters for taxonomic assignments is proposed with the aim of increasing coverage and trustworthiness of metaproteomic data.     

Laminin 332 in junctional epidermolysis bullosa

Laminin 332 is an essential component of the dermal-epidermal junction, a highly specialized basement membrane zone that attaches the epidermis to the dermis and thereby provides skin integrity and resistance to external mechanical forces. Mutations in the LAMA3, LAMB3 and LAMC2 genes that encode the three constituent polypeptide chains, α3, β3 and γ2, abrogate or perturb the functions of laminin 332. The phenotypic consequences are diminished dermal-epidermal adhesion and, as clinical symptoms, skin fragility and mechanically induced blistering. The disorder is designated as junctional epidermolysis bullosa (JEB). This article delineates the signs and symptoms of the different forms of JEB, the mutational spectrum, genotype-phenotype correlations as well as perspectives for future molecular therapies.     

ERP Modulation during Observation of Abstract Paintings by Franz Kline

The aim of this study was to test the involvement of sensorimotor cortical circuits during the beholding of the static consequences of hand gestures devoid of any meaning.In order to verify this hypothesis we performed an EEG experiment presenting to participants images of abstract works of art with marked traces of brushstrokes. The EEG data were analyzed by using Event Related Potentials (ERPs). We aimed to demonstrate a direct involvement of sensorimotor cortical circuits during the beholding of these selected works of abstract art. The stimuli consisted of three different abstract black and white paintings by Franz Kline. Results verified our experimental hypothesis showing the activation of premotor and motor cortical areas during stimuli observation. In addition, abstract works of art observation elicited the activation of reward-related orbitofrontal areas, and cognitive categorization-related prefrontal areas. The cortical sensorimotor activation is a fundamental neurophysiological demonstration of the direct involvement of the cortical motor system in perception of static meaningless images belonging to abstract art. These results support the role of embodied simulation of artist’s gestures in the perception of works of art.     

Getting Your Sea Legs

Sea travel mandates changes in the control of the body. The process by which we adapt bodily control to life at sea is known as getting one''s sea legs. We conducted the first experimental study of bodily control as maritime novices adapted to motion of a ship at sea. We evaluated postural activity (stance width, stance angle, and the kinematics of body sway) before and during a sea voyage. In addition, we evaluated the role of the visible horizon in the control of body sway. Finally, we related data on postural activity to two subjective experiences that are associated with sea travel; seasickness, and mal de debarquement. Our results revealed rapid changes in postural activity among novices at sea. Before the beginning of the voyage, the temporal dynamics of body sway differed among participants as a function of their (subsequent) severity of seasickness. Body sway measured at sea differed among participants as a function of their (subsequent) experience of mal de debarquement. We discuss implications of these results for general theories of the perception and control of bodily orientation, for the etiology of motion sickness, and for general phenomena of perceptual-motor adaptation and learning.     

Lifelong Expression of Apolipoprotein D in the Human Brainstem: Correlation with Reduced Age-Related Neurodegeneration

The lipocalin apolipoprotein D (Apo D) is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus). In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32−96 years of age) with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial) than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.     

Cost-Effectiveness of Quantiferon?-TB Gold-In-Tube Versus Tuberculin Skin Testing for Contact Screening and Treatment of Latent Tuberculosis Infection in Brazil

Background

Latent tuberculosis infection (LTBI) is a reservoir for new TB cases. Isoniazid preventive therapy (IPT) reduces the risk of active TB by as much as 90%, but LTBI screening has limitations. Unlike tuberculin skin testing (TST), interferon-gamma release assays are not affected by BCG vaccination, and have been reported to be cost-effective in low-burden countries. The goal of this study was to perform a cost-effectiveness analysis from the health system perspective, comparing three strategies for LTBI diagnosis in TB contacts: tuberculin skin testing (TST), QuantiFERON®-TB Gold-in-Tube (QFT-GIT) and TST confirmed by QFT-GIT if positive (TST/QFT-GIT) in Brazil, a middle-income, high-burden country with universal BCG coverage.

Methodology/Principal Findings

Costs for LTBI diagnosis and treatment of a hypothetical cohort of 1,000 adult immunocompetent close contacts were considered. The effectiveness measure employed was the number of averted TB cases in two years. Health system costs were US$ 105,096 for TST, US$ 121,054 for QFT-GIT and US$ 101,948 for TST/QFT-GIT; these strategies averted 6.56, 6.63 and 4.59 TB cases, respectively. The most cost-effective strategy was TST (US$ 16,021/averted case). The incremental cost-effectiveness ratio was US$ 227,977/averted TB case for QFT-GIT. TST/QFT-GIT was dominated.

Conclusions

Unlike previous studies, TST was the most cost-effective strategy for averting new TB cases in the short term. QFT-GIT would be more cost-effective if its costs could be reduced to US$ 26.95, considering a TST specificity of 59% and US$ 18 considering a more realistic TST specificity of 80%. Nevertheless, with TST, 207.4 additional people per 1,000 will be prescribed IPT compared with QFT.