Elements of Neuroanthropology.

Neuroanthropology is the integration of neuroscience into anthropology and aims to understand "brains in the wild." This interdisciplinary field examines patterns of human variation in field settings and provides empirical research that complements work done in clinical and laboratory settings. Neuroanthropology often uses ethnography in combination with theories and methods from cognitive science as a way to capture how culture, mind, and brain interact. This article describes nine elements that outline how to do neuroanthropology research: (1) integrating biology and culture through neuroscience and biocultural anthropology; (2) extending focus of anthropology on what people say and do to include what people process; (3) sizing culture appropriately, from broad patterns of culture to culture in small-scale settings; (4) understanding patterns of cultural variation, in particular how culture produces patterns of shared variation; (5) considering individuals in interaction with culture, with levels of analysis that can go from biology to social structures; (6) focusing on interactive elements that bring together biological and cultural processes; (7) conceptual triangulation, which draws on anthropology, psychology, and neuroscience in conjunction with field, clinic, and laboratory; (8) critical complementarity as a way to integrate the strengths of critical scholarship with interdisciplinary work; and (9) using methodological triangulation as a way to advance interdisciplinary research. These elements are illustrated through three case studies: research on US combat veterans and how they use Brazilian Jiu Jitsu as a way to manage the transition to becoming civilians, work on human-raptor interactions to understand how and why these interactions can prove beneficial for human handlers, and adapting cue reactivity research on addiction to a field-based approach to understand how people interact with cues in naturalistic settings.

In Vivo Structure-Function Analysis and Redox Interactomes of Leishmania tarentolae Erv.

Import and oxidative folding of proteins in the mitochondrial intermembrane space differ among eukaryotic lineages. While opisthokonts such as yeast rely on the receptor and oxidoreductase Mia40 in combination with the Mia40:cytochrome c oxidoreductase Erv, kinetoplastid parasites and other Excavata/Discoba lack Mia40 but have a functional Erv homologue. Whether excavate Erv homologues rely on a Mia40 replacement or directly interact with imported protein substrates remains controversial. Here, we used the CRISPR-Cas9 system to generate a set of tagged and untagged homozygous mutants of LTERV from the kinetoplastid model parasite Leishmania tarentolae. Modifications of the shuttle cysteine motif of LtErv were lethal, whereas replacement of clamp residue Cys17 or removal of the kinetoplastida-specific second (KISS) domain had no impact on parasite viability under standard growth conditions. However, removal of the KISS domain rendered parasites sensitive to heat stress and led to the accumulation of homodimeric and mixed LtErv disulfides. We therefore determined and compared the redox interactomes of tagged wild-type LtErv and LtErvΔKISS using stable isotope labeling by amino acids in cell culture (SILAC) and quantitative mass spectrometry. While the Mia40-replacement candidate Mic20 and all but one typical substrate with twin Cx3/9C-motifs were absent in both redox interactomes, we identified a small set of alternative potential interaction partners with putative redox-active cysteine residues. In summary, our study reveals parasite-specific intracellular structure-function relationships and redox interactomes of LtErv with implications for current hypotheses on mitochondrial protein import in nonopisthokonts. IMPORTANCE The discovery of the redox proteins Mia40/CHCHD4 and Erv1/ALR, as well as the elucidation of their relevance for oxidative protein folding in the mitochondrial intermembrane space of yeast and mammals, founded a new research topic in redox biology and mitochondrial protein import. The lack of Mia40/CHCHD4 in protist lineages raises fundamental and controversial questions regarding the conservation and evolution of this essential pathway. Do protist Erv homologues act alone, or do they use the candidate Mic20 or another protein as a Mia40 replacement? Furthermore, we previously showed that Erv homologues in L. tarentolae and the human pathogen L. infantum are not only essential but also differ structurally and mechanistically from yeast and human Erv1/ALR. Here, we analyzed the relevance of such structural differences in vivo and determined the first redox interactomes of a nonopisthokont Erv homologue. Our data challenge recent hypotheses on mitochondrial protein import in nonopisthokonts.

Testing the CRISPR-Cas9 and glmS ribozyme systems in Leishmania tarentolae.

Leishmania parasites include important pathogens and model organisms and are even used for the production of recombinant proteins. However, functional genomics and the characterization of essential genes are often limited in Leishmania because of low-throughput technologies for gene disruption or tagging and the absence of components for RNA interference. Here, we tested the T7 RNA polymerase-dependent CRISPR-Cas9 system by Beneke et al. and the glmS ribozyme-based knock-down system in the model parasite Leishmania tarentolae. We successfully deleted two reference genes encoding the flagellar motility factor Pf16 and the salvage-pathway enzyme adenine phosphoribosyltransferase, resulting in immotile and drug-resistant parasites, respectively. In contrast, we were unable to disrupt the gene encoding the mitochondrial flavoprotein Erv. Cultivation of L. tarentolae in standard BHI medium resulted in a constitutive down-regulation of an episomal mCherry-glmS reporter by 40 to 60%. For inducible knock-downs, we evaluated the growth of L. tarentolae in alternative media and identified supplemented MEM, IMDM and McCoy's 5A medium as candidates. Cultivation in supplemented MEM allowed an inducible, glucosamine concentration-dependent down-regulation of the episomal mCherry-glmS reporter by more than 70%. However, chromosomal glmS-tagging of the genes encoding Pf16, adenine phosphoribosyltransferase or Erv did not reveal a knock-down phenotype. Our data demonstrate the suitability of the CRISPR-Cas9 system for the disruption and tagging of genes in L. tarentolae as well as the limitations of the glmS system, which was restricted to moderate efficiencies for episomal knock-downs and caused no detectable phenotype for chromosomal knock-downs.

Macroscopic and Histological Morphology of the Equine Digital Cushion and Its Association with Subcutaneous Fat Thickness.

This study evaluated the influence of the Body Condition Score (BCS) and subcutaneous fat thickness on the tissue composition of the digital cushion in horses. Sixty mixed breeds of Criollo horses (21 males and 39 females) were sent for slaughter. All animals were submitted to BCS analysis, through visual antemortem evaluation, and then ultrasound evaluation to estimate the subcutaneous fat thickness. Macroscopic analyses of the thoracic and a pelvic limb (weight, volume, and density of the hooves and digital cushions) were performed. In addition, measurements of the area of internal structures to the hoof and histological analyzes were carried out to measure the areas of adipose, fibroelastic, and collagen fibers of the digital cushion. There were no macroscopic differences in the digital cushion between thoracic and pelvic limbs or between genders (P > .05). Likewise, the histological characteristics between the limbs and the genders were similar (P > .05). There was no correlation between the weight, volume, and density of the digital cushion with the BCS (P > .05). A positive correlation was observed with the area of adipose tissue (P = .038, R2 = 0.28) and a negative correlation with area of fibroelastic tissue (P = .005, R2 = -0.37) and collagen fibers (P = .003, R2 = -0.39). In conclusion, the adipose tissue, fibroelastic tissue, and collagen fibers of equine digital cushion alter their areas in the functions of the various subcutaneous fat patterns in horses.

Systematic review with meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma.

BACKGROUND: Calcineurin-inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure-related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. AIM: To clarify the potential benefit of mTOR-inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin-inhibitor-based immunosuppression. METHODS: A systematic review and meta-analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early-initiated (<6 months post-transplant) mTOR-inhibitor-based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin-inhibitor-based therapy. RESULTS: Meta-analysis demonstrated that compared with calcineurin-inhibitor controls, recurrence-free-survival was significantly increased with mTOR-inhibitor-based therapy at 1-year (Risk-Ratio (RR): 1.09, 95% CI: 1.01-1.18) and 3-years (RR: 1.1, 95% CI: 1.01-1.21) post-transplant, with a nonsignificant increase at 5-years (RR: 1.15, 95% CI: 0.99-1.35). Overall survival was improved at 1-year (RR: 1.07, 95% CI: 1.02-1.12), 3-years (RR: 1.1, 95% CI: 1.02-1.19), and 5-years (RR: 1.18, 95% CI: 1.08-1.29). Recurrence-rate was lower in the mTOR-inhibitor arm (RR: 0.67, 95% CI: 0.56-0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94-1.28). CONCLUSIONS: mTOR-inhibitor-based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence-free-survival over at least three years and reduces the recurrence rate compared with standard calcineurin-inhibitor-based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.

Helicobacter pylori and low-dose aspirin ulcer risk: A meta-analysis.

BACKGROUND AND AIM: Owing to wide-spread use, low-dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta-analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy. METHODS: Literature screening was performed in MEDLINE and EMBASE from inception to May 2018. Original studies reporting prevalence or incidence of uncomplicated ulcers in LDA users were included. Ulcer endpoints needed to be specified separately, according to H. pylori infection status. Meta-analysis was performed in MIX 2.0 Pro. RESULTS: Ten cross-sectional studies and seven randomized controlled trials were included (n = 5964). The pooled odds ratios with 95% confidence intervals (CI) for the risk of LDA ulcers in H. pylori-positive versus H. pylori-negative individuals were 1.68 (95%CI 1.40-2.02) and 1.65 (95%CI 1.29-2.08) under fixed-effects and random-effects models, respectively. Heterogeneity among studies was minimal (I2  = 26.9%). After adjusting for the protective effects of antisecretory drugs, the odds ratios increased to 1.94 (95%CI 1.54-2.46). CONCLUSION: This analysis suggests that H. pylori increases the risk of LDA ulcers by almost 70% in a population where some were taking proton pump inhibitors and/or other acid suppressants. Without antisecretory drugs, the risk almost doubles. Clinically, these findings may support the use of a test-and-treat approach to H. pylori in LDA users, particularly those already at higher risk of developing peptic ulcers.

Structure of the novel monomeric glyoxalase I from Zea mays.

The glyoxalase system is ubiquitous among all forms of life owing to its central role in relieving the cell from the accumulation of methylglyoxal, a toxic metabolic byproduct. In higher plants, this system is upregulated under diverse metabolic stress conditions, such as in the defence response to infection by pathogenic microorganisms. Despite their proven fundamental role in metabolic stresses, plant glyoxalases have been poorly studied. In this work, glyoxalase I from Zea mays has been characterized both biochemically and structurally, thus reporting the first atomic model of a glyoxalase I available from plants. The results indicate that this enzyme comprises a single polypeptide with two structurally similar domains, giving rise to two lateral concavities, one of which harbours a functional nickel(II)-binding active site. The putative function of the remaining cryptic active site remains to be determined.

Hydatidosis in the province of La Pampa, Argentina, 1998.

Echinococcus granulosus is the agent that causes the classical hydatidosis or cystic echinococcosis. The most spread cycle in South America is the sheep-dog cycle, and offers favorable conditions for the development of the parasite. As the province of La Pampa shows an endemic presence with notification of cases and infected dogs, the present work has the aim of contributing to the study of the distribution and prevalence of the disease in the district of Maracó, La Pampa, Argentina. Dogs of 36 farms that had ovines, were dosed with arecoline hydrobromide at a dose of 3.5 mg/kg. Dogs from 27 (75%) farms resulted positive to Tenia sp. and 3 (8.3%) to E. granulosus. Blood samples were taken to all the people living in all the inquired farm and were processed by the ELISA test for hydatidosis. A retrospective survey on cases of human hydatidosis attended in the Hospital of General Pico, head if the sanitary region, and in two private clinics was performed. Analysis of clinical records indicated 11 cases operated during the period 1996/1997 (annual incidence rate of 6.8 per 100,000 inhabitants). It is of public health interest to fulfill epidemiologic investigations in other districts of the Province of La Pampa with the aim of delimitating the endemic distribution within the province and also organizing surveillance systems on human hydatidosis.

[Hydatidosis/echinococcosis in General Acha, La Pampa Province, Argentina]. / Hidatidosis/equinococosis en el área de General Acha, Provincia de la Pampa, Argentina.

Hydatidosis situation in the General Acha area (La Pampa Province) is described herein. The work comprises a retrospective compilacion of new hydatidosis human cases, the findings in seroepidemiological surveys with enzyme immuno assay (EIA) for hydatidosis in human population, and investigation on dog Echinococcus granulosus infection prevalence carried out on the basis of arecoline bromhydrate application. Sixteen human cases were detected during 1994 (incidence rate: 26.7/100,000), founding a serological prevalence of 1.3%. Studies on dog echinococosis have shown a prevalence rate of 2.3%. The epidemiological situation of hydatidosis is analyzed by comparison with values from other endemic areas. These results suggest the necessity of completing surveys in the whole provincial territory, and the implementation of educational and sanitary measures aimed to controlling this zoonosis.