In the Brazilian Amazon, the suspected source of infection in an outbreak of acute Chagas disease involving 10 patients was Euterpe oleracea (açaí berry) juice. Patient blood and juice samples contained Trypanosoma cruzi TcIV, indicating oral transmission of the Chagas disease agent.

It is commonly assumed that the brain's neural coding strategies are adapted to the statistics of natural stimuli. Specifically, to maximize information transmission, a sensory neuron's tuning function should effectively oppose the decaying stimulus spectral power, such that the neural response is temporally decorrelated (i.e. 'whitened'). However, theory predicts that the structure of neuronal variability also plays an essential role in determining how coding is optimized. Here, we provide experimental evidence supporting this view by recording from neurons in early vestibular pathways during naturalistic self-motion. We found that central vestibular neurons displayed temporally whitened responses that could not be explained by their tuning alone. Rather, computational modeling and analysis revealed that neuronal variability and tuning were matched to effectively complement natural stimulus statistics, thereby achieving temporal decorrelation and optimizing information transmission. Taken together, our findings reveal a novel strategy by which neural variability contributes to optimized processing of naturalistic stimuli.

Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called dynein axonemal assembly factors (DNAAFs) that act in the cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show that DNAAFs concentrate together with axonemal dyneins and chaperones into organelles that form specifically in multiciliated cells, which we term DynAPs, for dynein axonemal particles. These organelles display hallmarks of biomolecular condensates, and remarkably, DynAPs are enriched for the stress granule protein G3bp1, but not for other stress granule proteins or P-body proteins. Finally, we show that both the formation and the liquid-like behaviors of DynAPs are disrupted in a model of motile ciliopathy. These findings provide a unifying cell biological framework for a poorly understood class of human disease genes and add motile ciliopathy to the growing roster of human diseases associated with disrupted biological phase separation.

Celiac disease is a chronic immune-mediated enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals. Many genes involved in the pathogenesis have been identified and a crucial role is known to be played by the Human Leukocyte Antigen (HLA) system. The main determinants for genetic susceptibility are HLA-DQA1 and HLA-DQB1 genes encoding for HLA-DQ2 and HLA-DQ8 molecules, carried by almost all patients affected. However, since HLA-DQ2 and HLA-DQ8 heterodimers explain almost 40% of the disease heritability, HLA typing should not be applied in diagnosis, but exclusively to clarify uncertain diagnoses, considering its negative predictive value.

Contrast enhanced Computed Tomography (CCT) is the most used imaging test to investigate acute abdominal clinical conditions, because of its high sensitivity and specificity. It is mandatory to make a correct and prompt diagnosis when life threatening abdominal diseases as mesenteric ischemia are suspected. Contrast medium administration was linked to acute renal failure, therefore radiologist often prefer to perform CCT without contrast in patients needing to undergo the exam with increased serum creatinine.  The aim of the review was to focus on the incidence of contrast induced nephropathy in patients presenting non-traumatic acute abdominal clinical conditions, who underwent CCT with intravenous contrast agent administration in emergency setting.

Esophageal strictures in pediatric age are a quite common condition due to different etiologies. Esophageal strictures can be divided in congenital, acquired and functional. Clinical manifestations are similar and when symptoms arise, endoscopic dilation is the treatment of choice. Our aim was to consider the efficacy of this technique in pediatric population, through a wide review of the literature.

Tumor Necrosis Factor (TNF) has a crucial role in inflammation, cell proliferation and cell death. Dysregulation of TNF receptor 1 (TNFR1)-induced Nuclear Factor-kappa B (NF-κB) signaling leads to chronic inflammation and is associated with several human inflammatory pathologies. Hence, TNF neutralization suppresses inflammation and attenuates inflammatory pathology. However, despite its beneficial effects, anti-TNF therapy suffers from efficacy issues and severe immune side effects. There is thus an urging need to identify novel targets for pharmaceutical intervention in the NF-κB signaling pathway. Here, we present a protein-protein interaction dataset of the TNFR1-induced signaling pathway. For this, we used Virotrap, a novel method for studying protein complexes without disrupting the cellular integrity, on 12 central proteins controlling NF-κB and cell death signaling, both under resting conditions as well as upon TNF stimulation. Our dataset reveals dynamic interactions in TNFR1-induced NF-κB signaling and identifies both known as well as novel interactors that may help to further unravel the molecular mechanisms steering TNF-induced inflammatory signaling and pathology.

During calcium-regulated exocytosis, the constitutive fusion machinery is 'clamped' in a partially assembled state until synchronously released by calcium. The protein machinery involved in this process is known, but the supra-molecular architecture and underlying mechanisms are unclear. Here, we use cryo-electron tomography analysis in nerve growth factor-differentiated neuro-endocrine (PC12) cells to delineate the organization of the release machinery under the docked vesicles. We find that exactly six exocytosis modules, each likely consisting of a single SNAREpin with its bound Synaptotagmins, Complexin, and Munc18 proteins, are symmetrically arranged at the vesicle-PM interface. Mutational analysis suggests that the symmetrical organization is templated by circular oligomers of Synaptotagmin. The observed arrangement, including its precise radial positioning, is in-line with the recently proposed 'buttressed ring hypothesis'.

Analysis of large data sets is currently a major challenge. Strong efforts are being undertaken to tackle this problem by developing new methods or modifying existing ones. The Z association method is a new method for describing directional association in contingency tables. It allows to arbitrarily group categories for each of the two variables, for which the contingency table is analyzed. The Z coefficient was calculated on a sample data set with gene mutations in different cancer types. Results showed some association with both gene mutations and annotation groups. Detailed results obtained for particular cancer types versus particular genes and annotation groups were in line with well-known facts in cancer genomics. The "MEUSassociation" R library allows to analyze the directional association between two categorical variables, and the mutual relationship is summarized in a contingency table, by means of the Z association coefficient. The method implemented in the library allows to compute the standard Z coefficient and to apply it in a case, where all possible singular coefficients Z(A:B) are computed at the same time, giving information of association between particular rows and columns. Investigating the ranked list of the highest singular coefficients allows to reduce the complexity of a large-scale data set. Both the Z coefficient and its R implementation are important tools in categorical data analysis.

Studies have shown ethnic differences in body fat distribution, characterised by greater peripheral and less central fat accumulation in black compared to white South African (SA) women. As sex hormones play an important role in body fat distribution, our study aimed to determine whether differences in body fat distribution between black and white SA women were associated with subcutaneous adipose tissue (SAT) expression of oestrogen receptors (ERA and ERB) and aromatase (CYP19A1). Body fat distribution (DXA and CT) and ERA, ERB and CYP19A1 expression in abdominal and gluteal SAT were measured in 26 black and 22 white SA women. Abdominal SAT ERA and ERB did not differ by ethnicity or BMI. Gluteal ERA was higher (1.08 ± 0.06 vs 0.99 ± 0.05, P < 0.001) and ERB was lower (0.99 ± 0.06 vs 1.10 ± 0.07, P < 0.001) in black vs white SA women. CYP19A1 increased with obesity in all depots (P < 0.001). In both black and white SA women, gluteal ERA was associated with lower central fat mass (FM) and greater gynoid FM (P < 0.05), while the inverse association was shown for CYP19A1 in all depots (P < 0.01). In conclusion, ethnic differences in gluteal ERA expression were associated with differences in body fat distribution previously reported between black and white SA women.

The success of terrestrial carbon sequestration projects for rural development in sub-Saharan Africa lies in the (i) involvement of local populations in the selection of woody species, which represent the biological assets they use to meet their daily needs, and (ii) information about the potential of these species to store carbon. Although the latter is a key prerequisite, there is very little information available. To help fill this gap, the present study was undertaken in four pilot villages (Kou, Dao, Vrassan and Cassou) in Ziro Province, south-central Burkina Faso. The objective was to determine carbon storage potential for top-priority woody species preferred by local smallholders. We used (i) participatory rural appraisal consisting of group discussions and key informant interviews to identify priority species and functions, and (ii) landscape assessment of carbon stocks in the preferred woody species. Results revealed 79 priority tree and shrub species grouped into six functions, of which medicine, food and income emerge as the most important ones for the communities. For these functions, smallholders overwhelmingly listed Vitellaria paradoxa, Parkia biglobosa, Afzelia africana, Adansonia digitata, Detarium microcarpum, and Lannea microcarpa among the most important tree species. Among the preferred woody species in Cassou and Kou, the highest quantity of carbon was stored by V. paradoxa (1180 ±209 kg C ha-1 to 2089±522 kg C ha-1) and the lowest by Grewia bicolor (5±1.2 kg C ha-1). The potential carbon stored by the preferred tree communities was estimated at 587.9 Mg C ha-1 (95% CI: 456.7; 719.1 Mg C ha-1) in Kou and256.8 Mg C ha-1 (95% CI: 67.6; 324.4 Mg C ha-1) in Cassou. The study showed that the species that farmers preferred most stored more carbon than species that were less preferred.

We tested the hypothesis that the expression of IL-33 in MS is dynamic and is likely to reflect the clinical and radiological changes during the course of RRMS.

A combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy.

A study has been made of the effect of chronic exercise on myocardial electrophysiological heterogeneity and stability, as well as of the role of cholinergic neurons in these changes. Determinations in hearts from untrained and trained rabbits on a treadmill were performed. The hearts were isolated and perfused. A pacing electrode and a recording multielectrode were located in the left ventricle. The parameters determined during induced VF, before and after atropine (1μM), were: fibrillatory cycle length (VV), ventricular functional refractory period (FRPVF), normalized energy (NE) of the fibrillatory signal and its coefficient of variation (CV), and electrical ventricular activation complexity, as an approach to myocardial heterogeneity and stability. The VV interval was longer in the trained group than in the control group both prior to atropine (78±10 vs. 68±10 ms) and after atropine (76±8 vs. 67±10 ms). Likewise, FRPVF was longer in the trained group than in the control group both prior to and after atropine (53±8 vs. 42±7 ms and 50±6 vs. 40±6 ms, respectively), and atropine did not modify FRPVF. The CV of FRPVF was lower in the trained group than in the control group prior to atropine (12.5±1.5% vs. 15.1±3.8%) and, decreased after atropine (15.1±3.8% vs. 12.2±2.4%) in the control group. The trained group showed higher NE values before (0.40±0.04 vs. 0.36±0.05) and after atropine (0.37±0.04 vs. 0.34±0.06; p = 0.08). Training decreased the CV of NE both before (23.3±2% vs. 25.2±4%; p = 0.08) and after parasympathetic blockade (22.6±1% vs. 26.1±5%). Cholinergic blockade did not modify these parameters within the control and trained groups. Activation complexity was lower in the trained than in the control animals before atropine (34±8 vs. 41±5), and increased after atropine in the control group (41±5 vs. 48±9, respectively). Thus, training decreases the intrinsic heterogeneity of the myocardium, increases electrophysiological stability, and prevents some modifications due to muscarinic block.

This review aimed at examining the prevalence of musculoskeletal diseases and pain among dental professionals in Western countries. Furthermore, possible occupational risk factors were analyzed.

Kenya is 1 of 14 priority countries in Africa scaling up voluntary medical male circumcision (VMMC) for HIV prevention following the recommendations of the World Health Organization and the Joint United Nations Programme on HIV/AIDS. To inform VMMC target setting, we modeled the impact of circumcising specific client age groups across several Kenyan geographic areas.

Epithelial cell polarity, adhesion, proliferation, differentiation and survival are essential for morphogenesis of various organs and tissues including the ocular lens. The molecular mechanisms regulating the lens epithelial phenotype however, are not well understood. Here we investigated the role of scaffolding protein ankyrin-G (AnkG) in mouse lens development by conditional suppression of AnkG expression using the Cre-LoxP recombination approach. AnkG, which serves to link integral membrane proteins to the spectrin/actin cytoskeleton, was found to distribute predominantly to the lateral membranes of lens epithelium with several isoforms of the protein being detected in the mouse lens. Conditional deficiency of AnkG impaired mouse lens morphogenesis starting from embryonic stage E15.5, with neonatal (P1) AnkG cKO lenses exhibiting overt abnormalities in shape, size, epithelial cell height, sheet length and lateral membrane assembly together with defective fiber cell orientation relative to lenses from littermate AnkG floxed or Cre expressing mice. Severe disruptions in E-cadherin/β-catenin-based adherens junctions, and the membrane organization of spectrin-actin cytoskeleton, ZO-1, connexin-50 and Na+-K+-ATPase were noted in AnkG deficient lenses, along with detection in lens epithelium of α-smooth muscle actin, a marker of epithelial to mesenchymal transition. Moreover, lens epithelial cell proliferation and survival were severely compromised while differentiation appears to be normal in AnkG deficient mouse lenses. Collectively, these results indicate that AnkG regulates establishment of the epithelial phenotype via lateral membrane assembly, stabilization of E-cadherin-based cell-cell junctions, polarity and membrane organization of transport and adhesion proteins and the spectrin-actin skeleton, and provide evidence for an obligatory role for AnkG in lens morphogenesis and growth.

Peptidoglycan (PG) is the main constituent of the bacterial cell wall. The enzyme UDP‑N‑acetylglucosamine enolpyruvyl transferase (MurA) catalyzes the transfer of enolpyruvate from phosphoenolpyruvate to uridinediphospho‑N‑acetylglucosamine, which is the first committed step of PG biosynthesis. In this study, we have systematically examined the urea-induced unfolding of Acinetobacter baumannii MurA (AbMurA) using various optical spectroscopic techniques and molecular dynamics (MD) simulations. The urea-induced unfolding of AbMurA was a three-state process, where a metastable intermediate conformation state is populated between 3.0 and 4.0 M. Above 6.0 M urea, AbMurA gets completely unfolded. The transition from the native structure to the partially unfolded metastable state involves ~30% loss of native contacts but little change in the radius of gyration or core hydration properties. The intermediate-to-unfolded state transition was characterized by a large increase in the radius of gyration. MD trajectories simulated in different unfolding conditions suggest that urea destabilizes AbMurA structure weakening hydrophobic interactions and the hydrogen bond network. We observed a clear correlation between both in vitro and in silico studies. To our knowledge, this is also the first report on unfolding/stability analysis of any MurA enzyme.

The purpose of the present study was to determine whether responding to multiple concurrent conflicts results in a simultaneous or sequential conflict resolution. To this end, we measured event-related potentials (ERPs) in a paradigm combining a Stroop and a flanker task. In this paradigm, participants were asked to respond to the color of the central letter while ignoring the meaning of the word (Stroop task) and the color of the flanking letters (flanker task). Trials were either incongruent (i.e., inducing a conflict between two response alternatives) or congruent (i.e., inducing no response conflict) in both tasks, or incongruent in one task and congruent in the other task. The behavioral results showed a smaller Stroop congruency effect (i.e., a smaller difference between Stroop incongruent and congruent trials) for flanker incongruent than for flanker congruent trials, replicating previous findings. The ERP results showed that an early ERP component (i.e., P2) was associated with the resolution of the flanker conflict, whereas a later component (i.e., N450) was associated with the resolution of the Stroop conflict. Together, these findings emphasize a sequential organization of conflict resolution processes in the brain which is adaptive when facing multiple concurrent conflicts.

Aberrant promoter methylation plays a vital role in colorectal carcinogenesis. However, its role in treatment responses is unclear, especially for metastatic disease. Here, we investigated the association between promoter methylation and treatment outcomes of irinotecan-based chemotherapy in 102 patients with metastatic colorectal cancer. Promoter methylation was examined by methylation-specific polymerase chain reaction for three loci (CHFR, WRN, and SULF2) associated with chemotherapy response and five CpG island methylator phenotype (CIMP)-specific markers (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). Association between CHFR methylation and in vitro sensitivity to irinotecan was also evaluated. Promoter methylation of CHFR, WRN, and SULF2 was identified in 16 (15.7%), 24 (23.5%), and 33 (32.4%) patients, respectively. CIMP status was positive in 22 (21.6%) patients. CHFR methylation was associated with a significantly longer time to progression (TTP) (median: 8.77 vs. 4.43 months, P = .019), with trends favoring higher overall survival (OS) (median: 22.83 vs. 20.17 months, P = .300) and response rates (31.3% vs. 17.4%, P = .300). For patients with unmethylated CHFR, TTP (median: 5.60 vs. 3.53, P = .020) and OS (median: 20.57 vs. 9.23, P = .006) were significantly different according to CIMP status. Colorectal cancer cell lines with CHFR methylation demonstrated increased sensitivity to irinotecan. Both CHFR overexpression and combination with 5-aza-2'-deoxycytidine reversed irinotecan sensitivity in CHFR-methylated cell lines, whereas CHFR knockdown in unmethylated cells restored sensitivity to irinotecan. These data suggest that CHFR methylation may be associated with favorable treatment outcomes of irinotecan-based chemotherapy in patients with metastatic colorectal cancer.