Prefrontal-occipitoparietal coupling underlies late latency human neuronal responses to emotion

Enhanced late positive potentials (LPPs) evoked by highly arousing unpleasant and pleasant stimuli have been consistently observed in event-related potential experiments in humans. Although the psychological factors modulating the LPP have been studied in detail, the neurobiological underpinnings of this response remain poorly understood. Current models suggest that the LPP is a product of both an automatic facilitation of perceptual activity, as well as postperceptual processing under cognitive control. Here we applied magnetoencephalography (MEG) and beamformer analysis combined with Granger causality measures to provide a mechanistic account for LPP generation that reconciles these two models. We demonstrate that the magnetic homolog of the LPP, mLPP, is localized within bilateral occipitoparietal and right prefrontal cortex. Critically, directed functional connectivity analysis between these brain regions, indexed by Granger causality, demonstrates stronger bidirectional influences between frontal and occipitoparietal cortex for high arousing emotional relative to low arousing neutral pictures. Thus, both bottom-up and top-down accounts of the late latency response to emotion derived from psychological studies can be explained by a reciprocal codependency between activity in prefrontal and occipitoparietal cortex

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes

The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions

Stochastic vs. deterministic magnetic coding in designed cylindrical nanowires for 3D magnetic networks

[EN] Advances in cylindrical nanowires for 3D information technologies profit from intrinsic curvature that introduces significant differences with regards to planar systems. A model is proposed to control the stochastic and deterministic coding of remanent 3D complex vortex configurations in designed multilayered (magnetic/non-magnetic) cylindrical nanowires. This concept, introduced by micromagnetic simulations, is experimentally confirmed by magnetic imaging in FeCo/Cu multilayered nanowires. The control over the random/deterministic vortex states configurations is achieved by a suitable geometrical interface tilting of almost non-interacting FeCo segments with respect to the nanowire axis, together with the relative orientation of the perpendicular magnetic field. The proper design of the segments' geometry (e.g. tilting) in cylindrical nanowires opens multiple opportunities for advanced nanotechnologies in 3D magnetic networks.Spanish Ministry of Science and Innovation under Projects MAT2016-76824-C3-1-R, PID2019-108075RB-C31/ AEI / 10.13039/501100011033 and PGC2018-097789-B-I00 and the Regional Government of Madrid under Project S2018/NMT-4321 NANOMAGCOST-CM. LA and MF acknowledge project RTI2018-095303-B-C53.Peer reviewe

Domain wall propagation and pinning induced by current pulses in cylindrical modulated nanowires

The future developments in 3D magnetic nanotechnology require the control of domain wall dynamics by means of current pulses. While this has been extensively studied in 2D magnetic strips (planar nanowires), few reports on this exist in cylindrical geometry, where Bloch point domain walls are expected to have intriguing properties. Here, we report an investigation on cylindrical magnetic Ni nanowires with geometrical notches. An experimental work based on synchrotron X-ray magnetic circular dichroism (XMCD) combined with photoemission electron microscopy (PEEM) indicates that large current densities induce domain wall nucleation, while smaller currents move domain walls preferably antiparallel to the current direction. In the region where no pinning centers are present, we found a domain wall velocity of about 1 km s. Thermal modelling indicates that large current densities temporarily raise the temperature in the nanowire above the Curie temperature, leading to nucleation of domain walls during the system cooling. Micromagnetic modelling with a spin-torque effect shows that for intermediate current densities, Bloch point domain walls with chirality parallel to the Oersted field propagate antiparallel to the current direction. In other cases, domain walls can be bounced from the notches and/or get pinned outside their positions. We thus found that current is not only responsible for domain wall propagation, but also is a source of pinning due to the Oersted field action.Grants PID2019-108075RB-C31 funded by the Ministry of Science and Innovation MCIN/AEI/10.13039/501100011033 and S2018/NMT-4321 NANOMAGCOST-CM funded by the Government of Madrid Region, Spain. We acknowledge the service from the MiNa Laboratory at IMN and the funding from CM (project SpaceTec, S2013/ICE2822), MINECO (project CSIC13-4E-1794), and EU (FEDER, FSE).Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d3nr00455

Field and laboratory comparative evaluation of a LAMP assay for the diagnosis of urogenital schistosomiasis in Cubal, Central Angola

Objetive: To evaluate the performance of Rapid-Heat LAMPellet assay in field conditions for diagnosis of urogenital schistosomiasis in an endemic area in Cubal, Angola, and to assess the reproducibility in a reference laboratory. Methods: A total of 172 urine samples from school-age children were tested for microhaematuria, microscopic detection of Schistosoma haematobium eggs and LAMP for DNA detection. Urine samples were stored in a basic equipped laboratory. Field-LAMP tests were performed with and without prior DNA extraction from urine samples, and the results were read by turbidity and by colour change. When field procedures were finished, samples were sent to a reference laboratory to be reanalysed by LAMP. Results: A total of 83 of 172 (48.3%) were positive for microhaematuria, 87/172 (50.6%) were microscopy-positive for S. haematobium eggs detection, and 127/172 (73.8%) showed LAMP-positive results for detecting S. haematobium using purified DNA and 109/172 (63.4%) without prior DNA extraction. MacNemar's test showed a statistical significant relation between LAMP results and microscopy-detected S. haematobium infections and microhaematuria (P < 0.001 in both cases), respectively. When samples of purified DNA were reanalysed in a reference laboratory in Spain using the same LAMP methodology, the overall reproducibility achieved 72.1%. Conclusions: The ease of use, simplicity and feasibility demonstrated by LAMP assay in field conditions together with the acceptable level of reproducibility achieved in a reference laboratory support the use of LAMP assay as an effective test for molecular diagnosis of urogenital schistosomiasis in endemic remote areas.This study was supported by Mundo Sano Foundation (www.mundosano.org) and by the Institute of Health Carlos III, ISCIII, Spain (www.isciii.es), grants: RICET RD16/0027/0018, DTS16/00207, PI16/01784 European Union cofinancing by FEDER (Fondo Europeo de Desarrollo Regional) ‘Una manera de hacer Europa’.S

Asymptomatic Strongyloidiasis among Latin American Migrants in Spain: A Community-Based Approach

Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. Aim: To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Methodology: Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Results: Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Conclusion: Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.This study was partially supported by the 3rd call for research project grants for the Institute of Health and Biometric Research of Alicante (ISABIAL)/FISABIO Foundation (UGP-16-158), and by the collaboration agreement regulated under the Law of Patronage between ISABIAL/FISABIO and the Foundation Mundo Sano, Spain.S

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes

9 p.-2 tab.-3 fig.The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Δhsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Δhsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Δhsp70-II mutant was determined by flow cytometry. Furthermore, Δhsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Δhsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes reexpressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions.This work was supported by grants from the Spanish Ministry of Science and Technology (BFU2006-08346) and the Fondo de Investigaciones Sanitarias (ISCIII-RETIC RD06/0021/0008-FEDER and ISCIII-RETIC-RD06/0021/0009-FEDER). Also, a grant from Fundación Ramón Areces (Madrid, Spain) is acknowledged.Peer reviewe

Identification of new leishmanicidal peptide lead structures by automated real-time monitoring of changes in intracellular ATP.

Leishmanicidal drugs interacting stoichiometrically with parasite plasma membrane lipids, thus promoting permeability, have raised significant expectations for Leishmania chemotherapy due to their nil or very low induction of resistance. Inherent in this process is a decrease in intracellular ATP, either wasted by ionic pumps to restore membrane potential or directly leaked through larger membrane lesions caused by the drug. We have adapted a luminescence method for fast automated real-time monitoring of this process, using Leishmania donovani promastigotes transfected with a cytoplasmic luciferase form, previously tested for anti-mitochondrial drugs. The system was first assayed against a set of well-known membrane-active drugs [amphotericin B, nystatin, cecropin A-melittin peptide CA(1-8)M(1-18)], plus two ionophoric polyethers (narasin and salinomycin) not previously tested on Leishmania, then used to screen seven new cecropin A-melittin hybrid peptides. All membrane-active compounds showed a good correlation between inhibition of luminescence and leishmanicidal activity. Induction of membrane permeability was demonstrated by dissipation of membrane potential, SYTOX trade mark Green influx and membrane damage assessed by electron microscopy, except for the polyethers, where ATP decrease was due to inhibition of its mitochondrial synthesis. Five of the test peptides showed an ED50 around 1 microM on promastigotes. These peptides, with equal or better activity than 26-residue-long CA(1-8)M(1-18), are the shortest leishmanicidal peptides described so far, and validate our luminescence assay as a fast and cheap screening tool for membrane-active compounds

Strong-LAMP: A LAMP Assay for <i>Strongyloides</i> spp. Detection in Stool and Urine Samples. Towards the Diagnosis of Human Strongyloidiasis Starting from a Rodent Model

<div><p>Background</p><p><i>Strongyloides stercoralis</i>, the chief causative agent of human strongyloidiasis, is a nematode globally distributed but mainly endemic in tropical and subtropical regions. Chronic infection is often clinically asymptomatic but it can result in severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. There is a great diversity of techniques used in diagnosing the disease, but definitive diagnosis is accomplished by parasitological examination of stool samples for morphological identification of parasite. Until now, no molecular method has been tested in urine samples as an alternative to stool samples for diagnosing strongyloidiasis. This study aimed to evaluate the use of a new molecular LAMP assay in a well-established Wistar rat experimental infection model using both stool and, for the first time, urine samples. The LAMP assay was also clinically evaluated in patients´ stool samples.</p><p>Methodology/Principal Findings</p><p>Stool and urine samples were obtained daily during a 28-day period from rats infected subcutaneously with different infective third-stage larvae doses of <i>S</i>. <i>venezuelensis</i>. The dynamics of parasite infection was determined by daily counting the number of eggs per gram of feces from day 1 to 28 post-infection. A set of primers for LAMP assay based on a DNA partial sequence in the 18S rRNA gene from <i>S</i>. <i>venezuelensis</i> was designed. The set up LAMP assay (namely, Strong-LAMP) allowed the sensitive detection of <i>S</i>. <i>venezuelensis</i> DNA in both stool and urine samples obtained from each infection group of rats and was also effective in <i>S</i>. <i>stercoralis</i> DNA amplification in patients´ stool samples with previously confirmed strongyloidiasis by parasitological and real-time PCR tests.</p><p>Conclusions/Significance</p><p>Our Strong-LAMP assay is an useful molecular tool in research of a strongyloidiasis experimental infection model in both stool and urine samples. After further validation, the Strong-LAMP could also be potentially applied for effective diagnosis of strongyloidiasis in a clinical setting.</p></div

Monitoring of <i>Strongyloides venezuelensis</i> infection by counting eggs in rats’ stool samples.

<p>Rats were experimentally infected with different infective third-stage larvae (iL3) doses of <i>S</i>. <i>venezuelensis</i>. (A) Group 1: rats infected with 40 iL3. (B) Group 2: rats infected with 400 iL3. (C) Group 3: rats infected with 4,000 iL3. X axis represent days post-infection. Y axis represent number of eggs per gram of feces (EPG) and (mean±SE).</p