Pilot survey of expressed sequence tags (ESTs) from the asexual blood stages of Plasmodium vivax in human patients

BACKGROUND: Plasmodium vivax is the most widely distributed human malaria, responsible for 70–80 million clinical cases each year and large socio-economical burdens for countries such as Brazil where it is the most prevalent species. Unfortunately, due to the impossibility of growing this parasite in continuous in vitro culture, research on P. vivax remains largely neglected. METHODS: A pilot survey of expressed sequence tags (ESTs) from the asexual blood stages of P. vivax was performed. To do so, 1,184 clones from a cDNA library constructed with parasites obtained from 10 different human patients in the Brazilian Amazon were sequenced. Sequences were automatedly processed to remove contaminants and low quality reads. A total of 806 sequences with an average length of 586 bp met such criteria and their clustering revealed 666 distinct events. The consensus sequence of each cluster and the unique sequences of the singlets were used in similarity searches against different databases that included P. vivax, Plasmodium falciparum, Plasmodium yoelii, Plasmodium knowlesi, Apicomplexa and the GenBank non-redundant database. An E-value of <10(-30 )was used to define a significant database match. ESTs were manually assigned a gene ontology (GO) terminology RESULTS: A total of 769 ESTs could be assigned a putative identity based upon sequence similarity to known proteins in GenBank. Moreover, 292 ESTs were annotated and a GO terminology was assigned to 164 of them. CONCLUSION: These are the first ESTs reported for P. vivax and, as such, they represent a valuable resource to assist in the annotation of the P. vivax genome currently being sequenced. Moreover, since the GC-content of the P. vivax genome is strikingly different from that of P. falciparum, these ESTs will help in the validation of gene predictions for P. vivax and to create a gene index of this malaria parasite

Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics

[EN] The aims of this study were to assess, in vitro, the possibility of administering propranolol transdermally and to evaluate the usefulness of the dermatopharmacokinetic (DPK) method in assessing the transport of drugs through stratum corneum, using propranolol as a model compound. Four chemical enhancers (decenoic and oleic acid, laurocapram, and R-(+)-limonene) and iontophoresis at two current densities, 0.25 and 0.5 mA/cm(2) were tested. R-(+)-limonene, and iontophoresis at 0.5 mA/cm(2) were proven to be the most efficient in increasing propranolol transdermal flux, both doubled the original propranolol transdermal flux. Iontophoresis was demonstrated to be superior than the chemical enhancer because it allowed faster delivery of the drug. The DPK method was sufficiently sensitive to detect subtle vehicle-induced effects on the skin permeation of propranolol. The shorter duration of these experiments and their ability to provide mechanistic information about partition between vehicle and skin and diffusivity through skin place them as practical and potentially insightful approach to quantify and, ultimately, optimize topical bioavailability.This research was funded by Ministerio de Ciencia e Innovación (AP2007-03456) and the Universidad CEU Cardenal Herrera.Calatayud-Pascual, M.; Sebastian-Morelló, M.; Balaguer-Fernandez, C.; Delgado-Charro, M.; Lopez-Castellano, A.; Merino Sanjuán, V. (2018). Influence of Chemical Enhancers and Iontophoresis on the In Vitro Transdermal Permeation of Propranolol: Evaluation by Dermatopharmacokinetics. Pharmaceutics. 10(4):1-15. https://doi.org/10.3390/pharmaceutics10040265S11510

Charm Production in DPMJET

In this work, charm production in the {\sc dpmjet} hadronic jet simulation is compared to experimental data. Since the major application of {\sc dpmjet} is the simulation of cosmic ray-induced air showers, the version of the code integrated in the CORSIKA simulation package has been used for the comparison. Wherever necessary, adjustments have been made to improve agreement between simulation and data. With the availability of new muon/neutrino detectors that combine a large fiducial volume with large amounts of shielding, investigation of prompt muons and neutrinos from cosmic ray interactions will be feasible for the first time. Furthermore, above $\gtrsim 100$ TeV charmed particle decay becomes the dominant background for diffuse extraterrestrial neutrino flux searches. A reliable method to simulate charm production in high-energy proton-nucleon interactions is therefore required.Comment: 10 pages, to be published in JCA

Tailoring block copolymer nanoporous thin films with acetic acid as a small guest molecule

Block copolymers offer the fabrication of mesoporous thin films with distinct nanoscale structural features. In this contribution, we present the use of acetic acid (CH3COOH) as a low‐molecular‐weight guest molecule to tune the supramolecular assembly of poly[styrene‐block‐(4‐vinylpyridine)] (PS‐b‐P4VP), offering a versatile and straightforward method to obtain tailored nanostructured films with controlled topography and pore size. Spin‐coating toluene solutions of PS‐b‐P4VP, with a variable amount of CH3COOH, leads to micellar thin films, where the micelles contain the carboxylic acid as a guest molecule. The size can be conveniently modified in these films (from 48 to 75 nm) by varying the amount of organic acid in the starting solutions. Subsequent surface reconstruction of micellar films using ethanol leads to ring‐shaped copolymer nanoporous films with modulated diameter. Controlling the micelle reconstruction process, cylindrical porous films are also obtained. Interestingly, changing the type of aliphatic carboxylic acid leads to a modification of the observed film morphology from micelles to out‐of‐plane P4VP cylinders (or lamellae) in a PS matrix

Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients’ leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 showed statistical significance in its discriminative capacity (p &lt; 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003–3.229; p &lt; 0.05). Moreover, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset

Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis.In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age???65?years), and 23 old healthy controls (>65?years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture.We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p?<?0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ?4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p?<?0.05).Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ?4 status to a specific decline in memory performance in EOAD.© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association

Whole Genome Sequence Analysis of Burkholderia contaminans FFH2055 Strain Reveals the Presence of Putative β-Lactamases

Burkholderia contaminans is a member of the Burkholderia cepacia complex (Bcc), a pathogen with increasing prevalence among cystic fibrosis (CF) patients and the cause of numerous outbreaks due to the use of contaminated commercial products. The antibiotic resistance determinants, particularly β-lactamases, have been poorly studied in this species. In this work, we explored the whole genome sequence (WGS) of a B. contaminans isolate (FFH 2055) and detected four putative β-lactamase-encoding genes. In general, these genes have more than 93% identity with β-lactamase genes found in other Bcc species. Two β-lactamases, a class A (Pen-like, suggested name PenO) and a class D (OXA-like), were further analyzed and characterized. Amino acid sequence comparison showed that Pen-like has 82% and 67% identity with B. multivorans PenA and B. pseudomallei PenI, respectively, while OXA-like displayed strong homology with class D enzymes within the Bcc, but only 22–44% identity with available structures from the OXA family. PCR reactions designed to study the presence of these two genes revealed a heterogeneous distribution among clinical and industrial B. contaminans isolates. Lastly, bla PenO gene was cloned and expressed into E. coli to investigate the antibiotic resistance profile and confers an extended-spectrum β-lactamase (ESBL) phenotype. These results provide insight into the presence of β-lactamases in B. contaminans, suggesting they play a role in antibiotic resistance of these bacteria.Fil: Degrossi, José J.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Merino, Cindy. University Fullerton; Estados UnidosFil: Isasmendi, Adela M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Ibarra, Lorena M.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Collins, Chelsea. University Fullerton; Estados UnidosFil: Bo, Nicolás E.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Papalia, Mariana Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Fernandez, Jennifer S.. University Fullerton; Estados UnidosFil: Hernandez, Claudia M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Papp Wallace, Krisztina M.. Case Western Reserve University; Estados UnidosFil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosFil: Vazquez, Miryam S.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Power, Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Microbiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ramirez, María S.. University Fullerton; Estados Unido

An Integrated Research Infrastructure for Validating Cyber-Physical Energy Systems

Renewables are key enablers in the plight to reduce greenhouse gas emissions and cope with anthropogenic global warming. The intermittent nature and limited storage capabilities of renewables culminate in new challenges that power system operators have to deal with in order to regulate power quality and ensure security of supply. At the same time, the increased availability of advanced automation and communication technologies provides new opportunities for the derivation of intelligent solutions to tackle the challenges. Previous work has shown various new methods of operating highly interconnected power grids, and their corresponding components, in a more effective way. As a consequence of these developments, the traditional power system is being transformed into a cyber-physical energy system, a smart grid. Previous and ongoing research have tended to mainly focus on how specific aspects of smart grids can be validated, but until there exists no integrated approach for the analysis and evaluation of complex cyber-physical systems configurations. This paper introduces integrated research infrastructure that provides methods and tools for validating smart grid systems in a holistic, cyber-physical manner. The corresponding concepts are currently being developed further in the European project ERIGrid.Comment: 8th International Conference on Industrial Applications of Holonic and Multi-Agent Systems (HoloMAS 2017

TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider

The TESLA Technical Design Report Part III: Physics at an e+e- Linear ColliderComment: 192 pages, 131 figures. Some figures have reduced quality. Full quality figures can be obtained from http://tesla.desy.de/tdr. Editors - R.-D. Heuer, D.J. Miller, F. Richard, P.M. Zerwa

Search for the glueball candidates f0(1500) and fJ(1710) in gamma gamma collisions

Data taken with the ALEPH detector at LEP1 have been used to search for gamma gamma production of the glueball candidates f0(1500) and fJ(1710) via their decay to pi+pi-. No signal is observed and upper limits to the product of gamma gamma width and pi+pi- branching ratio of the f0(1500) and the fJ(1710) have been measured to be Gamma_(gamma gamma -> f0(1500)). BR(f0(1500)->pi+pi-) < 0.31 keV and Gamma_(gamma gamma -> fJ(1710)). BR(fJ(1710)->pi+pi-) < 0.55 keV at 95% confidence level.Comment: 10 pages, 3 figure