Understanding the role of temporal variation of environmental variables in predicting Aedes aegypti oviposition activity in a temperate region of Argentina

Environmental variables related to vegetation and weather are some of the most influential factors that impacting Aedes (Stegomya) aegypti, a mosquito vector of dengue, chikungunya and Zika viruses. In this paper, we aim to develop temporal predictive models for Ae. aegypti oviposition activity utilizing vegetation and meteorological variables as predictors in Córdoba city (Argentina). Eggs were collected using ovitraps placed throughout the city from 2009 to 2012 that were replaced weekly. Temporal generalized linear mixed models were developed with negative binomial distributions of errors that model average number of eggs collected weekly as a function of vegetation and meteorological variables with time lags. The best model included a vegetation index, vapor pressure of water, precipitation and photoperiod. With each unit of increment in vegetation index per week the average number of eggs increased by 1.71 in the third week. Furthermore, each millimeter increase of accumulated rain during 4 weeks was associated with a decrease of 0.668 in the average number of eggs found in the following week. This negative effect of precipitation could occur during abundant rainfalls that fill containers completely, thereby depriving females of oviposition sites and leading them to search for other suitable breeding sites. Furthermore, the average number of eggs increased with the photoperiod at low values of mean vapor pressure; however the average number of eggs decreased at high values of mean vapor pressure, and the positive relationship between the response variable and mean vapor pressure was stronger at low values of photoperiod. Additionally, minimum temperature was associated positively with oviposition activity and that low minimum temperatures could be a limiting factor in Ae. aegypti oviposition activity. Our results emphasize the important role that climatic variables such as temperature, precipitation, and vapor pressure play in Ae. aegypti oviposition activity and how these variables along with vegetation indices can be used to inform predictive temporal models of Ae. aegypti population dynamics that can be used for informing mosquito population control and arbovirus mitigation strategies.Fil: Benitez, Elisabet Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estallo, Elizabet Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Frías Céspedes, Maria. Provincia de Córdoba. Ministerio de Salud; ArgentinaFil: Almiron, Walter Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Robert, Michael A.. Virginia Commonwealth University; Estados UnidosFil: Ludueña Almeida, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Specific Plasma MicroRNA Signatures Underlying the Clinical Outcomes of Hepatitis E Virus Infection

The pathogenic mechanisms determining the diverse clinical outcomes of HEV infection (e.g., self-limiting vs chronic or symptomatic vs asymptomatic) are not yet understood. Because specific microRNA signatures during viral infection inform the cellular processes involved in virus replication and pathogenesis, we investigated plasma microRNA profiles in 44 subjects, including patients with symptomatic acute (AHE, n = 7) and chronic (CHE, n = 6) hepatitis E, blood donors with asymptomatic infection (HEV BDs, n = 9), and anti-HEV IgG+IgM- (exposed BDs, n = 10) and anti-HEV IgG-IgM- (naïve BDs, n = 12) healthy blood donors. By measuring the abundance of 179 microRNAs in AHE and naïve BDs by RT-qPCR, we identified 51 potencial HEV-regulated microRNAs (PBH < 0.05). Further analysis showed that HEV genotype 3 infection is associated with miR-122, miR-194, miR-885, and miR-30a upregulation and miR-221, miR-223, and miR-27a downregulation. AHE showed significantly higher levels of miR-122 and miR-194, and lower levels of miR-221, miR-27a, and miR-335 compared to HEV BDs. This specific microRNA signature in AHE could promote virus replication and reduce antiviral immune responses, contributing to the development of clinical symptoms. We found that mir-194, miR-335, and miR-221 can discriminate between asymptomatic HEV infections and those developing acute symptoms, whereas miR-335 correctly classify AHE and CHE. Conclusions: Our data suggest that diverse outcomes of HEV infection result from different HEV-induced microRNA dysregulations. The specific microRNA signatures described offer novel information that may serve to develop biomarkers of HEV infection outcomes and improve our understanding of HEV pathogenesis, which may facilitate the identification of antiviral targets

A large, ten-generation family with autosomal dominant preaxial polydactyly/triphalangeal thumb: Historical, clinical, genealogical, and molecular studies

We present a large, ten-generation family of 273 individuals with 84 people having preaxial polydactyly/triphalangeal thumb due to a pathogenic variant in the zone of polarizing activity regulatory sequence (ZRS) within the exon 5 of LMBR1. The causative change maps to position 396 of the ZRS, located at position c.423 + 4909C > T (chr7:156791480; hg38; LMBR1 ENST00000353442.10; rs606231153 NG_009240.2) in the intron 5 of LMBR1. The first affected individual with the disorder was traced back to mid-1700, when some settlers and workers established in Cervera de Buitrago, a small village about 82 km North to Madrid. Clinical and radiological studies of most of the affected members have been performed for 42 years (follow-up of the family by LFGA). Molecular studies have confirmed a pathogenic variant in the ZRS that segregates in this family. To the best of our knowledge, this is the largest family with preaxial polydactyly/triphalangeal thumb reported so far.Instituto de Salud Carlos III, Grant/Award Number: PI20/0105

Preclinical Efficacy of Endoglin-Targeting Antibody–Drug Conjugates for the Treatment of Ewing Sarcoma

[EN] Endoglin (ENG; CD105) is a coreceptor of the TGFb family that is highly expressed in proliferating endothelial cells. Often coopted by cancer cells, ENG can lead to neo-angiogenesis and vasculogenic mimicry in aggressive malignancies. It exists both as a transmembrane cell surface protein, where it primarily interacts with TGFb, and as a soluble matricellular protein (sENG) when cleaved by matrix metal-loproteinase 14 (MMP14). High ENG expression has been associated with poor prognosis in Ewing sarcoma, an aggressive bone cancer that primarily occurs in adolescents and young adults. However, the therapeutic value of ENG targeting has not been fully explored in this disease. Experimental Design: We characterized the expression pattern of transmembrane ENG, sENG, and MMP14 in preclinical and clinical samples. Subsequently, the antineoplastic potential of two novel ENG-targeting monoclonal antibody–drug conjugates (ADC), OMTX503 and OMTX703, which differed only by their drug payload (nigrin-b A chain and cytolysin, respectively), was assessed in cell lines and preclinical animal models of Ewing sarcoma. Results: Both ADCs suppressed cell proliferation in proportion to the endogenous levels of ENG observed in vitro. Moreover, the ADCs significantly delayed tumor growth in Ewing sarcoma cell line–derived xenografts and patient-derived xenografts in a dose-dependent manner. Conclusions: Taken together, these studies demonstrate potent preclinical activity of first-in-class anti-ENG ADCs as a nascent strategy to eradicate Ewing sarcoma

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.The VACCELERATE Site Network has received funding from the European Union’s Horizon 2020 research and innovation pro gramme (grant agreement No 101037867) and the German Federal Ministry of Education and Research (Bundesministerium für Bil dung und Forschung [BMBF]) (grant agreement No BMBF01KX2040).S

Biología I: una experiencia de aprendizaje activo para asumir competencias generales y específicas

Podeu consultar la versió catalana a recurs relacionat.[spa] En este cuaderno se describe el proceso de gestación y desarrollo de la Biología I, una asignatura de 6 ECTS que se imparte en los grados de Biología, Bioquímica, Biotecnología y Ciencias Biomédicas en la Facultad de Biología de la Universidad de Barcelona. Para impartir la Biología I se constituyó un equipo docente multidisciplinar, formado por 30 profesores de diferentes departamentos. Es importante destacar la labor de coordinación y colaboración entre todos los integrantes. Consideramos esta experiencia muy importante, ya que en ninguna asignatura había participado un número tan elevado de profesores y departamentos de la Facultad de Biología. En los distintos apartados se explican detalladamente todas las actividades que se han llevado a cabo: clases de teoría, aprendizaje basado en problemas (ABP), seminarios, prácticas de campo y visitas a diferentes centros de investigación u hospitalarios. También se presentan y se discuten los resultados obtenidos. Analizando la asignatura de Biología I, tanto desde el punto de vista de la actividad docente realizada como de los resultados obtenidos, llegamos a la conclusión de que es una experiencia de aprendizaje activo que ha permitido la adquisición con éxito tanto de competencias generales como específicas.[eng] This book describes the process of conception and development of Biology I, a course of 6 ECTS, taught in the degrees of Biology, Biochemistry, Biotechnology and Biomedical Sciences at the Faculty of Biology, University of Barcelona. To teach Biology I a multidisciplinary teaching team, comprising 30 teachers from different departments, was created. It is important to highlight the work of coordination and cooperation between all those members. We consider this experience as very important because, never before, such a large number of teachers and departments of the Faculty of Biology were involved in one single course. Through the different book sections, all the activities that took place are explained in detail: lecturers, problem based learning (PBL), seminars, field practicals and visits to research centers or hospitals. Results are also presented and discussed. Both from the standpoint of the work done and the final results, we conclude that this Biology I course proposal is an experience of active learning which allowed the successful achievement of general and specific skills by the students