Adenovirus core protein V reinforces the capsid and enhances genome release from disrupted particles

Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entry

Adenovirus core protein V reinforces the capsid and enhances genome release from disrupted particles

Out of the three core proteins in human adenovirus, protein V is believed to connect the inner capsid surface to the outer genome layer. Here, we explored mechanical properties and in vitro disassembly of particles lacking protein V (Ad5-ΔV). Ad5-ΔV particles were softer and less brittle than the wild-type ones (Ad5-wt), but they were more prone to release pentons under mechanical fatigue. In Ad5-ΔV, core components did not readily diffuse out of partially disrupted capsids, and the core appeared more condensed than in Ad5-wt. These observations suggest that instead of condensing the genome, protein V antagonizes the condensing action of the other core proteins. Protein V provides mechanical reinforcement and facilitates genome release by keeping DNA connected to capsid fragments that detach during disruption. This scenario is in line with the location of protein V in the virion and its role in Ad5 cell entryThis work was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (FIS2017-89549-R; “Maria de Maeztu” Program for Units of Excellence in R&D MDM-2014-0377 and FIS2017-90701-REDT) and from the Human Frontiers Science Program (HFSPO RGP0012/2018) to P.J.d.P., as well as grant PID2019-104098GB-I00/AEI/10.13039/501100011033, cofunded by the Spanish State Research Agency and the European Regional Development Fund to C.S.M. The CNB-CSIC was further supported by a Spanish State Research Agency Severo Ochoa Excellence grant (SEV 2017-0712). C.S.M. is a member of the CSIC funded consortium LifeHub (CSIC grant number: 202120E47). M.H.-P. was a recipient of a Juan de la Cierva postdoctoral contract and currently holds a Ramón y Cajal position (RyC2021-030929-I) funded by the Spanish State Research Agency. M.H.-P. acknowledges funding from Ayudas a Proyectos de I+D para Jóvenes Doctores de la Universidad Autónoma de Madrid 2021, SI3/PJI/2021-00216 supported by the Community of Madrid and the University Autónoma de Madrid, and TED2021-129937B-I00 from Spanish Ministry of Science and Innovation. Financial support of the Community of Madrid and the European Union through the European Regional Development Fund (ERDF), financed as part of the Union response to Covid-19 pandemic (VIRMAT-REACT), is also acknowledged. Access to the cryo-EM CNB-CSIC facility was carried out via the CRIOMECORR project (ESFRI-2019-01- CSIC-16). Work in the Greber laboratory was supported by a grant to UFG from Schweizerischer Nationalfonds (Swiss National Science Foundation, 31003A_179256/1). Author contributions: N.M.-G. performed AFM experiments and analyzed the data. M.H.-P. and C.S.M. carried out cryoEM analyses. A.G.-G. and M.B. produced the viral samples and carried out thermostability analyses. U.F.G., C.S.M., and P.J.d.P. designed research. N.M.-G. wrote the manuscript, with input from U.F.G., C.S.M., and P.J.d.P. All authors read and edited the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: The Ad5-ΔV cryo-EM map is deposited at the Electron Microscopy Data Bank (EMDB; www.ebi.ac.uk/pdbe/emdb) with accession number EMD-15694. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Material

Implementación de un sistema de información geográfica en municipios de la zona norte de la provincia de Santa Cruz

Los Sistemas de Información Geográfica, nacen de la necesidad constante de la sociedad de obtener información acerca de los territorios, constituyendo uno de los campos más dinámicos y novedosos de aplicación de la Informática, con un indudable efecto en la sociedad. Este artículo pretende presentar la iniciativa de investigación acerca de Sistemas de Información Geográfica (SIG) en general, y en particular aplicados en la Subsecretaría de Planeamiento de la Municipalidad de Caleta Olivia (MCO), en la provincia de Santa Cruz, en áreas tales como Catastro, Obras Particulares, Tierras, Topografía, Infraestructura Urbana y Producción. Esta investigación se está realizando en el Laboratorio de Tecnologías Emergentes de la Universidad Nacional de la Patagonia Austral, con el objetivo de desarrollar una aplicación de Software Libre y permitir la unificación de la información de dicha Municipalidad que posibilite agilizar la gestión administrativa.Eje: Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

Implementación de un sistema de información geográfica en municipios de la zona norte de la provincia de Santa Cruz

Los Sistemas de Información Geográfica, nacen de la necesidad constante de la sociedad de obtener información acerca de los territorios, constituyendo uno de los campos más dinámicos y novedosos de aplicación de la Informática, con un indudable efecto en la sociedad. Este artículo pretende presentar la iniciativa de investigación acerca de Sistemas de Información Geográfica (SIG) en general, y en particular aplicados en la Subsecretaría de Planeamiento de la Municipalidad de Caleta Olivia (MCO), en la provincia de Santa Cruz, en áreas tales como Catastro, Obras Particulares, Tierras, Topografía, Infraestructura Urbana y Producción. Esta investigación se está realizando en el Laboratorio de Tecnologías Emergentes de la Universidad Nacional de la Patagonia Austral, con el objetivo de desarrollar una aplicación de Software Libre y permitir la unificación de la información de dicha Municipalidad que posibilite agilizar la gestión administrativa.Eje: Ingeniería de Software y Base de DatosRed de Universidades con Carreras en Informática (RedUNCI

On the Effects of N-P-K Fertilizer to the Electricity Generated by Aloe barbadensis miller

Nowadays, electricity is a pressing conflict due to the increase in demand by the populace. Thus, energy prices have also increased, making it considerably inaccessible to several population members. Considering this, the researchers have studied the type of N-PK fertilizer that can improve the efficiency of producing electricity from a living plant. There were four experimental setups of Aloe barbadensis miller that were utilized in the experiment. Every variable and component of each setup was constant, except the type of fertilizer that was added to the soil. The first setup did not have any fertilizer, the second group had Nitrogen-based (N-P-K 21:0:0), the third group had Phosphorus-based (N-P-K 0:22:0), and the fourth group had Potassium-based (N-P-K 0:0:50). The researchers gathered data on electricity generated in the Aloe vera derived from a capacitor using a multimeter every 12 hours for 16 days. Descriptive statistics and repeated measures of ANOVA statistical tests were utilized to perform the data analysis. Results showed that the setup with potassium-based fertilizer had produced significantly greater electricity (p \u3c .05) among the four setups whose differences were insignificant (p \u3e .05). Time had a moderate but negligible effect on the electricity produced by the Aloe vera. It is advised to increase the time taken to observe the plant if further research will be done on the topic

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely