A transversal approach to predict gene product networks from ontology-based similarity

<p>Abstract</p> <p>Background</p> <p>Interpretation of transcriptomic data is usually made through a "standard" approach which consists in clustering the genes according to their expression patterns and exploiting Gene Ontology (GO) annotations within each expression cluster. This approach makes it difficult to underline functional relationships between gene products that belong to different expression clusters. To address this issue, we propose a transversal analysis that aims to predict functional networks based on a combination of GO processes and data expression.</p> <p>Results</p> <p>The transversal approach presented in this paper consists in computing the semantic similarity between gene products in a Vector Space Model. Through a weighting scheme over the annotations, we take into account the representativity of the terms that annotate a gene product. Comparing annotation vectors results in a matrix of gene product similarities. Combined with expression data, the matrix is displayed as a set of functional gene networks. The transversal approach was applied to 186 genes related to the enterocyte differentiation stages. This approach resulted in 18 functional networks proved to be biologically relevant. These results were compared with those obtained through a standard approach and with an approach based on information content similarity.</p> <p>Conclusion</p> <p>Complementary to the standard approach, the transversal approach offers new insight into the cellular mechanisms and reveals new research hypotheses by combining gene product networks based on semantic similarity, and data expression.</p

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation

Lactate dehydrogenase 5 (LDH5) is overexpressed in many cancers and is a potential target for anticancer therapy due to its role in aerobic glycolysis. Small-molecule drugs have been developed as competitive inhibitors to bind substrate/cofactor sites of LDH5, but none reached the clinic to date. Recently, we designed the first LDH5 non-competitive inhibitor, cGmC9, a peptide that inhibits protein-protein interactions required for LDH5 enzymatic activity. Peptides are gaining a large interest as anticancer agents to modulate intracellular protein-protein interactions not targetable by small molecules, however delivery of these peptides to the cytosol, where LDH5 and other anticancer targets are located, remains a challenge for this class of therapeutics. In this study, we focused on the cellular internalisation of cGmC9 to achieve LDH5 inhibition in the cytosol. We designed cGmC9 analogues and compared them for LDH5 inhibition, cellular uptake, toxicity, and antiproliferation against a panel of cancer cell lines. The lead analogue, [R/r]cGmC9, specifically impairs proliferation of cancer cell lines with high glycolytic profiles. Proteomics analysis showed expected metabolic changes in response to decreased glycolysis. This is the first report of a peptide-based LDH5 inhibitor able to modulate cancer metabolism and kill cancer cells that are glycolytic. The current study demonstrates the potential of using peptides as inhibitors of intracellular protein-protein interactions relevant for cancer pathways and shows that active peptides can be rationally designed to improve their cell permeation

Consumo de Uroleucon ambrosiae (Thomas, 1878) (Hemiptera: Aphididae) por larvas de Chrysoperla externa (Hagen, 1861) (Neuroptera: Chrysopidae) em casa-de-vegetação Consumption of Uroleucon ambrosiae (Thomas, 1878) (Hemiptera: Aphididae) BY Chrysoperla externa (Hagen, 1861) (Neuroptera: Chrysopidae) larvae in greenhouse

Com esta pesquisa objetivou-se verificar o consumo de Uroleucon ambrosiae em diferentes densidades, por larvas de Chrysoperla externa provenientes de diferentes regimes alimentares, em casa-de-vegetação. Ninfas de 3º e 4º ínstares do afídeo foram separadas nas densidades 30, 40 e 50, e colocadas nas plantas de alface (35 dias de idade), as quais, foram envolvidas por gaiola de armação de ferro de 27x27x26 cm cobertas com tecido “voil” e acoplada nos tubos de PVC do cultivo hidropônico. Quatro horas após, uma larva de C. externa, de diferentes ínstares e previamente alimentadas com U. ambrosiae ou ovos de Sitotroga cerealella (Olivier, 1819), foi liberada próximo à colônia de afídeos, sendo a gaiola fechada imediatamente; o mesmo procedimento foi adotado sem que a larva fosse confinada. Após quarenta e oito horas, realizou-se a contagem do número de afídeos consumidos em cada densidade de presa disponível. A eficiência do predador, confinado em gaiola, foi de 12,46%, 13,63% e 25,76% para larvas de 1º, 2º e 3º ínstares previamente alimentadas com ovos de S. cerealella; 9,59% e 17,63% para aquelas de 2º e 3º ínstares alimentadas anteriormente com ninfas de U. ambrosiae, respectivamente e de 18,62% para larvas de 3º ínstar previamente alimentadas com ovos do lepidóptero no 1º ínstar e ninfas dos afídeos no 2º instar; no entanto, para larvas não confinadas, não foram verificadas diferenças significativas na eficiência. Nas densidades de 40 e 50 afídeos, as porcentagens de predação (18,30 e 18,72, respectivamente) foram significativamente superiores quando comparada à densidade 30 (11,79); para testes sem confinamento, não houve influência da densidade da presa na resposta do predador. Assim, o alimento fornecido às larvas de C. externa antes de serem liberadas em casa-de-vegetação, o confinamento das mesmas e a densidade de U. ambrosiae disponível influenciaram o potencial de consumo do predador.<br>The objective of this research was to evaluate the consumption of Uroleucon ambrosiae in different densities by Chrysoperla externa larvae derived from different alimentary regimes, in greenhouse conditions. The 3rd and 4th instars nymphs of the aphid were separated in the densities 30, 40, 50 and put on the lettuce plants (35 days old) which were kepted in a voil cage of 27x27x26 cm connected to the PVC tube used for hydroponic cultivation. After four hours, one larva of C. externa previously fed with U. ambrosiae or eggs of Sitotroga cerealella (Olivier, 1819) was released near the aphid colony, with the lettuce plant being immediately covered. The same procedure was adopted without confinement of the larvae. The different instars of C. externa were evaluated, through counting of the aphids after forty eight hours. The efficiencies of the predator, confined in a cage, were 12.46, 13.63 and 25.76% for 1st, 2nd and 3th instars which were previously fed with eggs of S. cerealella. For 2nd and 3rd instar larvae fed with aphids, the efficiencies were 9.59 and 17.63%, respectively. Efficiency was 18.62% for 3th instar larvae fed previously with eggs of the lepidopterous in the 1st instar and with nymphs of aphids in the 2nd ínstar.However, for larvae without confinement, there were no differences among the instars or alimentary regimes. In the densities of 40 and 50 aphids, the percentages of predation (18.3 and 18.72, respectively) were significantly superior as compared with density 30 (11.79). There was no influence of density of prey in response to predator in the experiments without confinement. Thus, the food provided to C. externa larvae before releasing into a greenhouse, their confinement and available density of U. ambrosiae influenced the potential of consumption of the predator

Joint effect of obesity and TNFA variability on asthma: two international cohort studies

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-a (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-a (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7–3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1–1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5–14.4; OR for G/G genotype 1.7, 95% CI 0.8–3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma

Pharmacological treatment of asthma in a cohort of adults during a 20-year period: results from the European Community Respiratory Health Survey I, II and III

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma

Human Early Life Exposome (HELIX) study: a European population-based exposome cohort

e021311Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6–11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6–11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. [...]Aplinkotyros katedraVytauto Didžiojo universiteta

Association of Country Income Level With the Characteristics and Outcomes of Critically Ill Patients Hospitalized With Acute Kidney Injury and COVID-19

Introduction: Acute kidney injury (AKI) has been identified as one of the most common and significant problems in hospitalized patients with COVID-19. However, studies examining the relationship between COVID-19 and AKI in low- and low-middle income countries (LLMIC) are lacking. Given that AKI is known to carry a higher mortality rate in these countries, it is important to understand differences in this population. Methods: This prospective, observational study examines the AKI incidence and characteristics of 32,210 patients with COVID-19 from 49 countries across all income levels who were admitted to an intensive care unit during their hospital stay. Results: Among patients with COVID-19 admitted to the intensive care unit, AKI incidence was highest in patients in LLMIC, followed by patients in upper-middle income countries (UMIC) and high-income countries (HIC) (53%, 38%, and 30%, respectively), whereas dialysis rates were lowest among patients with AKI from LLMIC and highest among those from HIC (27% vs. 45%). Patients with AKI in LLMIC had the largest proportion of community-acquired AKI (CA-AKI) and highest rate of in-hospital death (79% vs. 54% in HIC and 66% in UMIC). The association between AKI, being from LLMIC and in-hospital death persisted even after adjusting for disease severity. Conclusions: AKI is a particularly devastating complication of COVID-19 among patients from poorer nations where the gaps in accessibility and quality of healthcare delivery have a major impact on patient outcomes