Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Study Of Osmotic Dehydration Of Tomato In Ternary Solutions Through Response Surface Methodology [estudo Da Desidratação Osmótica De Tomate Em Soluções Ternárias Pela Metodologia De Superfície De Resposta]

The objective of this work was to study the influence of temperature (20-40°C), solution composition (0% NaCl/65% sucrose - 10% NaCl/55% sucrose) and agitation level (0 - 1000 rpm), on the osmotic dehydration of tomato's halves. The process was carried out in a jacketed tank connected to a thermostatic bath, and osmotic solution agitation was promoted by a mechanical stirrer and measured by a digital tachometer. Results were analyzed through response surface methodology, according to a 23 factorial experimental design. Water loss, salt and sucrose gain and final water activity of the product were positively influenced by temperature and by increasing salt content on the solution. Agitation influenced only on water loss, indicating that in this case, mass transfer is not governed only by a diffusion internal mechanism. Equilibrium proximity reached in each test was verified through the relationship between solution and samples water activities. The samples processed in solutions with higher salt content seemed to be more distant of equilibrium, after 3 hours of process.263715723(2002) Anuário Da Agricultura Brasileira, , AGRIANUAL 2003. São Paulo: FNP - Consultoria e Comércio(1995) Official Methods of Analysis of the Association of Official Analytical Chemists, 16th Edition, , A.O.A.C. (Association of Official Analytical Chemists) Arlington: A.O.A.CBaroni, A.F., (2004) Propriedades Mecânicas, Termodinâmicas e de Estado de Tomate Submetido à Desidratação Osmótica e Secagem, 226p. , Campinas, Tese (Doutor em Engenharia de Alimentos) - Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas (UNICAMP)Bligh, E.G., Dyer, W.J., A rapid method of total lipid extraction and purification (1959) Canadian Journal of Biochemistry and Physiology, 37 (8), pp. 911-917Bohuon, P., Collignan, A., Rios, G.M., Raoultwack, A.L., Soaking process in ternary liquids: Experimental study of mass transport under natural and forced convection (1998) Journal of Food Engineering, 37 (4), pp. 451-469Box, G.E.P., Wetz, J., Criteria for judging adequacy of estimation by an approximate response function (1973) University of Wiscosin Technical Report, (9)Chenlo, F., Moreira, G., Pereira, G., Ampudia, A., Viscosities of aqueous solutions of sucrose and sodium chloride of interest in osmotic dehydration processes (2002) Journal of Food Engineering, 54 (4), pp. 347-352Collignan, A., Raoult-Wack, A.L., Dewatering and salting of cod by immersion in concentrated sugar/salt solutions (1994) Lebensmittel-Wissenschaft und Technologie, 27 (3), pp. 259-264Hortaliças Em Numéros - Dados Socioeconômicos, , www.cnph.embrapa.br, Disponível em: Acesso em: 20 de novembro de 2005Giraldo, G., Talens, P., Fito, P., Chiralt, A., Influence of sucrose solution concentration on kinetics and yield during osmotic dehydration of mango (2003) Journal of Food Engineering, 58 (1), pp. 33-43Lazarides, H.N., Katsanidis, E., Nickolaidis, A., Mass transfer kinetics during osmotic preconcentration aiming at minimal solid uptake (1995) Journal of Food Engeneering, 25 (2), pp. 151-166Lenart, A., Flink, J.N., Osmotic concentration of potatoes: Criteria for the end point of the osmotic effect (1984) Journal of Food Technology, 19 (1), pp. 65-89Mayor, L., Moreira, R., Chenlo, F., Sereno, A.M., Kinetics of osmotic dehydration of pumpkim with sodium chloride solutions (2005) Journal of Food Engineering, 74 (2), pp. 253-262Medina-Vivanco, M.L., (2003) Desidratação Osmótica Em Soluções Ternárias, Secagem e Transições Térmicas de Filé de Tilápia (Oreochromis Niloticus), 211p. , Campinas, Tese (Doutor em Engenharia de Alimentos) - Faculdade de Engenharia de Alimentos, Universidade Estadual de Campinas (UNICAMP)Medina-Vivanco, M., Sobral, P.J.A., Hubinger, M.D., Osmotic dehydration of tilapia fillets in limited volume of ternary solutions (2002) Chemical Engineering Journal, 86 (1-2), pp. 199-205Moreira, R., Sereno, A.M., Evaluation of mass transfer coefficients and volumetric shrinkage during osmotic dehydration of apple using sucrose solutions in static and non-static conditions (2003) Journal of Food Engineering, 57 (1), pp. 25-31Qi, H., Le Maguer, M., Sharma, S.K., Design and selection of processing conditions of a pilot scale contactor for continuous osmotic dehydration of carrots (1998) Journal of Food Process Engineering, 21 (1), pp. 75-88Ranganna, S., (1977) Manual of Analysis of Fruit and Vegetable Products, , New Delhi, India: Mc Graw-Hill Publishing Company LimitedRaoult-Wack, A.L., Recent advances in the osmotic dehydration of foods (1994) Trends in Food Science & Technology, 5 (8), pp. 255-260Rastogi, N.K., Raghavarao, K.S.M.S., Mass transfer during osmotic dehydration of pineapple: Considering Fickian diffusion in cubical configuration (2004) Lebensmittel-Wissenschaft und Technologie, 37 (1), pp. 43-47Sereno, A.M., Moreira, R., Martínez, E., Mass transfer coefficients during osmotic dehydration of apple in single and combined aqueous solutions of sugar and salt (2001) Journal of Food Engineering, 47 (1), pp. 43-49Shi, J., Le Maguer, M., Kakuda, Y., Liptay, A., Niekamr, F., Lycopene degradation and isomerization in tomato dehydration (1999) Food Research International, 32 (1), pp. 15-21Telis, V.R.N., Murari, R.C.B.D.L., Yamashita, F., Diffusion coefficients during osmotic dehydration of tomatoes in ternary solutions (2004) Journal of Food Engineering, 61 (2), pp. 253-25

Combined Reconstruction of the Medial Patellofemoral Ligament and Medial Quadriceps Tendon–Femoral Ligament

Most patellar dislocations are associated with disruption of the proximal medial patellar restraints (PMPRs). The PMPRs comprise the medial patellofemoral ligament (MPFL) and medial quadriceps tendon–femoral ligament (MQTFL). Although isolated MPFL reconstruction is the most frequently performed procedure for the surgical management of recurrent dislocation, recent studies have shown that the MQTFL has a synergistic role with the MPFL in resisting lateral patellar displacement close to full extension. It has therefore been suggested that surgical techniques that gain the benefits of both proximal and distal PMPR biomechanical behavior may be best. This article describes an established technique for combined MPFL and MQTFL reconstruction using semitendinosus autograft

Mutation and Evolutionary Rates in Adélie Penguins from the Antarctic

Precise estimations of molecular rates are fundamental to our understanding of the processes of evolution. In principle, mutation and evolutionary rates for neutral regions of the same species are expected to be equal. However, a number of recent studies have shown that mutation rates estimated from pedigree material are much faster than evolutionary rates measured over longer time periods. To resolve this apparent contradiction, we have examined the hypervariable region (HVR I) of the mitochondrial genome using families of Ade´ lie penguins (Pygoscelis adeliae) from the Antarctic. We sequenced 344 bps of the HVR I from penguins comprising 508 families with 915 chicks, together with both their parents. All of the 62 germline heteroplasmies that we detected in mothers were also detected in their offspring, consistent with maternal inheritance. These data give an estimated mutation rate (m) of 0.55 mutations/site/Myrs (HPD 95% confidence interval of 0.29–0.88 mutations/site/Myrs) after accounting for the persistence of these heteroplasmies and the sensitivity of current detection methods. In comparison, the rate of evolution (k) of the same HVR I region, determined using DNA sequences from 162 known age sub-fossil bones spanning a 37,000-year period, was 0.86 substitutions/site/Myrs (HPD 95% confidence interval of 0.53 and 1.17). Importantly, the latter rate is not statistically different from our estimate of the mutation rate. These results are in contrast to the view that molecular rates are time dependent

Chromosome separation and exit from mitosis in budding yeast: dependence on growth revealed by cAMP-mediated inhibition.

IF2003=3.94