Short linear motif candidates in the cell entry system used by SARS-CoV-2 and their potential therapeutic implications

The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the μ2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin β3 and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions.Fil: Mészáros, Bálint. European Molecular Biology Laboratory; AlemaniaFil: Sámano Sánchez, Hugo. European Molecular Biology Laboratory; AlemaniaFil: Alvarado Valverde, Jesús. European Molecular Biology Laboratory; Alemania. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Čalyševa, Jelena. European Molecular Biology Laboratory; Alemania. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Martinez Perez, Elizabeth. Fundación Instituto Leloir; Argentina. European Molecular Biology Laboratory; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alves, Renato. European Molecular Biology Laboratory; AlemaniaFil: Shields, Denis C.. Universidad de Dublin; IrlandaFil: Kumar, Manjeet. European Molecular Biology Laboratory; AlemaniaFil: Rippmann, Friedrich. Computational Chemistry & Biology; AlemaniaFil: Chemes, Lucia Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Gibson, Toby James. European Molecular Biology Laboratory; Alemani

Lower IgG somatic hypermutation rates during acute dengue virus infection is compatible with a germinal center-independent B cell response

Reads, clonal groups, and lineages numbers per individual and condition. The table shows the number of raw and used sequences as well as the number of clonotypes and lineages per individual. (XLS 30 kb

Asociación del índice de masa corporal y conductas de riesgo en el desarrollo de trastornos de la conducta alimentaria en adolescentes mexicanos

La percepción corporal y su insatisfacción se relacionan con las conductas alimentarias de riesgo (CAR), pudiendo desarrollar trastornos de la conducta alimentaria (TAC) frecuentemente identificados en los adolescentes. El objetivo fue describir la asociación del índice de masa corporal (IMC) con los hábitos y las CAR en un grupo de adolescentes. Fue un estudio transversal, descriptivo realizado con 671 adolescentes de 12 a 15 años de edad, ambos sexos. Se aplicó una encuesta validada en población mexicana que identificó las CAR para el desarrollo de los TAC. Se obtuvo el IMC, además de información sobre práctica y conocimiento del consumo de alimentos. La prevalencia promedio de las CAR fue 12%, el sobrepeso u obesidad se presentó en 48% de los participantes, 20% de ellos no desayunaba, y sólo el 16% tomaba sus alimentos sin ningún distractor (p=0.012). La variables asociadas a las CAR para el desarrollo de TAC fueron: realizar cualquier actividad simultánea al consumo de alimentos (RM:4.23, p=0.006), sobrepeso u obesidad (RM:2.59, p=0.001), comer sin compañía (RM:2.04, p=0.005), no comer frutas (RM:1.96, p=0.008) y/o leche (RM:1.79, p=0.026), ser mujer (RM:1.74 p=0.024) y no desayunar (RM:1.57, p=0.035). El consumo de alimentos que los adolescentes practicaron fue diferente del que recomendaron para estar sanos, fue menor en verduras, frutas y leguminosas, y mayor en azúcares, lípidos y bebidas gaseosas. Se concluye que existe una asociación entre el IMC y las CAR. No se encontró coherencia entre lo que los adolescentes refirieron comer y lo que ellos recomiendan, según sus conocimientos

Characteristics of the Family Support Network of Pregnant Adolescents and Its Association with Gestational Weight Gain and Birth Weight of Newborns

It has been proposed that, in the Mexican culture, family support can be a factor that contributes to protect the maternal and child health of pregnant adolescents. There may be complex associations between family support and the circumstances of a pregnancy during adolescence. The aim of the study was to analyze the association between the family support network (FSN) characteristic and the maternal and neonatal outcomes in Mexican adolescents. A cross-sectional study was conducted, and 352 pregnant adolescents participated; their FSN during pregnancy was assessed. The gestational weight gain and birth weight/length of newborns were registered. The size of the FSN was described and divided into quartiles; the main members for each quartile were identified. Then, sociodemographic and clinical variables were compared by FSN quartiles. Logistic regression models were performed to assess the association of FSN size and pregnancy and neonatal outcomes. Our results indicate that the mean age was 15 ± 1 year old. The primary support member in the FSN was the mother of the adolescent in each quartile, except for quartile 3, where the primary support was the mother-in-law. In quartile 3 there was a significantly lower gestational weight gain compared to quartile 4 (11.8 ± 5 vs. 13 ± 5 kg, p = 0.054). According to the regression model, a higher risk of small for gestational age (OR 2.99, CI 95% 1.25–7.15) newborns was found in quartile 3. We conclude that the maternal and neonatal outcomes did not differ between quartiles of FSN size, except for quartile 3. Small for gestational age newborns were observed when a non-blood relative was present in the FSN. The quality rather than the network size might be more important for improving pregnancy outcomes

Pre-pregnancy body mass index classification and gestational weight gain on neonatal outcomes in adolescent mothers: A follow-up study.

INTRODUCTION:Institute of Medicine gestational weight gain recommendations are based on body mass index (BMI) status using adult cut-off points for women of all ages, even though adolescents have specific criteria, like WHO and CDC, so adolescents can receive inadequate weight gain recommendations. OBJECTIVES:To estimate the proportion of classification disparity between the three criteria (WHO, CDC and IOM) of pre-pregnancy BMI status; and to analyze neonatal outcomes according to weight gain recommendation based on pre-pregnancy BMI using the three criteria. METHODS:Follow-up study in pregnant adolescents 12-19 years. Sociodemographic, anthropometric and pregnancy data were obtained. Percentage of pre-pregnancy BMI classification disparity was calculated between three criteria. Gestational weight gain was categorized in adequate, low and high according to IOM. Regression models were used to analyze negative neonatal outcomes. RESULTS:601 pregnant adolescents were included, mean age was 16±1.4 years. For pre-pregnancy BMI classification, 28.5% had classification disparity using IOM vs WHO, and 14% when comparing IOM vs CDC. Greater classification disparity was observed as BMI increased. When using WHO categories, a high weight gain was associated with increased risk of having a low birth weight baby (OR: 1.91, CI95%: 1.03-3.53). For CDC criteria, a low weight gain was associated with increased risk of having a preterm baby (OR: 2.65; CI95%: 1.16-6.08) and a high weight gain was associated with low birth weight (OR: 2.10; CI95%: 1.10-4.01). For IOM criteria, a weight gain either low or high were associated with increased risk of low birth weight and preterm birth. CONCLUSION:There is pre-pregnancy BMI classification disparity using criteria for adolescents compared to adult criteria. Nevertheless, with WHO and CDC only a high gestational weight gain was a risk for negative neonatal outcome. It is important to have a BMI classification system for adolescents that better predicts neonatal outcomes

Serum Concentration of Leptin in Pregnant Adolescents Correlated with Gestational Weight Gain, Postpartum Weight Retention and Newborn Weight/Length

Introduction: Gestational weight gain is an important modifiable factor known to influence fetal outcomes including birth weight and adiposity. Leptin is normally correlated with adiposity and is also known to increase throughout pregnancy, as the placenta becomes a source of leptin synthesis. Several studies have reported positive correlations between cord blood leptin level and either birthweight or size for gestational age, as well as body mass index (BMI). Objective: To determine the correlation of prenatal leptin concentration in pregnant adolescents with their gestational weight gain, postpartum weight retention, and weight/length of their newborn. Methods: A cohort study was conducted on pregnant Mexican adolescents from Gestational Week 26–28 to three months postpartum (n = 168 mother–child dyads). An anthropometric assessment was made of each pregnant adolescent, and the serum level of leptin and the intake of energy were determined. The newborn was evaluated each month during postpartum. Clinical records were reviewed to obtain sociodemographic data. Bivariate correlations, tests for repeating measurements and logistic regression models were performed. Results: Leptin concentration gradually increased during the third trimester of pregnancy. At Gestation Week 36, leptin level correlated with gestational weight gain. When comparing adolescents that had the lowest and highest concentration of leptin, the former presented a mean of 6 kg less in gestational weight gain (inter-subject leptin concentration, p = 0.001; inter-subject energy intake, p = 0.497). Leptin concentration and gestational weight gain exerted an effect on the weight of the newborn (inter-subject leptin concentration for Week 32, p = 0.024; inter-subject gestational weight gain, p = 0.011). Newborn length was associated with leptin concentration at Week 28 (leptin effect, p = 0.003; effect of gestational weight gain, p = 0.722). Conclusions: Pregnant adolescents with leptin concentration over 20 ng/mL showed a greater gestational weight gain. Leptin concentration correlated with length and weight of the newborn

Family context and individual situation of teens before, during and after pregnancy in Mexico City

Abstract Background In the last 20 years, adolescent pregnancy has become one of the most critical problems affecting women in Latin America and the Caribbean. Methods This qualitative study was based on in-depth interviews with 29 teen mothers. All of the pregnant teens were from low- to lower-middle-class social strata in the Mexico City metropolitan area. The family (living with the girl) and the individual context of pregnant teens were analysed on the basis of data from at least three interviews: during pregnancy and at approximately 6 and 24 months following delivery. Additionally, six mothers, four fathers, and four partners of the pregnant girls of the group were interviewed. The information on the individual and family situation before, during and after the pregnancy was recorded and transcribed, then analysed in three phases, comprising pre-analysis, exploration and interpretation. Results The pregnant teens had a family background of teen pregnancy. The girls disclosed feelings of repression, loneliness and indifference to their parents, leading them to unprotected sexual relations without fear of pregnancy. After the pregnancy, communication improved between the girls and their parents, but became worse with their partner. Consequently, these teens returned to feeling as they did before getting pregnant. They stated that they would make their situation work for the sake of their child, and regretted dropping out of school and getting pregnant so young. Almost all said they were seeking love outside the family, which revealed a scenario of limited communication and unsatisfactory relations within the family. Conclusions Understanding how communication works between parents and children is necessary to avoid teenage pregnancy, as well as early marriage or cohabitation, resulting in dropping out of school and financial constraints, which lead to great frustrations between the couple and affects the child. In addition, it is vitally important that adolescents be motivated in the family setting in order for them to continue their studies. There is also an urgent need to implement measures that compensate for educational inequality, as well as to strengthen strategies aimed at adolescent mothers and pregnant teens that encourage their school performance through the support of scholarship programs and day care centres. Many of the problems inherent in adolescence are related to the lack of affection and support, and in many cases are a reaction to authoritarian rules or limits established unilaterally by parents with little or no dialogue involved

Sociodemographic Factors Associated with the Knowledge and Use of Birth Control Methods in Adolescents before and after Pregnancy

Adolescent pregnancy rates are high worldwide. However, insufficient information exists regarding the frequency of birth control methods used before the first pregnancy and postpartum. In the current study, we analyzed the association of sociodemographic factors with the knowledge of birth control methods and their use before and after pregnancy in a sample of adolescents in Mexico City. A cohort study was conducted on 600 pregnant adolescents in Mexico City, from 2013 to 2017, at a health care institution providing prenatal care. Participants were assessed during the second trimester and four months postpartum. The questionnaire explored the knowledge of birth control methods, their use, and other associated factors. Two logistic regression models were implemented to identify potential variables associated with the lack of birth control method use before and after pregnancy. The mean age of participants was 15.4 + 1 years, of which, 48% and 65.2% used a birth control method before pregnancy and postpartum, respectively. We found that the main factors associated with increased risk of not using any birth control method before pregnancy included being under the age of 15 years, school dropout, having an educational lag, initiation of sexual life before the age of 15, and having a mother who did not inform their child about contraceptives. By contrast, variables associated with a higher risk of not using any contraceptive methods after pregnancy included educational lag, lower level of education, and the fact that the adolescent had not used any birth control prior to the pregnancy