High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple cafe-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P<0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients

High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation: HUMAN MUTATION

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype–phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café‐au‐lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan‐like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1‐patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi‐exon deletion, providing genetic evidence that p.Arg1809Cys is a loss‐of‐function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype–phenotype correlation will affect counseling and management of a significant number of patients

La unión del péptido de la proteína L1 del virus del papiloma humano tipo 16 y 18 a las células VERO y HeLa inhibe la unión de sus VLP

Human papillomaviruses (HPVs) are the cause of epithelial lesions, HPV type 16 and type 18 being associated with the development of anogenital cancer. The L1 Major Capsid Protein (L1) represents about 90% of total HPV protein and is involved in virus?host cell interaction, but little is known about this binding process. L1 sequences from HPV types 16 and 18 were synthesized in 56 20?mer peptides, covering the entire protein, HPLC?purified, 125I?radiolabeled and tested in VERO and HeLa cell?binding assays to identify those peptides with high specific binding activity. Peptides 18283 (residues 54–77) and 18294 (274–308) from HPV16 L1, as well as 18312 (59–78) and 18322 (259–278) from HPV18 L1, presented high specific target cell binding activity. Peptide 18283 and 18294 affinity constants were 300 and 600 nM, respectively. Enzyme cell treatment before binding assay indicated that VERO and HeLa cell peptide receptor is a surface?exposed protein. There was a 60% reduction in peptide 18283 binding to heparin lyase?treated cells. Cross?linking assays showed that these proteins molecular weights were around 69 and 54 kDa. Peptides 18283 and 18294 specifically inhibited HPV?16 VLP binding to HeLa cells. According to the L1? and VLP?reported structure, both peptides are close on the VLP?surface, belonging to the outer surface broad pockets suggested as being potential receptor sites. Furthermore, it has been reported that a conserved motif from peptide 18294 is the target for neutralizing antibodies. These results suggest that such binding sequences are used by the virus as cell?binding regions

La unión del péptido de la proteína L1 del virus del papiloma humano tipo 16 y 18 a las células VERO y HeLa inhibe la unión de sus VLP

Human papillomaviruses (HPVs) are the cause of epithelial lesions, HPV type 16 and type 18 being associated with the development of anogenital cancer. The L1 Major Capsid Protein (L1) represents about 90% of total HPV protein and is involved in virus?host cell interaction, but little is known about this binding process. L1 sequences from HPV types 16 and 18 were synthesized in 56 20?mer peptides, covering the entire protein, HPLC?purified, 125I?radiolabeled and tested in VERO and HeLa cell?binding assays to identify those peptides with high specific binding activity. Peptides 18283 (residues 54–77) and 18294 (274–308) from HPV16 L1, as well as 18312 (59–78) and 18322 (259–278) from HPV18 L1, presented high specific target cell binding activity. Peptide 18283 and 18294 affinity constants were 300 and 600 nM, respectively. Enzyme cell treatment before binding assay indicated that VERO and HeLa cell peptide receptor is a surface?exposed protein. There was a 60% reduction in peptide 18283 binding to heparin lyase?treated cells. Cross?linking assays showed that these proteins molecular weights were around 69 and 54 kDa. Peptides 18283 and 18294 specifically inhibited HPV?16 VLP binding to HeLa cells. According to the L1? and VLP?reported structure, both peptides are close on the VLP?surface, belonging to the outer surface broad pockets suggested as being potential receptor sites. Furthermore, it has been reported that a conserved motif from peptide 18294 is the target for neutralizing antibodies. These results suggest that such binding sequences are used by the virus as cell?binding regions

Identification of a novel gene on chromosome 7q11.2 interrupted by a translocation breakpoint in a pair of autistic twins

We report here the identification and characterization of a novel gene (AUTS2) that spans the 7q11.2 breakpoint in a monozygotic twin pair concordant for autism and a t(7;20) (q11.2; p11.2) translocation. AUTS2 is 1.2 Mb and has 19 exons. The predicted protein is 1295 amino acids and does not correspond to any known protein. DNA sequence analysis of autism subjects and controls revealed 22 biallelic polymorphic sites. For all sites, both alleles were observed in both cases and controls. Thus no autism-specific mutation was observed. Association analysis with two exonic polymorphic sites and linkage analysis of four dinucleotide repeat markers, two within and two flanking AUTS2, was negative. Thus, although it is unlikely that AUTS2 is an autism susceptibility gene for idiopathic autism, it may be the gene responsible for the disorder in the twins studied here

Prevention and care of hepatitis B in the rural region of Fatick in Senegal : a healthcare workers' perspective using a mixed methods approach

Background In countries where hepatitis B virus (HBV) is endemic, including Senegal, the World Health Organization recommends systematic HBV screening of pregnant women and vaccination at birth to prevent mother-to-child transmission (MTCT). This study investigated healthcare workers' (HCW) knowledge and practices regarding HBV prevention and care in the rural region of Fatick in Senegal, as well as challenges they faced in implementing prevention activities related to HBV MTCT. Methods A mixed-methods survey was conducted between May-July 2017 among 112 HCW working in 15 healthcare facilities in two districts of the Fatick region using face-to-face questionnaires and semi-structured interviews. Descriptive statistics and chi-square/Mann-Whitney tests were used to analyze quantitative data, while qualitative data were analyzed thematically. Results The study population included 87 HCW in the quantitative component (83% women, median age [interquartile range, IQR] = 35 [31-40] years) and 11 in the qualitative component. A knowledge gap was observed in key areas of HBV infection: only 24, 51 and 38%, respectively, correctly reported that early HBV acquisition is associated with a high risk of developing chronic infection, that perinatal transmission is one of the main modes of HBV transmission in Senegal, and that three to four doses of HBV vaccine are required to ensure immunization in children. Despite good acceptability of systematic screening of pregnant women and vaccination at birth, only 48% of HCW mainly involved in prenatal care and 71% of those involved exclusively in vaccination routinely performed these two key interventions. HCW reported several structural barriers that may hinder their implementation: a lack of training in HBV and in counseling, poor availability of rapid diagnostic tests (RDT), high costs of both screening and treatment, a lack of adequate information on treatment options and missed opportunities for vaccination at birth. Conclusions HCW working in the Fatick region may be insufficiently trained and supported to effectively implement HBV prevention strategies. Our findings suggest an urgent need to strengthen MTCT prevention in this region, by improving HCW knowledge in key areas of HBV infection, providing RDT and antiviral treatment at low cost, and enhancing community-based interventions for the timely vaccination of newborns

Correction to: NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer

After the publication of this work [1] the authors have reported that in Table\ua03 The letter "T" in columns 5 and 7 should not be there

FULL Investiga Enero a Junio 2021 Número 3.

Contiene: 1. Ciencia, tecnología e innovación. -- La conciencia y el inconsciente en la obra de John B.Watson / Laura Bayona-Pérez, Andrés L. Cortés-Valencia, Jairo A. Rozo Castillo y Andrés M. Pérez-Acosta -- La integración espontánea de nuestro cerebro: un sustento para la capacidad atencional / Adriana Lucía Ruiz Rizzo -- Creación y consolidación de la Línea de Investigación en Internet de las Cosas en la Facultad de Ingeniería y Ciencias Básicas / John Petearson Anzola, Lida Rubiela Fonseca G., Duván Santiago Beltrán M. y Edwin Enrique Bojacá -- 2. Creación, cultura y sociedad. Lineamientos de una estrategia didáctica para el área de educación artística / Raquel Caicedo Caicedo -- La investigación en América Latina: entre el pensamiento creativo, la inteligencia y la vida cotidiana / Marilena Caicedo López -- Producción escrita una alternativa idónea, en la solución de problemáticas de convivencia escolar / Clara Adriana Bohórquez Chautá -- 3. Iniciación científica. -- Identificación de mascotas extraviadas por medio de un sistema inteligente / Lucy Nohemy Medina Velandia, Johan Sebastián Ciprian Anzola y Juan Camilo Castro Yara -- Consideraciones ambientales delfracturamiento hidráulico en Colombia / Rosa Eugenia Reyes Gil -- 4. Reflexiones. -- La indocilidad reflexiva: una apuesta de resistencia de pacientes terminales en las luchas por la salud en el contexto colombiano / Lu An Gonzalez Santiago -- Educación y TIC en tiempos de pandemia: desafíos de aplicación / Fanny Margarita López Valek y Luis Eduardo Ospina Lozano -- Hablemos de Diplomacia Científica durante la pandemia / Luisa Fernanda Echeverría King -- Reflexiones en torno a la divulgación de la ciencia, la tecnología, la innovación y la creación por medio de la comunicación y el periodismo científico / Alejandro Pachajoa-Londoño.Fundación Universitaria Los Libertadore