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[This corrects the article DOI: 10.1371/journal.pgph.0000970.].
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PURPOSE OF REVIEW: Almost half of people diagnosed with diabetes mellitus will develop painful diabetic neuropathy (PDN), a condition greatly impacting quality of life with complicated pathology. While there are different FDA approved forms of treatment, many of the existing options are difficult to manage with comorbities and are associated with unwanted side effects. Here, we summarize the current and novel treatments for PDN. RECENT FINDINGS: Current research is exploring alternative pain management treatments from the first line options of pregabalin, gabapentin, duloxetine, and amitriptyline which often have side effects. The use of FDA approved capsaicin and spinal cord stimulators (SCS) has been incredibly beneficial in addressing this. In addition, new treatments looking at different targets, such as NMDA receptor and the endocannabinoid system, show promising results. There are several treatment options that have been shown to be successful in helping treat PDN, but often require adjunct treatment or alterations due to side effects. While there is ample research for standard medications, treatments such as palmitoylethanolamide and endocannabinoid targets have extremely limited clinical trials. We also found that many studies did not evaluate additional variables other than pain relief, such as functional changes nor were there consistent measurement methods. Future research should continue trials comparing treatment efficacies along with more quality of life measures.
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Diabetes Mellitus , Neuropatías Diabéticas , Humanos , Neuropatías Diabéticas/tratamiento farmacológico , Calidad de Vida , Endocannabinoides , Gabapentina/uso terapéutico , Pregabalina/uso terapéuticoRESUMEN
Few studies have investigated retention in HIV care in West Africa. We measured retention in antiretroviral therapy (ART) programmes among people living with HIV and re-engagement in care among those lost to follow up (LTFU) in Guinea and identified associated risk factors using survival analysis. Patient-level data were analysed from 73 ART sites. Treatment interruptions and LTFU were defined as missing a ART refill appointment by over 30 days and by over 90 days respectively. A total of 26,290 patients initiating ART between January 2018 and September 2020 were included in the analysis. The mean age at ART initiation was of 36.2 years, with women accounting for 67% of the cohort. Retention 12 months after ART initiation was 48.7% (95%CI 48.1-49.4%). The LTFU rate was 54.5 per 1000 person-months (95% CI 53.6-55.4), with the peak hazards of LTFU occurring after the first visit and decreasing steadily over time. In an adjusted analysis, the hazards of LTFU were higher among men compared to women (aHR = 1.10; 95%CI 1.08-1.12), being aged 13-25 years old versus older patients (aHR = 1.07; 95%CI = 1.03-1.13), and among those initating ART in smaller health facilities (aHR = 1.52; 95%CI 1.45-1.60). Among 14,683 patients with an LTFU event, 4,896 (33.3%) re-engaged in care, of whom 76% did so within six months from LTFU. The re-engagement rate was 27.1 per 1000 person-months (95%CI 26.3-27.9). Treatment interruptions were correlated with rainfall patterns and end of year mobility patterns. Rates of retention and re-engagement in care are very low in Guinea, undermining the effectiveness and durability of first-line ART regimens. Tracing interventions and differentiated service delivery of ART, including multi-month dispensing may improve care engagement, especially in rural areas. Further research should investigate social and health systems barriers to retention in care.
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BACKGROUND: One out of ten deaths of children under five are attributable to indoor air pollution. And Acute Respiratory Illness (ARI) is among the direct causes. OBJECTIVE: This study showed the possibilities of characterizing indoor air pollution in West African Economic and Monetary Union (WAEMU) area and it also made it possible to estimate its impact on the occurrence of ARI in children under five. METHODS: It has been a secondary analysis based on Demographic and Health Surveys (DHSs) from WAEMU countries' data.. "Household level of air pollution" is the created composite variable, from questions on the degradation factors of indoor air quality (domestic combustion processes) which served to characterize indoor air pollution and to measure its impact by a logistic regression. RESULTS: Burkina Faso stands out with a greater number of households with a high level of pollution (63.7%) followed by Benin (43.7%) then Togo (43.0%). The main exposure factor "Household level of air pollution" was associated with ARI symptoms (Togo: prevalence = 51.3%; chi-squared test's p-value < 0.001). Exposure to high level of pollution constitutes a risk (AOR [95 CI]), even though it is not significant ( Ivory Coast: 1.29 [0.72-2.30], Senegal: 1.39 [0.94-2.05] and Togo: 1.15 [0.67-1.95]) and this could be explained by the high infectious etiology of the ARI.
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Contaminación del Aire Interior , Contaminación del Aire , Infecciones del Sistema Respiratorio , Niño , Humanos , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/etiología , Factores de Riesgo , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminación del Aire Interior/efectos adversos , Contaminación del Aire Interior/análisis , Prevalencia , Burkina Faso , CulinariaRESUMEN
Diarrheal diseases are the second leading cause of child mortality worldwide, occurring in about one in every nine child deaths, and were associated with water, sanitation, and hygiene (WASH) access. In this study, we provided an overview of WASH indicators' evolution from 2000 to 2017 and their impact on the occurrence of diarrhea in children under 5 years old in Senegal. It was a retrospective cross-sectional study, in which we did a secondary analysis of data from the Joint Monitoring Program (JMP) for water supply and sanitation and from the Senegal Demographic and Health Survey 2018. Our results showed that access to safely managed services increased by 18.1 and 19.1%, respectively, for water and sanitation. The prevalence of diarrhea estimated at 18.16% was associated with straining water through a cloth (adjusted odds ratio (AOR) [95% confidence interval (CI)]: 1.21 [1.00-1.45]) and getting water supplies from a source not located in a dwelling (AOR [95% CI]: 1.59 [1.21-2.09]). The prevalence of diarrhea among children under 5 years old was still relatively high in Senegal and was significantly associated with a lack of WASH access. Although the latter continues to increase, additional efforts to make water safer to drink will significantly reduce the occurrence of diarrheal diseases among children under 5 years old in Senegal.
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Higiene , Saneamiento , Niño , Humanos , Preescolar , Estudios Transversales , Estudios Retrospectivos , Senegal/epidemiología , Diarrea/epidemiologíaRESUMEN
Cancer is caused by abnormal cell growth and metastasis to other tissues. Development of cancers is complex and underlining mechanisms are mostly unknown. Disco-interacting protein 2 homolog B (DIP2B) is a member of Dip2. There have been reports suggesting that Dip2B may participate in tumor growth and development. However, direct link between DIP2B and cancer development is missing. In this study, Dip2btm1a/+ heterozygous knockout mouse model was used to investigate tumor growth and metastasis. Results show that one allele knockout of Dip2B significantly promoted tumor growth and metastasis, decreased tumor cell apoptosis and reduced immune cell infiltration in tumors, most likely by altering immune system that includes reduction of macrophage and cytotoxic T-cells infiltration into tumor microenvironment.
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Neoplasias , Proteínas del Tejido Nervioso , Microambiente Tumoral , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Macrófagos , Ratones , Ratones Noqueados , Metástasis de la Neoplasia , Neoplasias/genética , Neoplasias/inmunología , Proteínas del Tejido Nervioso/genética , Microambiente Tumoral/genéticaRESUMEN
Bex2 is well known for its role in the nervous system, and is associated with neurological disorders, but its role in the lung's physiology is still not reported. To elucidate the functional role of Bex2 in the lung, we generated a Bex2 knock-out (KO) mouse model using the CRISPR-Cas9 technology and performed transcriptomic analysis. A total of 652 genes were identified as differentially expressed between Bex2 -/- and Bex2 +/+ mice, out of which 500 were downregulated, while 152 were upregulated genes. Among these DEGs, Ucp1, Myh6, Coxa7a1, Myl3, Ryr2, RNaset2b, Npy, Enob1, Krt5, Myl2, Hba-a2, and Nrob2 are the most prominent genes. Myl2, was the most downregulated gene, followed by Npy, Hba-a2, Rnaset2b, nr0b2, Klra8, and Ucp1. Tcte3, Eno1b, Zfp990, and Pcdha9 were the most upregulated DEGs. According to gene enrichment analysis, PPAR pathway, cardiac muscle contraction, and cytokine-cytokine receptor interaction were the most enriched pathways. Besides, the nuclear factor-κB signaling pathway and hematopoietic cell linage pathways were also enriched. Chronic obstructive pulmonary disease (COPD) is enriched among KEGG disease pathways. RT-qPCR assays confirmed the RNA-Seq results. This study opens a new window toward the biological functions of Bex2 in different systems.
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Disconnected (disco)-interacting protein 2 homolog B (Dip2B) is a member of the Dip2 superfamily and plays an essential role in axonal outgrowth during embryogenesis. In adults, Dip2B is highly expressed in different brain regions, as shown by in situ analysis, and may have a role in axon guidance. However, the expression and biological role of Dip2B in other somatic tissues remain unknown. To better visualize Dip2B expression and to provide insight into the roles of Dip2B during postnatal development, we used a Dip2btm1a(wtsi)komp knock-in mouse model, in which a LacZ-Neo fusion protein is expressed under Dip2b promoter and allowed Dip2B expression to be analyzed by X-gal staining. qPCR analyses showed that Dip2b mRNA was expressed in a variety of somatic tissues, including lung and kidney, in addition to brain. LacZ staining indicated that Dip2B is broadly expressed in neuronal, reproductive, and vascular tissues as well as in the kidneys, heart, liver, and lungs. Moreover, neurons and epithelial cells showed rich staining. The broad and intense patterns of Dip2B expression in adult mice provide evidence of the distribution of Dip2B in multiple locations and, thereby, its implication in numerous physiological roles.
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Expresión Génica , Genes Reporteros , Operón Lac , Proteínas del Tejido Nervioso/genética , Animales , Biomarcadores , Femenino , Técnicas de Genotipaje , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Proteínas del Tejido Nervioso/metabolismo , Especificidad de ÓrganosRESUMEN
As part of a validation program of antimalarial traditional recipes, an ethnotherapeutic approach was applied in Dionfo, a meso-endemic Guinean rural area where conventional health facilities are insufficient. A prevalence investigation indicated a malarial burden of 4.26%. Ethnomedical and ethnobotanical surveys led to a collection of 63 plant species used against malaria from which Terminalia albida (Combretaceae) was one of the most cited. Ethnotherapeutic evaluation of a remedy based on T. albida was applied to 9 voluntary patients suffering from uncomplicated malaria. Treatment of 7 to 14 days led to an improvement of clinical symptoms and a complete parasite clearance achievement of 8/9 patients without side effects. In addition to antiplasmodial activity in vitro and in vivo previously described, this study indicates an efficacy to support the antimalarial traditional use of T. albida, which could constitute a first-aid treatment when access to other medicines is delayed in the Dionfo community. Ethnotherapeutical investigation could be a valuable approach to guide subsequent investigations on traditional remedies.
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Antimaláricos , Malaria , Terminalia , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Etnobotánica , Humanos , Malaria/tratamiento farmacológico , Malaria/epidemiología , PrevalenciaRESUMEN
BACKGROUND: Many human genetic diseases arise from point mutations. These genetic diseases can theoretically be corrected through gene therapy. However, gene therapy in clinical application is still far from mature. Nearly half of the pathogenic single-nucleotide polymorphisms (SNPs) are caused by G:C>A:T or T:A>C:G base changes and the ideal approaches to correct these mutations are base editing. These CRISPR-Cas9-mediated base editing does not leave any footprint in genome and does not require donor DNA sequences for homologous recombination. These base editing methods have been successfully applied to cultured mammalian cells with high precision and efficiency, but BE4 has not been confirmed in mice. Animal models are important for dissecting pathogenic mechanism of human genetic diseases and testing of base correction efficacy in vivo. Cytidine base editor BE4 is a newly developed version of cytidine base editing system that converts cytidine (C) to uridine (U). RESULTS: In this study, BE4 system was tested in cells to inactivate GFP gene and in mice to introduce single-base substitution that would lead to a stop codon in tyrosinase gene. High percentage albino coat-colored mice were obtained from black coat-colored donor zygotes after pronuclei microinjection. Sequencing results showed that expected base changes were obtained with high precision and efficiency (56.25%). There are no off-targeting events identified in predicted potential off-target sites. CONCLUSIONS: Results confirm BE4 system can work in vivo with high precision and efficacy, and has great potentials in clinic to repair human genetic mutations.
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Animales , Ratones , Adenosina Desaminasa , Citosina , Sistemas CRISPR-Cas , Edición Génica/métodos , Secuencia de Bases , Western Blotting , Modelos Animales , Reacción en Cadena en Tiempo Real de la Polimerasa , MutaciónRESUMEN
The aim of this study was to assess the integrity and kidney overall functional capacity of subjects exposed to landfill emissions. Urine and blood levels of Pb and Cd, and several of the newly biomarkers of nephrotoxicity (Kim Injury Molecule 1 (KIM-1), alpha-1 Microglobulin (α1 M), beta-2 Microglobulin (ß2 M), Cystatin-C (Cyst C), Clusterin, alpha-glutathione S-transferase (GSTα), pi-glutathione S-transferase (GSTπ), Tissue Inhibitor of Metalloproteinase-1 (TIMP1), Calbindin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Osteopontin (OPN), (Retinol Binding Protein(RBP), Liver-type Fatty Acid-Binding Protein (FABP-1), Trefoil Factor 3 (TFF3), Collagen VI) were measured in order to assess glomerular and tubule damage in adults living near a landfill. Our results indicate glomerular dysfunction in exposed subjects, and supported evidence of necrosis of proximal and distal tubule epithelial cells as specific biomarkers began to appear in the urine. Positive correlation by Pearson test were obtained between : blood Pb and B-OPN, B-Cyst C, Calbindin, U-KIM-1, TIMP1, U-OPN, and U-Clusterin; and also, between urinary Cd and TIMP1, B-Clusterin, U-OPN, FABP-1, Albumin, and U-Clusterin. The relation between biomarkers of Cd/Pb exposure and early effect biomarkers in this study clearly predicts the future risk of severe kidney injury in subjects living close to the landfill.
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Vascular endothelial growth factor (VEGF) is important for lung development and function but ideal mouse models are limited to decipher the quantitative relationship between VEGF expression levels and its proper development and pathogenesis. Human SPC promoter has been used to faithfully express genes or cDNAs in the pulmonary epithelium in many transgenic mouse models. In the study, a mouse model of lung-specific and reversible VEGF repression (hspc-rtTRtg/+/VegftetO/tetO) was generated. Human SPC promoter was used to drive lung-specific rtTR expression, a cDNA coding for doxycycline-regulated transcription repression protein. By crossing with VegftetO/tetO mice, that has tetracycline operator sequences insertion in 5'-UTR region, it allows us to reversibly inhibit lung VEGF transcription from its endogenous level through doxycycline food, water or injection. The tissue-specific inhibition of VEGF is used to mimic abnormal expression levels of VEGF in lung. Reduced VEGF expression in lung is confirmed by quantitative real time PCR and immunoblotting. Lung development and structure was analyzed by histology analysis and found significantly affected under low VEGF. The pulmonary epithelium and alveolarization are found abnormal with swelling alveolar septum and enlargement of air space. Genome-wide gene expression analysis identified that immune activities are involved in the VEGF-regulated lung functions. The transgenic mouse model can be used to mimic human pulmonary diseases. The mouse model confirms the important regulatory roles of epithelial expressed VEGF in lung development and function. This mouse model is valuable for studying VEGF-regulated lung development, pathogenesis and drug screening under low VEGF expression.
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Enfermedades Pulmonares/genética , Pulmón/metabolismo , Organogénesis/genética , Proteína C Asociada a Surfactante Pulmonar/genética , Factor A de Crecimiento Endotelial Vascular/genética , Animales , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Regulación del Desarrollo de la Expresión Génica/genética , Humanos , Pulmón/crecimiento & desarrollo , Pulmón/patología , Enfermedades Pulmonares/patología , Ratones , Ratones Transgénicos , Regiones Promotoras Genéticas/genéticaRESUMEN
Molecular and anatomical functions of mammalian Dip2 family members (Dip2A, Dip2B and Dip2C) during organogenesis are largely unknown. Here, we explored the indispensable role of Dip2B in mouse lung development. Using a LacZ reporter, we explored Dip2B expression during embryogenesis. This study shows that Dip2B expression is widely distributed in various neuronal, myocardial, endothelial, and epithelial cell types during embryogenesis. Target disruption of Dip2b leads to intrauterine growth restriction, defective lung formation and perinatal mortality. Dip2B is crucial for late lung maturation rather than early-branching morphogenesis. The morphological analysis shows that Dip2b loss leads to disrupted air sac formation, interstitium septation and increased cellularity. In BrdU incorporation assay, it is shown that Dip2b loss results in increased cell proliferation at the saccular stage of lung development. RNA-seq analysis reveals that 1431 genes are affected in Dip2b deficient lungs at E18.5 gestation age. Gene ontology analysis indicates cell cycle-related genes are upregulated and immune system related genes are downregulated. KEGG analysis identifies oxidative phosphorylation as the most overrepresented pathways along with the G2/M phase transition pathway. Loss of Dip2b de-represses the expression of alveolar type I and type II molecular markers. Altogether, the study demonstrates an important role of Dip2B in lung maturation and survival.
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Genes Letales , Pulmón/embriología , Proteínas del Tejido Nervioso/genética , Organogénesis/genética , Animales , Embrión de Mamíferos , Femenino , Muerte Fetal , Eliminación de Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Embarazo , Isoformas de Proteínas/genéticaRESUMEN
Disco-interacting protein 2 homolog B (Dip2B) is a member of Dip2 family encoded by Dip2b gene. Dip2B has been reported to regulate murine epithelial KIT+ progenitor cell expansion and differentiation epigenetically via exosomal miRNA targeting during salivary gland organogenesis. However, its molecular functions, cellular activities and biological process remain unstudied. Here, we investigated the transcriptome of Dip2B-deficient mouse embryonic lung fibroblasts (MELFs) isolated from E14.5 embryos by RNA-Seq. Expression profiling identified 1369 and 1104 differentially expressed genes (DEGs) from Dip2b-/- and Dip2b+/- MELFs in comparisons to wild-type (Dip2b+/+ ). Functional clustering of DEGs revealed that many gene ontology terms belong to membrane activities such as 'integral component of plasma membrane', and 'ion channel activity', suggesting possible roles of Dip2B in membrane integrity and membrane function. KEGG pathway analysis revealed that multiple metabolic pathways are affected in Dip2b- / - and Dip2b +/ - when compared to Dip2b +/+ MELFs. These include 'protein digestion and absorption', 'pancreatic secretion' and 'steroid hormone synthesis pathway'. These results suggest that Dip2B may play important roles in metabolism. Molecular function analysis shows transcription factors including Hox-genes, bHLH-genes, and Forkhead-genes are significantly down-regulated in Dip2b- / - MELFs. These genes are critical in embryo development and cell differentiation. In addition, Dip2B-deficient MELFs demonstrated a reduction in cell proliferation and migration, and an increase in apoptosis. All results indicate that Dip2B plays multiple roles in cell proliferation, migration and apoptosis during embryogenesis and may participate in control of metabolism. This study provides valuable information for further understanding of the function and regulatory mechanisms of Dip2B.
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INTRODUCTION: Information Technologies (IT) may serve assistive roles that facilitate the interaction of people living with cognitive disabilities (CD) within their environments. However, there are some notable concerns related to privacy threats associated with the use of IT. The purpose of this study was to examine how assistive technology developers may best adapt over time to develop their IT to be resilient against threats to privacy. We therefore focused on the following areas: (1) developers' knowledge and practices related to privacy protection; (2) challenges when applying recommended practices, and; (3) preferred channels to acquire knowledge. METHOD: We conducted semi-structured interviews with ten technology developers who are members of the AGE-WELL network undertaking research and development of assistive technologies to be used by people who have cognitive disabilities. We used an inductive-deductive method for the analysis of qualitative data to examine participant responses and generate themes related to the study goals. RESULTS: Principal themes that emerged from the data include practices specific to populations with CD, challenges to obtaining consent to use of information, and preferred channels to acquire knowledge. CONCLUSION: We identify areas of focus for developing a knowledge mobilization strategy to improve relevant policies and practices.
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Dip2C is highly expressed in brain and many other tissues but its biological functions are still not clear. Genes regulated by Dip2C in brain have never been studied. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) systems, adaptive immune systems of bacteria and archaea, have been recently developed and broadly used in genome editing. Here, we describe targeted gene deletions of Dip2c gene in mice via CRISPR/Cas9 system and study of brain transcriptome under Dip2C regulation. The CRISPR/Cas9 system effectively generated targeted deletions of Dip2c by pronuclei injection of plasmids that express Cas9 protein and two sgRNAs. We achieved targeted large fragment deletion with efficiencies at 14.3% (1/7), 66.7% (2/3) and 20% (1/5) respectively in 3 independent experiments, averaging 26.7%. The large deletion DNA segments are 160.4 kb (Dip2CΔ160kb), spanning from end of exon 4 to mid of exon 38. A mouse with two base pair deletion was generated from a single sgRNA targeting in exon 4 (Dip2cΔ2bp) by non-homologous end joining (NHEJ). Loss of gene expression for Dip2c mRNA was confirmed by quantitative real-time PCR (qPCR). Dip2C-regulated genes and pathways in brain were investigated through RNAseq of Dip2cΔ2bp. In total, 838 genes were found differentially regulated, with 252 up and 586 down. Gene ontology (GO) analysis indicated that DEGs in brain are enriched in neurological functions including 'memory', 'neuropeptide signaling pathway', and 'response to amphetamine' while KEGG analysis shows that 'neuroactive ligand-receptor interaction pathway' is the most significantly enriched. DEGs Grid2ip, Grin2a, Grin2c, Grm4, Gabbr2, Gabra5, Gabre, Gabrq, Gabra6 and Gabrr2 are among the highly regulated genes by Dip2C. Results confirm Dip2C may play important roles in brain development and function.
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Encéfalo/metabolismo , Regulación de la Expresión Génica/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de Neoplasias/genética , Transcriptoma/genética , Animales , Encéfalo/citología , Encéfalo/crecimiento & desarrollo , Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Femenino , Eliminación de Gen , Edición Génica/métodos , Técnicas de Inactivación de Genes , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , ARN Guía de Kinetoplastida/genéticaRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0213702.].
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Disconnected interacting protein 2 homolog A (DIP2A) is highly expressed in nervous system and respiratory system of developing embryos. However, genes regulated by Dip2a in developing brain and lung have not been systematically studied. Transcriptome of brain and lung in embryonic 19.5 day (E19.5) were compared between wild type and Dip2a-/- mice. An average of 50 million reads per sample was mapped to the reference sequence. A total of 214 DEGs were detected in brain (82 up and 132 down) and 1900 DEGs in lung (1259 up and 641 down). GO enrichment analysis indicated that DEGs in both Brain and Lung were mainly enriched in biological processes 'DNA-templated transcription and Transcription from RNA polymerase II promoter', 'multicellular organism development', 'cell differentiation' and 'apoptotic process'. In addition, COG classification showed that both were mostly involved in 'Replication, Recombination, and Repair', 'Signal transduction and mechanism', 'Translation, Ribosomal structure and Biogenesis' and 'Transcription'. KEGG enrichment analysis showed that brain was mainly enriched in 'Thyroid cancer' pathway whereas lung in 'Complement and Coagulation Cascades' pathway. Transcription factor (TF) annotation analysis identified Zinc finger domain containing (ZF) proteins were mostly regulated in lung and brain. Interestingly, study identified genes Skor2, Gpr3711, Runx1, Erbb3, Frmd7, Fut10, Sox11, Hapln1, Tfap2c and Plxnb3 from brain that play important roles in neuronal cell maturation, differentiation, and survival; genes Hoxa5, Eya1, Errfi1, Sox11, Shh, Igf1, Ccbe1, Crh, Fgf9, Lama5, Pdgfra, Ptn, Rbp4 and Wnt7a from lung are important in lung development. Expression levels of the candidate genes were validated by qRT-PCR. Genome wide transcriptional analysis using wild type and Dip2a knockout mice in brain and lung at embryonic day 19.5 (E19.5) provided a genetic basis of molecular function of these genes.
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Encéfalo/metabolismo , Pulmón/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Animales , Encéfalo/embriología , Diferenciación Celular/genética , Supervivencia Celular/genética , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Pulmón/embriología , Ratones , Ratones Noqueados , Anotación de Secuencia Molecular , Neuronas/citología , Neuronas/metabolismo , Proteínas Nucleares/deficiencia , Análisis de Secuencia de ARN , Factores de Transcripción/genéticaRESUMEN
Isomaltose-oligosaccharides (IMOs), as food ingredients with prebiotic functionality, can be prepared via enzymatic synthesis using α-glucosidase. In the present study, the α-glucosidase (GSJ) from Geobacillus sp. strain HTA-462 was cloned and expressed in Escherichia coli BL21 (DE3). Recombinant GSJ was purified and biochemically characterized. The optimum temperature condition of the recombinant enzyme was 65 °C, and the half-life was 84 h at 60 °C, whereas the enzyme was active over the range of pH 6.0-10.0 with maximal activity at pH 7.0. The α-glucosidase activity in shake flasks reached 107.9 U/mL and using 4-Nitrophenyl ß-D-glucopyranoside (pNPG) as substrate, the Km and Vmax values were 2.321 mM and 306.3 U/mg, respectively. The divalent ions Mn2+ and Ca2+ could improve GSJ activity by 32.1% and 13.8%. Moreover, the hydrolysis ability of recombinant α-glucosidase was almost the same as that of the commercial α-glucosidase (Bacillus stearothermophilus). In terms of the transglycosylation reaction, with 30% maltose syrup under the condition of 60 °C and pH 7.0, IMOs were synthesized with a conversion rate of 37%. These studies lay the basis for the industrial application of recombinant α-glucosidase.
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Proteínas Bacterianas/química , Escherichia coli/metabolismo , Geobacillus/genética , Isomaltosa/química , alfa-Glucosidasas/química , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Clonación Molecular , Estabilidad de Enzimas , Escherichia coli/genética , Geobacillus/enzimología , Oligosacáridos/síntesis química , Oligosacáridos/química , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Especificidad por Sustrato , alfa-Glucosidasas/biosíntesis , alfa-Glucosidasas/genéticaRESUMEN
INTRODUCTION: The main health problems encountered in pediatric population in Senegal are low birth weigth malnutrition and infection. However, there is a lack of data on pediatric ENT diseases from west african population. This is no published data on any research work on pattern ENT pediatric done in Senegal. This study aimed at determining the pattern of common pediatric ENT diseases. PATIENTS AND METHODS: This was a retrospective descriptive study involving review of medical record of patients aged 0-16 years who presented ENT diseases from April 2011 to May 2013 (2 years). RESULTS: within the study period a total of 1329 children were seen. We found 696 children male and 633 female, sex ratio (M/F) is 1.1. Mean age of patients seen was 06 years. Nasal disorders (54,6%) were found to be the commonest group of ENT, followed by ear disorders (22,8%) thorat (22,7%). Hypertrophic adenoid (27,9%) allergic rhinitis (22,9%) and pharyngitis (17,7%) are the most common ENT problems in our pediatric population. CONCLUSION: The main health problems encountered in pediatric population in Senegal are low birth weigth malnutrition and infection. This study indicated hypertrophic adenoid (27,9%) allergic rhinitis (22,9%) and pharyngitis (17,7%) are the most common ENT problems in our pediatric population. However, this study can provide basic data for heath plan and future local research work.