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1.
Appl Environ Microbiol ; 89(8): e0094023, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37439674

ABSTRACT

Entomopathogenic fungi (EPF) exhibit direct and indirect mechanisms to increase plant resistance against biotic and abiotic stresses. Plant responses to these stresses are interconnected by common regulators such as ethylene (ET), which is involved in both iron (Fe) deficiency and induced systemic resistance responses. In this work, the roots of cucurbit seedlings were primed with Metarhizium brunneum (EAMa 01/58-Su strain), and relative expression levels of 18 genes related to ethylene (ET), jasmonic acid (JA), and salicylic acid (SA) synthesis, as well as pathogen-related (PR) protein genes, were studied by reverse transcription-quantitative PCR (qRT-PCR). Effects of priming on Spodoptera littoralis were studied by feeding larvae for 15 days with primed and control plants. Genes showed upregulation in studied species; however, the highest relative expression was observed in roots and shoots of plants with Fe deficiency, demonstrating the complexity and the overlapping degree of the regulatory network. EIN2 and EIN3 should be highlighted; both are key genes of the ET transduction pathway that enhanced their expression levels up to eight and four times, respectively, in shoots of primed cucumber. Also, JA and SA synthesis and PR genes showed significant upregulation during the observation period (e.g., the JA gene LOX1 increased 506 times). Survival and fitness of S. littoralis were affected with significant effects on mortality of larvae fed on primed plants versus controls, length of the larval stage, pupal weight, and the percentage of abnormal pupae. These results highlight the role of the EAMa 01/58-Su strain in the induction of resistance, which could be translated into direct benefits for plant development. IMPORTANCE Entomopathogenic fungi are multipurpose microorganisms with direct and indirect effects on insect pests. Also, EPF provide multiple benefits to plants by solubilizing minerals and facilitating nutrient acquisition. A very interesting and novel effect of these fungi is the enhancement of plant defense systems by inducing systematic and acquired resistance. However, little is known about this function. This study sheds light on the molecular mechanisms involved in cucurbits plants' defense activation after being primed by the EPF M. brunneum. Furthermore, the subsequent effects on the fitness of the lepidopteran pest S. littoralis are shown. In this regard, a significant upregulation was recorded for the genes that regulate JA, SA, and ET pathways. This increased expression of defense genes caused lethal and sublethal effects on S. littoralis. This could be considered an added value for the implementation of EPF in integrated pest management programs.


Subject(s)
Ethylenes , Plants , Animals , Spodoptera/metabolism , Ethylenes/metabolism , Plants/metabolism , Larva/metabolism , Fungi/metabolism , Defense Mechanisms
2.
Sci Rep ; 12(1): 9009, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35637273

ABSTRACT

Udder measures have been used to assess milk yield of sheep through classical methods of estimation. Artificial neural networks (ANN) can deal with complex non-linear relationships between input and output variables. In the current study, ANN were applied to udder measures from Pelibuey ewes to estimate their milk yield and this was compared with linear regression. A total of 357 milk yield records with its corresponding udder measures were used. A supervised learning was used to train and teach the network using a two-layer ANN with seven hidden structures. The globally convergent algorithm based on the resilient backpropagation was used to calculate ANN. Goodness of fit was evaluated using the mean square prediction error (MSPE), root MSPE (RMSPE), correlation coefficient (r), Bayesian's Information Criterion (BIC), Akaike's Information Criterion (AIC) and accuracy. The 15-15 ANN architecture showed that the best predictive milk yield performance achieved an accuracy of 97.9% and the highest values of r2 (0.93), and the lowest values of MSPE (0.0023), RMSPE (0.04), AIC (- 2088.81) and BIC (- 2069.56). The study revealed that ANN is a powerful tool to estimate milk yield when udder measures are used as input variables and showed better goodness of fit in comparison with classical regression methods.


Subject(s)
Mammary Glands, Animal , Milk , Animals , Bayes Theorem , Female , Linear Models , Neural Networks, Computer , Sheep
3.
Rev Gastroenterol Mex (Engl Ed) ; 87(2): 149-158, 2022.
Article in English | MEDLINE | ID: mdl-34362678

ABSTRACT

INTRODUCTION AND AIMS: Surgery is the main treatment for gastric cancer. D2 radical gastrectomy is associated with a variable postoperative morbidity and mortality rate worldwide. The aim of the present study was to identify the risk factors associated with the postoperative morbidity and mortality of D2 radical gastrectomy, with curative intent, for gastric cancer. MATERIALS AND METHODS: A retrospective case series was conducted, in which the medical records were reviewed of patients with gastric cancer that underwent D2 radical gastrectomy, within the time frame of January 2014 and December 2018. Univariate and multivariate analyses were carried out to identify the risk factors related to postoperative morbidity and mortality within 90 days. RESULTS: The percentages of postoperative morbidity and mortality in 691 patients were 23.3% and 3.3%, respectively. In the multivariate analysis, age ≥70 years (OR = 1.85, 95% CI: 1.25-2.76), ASA III-IV (OR = 2.06, 95% CI: 1.28-3.34), total gastrectomy (OR = 1.96, 95% CI:1.19-3.23), and pancreatosplenectomy (OR = 5.41, 95% CI: 1.42-20.61) were associated with greater postoperative morbidity, and age ≥70 years (OR = 4.92, 95% CI:1.78-13.65), lower BMI (OR = 0.81, 95% CI: 0.71-0.92), and hypoalbuminemia (OR = 0.91, 95% CI: 0.85-0.98) were associated with greater mortality in distal and total D2 radical gastrectomy. CONCLUSIONS: D2 radical gastrectomy for gastric cancer was shown to be a safe treatment, with low postoperative morbidity and mortality rates. Age ≥70 years, ASA III-IV, total gastrectomy, and pancreatosplenectomy were factors associated with a higher complication rate. Age ≥70 years, lower BMI, and hypoalbuminemia were mortality predictors in distal and total radical gastrectomy.


Subject(s)
Hypoalbuminemia , Stomach Neoplasms , Aged , Gastrectomy/adverse effects , Humans , Hypoalbuminemia/complications , Hypoalbuminemia/epidemiology , Morbidity , Retrospective Studies , Risk Factors , Stomach Neoplasms/etiology , Stomach Neoplasms/surgery
4.
Development ; 148(19)2021 10 01.
Article in English | MEDLINE | ID: mdl-34486668

ABSTRACT

Birth defects result from interactions between genetic and environmental factors, but the mechanisms remain poorly understood. We find that mutations and teratogens interact in predictable ways to cause birth defects by changing target cell sensitivity to Hedgehog (Hh) ligands. These interactions converge on a membrane protein complex, the MMM complex, that promotes degradation of the Hh transducer Smoothened (SMO). Deficiency of the MMM component MOSMO results in elevated SMO and increased Hh signaling, causing multiple birth defects. In utero exposure to a teratogen that directly inhibits SMO reduces the penetrance and expressivity of birth defects in Mosmo-/- embryos. Additionally, tissues that develop normally in Mosmo-/- embryos are refractory to the teratogen. Thus, changes in the abundance of the protein target of a teratogen can change birth defect outcomes by quantitative shifts in Hh signaling. Consequently, small molecules that re-calibrate signaling strength could be harnessed to rescue structural birth defects.


Subject(s)
Abnormalities, Drug-Induced/genetics , Gene-Environment Interaction , Hedgehog Proteins/metabolism , Penetrance , Animals , Cells, Cultured , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , NIH 3T3 Cells , Signal Transduction , Smoothened Receptor/genetics , Smoothened Receptor/metabolism
5.
Article in English, Spanish | MEDLINE | ID: mdl-33752940

ABSTRACT

INTRODUCTION AND AIMS: Surgery is the main treatment for gastric cancer. D2 radical gastrectomy is associated with a variable postoperative morbidity and mortality rate worldwide. The aim of the present study was to identify the risk factors associated with the postoperative morbidity and mortality of D2 radical gastrectomy, with curative intent, for gastric cancer. MATERIALS AND METHODS: A retrospective case series was conducted, in which the medical records were reviewed of patients with gastric cancer that underwent D2 radical gastrectomy, within the time frame of January 2014 and December 2018. Univariate and multivariate analyses were carried out to identify the risk factors related to postoperative morbidity and mortality within 90 days. RESULTS: The percentages of postoperative morbidity and mortality in 691 patients were 23.3% and 3.3%, respectively. In the multivariate analysis, age ≥ 70 years (OR=1.85, 95% CI: 1.25-2.76), ASA III-IV (OR=2.06, 95% CI: 1.28-3.34), total gastrectomy (OR=1.96, 95% CI:1.19-3.23), and pancreatosplenectomy (OR=5.41, 95% CI: 1.42-20.61) were associated with greater postoperative morbidity, and age≥70 years (OR=4.92, 95% CI:1.78-13.65), lower BMI (OR=0.81, 95% CI: 0.71-0.92), and hypoalbuminemia (OR=0.91, 95% CI: 0.85-0.98) were associated with greater mortality in distal and total D2 radical gastrectomy. CONCLUSIONS: D2 radical gastrectomy for gastric cancer was shown to be a safe treatment, with low postoperative morbidity and mortality rates. Age≥70 years, ASA III-IV, total gastrectomy, and pancreatosplenectomy were factors associated with a higher complication rate. Age≥70 years, lower BMI, and hypoalbuminemia were mortality predictors in distal and total radical gastrectomy.

6.
Rev. Fac. Odontol. (B.Aires) ; 36(82): 67-75, 2021. ilus
Article in Spanish | LILACS | ID: biblio-1292310

ABSTRACT

El objetivo del presente informe clínico es describir una manera de lograr resultados predecibles en las restauraciones estéticas, con una rehabilitación integral. Se emplearon distintos materiales, centrados en la nueva generación de materiales cerámicos para la confección de frentes estéticos. Se realizó un diagnóstico seguido de un plan de tratamiento que integró tanto la correcta función como la estética. Se tuvo en cuenta que la responsabilidad estética no se limita sólo a la forma, el tamaño y el color de los dientes, sino que, además, es importante preservar o recuperar la armonía dentogingival (AU)


Subject(s)
Humans , Male , Middle Aged , Ceramics , Dental Veneers , Dentistry, Operative , Esthetics, Dental , Mouth Rehabilitation/methods , Patient Care Planning , Argentina , Schools, Dental , Crowns , Diagnosis, Oral , Inlays
7.
J Clin Invest ; 130(10): 5562-5575, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32673288

ABSTRACT

Pathologic lymphatic remodeling in lymphedema evolves during periods of tissue inflammation and hypoxia through poorly defined processes. In human and mouse lymphedema, there is a significant increase of hypoxia inducible factor 1 α (HIF-1α), but a reduction of HIF-2α protein expression in lymphatic endothelial cells (LECs). We questioned whether dysregulated expression of these transcription factors contributes to disease pathogenesis and found that LEC-specific deletion of Hif2α exacerbated lymphedema pathology. Even without lymphatic vascular injury, the loss of LEC-specific Hif2α caused anatomic pathology and a functional decline in fetal and adult mice. These findings suggest that HIF-2α is an important mediator of lymphatic health. HIF-2α promoted protective phosphorylated TIE2 (p-TIE2) signaling in LECs, a process also replicated by upregulating TIE2 signaling through adenovirus-mediated angiopoietin-1 (Angpt1) gene therapy. Our study suggests that HIF-2α normally promotes healthy lymphatic homeostasis and raises the exciting possibility that restoring HIF-2α pathways in lymphedema could mitigate long-term pathology and disability.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/deficiency , Lymphatic System/metabolism , Lymphatic System/pathology , Lymphedema/metabolism , Lymphedema/pathology , Angiopoietin-1/genetics , Angiopoietin-1/therapeutic use , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/pathology , Female , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Lymphatic System/embryology , Lymphedema/etiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , Pregnancy , Receptor, TIE-2/metabolism , Signal Transduction
8.
Plant Biol (Stuttg) ; 21(2): 267-277, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30382601

ABSTRACT

Paspalum is a noteworthy grass genus due to the forage quality of most species, with approximately 330 species, and the high proportion of those that reproduce via apomixis. Harnessing apomictic reproduction and widening knowledge about the cytogenetic relationships among species are essential tools for plant breeding. We conducted cytogenetic analyses of inter- and intraspecific hybridisations involving a sexual, colchicine-induced autotetraploid plant of P. plicatulum Michx. and five indigenous apomictic tetraploid (2n = 40) species: P. compressifolium Swallen, P. lenticulare Kunth, two accessions of P. nicorae Parodi, P. rojasii Hack. and two accessions of P. plicatulum. Fertility of the hybrids was investigated and their reproductive system was analysed considering the relative embryo:endosperm DNA content from flow cytometry. Morphological, nomenclatural and taxonomic issues were also analysed. Cytogenetic analysis suggested that all indigenous tetraploid accessions of five apomictic species are autotetraploid or segmental allotetraploid. If segmental allotetraploids, they probably originated through autoploidy followed by diploidisation processes. Autosyndetic male chromosome pairing observed in all hybrid families supported this assertion. Allosyndetic chromosome associations were also observed in all hybrid families. In the hybrids, the proportion of male parent chromosomes involved in allosyndesis per pollen mother cell varied from 5.5% to 35.0% and the maximum was between 25% and 60%. The apomictic condition of the indigenous male parents segregated in the hybrids. These results confirm a strong association between autoploidy and apomixis in Paspalum, and the existence of cytogenetic relationships between different species of the Plicatula group. Allosyndetic chromosome pairing and seed fertility of the hybrids suggest the feasibility of gene transfer among species.


Subject(s)
Hybridization, Genetic/genetics , Paspalum/genetics , Polyploidy , Tetraploidy , Chromosomes, Plant/genetics , Cytogenetics , Meiosis , Paspalum/anatomy & histology , Paspalum/classification , Phylogeography , Plant Breeding
9.
Arq. bras. med. vet. zootec. (Online) ; 70(5): 1565-1568, set.-out. 2018. ilus
Article in English | LILACS, VETINDEX | ID: biblio-947401

ABSTRACT

Skeletal deformities are frequent problems in cultured fish populations due mainly to unfavorable abiotic conditions, inappropriate nutrition, and genetic factors. These may cause erratic swimming, decrease of conversion rate, growth, and market value. The aim of this case report was to present the occurrence of deformities in juvenile cobia and groupers from an offshore marine farm in Ilhabela, São Paulo, Brazil. Nine cobias and seven juvenile groupers, that presented deformities, were euthanized and fixed in 10% formaldehyde. They were tagged, processed, and stained with "Alcian Blue" (AB) and "Alizarin Red-S" (ARS) for visualization of cartilage and bone tissue, respectively. After evisceration, radiographic examination was performed. The deformities observed in cobia were atrophy of the operculum, disorganization of the gill lamellae, deformity of the lower jaw, kyphosis, and scoliosis. Groupers presented lower jaw deformity and saddleback syndrome. The farm studied in this case report had poor management standards, fed commercial feed for freshwater herbivorous fish and cooked sardines, high inbreeding and absence of adequately trained professionals to manage these species. The sum of these factors must have directly influenced the appearance of these deformities. It is necessary to control this situation to minimize the incidence of malformations that have economic impacts to farmers.(AU)


As deformidades esqueléticas são problemas frequentes em populações de peixes cultivados devido, principalmente, a condições abióticas desfavoráveis, nutrição inapropriada e fatores genéticos. Estas podem causar natação errática, diminuição do índice de conversão, do crescimento e do valor no mercado. O objetivo deste relato de caso foi apresentar a ocorrência de deformidades em cobias e garoupas juvenis provenientes de uma fazenda marinha em sistema offshore, em Ilhabela, São Paulo, Brasil. Nove cobias e sete garoupas juvenis, que apresentavam deformidades, foram sujeitos à eutanásia e fixados em formol a 10%. Os espécimes foram registrados, processados e corados com "Alcian Blue" (AB) e "Alizarin Red-S" (ARS) para visualização de tecido cartilaginoso e ósseo, respectivamente. Os peixes foram eviscerados para o exame radiográfico. As deformidades observadas em cobia foram: atrofia do opérculo, desorganização das lamelas branquiais, deformidade do maxilar inferior, cifose e escoliose. As garoupas apresentaram deformidade do maxilar inferior e síndrome de Saddleback. Os peixes deste relato de caso estiveram sob manejo deficiente, alimentados com ração comercial para peixes herbívoros de água doce e sardinhas cozinhadas, alta consanguinidade e ausência de profissionais adequadamente treinados para o manejo dessas espécies. A soma desses fatores influenciou diretamente na aparição dessas deformidades, precisando ser controlados para minimizar a incidência de malformações que tenham impacto econômico para os produtores.(AU)


Subject(s)
Animals , Kyphosis/veterinary , Perciformes/abnormalities , Fisheries
10.
Epidemiol Infect ; 145(8): 1597-1605, 2017 06.
Article in English | MEDLINE | ID: mdl-28241898

ABSTRACT

Norovirus is detected in one in five diarrhoea episodes in children, yet little is known about environmental risk factors associated with this disease, especially in low-income settings. The objective of this study was to examine environmental risk factors, and spatial and seasonal patterns of norovirus diarrhoea episodes in children in León, Nicaragua. We followed a population-based cohort of children under age 5 years for norovirus diarrhoea over a 1-year period. At baseline, characteristics of each household were recorded. Households were geocoded and spatial locations of garbage dumps, rivers, and markets were collected. In bivariate analysis we observed younger children and those with animals in their households were more likely to have experienced norovirus episodes. In adjusted models, younger children remained at higher risk for norovirus episodes, but only modest associations were observed with family and environmental characteristics. We next identified symptomatic children living in the same household and within 500 m buffer zones around the household of another child infected with the same genotype. Norovirus diarrhoea episodes peaked early in the rainy season. These findings contribute to our understanding of environmental factors and norovirus infection.


Subject(s)
Caliciviridae Infections/epidemiology , Developing Countries , Diarrhea/epidemiology , Environment , Norovirus/physiology , Caliciviridae Infections/virology , Child, Preschool , Cohort Studies , Diarrhea/virology , Female , Humans , Infant , Infant, Newborn , Male , Nicaragua/epidemiology , Risk Factors , Seasons , Socioeconomic Factors
11.
J Plant Res ; 129(4): 697-710, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26965283

ABSTRACT

It is generally accepted that polyploids have downsized basic genomes rather than additive values with respect to their related diploids. Changes in genome size have been reported in correlation with several biological characteristics. About 75 % of around 350 species recognized for Paspalum (Poaceae) are polyploid and most polyploids are apomictic. Multiploid species are common with most of them bearing sexual diploid and apomictic tetraploid or other ploidy levels. DNA content in the embryo and the endosperm was measured by flow cytometry in a seed-by-seed analysis of 47 species including 77 different entities. The relative DNA content of the embryo informed the genome size of the accession while the embryo:endosperm ratio of DNA content revealed its reproductive mode. The genome sizes (2C-value) varied from 0.5 to 6.5 pg and for 29 species were measured for the first time. Flow cytometry provided new information on the reproductive mode for 12 species and one botanical variety and supplied new data for 10 species concerning cytotypes reported for the first time. There was no significant difference between the mean basic genome sizes (1Cx-values) of 32 sexual and 45 apomictic entities. Seventeen entities were diploid and 60 were polyploids with different degrees. There were no clear patterns of changes in 1Cx-values due to polyploidy or reproductive systems, and the existing variations are in concordance with subgeneric taxonomical grouping.


Subject(s)
DNA, Plant/genetics , Diploidy , Paspalum/classification , Paspalum/physiology , Polyploidy , Chromosomes, Plant/genetics , Flow Cytometry , Paspalum/genetics , Reproduction/genetics , Species Specificity
12.
Science ; 346(6211): 1258810, 2014 Nov 14.
Article in English | MEDLINE | ID: mdl-25395543

ABSTRACT

Most vertebrate organs are composed of epithelium surrounded by support and stromal tissues formed from mesenchyme cells, which are not generally thought to form organized progenitor pools. Here, we use clonal cell labeling with multicolor reporters to characterize individual mesenchymal progenitors in the developing mouse lung. We observe a diversity of mesenchymal progenitor populations with different locations, movements, and lineage boundaries. Airway smooth muscle (ASM) progenitors map exclusively to mesenchyme ahead of budding airways. Progenitors recruited from these tip pools differentiate into ASM around airway stalks; flanking stalk mesenchyme can be induced to form an ASM niche by a lateral bud or by an airway tip plus focal Wnt signal. Thus, mesenchymal progenitors can be organized into localized and carefully controlled domains that rival epithelial progenitor niches in regulatory sophistication.


Subject(s)
Lung/growth & development , Mesenchymal Stem Cells/physiology , Stem Cell Niche/physiology , Animals , Cell Differentiation , Cell Lineage , Cell Movement , Cell Proliferation , Cell Tracking , Clone Cells , Lung/cytology , Mesenchymal Stem Cells/cytology , Mice , Mice, Transgenic , Single-Cell Analysis/methods , Wnt Signaling Pathway
13.
Nature ; 509(7500): 371-5, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24739965

ABSTRACT

The mammalian lung is a highly branched network in which the distal regions of the bronchial tree transform during development into a densely packed honeycomb of alveolar air sacs that mediate gas exchange. Although this transformation has been studied by marker expression analysis and fate-mapping, the mechanisms that control the progression of lung progenitors along distinct lineages into mature alveolar cell types are still incompletely known, in part because of the limited number of lineage markers and the effects of ensemble averaging in conventional transcriptome analysis experiments on cell populations. Here we show that single-cell transcriptome analysis circumvents these problems and enables direct measurement of the various cell types and hierarchies in the developing lung. We used microfluidic single-cell RNA sequencing (RNA-seq) on 198 individual cells at four different stages encompassing alveolar differentiation to measure the transcriptional states which define the developmental and cellular hierarchy of the distal mouse lung epithelium. We empirically classified cells into distinct groups by using an unbiased genome-wide approach that did not require a priori knowledge of the underlying cell types or the previous purification of cell populations. The results confirmed the basic outlines of the classical model of epithelial cell-type diversity in the distal lung and led to the discovery of many previously unknown cell-type markers, including transcriptional regulators that discriminate between the different populations. We reconstructed the molecular steps during maturation of bipotential progenitors along both alveolar lineages and elucidated the full life cycle of the alveolar type 2 cell lineage. This single-cell genomics approach is applicable to any developing or mature tissue to robustly delineate molecularly distinct cell types, define progenitors and lineage hierarchies, and identify lineage-specific regulatory factors.


Subject(s)
Cell Lineage/genetics , Epithelial Cells/cytology , Epithelial Cells/metabolism , Lung/cytology , Sequence Analysis, RNA/methods , Single-Cell Analysis/methods , Animals , Bronchi/cytology , Cell Differentiation/genetics , Epithelial Cells/classification , Female , Genetic Markers , Genome/genetics , Genomics , Lung/embryology , Mice , Mice, Inbred C57BL , Pulmonary Alveoli/cytology , Pulmonary Gas Exchange , Stem Cells/cytology , Transcriptome/genetics
14.
Development ; 140(20): 4277-86, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24048590

ABSTRACT

The transcriptional control of primary cilium formation and ciliary motility are beginning to be understood, but little is known about the transcriptional programs that control cilium number and other structural and functional specializations. One of the most intriguing ciliary specializations occurs in multiciliated cells (MCCs), which amplify their centrioles to nucleate hundreds of cilia per cell, instead of the usual monocilium. Here we report that the transcription factor MYB, which promotes S phase and drives cycling of a variety of progenitor cells, is expressed in postmitotic epithelial cells of the mouse airways and ependyma destined to become MCCs. MYB is expressed early in multiciliogenesis, as progenitors exit the cell cycle and amplify their centrioles, then switches off as MCCs mature. Conditional inactivation of Myb in the developing airways blocks or delays centriole amplification and expression of FOXJ1, a transcription factor that controls centriole docking and ciliary motility, and airways fail to become fully ciliated. We provide evidence that MYB acts in a conserved pathway downstream of Notch signaling and multicilin, a protein related to the S-phase regulator geminin, and upstream of FOXJ1. MYB can activate endogenous Foxj1 expression and stimulate a cotransfected Foxj1 reporter in heterologous cells, and it can drive the complete multiciliogenesis program in Xenopus embryonic epidermis. We conclude that MYB has an early, crucial and conserved role in multiciliogenesis, and propose that it promotes a novel S-like phase in which centriole amplification occurs uncoupled from DNA synthesis, and then drives later steps of multiciliogenesis through induction of Foxj1.


Subject(s)
Centrioles/metabolism , Cilia/metabolism , Forkhead Transcription Factors/metabolism , Proto-Oncogene Proteins c-myb/metabolism , Animals , Brain/embryology , Brain/metabolism , Cell Differentiation , Cell Movement , Cells, Cultured , Centrioles/genetics , Cilia/genetics , Ependyma/embryology , Ependyma/metabolism , Epithelial Cells/metabolism , Forkhead Transcription Factors/biosynthesis , Lung/embryology , Lung/metabolism , Mice/embryology , Mice, Transgenic , Signal Transduction , Trachea/embryology , Trachea/metabolism , Xenopus laevis/embryology
15.
Cancer Gene Ther ; 20(10): 544-51, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23969884

ABSTRACT

Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating vector (RRV), can successfully and safely deliver a functional, optimized cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent, in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC) (Toca FC), is currently under investigation in patients with recurrent high-grade glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line treatment for patients with glioblastoma, the most common and aggressive form of primary brain cancer in adults. However, subsets of patients with certain genetic alterations do not respond well to TMZ treatment and the overall median survival for patients who respond remains modest, suggesting that combinatorial approaches may be necessary to significantly improve outcomes. We show that in vitro TMZ delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated cell killing in glioma tumor cells, and in vivo there is no significant hematologic effect from the combination of 5-FC and the clinically relevant dose of TMZ. A synergistic long-term survival advantage is observed in mice bearing an orthotopic TMZ-sensitive glioma after Toca 511 administration followed by coadministration of TMZ and 5-FC. These results provide support for the investigation of this novel combination treatment strategy in patients with newly diagnosed malignant glioma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Brain Neoplasms/therapy , Cytosine Deaminase/genetics , Dacarbazine/analogs & derivatives , Flucytosine/pharmacology , Glioblastoma/therapy , Animals , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cytosine Deaminase/biosynthesis , Cytosine Deaminase/metabolism , Dacarbazine/administration & dosage , Dacarbazine/pharmacology , Drug Synergism , Female , Flucytosine/administration & dosage , Flucytosine/pharmacokinetics , Gene Expression , Gene Transfer Techniques , Genetic Vectors/genetics , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/metabolism , Mice , Mice, Nude , Retroviridae/genetics , Temozolomide , Xenograft Model Antitumor Assays
16.
Dev Cell ; 23(3): 482-93, 2012 Sep 11.
Article in English | MEDLINE | ID: mdl-22975322

ABSTRACT

Some of the most serious diseases involve altered size and structure of the arterial wall. Elucidating how arterial walls are built could aid understanding of these diseases, but little is known about how concentric layers of muscle cells and the outer adventitial layer are assembled and patterned around endothelial tubes. Using histochemical, clonal, and genetic analysis in mice, here we show that the pulmonary artery wall is constructed radially, from the inside out, by two separate but coordinated processes. One is sequential induction of successive cell layers from surrounding mesenchyme. The other is controlled invasion of outer layers by inner layer cells through developmentally regulated cell reorientation and radial migration. We propose that a radial signal gradient controls these processes and provide evidence that PDGF-B and at least one other signal contribute. Modulation of such radial signaling pathways may underlie vessel-specific differences and pathological changes in arterial wall size and structure.


Subject(s)
Pulmonary Artery/physiology , Radial Artery/physiology , Signal Transduction , Animals , Cell Division , Lung/cytology , Mesoderm/cytology , Mice , Mice, Transgenic , Proto-Oncogene Proteins c-sis/metabolism , Pulmonary Artery/growth & development , Pulmonary Artery/metabolism , Radial Artery/metabolism
17.
In. Rojas Ochoa, Francisco; Márquez, Miguel. ALAMES en la memoria: selección de lectura. Ciudad de La Habana, Editorial Caminos, 2009. .
Monography in Spanish | CUMED | ID: cum-68885
18.
Rev. chil. ortop. traumatol ; 49(2): 84-87, 2008. ilus
Article in English, Spanish | LILACS | ID: lil-559491

ABSTRACT

The tibialis anterior muscle is the main ankle extensor. Its tendon ruptures are very infrecuent, and there are only a few case reports about them in literature. Treatment in these patients must be tailored to their functional activity, being only those who are inactive candidates to orthopedic treatment. In most cases treatment is surgical, by termino-terminal repair, augmentation techniques with extensor hallucis longus (EHL) or tibialis anterior tendon allografting, among other techniques, depending mainly on the type of lesion and the time of evolution. In this case report we present a male 60 year old patient with End Stage Chronic Kidney Disease on Hemodialysis, who after a minor trauma in left foot while on plantar flexion presents acute pain in ankle’s medial aspect and step page gait. In the Emergency Department evaluation he was unable to stand in his heels, despite an adequate foot dorsiflexion. On Magnetic Resonance Imaging a rupture of the distal part of the tibialis anterior tendon was shown. Two weeks later a surgical termino-terminal repair with ethibond was performed, followed by 9 weeks of inmobilization and then rehabilitation. Twelve weeks after the surgical procedure the patient regain his normal activities, without gait limitation.


El músculo tibial anterior es el principal extensor del tobillo. Las roturas de su tendón son muy poco frecuentes y existen en la literatura sólo casos aislados que reportan su existencia. El tratamiento en estos pacientes debe basarse en la actividad funcional de estos, siendo sólo los pacientes inactivos candidatos al tratamiento ortopédico con órtesis. En la mayoría de los casos el tratamiento es quirúrgico, indicándose reparación término-terminal, técnicas de transferencia tendínea con extensor hallucis longus (EHL) o la utilización de aloinjerto entre otras técnicas, dependiendo del tipo de rotura y tiempo de evolución. En este reporte se relata el caso de un hombre de 60 años, con antecedentes de insuficiencia renal crónica, en diálisis, quien al sufrió un trauma menor en flexión plantar del pie izquierdo, presentó dolor agudo en la región medial del tobillo y posteriorincapacidad de extender el tobillo al realizar la marcha. Fue evaluado en el servicio de urgencia destacando la imposibilidad de mantenerse en talones, pese a tener una dorsiflexión adecuada al examen físico. Se solicitó una Resonancia Magnética (RM), donde se evidenció una rotura completa en la región distal del tendón tibial anterior. Se operó a las 2 semanas, realizándose una reparación término-terminal con sutura no reabsorbible. El post operatorio se manejó con inmovilización por 9 semanas y posterior rehabilitación. El paciente no presentó complicaciones, logrando reintegrarse a sus actividades laborales a las 12 semanas.


Subject(s)
Humans , Male , Middle Aged , Orthopedic Procedures/methods , Tendon Injuries/surgery , Rupture/surgery , Treatment Outcome
19.
Rev. chil. ortop. traumatol ; 49(2): 94-96, 2008. ilus
Article in Spanish | LILACS | ID: lil-559493

ABSTRACT

Isolated fractures of the acromion are rare, especially those of the posterolateral angle. Khun, in the year 1996, proposed a classification system. He recommended open reduction and internal fixation for type III fractures. We present an isolated fracture of the posterolateral angle of the acromion. A 60-year-old man was driving a truck when it overturned suffering a direct trauma on his left shoulder. The acromial fracture was exposed through a direct posterior approach and fixated with two cannulated screws. Post op X rays films showed anatomical reduction of the fracture. The shoulder range of motion was complete eleven weeks after surgery and patient had total functional recovery.


Las fracturas aisladas del acromion son poco frecuentes, siendo las del borde posterolateral muy infrecuentes. Kuhn, en el año 1996 propuso un sistema de clasificación en el cual recomienda el tratamiento quirúrgico con reducción abierta más fijación interna para las fracturas tipo III. Este reporte describe el tratamiento quirúrgico de una fractura aislada del borde posterolateral del acromion. La fractura ocurrió en un hombre de 60 años como resultado de una contusión directa producto de un volcamiento en camioneta. Se realizó un abordaje posterior directo a nivel del sitio de la fractura, la cual se fijó con 2 tornillos canulados de 3,5 mm. Las radiografías post operatorias mostraron una reducción anatómica de la fractura. A las 11 semanas posterior a la cirugía el paciente presentaba rangos de movilidad completos del hombro afectado, retornando sin limitaciones a sus actividades de chofer.


Subject(s)
Humans , Male , Middle Aged , Acromion/surgery , Acromion/injuries , Fracture Fixation, Internal , Fractures, Bone/surgery , Bone Screws , Treatment Outcome
20.
Rev. gastroenterol. Perú ; 26(3): 271-277, jul.-sept. 2006. ilus, tab
Article in Spanish | LILACS, LIPECS | ID: lil-533749

ABSTRACT

Introducción: La dehiscencia de la anastomosis pancreatoyeyunal es la complicación más temida de la pancreatoduodenectomía proximal (PDP) y puede ocasionar la muerte del paciente. Objetivo: Presentamos nuestra experiencia acumulada en 198 PDPs reconstruídos utilizando la técnica simplificada de la anastomosis pancreatoyeyunal. Técnica Operatoria: Consiste en realizar una sutura en bolsa de tabaco alrededor del borde libre del yeyuno para introducir 4cm de muñon pancreático guiado por dos suturas transfixiantes entre el páncreas y el intestino, cerrar el yeyuno sobre el páncreas ajustando la sutura en bolsa de tabaco y colocar 4 puntos separados para "anclar" la anastomosis. Se descomprime las anastomosis pancreática y biliar mediante yeyunostomía. Material y métodos: Estudio prospectivo de 198 pacientes consecutivos que tuvieron PDP en el Instituto de Enfermedades Neoplásicas en el periodo 1995-2005. Resultados: La morbilidad post operatoria global fue 38.4 por ciento (76 de 198 pacientes). Trece pacientes (6.6 por ciento) presentaron dehiscencia de anastomosis pancreatoyeyunal. La mortalidad post operatoria a 30 días y la mortalidad hospitalaria fue 2 por ciento y 3.5 por ciento, respectivamente. Conclusión: Nuestra técnica modificada de anastomosis pancreatoyeyunal es simple, aplicable a todo tipo de páncreas y sobretodo segura, logrando reducir de manera importante la incidencia de dehiscencia de la anastomosis pancreatoyeyunal, la morbilidad y la mortalidad post operatorias.


Introduction: Pancreatojejunal anastomosis dehiscence is the most feared complication of proximal pancreatoduodenectomies and it is the cause of other complications, including death. OBJECTIVE: We present our cumulative experience gathered with 198 proximal pancreatoduodenectomies reconstructed by using the simplified pancreatojejunal anastomosis technique.OPERATION TECHNIQUE: It consists of performing a tobacco-pouch suture around the free edge of the jejunum in order to introduce 4 cm of the pancreatic stump guided by two transfixing sutures between the pancreas and the intestine, closing the jejunum over the pancreas tighteningthe tobacco-pouch suture and making four separate stitches to ìanchorî the anastomosis. The pancreatic and bile anastomoses are decompressed by jejunostomy. MATERIAL AND METHOD: Prospective study in 198 consecutive patients who had proximal pancreatoduodenectomies at the Institute for Neoplastic Diseases during the 1995 - 2005 period. RESULTS: Overall post-operative morbidity was 38.4 per cent (76 out of 198 patients). Thirteen patients (6.6 per cent) showed pancreatojejunal anastomosis dehiscence. Post-operative mortality after 30 days and hospital mortality were 2 per cent and 3.5 per cent, respectively. CONCLUSIONS: Our modified pancreatojejunal anastomosis technique is simple, applicable to alltypes of pancreata and, most importantly, safe. It greatly reduces incidences of pancreatojejunal anastomosis dehiscence as well as post-operative morbidity and mortality.


Subject(s)
Humans , Male , Female , Anastomosis, Surgical , Surgical Wound Dehiscence , Pancreaticoduodenectomy , Pancreaticojejunostomy , Prospective Studies
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