Large sheath folds in the Brian\ue7onnais of the Ligurian Alps reconstructed by analysis of minor structures and stratigraphic mapping

This study presents a geometric and structural analysis of curvilinear sheath folds exposed in blueschist rocks of the Ligurian Alps. Field data are presented in a geological map of the structural synthesis with related geological sections (at the 1:10,000 scale) that illustrate the relationships and evolution of large-scale, sheath folds within metamorphic rocks. We based our analyses on the geometric parameters of more than 40 minor folds, as shape (hinge-Lm1 angle, main axial plane/S1 angle, interlimb angle and hinge curvature), asymmetry, fold hinge/stretching lineation obliquity and structural facing pattern. The summary of the whole data depicts a coherent 3D structure showing several orders of minor folds. Sense of asymmetry of minor folds and stratigraphic order has been used to reconstruct a reliable large-scale structure, and to define the sheath fold shape

Risk factors for monozygotic twinning after in vitro fertilization : a systematic review and meta-analysis

Objectives: To establish the risk factors for monozygotic twin (MZT) and monochorionic twin (MCT) pregnancies after in vitro fertilization (IVF). Design: Systematic review and meta-analysis. Setting: Not applicable. Patient(s): Women who achieved MZT and non-MZT pregnancies through IVF. Intervention(s): Systematic search of Medline from January 1995 to October 2018 with cross-checking of references from relevant articles in English. Main Outcome Measure(s): Possible risk factors for MZT or MCT pregnancies after IVF, comprising extended embryo culture, insemination method (conventional IVF and intracytoplasmic sperm injection [ICSI]), embryo biopsy for preimplantation genetic testing for aneuploidies or for monogenic/single-gene defects (PGT-A or PGT-M) programs, assisted hatching (AH), oocytes donation, female age, and embryo cryopreservation. Result(s): A total of 40 studies were included. Blastocyst transfer compared with cleavage-stage embryo transfer, and female age <35 years were associated with a statistically significant increase in the MZT and MCT pregnancy rate after IVF: (23 studies, OR 2.16, 95% CI, 1.74\u20132.68, I 2 =78%; 4 studies, OR 1.29; 95% CI, 1.03\u20131.62, I 2 =62%; and 3 studies, OR 1.90, 95% CI, 1.21\u20132.98, I 2 =59%; 2 studies, OR 2.34; 95% CI, 1.69\u20133.23, I 2 =0, respectively). Conventional IVF compared with ICSI and assisted hatching were associated with a statistically significantly increased risk of MZT pregnancy (9 studies, OR 1.19, 95% CI, 1.04\u20131.35, I 2 =0; 16 studies, OR 1.17, 95% CI, 1.09\u20131.27, I 2 =29%, respectively). Embryo biopsy for PGT-A or PGT-M, embryo cryopreservation, and oocytes donation were not associated with MZT pregnancies after IVF. Conclusion(s): Blastocyst transfer is associated with an increased risk of both MZT and MCT pregnancies after IVF. Further evidence is needed to clarify the impact of female age, insemination method and AH on the investigated outcomes

Improving the Therapeutic Ability of Mesenchymal Stem/Stromal Cells for the Treatment of Conditions Influenced by Immune Cells

Mesenchymal stem/stromal cells (MSCs) have been initially described decades ago as fibroblastic precursors that could be isolated from the bone marrow and establish cultures of fibroblastic cells. These fibroblastic cells were shown tosupport hematopoiesis in vitro, which is a characteristic of stromal cells, and, later, to give rise to mature mesenchymal cells such as bone, cartilage, and fat cells when cultured under appropriate conditions. The proposition that a mesenchymal stem cell exists in postnatal bone marrow and other tissues asblood vessel-associated cells provided further momentum to research on these cells, as well as divergences on how to call them. The impetus of using MSCs to replace cells lost in various types of conditions eventually decreased, as the therapeutic benefits provided by these cells were found to be mostly due to the secretion of paracrine signaling molecules,which can be carried by extracellular vesicles. In the meantime, MSCs were found to modulate the behavior of immunecells by means of secretion of molecules that could, in different scenarios, inhibit the activation of T cells that promote adaptive immune responses. Subsequently, the effects of MSCs on other cells of the immune system were alsodescribed. Today, a number of clinical trials using MSCs to treat conditions influenced by immune cells are under way. While preclinical data indicates that MSCs have important immunomodulatory properties, further studies are still in progress to increase the knowledge on the differences regarding the action of MSCs on immune cells according to their tissue of origin, on how MSCs exert their effects on the different types of immune cells, and on ways to improve the outcome of conditions influenced by immune cells when treated using MSCS.Fil: da Silva Meirelles, Lindolfo. Universidad Luterana; BrasilFil: Bolontrade, Marcela Fabiana. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Hospital Italiano. Instituto de Medicina Traslacional E Ingenieria Biomedica. - Instituto Universitario Hospital Italiano de Buenos Aires. Instituto de Medicina Traslacional E Ingenieria Biomedica.; ArgentinaFil: Medeiros Markoski, Melissa. Universidad Federal de Ciencias de la Salud ; BrasilFil: Dallagiovanna, Bruno. Carlos Chagas Institute - Fiocruz; BrasilFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin

A new candidate mutation, G1629R, in a patient with type 2A von Willebrand's disease: basic mechanisms and clinical implications

Type 2A von Willebrand's disease (VWD) refers to disease variants with decreased platelet-dependent function of von Willebrand factor (VWF) associated with the absence of high molecular weight (HMW) multimers. The candidate G1629R mutation, identified in an Italian patient with type 2A VWD, was expressed to confirm the relationship between phenotype and genotype. Plasma samples from the patient were studied after DDAVP or FVIII/VWF concentrate injections. Furthermore, an expression vector carrying the G1629R mutation was constructed by site-directed mutagenesis and transiently expressed in Cos-7 cells. The characteristics of the corresponding recombinant protein were analyzed. After 1-deamino-8-D-argine vasopressin (DDAVP) infusion, factor VIII and VWF activities increased and HMW VWF multimers were transiently observed in the patient's plasma. VWF activity increased only after administration of a dual FVIII/VWF concentrate. ADAMTS-13 activity did not change significantly before or after the therapies. Secretion, in culture medium, of the corresponding mutated protein (R1629-rVWF) was slightly decreased and this rVWF contained intermediate and HMW multimers. Furthermore, binding of R1629-rVWF to platelet GPIb was moderately reduced compared to that of the wild-type rVWF. Based on the DDAVP and in vitro expression results, we classified the G1629R mutation in group 2 type 2A mutations. Our findings could explain why DDAVP may only be partially effective and suggest that FVIII/VWF concentrates should be used in cases of prolonged mucosal bleeding and major surgery when functional VWF is required

The Trypanosoma cruzi nucleic acid binding protein Tc38 presents changes in the intramitochondrial distribution during the cell cycle

Background: Tc38 of Trypanosoma cruzi has been isolated as a single stranded DNA binding protein with high specificity for the poly [dT-dG] sequence. It is present only in Kinetoplastidae protozoa and its sequence lacks homology to known functional domains. Tc38 orthologues present in Trypanosoma brucei and Leishmania were proposed to participate in quite different cellular processes. To further understand the function of this protein in Trypanosoma cruzi, we examined its in vitro binding to biologically relevant [dT-dG] enriched sequences, its expression and subcellular localization during the cell cycle and through the parasite life stages.Results: By using specific antibodies, we found that Tc38 protein from epimastigote extracts participates in complexes with the poly [dT-dG] probe as well as with the universal minicircle sequence (UMS), a related repeated sequence found in maxicircle DNA, and the telomeric repeat. However, we found that Tc38 predominantly localizes into the mitochondrion. Though Tc38 is constitutively expressed through non-replicating and replicating life stages of T. cruzi, its subcellular localization in the unique parasite mitochondrion changes according to the cell cycle stage. in epimastigotes, Tc38 is found only in association with kDNA in G1 phase. From the S to G2 phase the protein localizes in two defined and connected spots flanking the kDNA. These spots disappear in late G2 turning into a diffuse dotted signal which extends beyond the kinetoplast. This later pattern is more evident in mitosis and cytokinesis. Finally, late in cytokinesis Tc38 reacquires its association with the kinetoplast. in non-replicating parasite stages such as trypomastigotes, the protein is found only surrounding the entire kinetoplast structure.Conclusions: the dynamics of Tc38 subcellular localization observed during the cell cycle and life stages support a major role for Tc38 related to kDNA replication and maintenance.FIRCAFondo Clemente Estable (DICyT)FAPESConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)PROSULPEDECIBAAMSUD-PasteurFac Ciencias, Lab Interacc Mol, Montevideo, UruguayFac Med, Dept Genet, Montevideo, UruguayFac Ciencias, Dept Biol Celular & Mol, Montevideo, UruguayInst Invest Biol Clemente Estable Montevideo Urug, Dept Neurobiol Celular & Mol, Montevideo, UruguayUniv Nacl Gen San Martin, CONICET, INTECH, Inst Invest Biotecnol, Buenos Aires, DF, ArgentinaUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilSUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14260 USAInst Biol Mol Parana, Curitiba, Parana, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFIRCA: R03 TW05665-01Fondo Clemente Estable (DICyT): 7109Web of Scienc

Perspectivas e desafios regulatórios no uso de células-tronco em métodos alternativos ao uso de animais

Introduction: The use of stem cells for toxicological evaluations seems to be a promising strategy since it allows a greater prediction of human effects. However, in Brazil, there is no specific legislation regulating the use of stem cells for non-therapeutic purposes, technological development, diagnosis or as an alternative method to animal testing. Objective: To review the literature and to provide an overview of the current situation of the non-therapeutic use of stem cells in Brazil and in the world. Method: A non-systematic bibliographic survey was carried out bringing together scientific articles and legislation. Results: This review brings the current approach of Brazilian legislation regarding the non-therapeutic use of human material and briefly discusses international regulatory approaches that allow the non-therapeutic use of stem cells. On the other hand, the Brazilian legislation for use of blood and blood products is quite broad and mature and could serve as a model for the non-therapeutic use of stem cells or other materials of human origin. Conclusions: The encouragement of the debate by the interested bodies and entities is the first step to initiate the development of specific legislation that could allow the scientific and technological development of Brazil in order to follow the world’s biotechnological advances.Introdução: Utilizar células-tronco para avaliações toxicológicas parece ser uma estratégia promissora para permitir uma maior predição de efeitos em humanos. Entretanto, no Brasil, não existe legislação específica que regulamente o uso de células-tronco para fins não terapêuticos de desenvolvimento tecnológico, diagnóstico ou como método alternativo ao uso de animais. Objetivo: Revisar a literatura e fundamentar um panorama da situação atual do uso não terapêutico de células-tronco no Brasil e no mundo. Método: Realizado levantamento bibliográfico não sistemático reunindo artigos científicos e legislação. Resultados: Essa revisão traz a abordagem atual da literatura científica e da legislação brasileira e discorre brevemente sobre abordagens regulatórias internacionais no que concerne ao uso não terapêutico de células-tronco. Em contrapartida, a legislação brasileira é bastante abrangente e madura na regulamentação de sangue e hemoderivados e pode servir de modelo para o uso não terapêutico de células-tronco ou outros materiais de origem humana. Conclusões: O incentivo do debate pelos órgãos e entidades interessadas é o primeiro passo para iniciar o desenvolvimento de uma legislação específica que permita o desenvolvimento científico-tecnológico do Brasil de maneira a acompanhar os avanços biotecnológicos mundiais

The steady-state transcriptome of the four major life-cycle stages of Trypanosoma cruzi

<p>Abstract</p> <p>Background</p> <p>Chronic chagasic cardiomyopathy is a debilitating and frequently fatal outcome of human infection with the protozoan parasite, <it>Trypanosoma cruzi</it>. Microarray analysis of gene expression during the <it>T. cruzi </it>life-cycle could be a valuable means of identifying drug and vaccine targets based on their appropriate expression patterns, but results from previous microarray studies in <it>T. cruzi </it>and related kinetoplastid parasites have suggested that the transcript abundances of most genes in these organisms do not vary significantly between life-cycle stages.</p> <p>Results</p> <p>In this study, we used whole genome, oligonucleotide microarrays to globally determine the extent to which <it>T. cruzi </it>regulates mRNA relative abundances over the course of its complete life-cycle. In contrast to previous microarray studies in kinetoplastids, we observed that relative transcript abundances for over 50% of the genes detected on the <it>T. cruzi </it>microarrays were significantly regulated during the <it>T. cruzi </it>life-cycle. The significant regulation of 25 of these genes was confirmed by quantitative reverse-transcriptase PCR (qRT-PCR). The <it>T. cruzi </it>transcriptome also mirrored published protein expression data for several functional groups. Among the differentially regulated genes were members of paralog clusters, nearly 10% of which showed divergent expression patterns between cluster members.</p> <p>Conclusion</p> <p>Taken together, these data support the conclusion that transcript abundance is an important level of gene expression regulation in <it>T. cruzi</it>. Thus, microarray analysis is a valuable screening tool for identifying stage-regulated <it>T. cruzi </it>genes and metabolic pathways.</p