Variabilidade genética em café conilon relativa aos atributos dos grãos em cultivo irrigado no Cerrado

O objetivo deste trabalho foi quantificar a variabilidade genética de 213 acessos de café conilon, da cultivar Robusta Tropical, quanto às características químicas de qualidade dos grãos de café crus, bem como identificar acessos promissores para o programa de melhoramento do café conilon irrigado no Cerrado. As características químicas avaliadas foram: teores de proteína e cafeína, sólidos solúveis e lipídeos totais, extrato etéreo, pH e acidez titulável total. Os dados foram submetidos à análise de componentes principais e à análise de cluster com base nas semelhanças observadas nos dois primeiros componentes principais, com uso do método de variância mínima (Wards) e da distância Euclidiana, como medida da dissimilaridade. Os três principais componentes explicaram 72,64% da variação total dos dados. Todas as características, exceto o pH, foram correlacionadas com os três primeiros componentes. Foi possível separar os genótipos em três grupos de acordo com as semelhanças no comportamento das variáveis. Os acessos avaliados apresentam variabilidade genética em relação às características de qualidade de grãos avaliadas, e o CPAC 160 e o CPAC 32 são os mais promissores o programa de melhoramento do café conilon irrigado no Cerrado.The objective of this work was to quantify the genetic variability of 213 conilon coffee accessions of the Robusta Tropical cultivar, based on chemical characteristics related to the quality of green coffee beans, as well as to identify promising accessions for the breeding program of irrigated conilon coffee in the Brazilian Cerrado. The chemical characteristics evaluated were: protein and caffeine contents, total soluble solids and total lipids, ether extract, pH, and total titratable acidity. The data were subjected to the principal component analysis and cluster analysis based on the similarities observed within the first two principal components using the minimum variance method (Wards) and, as a measure of similarity, the Euclidean distance. The three main components explained 72.64% of the total variation of the data. All characteristics, except pH, were correlated with the first three components. It was possible to separate the genotypes in three clusters, according to the similarities observed in the behavior of the variables. The evaluated accessions present genetic variability regarding the assessed quality characteristics of green coffee beans, and CPAC 160 and CPAC 32 are the most promising for the breeding program of conilon coffee for cultivation under irrigation in the Cerrado

Redox imbalance and morphological changes in skin fibroblasts in typical Rett syndrome.

Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16) we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs), F4-Neuroprostanes (F4-NeuroPs), nonprotein bound iron (NPBI), and (4-HNE PAs), and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds), F2-IsoPs (7.5-folds) NPBI (2.3-folds), 4-HNE PAs (1.48-folds), and GSSG (1.44-folds) were detected, with significantly decreased GSH (−43.6%) and GSH/GSSG ratio (−3.05 folds). A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients

Imbalance of excitatory/inhibitory synaptic protein expression in iPSC-derived neurons from FOXG1^+/- patients and in foxg1^+/- mice

Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with mutations in either MECP2, CDKL5 or FOXG1. The precise molecular mechanisms that lead to the pathogenesis of RTT have yet to be elucidated. We recently reported that expression of GluD1 (orphan glutamate receptor δ-1 subunit) is increased in iPSC-derived neurons obtained from patients with mutations in either MECP2 or CDKL5. GluD1 controls synaptic differentiation and shifts the balance between excitatory and inhibitory synapses toward the latter. Thus, an increase in GluD1 might be a critical factor in the etiology of RTT by affecting the excitatory/inhibitory balance in the developing brain. To test this hypothesis, we generated iPSC-derived neurons from FOXG1(+/−) patients. We analyzed mRNA and protein levels of GluD1 together with key markers of excitatory and inhibitory synapses in these iPSC-derived neurons and in Foxg1(+/−) mouse fetal (E11.5) and adult (P70) brains. We found strong correlation between iPSC-derived neurons and fetal mouse brains, where GluD1 and inhibitory synaptic markers (GAD67 and GABA AR-α1) were increased, whereas the levels of a number of excitatory synaptic markers (VGLUT1, GluA1, GluN1 and PSD-95) were decreased. In adult mice, GluD1 was decreased along with all GABAergic and glutamatergic markers. Our findings further the understanding of the etiology of RTT by introducing a new pathological event occurring in the brain of FOXG1(+/−) patients during embryonic development and its time-dependent shift toward a general decrease in brain synapses

Targeted molecular profiling of epithelial ovarian cancer from Italian BRCA wild-type patients with a BRCA and PARP pathways gene panel

Ovarian cancer (OC) is the fifth most common type of cancer in women and the fourth most common cause of cancer death in women. Identification of pathogenic variants in OC tissues has an important clinical significance for therapeutic and prevention purposes. This study aims to evaluate the mutational profile of a patient cohort, negative for BRCA1/2 germinal variants and Mismatch Repair defects, using next-generation sequencing (NGS) approach on DNA from formalin-fixed paraffin-embedded samples. We used a custom NGS panel, targeting 34 cancer-related genes, mainly of the BRCA and PARP pathways, and analyzed NGS data to identify somatic and germline variants in Italian patients affected by primary epithelial ovarian cancer. We analyzed 75 epithelial ovarian cancer tissues and identified 54 pathogenic variants and 56 variants of unknown significance. TP53 was characterized by the highest mutational rate, occurring in 55% of tested epithelial ovarian cancers (EOCs). Interestingly, a subset of 8 EOCs showed pathogenic variants of homologous recombination pathway, which could be sensitive to PARP-inhibitor therapies. Germline analysis of actionable genes revealed 4 patients carrier of pathogenic germline variants respectively of RAD51C (2 patients), RAD51D, and PALB2. Molecular profiling of EOCs using our custom NGS panel has enabled the detection of both somatic and germline variants, allowing the selection of patients suitable for targeted therapies, and the identification of high-risk OC families that can benefit from genetic counseling and testing

Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma

Purpose: To assess the clinical relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM), 50 patients were monitored while they were in complete clinical remission (CCR) after autologous or allogeneic stem-cell transplantation. Patients and Methods: Stringent molecular monitoring using clonal markers based on rearranged immunoglobulin heavy-chain genes was performed in 44 of 50 MM patients in CCR. Molecular clinical remission (MCR) was defined as more than one consecutive negative polymerase chain reaction (PCR) test result. Results: Twelve (27%) of 44 molecularly monitored patients achieved MCR; four of the 12 became PCR- positive, and one of these four relapsed. In comparison with patients who did not achieve MCR, patients who achieved MCR had a significantly lower relapse rate (41% v 16%; P < .05) and longer relapse-free survival (35 v 110 months; P < .005). Fourteen of 26 patients in CCR who had received allografts were evaluated on a molecular basis: seven (50%) of the 14 achieved MCR and did not relapse; one of the seven remaining patients relapsed. Thirty of 47 patients in CCR who received autografts were evaluated on a molecular basis: five (16%) of the 30 achieved MCR; two of these five became PCR-negative, and one of these two relapsed. Ten of the 25 remaining patients later relapsed. For these nonrandomized groups, the higher MCR rate after allograft procedures was statistically significant (P < .01; Fisher's exact test). Conclusion: MCR can be obtained in a relatively high proportion of MM patients who have achieved CCR after undergoing allograft procedures and in a smaller fraction of patients after undergoing autograft procedures. In approximately one fourth of MM patients who achieve CCR after transplantation, it may be possible to keep the disease burden constantly below the PCR threshold. Because MCR was associated with prolonged relapse- free survival, these patients could have a relatively favorable clinical outcome. (C) 2000 by American Society of Clinical Oncology

Digitalisierung und Partizipation : Brauchen wir ein neues Skill Set für Führungskräfte?

Debatten um Industrie 4.0 oder Digitalisierung versetzen derzeit Organisationen in Aufruhr. Die viel beschworene „VUCA-Welt“ lässt Forderungen nach einem neuen Führungsverständnis laut werden (Gebhard et al. 2015). Daher wird in diesem Beitrag der Frage nachgegangen, welches Skill Set Führungskräfte heutzutage benötigen

Whole-Exome Sequencing Revealed New Candidate Genes for Human Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a complex disease affecting young adults. It is a pathological condition impairing myocardium activity that leads to heart failure and, in the most severe cases, transplantation, which is currently the only possible therapy for the disease. DCM can be attributed to many genetic determinants interacting with environmental factors, resulting in a highly variable phenotype. Due to this complexity, the early identification of causative gene mutations is an important goal to provide a genetic diagnosis, implement pre-symptomatic interventions, and predict prognosis. The advent of next-generation sequencing (NGS) has opened a new path for mutation screening, and exome sequencing provides a promising approach for identifying causal variants in known genes and novel disease-associated candidates. We analyzed the whole-exome sequencing (WES) of 15 patients affected by DCM without overloading (hypertension, valvular, or congenital heart disease) or chronic ischemic conditions. We identified 70 pathogenic or likely pathogenic variants and 1240 variants of uncertain clinical significance. Gene ontology enrichment analysis was performed to assess the potential connections between affected genes and biological or molecular function, identifying genes directly related to extracellular matrix organization, transcellular movement through the solute carrier and ATP-binding cassette transporter, and vitamin B12 metabolism. We found variants in genes implicated to a different extent in cardiac function that may represent new players in the complex genetic scenario of DCM