Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Bax translocation to mitochondria subsequent to a rapid loss of mitochondrial membrane potential

Bax, a pro-apoptotic member of the Bcl-2 family, is a cytosolic protein that inserts into mitochondrial membranes upon induction of cell death. Using the green fluorescent protein fused to Bax (GFP-Bax) to quantitate mitochondrial binding in living cells we have investigated the cause of Bax association with mitochondria and the time course relative to endogenous and induced changes in mitochondrial membrane potential (Delta Psi (m)). We have found that staurosporine (STS) induces a loss in Delta Psi (m) before GFP-Bax translocation can be measured. the onset of the Delta Psi (m) loss is followed by a rapid and complete collapse of Delta Psi (m) which is followed by Bax association with mitochondria. the mitochondria uncoupler FCCP, in the presence of the F-1-F-0 ATPase inhibitor oligomycin, can trigger Bax translocation to mitochondria suggesting that when ATP levels are maintained a collapse of Delta Psi (m) induces Bax translocation. Neither FCCP nor oligomycin alone alters Bax location. Bax association with mitochondria is also triggered by inhibitors of the electron transport chain, antimycin and rotenone, compounds that collapse Delta Psi (m) without inducing rapid ATP hydrolysis that typically occurs with uncouplers such as FCCP. Taken together, our results suggest that alterations in mitochondrial energization associated with apoptosis can initiate Bax docking to mitochondria.NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilNICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USAMed Univ S Carolina, Charleston, SC 29425 USAUniversidade Federal de São Paulo, Dept Farmacol, São Paulo, BrazilWeb of Scienc

Monitoring biological wastewater treatment processes: Recent advances in spectroscopy applications

Biological processes based on aerobic and anaerobic technologies have been continuously developed to wastewater treatment and are currently routinely employed to reduce the contaminants discharge levels in the environment. However, most methodologies commonly applied for monitoring key parameters are labor intensive, time-consuming and just provide a snapshot of the process. Thus, spectroscopy applications in biological processes are, nowadays, considered a rapid and effective alternative technology for real-time monitoring though still lacking implementation in full-scale plants. In this review, the application of spectroscopic techniques to aerobic and anaerobic systems is addressed focusing on UV--Vis, infrared, and fluorescence spectroscopy. Furthermore, chemometric techniques, valuable tools to extract the relevant data, are also referred. To that effect, a detailed analysis is performed for aerobic and anaerobic systems to summarize the findings that have been obtained since 2000. Future prospects for the application of spectroscopic techniques in biological wastewater treatment processes are further discussed.The authors thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the financial support to Daniela P. Mesquita and Cristina Quintelas through the postdoctoral Grants (SFRH/BPD/82558/2011 and SFRH/BPD/101338/2014) provided by FCT - Portugal.info:eu-repo/semantics/publishedVersio

Limited Genetic Diversity Preceded Extinction of the Tasmanian Tiger

The Tasmanian tiger or thylacine was the largest carnivorous marsupial when Europeans first reached Australia. Sadly, the last known thylacine died in captivity in 1936. A recent analysis of the genome of the closely related and extant Tasmanian devil demonstrated limited genetic diversity between individuals. While a similar lack of diversity has been reported for the thylacine, this analysis was based on just two individuals. Here we report the sequencing of an additional 12 museum-archived specimens collected between 102 and 159 years ago. We examined a portion of the mitochondrial DNA hyper-variable control region and determined that all sequences were on average 99.5% identical at the nucleotide level. As a measure of accuracy we also sequenced mitochondrial DNA from a mother and two offspring. As expected, these samples were found to be 100% identical, validating our methods. We also used 454 sequencing to reconstruct 2.1 kilobases of the mitochondrial genome, which shared 99.91% identity with the two complete thylacine mitochondrial genomes published previously. Our thylacine genomic data also contained three highly divergent putative nuclear mitochondrial sequences, which grouped phylogenetically with the published thylacine mitochondrial homologs but contained 100-fold more polymorphisms than the conserved fragments. Together, our data suggest that the thylacine population in Tasmania had limited genetic diversity prior to its extinction, possibly as a result of their geographic isolation from mainland Australia approximately 10,000 years ago

Influence of fissuring and karstification of the carbonate aquifer unsaturated zone on its vulnerability to contamination (Cracow Upper Jurassic Region, Poland)

The carbonate fissure–karstic aquifer of Upper Jurassic age is the main aquifer in the Cracow Upper Jurassic Region (CUJR). The aquifer is recharged directly or indirectly by Quaternary or Quaternary–Cretaceous overburden of varying permeability, which predominates diffused recharge. Concentrated recharge occurs locally and has a diverse nature. Field studies carried out in 20 quarries show moderate permeability of the unsaturated zone of carbonate massif. Karst funnels are filled with rubble and clay material and dominate filled fissures with an opening b < 10 mm. The average surface fissure porosity of massive with chalky limestones and bedded limestones reach 0.12 and 0.45 %, respectively, while fissure permeability coefficient is, respectively, k S 6.60 × 10−5 and 1.27 × 10−3 m/s. The average karstification in quarries was determined as n k = 2.5 %. Tracer studies, carried out in an unconfined carbonate Zakrzówek horst in Cracow (Kraków), document vertical migration of infiltrating water through the systems with different hydraulic resistance, with a flow rate from 8.1 × 10−6 to 4.9 × 10−5 m/s and the lateral migration velocity between communicated caves from 6.94 × 10−6 to 1.06 × 10−4 m/s. The significant presence of poorly permeable overburden and moderate fissuring and karstification of rock in the unsaturated zone of CUJR are reflected in the assessment of the Upper Jurassic aquifer vulnerability to contamination, performed by a modified DRASTIC method. In the area of unconfined karst, occupying 55 % of the area, vulnerability to contamination is high, while as much as 45 % of the area is characterized by medium and low vulnerability

Expression of caspases 3, 6 and 8 is increased in parallel with apoptosis and histological aggressiveness of the breast lesion

The aim of this investigation was to study the expression of caspases 3, 6 and 8 and their association to apoptosis in preneoplastic and neoplastic lesions of the breast. The material consisted of nine benign breast epithelial hyperplasias, 15 atypical hyperplasias, 74 in situ and 82 invasive carcinomas. The extent of apoptosis was assessed by the TUNEL method and caspase 3, 6 and 8 expression by immunohistochemistry with specific antibodies. Increased caspase 3 immunopositivity, as compared to staining of normal breast ductal epithelium, was seen in 22% of benign epithelial hyperplasias, 25% of atypical hyperplasias, 58% of in situ carcinomas and 90% of invasive carcinomas. The corresponding percentages for caspase 6 and 8 were 11%, 25%, 60%, 87% and 22%, 57%, 84%, 83% respectively. In high-grade in situ lesions there were significantly more cases with strong caspase 3, 6 and 8 immunoreactivity than in low- and intermediate-grade lesions (P = 0.0045, P = 0.049 and P = 0.0001 respectively). In invasive carcinomas, however, no association between a high tumour grade and caspase 3, 6 or 8 expression was found (P = 0.27, P = 0.26 and P = 0.69 respectively). The mean apoptotic index was 0.14 ± 0.14% in benign epithelial hyperplasias, 0.17 ± 0.12% in atypical hyperplasias, 0.61 ± 0.88% in in situ carcinomas and 0.94 ± 1.21% in invasive carcinomas. In all cases strong caspase 3, 6 and 8 positivity was significantly associated with the extent of apoptosis (P < 0.001, P = 0.015 and P = 0.050 respectively). The results show that synthesis of caspases 3, 6 and 8 is up-regulated in neoplastic breast epithelial cells in parallel to the increase in the apoptotic index and progression of the breast lesions. © 1999 Cancer Research Campaig

Interaction of SET domains with histones and nucleic acid structures in active chromatin

Changes in the normal program of gene expression are the basis for a number of human diseases. Epigenetic control of gene expression is programmed by chromatin modifications—the inheritable “histone code”—the major component of which is histone methylation. This chromatin methylation code of gene activity is created upon cell differentiation and is further controlled by the “SET” (methyltransferase) domain proteins which maintain this histone methylation pattern and preserve it through rounds of cell division. The molecular principles of epigenetic gene maintenance are essential for proper treatment and prevention of disorders and their complications. However, the principles of epigenetic gene programming are not resolved. Here we discuss some evidence of how the SET proteins determine the required states of target genes and maintain the required levels of their activity. We suggest that, along with other recognition pathways, SET domains can directly recognize the nucleosome and nucleic acids intermediates that are specific for active chromatin regions

Whole number thinking, learning and development: neuro-cognitive, cognitive and developmental approaches

The participants of working group 2 presented a broad range of studies, 11 papers in total, related to whole number learning representing research groups from 11 countries as follows. Two large cross-sectional studies focused on developmental aspects of young children’s number learning provide a lens for re-examining ‘traditional’ features of number acquisition. van den Heuvel-Panhuizen (the Netherlands) presented a co-authored paper with Elia (Cyprus; Elia and van den Heuvel-Panhuizen 2015) on a cross-cultural study of kindergartners’ number competence focused on counting, additive and multiplicative thinking. Second, Milinković (2015) examined the development of young Serbian children’s initial understanding of representations of whole numbers and counting strategies in a large study of 3- to 7-year-olds. Children’s invented (formal) representations such as set representation and the number line were found to be limited in their recordings. In a South African study focused on early counting and addition, Roberts (2015) directs attention to the role of teachers by providing a framework to support teachers’ interpretation of young disadvantaged learners’ representations of number when engaging with whole number additive tasks. Some papers reflected the increasing role of neuroscientific concepts and methodologies utilised in research on WNA learning and development. Sinclair and Coles (2015) drew upon neuroscientific research to highlight the significant role of symbol-to-symbol connections and the use of fingers and touch counting exempli- fied by the TouchCounts iPad app. Gould (2015) reported aspects of a large Australian large study of children in the first years of schooling aimed at improving numeracy and literacy in disadvantaged communities. A case study exemplified how numerals were identified by relying on a mental number line by using location to retrieve number names. This raised the question addressed in the neuroscientific work of Dehaene and other papers focused on individual differences in how the brain processes numbers. The Italian PerContare1 project (Baccaglini-Frank 2015) built upon the collaboration between cognitive psychologists and mathematics educators, aimed at developing teaching strategies for preventing and addressing early low achievement in arithmetic. It takes an innovative approach to the development of number sense that is grounded upon a kinaesthetic and visual-spatial approach to part-whole relationships. Mulligan and Woolcott (2015) provided a discussion paper on the underlying nature of number. They presented a broader view of mathematics learning (including WNA) as linked to spatial interaction with the environment; the concept of connectivity across concepts and the development of underlying pattern and structural relationships are central to their approach