An Electrochemical Outlook on Tamoxifen Biotransformation: Current and Future Prospects

Tamoxifen is a nonsteroidal antiestrogen that is currently and widely used in the treatment of breast cancer in all of its stages, in adjuvant therapy as a long-term suppressant of tumor recurrence and also as a chemopreventive agent in women that are in high risk of developing this type of estrogen-dependent cancer. From a toxicological and (bio)analytical point of view the knowledge of the metabolic pathways of a drug is found to be extremely important. So, in the present work the most important tamoxifen biotransformation steps were reviewed in the light of recent pharmacological data. This overview also includes the current controversy concerning tamoxifen DNA-damaging (genotoxic) versus non-genotoxic mechanisms. A special focus will be given to the putative application of electrochemical methods as a modern and reliable analytical tool for determination of tamoxifen and its metabolites. Moreover, the potential of DNA electrochemical sensors for detection of structural damage to DNA as a basis for toxicity screening is highlighted. Future prospects looking for the importance of developing new analytical methodologies are also discussed.info:eu-repo/semantics/publishedVersio

Bioelectroanalysis of pharmaceutical compounds

Abstract Recent developments in the bioelectroanalysis of pharmaceutical compounds are reviewed, concentrating particularly on the development of electrode materials and measurement strategies and on their application. The advantages of electroanalytical techniques as alternatives to other analytical procedures such as rapid response, sensitivity and low detection limits are highlighted and illustrated. Particular emphasis is given to carbon-based materials for voltammetric electroanalysis; new potentiometric sensors and electrochemical biosensors are also reviewed

Full genome sequence and sfRNA interferon antagonist activity of Zika virus from Recife, Brazil

Background: The outbreak of Zika virus (ZIKV) in the Americas has transformed a previously obscure mosquito-transmitted arbovirus of the Flaviviridae family into a major public health concern. Little is currently known about the evolution and biology of ZIKV and the factors that contribute to the associated pathogenesis. Determining genomic sequences of clinical viral isolates and characterization of elements within these are an important prerequisite to advance our understanding of viral replicative processes and virus-host interactions. Methodology/Principal findings: We obtained a ZIKV isolate from a patient who presented with classical ZIKV-associated symptoms, and used high throughput sequencing and other molecular biology approaches to determine its full genome sequence, including non-coding regions. Genome regions were characterized and compared to the sequences of other isolates where available. Furthermore, we identified a subgenomic flavivirus RNA (sfRNA) in ZIKV-infected cells that has antagonist activity against RIG-I induced type I interferon induction, with a lesser effect on MDA-5 mediated action. Conclusions/Significance: The full-length genome sequence including non-coding regions of a South American ZIKV isolate from a patient with classical symptoms will support efforts to develop genetic tools for this virus. Detection of sfRNA that counteracts interferon responses is likely to be important for further understanding of pathogenesis and virus-host interactions

Global Women’s Breakfast (GWB): #UnidaspelaQuímica

Global Women’s Breakfast (GWB): #BoundbyChemistry. Global Women’s Breakfast is an initiative of the International Union of Pure and Applied Chemistry, aiming to give women scientists, from all over the world, the opportunity to know each other, communicating virtually and sharing their experiences. Many countries joined this initiative and Portugal was not an exception, with its participation already at the first Networking Breakfast in 2011, celebrating the year of the centenaries of Marie Curie Nobel Prize in Chemistry, the Portuguese Chemical Society and the Faculdade de Ciências da Universidade de Lisboa as well. The success of these networking breakfasts, involving students, young researchers, and scientists, encouraged its further organization in Portugal, annually since 2019. This article describes the interventions of Portuguese women scientists, coming from Institutions throughout Portugal, in the Global Women’s Breakfast as partners in their mission as scientists, creative and open to international collaborations. Global Women's Breakfast é uma iniciativa criada pela International Union of Pure and Applied Chemistry para dar oportunidade às mulheres cientistas de todo o mundo de se conhecerem, comunicando virtualmente e compartilhando as suas experiências. A adesão dos países foi muito elevada e Portugal não foi exceção, participando já no primeiro Networking Breakfast em 2011, Ano Internacional da Química, no qual se celebraram os centenários do Prémio Nobel da Química a Marie Curie, da Sociedade Portuguesa de Química e da Faculdade de Ciências da Universidade de Lisboa. O sucesso destes pequenos-almoços em rede, que envolvem estudantes, jovens investigadoras e cientistas, encorajou a continuação da participação de Portugal anualmente, desde 2019. Este artigo descreve a intervenção de mulheres cientistas portuguesas, pertencentes a instituições de Norte a Sul do país, no Global Women’s Breakfast, cúmplices na sua missão de cientistas, criativas e abertas à colaboração internacional

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery