Muon-Tau Symmetry and Leptogenesis in the Minimal Seesaw Model

The measured values for the mixture angles in neutrino oscillations suggest the existence of a symmetry of interchange of flavor between muon and tau neutrinos. Using this symmetry we analyzed the minimal seesaw model for neutrino masses, where the Majorana mass was diagonalized, and it is demonstrated that the model supports at most 3 CP violation phases and 5 real masses at high energies. Nevertheless, at low energies, only 4 parameters of mass and one relative Majorana CP phase remain. Therefore using the experimental values of the masses square differences, the mixture angles and the hierarchy, we can determine some parameters of the model but not all. Also we propose the use of the parameter of baryonic asymmetry of the universe due to leptogenesis to determine one more phase of the model. Finally we used a normal hierarchy for the masses of the right handed neutrinos to make an approximation, that allowed us to completely reconstruct the mass matrix for left handed neutrinos. In special the value of mee is determined which can be compared with the results of the neutrinoless double decay beta.Comment: This is a thesis written to obtain a Master in Science degree, made under the advise of Abdel Perez Lorenzana, Ph

Superspreading event of COVID-19 in adolescents: is there a difference between the vaccinated and the unvaccinated?

Objective: The aim of this study is to estimate the incidence of COVID-19 in a vaccinated and an unvaccinated group of adolescents and describe their symptoms.   Methods: In May 2021 a private indoor event for high school adolescents took place resulting in a superspreading event. As part of the study, an anonymous questionnaire was sent to all adolescents invited to the event and details about symptoms, previous COVID-19 infection, vaccination status and behaviour during the event was assessed. Two groups were formed, one of vaccinated individuals and the other of unvaccinated individuals. A sample from a fully vaccinated symptomatic individual was sequenced. General characteristics for the studied groups are described using categorical and continuous data. The incidence of COVID-19 in each group was estimated by taking the total number of COVID-19 positive cases (numerator) divided by the total number of individuals (denominator) multiplied by 100.   Results: A total of 41 out of the 164 adolescents (incidence 25%, 95%CI 18.6- 32.4) that attended the private indoor event developed COVID-19. A sample was sequenced from one of the symptomatic and fully vaccinated individuals with BNT162b2 (Pfizer-BioNTech vaccine) finding SARS-CoV-2 Delta (B.1.617.2) variant of concern. The incidence of COVID-19 in the unvaccinated was 35.1% (95%CI 25.5-45.6), and in the vaccinated 11.4% (95%CI 5.1-21.3). There were more unvaccinated than vaccinated teenagers that developed COVID-1

Fanconi anemia cells with unrepaired DNA damage activate components of the checkpoint recovery process

International audienceBACKGROUND:The FA/BRCA pathway repairs DNA interstrand crosslinks. Mutations in this pathway cause Fanconi anemia (FA), a chromosome instability syndrome with bone marrow failure and cancer predisposition. Upon DNA damage, normal and FA cells inhibit the cell cycle progression, until the G2/M checkpoint is turned off by the checkpoint recovery, which becomes activated when the DNA damage has been repaired. Interestingly, highly damaged FA cells seem to override the G2/M checkpoint. In this study we explored with a Boolean network model and key experiments whether checkpoint recovery activation occurs in FA cells with extensive unrepaired DNA damage.METHODS:We performed synchronous/asynchronous simulations of the FA/BRCA pathway Boolean network model. FA-A and normal lymphoblastoid cell lines were used to study checkpoint and checkpoint recovery activation after DNA damage induction. The experimental approach included flow cytometry cell cycle analysis, cell division tracking, chromosome aberration analysis and gene expression analysis through qRT-PCR and western blot.RESULTS:Computational simulations suggested that in FA mutants checkpoint recovery activity inhibits the checkpoint components despite unrepaired DNA damage, a behavior that we did not observed in wild-type simulations. This result implies that FA cells would eventually reenter the cell cycle after a DNA damage induced G2/M checkpoint arrest, but before the damage has been fixed. We observed that FA-A cells activate the G2/M checkpoint and arrest in G2 phase, but eventually reach mitosis and divide with unrepaired DNA damage, thus resolving the initial checkpoint arrest. Based on our model result we look for ectopic activity of checkpoint recovery components. We found that checkpoint recovery components, such as PLK1, are expressed to a similar extent as normal undamaged cells do, even though FA-A cells harbor highly damaged DNA.CONCLUSIONS:Our results show that FA cells, despite extensive DNA damage, do not loss the capacity to express the transcriptional and protein components of checkpoint recovery that might eventually allow their division with unrepaired DNA damage. This might allow cell survival but increases the genomic instability inherent to FA individuals and promotes cancer

CUBREBOCAS EN TIEMPOS DE PANDEMIA, REVISIÓN HISTÓRICA, CIENTÍFICA Y RECOMENDACIONES PRÁCTICAS

The aim of this article is to present the medical and scientific literature (including an umbrella review) related to the use of face masks for the prevention of viral respiratory infections, to make an informed decision on the use of face masks during a pandemic. Since the beginning of the 20th Century, it was determined that the use of face masks is effective in reducing the transmission of respiratory infections. The first time face masks were used amongst the general public was during the 1918 Pandemic. Research on face masks during the 20th Century focused mainly on the effectiveness of the materials. It was determined that the best protection was achieved by using several layers of different close knit materials, preferably three. Meta-analyses showed that the use of face masks decreased the risk of contagion of respiratory viral diseases, including COVID-19, compared with not using them. Face masks protect both the user and other people in the population by limiting the exposure to SARS-CoV-2, minimizing the viral load, hence decreasing the risk of developing severe COVID-19. It has been established that any type of face mask is better than not using any mask at all. When deciding upon the use of face masks one should consider the risks and benefits. We conclude that there is sufficient evidence to support that the benefits of using face masks outweigh the risks.El objetivo de este artículo es revisar la literatura médica y científica (incluida una revisión paraguas) relacionada con el uso de cubrebocas como medida de prevención en la transmisión de enfermedades respiratorias virales para tomar decisiones informadas durante una pandemia. Desde inicios del siglo XX se estableció que el cubrebocas es efectivo para reducir infecciones respiratorias.  El uso entre la población general inició hasta la pandemia de 1918. Desde entonces, las investigaciones se han enfocado principalmente en determinar los mejores materiales para su elaboración, encontrando que la efectividad del cubrebocas aumenta con el número de las capas, siendo ideal tres, de punto cerrado y de diversos materiales. Los meta-análisis demostraron que el uso de cubrebocas disminuye el riesgo de contagio de enfermedades respiratorias virales, incluido COVID-19, comparado a no usarlo. Los cubrebocas evitan el paso de una gran proporción de partículas del virus SARS-CoV-2 protegiendo tanto al portador como al resto de la población al reducir la carga viral a la que se está expuesto, disminuyendo así el riesgo de desarrollar enfermedad grave de COVID-19. Cuando las personas están en espacios públicos es preferible elegir usar cualquier cubrebocas, a no usar ninguna protección naso bucal. Para decidir sobre el uso del cubrebocas es importante evaluar el riesgo-beneficio. Con este análisis concluimos que según la evidencia, los beneficios del uso del cubrebocas superan los riesgos, por lo que recomendamos que el uso de cubrebocas de forma generalizada

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Causes of genome instability: the effect of low dose chemical exposures in modern society.

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis

Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis

Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes