Extra gauge bosons and lepton flavor universality violation in Υ\Upsilon and BB meson decays

Lepton flavor universality can be tested through the ratio of semileptonic $B$ meson decays and leptonic $\Upsilon$ meson decays, with $\Upsilon \equiv \Upsilon(nS)$ ($n=1,2,3$). For the charged-current transitions $b \to c\tau\bar{\nu}_\tau$, discrepancies between the experiment and the Standard Model (SM) have been observed in recent years by different flavor facilities as BABAR, Belle, and LHCb. While for the neutral-current transitions $b \bar{b} \to \tau\bar{\tau}$, the BABAR experiment reported recently a new measurement of leptonic decay ratio $R_{\Upsilon(3S)} = {\rm BR}(\Upsilon(3S) \to \tau^+\tau^-)/{\rm BR}(\Upsilon(3S) \to \mu^+\mu^-)$, showing an agreement with the SM at the $1.8 \sigma$ level. In light of this new BABAR result and regarding the connection between new physics (NP) interpretations to the charged-current $b \to c \tau \bar{\nu}_{\tau}$ anomalies and neutral-current $b \bar{b} \to \tau \bar{\tau}$ processes, in this study, we revisit the NP consequences of this measurement within a simplified model with extra massive gauge bosons that coupled predominantly to left-handed leptons of the third-generation. We show that the BABAR measurement of $R_{\Upsilon(3S)}$ cannot be easily accommodated (within its experimental $1\sigma$ range) together with the other $b \to c\tau\bar{\nu}_\tau$ data, hinting towards a new anomalous observable.Comment: 8 pages, 3 figures. v2: Discussion improved, references adde

Nitric oxide-inhibited chloride transport in cortical thick ascending limbs is reversed by 8-iso-prostaglandin-F2α

Background: Salt reabsorption in the cortical thick ascending limb (cTAL) is regulated by opposing effects. Thus, while nitric oxide (NO) inhibits sodium chloride (NaCl) reabsorption, 8-iso-prostaglandin-F2α (8-iso-PGF2α) stimulates it. Their interaction, however, has not been evaluated in the cTAL. Because 8-iso-PGF2α has considerable stability while NO is a free radical with a short half-life, we hypothesized that, in the cTAL, the inhibition of NaCl absorption will be reversed by 8-iso-PGF2α. Methods: Chloride absorption (JCl) was measured in isolated perfused cTALs. We also evaluated whether activation of protein kinase A (PKA) is required for this interaction. Since cyclic adenosine monophosphate (cAMP) is a major messenger for the 8-iso-PGF2α signaling cascade, and NO inhibits JCl by decreasing cAMP bioavailability, we measured 8-iso-PGF2α-stimulated cAMP in the presence of sodium nitroprusside (SNP). Results: Basal JCl was 274 ± 85 pmol/min/mm. The NO donor, SNP (10-6 M), decreased JCl by 41% (333.5 ± 35.2 pmol/min/mm vs. 195.9 ± 26.1 pmol/min/mm), while 8-iso-PGF2α (100 μM) increased JCl to 315 ± 46 pmol/min/mm (p \u3c 0.01), reversing the effects of the NO donor. While SNP inhibited JCl, 8-iso-PGF2α failed to increase JCl in the presence of H89. Basal cAMP was 56.3 ± 13.1 fmol/min/mm, that in the presence of the NO donor was 57.8 ± 6.1 fmol/min/mm, and that with 8-iso-PGF2α increased it to 92.1 ± 2.9 fmol/min/mm (n = 10, p \u3c 0.04). Conclusion: We concluded that 1) NO-induced inhibition of JCl in the cTAL can be reversed by 8-iso-PGF2α, 2) 8-iso-PGF2α and NO interaction requires PKA to control JCl in this nephron segment, and 3) in the presence of NO, 8-iso-PGF2α continues to stimulate JCl because NO cannot reverse 8-iso-PGF2α-stimulated cAMP level

Singlet vector leptoquark model facing recent LHCb and BABAR measurements

Muy recientemente el experimento LHCb publicó la primera medida de la relación R(Λc) = BR(Λb → Λcτν¯τ )/BR(Λb → Λcµν¯µ). Además, el experimento BABAR comunicó un nuevo resultado de la relación de desintegración leptónica del mesón Upsilon Υ(3S), a saber, RΥ(3S) = BR(Υ(3S) → τ +τ -)/BR(Υ(3S) → µ +µ -). Ambas medidas están por debajo de sus correspondientes predicciones del Modelo Estándar (déficit), desviándose en ∼ 1,1σ y ∼ 1,8σ, respectivamente. Además, el LHCb ha presentado recientemente la primera búsqueda de la desintegración B 0 → K∗0µ ±τ ∓. Motivados por estos nuevos datos, en este trabajo se estudiamos su impacto en la fenomenología del modelo de leptoquark vectorial singlete (U1) abordando los indicios de violación de la universalidad del sabor leptónico en las desintegraciones semileptónicas de los mesones B (anomalías del mesón B anomalies), llevando a cabo un análisis de ajuste global. En general, encontramos que una versión mínima de del modelo U1 con una masa de 1.8 TeV puede explicar con éxito las anomalías del mesón B, siendo al mismo tiempo compatible con el resto de observables de sabor y con los límites del LHC. Curiosamente, nuestro estudio muestra que los nuevos observables R(Λc) y RΥ(3S) generan una fuerte tensión, dando lugar a efectos no triviales en el ajuste global. ajuste global. Futuras mejoras en los experimentos LHCb y Belle II ayudarían a comprender su complementariedad. Además, también analizamos el impacto de la sensibilidad esperada en los observables de sabor en Belle II para proporcionar una prueba adicional del modelo U1. Por último, estudiamos los supuestos mínimos supuestos mínimos bajo los cuales el modelo U1 podría, además, proporcionar una explicación combinada del momento magnético anómalo del muón

Ibuprofen, a traditional drug that may impact the course of COVID-19 new effective formulation in nebulizable solution

The traditional formulation of ibuprofen is poorly soluble in water, so the administered dose must be 10 times higher than the dose required for a therapeutic effect. The development of a hydrosoluble form of ibuprofen can be a strategy to reach a high concentration in the lungs by using modern inhalation devices. Therefore, the development of an inhalable formulation with high bioavailability in the lungs was the leitmotiv of our investigation. The hypertonic ibuprofen solution to be nebulized (NIH) presents great relevant characteristics: bactericidal, virucidal, mucolytic and has a known anti-inflammatory property. Bactericidal and virucidal effects are related to the physico-chemical properties of Na-ibuprofenate as an amphipathic molecule. It has the capability to insert into the bilayer membranes destabilizing the structure, altering its biological properties and avoiding the duplication or infection. Our preliminary results indicate that the presence of this high ionic strength solution reduces 10 times the amount of ibuprofen necessary to kill bacteria, but also the time to kill 1x106 bacteria, from 4 h (in its absence) to only three minutes (in its presence). That was observed using Pseudomona aeruginosa, methicillin-resistant Staphylococcus aureus and Burkholderia cepacia. Also, ?in vitro´´ ibuprofen demonstrated virucidal activity against the so-called enveloped virus, a family that includes coronavirus strain (2019-nCoV). We observed too, the markedly reduced local inflammation in the airways after administering NIH lays on its ability to inhibit the enzyme cyclooxygenase and to markedly diminish reactive oxygen species (ROS). Other investigators also showed the importance of actin in the rapid spread of virus infection. Furthermore, reorganization of the actin filaments is a key step in lung inflammation induced by systemic inflammatory responses caused by SARS-CoV-2. These findings suggest that the interaction between actin proteins and S1 is involved in the 2019-nCoV infection and pathogenesis.Consequently, the possibility of interfering in this interaction could represent a valid hypothesis for the development of promising therapeutic and prevention strategies. In conclusion, we consider that treating people with COVID-19 with NIH may be beneficial and an opportunity to contribute for the current global health emergency.publishedVersionFil: García Canclini, Néstor. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: García Canclini, Néstor. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Porta, Daniela Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina.Fil: Porta, Daniela Josefina. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Muñoz, Sonia Edith. Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina. Instituto de Investigaciones en Ciencias de la Salud; Argentina; Argentina.Fil: Muñoz, Sonia Edith. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Alasino, Roxana Valeria. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina.Fil: Beltramo, Dante MiguelIcon. Ministerio de Ciencia y Tecnología de Córdoba. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina

Longitudinal relationship of liver injury with inflammation biomarkers in COVID-19 hospitalized patients using a joint modeling approach

The mechanisms underlying liver disease in patients with COVID-19 are not entirely known. The aim is to investigate, by means of novel statistical techniques, the changes over time in the relationship between inflammation markers and liver damage markers in relation to survival in COVID-19. The study included 221 consecutive patients admitted to the hospital during the first COVID-19 wave in Spain. Generalized additive mixed models were used to investigate the influence of time and inflammation markers on liver damage markers in relation to survival. Joint modeling regression was used to evaluate the temporal correlations between inflammation markers (serum C-reactive protein [CRP], interleukin-6, plasma D-dimer, and blood lymphocyte count) and liver damage markers, after adjusting for age, sex, and therapy. The patients who died showed a significant elevation in serum aspartate transaminase (AST) and alkaline phosphatase levels over time. Conversely, a decrease in serum AST levels was observed in the survivors, who showed a negative correlation between inflammation markers and liver damage markers (CRP with serum AST, alanine transaminase [ALT], and gamma-glutamyl transferase [GGT]; and D-dimer with AST and ALT) after a week of hospitalization. Conversely, most correlations were positive in the patients who died, except lymphocyte count, which was negatively correlated with AST, GGT, and alkaline phosphatase. These correlations were attenuated with age. The patients who died during COVID-19 infection displayed a significant elevation of liver damage markers, which is correlated with inflammation markers over time. These results are consistent with the role of systemic inflammation in liver damage during COVID-19S

Exploring digital biomarkers of illness activity in mood episodes:Hypotheses generating and model development study

Background: Depressive and manic episodes within bipolar disorder (BD) and major depressive disorder (MDD) involve altered mood, sleep, and activity, alongside physiological alterations wearables can capture. Objective: Firstly, we explored whether physiological wearable data could predict (aim 1) the severity of an acute affective episode at the intra-individual level and (aim 2) the polarity of an acute affective episode and euthymia among different individuals. Secondarily, we explored which physiological data were related to prior predictions, generalization across patients, and associations between affective symptoms and physiological data.Methods: We conducted a prospective exploratory observational study including patients with BD and MDD on acute affective episodes (manic, depressed, and mixed) whose physiological data were recorded using a research-grade wearable (Empatica E4) across 3 consecutive time points (acute, response, and remission of episode). Euthymic patients and healthy controls were recorded during a single session (approximately 48 h). Manic and depressive symptoms were assessed using standardized psychometric scales. Physiological wearable data included the following channels: acceleration (ACC), skin temperature, blood volume pulse, heart rate (HR), and electrodermal activity (EDA). Invalid physiological data were removed using a rule-based filter, and channels were time aligned at 1-second time units and segmented at window lengths of 32 seconds, as best-performing parameters. We developed deep learning predictive models, assessed the channels’ individual contribution using permutation feature importance analysis, and computed physiological data to psychometric scales’ items normalized mutual information (NMI). We present a novel, fully automated method for the preprocessing and analysis of physiological data from a research-grade wearable device, including a viable supervised learning pipeline for time-series analyses.Results: Overall, 35 sessions (1512 hours) from 12 patients (manic, depressed, mixed, and euthymic) and 7 healthy controls (mean age 39.7, SD 12.6 years; 6/19, 32% female) were analyzed. The severity of mood episodes was predicted with moderate (62%-85%) accuracies (aim 1), and their polarity with moderate (70%) accuracy (aim 2). The most relevant features for the former tasks were ACC, EDA, and HR. There was a fair agreement in feature importance across classification tasks (Kendall W=0.383). Generalization of the former models on unseen patients was of overall low accuracy, except for the intra-individual models. ACC was associated with “increased motor activity” (NMI>0.55), “insomnia” (NMI=0.6), and “motor inhibition” (NMI=0.75). EDA was associated with “aggressive behavior” (NMI=1.0) and “psychic anxiety” (NMI=0.52).Conclusions: Physiological data from wearables show potential to identify mood episodes and specific symptoms of mania and depression quantitatively, both in BD and MDD. Motor activity and stress-related physiological data (EDA and HR) stand out as potential digital biomarkers for predicting mania and depression, respectively. These findings represent a promising pathway toward personalized psychiatry, in which physiological wearable data could allow the early identification and intervention of mood episodes

BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis

Deficiencies in the BRCA1 tumor suppressor gene are the main cause of hereditary breast and ovarian cancer. BRCA1 is involved in the Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer with ubiquitin E3 activity. The relevance of the BRCA1/BARD1 ubiquitin E3 activity for tumor suppression and DNA repair remains controversial. Here, we observe that the BRCA1/BARD1 ubiquitin E3 activity is not required for Homologous Recombination or resistance to Olaparib. Using TULIP2 methodology, which enables the direct identification of E3-specific ubiquitination substrates, we identify substrates for BRCA1/BARD1. We find that PCNA is ubiquitinated by BRCA1/BARD1 in unperturbed conditions independently of RAD18. PCNA ubiquitination by BRCA1/BARD1 avoids the formation of ssDNA gaps during DNA replication and promotes continuous DNA synthesis. These results provide additional insight about the importance of BRCA1/BARD1 E3 activity in Homologous Recombination.Research and publication of this work was funded by the EMERGIA 2020 program (EMERGIA20_00276) from the Consejería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Spain to R.G.-P. Research was additionally supported by a Young Investigator Grant from the Dutch Cancer Society (KWF-KIG 11367/2017-2) and Plan Propio de Investigación VI-PP-A.Talento-IV.2 from the University of Sevilla, grants CNS2022-135216 funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR and PID2021-122361NA-I00 by MICIU/AEI/10.13039/501100011033 and by European Union to R.G.-P. Work in the laboratory of A.C.O.V. has been supported by the European Research Council (ERC; grant 310913) and the Dutch Research Council (NWO; grant 724.016.003). N.G.-R. was supported by the EMERGIA 2021 program (EMERGIA21_00057) from the Consejería de Universidad, Investigación e Innovación, Andalusian Regional Government- Junta de Andalucía to NG-R.Peer reviewe

Reflexión Política. Volumen 5 No. 10 de 2003

La democracia local es tema de la mayor importancia. Las instituciones colombianas desde 1991 la fortalecieron, a efecto de diputar a todo el pueblo para que, en cada lugar, atienda directamente sus propios problemas, y proteja mediante su acción de control administrativo los programas que, el mismo pueblo anhela, y plantea antes de la escogencia de sus mandatarios. En Colombia se está implantando una reforma política que ha modificado el sistema electoral, orientada a fortalecer los partidos políticos, fuentes del poder y sustento de la democracia como sistemaLocal democracy is a matter of the greatest importance. Since 1991, Colombian institutions have strengthened it, in order to deputize all the people so that, in each place, they directly address their own problems, and protect through their action of administrative control the programs that the people themselves long for, and propose before the choice of their leaders. In Colombia, a political reform is being implemented that has modified the electoral system, aimed at strengthening political parties, sources of power and support of democracy as a system

Adapting Agriculture to Climate Change: A Synopsis of Coordinated National Crop Wild Relative Seed Collecting Programs across Five Continents

The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges.info:eu-repo/semantics/publishedVersio