Cold exposure and adipose nitric oxide and mast cells: influence on aorta contractility

Both nitric oxide (NO) and mast cells play important roles in adipose and vascular tissue biology. Chronic cold stress decreases the sensitivity of vascular smooth muscle to various contractile agents including norepinephrine (NE). In our previous cold exposure study we found that the contractile response of isolated rat aortas to NE was significantly reduced, and the number of rat aortic adventitial mast cells decreased. Histologically and functionally, white and brown adipose tissue (WAT and BAT) can be distinguished. Beyond its significance in energy store/release and heat production, adipose tissue secretes multiple signaling molecules that have endocrine and paracrine role in the regulation of vascular functions. The aims of the present study were to examine chronic cold exposure-induced alterations in (i) the concentration of NO released from selected regions of WAT and BAT in female and male rats, (ii) the histochemistry of white and brown adipose mast cells, and (iii) whether adipose-derived NO affects the contraction of isolated rat aorta to NE. Twelve females and 12 males Spraque-Dawley rats (150-200 g body weight) were used. The rats were exposed to a cold/freely moving stress for 2 hours each day for 5 consecutive days. At the end of cold exposure, the rats were sacrificed, and samples of thoracic aorta with associated periadventitial adipose tissue (tunica adiposa) were obtained. WAT and BAT were isolated from subcutaneous abdominal and interscapular areas, respectively. The concentration of NO was measured by capillary electrophoresis and mast cells were evaluated histochemically. The response of aorta smooth muscles to NE was recorded in the isolated organ bath. To determine whether adipose-derived NO affects aorta contraction to NE, cumulative dose response curves to NE (10-8-10-3 M) were obtained with or without isolated WAT/BAT suspended in the organ bath medium. In control animals, a gender-related significant difference in NO production in both WAT and BAT was found, NO levels being significantly higher in female than male rats. Data from the contractile response of isolated aorta to NE suggest that receptor affinity to NE is significantly different between female and male controls. Presence of BAT and WAT (isolated from cold-exposure animals) in the bath changed the response of aorta smooth muscle to NE. Displaying a gender dimorphism, BAT/WAT-derived NO, or other vasorelaxing factors, seem to reduce receptor density and/or affinity to NE. Adipose mast cell histochemistry also showed diversity in respect to subtype, gender, and cold exposure. Altogether, we found (i) a gender difference in adipose-released NO and in adipose mast cell histochemistry to cold exposure, and (ii) peripheral adipose tissues affect aortic contractile responses to NE likely by a NO-mediated pathway during cold exposure, suggesting that adipose tissue may limit cold-induced excessive vasoconstriction. Our ongoing study aims at the evaluation of whether aortic tunica adiposa itself could also contribute to this phenomenon.Adipobiology 2009; 1: 67-75

Comparação de Soluções Cardioplégicas em Cirurgia de Revascularização Miocárdica sobre Mecanismos de Autofagia e Apoptose

Resumo Fundamento A doença arterial coronariana (DAC) devido à isquemia miocárdica causa perda permanente de tecido cardíaco. Objetivos Nosso objetivo foi demonstrar o possível dano ao miocárdio em nível molecular através dos mecanismos de autofagia e apoptose em pacientes submetidos à cirurgia de revascularização miocárdica. Métodos Um grupo recebeu uma solução de cardioplegia Custodiol e o outro grupo uma solução de cardioplegia sanguínea. Duas amostras miocárdicas foram coletadas de cada paciente durante a operação, imediatamente antes da parada cardíaca e após a liberação do pinçamento aórtico. Foram avaliadas as expressões de marcadores de autofagia e apoptose. O nível de significância estatística adotado foi de 5%. Resultados A expressão do gene BECLIN foi significativa nos tecidos miocárdicos do grupo CS (p=0,0078). Os níveis de expressão dos genes CASPASE 3, 8 e 9 foram significativamente menores no grupo CC. Os níveis pós-operatórios de TnT foram significativamente diferentes entre os grupos (p=0,0072). As expressões dos genes CASPASE 8 e CASPASE 9 foram semelhantes antes e depois do pinçamento aórtico (p=0,8552, p=0,8891). No grupo CC, os níveis de expressão gênica de CASPASE 3, CASPASE 8 e CASPASE 9 não foram significativamente diferentes em amostras de tecido coletadas após pinçamento aórtico (p=0,7354, p=0,0758, p=0,4128, respectivamente). Conclusões Com nossos achados, acreditamos que as soluções CC e CS não apresentam diferença significativa em termos de proteção miocárdica durante as operações de by-pass

Heterozygous Cc2d1a mice show sex-dependent changes in the Beclin-1/p62 ratio with impaired prefrontal cortex and hippocampal autophagy

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders characterized by repetitive behaviors, lack of social interaction and communication. CC2D1A is identified in patients as an autism risk gene. Recently, we suggested that heterozygous Cc2d1a mice exhibit impaired autophagy in the hippocampus. We now report the analysis of autophagy markers (Lc3, Beclin and p62) in different regions hippocampus, prefrontal cortex, hypothalamus and cerebellum, with an overall decrease in autophagy and changes in Beclin-1/p62 ratio in the hippocampus. We observed sex-dependent variations in transcripts and protein expression levels. Moreover, our analyses suggest that alterations in autophagy initiated in Cc2d1a heterozygous parents are variably transmitted to offspring, even when the offspring's genotype is wild type. Aberration in the autophagy mechanism may indirectly contribute to induce synapse alteration in the ASD brain

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Detection of the Diffuse Supernova Neutrino Background with JUNO

As an underground multi-purpose neutrino detector with 20 kton liquid scintillator, Jiangmen Underground Neutrino Observatory (JUNO) is competitive with and complementary to the water-Cherenkov detectors on the search for the diffuse supernova neutrino background (DSNB). Typical supernova models predict 2-4 events per year within the optimal observation window in the JUNO detector. The dominant background is from the neutral-current (NC) interaction of atmospheric neutrinos with 12C nuclei, which surpasses the DSNB by more than one order of magnitude. We evaluated the systematic uncertainty of NC background from the spread of a variety of data-driven models and further developed a method to determine NC background within 15\% with {\it{in}} {\it{situ}} measurements after ten years of running. Besides, the NC-like backgrounds can be effectively suppressed by the intrinsic pulse-shape discrimination (PSD) capabilities of liquid scintillators. In this talk, I will present in detail the improvements on NC background uncertainty evaluation, PSD discriminator development, and finally, the potential of DSNB sensitivity in JUNO

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Effect of Hypotensive Anesthesia on Cognitive Functions - A Comparison of Esmolol and Remifentanil During Tympanoplasty

Objective: To compare the effects of esmolol and remifentanil, used as adjuncts for induced hypotension on surgical conditions and short-term cognitive functions, during tympanoplasty. Methods: The study was conducted in Hacettepe University, School of Medicine, Ankara, Turkey between January 2005 and December 2006 following Institutional Ethical Committee approval, 40 ASA I-II patients, between 18 and 60 years of age were included in this study. With the induction of anesthesia, for group E, an esmolol infusion of 50-250 mu g.kg(-1).min(-1) was titrated, following a bolus of 0.5 mg.kg(-1); for group R, a remifentanil infusion of 0.2-0.5 mu g.kg(-1).min(-1) was titrated; to achieve a mean blood pressure (BP) of 55-65 mm Hg. Arterial BP were recorded continuously throughout the operation. Mini Mental State Test (MMS) was performed at the preoperative 30th minute (MMSP), postoperative 30th minute (MMS30), 60th minute (MMS60) and 24th hour (MMS24). Surgical field was evaluated by the blinded surgeon, using a 6 point category scale. Results: Patient demographics were similar in both groups. Sustained controlled hypotension was sufficient in A of the groups throughout surgery. Surgical field scores were lower in group R (p<0.05), although the scores were <= 2 in both groups, which was regarded as adequate for tympanoplasty. Four patients in group R (20%) and one patient in group E (5%) showed cognitive function decline between MMSP and MMS30. Within both groups, there were statistically significant differences between MMS60 and MMSP, MMS24 and MMSP, MMS60 and MMS30, MMS24 and MMS30, but the results were similar between the groups. Conclusion: Remifentanil or esmolol provided adequate induced hypotension and similar operating conditions and their effects on cognitive functions in the short postoperative period are similar for tympanoplasty.Wo