Abstract
The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the ...mitonuclear imbalance and mitochondrial unfolded protein response (UPR
mt
) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPR
mt
in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPR
mt
markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPR
mt
in hypothalamic cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
The impairment of the mitochondrial functions is a hallmark of aging. During aging, there is a downregulation of two mechanisms strictly associated with mitochondrial integrity, including ...the mitonuclear imbalance (eg, imbalance in mitochondrial- versus nuclear-encoded mitochondrial proteins) and the mitochondrial unfolded protein response (UPRmt). Here, we evaluated the effects of aerobic exercise in the mitonuclear imbalance and UPRmt markers in the skeletal muscle of old mice. We combined the physiological tests, molecular and bioinformatic analyzes to evaluate the effects of 4 weeks of aerobic exercise training on mitonuclear imbalance and UPRmt markers in the skeletal muscle of young (2 months) and aged (24 months) C57BL/6J mice. Initially, we found that aging reduced several mitochondrial genes in the gastrocnemius muscle, and it was accompanied by the low levels of UPRmt markers, including Yme1l1 and Clpp mRNA. As expected, physical training improved the whole-body metabolism and physical performance of aged mice. The aerobic exercise increased key proteins involved in the mitochondrial biogenesis/functions (VDAC and SIRT1) along with mitochondrial-encoded genes (mtNd1, mtCytB, and mtD-Loop) in the skeletal muscle of old mice. Interestingly, aerobic exercise induced the mitonuclear imbalance, increasing MTCO1/ATP5a ratio and UPRmt markers in the skeletal muscle, including HSP60, Lonp1, and Yme1L1 protein levels in the gastrocnemius muscle of aged mice. These data demonstrate that aerobic exercise training induced mitonuclear imbalance and UPRmt in the skeletal muscle during aging. These phenomena could be involved in the improvement of the mitochondrial metabolism and oxidative capacity in aged individuals.
Nicotinamide Riboside (NR) is a NAD+ booster with wide physiological repercussion including the improvement on glucose and lipid homeostasis, increasing the life expectancy in mammals. However, the ...effects of NR on metabolism are only partially known. Here, we evaluated the effects of NR on the thermogenic response, highlighting the brown adipose tissue (BAT) in lean mice.
Male C57BL/67 mice were supplement with NR (400 mg/Kg/day) during 5 weeks. The Comprehensive Lab Animal Monitoring System (CLAMS) and thermographic images were used to evaluated the physiological effects of NR treatment. The BAT were extracted and analyzed by Western Blotting and qPCR. Also, bioinformatics analyses were performed to establish the connection between the NAD+ synthesis pathway in BAT and thermogenic response in several isogenic strains of BXD mice.
Transcriptomic analysis revealed that genes involved in NAD+ synthesis (Nampt and Nmnat1) in the BAT were negatively correlated with body weight and fat mass. The heat map showed a strong positive correlation between Nampt and Ucp1 mRNA in BAT and body temperature in several strains of BXD lean mice. The experimental approaches demonstrated that oral NR supplementation reduced the abdominal visceral fat depots, with discrete impact on oxygen consumption in C57BL/6J mice. Interestingly, NR significantly increased the body temperature, and this phenomenon was accompanied by high levels of UCP1 protein content and Pgc1α mRNA in BAT.
This study demonstrated the oral NR supplementation was sufficient to induce the thermogenic response in lean mice changing the BAT metabolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
4.
Integral unicyclic graphs Braga, Rodrigo O.; Del-Vecchio, Renata R.; Rodrigues, Virgínia M.
Linear algebra and its applications,
04/2021, Volume:
614
Journal Article
Peer reviewed
A graph is integral if the spectrum of its adjacency matrix consists entirely of integers. The question about which unicyclic graphs are integral remains open. We contribute to this problem by ...presenting three infinite families of integral unicyclic graphs. These families are generated by distinct particular solutions of a Diophantine equation. We also show that two integral unicyclic graphs found through a computer search that do not belong to the families we present are unique with their shapes. Necessary conditions for certain unicyclic graphs to be integral are also given.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose
Nicotinamide riboside (NR) acts as a potent NAD
+
precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR ...supplementation on aerobic performance remain unclear. Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice.
Methods
Male C57BL/6 J mice were supplemented with NR (400 mg/Kg/day) over 5 and 10 weeks. The training protocol consisted of 5 weeks of treadmill aerobic exercise, for 60 min a day, 5 days a week. Bioinformatic and physiological assays were combined with biochemical and molecular assays to evaluate the experimental groups.
Results
NR supplementation by itself did not change the aerobic performance, even though 5 weeks of NR supplementation increased NAD
+
levels in the skeletal muscle. However, combining NR supplementation and aerobic training increased the aerobic performance compared to the trained group. This was accompanied by an increased protein content of NMNAT3, the rate-limiting enzyme for NAD + biosynthesis and mitochondrial proteins, including MTCO1 and ATP5a. Interestingly, the transcriptomic analysis using a large panel of isogenic strains of BXD mice confirmed that the
Nmnat3
gene in the skeletal muscle is correlated with several mitochondrial markers and with different phenotypes related to physical exercise. Finally, NR supplementation during aerobic training markedly increased the amount of type I fibers in the skeletal muscle.
Conclusion
Taken together, our results indicate that NR may be an interesting strategy to improve mitochondrial metabolism and aerobic capacity.
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DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Dysfunction of the adipose tissue metabolism is considered as a significant hallmark of aging. It has been proposed that α‐β hydrolase domain containing 5 (ABHD5) plays a critical role in the control ...of lipolysis. However, the role of ABHD5 in the control of lipolysis during aging or exercise is unknown. Here we combined the experimental mouse model with transcriptomic analyzes by using murine and human databases to explore the role of ABHD5 in the adipose tissue during aging and in response to exercise. Transcriptomic data revealed a downregulation of Abhd5 messenger RNA levels in the subcutaneous white adipose tissue (scWAT) over time in individuals from 20 to 69 years old. Aged mice displayed dramatic reduction of ABHD5 protein content and lipolytic‐related proteins in the scWAT. Interestingly, 4 weeks of high‐intensity interval training increased ABHD5 protein level and restored the lipolytic pathway in the scWAT of aged mice. Altogether, our findings demonstrated that aging affects ABHD5 content in the adipose tissue of mice and humans. Conversely, exercise increases ABHD5 activity, recovering the lipolytic activity in aged mice.
Significance statement
Dysfunction of the adipose tissue metabolism is considered as a significant hallmark of aging. Here we identify that a pivotal protein involved in the lipolysis mechanism called α‐β hydrolase domain containing 5 (ABHD5) is downregulated in adipose tissue of aged mice. Conversely, high‐intensity interval training (HIIT) recovered ABHD5 protein content and lipolysis mechanism in the subcutaneous adipose tissue of aged mice.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
RESUMO Urbanização afeta a composição e funções ecossistêmicas das comunidades de morcegos em várias regiões do planeta. Entretanto, este ainda é um tema pouco explorado no Neotrópico. No Brasil, ...embora poucas cidades apresentem inventários de quirópteros, órgãos municipais de saúde pública (e.g., Centro de Controle de Zoonoses) realizam a vigilância passiva dos morcegos infectados pelo vírus da raiva. Estas instituições fazem a identificação dos espécimes oriundos principalmente de áreas urbanas e coletam dados biológicos importantes para o manejo ambiental, controle populacional, ecologia e conservação das espécies. O presente estudo analisou os dados de recebimento de morcegos, de 2001 a 2017, oriundos da cidade de Guarulhos, comparando as taxas de recebimento, frequência, riqueza e dominância das espécies com estudos prévios conduzidos em cidades brasileiras. Os dados da vigilância em saúde pública demonstraram uma alta riqueza de espécies (n = 29), representadas por três famílias mais comuns em áreas urbanas brasileiras (Phyllostomidae, Molossidae e Vespertilionidae). Molossus molossus (Pallas, 1766), Glossophaga soricina (Pallas, 1766) e Myotis nigricans (Schinz, 1821) representaram a maioria (70%) dos dados da quiropterofauna de Guarulhos. Esta dominância pode estar relacionada com a flexibilidade da dieta dessas espécies (insetívoras e nectarívoras não obrigatórias) e abrigos diurnos em edificações, recursos estes altamente disponíveis nas cidades brasileiras. Assim, para mitigar os efeitos da urbanização sobre a rica quiropterofauna regional, recomenda-se que o planejamento ambiental das cidades considere suas diretrizes urbanísticas e florísticas como uma ferramenta ao manejo integrado da fauna silvestre e saúde pública, além de implantar estratégias para aumentar o potencial de conservação da biodiversidade nestes ambientes.
ABSTRACT Urban bats from Guarulhos city: high species richness and dominance of ecologically bats revealed from the rabies monitoring data. Urbanization has impacted bat communities and their ecosystemic services in various regions of the world. However, this impact has been few studied in the Neotropic. In Brazil, although urban bat inventories are scarce, public health organs (e.g., Zoonoses Control Center) perform passive surveillance of infected bats by the rabies virus. These institutions carry out bat identification and collect biologic data essentials to the environment management, population control, ecology, and bat conservation. The present study analyzed bat data (from 2001 to 2017) recorded in Guarulhos city, which integers São Paulo metropolitan region. We compared bat receivement rate, richness, and dominance with other studies. The health surveillance data demonstrated high species richness (n = 29), represented by the three bat families most commonly recorded in Brazilian cities (Phyllostomidae, Molossidadae and Vespertilionidae). Molossus molossus (Pallas, 1766), Glossophaga soricina (Pallas, 1766) and Myotis nigricans (Schinz, 1821) represented most bat data (70%) from Guarulhos city. This dominance can be explained by the diet flexibility (insectivores and non-obligate nectarivores) and shelter occupation in buildings of these species, resources highly available in cities. The understood of the urban characteristics associated with urban bat dominance is important by the provide insights on how to mitigate the impacts of urbanization on the richest regional bat community. Thus, it is recommended that citiesʼ environmental planning consider urbanistic and floristic guidelines as a tool integrated for wild life and public health management, and implement strategies to increase the conservation potential in urban ecosystems.
We develop a tool for locating eigenvalues of the normalized Laplacian matrix of trees. This is obtained by extending an algorithm designed for the adjacency matrix, due to Jacobs and Trevisan ...(2011). As an application, we study the multiplicity of normalized Laplacian eigenvalues of small diameter trees. Our main result is the characterization of the trees that have 4 or 5 distinct normalized Laplacian eigenvalues. We also show that with a fixed diameter these trees are determined by their normalized Laplacian spectrum.
Full text
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The maintenance of mitochondrial activity in hypothalamic neurons is determinant to the control of energy homeostasis in mammals. Disturbs in the mitochondrial proteostasis can trigger the ...mitonuclear imbalance and mitochondrial unfolded protein response (UPR
) to guarantee the mitochondrial integrity and function. However, the role of mitonuclear imbalance and UPR
in hypothalamic cells are unclear. Combining the transcriptomic analyses from BXD mice database and in vivo experiments, we demonstrated that physical training alters the mitochondrial proteostasis in the hypothalamus of C57BL/6J mice. This physical training elicited the mitonuclear protein imbalance, increasing the mtCO-1/Atp5a ratio, which was accompanied by high levels of UPR
markers in the hypothalamus. Also, physical training increased the maximum mitochondrial respiratory capacity in the brain. Interestingly, the transcriptomic analysis across several strains of the isogenic BXD mice revealed that hypothalamic mitochondrial DNA-encoded genes were negatively correlated with body weight and several genes related to the orexigenic response. As expected, physical training reduced body weight and food intake. Interestingly, we found an abundance of mt-CO1, a mitochondrial DNA-encoded protein, in NPY-producing neurons in the lateral hypothalamus nucleus of exercised mice. Collectively, our data demonstrated that physical training altered the mitochondrial proteostasis and induced the mitonuclear protein imbalance and UPR
in hypothalamic cells.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The analysis of 'cutting' or additive agents in cocaine, like benzocaine (BZC), allows police analysts to identify each component of the sample, thus obtaining information like the drugs' ...provenience. This kind of drug profiling is of great value in tackling drug trafficking. Electropolymerized molecularly imprinted polymers (e-MIPs) on portable screen-printed carbon electrodes (SPCEs) were developed in this study for BZC determination. The MIPs' electropolymerization was performed on a carbon surface using the anaesthetic BZC as the template molecule and 3-amino-4-hydroxybenzoic acid (3,4-AHBA) as the functional monomer. The build-up of this biomimetic sensor was carefully characterized by cyclic voltammetry (CV) and optimized. Cyclic voltammetric investigation demonstrated that BZC oxidation had a complex and pH-dependent mechanism, but at pH 7.4 a single, well-defined oxidation feature was observed. The BZC-MIP interactions were studied by computer-aided theoretical modeling by means of density functional theory (DFT) calculations. The electroanalytical methodology was effectively applied to artificial urine samples; BZC molecular recognition was achieved with a low limit of detection (LOD) of 2.9 nmol L
−1
employing square-wave voltammetry (SWV). The e-MIPs were then used to 'fingerprint' genuine cocaine samples, assisted by principal component analysis (PCA), at the central forensic laboratory of the Brazilian Federal Police (BFP) with a portable potentiostat. This electroanalysis provided proof-of-concept that the drugs could be voltammetrically 'fingerprinted' using e-MIPs supported by chemometric analysis.
Cocaine samples were 'finger-printed' using e-MIPs, constructed on the surface of portable SPCEs. The SWV data with suitable chemometric analysis provides valuable information about the drugs' provenience which is crucial to tackle drug traffic.
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