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OBJECTIVE: This study was conducted with the aim to establish standard technique of closed reduction (CR) and compare functional outcomes in patients of moderately displaced unilateral extracapsular condylar fractures. MATERIAL AND METHODS: This study is a retrospective randomized controlled trial, conducted at a tertiary care hospital setting from August, 2013 to November, 2018. Patients of unilateral extracapsular condylar fractures with ramus shortening < 7mm and deviation < 35° were divided in two groups by drawing lots and were treated by dynamic elastic therapy and maxillomandibular fixation (MMF). Mean and standard deviation were calculated for quantitative variables, and one way analysis of variance (ANOVA) and Pearson's Chi-square test were used to determine significance of outcomes between two modalities of CR. P value < 0.05 was taken as significant. RESULTS: The numbers of patients treated by dynamic elastic therapy and MMF were 76 (38 in each group). Out of which 48 (63.15%) were male and 28 (36.84%) were female. The ratio of male to female was 1.7:1. The mean ± standard deviation (SD) of age was 32 ± 9.57 years. In patients treated by dynamic elastic therapy, the mean ± SD (at 6-month follow-up) of loss of ramus height (LRH), maximum incisal opening (MIO) and opening deviation were 4.6mm ± 1.08mm, 40.4mm ± 1.57mm and 1.1mm ± 0.87mm respectively. Whereas, LRH, MIO and opening deviation were 4.6mm ± 0.85mm, 40.4mm ± 2.37mm and 0.8mm ± 0.63mm respectively by MMF therapy. One-way ANOVA was statistically insignificant (P value > 0.05) for above mentioned outcomes. Pre-traumatic occlusion was achieved in 89.47% of patients by MMF and in 86.84% patients by dynamic elastic therapy. Pearson's Chi-square test was statistically insignificant (p value < 0.05) for occlusion. CONCLUSION: Parallel results were obtained for both modalities; thus, the technique as dynamic elastic therapy, which promotes early mobilization and functional rehabilitation, can be favored as standard technique of closed reduction for moderately displaced extracapsular condylar fractures. This technique eases patients' stress associated with MMF and prevents ankylosis.
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Fraturas Mandibulares , Anquilose Dental , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine the role of Doppler ultrasound in the detection of vascular complications in recipients of living donor liver transplant, keeping contrast-enhanced computerised tomography of abdomen as the gold standard. METHODS: The retrospective study was conducted from February 16 to April 1, 2022, at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data of living donor liver transplant recipients who had undergone contrast-enhanced computerised tomography of abdomen within 24 hours of Doppler ultrasound between January 2021 and January 2022. For the diagnosis of hepatic vascular complications, the diagnostic values of Doppler ultrasound parameters were derived by correlating Doppler ultrasound findings with contrast-enhanced computerised tomography results. Data was analysed using SPSS 20. RESULTS: Of the 35 patients, 24(68.6%) were men and 11(31.4%) were women. The overall mean age was 45.86±13.8 years. For hepatic artery thrombosis, the use of Doppler ultrasound criteria yielded a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 96.6%, 83.3%, 100%, and 97.1% respectively. For hepatic artery stenosis, overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Doppler ultrasound was 100%, 96.8%, 75%, 100% and 97.1% respectively. Doppler ultrasound parameters resulted in a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each in detecting portal vein and hepatic venous outflow tract thrombosis. Overall, Doppler ultrasound sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy was found to be 100%, 88.8%, 89.4%, 100% and 94.2% respectively. CONCLUSIONS: Doppler ultrasound was adequate to document vascular complications after living donor liver transplant in majority of the cases with high accuracy and sensitivity.
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Hepatopatias , Transplante de Fígado , Trombose , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos , Estudos Retrospectivos , Ultrassonografia Doppler , Trombose/diagnóstico por imagem , Trombose/etiologiaRESUMO
Adipose tissue develops lipids, aberrant adipokines, chemokines, and pro-inflammatory cytokines as a consequence of the low-grade systemic inflammation that characterizes obesity. This low-grade systemic inflammation can lead to insulin resistance (IR) and metabolic complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Although the CXC chemokines consists of numerous regulators of inflammation, cellular function, and cellular migration, it is still unknown that how CXC chemokines and chemokine receptors contribute to the development of metabolic diseases (such as T2D and NAFLD) during obesity. In light of recent research, the objective of this review is to provide an update on the linkage between the CXC chemokine, obesity, and obesity-related metabolic diseases (T2D and NAFLD). We explore the differential migratory and immunomodulatory potential of CXC chemokines and their mechanisms of action to better understand their role in clinical and laboratory contexts. Besides that, because CXC chemokine profiling is strongly linked to leukocyte recruitment, macrophage recruitment, and immunomodulatory potential, we hypothesize that it could be used to predict the therapeutic potential for obesity and obesity-related diseases (T2D and NAFLD).
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Quimiocinas CXC/metabolismo , Obesidade/metabolismo , Inflamação/metabolismo , Fígado/metabolismoRESUMO
INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.
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Transtorno Depressivo Maior , Humanos , Feminino , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/genética , Estudos de Casos e Controles , Paquistão/epidemiologia , Saúde Mental , Fatores de RiscoRESUMO
Coronavirus disease 19 (COVID-19) is caused by viral infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where upregulation of several important biomarkers and multiple organ dysfunction occurs, this study aimed to evaluate the association of cardiac biomarkers and CS induced acute lung damage with disease severity and mortality in survival of COVID-19 patients. A total of 500 COVID-19 patients with elevated cardiac biomarkers were studied for the analysis of myocardial abnormality through cardiac enzymes, inflammatory biomarkers, and the expression analysis of various cytokines, including IL-1, IL-6, IL-10, IL-17, and IL-25 genes. The elevation of various cardiac enzymes including LDH (87%), CK (78.4%), TNI (80.4%), CK-MB (83%), and D-dimer (80.8%) were found correlated (p < 0.001) with COVID-19 infection. Cardiac enzyme elevation was highly associated with an increased level of inflammatory biomarkers such as CRP (14.2%), SAA (11.4%) and erythrocyte sedimentation rate (ESR) (7.8%) (p = 0.001 for all). The quantitative expression analysis of IL-10, 1L-17, and 1L-25 were found to be high, while those of IL-1 and IL-6 were moderately elevated. The death-to-live ratio of COVID-19 patients was 457:43 indicating that the patients having elevated levels of both CKMB, D-dimer, CK and IL-1, IL-6, IL-10 and D-dimer, Troponin, CK and IL-1, IL-10 had high fatality rate (73% and 12% respectively). The current finding concludes that the evaluation of cardiac biomarkers with cytokine storm plays a significant role in COVID-19-associated anatomical organ damage, myocardial injury, and mortality. Physicians should pay special attention to cardiac biomarkers in patients with old age, inflammation, and comorbidities among COVID-19 infections.
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COVID-19 , Humanos , SARS-CoV-2 , Interleucina-6 , Interleucina-10 , Interleucina-17/genética , Paquistão , Biomarcadores , Citocinas , Troponina , Interleucina-1RESUMO
Cytoplasmic Dynein 1, or Dynein, is a microtubule minus end-directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. Thus, our work illustrates how specific Dynein activation at a defined cellular locale may require multiple factors.
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Proteínas de Ciclo Celular , Dineínas do Citoplasma , Complexo Dinactina , Proteínas de Ciclo Celular/metabolismo , Dineínas do Citoplasma/metabolismo , Complexo Dinactina/metabolismo , Cinetocoros/metabolismo , Conformação ProteicaRESUMO
Variation in food and diet shapes the diversity of the gut microbiota of ruminants. The present study investigated the microbial diversity in the fecal microbiota of yaks reared under natural grazing and feedlot system. A total of 48 domestic yaks with an average age of 7.5 years were selected from two different grazing habitats: one group grazed on natural pasture (grazing yaks-GY) while the other group was fed fodder and concentrate (feedlot yaks-FY). Crude protein, non-fiber carbohydrate, hemicelluloses, and digestible dry matter contents of natural pastures were higher than those in the feedlot. The lower insoluble fiber contents were found in grazing land. The 16S rRNA gene sequencing revealed 675 and 348 unique operational taxonomic units (OTUs) in the GY and FY, respectively, in addition to 1,778 common OTUs. Overall, a total of 9,891 OTUs were identified as a whole, of which 6,160 OTUs were from GY and 3,731 were from FY. Shannon index analysis revealed a higher bacterial diversity in GY than FY. At the phylum level, Firmicutes were dominant bacterial taxa in both groups. The relative abundance of Firmicutes in GY (56% ± 0.05) was higher than in FY (41% ± 0.08). At the family level, GY had a significantly higher abundance of Ruminococcaceae (p < 0.001) and Rikenellaceae (p < 0.001) than FY, but FY had a significantly higher abundance of Prevotellaceae than GY (p < 0.001). At the genus level, abundances of Faecalibacterium, Alloprevotella, and Succinivibrio were higher in FY than in GY. This study presents novel information on fecal bacterial composition and diversity in yaks reared under two different production systems.
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With the implementation of modern scientific protocols, the average human lifespan has significantly improved, but age-related problems remain a challenge. With the advent of ageing, there are alterations in gut microbiota and gut barrier functions, weak immune responses, increased oxidative stress, and other age-related disorders. This review has highlighted and discussed the current understanding on the significance of gut microbiota dysbiosis and ageing and its inherent effects against age-related oxidative stress as well as on the gut health and gut-brain axis. Further, we have discussed the key mechanism of action of Lactobacillus strains in the longevity of life, alleviating gut dysbiosis, and improving oxidative stress and inflammation to provide an outline of the role of Lactobacillus strains in restoration of gut microbiota dysbiosis and alleviating certain conditions during ageing. Microbiota-targeted interventions of some characterized strains of probiotic Lactobacillus for the restoration of gut microbial community are considered as a potential approach to improve several neurological conditions. However, very limited human studies are available on this alarmed issue and recommend further studies to identify the unique Lactobacillus strains with potential anti-ageing properties and to discover its novel core microbiome-association, which will help to increase the therapeutic potential of probiotic Lactobacillus strains to ageing.
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Bex2 is well known for its role in the nervous system, and is associated with neurological disorders, but its role in the lung's physiology is still not reported. To elucidate the functional role of Bex2 in the lung, we generated a Bex2 knock-out (KO) mouse model using the CRISPR-Cas9 technology and performed transcriptomic analysis. A total of 652 genes were identified as differentially expressed between Bex2 -/- and Bex2 +/+ mice, out of which 500 were downregulated, while 152 were upregulated genes. Among these DEGs, Ucp1, Myh6, Coxa7a1, Myl3, Ryr2, RNaset2b, Npy, Enob1, Krt5, Myl2, Hba-a2, and Nrob2 are the most prominent genes. Myl2, was the most downregulated gene, followed by Npy, Hba-a2, Rnaset2b, nr0b2, Klra8, and Ucp1. Tcte3, Eno1b, Zfp990, and Pcdha9 were the most upregulated DEGs. According to gene enrichment analysis, PPAR pathway, cardiac muscle contraction, and cytokine-cytokine receptor interaction were the most enriched pathways. Besides, the nuclear factor-κB signaling pathway and hematopoietic cell linage pathways were also enriched. Chronic obstructive pulmonary disease (COPD) is enriched among KEGG disease pathways. RT-qPCR assays confirmed the RNA-Seq results. This study opens a new window toward the biological functions of Bex2 in different systems.
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Evolutionary robustness requires that the number of highly conserved amino acid residues in proteins is minimized. In enzymes, such conservation is observed for catalytic residues but also for some residues in the second shell or even further from the active site. ß-Lactamases evolve in response to changing antibiotic selection pressures and are thus expected to be evolutionarily robust, with a limited number of highly conserved amino acid residues. As part of the effort to understand the roles of conserved residues in class A ß-lactamases, we investigate the reasons leading to the conservation of two amino acid residues in the ß-lactamase BlaC, Glu37, and Trp229. Using site-directed mutagenesis, we have generated point mutations of these residues and observed a drastic decrease in the levels of soluble protein produced in Escherichia coli, thus abolishing completely the resistance of bacteria against ß-lactam antibiotics. However, the purified proteins are structurally and kinetically very similar to the wild-type enzyme, only differing by exhibiting a slightly lower melting temperature. We conclude that conservation of Glu37 and Trp229 is solely caused by an essential role in the folding process, and we propose that during folding Glu37 primes the formation of the central ß-sheet and Trp229 contributes to the hydrophobic collapse into a molten globule. ENZYME: EC 3.5.2.6. DATABASE: Structural data are available in PDB database under the accession number 7A5U.
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Farmacorresistência Bacteriana/genética , Conformação Proteica , Dobramento de Proteína/efeitos dos fármacos , beta-Lactamases/genética , Sequência de Aminoácidos/genética , Substituição de Aminoácidos/genética , Antibacterianos/efeitos adversos , Antibacterianos/química , Antibacterianos/uso terapêutico , Domínio Catalítico/genética , Sequência Conservada/genética , Escherichia coli/química , Escherichia coli/enzimologia , Humanos , Cinética , Mutagênese Sítio-Dirigida , beta-Lactamases/ultraestruturaRESUMO
Introduction. Since mcr-1 was first reported in China, there have been ten variants of MCR appearing nationwide so far. Multidrug-resistant Enterobacteriaceae bacteria carrying both NDM and MCR have become a serious threat to global public health.Hypothesis/Gap Statement. The genetic structure of mcr-9 needs to be better understood in order to better prevent and control the transmission of drug-resistant genes.Aims. The aim of this study was to characterize the presence of two Enterobacter hormaechei isolates, which carries bla NDM-5 CME2 and the coexistence of mcr-9 and bla NDM-1 strain CMD2, which were isolated from a patient with diabetes in Sichuan, China.Methodology. The microbroth dilution method was used for antibiotic susceptibility. Conjugation experiment was used to investigate the transferability of bla NDM-1, bla NDM-5 and mcr-9. Whole-genome sequencing was performed on Illumina HiSeq platform. The ability of biofilm formation was detected by crystal-violet staining, the virulence of the bacteria was measured by Galleria mellonella killing assay.Results. bla NDM-5 carrier CME2 and CMD2 with bla NDM-1 and mcr-9 were resistant to carbapenems, ß-lactam, aminoglycoside, quinolone and tetracycline, while CMD2 was also resistant to colistin. Conjugation assay and plasmid replicon typing further demonstrated that both bla NDM-1 and bla NDM-5 were respectively present on the self-transferrable IncX3 plasmid, mcr-9 was located on the self-transferrable IncHI2 plasmid. Through the analysis of mcr-9 gene context, the structure was DUF4942-rcnR-rcnA-copS-IS903-mcr-9-wbuC-qseC-qseB-IS1R-ΔsilR-IS903, bla NDM-1 context was IS3000-ΔISAba125-IS5-bla NDM-1-ble-trpF-groS-groL-insE-ΔIS26 structure, bla NDM-5 structure was IS3000-bla NDM-5-ble-trpF-dsbC-ΔIS26-umuD-ISKox3-tnpR-parA. Biofilm formation of CME2 was stronger than CMD2. There was no significant difference in virulence between the two strains.Conclusion. This study reveals two multiple drug-resistant E. hormaechei isolates from diabetes patient samples. E. hormaechei carrying two NDM-resistant genes is already a serious threat, where MCR is an important cause of treatment failure in bacterial infections. This study is a reminder not only to prevent infection in patients with diabetes, but also to constantly monitor the epidemic and spread of the drug-resistant gene.
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Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Coinfecção/microbiologia , Complicações do Diabetes/microbiologia , Enterobacter/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Enterobacter/efeitos dos fármacos , Enterobacter/genética , Genoma Bacteriano/genética , Humanos , Masculino , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Fatores de Virulência/genética , Adulto JovemRESUMO
Integrons are hot spots for acquiring gene cassettes from the environment and play a major role in the bacterial evolution and dissemination of antimicrobial resistance (AMR), thus posing a serious threat. There are currently studies on integrons and antibiotic resistance genes; however, the presence and association of integrons in different agricultural crops and their subsequent dissemination and role in AMR have not been reported previously. This study examines the abundance of integrons, their gene cassette diversity in various crop soils, and their role in the dissemination of AMR in the southern region of China. Samples from different agri-crop soil, such as rice (R.S), sugarcane (S.S), citrus (C.S), banana (B.S), agricultural runoff (the point where the runoff of all sites meet (R.O)), and wild (non-agricultural) soil (W.S), were collected. Quantitative PCR was used to determine the abundance of integrons, and clone libraries were constructed to examine the gene cassette arrays. All the tested samples were found positive for Class-I (CL1) integrons and revealed a higher concentration and higher relative abundance of R.S than the others, with the least found at the W.S site. The W.S CL1 cassette arrays were found empty, and no putative conserved domains were found. The R.O was found to contain a high number of gene cassettes with various functions, while the smallest number of gene cassettes was found in the S.S among the crop soils. Most of the gene cassettes presented by the R.O were primarily shared with other sites, and the antibiotic-resistant genes were consistently observed to be dominant. The constructed clone libraries represented a diverse gene cassette array with 16% novel gene cassettes that play a vital role in pathogenesis, transportation, biosynthesis, and AMR. Most resistance-related gene cassettes were associated with the genes encoding resistance to quaternary ammonium compound (QAC) and aminoglycosides. This study highlights the significant differences in the abundance of integrons among various agricultural soils and offers deep insight into the pools of gene cassettes that play a key role in the dissemination of integrons and AMR.
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Antibacterianos/farmacologia , Bactérias/genética , Produtos Agrícolas/genética , Farmacorresistência Bacteriana/genética , Variação Genética , Integrons/genética , Solo/química , Bactérias/efeitos dos fármacos , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/microbiologia , Microbiologia do SoloRESUMO
Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36â¯h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36â¯h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.
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Fenômenos Fisiológicos Cardiovasculares , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo II , Fosfatidilinositol 3-Quinase , Transdução de Sinais , Ausência de Peso , Peixe-Zebra , Animais , Embrião não Mamífero , Morfogênese , Neovascularização Fisiológica/fisiologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Transdução de Sinais/fisiologia , Peixe-Zebra/embriologiaRESUMO
In many hyperthermophilic archaea the DNA binding protein TrmBL2 or one of its homologues is abundantly expressed. TrmBL2 is thought to play a significant role in modulating the chromatin architecture in combination with the archaeal histone proteins and Alba. However, its precise physiological role is poorly understood. It has been previously shown that upon binding TrmBL2 covers double-stranded DNA, which leads to the formation of a thick and fibrous filament. Here we investigated the filament formation process as well as the stabilization of DNA by TrmBL2 from Pyroccocus furiosus in detail. We used magnetic tweezers that allow to monitor changes of the DNA mechanical properties upon TrmBL2 binding on the single-molecule level. Extended filaments formed in a cooperative manner and were considerably stiffer than bare double-stranded DNA. Unlike Alba, TrmBL2 did not form DNA cross-bridges. The protein was found to bind double- and single-stranded DNA with similar affinities. In mechanical disruption experiments of DNA hairpins this led to stabilization of both, the double- (before disruption) and the single-stranded (after disruption) DNA forms. Combined, these findings suggest that the biological function of TrmBL2 is not limited to modulating genome architecture and acting as a global repressor but that the protein acts additionally as a stabilizer of DNA secondary structure.
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Proteínas Arqueais/metabolismo , DNA Arqueal/metabolismo , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Pyrococcus furiosus , Proteínas Arqueais/química , Proteínas Arqueais/genética , Células Cultivadas , Clonagem Molecular , DNA/química , DNA Arqueal/química , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Instabilidade Genômica/genética , Conformação de Ácido Nucleico , Ligação Proteica , Pyrococcus furiosus/genética , Pyrococcus furiosus/metabolismoRESUMO
AIM: There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure. METHODS: Renal failure was induced using cisplatin (5 mg kg(-1) , i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympathetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load. RESULTS: Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilateral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values. CONCLUSION: These findings reveal a significant role of the renal sensory innervation in cisplatin-damaged kidneys which blunt the normal baroreflex control of renal sympathetic nerve activity.
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Barorreflexo/fisiologia , Frequência Cardíaca/fisiologia , Rim/inervação , Rim/fisiologia , Insuficiência Renal/fisiopatologia , Animais , Cisplatino/toxicidade , Reagentes de Ligações Cruzadas/toxicidade , Modelos Animais de Doenças , Masculino , Ratos , Ratos Endogâmicos WKY , Insuficiência Renal/induzido quimicamente , SimpatectomiaRESUMO
A 17alpha-ethynylestradiol (EE2)-degrading bacterium was isolated from the activated sludge of the wastewater treatment plant (WWTP) of an oral contraceptives producing factory in Beijing, China. On the basis of its morphology, biochemical properties and the 16S rDNA sequence analysis, this strain was identified as Sphingobacterium sp. JCR5. This strain grew on EE2 as sole source of carbon and energy, and metabolized up to 87% of the substrate added (30 mgl-1) within 10 d at 30 degrees C. In addition to EE2 the strain could be cultivated on steroidal estrogens like estrone (E1), 17beta-estradiol (E2), estriol (E3) and mestranol (MeEE2), the intermediates of contraceptive medicine processing and on some aromatic compounds. Mass spectrum analysis of the EE2 degradation showed that in the first step it is oxygenized to E1, 2-hydroxy-2,4-dienevaleric acid and 2-hydroxy-2,4-diene-1,6-dioic acid, which are the main catabolic intermediates. The former was analogous to the pathway of a previously reported testosterone-degrading bacterium Comamonas testosteroni TA441 and the latter is a metabolite with a different cleavage position of 3-hydroxy-4,5-9,10-disecoestrane-1(10),2-diene-5,9,17-trione-4-oic acid from the former.