RESUMEN
Soil heavy metal speciation has received much attention for their different ecological and environmental effects. However, the effects of climate and soil geochemical properties on them in uncontaminated soils at macroscale were still unclear. Therefore, a transect more than 4000 km was chosen to study the effects of these factors on soil Cd, Pb and Cr forms. The results revealed that mean annual temperature and precipitation showed significant positive relations with the exchangeable and Fe-Mn oxide bound states of Cd, Pb and Cr, and residual Cr. And humidity and drought indexes were significantly positively correlated with their organic and carbonate bound forms, respectively. As for soil geochemical properties, pH displayed significant negative relationships with exchangeable, Fe-Mn oxide and organic bound Pb and Cr, and exchangeable Cd. Fe2O3 was significantly positively with the exchangeable and Fe-Mn oxide bound Cd, Pb and Cr, and residual Cr. And soil organic matter showed positive relations with organic bound Pb and Cr, and residual Cd and Cr, displayed negative relationships with carbonated bound Pb and Cr. Overall, climate and soil geochemical properties together affect the transformation and transport of heavy metals between different forms in uncontaminated soils.
RESUMEN
The structural evolution of local coordination environments of single-atom catalysts (SACs) under reaction conditions plays an important role in the catalytic performance of SACs. Using density functional theory calculations, the possible structural evolution of transition metal single atoms supported by B/N codoped-graphene (TM-B2N2/G) under nitrogen reduction reaction (NRR) conditions is explored and the catalytic performance based on reconstructed SACs is theoretically evaluated. A novel nitrogen adsorption mode on TM-B2N2/G is discovered and the protonation of one of the N atoms results in the TM atoms binding with three N atoms, among which one associates with two B atoms (TM-N3B2/G). It is suggested that the N3B2/G supported tungsten single atom (W-N3B2/G) exhibits excellent N2 activity with a limiting potential of -0.27 V and high ammonia selectivity. Electronic structure analysis indicates that the coordination of N3B2/G redistributes the charge density of central W, shifts its d band center upward and strengthens the interaction of W and the adsorbed nitrogen molecule, thereby endowing it with better NRR performance, compared with that supported by pyridine-3N-doped graphene and pyrrolic-3N-doped graphene.
RESUMEN
Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.
RESUMEN
Cellular FLICE-like inhibitory protein (c-FLIP) regulates extrinsic apoptosis by controlling procaspase-8 activation through its tandem N-terminal death effector domains (DEDs). Here, we present the expression and purification of c-FLIP tandem DEDs (tDED) from Escherichia coli. We observed that the c-FLIPtDED maintains monomeric form under near-physiological pH condition in vitro. Our results also reveal a significant correlation between the pH conditions and the structure of c-FLIPtDED (F114A). The described methods and results would be helpful for follow-up study on the structural and functional of c-FLIP.
Asunto(s)
Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Dominio Efector de Muerte , Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Caspasa 8/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Estudios de SeguimientoRESUMEN
PURPOSE: To investigate the role of ADC and kinetic parameters derived from DCE-MRI in selecting eligible candidates for fertility-sparing vaginal radical trachelectomy (VRT). METHOD: Female patients with FIGO stage IB cervical cancers between March 2019 and January 2022 were retrospectively included. All patients underwent hysterectomy and bilateral lymphadenectomy. According to the surgical pathology, the study population was divided into VRT-eligible group and VRT-ineligible group. ADC, semi-quantitative and quantitative kinetic parameters of the primary tumor were compared between the two groups. Logistic regression analysis was used to determine the independent predictors for VRT eligibility and ROC curve was used to evaluate the predictive performance. RESULTS: 19 patients were deemed eligible for VRT and 50 were ineligible. Compared with VRT-eligible group, time to peak and ADC were significantly lower in VRT-ineligible group (P = 0.004 and 0.001, respectively) while volume fraction of plasma (Vp) was higher in VRT ineligible group (P = 0.001). ADC and Vp were independent predictors for VRT eligibility. Combining Vp and ADC yielded the highest area under the ROC curve of 0.853 compared with that of 0.766 for Vp and 0.764 for ADC, though marginal differences were found (P = 0.109 and 0.078, respectively). CONCLUSIONS: ADC and the kinetic DCE-MRI parameter Vp can be used as surrogate markers to select eligible candidates for fertility-sparing VRT.
Asunto(s)
Traquelectomía , Neoplasias del Cuello Uterino , Biomarcadores , Femenino , Humanos , Estadificación de Neoplasias , Estudios Retrospectivos , Traquelectomía/métodos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/cirugíaRESUMEN
The formation of death-inducing signaling complex (DISC) and death effector domain (DED) filament initiates extrinsic apoptosis. Recruitment and activation of procaspase-8 at the DISC are regulated by c-FLIP. The interaction between c-FLIP and procaspase-8 is mediated by their tandem DEDs (tDED). However, the structure of c-FLIPtDED and how c-FLIP interferes with procaspase-8 activation at the DISC remain elusive. Here, we solved the monomeric structure of c-FLIPtDED (F114G) at near physiological pH by solution nuclear magnetic resonance (NMR). Structural superimposition reveals c-FLIPtDED (F114G) adopts a structural topology similar to that of procaspase-8tDED. Our results provide a structural basis for understanding how c-FLIP interacts with procaspase-8 and the molecular mechanisms of c-FLIP in regulating cell death.
Asunto(s)
Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , Dominio Efector de Muerte , Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Caspasa 8/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: The primary objective of the present study was to investigate the correlations among cervical paraspinal muscle morphology changes (fatty infiltration [FI] and muscle atrophy), cervical degeneration, and clinical features in patients with chronic nonspecific neck pain (CNSNP). METHODS: The magnetic resonance imaging data for 55 consecutive patients (average age, 35.80 years) with CNSNP were analyzed in the present cross-sectional study. The muscle morphology changes in 7 groups of paraspinal muscles, indicated by the adjusted cross-sectional area (aCSA) and FI ratio (FI%), were measured from C3/4 to C6/7. The correlations of these changes with disc degeneration, cervical balance (C2-C7 angle and cervical alignment), and clinical features (severity of neck pain and related disability and frequency of acute neck pain recurrence) were evaluated. RESULTS: Significant correlations between FI% and aCSA and the grade of disc degeneration were observed in specific muscle groups at each level (P < 0.05). Morphological changes in the deep extensors and superficial paraspinal muscles were significantly associated with the cervical balance parameters (P < 0.05). The FI% showed a significant positive correlation, and the aCSA showed a significant negative correlation with the severity of neck pain and related disability (P < 0.05). Correlations between the morphological changes and the frequency of acute neck pain recurrence were also present in specific muscles (P < 0.05). CONCLUSIONS: Correlations among the muscle morphology changes, cervical degeneration, and clinical features were established for patients with CNSNP. Muscle volume changes and FI might affect CNSNP diversely through different paraspinal muscle groups. These results imply a complex contribution of muscle morphological changes to cervical degeneration and the clinical course of CNSNP.
Asunto(s)
Dolor Crónico , Degeneración del Disco Intervertebral , Osteoartritis de la Columna Vertebral , Adulto , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/patología , Dolor Crónico/diagnóstico por imagen , Dolor Crónico/patología , Estudios Transversales , Humanos , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/patología , Imagen por Resonancia Magnética/métodos , Músculos , Dolor de Cuello/diagnóstico por imagen , Dolor de Cuello/patología , Músculos Paraespinales/diagnóstico por imagen , Músculos Paraespinales/patologíaRESUMEN
BACKGROUND: Primary dysmenorrhoea (PDM) is known to alter brain static functional activity. This study aimed to explore the dynamic topological properties (DTP) of dynamic brain functional network in women with PDM in the pain-free phase and their performance in distinguishing PDM in the pain-free phase from healthy controls. METHODS: Thirty-five women with PDM and 38 healthy women without PDM were included. A dynamic brain functional network was constructed using the slide-window approach. The stability (TP-Stab) and variability (TP-Var) of the DTP of the dynamic functional network were computed using the graph-theory method. A support vector machine (SVM) was used to evaluate the performance of DTP in identifying PDM in the pain-free phase. RESULTS: Compared with healthy controls, women with PDM had not only lower TP-Stab in global DTP, which included cluster clustering coefficient (Cp ), characteristic path length (Lp ), global efficiency (Eg ) and local efficiency (Eloc ), but also lower TP-Stab and higher TP-Var in nodal DTP (nodal efficiency, Enod ), mainly in the prefrontal cortex, anterior cingulate cortex, parahippocampal regions and insula. The TP-Stab and TP-Var were significantly correlated with psychological variables, that is positive emotions, sense of control and meaningful existence. SVM analysis showed that the DTP could identify PDM in the pain-free phase from healthy controls with an accuracy of 79.31%, sensitivity of 82.61% and specificity of 76%. CONCLUSIONS: Women with PDM in the pain-free phase have altered global DTP and nodal DTP, mainly involving pain-related neurocircuits. The highly variable brain network is helpful for identifying PDM in the pain-free phase. SIGNIFICANCE: This study shows that women with primary dysmenorrhoea (PDM) have decreased stability of dynamic network topological properties (DTP) and increased DTP variability in the pain-free phase. The altered DTP can be used to identify PDM in the pain-free phase. These findings demonstrate the presence of unstable characteristics in the whole network and disrupted pain-related neurocircuits, which might be used as potential classifiers for PDM in the pain-free phase. This study improves our knowledge of the brain mechanisms underlying PDM.
Asunto(s)
Mapeo Encefálico , Dismenorrea , Encéfalo/diagnóstico por imagen , Corteza Cerebral , Femenino , Giro del Cíngulo , Humanos , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long-term trends of mortality rates for cervical cancer in three high-income countries-Canada, Korea, and Italy-and analyzing the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: Joinpoint regression was used in this study, and the age-period-cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. RESULTS: For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. CONCLUSIONS: Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.
Asunto(s)
Neoplasias del Cuello Uterino/mortalidad , Adulto , Factores de Edad , Canadá , Estudios de Cohortes , Femenino , Humanos , Italia , Persona de Mediana Edad , República de Corea , Neoplasias del Cuello Uterino/epidemiología , Adulto JovenRESUMEN
PURPOSE: To investigate the role of kinetic parameters of primary tumor derived from dynamic contrast-enhanced MRI (DCE-MRI) in predicting pelvic lymph node metastasis (PLNM) in patients with cervical cancer. METHODS: 66 women with newly diagnosed cervical cancer were included between July 2017 and August 2019. All patients had a FIGO stage IB-IIA cancer and treated with hysterectomy and bilateral lymphadenectomy. Kinetic parameters of the primary tumor were derived from DCE-MRI data. The tumor diameter, ADC value, kinetic parameters, and nodal short-axis diameter were compared between patients with or without PLNM. Logistic regression analysis was used to determine the independent predictors for PLNM and receiver operator characteristic curve was used to evaluate the predictive performance. RESULTS: There were 20 patients with PLNM and 46 patients without PLNM. Tumor diameter, the efflux rate constant (Kep), and nodal short-axis diameter were significantly higher in patients with PLNM (P < 0.01). Multivariate logistic regression analysis showed that Kep and short-axis diameter were independent predictors for PLNM. Combining Kep and nodal short-axis diameter yielded the highest area under the curve (AUC) of 0.839. Combined with Kep, the sensitivity, specificity, negative predictive value, and positive predictive value of nodal short-axis diameter increased from 0.500, 0.957, 0.815, and 0.833 to 0.600, 0.978, 0.923, and 0.849, respectively. With 1.113 min-1 as threshold, the sensitivity and specificity values of Kep in predicting PLNM in patients with normal-sized lymph nodes were 0.909 and 0.667, respectively. CONCLUSIONS: Kep of primary tumor can be used as a surrogate marker to predict PLNM in cervical cancer.
Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/diagnóstico por imagen , Metástasis Linfática/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Neoplasias del Cuello Uterino/diagnóstico por imagenRESUMEN
K63-linked polyubiquitination requires the ubiquitin-conjugating enzyme Ubc13 and a Ubc/E2 variant Uev. Lower eukaryotic organisms contain one UEV gene required for DNA-damage tolerance, while vertebrates and higher plants contain multiple UEV genes with distinct functions. In contrast, Drosophila contains only one UEV gene designated dUev1a. Here we report that dUev1a forms a stable heterodimer with Ben, the Drosophila Ubc13 ortholog, that dUev1a-F15E completely abolishes the interaction, and that a conserved dUev1a-F15Y substitution severely reduces its interaction with Ben. dUev1a functionally rescues the corresponding yeast mms2 null mutant from killing by various DNA-damaging agents in a Ben-dependent manner, and the heterozygous dUev1a mutant flies are more sensitive to DNA-damaging agent, indicating that the function of UEV in DNA-damage response is conserved throughout eukaryotes. Meanwhile, dUev1a+/- mutant flies displayed reduced mobility characteristic of defects in the central nervous system and reminiscent of the bendless phenotypes, suggesting that dUev1a acts together with Ben in this process. Our observations collectively imply that dUev1a is dually required for DNA-damage response and neurological signaling in Drosophila, and that these processes are mediated by the Ben-dUev1a complex that promotes K63-linked polyubiquitination.
Asunto(s)
Sistema Nervioso Central , Reparación del ADN , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Factores de Transcripción/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Animales , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , MovimientoRESUMEN
Cellular FLICE-inhibitory protein (c-FLIP), which is involved in regulating the apoptosis of the extrinsic cell death pathway contains two death effector domains (DED). There are several splicing variants including short-form (c-FLIPS) and long-form (c-FLIPL). The death-inducing signaling complex (DISC) initiates apoptosis and programmed necrosis, DISC assembly and activation are regulated by c-FLIP. Here we report the NMR chemical shift assignments of c-FLIPs, which pave the way for investigating the molecular basis of the anti-apoptotic function of c-FLIPS.
Asunto(s)
Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/análisis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/química , Resonancia Magnética Nuclear Biomolecular , Humanos , Isótopos de Nitrógeno , Estructura Secundaria de Proteína , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
Diverse derivatives of amino acids with different steric configurations are important biosynthetic building blocks. In biology, epimerization is an important way to generate steric diversity. MarH catalyzes the epimerization of the ß-position of (3R)-ß-methyl-indolepyruvate (MeInPy), forming (3S)-ß-MeInPy. Both compounds are derivatives of l-tryptophan (l-Trp) and are important precursors of bioactive natural products. Here, we report the crystal structures of MarH and the NMR structure of its complex with l-Trp, an analogue of its native substrate, (3R)-ß-MeInPy. Structural analysis and mutagenesis studies indicated that His25 acts as a base to remove Hß and generate a planar carbanion intermediate, which is then putatively reprotonated on the opposite face by a water molecule to form (3S)-ß-MeInPy in a stereospecific manner. The details of ß-site isomerization at the atomic level provide deeper insights into the epimerization mechanism of MarH and will facilitate further enzyme design to extend the substrate scope.
Asunto(s)
Racemasas y Epimerasas/química , Indoles/química , Indoles/metabolismo , Modelos Moleculares , Resonancia Magnética Nuclear Biomolecular , Conformación Proteica , Piruvatos/química , Piruvatos/metabolismo , Racemasas y Epimerasas/metabolismoRESUMEN
OBJECTIVES: A no-flap design based on actual tongue anatomy has been reported to achieve precise reconstruction, but large carcinologic tongue defects remain extremely challenging to treat. The aim of this pilot study was to explore an anatomy-based flap design for precision subtotal tongue reconstruction. MATERIAL AND METHODS: Thirty-five patients were randomly divided into two groups, a "five-points eight-line-segments" (FIPELS) technique flap design group (18 patients) and a conventional surgery group (17 patients), to undergo subtotal tongue reconstruction. All patients received an anterolateral thigh flap with nerve coaptation to the lingual or glossopharyngeal nerve. Swallowing function, speech intelligibility, and cosmetic results were assessed with a Likert scale, and epicritic and proprioceptive sensitivity and thermosensation of the neotongue were investigated. Outcomes were analyzed, and a p-valueâ¯<â¯0.05 was considered significant. RESULTS: The FIPELS flaps were significantly larger than conventionally designed flaps. All flaps healed uneventfully, except in two patients who presented with partial necrosis. Relative to patients in the conventional group, patients in the FIPELS group showed significantly improved swallowing function (pâ¯=â¯0.043) and cosmetic results (pâ¯=â¯0.017) but not speech intelligibility (pâ¯=â¯0.154). Patients in the two groups recovered comparably in terms of epicritic and proprioceptive sensitivity and thermosensation. CONCLUSION: The anatomy-based FIPELS technique is an innovative and effective solution for subtotal tongue reconstruction.
Asunto(s)
Procedimientos de Cirugía Plástica/métodos , Neoplasias de la Lengua/cirugía , Lengua/patología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Lengua/cirugíaRESUMEN
MarH is an essential epimerase that catalyzes the isomerization of 3R-ß-methyl-indolepyruvate (ß-MeInPy) to 3S-ß-MeInPy, which is the important precursor for biosynthesis of Maremycins. Biophysical study of the structure of MarH would be informative for better understanding of its catalytic mechanism and feasible application of the enzyme in isomerization reaction. Here, we report the backbone and side-chain NMR chemical shift assignments of MarH, which lays a foundation for further structural and mechanical study of the enzyme.
Asunto(s)
Indoles/metabolismo , Resonancia Magnética Nuclear Biomolecular , Racemasas y Epimerasas/química , Racemasas y Epimerasas/metabolismo , Streptomyces/enzimología , Streptomyces/metabolismoRESUMEN
BACKGROUND: Cyclophilin A is involved in many inflammatory diseases and its expression is up-regulated after brain injury. We determined if serum cyclophilin A could be used as a marker for severity and 90-day outcome in patients with traumatic brain injury (TBI). METHODS: Serum cyclophilin A concentrations were quantified in 105 severe TBI patients and 105 healthy individuals. Its association with Glasgow Coma Scale (GCS) score, 90-day mortality and 90-day poor outcome (Glasgow Outcome Scale score of 1-3) were investigated. RESULTS: Serum cyclophilin A concentrations were significantly higher in TBI patients than in healthy individuals. Cyclophilin A concentrations had a close relation to GCS scores and showed a high discriminatory ability for 90-day mortality and poor outcome according to area under receiver operating characteristic curve (AUC). Its AUC was in the range of GCS scores. Moreover, its combination with GCS scores significantly improved the predictive performance of GCS scores alone. In addition, serum cyclophilin A emerged as an independent predictor for 90-day mortality, overall survival and poor outcome. CONCLUSIONS: Increased serum cyclophilin A concentrations could reflect trauma severity and unfavorable outcome after head trauma, substantializing cyclophilin A as a potential biomarker for prognostic prediction of TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo/sangre , Lesiones Traumáticas del Encéfalo/diagnóstico , Ciclofilina A/sangre , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Reproductive system cancer is an important cause of morbidity and mortality worldwide which threatens women's health and lives. Breast, cervical, and ovarian cancer have the higher incidence and mortality among a series of gynecology malignant tumor. We aimed to compare and assess the temporal trends of common female malignances on breast, cervical, and ovarian cancer mortality in developed regions of Asia including Japan, Republic of Korea, and Singapore and analyze the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: The mortality data for these three cancers were collected from the WHO Mortality Database in Japan, Republic of Korea, and Singapore from 1954 to 2013, from 1989 to 2013, and from 1964 to 2013, respectively. We fitted an age-period-cohort model and intrinsic estimator method to estimate the independent effect of each age, time period, and birth cohort on cancer mortality and describe the secular changes in three Asian countries. RESULTS: For the overall trends of breast cancer, the ASMRs of breast cancer showed a general increasing trend among three countries during the study periods while the change pattern in Singapore was different from the rest of the two countries for cervical and ovarian cancer. By APC analysis, the three cancer mortality risks generally increased with age and decreased with birth cohort. For period effects of breast and ovarian cancer, increasing effects with time were observed; however, for period effects of cervical cancer, converse change pattern was presented among three countries. CONCLUSIONS: Our study shows that the ASMRs of breast, cervical, and ovarian cancer remain high in Singapore compared to Japan and Korea. Generally speaking, the mortality risk of three cancers increased with age, and period and cohort effects may collectively affect the common female malignances mortality for East Asian women.
Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias Ováricas/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Adulto , Factores de Edad , Anciano , Mama/patología , Cuello del Útero/patología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Japón/epidemiología , Persona de Mediana Edad , Ovario/patología , República de Corea/epidemiología , Singapur/epidemiología , Adulto JovenRESUMEN
In this study, we report the identification and functional characterization of the Drosophila ben/ubc13 gene, encoding a unique ubiquitin-conjugating enzyme (Ubc or E2), in DNA-damage response. Ben forms a heterodimer with DmUev1a, the only Ubc/E2 variant (Uev) in Drosophila. Ben and DmUev1a act together to catalyze K63-linked polyubiquitination in vitro. ben can functionally rescue the yeast ubc13 null mutant from killing by DNA-damaging agents. We also find that BenP97S, which was previously described to affect the connectivity between the giant fiber and the tergotrochanter motor neuron, fails to interact with the RING protein Chfr but retains interaction with DmUev1a as well as Uevs from other species. The corresponding yeast Ubc13P97S interacts with Mms2 but fails to bind Rad5. Consequently, neither benP97S nor ubc13P97S is able to complement the yeast ubc13 mutant defective in error-free DNA-damage tolerance. More importantly, the benP97S mutant flies are more sensitive to a DNA-damaging agent, suggesting that Ben functions in a manner similar to its yeast and mammalian counterparts. Collectively, our observations imply that Ben-DmUev1a-promoted K63-linked polyubiquitination and involvement in DNA-damage response are highly conserved in eukaryotes including flies.
Asunto(s)
Daño del ADN , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Lisina/metabolismo , Mutación , Enzimas Ubiquitina-Conjugadoras/metabolismo , Ubiquitina/metabolismo , Secuencia de Aminoácidos , Animales , Drosophila/genética , Drosophila/crecimiento & desarrollo , Proteínas de Drosophila/genética , Femenino , Lisina/genética , Masculino , Homología de Secuencia , Enzimas Ubiquitina-Conjugadoras/genética , UbiquitinaciónRESUMEN
OBJECTIVE: To determine the role of quantitative tibial nerve T2 value in the diagnosis of diabetic peripheral neuropathy (DPN). METHODS: MR imaging and T2 mapping of the tibial nerve were performed in 22 diabetic patients with DPN, 20 diabetic patients without DPN and 20 healthy controls. Nerve T2 values were measured, and compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic ability of T2 value to identify DPN. RESULTS: Nerve T2 value was 55.06 ± 4.05 ms, 48.91 ± 3.06 ms and 45.61 ± 1.86 ms in patients with DPN, patients without DPN and controls, respectively. Patients with DPN had significantly higher nerve T2 values than patients without DPN (P < 0.001). Nerve T2 values in patients without DPN were higher than in controls (P < 0.001). ROC analysis showed that T2 values had a diagnostic sensitivity of 81.8 %, specificity of 89.2 % and area under the curve of 0.922 for identifying patients with DPN from patients without DPN plus controls when the cutoff point was 51.34 ms. CONCLUSION: T2 value of the tibial nerve can be used as an alternative, non-invasive quantitative parameter to assess DPN in diabetic patients. KEY POINTS: ⢠Tibial nerves in patients with DPN showed T2 hyperintensity and enlargement. ⢠Tibial nerves in patients with DPN had an increased T2 value. ⢠T2 value might be used as a quantitative biomarker for DPN.
Asunto(s)
Tobillo/irrigación sanguínea , Neuropatías Diabéticas/diagnóstico , Imagen por Resonancia Magnética/métodos , Nervio Tibial/diagnóstico por imagen , Anciano , Tobillo/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROCRESUMEN
Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for treating obesity and associated metabolic disorders. To provide a comprehensive picture of the gene regulatory network in these processes, we conducted a series of transcriptome studies by RNA sequencing (RNA-seq) and quantified the mRNA and long noncoding RNA (lncRNA) changes during white fat browning (chronic cold exposure, beta-adrenergic agonist treatment, and intense exercise) and brown fat activation or inactivation (acute cold exposure or thermoneutrality, respectively). mRNA-lncRNA coexpression networks revealed dynamically regulated lncRNAs to be largely embedded in nutrient and energy metabolism pathways. We identified a brown adipose tissue-enriched lncRNA, lncBATE10, that was governed by the cAMP-cAMP response element-binding protein (Creb) axis and required for a full brown fat differentiation and white fat browning program. Mechanistically, lncBATE10 can decoy Celf1 from Pgc1α, thereby protecting Pgc1α mRNA from repression by Celf1. Together, these studies provide a comprehensive data framework to interrogate the transcriptomic changes accompanying energy homeostasis transition in adipose tissue.