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1.
Nat Methods ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961277

RESUMEN

Whole-brain analysis of single-neuron morphology is crucial for unraveling the complex structure of the brain. However, large-scale neuron reconstruction from terabyte and even petabyte data of mammalian brains generated by state-of-the-art light microscopy is a daunting task. Here, we developed 'Gapr' (Gapr accelerates projectome reconstruction) that streamlines deep learning-based automatic reconstruction, 'automatic proofreading' that reduces human workloads at high-confidence sites, and high-throughput collaborative proofreading by crowd users through the Internet. Furthermore, Gapr offers a seamless user interface that ensures high proofreading speed per annotator, on-demand conversion for handling large datasets, flexible workflows tailored to diverse datasets and rigorous error tracking for quality control. Finally, we demonstrated Gapr's efficacy by reconstructing over 4,000 neurons in mouse brains, revealing the morphological diversity in cortical interneurons and hypothalamic neurons. Here, we present Gapr as a solution for large-scale single-neuron reconstruction projects.

2.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4253-4260, 2023 Aug.
Artículo en Zh | MEDLINE | ID: mdl-37802794

RESUMEN

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.


Asunto(s)
Medicamentos Herbarios Chinos , Lamiaceae , Cinamatos , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Ácido Rosmarínico
3.
Int Urogynecol J ; 33(7): 1917-1925, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34213602

RESUMEN

INTRODUCTION AND HYPOTHESIS: Hysteropreservation and hysterectomy for uterine prolapse have been compared in several randomized controlled trials (RCTs), as the best treatment has not been definitively determined. This study aimed to summarize the available evidence in RCTs of hysteropreservation versus hysterectomy. METHODS: We performed electronic searches in the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure databases for eligible RCTs from inception to June 2020. The relative risks (RRs) and weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were calculated for categorical and continuous variables using random-effects models. RESULTS: Twelve RCTs involving 1177 patients were selected for meta-analysis. There were no significant differences between hysteropreservation and hysterectomy for the incidences of recurrence (RR, 0.55; 95% CI, 0.26-1.19; P = 0.130) and reoperation (RR, 1.15; 95% CI, 0.56-2.37; P = 0.705). Moreover, neither hysteropreservation nor hysterectomy had any significant effect on the risk of constipation (RR, 0.72; 95% CI, 0.15-3.46; P = 0.681), voiding dysfunction (RR, 0.99; 95% CI, 0.54-1.84; P = 0.981), intraoperative bleeding (RR, 0.35; 95% CI, 0.05-2.26; P = 0.271), upper leg dullness (RR, 0.70; 95% CI, 0.15-3.17; P = 0.643), dyspareunia (RR, 1.47; 95% CI, 0.69-3.13; P = 0.317), and wound infection (RR, 1.38; 95% CI, 0.24-7.80; P = 0.714). Furthermore, hysteropreservation was associated with less intraoperative blood loss (WMD, -25.68; 95% CI, -44.39 to -6.96; P = 0.007), shorter duration of surgery (WMD, -11.30; 95% CI, -19.04 to -3.55; P = 0.004), and shorter duration of hospitalization (WMD, -0.63; 95% CI, -1.10 to -0.16; P = 0.009) compared with hysterectomy. CONCLUSION: This study found that both hysteropreservation and hysterectomy have similar effects on recurrence and reoperation rates, while hysteropreservation was superior to hysterectomy in reducing intraoperative blood loss and shortening the duration of surgery and hospitalization.


Asunto(s)
Dispareunia , Prolapso Uterino , Pérdida de Sangre Quirúrgica , Dispareunia/cirugía , Femenino , Humanos , Histerectomía/efectos adversos , Reoperación , Prolapso Uterino/cirugía
4.
Cell Mol Life Sci ; 78(23): 7289-7307, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34687319

RESUMEN

Individuals of many species fight with conspecifics to gain access to or defend critical resources essential for survival and reproduction. Such intraspecific fighting is evolutionarily selected for in a species-, sex-, and environment-dependent manner when the value of resources secured exceeds the cost of fighting. One such example is males fighting for chances to mate with females. Recent advances in new tools open up ways to dissect the detailed neural circuit mechanisms that govern intraspecific, particularly inter-male, aggression in the model organism Mus musculus (house mouse). By targeting and functional manipulating genetically defined populations of neurons and their projections, these studies reveal a core neural circuit that controls the display of reactive male-male attacks in mice, from sensory detection to decision making and action selection. Here, we summarize these critical results. We then describe various modulatory inputs that route into the core circuit to afford state-dependent and top-down modulation of inter-male attacks. While reviewing these exciting developments, we note that how the inter-male attack circuit converges or diverges with neural circuits that mediate other forms of social interactions remain not fully understood. Finally, we emphasize the importance of combining circuit, pharmacological, and genetic analysis when studying the neural control of aggression in the future.


Asunto(s)
Agresión/fisiología , Fenómenos Fisiológicos del Sistema Nervioso , Núcleos Septales/fisiología , Conducta Sexual Animal/fisiología , Núcleo Hipotalámico Ventromedial/fisiología , Animales , Toma de Decisiones/fisiología , Receptor alfa de Estrógeno/metabolismo , Femenino , Instinto , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Endogámicos ICR , Sistema Nervioso , Neuronas/fisiología , Sensación/fisiología
5.
Cardiovasc Diabetol ; 19(1): 128, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32787939

RESUMEN

BACKGROUND: Bempedoic acid is an oral, once-daily, first-in-class drug being developed for the treatment of hyperlipidemia. However, evidence of bempedoic acid use for the prevention of cardiovascular events and diabetes is lacking. Thus, we aim to evaluate the benefit and safety of bempedoic acid use for the prevention of cardiovascular events and diabetes. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials with no language restriction from inception until March 3, 2020. Pairs of reviewers independently identified randomized controlled trials comparing the use of bempedoic acid with placebo or no treatment for primary prevention of cardiovascular events in statin-intolerant patients with hypercholesterolemia. The primary outcomes were major adverse cardiac events, and percent change in LDL-C. RESULTS: We identified 11 trials including a total of 4391 participants. Bempedoic acid use was associated with a reduction in composite cardiovascular outcome (RR 0.75, 95% CI 0.56-0.99; I2 = 0%). Bempedoic acid reduced LDL-C levels (MD - 22.91, 95% CI - 27.35 to - 18.47; I2 = 99%), and similarly reduced CRP levels (MD -24.70, 95% CI - 32.10 to - 17.30; I2 = 53%). Bempedoic acid was associated with a reduction in rates of new-onset or worsening diabetes (RR 0.65, 95% CI 0.44-0.96; I2 = 23%). CONCLUSIONS: Bempedoic acid in patients with hypercholesterolemia was associated with a lower risk of cardiovascular events and diabetes.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , LDL-Colesterol/sangre , Diabetes Mellitus/prevención & control , Ácidos Dicarboxílicos/uso terapéutico , Ácidos Grasos/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Ácidos Dicarboxílicos/efectos adversos , Regulación hacia Abajo , Ácidos Grasos/efectos adversos , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/epidemiología , Hipolipemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
6.
Nature ; 512(7513): 194-7, 2014 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-25043035

RESUMEN

As modern humans migrated out of Africa, they encountered many new environmental conditions, including greater temperature extremes, different pathogens and higher altitudes. These diverse environments are likely to have acted as agents of natural selection and to have led to local adaptations. One of the most celebrated examples in humans is the adaptation of Tibetans to the hypoxic environment of the high-altitude Tibetan plateau. A hypoxia pathway gene, EPAS1, was previously identified as having the most extreme signature of positive selection in Tibetans, and was shown to be associated with differences in haemoglobin concentration at high altitude. Re-sequencing the region around EPAS1 in 40 Tibetan and 40 Han individuals, we find that this gene has a highly unusual haplotype structure that can only be convincingly explained by introgression of DNA from Denisovan or Denisovan-related individuals into humans. Scanning a larger set of worldwide populations, we find that the selected haplotype is only found in Denisovans and in Tibetans, and at very low frequency among Han Chinese. Furthermore, the length of the haplotype, and the fact that it is not found in any other populations, makes it unlikely that the haplotype sharing between Tibetans and Denisovans was caused by incomplete ancestral lineage sorting rather than introgression. Our findings illustrate that admixture with other hominin species has provided genetic variation that helped humans to adapt to new environments.


Asunto(s)
Adaptación Fisiológica/genética , Altitud , ADN/genética , Variación Genética , Hominidae/genética , Animales , Pueblo Asiatico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Frecuencia de los Genes , Haplotipos , Humanos , Polimorfismo de Nucleótido Simple , Tibet
7.
J Sep Sci ; 43(5): 905-911, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31778034

RESUMEN

Surfactant cetyltrimethylammonium bromide enhanced molybdenum disulfide was used as an adsorbent in pipette-tip solid-phase extraction for the pretreatment of sulfonamides in environmental water samples. The factors affecting the extraction recoveries of the analytes, including the sample pH value, amount of sorbent, type and volume of eluent solution, and salt concentration were optimized. This pipette-tip solid-phase extraction method demonstrated good linearity (0.05-10.0 µg/L) with a coefficient of determination of 0.9984-0.9996, limit of detection (0.2-0.4 ng/L) and limit of quantitation (0.5-1.0 ng/L), good analyte recoveries (76-91), and acceptable limit of quantitation (<10%) under the optimized conditions. These results indicated that the proposed method was a good tool for monitoring sulfonamides in environmental water samples.

8.
Nephrology (Carlton) ; 21(3): 200-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26246161

RESUMEN

AIM: Maternal dietary protein restriction reduces nephron number in offspring and increases the risk of cardiovascular and chronic kidney diseases. Perlecan is the major basement membrane/extracellular matrix heparan sulfate proteoglycan (HSPG) that plays a crucial role in nephron formation. This study was to determine whether maternal dietary protein restriction during pregnancy leads to an abnormal perlecan expression pattern during kidney development and a correlation with aberrant cell proliferation and apoptosis. METHODS: Pregnant Sprague-Dawley rats were divided into two groups, maintained on either a low-protein diet (MLP group) or a normal-protein diet (MNP group). Kidneys were dissected from embryos of different kidney development stages. Real-time PCR and immunohistochemistry were performed to detect the transcript level of rHSPG2, the coding gene of perlecan, and its protein expression pattern. Apoptosis and proliferation cell were detected by TUNEL system and Ki67 marker. RESULTS: Embryonic weights and nephron number were significantly affected by maternal low protein diets. The transcript level of rHSPG2 in the MLP group was significantly lower at embryonic day 18 and the neonatal period. Immunohistochemistry study was consistent with the RT-PCR results. The proliferation level of the MLP group was significantly lower than the MNP group at E18 and more apoptotic cells was detected in MLP newborn. CONCLUSION: Maternal protein restriction reduced the expression of perlecan and lead aberrant cell proliferation and apoptosis during mid-metanephrogenesis in offspring. This data may provide new evidence to understand the mechanism of reduced nephron number due to maternal protein restriction and enlighten solution.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Dieta con Restricción de Proteínas , Proteoglicanos de Heparán Sulfato/metabolismo , Fenómenos Fisiologicos Nutricionales Maternos , Nefronas/metabolismo , Animales , Apoptosis , Proliferación Celular , Regulación hacia Abajo , Femenino , Regulación del Desarrollo de la Expresión Génica , Edad Gestacional , Proteoglicanos de Heparán Sulfato/genética , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Nefronas/embriología , Estado Nutricional , Organogénesis , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
Artículo en Zh | MEDLINE | ID: mdl-30130007

RESUMEN

Objective: To investigate the prevalence of parasitic infections in Lhasa, Tibet. Methods: The residents in Chengguan District, Dangxiong County, Dazi County and Qushui County were selected to participate in the study in 2014, using the stratified random sampling method. Infections with the soil-borne nematodes in feces were examined in triplicates using the Kato-Katz method. Further, the Enterobius vermicularis were examined using the cellophane anal swab method in children aged 3-12 years, and the intestinal protozoa were detected by iodine staining. The parasitic infection was analyzed by sex, age, and occupation. Comparisons were made using Chi-square test. Results: A total of 1 015 residents(39.3±18.2 years: age range, 1-89 years) participated in the study, including 391 males(38.6%) and 623 females(61.4%). Two hundred and forty-nine participants were positive for parasitic infections, with an overall infection rate of 24.5%(249/1 015). The infection rate was 21.7%(220/1 015) for Taenia sp., 0.2%(2/1 015) for Trichuris trichiura and E. vermicularis respectively, 4.1%(42/1 015) for Entamoeba coli, 0.4%(4/1 015) for Giardia lamblia, 0.2%(2/1 015) for Iodamoeba butschlii. No infection was found for other parasites. There was no significant sexual difference in the infection rate of Taenia (male 21.2%, 83/391; female 22.0%, 137/624), T. trichiura (male 0; female 0.3%, 2/624), E. vermicularis (male 0.3%, 2/391; female 0.2%, 1/624), E. coli (male 5.4%, 21/391; female 3.4%, 21/624), G. lamblia (male 0.8%, 3/391; female 0.2%, 1/624), or I. butschlii (male 0; female 0.3%, 2/624) (P>0.05). The Taenia sp. infection rate in the age groups of 0-17, 18-29, 30-39, 40-49, 50-59 and ≥ 60 years was 10.9%(18/165), 14.0%(18/129), 23.0%(43/187), 25.3%(61/241), 26.5%(41/155), and 28.3%(39/138), respectively, with significant differences between groups of 0-17 and 40-49 years and between groups of 50-59 and ≥ 60 years (P<0.01). The infection rate of E. coli, T. trichiura and I. butschlii was highest in the age group of 50-59 years(6.5%, 10/155; 0.7%, 1/155; 1.3%, 2/155 respectively). Among various occupations, farmers showed the highest infection rate for Taenia(44.5%, 147/330), E. coli(6.4%, 21/33), E. vermicularis (0.6%, 2/330) and I. butschlii(0.3%, 1/330); housewives had the highest infection rate for T. trichiura(2.5%, 1/40); and the students had the highest infection rate for G. lamblia (0.7%, 1/134). Conclusion: There are infections with various intestinal parasites in the participants of Lhasa City, among which taenia infection reaches 20.7% while others have a low level of infection.


Asunto(s)
Parasitosis Intestinales/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Enterobius , Escherichia coli , Agricultores , Heces , Femenino , Helmintos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Nematodos , Prevalencia , Suelo , Encuestas y Cuestionarios , Teniasis , Tibet/epidemiología , Adulto Joven
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(12): 1231-5, 2014 Dec.
Artículo en Zh | MEDLINE | ID: mdl-25523571

RESUMEN

OBJECTIVE: To study the clinical characteristics of childhood Henoch-Schonlein purpura (HSP) on the Tibetan Plateau, China. METHODS: One hundred and twenty-five HSP children admitted to Shannan People's Hospital, Tibet, were assigned to the observation group, and 96 HSP children admitted to Wuhan Children's Hospital were assigned to the control group. The disease characteristics, clinical manifestations, treatment, and prognosis in both groups were retrospectively analyzed and compared. RESULTS: The mean age of HSP onset and the female-to-male ratio in the observation group were both significantly higher than in the control group (P<0.05). There was a significant difference in seasonal onset between two groups. Significant differences in the etiological factors were observed between the two groups (P<0.05). The gastrointestinal manifestation was more prominent in the observation group compared with that in the control group (P<0.05). Laboratory findings showed that the mean erythrocyte sedimentation rate, counts of white blood cells and platelets, and percentage of neutrophil leucocytes were significantly lower, while the hemoglobin level was significantly higher in the observation group than in the control group (P<0.05). A total of 124 HSP patients (99.2%) in the observation group had a full recovery or improvement, and the overall cure rate and improvement rate showed no significant differences between two groups (P>0.05). Only 2.4% of the patients (3 cases) in the observation group had recurrent attack during follow-up, which was significantly lower than that in the control group (16.7%; P<0.05). CONCLUSIONS: Childhood HSP on the Tibetan Plateau shows partial differences in disease characteristics, clinical manifestations, and laboratory measurements compared with that in the plain area. The overall prognosis is better and the recurrent rate is lower among HSP children on the Tibetan Plateau.


Asunto(s)
Vasculitis por IgA/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/etiología , Masculino , Pronóstico , Tibet
11.
Pediatr Res ; 74(5): 511-6, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23999069

RESUMEN

BACKGROUND: Mutations in canonical transient receptor potential channel 6 (TRPC6) have been identified as responsible for the development of focal segmental glomerulosclerosis, a proteinuric disease with steroid resistance and poor prognosis. This study explores the prevalence of TRPC6 variants in Chinese children with idiopathic nephrotic syndrome (INS), the genotype/phenotype correlation of TRPC6 variants, the therapeutic response, and the underlying molecular mechanism. METHODS: Fifty-one children with sporadic INS were enrolled: 23 steroid-sensitive cases and 28 steroid-resistant cases Polymerase chain reaction was used to amplify 13 exons and the promoter sequences of TRPC6 before sequencing. The expression of TRPC6 in renal tissues was illustrated by immunohistochemistry staining. The transcriptional activity of variants in TRPC6 promoter was measured by the luciferase assay. RESULTS: Three variants (-254C>G, rs3824934; +43C/T, rs3802829; and 240 G>A, rs17096918) were identified. The allele frequency of the -254C>G single-nucleotide polymorphism (SNP) in the steroid-resistant nephrotic syndrome (SRNS) patients (40.5%) was higher than that in the steroid-sensitive nephrotic syndrome subjects (27.1%; P = 0.046). The -254C>G SNP enhanced transcription from TRPC6 promoter in vitro and was associated with increased TRPC6 expression in renal tissues of SRNS patients. CONCLUSION: -254C>G, a SNP underlying enhanced TRPC6 transcription and expression, may be correlated with the development of steroid resistance in Chinese children with INS.


Asunto(s)
Pueblo Asiatico/genética , Síndrome Nefrótico/congénito , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Canales Catiónicos TRPC/genética , Transcripción Genética/genética , Secuencia de Bases , Niño , Exones/genética , Frecuencia de los Genes , Humanos , Inmunohistoquímica , Riñón/metabolismo , Luciferasas , Datos de Secuencia Molecular , Síndrome Nefrótico/genética , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Canal Catiónico TRPC6
12.
Asian-Australas J Anim Sci ; 26(3): 323-33, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25049794

RESUMEN

This study investigated the geographic and pairwise distances of nine Chinese local Cashmere goat populations through the analysis of 20 microsatellite DNA markers. Fluorescence PCR was used to identify the markers, which were selected based on their significance as identified by the Food and Agriculture Organization of the United Nations (FAO) and the International Society for Animal Genetics (ISAG). In total, 206 alleles were detected; the average allele number was 10.30; the polymorphism information content of loci ranged from 0.5213 to 0.7582; the number of effective alleles ranged from 4.0484 to 4.6178; the observed heterozygosity was from 0.5023 to 0.5602 for the practical sample; the expected heterozygosity ranged from 0.5783 to 0.6464; and Allelic richness ranged from 4.7551 to 8.0693. These results indicated that Chinese Cashmere goat populations exhibited rich genetic diversity. Further, the Wright's F-statistics of subpopulation within total (FST) was 0.1184; the genetic differentiation coefficient (GST) was 0.0940; and the average gene flow (Nm) was 2.0415. All pairwise FST values among the populations were highly significant (p<0.01 or p<0.001), suggesting that the populations studied should all be considered to be separate breeds. Finally, the clustering analysis divided the Chinese Cashmere goat populations into at least four clusters, with the Hexi and Yashan goat populations alone in one cluster. These results have provided useful, practical, and important information for the future of Chinese Cashmere goat breeding.

13.
Curr Opin Neurobiol ; 81: 102749, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37421660

RESUMEN

Decades of knockout analyses have highlighted the crucial involvement of estrogen receptors and downstream genes in controlling mating behaviors. More recently, advancements in neural circuit research have unveiled a distributed subcortical network comprising estrogen-receptor or estrogen-synthesis-enzyme-expressing cells that transforms sensory inputs into sex-specific mating actions. This review provides an overview of the latest discoveries on estrogen-responsive neurons in various brain regions and the associated neural circuits that govern different aspects of male and female mating actions in mice. By contextualizing these findings within previous knockout studies of estrogen receptors, we emphasize the emerging field of "circuit genetics", where identifying mating behavior-related neural circuits may allow for a more precise evaluation of gene functions within these circuits. Such investigations will enable a deeper understanding of how hormone fluctuation, acting through estrogen receptors and downstream genes, influences the connectivity and activity of neural circuits, ultimately impacting the manifestation of innate mating actions.


Asunto(s)
Estrógenos , Receptores de Estrógenos , Animales , Masculino , Femenino , Ratones , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Neuronas/fisiología , Encéfalo/fisiología
14.
J Neuroendocrinol ; 35(2): e13195, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36072992

RESUMEN

Sex differences in emotional behaviors and affective disorders have been widely noted, of which sexually dimorphic secretion of gonadal steroid hormones such as estrogen is suspected to play a role. However, the underlying neural mechanisms remain poorly understood. We noted that the expression of estrogen receptor 2 (Esr2, or ERß), a key mediator of estrogen signaling in the brain, was enriched in the dorsal raphe nucleus (DRN), a region involved in emotion regulation. To investigate whether DRN Esr2 expression confers sex-specific susceptibility or vulnerability in emotional behaviors, we generated a conditional allele of Esr2 that allowed for site-specific deletion of Esr2 in the DRN via local injection of Cre-expressing viruses. DRN-specific Esr2 deletion mildly increased anxiety behaviors in females, as shown by decreased time spent in the center zone of an open field in knockout females. By contrast, DRN Esr2 deletion had no effects on anxiety levels in males, as demonstrated by knockout males spending comparable time in the center zone of an open field and open arms of an elevated-plus maze. Furthermore, in the tail suspension test, DRN Esr2 deletion reduced immobility, a depression-like behavior, in a male-biased manner. Together, these results reveal sex-specific functions of DRN Esr2 in regulating emotional behaviors and suggest targeted manipulation of DRN Esr2 signaling as a potential therapeutic strategy to treat sex-biased affective disorders.


Asunto(s)
Núcleo Dorsal del Rafe , Receptor beta de Estrógeno , Femenino , Masculino , Humanos , Núcleo Dorsal del Rafe/metabolismo , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Ansiedad/genética , Ansiedad/metabolismo , Depresión/genética , Depresión/metabolismo , Estrógenos/metabolismo
15.
Med Sci Monit ; 18(1): BR16-23, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22207105

RESUMEN

BACKGROUND: This study aimed to investigate the role of osteopontin and its receptor, integrin αv, in gallstone formation using human tissue specimens and a guinea pig lithogenic model. MATERIAL/METHODS: The nucleation role of osteopontin was determined in patients' and normal gallbladder bile samples in vitro. Normal gallbladder was the control, and gallstone gallbladders were divided into group I (with normal epithelia) and group II (with degenerated epithelia) based on pathology change. Immunostaining, mRNA and protein expressions of osteopontin and integrin αv were analyzed. The animals were randomly divided into a lithogenic diet group and a normal diet group; the osteopontin mRNA expression in gallbladder and liver and osteopontin concentrations were determined. RESULTS: Osteopontin prolonged nucleation time and inhibited the pro-nucleating role induced by calcium in human bile in vitro. Immunostaining for osteopontin and integrin αv in human gallbladder tissues showed a higher reactivity in Group I than control group and Group II. The immunostaining in Group II was weaker than control group; similar results were observed for mRNA and protein expression of osteopontin and integrin αv. In the animal assay, the mRNA expression and concentration of osteopontin in gallbladder and liver gradually increased at initial stages and decreased in later stages. The concentrations of osteopontin in bile and serum of guinea pig showed similar trends. CONCLUSIONS: Our results suggest that osteopontin is involved in cholesterol gallstone formation, and the role of osteopontin might correlate with integrin αv and calcium.


Asunto(s)
Bilis/metabolismo , Dieta , Cálculos Biliares/metabolismo , Integrina alfaV/metabolismo , Osteopontina/metabolismo , Animales , Western Blotting , Calcio/metabolismo , Femenino , Vesícula Biliar/metabolismo , Cálculos Biliares/patología , Cobayas , Humanos , Inmunohistoquímica , Hígado/metabolismo , Masculino , Osteopontina/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Yi Chuan ; 34(5): 584-90, 2012 May.
Artículo en Zh | MEDLINE | ID: mdl-22659430

RESUMEN

The maternal genetic effects on estimating genetic parameters for growth traits and wool traits of Qinghai fine-wool sheep were investigated.The genetic parameters for production traits of Qinghai fine-wool sheep were estimated by average information restricted maximum likelihood (AIREML) with different animal models, and the differences between different animal models were tested by likelihood ratio test. Fixed effects, direct genetic effects, and residual effects were included all models; and random effects were individual permanence environmental effects, maternal genetic effects, and maternal permanence environmental effects. The six models differ in the way of considering random effects: in model 1 individual permanence environmental effects, maternal genetic effects, and maternal permanence environmental effects were not contained; in model 2 maternal permanence environmental effects were included; in model 3 maternal genetic effects were included; in model 4 both maternal genetic effects and maternal permanence environmental effects were include; in model 5 both individual permanence environmental effects and maternal genetic effects were contained;in model 6 all random effects were contained. The direct heritabilities were 0.1896~0.3781, 0.2537~0.2890, 0.2244~0.3225, 0.2205~0.3983, 0.1218~0.1490, 0.0983~0.4802, and 0.1170~0.1311 for birth weight, weaning weight, yearling weight, hogget weight,greasy fleece weight, fiber diameter, and staple length,respectively. Compared with model 1, model 3 was-significant(P<0.01) for birth weight and weaning weight, other models were not significant (P>0.05)for Yearling weight, Hogget weight; and paralleled with model 6, both model 4 and model 5 were significant(P<0.01) for fiber diameter,model 4 was significant(P<0.05) for staple length, and other models were not significant(P>0.05) for greasy fleece weight by likelihood ratio test.The maternal effects were important determinants of estimated the genetic parameters for birth weight, weaning weigh, fiber diameter, and staple length, but were not significant for yearling weight, and hogget weight, and was slightly significant for greasy fleece weight.


Asunto(s)
Ovinos/genética , Lana , Animales , Modelos Animales , Ovinos/crecimiento & desarrollo
17.
ACS Nano ; 16(8): 11852-11861, 2022 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-35912431

RESUMEN

Spin-orbit torque (SOT) efficiency is one of the key issues of spintronics. However, enhancing the SOT efficiency is usually limited by the positive correlation between resistivity and the spin Hall ratio, where a high resistivity often accompanies a large spin Hall ratio. Here, we demonstrate that sub-nanometer ß-W intercalation has a considerable impact on the SOT efficiency in α-W (6 nm)/Co (8 nm)/Pt (3 nm) samples. The damping-like SOT efficiency per unit current density, ξDLj, of α-W (5.7 nm)/ß-W (0.3 nm)/Co (8 nm)/Pt (3 nm) shows a ∼ 296% enhancement compared to that of the α-W/Co/Pt system. Meanwhile, a resistivity similar to that of α-W and the spin Hall ratio larger than ß-W induce a giant damping-like SOT efficiency per applied electric field, ξDLE, which is about 12.1 times larger than that of ß-W. Our findings will benefit the SOT devices by reducing energy consumption.

18.
Clin Rheumatol ; 41(6): 1825-1832, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35091776

RESUMEN

OBJECTIVE: To assess the efficacy and safety of corticosteroid therapy including oral corticosteroid and intra-articular corticosteroid in patients with hand osteoarthritis (OA), to provide treatment recommendations, and provide data-driven suggestions for future studies. METHODS: A systematic review of the literature was performed from inception to February 19, 2020, and the study was conducted on February 20, 2020. All controlled trials in Ovid MEDLINE, EMBASE, and Cochrane library reporting the efficacy on pain, functional recovery, and adverse events of corticosteroids in hand osteoarthritis were selected. The primary outcome was pain assessed on a visual analogue scale (VAS) lasting for up to 24 weeks. Pooled mean difference (MD) for continuous variable and risk ratio (RR) for dichotomous variable, with 95% confidence intervals (CIs), was assessed by a random effects model. RESULTS: Overall, seven trials totaling 511 participants were included in this study. The pooled analysis showed a significant difference in VAS pain (MD, - 5.75; 95% CI, - 10.08 to - 1.42, I2 = 40%). No significant differences were observed in any of the adverse events. CONCLUSION: Our data suggest corticosteroids in hand OA might improve local pain and promote functional recovery. However, since these findings were based on only 7 studies and due to significant heterogeneity across the included studies, these findings need to be confirmed by future clinical trials with a higher number of patients. KEY POINTS: • Current evidences of glucocorticoids for the management of hand osteoarthritis (OA) were insufficient and more evidences were needed. • The results of the present meta-analysis revealed corticosteroids in hand OA might improve local pain and promote functional recovery. • These findings need to be confirmed by future clinical trials with a higher number of patients.


Asunto(s)
Osteoartritis , Corticoesteroides , Humanos , Inyecciones Intraarticulares , Osteoartritis/tratamiento farmacológico , Dolor/tratamiento farmacológico , Dolor/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto
19.
Cell Metab ; 34(6): 888-901.e5, 2022 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-35675799

RESUMEN

Homeostatic thermogenesis is an essential protective feature of endotherms. However, the specific neuronal types involved in cold-induced thermogenesis remain largely unknown. Using functional magnetic resonance imaging and in situ hybridization, we screened for cold-sensitive neurons and found preprodynorphin (PDYN)-expressing cells in the dorsal medial region of the ventromedial hypothalamus (dmVMH) to be a candidate. Subsequent in vivo calcium recording showed that cold temperature activates dmVMHPdyn neurons, whereas hot temperature suppresses them. In addition, optogenetic activation of dmVMHPdyn neurons increases the brown adipose tissue and core body temperature, heart rate, and blood pressure, whereas optogenetic inhibition shows opposite effects, supporting their role in homeostatic thermogenesis. Furthermore, we found that dmVMHPdyn neurons are linked to known thermoregulatory circuits. Importantly, dmVMHPdyn neurons also show activation during mouse social interaction, and optogenetic inhibition suppresses social interaction and associated hyperthermia. Together, our study describes dual functions of dmVMHPdyn neurons that allow coordinated regulation of body temperature and social behaviors.


Asunto(s)
Hipertermia Inducida , Interacción Social , Tejido Adiposo Pardo , Animales , Frío , Hipotálamo , Ratones , Neuronas/fisiología , Termogénesis/fisiología
20.
Nat Commun ; 13(1): 1650, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35347125

RESUMEN

Finding an effective way to greatly tune spin Hall angle in a low power manner is of fundamental importance for tunable and energy-efficient spintronic devices. Recently, topological insulator of Bi2Se3, having a large intrinsic spin Hall angle, show great capability to generate strong current-induced spin-orbit torques. Here we demonstrate that the spin Hall angle in Bi2Se3 can be effectively tuned asymmetrically and even enhanced about 600% reversibly by applying a bipolar electric field across the piezoelectric substrate. We reveal that the enhancement of spin Hall angle originates from both the charge doping and piezoelectric strain effet on the spin Berry curvature near Fermi level in Bi2Se3. Our findings provide a platform for achieving low power consumption and tunable spintronic devices.

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