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1.
Circ Res ; 134(7): 913-930, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38414132

RESUMEN

BACKGROUND: Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3's relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress. METHODS: We performed in vitro studies on cardiomyocytes and myocardial tissue samples from patients and performed in vivo investigation with SLIT3 and ROBO1 (roundabout homolog 1) mutant mice undergoing transverse aortic constriction to establish the role of SLIT3-ROBO1 in adverse cardiac remodeling. RESULTS: We first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from WT (wild-type) and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti-SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3's hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell-specific knockout of SLIT3 in mice resulted in decreased left ventricular hypertrophy and cardiac fibrosis after transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte-specific deletion of ROBO1 also preserved left ventricular function and abrogated hypertrophy, but not fibrosis, after transverse aortic constriction. CONCLUSIONS: Collectively, these results indicate a novel role for the SLIT3-ROBO1-signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.


Asunto(s)
Miocitos Cardíacos , Proteínas del Tejido Nervioso , Animales , Humanos , Ratones , Cardiomegalia/genética , Cardiomegalia/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Fibrosis , Hipertrofia Ventricular Izquierda/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Remodelación Ventricular
2.
Mol Cell Probes ; 73: 101947, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38122948

RESUMEN

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-ß1 (TGF-ß1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-ß1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-ß1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-ß1 in RTFs via the TGF-ß1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2-Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.


Asunto(s)
Obstrucción de las Vías Aéreas , Fibrosis Pulmonar , Animales , Humanos , Ratas , Obstrucción de las Vías Aéreas/metabolismo , Fibroblastos/metabolismo , Fibrosis , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Fibrosis Pulmonar/metabolismo , Receptores Inmunológicos/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/farmacología
3.
Nephrology (Carlton) ; 29(1): 48-54, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37772439

RESUMEN

BACKGROUND: Accurate genetic diagnosis of end-stage renal disease patients with a family history of renal dysfunction is very essential. It not only helps in proper prognosis, but becomes crucial in designating donor for live related renal transplant. We here present a case of family with deleterious mutations in INF2 and ROBO2 and its importance of genetic testing before preparing for kidney transplantation. CASE PRESENTATION: We report the case of a 29-year-female with end-stage renal disease and rapidly progressive renal failure. Mutational analysis revealed an Autosomal Dominant inheritance pattern and mutation in exon 4 of the INF2 gene (p. Thr215Ser) and exon 26 of the ROBO2 gene (p. Arg1371Cys). Her mother was diagnosed for CKD stage 4 with creatinine level of 4.3 mg/dL. Genetic variants (INF2 and ROBO2) identified in proband were tested in her sisters and mother. Her elder sister was positive for both heterozygous variants (INF2 and ROBO2). Her mother was positive for mutation in INF2 gene, and her donor elder sister did not showed mutation in INF2 gene and had mutation in ROBO2 gene without any clinical symptoms. CONCLUSION: This case report emphasize that familial genetic screening has allowed us in allocating the donor selection in family where family member had history of genetic defect of Chronic Kidney Disease. Information of the causative renal disorder is extremely valuable for risk-assessment and planning of kidney transplantation.


Asunto(s)
Glomeruloesclerosis Focal y Segmentaria , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Femenino , Anciano , Forminas/genética , Estudios de Seguimiento , Glomeruloesclerosis Focal y Segmentaria/genética , Mutación , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/genética , Fallo Renal Crónico/cirugía , Linaje , Proteínas Roundabout , Receptores Inmunológicos/genética
4.
Int J Mol Sci ; 25(7)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38612763

RESUMEN

Idiopathic intellectual disability (IID) encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology. However, in idiopathic ID, the effect of miRNAs is poorly understood. The aim of this study was to determine the miRNAs regulating the expression of mRNAs that may be involved in development of IID. Expression profiles were obtained using NPC-NEO cells from IID patients and healthy controls by microarray. A total of 796 miRNAs and 28,869 mRNAs were analyzed. Several miRNAs were overexpressed in the IID patients compared to controls. miR-25 had the greatest expression. In silico analysis showed that ROBO2 was the target for miR-25, with the highest specificity and being the most down-regulated. In vitro assay showed an increase of miR-25 expression induced a decrease in ROBO2 expression. In neurodevelopment, ROBO2 plays a crucial role in episodic learning and memory, so its down-regulation, caused by miR-25, could have a fundamental role in the intellectual disability that, until now, has been considered idiopathic.


Asunto(s)
Discapacidad Intelectual , MicroARNs , Humanos , Discapacidad Intelectual/genética , MicroARNs/genética , Encéfalo , Regulación hacia Abajo/genética , Aprendizaje , ARN Mensajero , Proteínas Roundabout , Receptores Inmunológicos/genética
5.
Int J Mol Sci ; 25(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125915

RESUMEN

Cashmere goats possess two types of hair follicles, with the secondary hair follicles producing valuable cashmere fiber used for textiles. The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. Transcription factors play crucial roles during this process. The transcription factor, cold-shock domain, containing C2 (Csdc2) plays a crucial role in modulating cell proliferation and differentiation. Our preceding research indicated that the expression of Csdc2 changes periodically during anagen to telogen. However, the mechanisms of Csdc2 in regulating SHF growth remain unclear. Here, we found that the knockdown of Csdc2 inhibits the proliferation of dermal papilla cells. ChIP-Seq analysis showed that Csdc2 had a unique DNA binding motif in SHFs. Through conjoint analysis of ChIP-Seq and RNA-Seq, we revealed a total of 25 candidate target genes of Csdc2. Notably, we discovered a putative Csdc2 binding site within roundabout guidance receptor 2 (Robo2) on chromosome 1 of the goat genome. Furthermore, qRT-PCR and dual-luciferase reporter assay confirmed Csdc2's positive regulatory influence on Robo2. These findings expand the research field of hair follicle transcriptional regulatory networks, offering insights into molecular breeding strategies to enhance cashmere production in goats.


Asunto(s)
Cabras , Folículo Piloso , Animales , Cabras/genética , Cabras/crecimiento & desarrollo , Folículo Piloso/metabolismo , Folículo Piloso/crecimiento & desarrollo , Proliferación Celular , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Regulación de la Expresión Génica , Sitios de Unión
6.
Cell Signal ; 120: 111225, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38735506

RESUMEN

Ubiquitin-specific proteases (USPs) have been proved to play important roles in the progression of diabetic retinopathy. In this study, we explored the role of USP5 and its possible mechanisms in diabetic retinopathy development. Cell proliferation, apoptosis, inflammation and oxidative stress were determined using CCK-8 assay, EdU staining assay, flow cytometry, and ELISA, respectively. The mRNA and protein expression of ROBO4 and USP5 were measured through RT-qPCR and western blot, respectively. Co-IP and deubiquitination assay were conducted to evaluate the interaction between ROBO4 and USP5. The results showed that high glucose (HG) stimulation significantly led to HRPE cell damage as described by suppressing proliferation, and promoting oxidative stress, inflammation and apoptosis. ROBO4 was markedly increased in diabetic retinopathy plasma samples and HG-triggered HRPE cells. Depletion of ROBO4 could alleviate HG-caused HRPE cell damage. USP5 was also significantly elevated in diabetic retinopathy plasma samples and HG-triggered HRPE cells. USP5 overexpression aggravated HG-induced HRPE cell damage. USP5 stabilized ROBO4 through deubiquitination. Moreover, USP5 knockdown decreased ROBO4 expression to mitigate HG-triggered cell damage in HRPE cells. USP5 stabilized ROBO4 via deubiquitination to repress cell proliferation, and facilitate inflammation, cell apoptosis and oxidative stress in HG-treated HRPE cells, thereby promoting the development of diabetic retinopathy.


Asunto(s)
Retinopatía Diabética , Receptores de Superficie Celular , Ubiquitinación , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Humanos , Receptores de Superficie Celular/metabolismo , Apoptosis , Proteasas Ubiquitina-Específicas/metabolismo , Proteasas Ubiquitina-Específicas/genética , Proliferación Celular , Estrés Oxidativo , Animales , Glucosa/metabolismo , Glucosa/farmacología , Línea Celular , Proteínas Roundabout
7.
Future Sci OA ; 10(1): 2340186, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39069888

RESUMEN

Aim: This study aimed to explore using peripheral blood mononuclear cell (PBMC)-derived chimeric antigen receptor (CAR) NK cells targeting ROBO1 as a personalized medicine approach for ovarian cancer. Methods: A two-step strategy generated ROBO1-targeted CAR NK cells from PBMCs of ovarian cancer patients. Efficacy was evaluated using xCELLigence RTCA, CCK-8 and Live/Dead fluorescence assays. Results: ROBO1-NK cells exhibited higher efficiency in eradicating primary ovarian cancer cells and lysing ovarian tumor organoids compared with primary NK cells without ROBO1-CAR modification. Conclusion: These findings highlight the potential of developing ROBO1-targeted CAR-NK cells from patients' PBMCs as a personalized treatment option for ovarian cancer.


Ovarian cancer represents a formidable clinical challenge necessitating the urgent exploration of novel therapeutic approaches. In this study, the focus was directed toward ROBO1, a molecule known to play a pivotal role in cancer angiogenesis and metastasis, while limited investigation in the context of ovarian cancer. Leveraging this knowledge, we sought to construct ROBO1-targeting chimeric antigen receptor natural killer (CAR-NK) cells utilizing peripheral blood mononuclear cells derived from the patients themselves. The overarching goal of this investigation was to harness the potential of immunotherapy using autologous resources to realize personalized treatment strategies for ovarian cancer in clinical settings.

8.
J Pediatr Genet ; 13(2): 116-122, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38721573

RESUMEN

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessively inherited disorder characterized by a congenital absence of conjugated horizontal eye movements with progressive scoliosis developing in childhood and adolescence. HGPPS is caused by mutations of the ROBO3 gene that disrupts the midline crossing of the descending corticospinal and ascending lemniscal sensory tracts in the medulla. We present two siblings, 5-year-old and 2-year-old boys with HGPPS, from non-consanguineous parents. The older brother was brought for the evaluation of moderate psychomotor retardation. He had bilateral horizontal gaze palsy with preserved vertical gaze and convergence. Scoliosis was absent. Cranial MRI showed brainstem abnormalities, and diffusion tensor imaging showed absent decussation of cortico-spinal tracts in the medulla. Clinical diagnosis of HGPPS was confirmed by sequencing of ROBO3 gene, IVS4-1G > A (c.767-1G > A) and c.328_329delinsCCC (p.Asp110Profs*57) compound heterozygous variations were found, and segregated in parents. The younger boy was first reported at 16 months of age and had the same clinical and neuroradiological findings, unlike mild psychomotor retardation. ROBO3 gene analysis showed the same variants in his brother. Our cases show the importance of evaluating eye movements in children with neurodevelopmental abnormalities and looking for brainstem abnormalities in children with bilateral horizontal gaze palsy.

9.
Eur J Med Res ; 29(1): 349, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937814

RESUMEN

BACKGROUND: Sepsis is one of the most common clinical diseases, which is characterized by a serious and uncontrollable inflammatory response. LPS-induced inflammation is a critical pathological event in sepsis, but the underlying mechanism has not yet been fully elucidated. METHODS: The animal model was established for two batches. In the first batch of experiments, Adult C57BL/6J mice were randomly divided into control group and LPS (5 mg/kg, i.p.)group . In the second batch of experiments, mice were randomly divided into control group, LPS group, and LPS+VX765(10 mg/kg, i.p., an inhibitor of NLRP3 inflammasome) group. After 24 hours, mice were anesthetized with isoflurane, blood and intestinal tissue were collected for tissue immunohistochemistry, Western blot analysis and ELISA assays. RESULTS: The C57BL/6J mice injected with LPS for twenty-four hours could exhibit severe inflammatory reaction including an increased IL-1ß, IL-18 in serum and activation of NLRP3 inflammasome in intestine. The injection of VX765 could reverse these effects induced by LPS. These results indicated that the increased level of IL-1ß and IL-18 in serum induced by LPS is related to the increased intestinal permeability and activation of NLRP3 inflammasome. In the second batch of experiments, results of western blot and immunohistochemistry showed that Slit2 and Robo4 were significant decreased in intestine of LPS group, while the expression of VEGF was significant increased. Meanwhile, the protein level of tight junction protein ZO-1, occludin, and claudin-5 were significantly lower than in control group, which could also be reversed by VX765 injection. CONCLUSIONS: In this study, we revealed that Slit2-Robo4 signaling pathway and tight junction in intestine may be involved in LPS-induced inflammation in mice, which may account for the molecular mechanism of sepsis.


Asunto(s)
Inflamación , Péptidos y Proteínas de Señalización Intercelular , Lipopolisacáridos , Ratones Endogámicos C57BL , Proteínas del Tejido Nervioso , Transducción de Señal , Uniones Estrechas , Animales , Lipopolisacáridos/toxicidad , Ratones , Transducción de Señal/efectos de los fármacos , Proteínas del Tejido Nervioso/metabolismo , Inflamación/metabolismo , Inflamación/inducido químicamente , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Masculino , Receptores de Superficie Celular/metabolismo , Receptores Inmunológicos/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Intestinos/efectos de los fármacos , Intestinos/patología , Modelos Animales de Enfermedad , Inflamasomas/metabolismo
10.
Biomed Mater Eng ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38995766

RESUMEN

BACKGROUND: Numerous studies have confirmed that stimulating the mid-brain motor nuclei can regulate movement forcibly for robo-pigeons, but research on behavior modulation using non-motor nuclei is scarce. OBJECTIVE: In this study, we constructed a spatial preference behavior by stimulating the stratum griseum periventriculare (SGP), a nucleus correlated with fear and escape, for robo-pigeons. METHODS: The study was carried out in a square-enclosed experimental field, with a designated box serving as the 'safe' area for the robo-pigeons. If the robo-pigeon exits this area, the SGP will be stimulated. After a brief training period, the robo-pigeons will have a clear spatial preference for the box. RESULTS: The result from five pigeons has shown that, after simple training, the animals develop a spatial preference for the box. They can quickly return to the box in any situation when the SGP is stimulated, with a success rate exceeding 80% (89.0 ± 6.5%). Moreover, this behavior is highly stable and remains consistent, unaffected by changes in the location of the box or the interference box. CONCLUSION: The results prove that using the electrical stimulus could enable animals to accomplish more complex tasks. It may offer a novel approach to regulating pigeon behavior and further advance the study of cyborg animals.

11.
Curr Biol ; 34(5): 980-996.e6, 2024 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-38350446

RESUMEN

Tissue-intrinsic error correction enables epithelial cells to detect abnormal neighboring cells and facilitate their removal from the tissue. One of these pathways, "interface surveillance," is triggered by cells with aberrant developmental and cell-fate-patterning pathways. It remains unknown which molecular mechanisms provide cells with the ability to compare fate between neighboring cells. We demonstrate that Drosophila imaginal discs express an array of cell surface molecules previously implicated in neuronal axon guidance processes. They include members of the Robo, Teneurin, Ephrin, Toll-like, or atypical cadherin families. Importantly, a mismatch in expression levels of these cell surface molecules between adjacent cells is sufficient to induce interface surveillance, indicating that differences in expression levels between neighboring cells, rather than their absolute expression levels, are crucial. Specifically, a mismatch in Robo2 and Robo3, but not Robo1, induces enrichment of actin, myosin II, and Ena/Vasp, as well as activation of JNK and apoptosis at clonal interfaces. Moreover, Robo2 can induce interface surveillance independently of its cytosolic domain and without the need for the Robo-ligand Slit. The expression of Robo2 and other cell surface molecules, such as Teneurins or the Ephrin receptor is regulated by fate-patterning pathways intrinsic and extrinsic to the wing disc, as well as by expression of oncogenic RasV12. Combined, we demonstrate that neighboring cells respond to a mismatch in surface code patterns mediated by specific transmembrane proteins and reveal a novel function for these cell surface proteins in cell fate recognition and removal of aberrant cells during development and homeostasis of epithelial tissues.


Asunto(s)
Proteínas de Drosophila , Receptores Inmunológicos , Humanos , Animales , Receptores Inmunológicos/metabolismo , Proteínas Roundabout , Drosophila/fisiología , Axones/fisiología , Proteínas de Drosophila/metabolismo , Efrinas/metabolismo
12.
Elife ; 132024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38591541

RESUMEN

Collective cell migration is fundamental for the development of organisms and in the adult for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact inhibition of locomotion (CIL), a local repulsive force, can propel the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell (SC) collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin is required to present the repulsive Slit2/Slit3 signal at the cell surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, nonmigratory cell clusters. Moreover, analysis of ex vivo explants from mice following sciatic nerve injury showed that inhibition of Slit2 decreased SC collective migration and increased clustering of SCs within the nerve bridge. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.


Asunto(s)
Cadherinas , Movimiento Celular , Inhibición de Contacto , Péptidos y Proteínas de Señalización Intercelular , Proteínas de la Membrana , Regeneración Nerviosa , Proteínas del Tejido Nervioso , Células de Schwann , Células de Schwann/metabolismo , Células de Schwann/fisiología , Animales , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Ratones , Cadherinas/metabolismo , Cadherinas/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Regeneración Nerviosa/fisiología , Locomoción/fisiología , Adhesión Celular , Transducción de Señal
13.
Ibrain ; 9(4): 369-380, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38680506

RESUMEN

The neural network hypothesis is one of the important pathogenesis of drug-resistant epilepsy. Axons guide molecules through synaptic remodeling and brain tissue remodeling, which may result in the formation of abnormal neural networks. Therefore, axon guidance plays a crucial role in disease progression. However, although Robo1 is one of the important components of axon guidance, the role of Robo1 in epilepsy remains unclear. In this study, we aimed to explore the mechanism of Robo1 in epilepsy. Male adult C57BL/6 mice were intraperitoneally injected with pentylenetetrazol to establish an epilepsy model. Lentivirus (LV) was given via intracranial injection 2 weeks before pentylenetetrazol injection. Different expressions of Robo1 between the control group, LV-mediated Robo1 short hairpin RNA group, empty vector control LV group, and normal saline group were analyzed using Western blot, immunofluorescence staining, Golgi staining, and video monitoring. Robo1 was increased in the hippocampus in the pentylenetetrazol-induced epilepsy mouse model; lentiviral Robo1 knockdown prolonged the latency of seizure and reduced the seizure grade in mice and resulted in a decrease in dendritic spine density, while the number of mature dendritic spines was maintained. We speculate that Robo1 has been implicated in the development and progression of epilepsy through its effects on dendritic spine morphology and density. Epileptic mice with Robo1 knockdown virus intervention had lower seizure grade and longer latency. Follow-up findings suggest that Robo1 may modulate seizures by affecting dendritic spine density and morphology. Downregulation of Robo1 may negatively regulate epileptogenesis by decreasing the density of dendritic spines and maintaining a greater number of mature dendritic spines.

14.
Rev. crim ; 65(1): 121-137, 2023. ilus, mapas
Artículo en Inglés | LILACS | ID: biblio-1428546

RESUMEN

The COVID-19 contingency gave rise to multiple social interactions for which neither governments nor citizens were prepared. The restrictive measures on mobility imposed by the National Government produced a series of changes not only in social dynamics and legal transactions, but also in the criminal context. The purpose of this study is to understand the space-time behavior of theft in the metropolitan area of Pereira, Colombia, and to compare this behavior observed under normal conditions and in times of pandemic. Data were obtained by consulting the Siedco application for the city studied in the 2019-2021 time window. The spatial analysis was performed using the technique known as pattern identification for space-time event networks (Ipree). The empirical evidence observed allows us to conclude that there is a space-time configuration that defines the dynamics of thefts in the city of Pereira and these patterns can be explained from the theory of environmental munificence for crime.


La contingencia provocada por el COVID-19 dio lugar a múltiples interacciones sociales, para las cuales no estaba preparado ni los gobiernos, ni la ciudadanía. Las medidas restrictivas a la movilidad impuestas por el Gobierno Nacional, produjeron una serie de cambios no solo en las dinámicas sociales y en las transacciones legales, sino también en el contexto criminal. El objetivo de este estudio es entender el comportamiento espacio-temporal del hurto en el área metropolitana de Pereira, Colombia, y comparar este comportamiento en tiempos normales y en tiempos de pandemia. Se obtuvieron los datos por medio de la consulta del aplicativo Siedco para la ciudad estudiada en la ventana temporal 2019-2021. El análisis espacial se realizó utilizando la técnica conocida como "identificación de patrones para redes de eventos espaciotemporales (Ipree)." La evidencia empírica observada permite concluir que existe una configuración espaciotemporal que define la dinámica de los hurtos en la ciudad de Pereira y estos patrones se pueden explicar desde la teoría de los entornos generosos del crimen.


A contingência provocada pela COVID-19 deu origem a múltiplas interações sociais para as quais nem os governos nem os cidadãos estavam preparados. As medidas restritivas de mobilidade impostas pelo governo nacional produziram uma série de mudanças não apenas na dinâmica social e nas transações legais, mas também no contexto criminal. O objetivo deste estudo é compreen-der o comportamento espaço-temporal do roubo na área metropolitana de Pereira, Colômbia, e comparar este comportamento em tempos normais e em tempos de pandemia. Os dados foram obtidos consultando a aplicação Siedco para a cidade estudada na janela de tempo 2019-2021. A análise espacial foi realizada utilizando a técnica conhecida como "identificação de padrões para redes de eventos espaço-temporais (Ipree)." As evidências empíricas observadas nos permitem concluir que existe uma configuração espaço-temporal que define a dinâmica do roubo na cidade de Pereira e estes padrões podem ser explicados a partir da teoria dos ambientes de crime generoso.


Asunto(s)
Humanos , Robo , Análisis Espacial , Análisis Espacio-Temporal , Colombia , Crimen , Criminales , Pandemias , COVID-19
15.
BioSCI. (Curitiba, Online) ; 81(1): 37-43, 2023.
Artículo en Portugués | LILACS | ID: biblio-1442614

RESUMEN

Introdução: As operações laparoscópicas, assistidas por robô e a abertas são técnicas cirúrgicas comumente utilizadas na vida diária. A viabilidade e os resultados em curto e longo prazos dos procedimentos laparoscópicos e robóticos têm sido amplamente relatados. Objetivos: Comparar os dados clínicos e oncológicos da cirurgia assistida por robô e laparoscópica no câncer retal. Métodos: Foram pesquisados o Pubmed/Medline, Embase, e Cochrane Library para artigos relevantes publicados até 2021. Estudos baseados na comparabilidade entre operação assistida por robô e laparoscópica para câncer retal foram designados. Os parâmetros analisados incluíram tempo operatório, conversão para procedimento aberto, perda estimada de sangue, tempo de recuperação da função intestinal, tempo de internação, vazamento da anastomose e complicações pós-operatórias. Resultados: Operação assistida por robô foi associada com maior tempo operatório (342 vs.192 min na cirurgia laparoscópica, p<0,001), menor conversão para procedimento aberto, menor tempo de internação hospitalar e recuperação mais rápida da função intestinal, menores complicações pós-operatórias de forma significativa (p=0,041). A perda estimada de sangue, a taxa de vazamento da anastomose e os resultados oncológicos, incluindo o número de linfonodos extraídos, não mostraram diferenças significativas entre os grupos. Conclusão: A cirurgia assistida por robô para câncer retal mostrou maior tempo operatório, menor conversão, taxas de recuperação da função intestinal mais rápidas e menor permanência no hospital. Seus resultados oncológicos forram semelhantes à cirurgia laparoscópica.


Introduction: Laparoscopic surgery, robot-assisted surgery and open surgery are the most commonly used surgical techniques in daily living. The feasibility and short- and long-term results of laparoscopic and robotic procedures have been widely reported. Objectives: To compare the clinical and oncological results of robot-assisted and laparoscopic surgery for rectal cancer. Methods: PubMed/Medline, Embase, The Cochrane Library were searched for relevant articles published until 2021. Studies based on comparability between robot-assisted and laparoscopic surgery for rectal cancer were designed. The parameters analyzed included operative time, conversion to open surgery, estimated blood loss, bowel function recovery time, length of hospital stay, anastomosis leak, and postoperative complications. Results: The robot-assisted surgery group was associated with longer operative time (342 vs. 192 min in laparoscopic surgery,p <0.001), lower conversion to open surgery, shorter length of hospital stay, faster bowel function recovery and lower postoperative complications significantly (p=0.041). Estimated blood loss, anastomosis leak rate, and oncological outcomes including the number of lymph nodes extracted showed no significant differences between groups. Conclusion: Robot-assisted surgery for rectal cancer showed longer operative time, lower conversion, faster bowel function recovery rates, shorter hospital stay, and similar oncological outcomes compared to laparoscopic surgery.


Asunto(s)
Humanos , Procedimientos Quirúrgicos Robotizados , Recto
16.
Estilos clín ; 26(3)2021.
Artículo en Portugués | LILACS, Index Psi Revistas Técnico-Científicas | ID: biblio-1438347

RESUMEN

Esta proposta, a partir da clínica psicanalítica, demonstra como o uso do robô, enquanto objeto tecnológico, poderá permitir à criança autista, no tratamento, maior interação e laço com o Outro. Faz-se uma aposta de que as intervenções mediadas pelo robô podem proporcionar um semblante das operações constitutivas do sujeito que não se realizaram. Considerando que os componentes da borda autística possibilitam ao sujeito enlaçar-se no meio social, destacam-se as possibilidades de "alargamento" dessa borda autística a partir de intervenções qualificadas como objeto. Assim, o uso do robô nas sessões torna as intervenções menos invasivas à criança, permitindo certa regulação pulsional, favorecendo um caminho privilegiado de comunicação e intervenção, e produzindo maior interação social


Nuestra propuesta en este artículo es demostrar, desde la clínica psicoanalítica, cómo el uso del robot, como objeto tecnológico, puede permitir al niño autista, en el tratamiento, una mayor interacción y lazo con el Otro. Apostamos a que las intervenciones mediadas por el robot pueden proporcionar un semblante de las operaciones constitutivas del sujeto que no se hicieron realidad.Considerando que los componentes del borde autístico le permiten al sujeto vincularse en el entorno social, se destacan las posibilidades de «dilatar¼ este borde autístico desde intervenciones calificadas con objeto. Así, el uso del robot en las sesiones hace con que las intervenciones sean menos invasivas para el niño, permitiendo una cierta regulación pulsional, favoreciendo un camino privilegiado de comunicación e intervención, produciendo una mayor interacción social


Our proposal, from the psychoanalytic clinic, is to demonstrate how the use of the robot, as a technological object, may allow the autistic child, in the treatment, greater interaction and bond with the Other. We place a bet that interventions mediated by the robot can provide a semblance of the subject's constitutive operations that have not taken place. Considering that the components of the autistic border allow the subject to bond in the social environment, the possibilities of 'widening' this autistic border are highlighted from qualified interventions with object. Thus, the use of the robot in the sessions makes the interventions less invasive to the child, allowing a certain drive regulation, favoring a privileged path of communication and intervention, producing greater social interaction


Notre proposition, à partir de la clinique psychanalytique, c'est de démontrer comme l'utilisation du robot, en tant qu'objet technologique, pourra permettre à l'enfant autiste, dans le traitement, des plus grands interaction et lien avec l'Autre. On parie que les interventions facilitées par le robot peuvent promouvoir un semblant des opérations constitutives du sujet qui n'ont pas été réalisées. En considérant que les composants de la borde autistique permettent au sujet de se lier au milieu social, on distingue les possibilités d''élargissement' de cette borde autistique à partir des interventions qualifiées avec objet. Ainsi, l'utilisation du robot dans les sessions rendent les interventions moins invasives pour l'enfant, en permettant une certaine régulation pulsionnelle qui favorise un chemin privilégié de communication et intervention, en ayant comme résultat une plus grande interaction sociale


Asunto(s)
Terapia Psicoanalítica , Trastorno Autístico/psicología , Robótica , Inconsciente en Psicología , Terapias Complementarias
17.
Rev. bras. anestesiol ; 70(6): 573-582, Nov.-Dec. 2020. tab, graf
Artículo en Inglés, Portugués | LILACS | ID: biblio-1155780

RESUMEN

Abstract Background: The present study investigated the association between Postoperative Cognitive Dysfunction (POCD) and increased serum S100B level after Robotic-Assisted Laparoscopic Radical Prostatectomy (RALRP). Methods: The study included 82 consecutive patients who underwent RALRP. Serum S100B levels were determined preoperatively, after anesthesia induction, and at 30 minutes and 24 hours postoperatively. Cognitive function was assessed using neuropsychological testing preoperatively, and at 7 days and 3 months postoperatively. Results: Twenty four patients (29%) exhibited POCD 7 days after surgery, and 9 (11%) at 3 months after surgery. Serum S100B levels were significantly increased at postoperative 30 minutes and 24 hours in patients displaying POCD at postoperative 7 days (p = 0.0001 for both) and 3 months (p = 0.001 for both) compared to patients without POCD. Duration of anesthesia was also significantly longer in patients with POCD at 7 days and 3 months after surgery compared with patients without POCD (p = 0.012, p = 0.001, respectively), as was duration of Trendelenburg (p = 0.025, p = 0.002, respectively). Composite Z score in tests performed on day 7 were significantly correlated with duration of Trendelenburg and duration of anesthesia (p = 0.0001 for both). Conclusions: S100B increases after RALRP and this increase is associated with POCD development. Duration of Trendelenburg position and anesthesia contribute to the development of POCD. Trial Registry Number: Clinicaltrials.gov (N° NCT03018522).


Resumo Introdução: O presente estudo investigou a associação entre Disfunção Cognitiva Pós-Operatória (DCPO) e aumento do nível sérico de S100B após Prostatectomia Radical Laparoscópica Assistida por Robô (PRLAR). Métodos: O estudo incluiu 82 pacientes consecutivos submetidos à PRLAR. Os níveis séricos de S100B foram determinados: no pré-operatório, após indução anestésica, e aos 30 minutos e 24 horas do pós-operatório. A função cognitiva foi avaliada com testes neuropsicológicos no pré-operatório, no 7° dia pós-operatório (7 DPO) e aos 3 meses após a cirurgia (3 MPO). Resultados: Observamos 24 pacientes (29%) com DCPO no 7 DPO e 9 pacientes com DCPO (11%) após 3 meses da cirurgia. Quando comparados com os pacientes sem DCPO, os níveis séricos de S100B estavam significantemente aumentados aos 30 minutos e às 24 horas do pós-operatório nos pacientes que apresentaram DCPO no 7 DPO (p= 0,0001 para os dois momentos) e 3 meses após a cirurgia (p= 0,001 para os dois momentos) A duração anestésica também foi significantemente maior em pacientes com DCPO no 7 DPO e 3 MPO em comparação com pacientes sem DCPO (p= 0,012, p= 0,001, respectivamente), assim como a duração da posição de Trendelenburg (p= 0,025, p= 0,002, respectivamente). O escore Z composto nos testes realizados no 7 DPO foi significantemente correlacionado com a duração da posição de Trendelenburg e a duração da anestesia (p= 0,0001 para ambos). Conclusão: S100B aumenta após PRLAR e o aumento está associado ao desenvolvimento de DCPO. A duração anestésica e o tempo decorrido em posição de Trendelenburg contribuem para o desenvolvimento de DCPO. Número de registro do estudo: Clinicaltrials.gov (n° NCT03018522)


Asunto(s)
Humanos , Masculino , Anciano , Complicaciones Posoperatorias/sangre , Prostatectomía/efectos adversos , Disfunción Cognitiva/sangre , Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Procedimientos Quirúrgicos Robotizados/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Prostatectomía/métodos , Factores de Tiempo , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios Prospectivos , Sensibilidad y Especificidad , Inclinación de Cabeza/efectos adversos , Área Bajo la Curva , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Tempo Operativo , Procedimientos Quirúrgicos Robotizados/métodos , Anestesia General/efectos adversos , Anestesia General/estadística & datos numéricos , Persona de Mediana Edad , Pruebas Neuropsicológicas
18.
Rev. crim ; 62(3): 25-38, sep.-dic. 2020. tab
Artículo en Español | LILACS | ID: biblio-1144418

RESUMEN

Resumen Perú no solo tiene una de las mayores tasas de victimización en Latinoamérica (24%), sino también la menor en delitos denunciados (15%) (Latinobarómetro, 2016). En este trabajo, el objetivo fue identificar las características del crimen y las características individuales que predicen la decisión de denunciar cuatro delitos patrimoniales distintos (robo de hogares, de auto, de autopartes y de moto). Para ello, se emplearon siete años de una encuesta de hogares a nivel nacional en Perú (2010-2016). Las estimaciones se realizaron mediante regresión logística multinivel de efectos mixtos a fin de controlar las características del ambiente que también influyen en la decisión de denuncia. El uso de arma de parte del delincuente es el factor que eleva en mayor proporción la probabilidad de denunciar cualquiera de los cuatro delitos evaluados. La victimización reiterada es también un predictor importante, aunque para menos delitos. La confianza en la policía no está asociada a la decisión de denunciar. Este estudio es el primero que analiza cuantitativamente los factores que afectan la decisión de denunciar en el Perú. Sus resultados son útiles para un mejor entendimiento de la baja tasa de denuncias en el país.


Abstract Peru has not only one of the highest victimization rates in Latin America (24%), but also the lowest rate of reported crimes (15%) (Latinobarometro, 2016) The purpose of this study was to identify the characteristics of the crimes and the characteristics of the individuals that predict the decision of reporting four different property crimes (burglary, auto theft, auto parts theft, and motorcycle theft). To this end, a seven-year survey of households at the national level in Peru was used (2010-2016). The estimations were made using multilevel mixed effects logistics regression, in order to control for characteristics of the environment that also influence the decision to report. Use of a weapon by the criminal is the factor that most increases the probability of reporting any of the four assessed crimes. Repeated victimization is also an important predictor, although for a lower number of crimes. Trust in the police is not associated to the decision to report. This is the first study to quantitatively analyze the factors that affect the decision to report in Peru. Its results are useful for a better understanding of the low reporting rates in the country.


Resumo O Peru não apenas tem uma das taxas mais altas de vitimização em América Latina (24%), mas também a mais baixa em crimes denunciados (15%) (Latinobarómetro, 2016). Neste trabalho, o objetivo foi identificar as características do crime e as características individuais que predizem a decisão de denunciar quatro diferentes crimes patrimoniais (furto de casa, carro, autopeças e motocicleta). Para isso, foram utilizados sete anos de dados de uma pesquisa domiciliar nacional no Peru (2010-2016). As estimativas foram feitas usando regressão logística multinível de efeitos mistos a fim de controlar as características ambientais que também influenciam na decisão de denunciar. O uso de arma de fogo pelo delinquente é o fator que aumenta em maior proporção a probabilidade de denúncia de qualquer um dos quatro crimes avaliados. A vitimização repetida também é um indicador importante, embora para menos crimes. A confiança na polícia não está associada à decisão de denunciar. Este estudo é o primeiro a analisar quantitativamente os fatores que afetam a decisão de denunciar no Peru. Seus resultados são úteis para um melhor entendimento da taxa baixa de denúncias no país.


Asunto(s)
Humanos , Robo , Víctimas de Crimen , Armas , Criminales
19.
Rev. urug. cardiol ; 34(2): 178-188, ago. 2019. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1014551

RESUMEN

Resumen: Las fístulas coronarias son una comunicación anómala directa entre las arterias coronarias y las cavidades cardíacas o alguno de los vasos sanguíneos próximos al corazón. Son poco comunes, con una incidencia angiográfica entre 0,1%-2%. Dependiendo de la magnitud de robo coronario, pueden ser asintomáticas o causar cuadros clínicos graves con alta repercusión funcional, como isquemia miocárdica, insuficiencia cardíaca congestiva, endocarditis, infecciones recurrentes del aparato respiratorio o en casos raros hipertensión pulmonar. Se presenta el caso de una paciente con fístulas coronarias que ocasionaron isquemia miocárdica por robo de flujo coronario con importante repercusión clínica y hemodinámica. El diagnóstico definitivo se llevó a cabo mediante intervencionismo coronario percutáneo y dadas las características anatómicas de las fístulas, se determinó tratamiento médico.


Summary: Coronary fistulas are an anomalous direct communication between the coronary arteries and one of the four cardiac cavities or one of the blood vessels near the heart, are uncommon with an angiographic incidence between 0.1% - 2%, and, depending of the magnitude of coronary steal, they may be asymptomatic or cause severe clinical symptoms with high functional repercussion, such as myocardial ischemia, congestive heart failure, endocarditis, recurrent respiratory infections or, in rare cases, pulmonary hypertension. We present a case of a female patient with coronary fistulas that caused myocardial ischemia due to coronary flow steal with important clinical and hemodynamic repercussions. The definitive diagnosis was made through percutaneous coronary intervention and given the anatomical characteristics of the fistulas, medical treatment was determined.


Resumo: As fístulas coronarianas são uma comunicação anômala direta entre as artérias coronárias e uma das quatro cavidades cardíacas ou um dos vasos sanguíneos próximos ao coração; são incomuns com uma incidência angiográfica entre 0,1% - 2% e, dependendo da magnitude do roubo coronariano, podem ser assintomáticos ou causar sintomas clínicos graves, com alta repercussão funcional, como isquemia miocárdica, insuficiência cardíaca congestiva, endocardite, infecções respiratórias de repetição ou, em raros casos, hipertensão pulmonar. Apresentamos um caso de uma paciente com fístulas coronarianas que causaram isquemia miocárdica por roubo de fluxo coronariano com importante repercussão clínica e hemodinâmica. O diagnóstico definitivo foi feito por meio de intervenção coronariana percutânea e, dadas as características anatômicas das fístulas, foi determinado tratamento médico.

20.
Rev. crim ; 60(2): 89-105, mayo-ago. 2018. tab, graf
Artículo en Español | LILACS | ID: biblio-990977

RESUMEN

Resumen Este artículo tiene como objetivos: i) describir las rutas de circulación de computadoras portátiles robadas en cuatro mercados del centro de Lima, ii) analizar los factores que inciden en la transformación de precio de las computadoras portátiles robadas, iii) determinar el carácter legal de los mercados en los que se comercializan estos objetos y iv) analizar la importancia del comercio de computadoras en la economía de los vendedores finales. Se ha recolectado información a través de entrevistas a vendedores, compradores y ladrones; a través de observaciones en terreno; y a través del método de informante-actor (asistiendo a los mercados para consultar precios de objetos robados). Los resultados muestran un circuito de fases concatenadas para la circulación de los objetos robados, donde a la fase inicial de la obtención (robo), le siguen las fases de acopio, acondicionamiento y venta final. El estudio muestra la importancia de la oferta final, realizada enmercados legales. Se trata de mercados autorizados para la venta de objetos de procedencia lícita en donde se insertan objetos robados, dada la alta precariedad y permeabilidad de los controles.


Abstract This document has stated as objectives: i) to describe the circulation paths of stolen laptops in four markets in Lima downtown; ii) to analyze the factors that influence in the price transformation of the stolen laptops; iii) to determine the legal character of the markets where these goods are traded; and iv) to analyze the importance of computers trade in the economy of the final sellers. The information has been collected by interviewing sellers, buyers and thieves, also through field observations and informant-actor method (visiting markets for asking prices of stolen goods). The results show a route of phases linked for the stolen objects circulation. The initial phase of the obtainment process (theft) is followed by the phases of storing, conditioning and final sale. This study presents the importance of the final offer carried out in legal markets, which are authorized markets for selling goods from licit sources, but stolen objects are placed there, because of the high precariousness and permeability of the controls.


Resumo Este artigo tem como objetivos: i) descrever as rotas de circulação de computadores portáteis roubados em quatro mercados do centro de Lima; ii) analisar os fatores que incidem na transformação do preço dos computadores portáteis roubados; iii) determinar o caráter legal dos mercados em que são comercializados esses objetos e; iv) analisar a importância do comercio de computadores na economia dos vendedores finais. Coletou-se informação por meio de entrevistas com os vendedores, compradores e ladrões, da observação do terreno e da metodologia informante-ator (comparecimento aos mercados, para consulta de preços dos objetos roubados). Os resultados mostram um conjunto de fases concatenadas para a circulação dos objetos roubados, no qual a fase inicial é a obtenção (roubo), seguida pelas fases de recolhida, acondicionamento e venda final. O estudo apresenta a importância da oferta final realizada em "mercados legais". Trata-se de mercados autorizados para a venda de objetos de procedência lícita, onde são inseridos objetos roubados, dadas a alta precariedade e a permeabilidade dos controles.


Asunto(s)
Ciencias Sociales , Perú , Robo , Estudio Comparativo
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