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1.
Proc Natl Acad Sci U S A ; 120(45): e2309910120, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37903274

RESUMEN

Pontocerebellar hypoplasia (PCH) is a group of rare neurodevelopmental disorders with limited diagnostic and therapeutic options. Mutations in WDR11, a subunit of the FAM91A1 complex, have been found in patients with PCH-like symptoms; however, definitive evidence that the mutations are causal is still lacking. Here, we show that depletion of FAM91A1 results in developmental defects in zebrafish similar to that of TBC1D23, an established PCH gene. FAM91A1 and TBC1D23 directly interact with each other and cooperate to regulate endosome-to-Golgi trafficking of KIAA0319L, a protein known to regulate axonal growth. Crystal structure of the FAM91A1-TBC1D23 complex reveals that TBC1D23 binds to a conserved surface on FAM91A1 by assuming a Z-shaped conformation. More importantly, the interaction between FAM91A1 and TBC1D23 can be used to predict the risk of certain TBC1D23-associated mutations to PCH. Collectively, our study provides a molecular basis for the interaction between TBC1D23 and FAM91A1 and suggests that disrupted endosomal trafficking underlies multiple PCH subtypes.


Asunto(s)
Enfermedades Cerebelosas , Pez Cebra , Animales , Humanos , Enfermedades Cerebelosas/genética , Variación Genética , Aparato de Golgi , Pez Cebra/genética
2.
Proc Natl Acad Sci U S A ; 120(22): e2301725120, 2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37216550

RESUMEN

Understanding of the evolution of metazoans from their unicellular ancestors is a fundamental question in biology. In contrast to fungi which utilize the Mon1-Ccz1 dimeric complex to activate the small GTPase RAB7A, metazoans rely on the Mon1-Ccz1-RMC1 trimeric complex. Here, we report a near-atomic resolution cryogenic-electron microscopy structure of the Drosophila Mon1-Ccz1-RMC1 complex. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1 on the surface opposite to the RAB7A-binding site, with many of the RMC1-contacting residues from Mon1 and Ccz1 unique to metazoans, explaining the binding specificity. Significantly, the assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions and organismal development in zebrafish. Our studies offer a molecular explanation for the different degree of subunit conservation across species, and provide an excellent example of how metazoan-specific proteins take over existing functions in unicellular organisms.


Asunto(s)
Proteínas de Drosophila , Proteínas de Unión al GTP rab , Animales , Microscopía por Crioelectrón , Proteínas de Unión al GTP rab/metabolismo , Pez Cebra/metabolismo , Drosophila , Proteínas de Drosophila/ultraestructura
3.
Mol Psychiatry ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830974

RESUMEN

Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.

4.
Cereb Cortex ; 34(2)2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38342683

RESUMEN

Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.


Asunto(s)
Epilepsia , Muerte Súbita e Inesperada en la Epilepsia , Humanos , Estudios Retrospectivos , Epilepsia/diagnóstico por imagen , Electroencefalografía/métodos , Convulsiones , Muerte Súbita
5.
Cereb Cortex ; 34(3)2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38521993

RESUMEN

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Red en Modo Predeterminado , Disfunción Cognitiva/patología , Giro del Cíngulo , Lóbulo Temporal/patología , Imagen por Resonancia Magnética , Encéfalo , Mapeo Encefálico
6.
Anal Biochem ; 691: 115534, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38621605

RESUMEN

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.


Asunto(s)
Medicamentos Herbarios Chinos , Hepatopatías Alcohólicas , Simulación del Acoplamiento Molecular , Farmacología en Red , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Animales , Ratones , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Comprimidos , Ciclooxigenasa 2/metabolismo , Ratones Endogámicos C57BL , Cromatografía Líquida de Alta Presión , Hígado/metabolismo , Hígado/efectos de los fármacos
7.
Psychol Med ; : 1-12, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38433595

RESUMEN

BACKGROUND: Mild cognitive deficits (MCD) emerge before the first episode of psychosis (FEP) and persist in the clinical high-risk (CHR) stage. This study aims to refine risk prediction by developing MCD models optimized for specific early psychosis stages and target populations. METHODS: A comprehensive neuropsychological battery assessed 1059 individuals with FEP, 794 CHR, and 774 matched healthy controls (HCs). CHR subjects, followed up for 2 years, were categorized into converters (CHR-C) and non-converters (CHR-NC). The MATRICS Consensus Cognitive Battery standardized neurocognitive tests were employed. RESULTS: Both the CHR and FEP groups exhibited significantly poorer performance compared to the HC group across all neurocognitive tests (all p < 0.001). The CHR-C group demonstrated poorer performance compared to the CHR-NC group on three sub-tests: visuospatial memory (p < 0.001), mazes (p = 0.005), and symbol coding (p = 0.023) tests. Upon adjusting for sex and age, the performance of the MCD model was excellent in differentiating FEP from HC, as evidenced by an Area Under the Receiver Operating Characteristic Curve (AUC) of 0.895 (p < 0.001). However, when applied in the CHR group for predicting CHR-C (AUC = 0.581, p = 0.008), the performance was not satisfactory. To optimize the efficiency of psychotic risk assessment, three distinct MCD models were developed to distinguish FEP from HC, predict CHR-C from CHR-NC, and identify CHR from HC, achieving accuracies of 89.3%, 65.6%, and 80.2%, respectively. CONCLUSIONS: The MCD exhibits variations in domains, patterns, and weights across different stages of early psychosis and diverse target populations. Emphasizing precise risk assessment, our findings highlight the importance of tailored MCD models for different stages and risk levels.

8.
Cereb Cortex ; 33(7): 3562-3574, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-35945683

RESUMEN

Quantitative magnetic resonance (MR) has been used to study cyto- and myelo-architecture of the human brain non-invasively. However, analyzing brain cortex using high-resolution quantitative MR acquisition can be challenging to perform using 3T clinical scanners. MR fingerprinting (MRF) is a highly efficient and clinically feasible quantitative MR technique that simultaneously provides T1 and T2 relaxation maps. Using 3D MRF from 40 healthy subjects (mean age = 25.6 ± 4.3 years) scanned on 3T magnetic resonance imaging, we generated whole-brain gyral-based normative MR relaxation atlases and investigated cortical-region-based T1 and T2 variations. Gender and age dependency of T1 and T2 variations were additionally analyzed. The coefficient of variation of T1 and T2 for each cortical-region was 3.5% and 7.3%, respectively, supporting low variability of MRF measurements across subjects. Significant differences in T1 and T2 were identified among 34 brain regions (P < 0.001), lower in the precentral, postcentral, paracentral lobule, transverse temporal, lateral occipital, and cingulate areas, which contain sensorimotor, auditory, visual, and limbic functions. Significant correlations were identified between age and T1 and T2 values. This study established whole-brain MRF T1 and T2 atlases of healthy subjects using a clinical 3T scanner, which can provide a quantitative and region-specific baseline for future brain studies and pathology detection.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Humanos , Adulto Joven , Adulto , Lactante , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Fantasmas de Imagen , Voluntarios Sanos , Procesamiento de Imagen Asistido por Computador/métodos
9.
Dev Psychobiol ; 66(5): e22498, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38698634

RESUMEN

The current study examined the characteristics of physiological synchrony between grandmothers and grandchildren in Chinese three-generation families, and the associations between physiological synchrony and child emotion regulation. The participants included 92 children (age 8-10-year old) and their grandmothers. Respiratory sinus arrhythmia (RSA) was collected from both grandmothers and their grandchildren throughout a collaborative drawing task and a conflict discussion task. Child emotion regulation was measured using the Children's Emotional Management Scale. We found no evidence for an overall pattern of concordant or discordant synchrony within dyads. Instead, there was great variability in patterns of synchrony across dyads. During the collaborative drawing task, concordance in grandmother's RSA and grandchildren's subsequent RSA was linked with better emotion regulation. During the conflict discussion, concordance in grandmother's RSA and grandchildren's simultaneous RSA was linked with poorer emotion regulation. These results suggest that grandmother-grandchild synchrony in different directions, time lags, and contexts has different influences on children's emotion regulation. The findings of this study highlight the importance of contextual physiological co-regulation between Chinese children and their grandmothers for children's social-emotional development.


Asunto(s)
Regulación Emocional , Abuelos , Arritmia Sinusal Respiratoria , Humanos , Arritmia Sinusal Respiratoria/fisiología , Femenino , Niño , Masculino , Regulación Emocional/fisiología , China , Relaciones Intergeneracionales , Persona de Mediana Edad , Adulto , Anciano , Pueblos del Este de Asia
10.
Eur J Clin Invest ; 53(10): e14040, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37337313

RESUMEN

BACKGROUND: Hypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK-mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion. METHODS: One hundred and ninety-two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high-speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin-eosin and TUNEL. The expressions of GRP78, p-perk, p-eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion. RESULTS: The number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p < .05). The GRP78 expression in the hypothermia group was statistically higher (p < .05) than in the ischaemia/reperfusion group. Optical densities of p-perk, p-eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p < .05). The CHOP expression in the hypothermia group was statistically lower (p < .05) than in the ischaemia/reperfusion group. CONCLUSION: Mild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p-PERK, p-eIF2α, ATF4 and CHOP.


Asunto(s)
Isquemia Encefálica , Hipotermia , Daño por Reperfusión , Animales , Masculino , Ratones , Apoptosis , Infarto Cerebral , Chaperón BiP del Retículo Endoplásmico , Ratones Endogámicos C57BL , Reperfusión , Daño por Reperfusión/metabolismo
11.
Psychol Med ; 53(7): 2868-2877, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-34991756

RESUMEN

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.


Asunto(s)
Esquizofrenia , Sustancia Blanca , Humanos , Sustancia Blanca/patología , Cuerpo Calloso/patología , Imagen de Difusión Tensora , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Esquizofrenia/patología , Herencia Multifactorial , Anisotropía , Encéfalo
12.
Epilepsia ; 64(2): 430-442, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36507762

RESUMEN

OBJECTIVE: We aim to quantify whole-brain tissue-property changes in patients with magnetic resonance imaging (MRI)-negative pharmacoresistant focal epilepsy by three-dimensional (3D) magnetic resonance fingerprinting (MRF). METHODS: We included 30 patients with pharmacoresistant focal epilepsy and negative MRI by official radiology report, as well as 40 age- and gender-matched healthy controls (HCs). MRF scans were obtained with 1 mm3 isotropic resolution. Quantitative T1 and T2 relaxometry maps were reconstructed from MRF and registered to the Montreal Neurological Institute (MNI) space. A two-sample t test was performed in Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) to evaluate significant abnormalities in patients comparing to HCs, with correction by the threshold-free cluster enhancement (TFCE) method. Subgroups analyses were performed for extra-temporal epilepsy/temporal epilepsy (ETLE/TLE), and for those with/without subtle abnormalities detected by morphometric analysis program (MAP), to investigate each subgroup's pattern of MRF changes. Correlation analyses were performed between the mean MRF values in each significant cluster and seizure-related clinical variables. RESULTS: Compared to HCs, patients exhibited significant group-level T1 increase ipsilateral to the epileptic origin, in the mesial temporal gray matter (GM) and white matter (WM), temporal pole GM, orbitofrontal GM, hippocampus, and amygdala, with scattered clusters in the neocortical temporal and insular GM. No significant T2 changes were detected. The ETLE subgroup showed a T1-increase pattern similar to the overall cohort, with additional involvement of the ipsilateral anterior cingulate GM. The subgroup of MAP+ patients also showed a T1-increase pattern similar to the overall cohort, with additional cluster in the ipsilateral lateral orbitofrontal GM. Higher T1 was associated with younger seizure-onset age, longer epilepsy duration, and higher seizure frequency. SIGNIFICANCE: MRF revealed group-level T1 increase in limbic/paralimbic structures ipsilateral to the epileptic origin, in patients with pharmacoresistant focal epilepsy and no apparent lesions on MRI, suggesting that these regions may be commonly affected by seizures in the epileptic brain. The significant association between T1 increase and higher seizure burden may reflect progressive tissue damage.


Asunto(s)
Epilepsias Parciales , Epilepsia , Humanos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Convulsiones , Epilepsias Parciales/diagnóstico por imagen
13.
Bipolar Disord ; 25(8): 671-682, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-36871135

RESUMEN

OBJECTIVES: The efficacy of electroconvulsive therapy (ECT) in treating mood disorders (MDs) is hypothesized to be mediated by the induction of neurotrophic factors (denoted "angioneurins") that trigger neuronal plasticity. This study aimed to assess the effects of ECT on serum angioneurin levels in patients with MD. METHODS: A total of 110 patients with MDs including 30 with unipolar depression, 25 with bipolar depression (BD), 55 with bipolar mania (BM), and 50 healthy controls were included in the study. Patients were subdivided into two groups: those who received ECT + medication (12 ECT sessions) and those who received only medication (no-ECT). Depressive and manic symptom assessments and measurements of vascular endothelial growth factor (VEGF), fibroblast growth factor-2, nerve growth factor (NGF), and insulin-like growth factor-1 levels in blood samples were performed at baseline and week 8. RESULTS: Patients in the ECT group, specifically those with BD and BM, had significantly increased levels of VEGF compared to their baseline VEGF levels (p = 0.002). No significant changes in angioneurin levels were observed in the no-ECT group. Serum NGF levels were significantly associated with a reduction in depressive symptoms. Angioneurin levels were not associated with manic symptom reduction. CONCLUSIONS: This study hints that ECT may increase VEGF levels with angiogenic mechanisms that amplify NGF signaling to promote neurogenesis. It may also contribute to changes in brain function and emotional regulation. However, further animal experiments and clinical validation are needed.


Asunto(s)
Trastorno Bipolar , Terapia Electroconvulsiva , Humanos , Trastornos del Humor/etiología , Trastornos del Humor/terapia , Trastorno Bipolar/terapia , Factor A de Crecimiento Endotelial Vascular , Factor de Crecimiento Nervioso , Manía , Resultado del Tratamiento
14.
J Immunol ; 206(9): 2160-2169, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33863788

RESUMEN

IL-27, a heterodimeric cytokine of the IL-12 family, has diverse influences on the development of multiple inflammatory diseases. In this study, we identified the protective role of IL-27/IL-27R in host defense against Chlamydia muridarum respiratory infection and further investigated the immunological mechanism. Our results showed that IL-27 was involved in C. muridarum infection and that IL-27R knockout mice (WSX-1-/- mice) suffered more severe disease, with greater body weight loss, higher chlamydial loads, and more severe inflammatory reactions in the lungs than C57BL/6 wild-type mice. There were excessive IL-17-producing CD4+ T cells and many more neutrophils, neutrophil-related proteins, cytokines, and chemokines in the lungs of WSX-1-/- mice than in wild-type mice following C. muridarum infection. In addition, IL-17/IL-17A-blocking Ab treatment improved disease after C. muridarum infection in WSX-1-/- mice. Overall, we conclude that IL-27/IL-27R mediates protective immunity during chlamydial respiratory infection in mice by suppressing excessive Th17 responses and reducing neutrophil inflammation.


Asunto(s)
Inflamación/inmunología , Interleucinas/inmunología , Neutrófilos/inmunología , Receptores de Interleucina/inmunología , Animales , Chlamydia muridarum/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Interleucina/deficiencia , Células Th17/inmunología
15.
Mol Biol Rep ; 50(11): 9273-9282, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37812351

RESUMEN

BACKGROUND: As the world's leading fiber crop and a major oil-producing crop, cotton fiber yield and fiber quality are affected by environmental stresses, especially heat, drought and salinity. The LAZ1 (Lazarus 1) family genes are responsive to abscisic acid, drought, and salt treatments. Currently, mining and functional analyses of LAZ1 family genes in cotton have not been reported. METHODS AND RESULTS: In this study, 20 GhLAZ1 genes, designated GhLAZ1-1 - GhLAZ1-20, were identified in the genome of Gossypium hirsutum through the construction of an HMM model, and their molecular properties, chromosomal localization, phylogeny, gene structure, evolutionary selection pressure, promoter cis elements and gene expression under salt stress were analyzed. With the exception of GhLAZ1-17 and GhLAZ1-20, the remaining 18 GhLAZ1 genes were unevenly localized on 13 chromosomes in G. hirsutum; evolutionary analysis showed that these genes could be divided into three subfamilies; and evolutionary selection pressure analysis demonstrated that the GhLAZ1 genes were all under purifying selection. Many elements related to light responses, hormone responses, and abiotic stresses were predicted on the GhLAZ1 family gene promoters, and real-time quantitative PCR results showed that GhLAZ1-2, GhLAZ1-8, and GhLAZ1-18 were upregulated significantly in salt-treated cotton leaves. CONCLUSIONS: Our results suggested that GhLAZ1 genes were involved in the salt tolerance mechanism in G. hirsutum and provided a reference for further exploring the function and molecular mechanism of LAZ1 genes.


Asunto(s)
Gossypium , Familia de Multigenes , Gossypium/genética , Estrés Fisiológico/genética , Regiones Promotoras Genéticas/genética , Ácido Abscísico , Regulación de la Expresión Génica de las Plantas/genética , Filogenia , Proteínas de Plantas/genética
16.
Brain ; 145(11): 3859-3871, 2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-35953082

RESUMEN

One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.


Asunto(s)
Epilepsias Parciales , Epilepsia , Malformaciones del Desarrollo Cortical , Humanos , Estudios Retrospectivos , Malformaciones del Desarrollo Cortical/complicaciones , Malformaciones del Desarrollo Cortical/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Aprendizaje Automático , Epilepsias Parciales/diagnóstico por imagen
17.
Eur Arch Psychiatry Clin Neurosci ; 273(3): 553-563, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35857090

RESUMEN

Eye movement abnormalities have been established as an "endophenotype" of schizophrenia. However, less is known about the possibility of these abnormalities as biomarkers for psychosis conversion among clinical high risk (CHR) populations. In the present study, 108 CHR individuals and 70 healthy controls (HC) underwent clinical assessments and eye-tracking tests, comprising fixation stability and free-viewing tasks. According to three-year follow-up outcomes, CHR participants were further stratified into CHR-converter (CHR-C; n = 21) and CHR-nonconverter (CHR-NC; n = 87) subgroups. Prediction models were constructed using Cox regression and logistic regression. The CHR-C group showed more saccades of the fixation stability test (no distractor) and a reduced saccade amplitude of the free-viewing test than HC. Moreover, the CHR-NC group exhibited excessive saccades and an increased saccade amplitude of the fixation stability test (no distractor; with distractor) compared with HC. Furthermore, two indices could effectively discriminate CHR-C from CHR-NC with an area under the receiver-operating characteristic (ROC) curve of 0.80, including the saccade number of the fixation stability test (no distractor) and the saccade amplitude of the free-viewing test. Combined with negative symptom scores of the Scale of Prodromal Symptoms, the area was 0.81. These findings support that eye movement alterations might emerge before the onset of clinically overt psychosis and could assist in predicting psychosis transition among CHR populations.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Movimientos Oculares , Trastornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Factores de Riesgo , Movimientos Sacádicos , Síntomas Prodrómicos
18.
Environ Res ; 216(Pt 1): 114535, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36223835

RESUMEN

The coexistence of chlorophenols (CPs) and total nitrogen (TN) is common in advanced purification of industrial secondary effluent, which brings challenges to conventional denitrification biofilters (DNBFs). Electrical stimulation is an effective method for the degradation of CPs, However, the application of electrical stimulation in DNBFs to enhance the treatment of secondary effluent containing CPs remains largely unknown. Herein, this study conducted a systematic investigation towards the effects of electrical stimulation on DNBF through eight lab-scale reactors at room and low temperatures and different hydraulic retention times (HRTs). Results showed that the electrical stimulation effect was not greatly affected by temperature and the optimal applied voltage was 3 V. Overall, the removal rates of TN and CPs were increased by 114%-334% and 2.68%-34.79% respectively after electrical stimulation. When the influent concentration of NO3--N, COD and each CP of 25 mg/L, 50 mg/L and 5 mg/L, about 15 mg/L of effluent TN could be achieved and the removals of p-chlorophenol, 2,4-dichlorophenol and 2,4,6-trichlorophenol were increased by 10.58%, 5.78% and 34.79% respectively, under the voltage of 3 V and HRT of 4 h. However, the reduction rate of biotoxicity was decreased and could not achieve low toxicity grade in general. Electrical stimulation promoted the elevation of Hydrogenophaga and thus enhanced the removal of TN, and the increase of Microbacterium and Ahniella was significantly associated with the improvement of CPs removal rate. In addition, the obvious accumulation of nitrite was found to be significantly negatively correlated with the abundance of Nitrospira. This study highlighted a further need for the optimization of electrical stimulation in DNBFs treating industrial secondary effluent containing CPs to achieve the goal of pollutant removal and toxicity reduction simultaneously.


Asunto(s)
Clorofenoles , Desnitrificación , Reactores Biológicos , Aguas Residuales , Nitrógeno , Estimulación Eléctrica
19.
Int J Mol Sci ; 24(10)2023 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-37240102

RESUMEN

The fall armyworm (FAW), Spodoptera frugiperda, has become one of the most important pests on corn in China since it invaded in 2019. Although FAW has not been reported to cause widespread damage to rice plants in China, it has been sporadically found feeding in the field. If FAW infests rice in China, the fitness of other insect pests on rice may be influenced. However, how FAW and other insect pests on rice interact remains unknown. In this study, we found that the infestation of FAW larvae on rice plants prolonged the developmental duration of the brown planthopper (BPH, Nilaparvata lugens (Stål)) eggs and plants damaged by gravid BPH females did not induce defenses that influenced the growth of FAW larvae. Moreover, co-infestation by FAW larvae on rice plants did not influence the attractiveness of volatiles emitted from BPH-infested plants to Anagrus nilaparvatae, an egg parasitoid of rice planthoppers. FAW larvae were able to prey on BPH eggs laid on rice plants and grew faster compared to those larvae that lacked available eggs. Studies revealed that the delay in the development of BPH eggs on FAW-infested plants was probably related to the increase in levels of jasmonoyl-isoleucine, abscisic acid and the defensive compounds in the rice leaf sheaths on which BPH eggs were laid. These findings indicate that, if FAW invades rice plants in China, the population density of BPH may be decreased by intraguild predation and induced plant defenses, whereas the population density of FAW may be increased.


Asunto(s)
Hemípteros , Oryza , Animales , Femenino , Larva , Crecimiento Demográfico , Spodoptera
20.
BMC Oral Health ; 23(1): 138, 2023 03 10.
Artículo en Inglés | MEDLINE | ID: mdl-36894923

RESUMEN

BACKGROUND: The anatomical position of the mandibular third molars (M3s) is located in the distal-most portions of the molar area. In some previous literature, researchers evaluated the relationship between retromolar space (RS) and different classifications of M3 in three­dimensional (3D) cone-beam computed tomography (CBCT). METHODS: Two hundred six M3s from 103 patients were included. M3s were grouped according to four classification criteria: PG-A/B/C, PG-I/II/III, mesiodistal angle and buccolingual angle. 3D hard tissue models were reconstructed by CBCT digital imaging. RS was measured respectively by utilizing the fitting WALA ridge plane (WP) which was fitted by the least square method and the occlusal plane (OP) as reference planes. SPSS (version 26) was used to analyze the data. RESULTS: In all criteria evaluated, RS decreased steadily from the crown to the root (P < 0.05), the minimum was at the root tip. From PG-A classification, PG-B classification to PG-C classification and from PG-I classification, PG-II classification to PG-III classification, RS both appeared a diminishing tendency (P < 0.05). As the degree of mesial tilt decreased, RS appeared an increasing trend (P < 0.05). RS in classification criteria of buccolingual angle had no statistical difference (P > 0.05). CONCLUSIONS: RS was associated with positional classifications of the M3. In the clinic, RS can be evaluated by watching the Pell&Gregory classification and mesial angle of M3.


Asunto(s)
Tercer Molar , Diente Impactado , Humanos , Adulto , Tercer Molar/diagnóstico por imagen , Mandíbula/diagnóstico por imagen , Diente Molar/diagnóstico por imagen , Corona del Diente , Tomografía Computarizada de Haz Cónico/métodos
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