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Abstract Background Growing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large‐scale functional networks of IE patients or their postoperative network‐level alterations. Methods Here, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting‐state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting‐state MRI scans. Linear mixed effects models were applied for cross‐sectional and longitudinal network‐level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables. Results In cross‐sectional analyses, network‐level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra‐ and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE. Conclusions Obviously, altered network‐level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

Abnormal brain structural and functional properties were demonstrated in patients with infantile esotropia (IE). However, few studies have investigated the interaction between structural and functional connectivity (SC-FC) in patients with IE. Structural network was generated with diffusion tensor imaging and functional network was constructed with resting-state functional magnetic resonance imaging for 18 patients with IE as well as 20 age- and gender- matched healthy subjects. The SC-FC coupling for global connectome, short connectome and long connectome were examined in IE patients and compared with those of healthy subjects. A linear mixed effects model was employed to examine the group-age interaction in terms of the coupling metrics. The Pearson correlation between coupling measures and strabismus degree was evaluated in IE patients, on which the regulatory effect of age was also investigated through hierarchical regression analysis. Significantly decreased SC-FC coupling score for short connections was observed in left caudate nucleus (CAU) in IE patients, whereas no brain regions exhibited altered coupling metrics for global connections or long connections. The group-age interaction was also evident in local coupling metrics of left CAU. The age-related regulatory effect on coupling-degree association was distinguishing between brain regions implicated in visual processing and cognition-related brain areas in IE patients. Local SC-FC decoupling in CAU was evident in patients with IE and was initiated in their early postnatal period, possibly interfering the visual cortico-striatal loop and subcortical optokinetic pathway subserving visual processing and nasalward optokinesis during neurodevelopment, which provides new insight into underlying neuropathological mechanism of IE.

Previous studies have shown that functional networks are present at birth and change dynamically throughout infancy and early childhood. However, the status of functional connectivity is still poorly understood in patients with infantile esotropia (IE). The aim of this study is to investigate the developmental trends of functional connectivity in patients with IE during a critical period of growth and development. A total of 17 patients with IE (9 males and 8 females; mean age: 3.36 ± 2.03 years, age range: 0.67–6.36 years) and 20 healthy subjects matched for age and gender were recruited and underwent resting-state functional magnetic resonance imaging. The whole-brain functional network connectivity was analyzed for the IE group and healthy control group. A general linear model was applied to assess the group-age interaction in terms of the functional connectivity. The discrepancy between the two groups in functional connectivity trajectories was also quantified across age and exhibited by the quadratic parabolic model. There were significant group-age interactions between the visual network and the default mode network, the visual network and the sensorimotor network, the limbic network and the default mode network, and within the limbic network in the functional connectivity. A U-shaped tendency across age, with an “inflection point” ranging from 3.1 to 4.0 years of age was exhibited in the difference between functional connectivity trajectories of the IE patients and normal controls. Abnormality in functional network connectivity could present in IE patients at birth, exhibiting aberrant developmental patterns over time. An abnormal functional network could reduce the ability of the cortex in visual information processing, further reactivating the subcortical visual information processing system, which is probably the pathogenesis of IE. Three to four years after birth is the critical time window for children with IE to establish normal network connections in the brain. Early surgery during this period may be helpful for affected children to have an opportunity to approach the normal development trajectory as early as possible.

Abstract Background In the agricultural areas of Qinghai-Tibet Plateau, temperature varies widely from day to night during the growing season, which makes the extreme temperature become one of the limiting factors of crop yield. Turnip (Brassica rapa var. rapa) is a traditional crop of Tibet grown in the Tibet Plateau, but its molecular and metabolic mechanisms of freezing tolerance are unclear. Results Here, based on the changes in transcriptional and metabolic levels of Tibetan turnip under freezing treatment, the expression of the arginine decarboxylase gene BrrADC2.2 exhibited an accumulative pattern in accordance with putrescine content. Moreover, we demonstrated that BrrICE1.1 (Inducer of CBF Expression 1) could directly bind to the BrrADC2.2 promoter, activating BrrADC2.2 to promote the accumulation of putrescine, which was verified by RNAi and overexpression analyses for both BrrADC2.2 and BrrICE1.1 using transgenic hair root. The function of putrescine in turnip was further analyzed by exogenous application putrescine and its inhibitor DL-α-(Difluoromethyl) arginine (DFMA) under freezing tolerance. In addition, the BrrICE1.1 was found to be involved in the ICE1-CBF pathway to increase the freezing stress of turnip. Conclusions BrrICE1.1 could bind the promoter of BrrADC2.2 or CBFs to participate in freezing tolerance of turnip by transcriptomics and targeted metabolomics analyses. This study revealed the regulatory network of the freezing tolerance process in turnip and increased our understanding of the plateau crops response to extreme environments in Tibet.

The purpose of this study was to investigate the effect of the E1 activating enzyme UBA2 on the expression of the SUMO-1 protein during in vitro maturation (IVM) of pig oocytes and embryonic development. In the 5 µg/ml UBA2 treatment group, the expression of the anti-apoptotic gene Bcl-2 and the embryo cleavage rate was significantly increased, while the proapoptotic gene Bax was significantly reduced. When 10 µg/ml UBA2 was added, the in vitro maturation rate, blastocyst rate, and SUMO-1 protein content of oocytes increased significantly (p < .05), and the expression of proapoptotic gene Caspase3 was significantly decreased (p < .05), while the viability of cumulus cells was extremely significantly reduced (p < .01). In summary, UBA2 can regulate the content of the SUMO-1 protein in mature pig oocytes in vitro, which in turn affects the maturation rate of oocytes, expression of apoptosis genes, cumulus cell viability, and the development of embryos after fertilization. [ABSTRACT FROM AUTHOR]

Aims: Our previous studies have shown that myocardial ischemia-reperfusion (I/R) injury is related closely with early growth response (Egr)-1 overexpression. The present study is to confirm thoroughly the effects of Egr-1 on the occurrance and development of myocardial I/R injury. Methods: The Sprague-Dawley rat myocardial I/R model and cultured cardiomyocyte hypoxia-reoxygenation (H/R) model were established. The synthesized Egr-1 antisense oligodeoxyribonucleotide (AS-ODN) was transfected into myocardial tissues and cells. Hemodynamic parameters, myeloperoxidase (MPO), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), morphology, spontaneous beat and cell viability were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Results: In vivo, Egr-1 AS-ODN significantly attenuated injury and inflammation of myocardial tissues caused by I/R evidenced by the amelioration of hemodynamics and the reduction in MPO activity. In vitro, Egr-1 AS-ODN significantly relieved injury and inflammation of cultured cardiomyocyte caused by H/R evidenced by the improvement in morphology, structure and beat as well as the decrease in leakage of cTnI and release of TNF-α from cultured cardiomyocyte. Conclusions: These data suggest that Egr-1 plays a vital role in the pathogenesis of myocardial I/R injury and Egr-1 AS-ODN could protect the myocardium from I/R injury. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aims: Our previous studies have shown that N-n-butyl haloperidol iodide (F2) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca2+ overload. The present study is to test the hypothesis that the protective effects of F2 on myocardial I/R injury is mediated by downregulating Egr-1 expression. Methods: The Sprague–Dawley rat myocardial I/R model and cardiomyocyte hypoxia/reoxygenation (H/R) model were established. With antisense Egr-1 oligodeoxyribonucleotide (ODN), the relationship between Egr-1 expression and myocardial I/R injury was investigated. Hemodynamic parameters, myeloperoxidase (MPO), cardiac troponin I (cTnI) and tumor necrosis factor-α (TNF-α) were measured to assess the degree of injury and inflammation of myocardial tissues and cells. Egr-1 mRNA and protein expressions were examined by Northern-blot and Western-blot analyses. Results: Treatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of myocardial tissues and cells. Meanwhile, treatment with F2 significantly inhibited the overexpression of Egr-1 mRNA and protein in myocardial tissues and cells. Consistent with downregulation of Egr-1 expression by F2, inflammation and other damages were significantly relieved evidenced by the amelioration of hemodynamics, the reduction in myocardial MPO activity as well as the decrease in leakage of cTnI and release of TNF-α from cardiomyocyte. Conclusions: These results suggested that the overexpression of Egr-1 was causative in myocardial I/R or H/R injury, and F2 could protect myocardial tissues and cells from I/R or H/R injury, which was largely due to the inhibition of Egr-1 overexpresssion. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]