视黄酸诱导蛋白16蛋白质结构功能分析

目的:分析Tec激酶区作用蛋白视黄酸诱导蛋白16(RAI16)的蛋白质结构和功能信息.方法:利用相应的计算机软件及数据库,对RAI16 cDNA序列进行分析和比较,并对编码的蛋白质氨基酸序列及其二级结构进行分析和预测.结果:RAI16 cDNA序列由2863个核苷酸组成,编码759氨基酸蛋白质,RAI16蛋白包括一段由31个氨基酸组成的信号肽,没有跨膜区,亚细胞定位于内质网上,有多种二级结构形式,为一紧密包裹的球状蛋白质,是一种分泌蛋白,有多个磷酸化和蛋白酶切位点.RAI16蛋白为不稳定蛋白,不稳定系数为53.11.疏水性GRAVY(grand average of hydropathicity)值为-0.136.结论:RAI16蛋白作为一种新的胞内信号蛋白,很可能在肝癌细胞的诱导分化信号转导转录中与Tec协同发挥重要作用.     

Vitamin D and cognitive functioning in the elderly population in Germany

Objectives

To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study.

Design

Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up.

Setting and participants

A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65 + years at baseline (2000-2002).

Intervention

Observational study.

Measurements

Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5 years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires.

Results

In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [− 0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels.

Conclusions

Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.     

Dynamic changes and surveillance function of prion protein expression in gastric cancer drug resistance

AIM:To explore the dynamic changes of prion protein (PrPc) in the process of gastric cancer drug resistance and the role of PrPc expression in the prognosis of gastric cancer patients receiving chemotherapy.METHODS:A series of gastric cancer cell lines resistant to different concentrations of adriamycin was established,and the expression of PrPc,Bcl-2 and Bax was detected in these cells.Apoptosis was determined using Annexin V staining.Western blotting and immunohisto-chemistry were performed to detect the ...     

The metabolic syndrome, atherosclerosis and cognitive functioning in a non-demented population: the Hoorn Study

Background

The metabolic syndrome (MetS) is associated with cognitive deficits and atherosclerotic vascular disease. We examined whether the relation between the MetS and cognitive dysfunction is mediated by measures of atherosclerosis or the presence of clinically manifest cardiovascular disease.

Methods

In 380 individuals (153 with MetS; 60–87 years) from the population based Hoorn Study, measures of atherosclerosis including carotid intima-media thickness (c-IMT), flow mediated dilation (FMD), ankle-brachial index and the presence of clinically manifest cardiovascular disease were assessed at baseline and 7 later years at follow-up. Cognitive functioning (information processing speed, memory, and attention and executive functioning) was assessed at follow-up. The relation between the MetS, atherosclerosis and cognitive functioning was assessed with linear regression analysis.

Results

Individuals with MetS showed worse performance on information processing speed (adjusted mean difference z-score ± SE: −0.22 ± 0.6; p = 0.01) and attention and executive functioning (−0.32 ± 0.07; p < 0.001), but not on the domain memory. The affected cognitive domains were also associated with measures of atherosclerosis (standardised B (95%CI) c-IMT: −0.14 (−0.24; −0.05); p < 0.01; FMD: 0.13 (0.02; 0.24), p < 0.05) and a history of clinically manifest cardiovascular disease: (−0.29 (−0.47; −0.11); p < 0.01). However, the relation between the MetS and cognitive functioning did not change after adjustment for c-IMT, FMD or a history of clinically manifest cardiovascular disease (p > 0.05).

Conclusion

In this population based cohort, the relation between the MetS and cognitive dysfunction was not mediated by atherosclerosis or a history of cardiovascular disease. These findings should stimulate future studies to elucidate alternative mechanisms underlying cognitive deficits in individuals with MetS.     

老年人认知功能减退影响因素的纵向研究

目的 通过对一个社区居住的老年人群的前瞻性研究,探讨对认知功能随增的或退有重要影响的因素。方法 在北京市５５岁以上的老年与老年前期 群抽取样本,分别于１９９２年和１９９７年测查简易智能量表（ＭＭＳＦ）。结果 基线调查时在正常范围者５年后２４．４％ＭＭＳＥ评分明显下降。多分析证实,基线调查时评分在临界水平者易出现进一步下降;对认知功能痕退有预测作用的因子主要有年龄、受教育程度、地区等人口学因素,健康     

老年人握力与认知功能的关联性

目的:探讨65岁及以上老年人握力与认知功能之间的关系。方法:在武汉市65岁以上老年人中开展现况研究,由经过统一专业培训的调查人员收集握力、认知功能和生活方式等信息,分别采用多重线性回归和Logistic回归分析握力值与认知功能得分和认知障碍之间的关系。结果:本次研究对象(70.7±5.1)岁,533例老年人的平均握力为...     

C-reactive protein is related to future cognitive impairment and decline in elderly individuals with cardiovascular disease

AimsTo explore the association of C-reactive protein (CRP) plasma levels with subsequent cognitive performance and decline among elderly individuals with pre-existing cardiovascular disease (CVD), and to assess the role of cerebrovascular indices in this relationship.MethodsCRP levels were measured in a subgroup of individuals with chronic CVD, who previously participated in a secondary prevention trial. Cognitive performance was evaluated 14.7 ± 1.9 and 19.9 ± 1.0 years after entry to the trial. A validated set of computerized cognitive tests was used (Neurotrax Computerized Cognitive Battery) to assess performance globally and in memory, executive function, visuospatial and attention domains. Linear regression and mixed models were used to assess the relationship of CRP plasma levels with cognitive scores and decline, respectively. In addition, we tested whether cerebrovascular reactivity, carotid intima media thickness and presence of carotid plaques modify these associations.ResultsAmong 536 participants (mean age at the first cognitive evaluation 72.6 ± 6.4 years; 95% males), CRP at the top tertile vs. the rest was associated with subsequent poorer performance overall (ß = −2.2 ± 1.0; p = 0.031) and on tests of executive function and attention (ß = −2.3 ± 1.1; p = 0.043 and ß = −2.0 ± 1.4; p = 0.047, respectively). Moreover, CRP levels were positively related to a greater decline in executive functions (ß = −2.4 ± 1.1; p = 0.03). These associations were independent of potential confounders and were not modified by cerebrovascular indices.ConclusionOur findings suggest that systemic chronic inflammation, potentially associated with underlying atherosclerosis, is related to cognitive impairment and decline two decades later, in elderly individuals with pre-existing CVD.     

朊病毒病实验室检测质量控制特点分析

目的分析朊病毒病重要实验室检测技术的质量控制环节,提高朊病毒病实验室诊断质量水平。方法从朊病毒常见检测方法,如脑组织的PrP^Sc免疫组化、脑组织的PrP^Sc的Westernblot检测、脑脊液中14—3-3蛋白的Westernblot检测以及血液样本中PRNP的基因检测技术等方面分析朊病毒病实验室诊断的质量控制要求。结果实验室检测过程质量控制是朊病毒检测结果准确与否的关键,有效蛋白酶K消化的时间和浓度是脑组织PrP“的Westernblot检测结果的保证,脑组织PrP^Sc的有效暴露和PrP^C的去除是朊病毒病脑组织IHC检测的核心环节,脑脊液的质量是14—3-3Westernblot检测的质量控制点,防止核酸污染是血液的PRNP序列测定的质量检测控制的关键。结论通过分析实验室检测的质量控制关键环节和控制措施,可有效加强朊病毒病实验室质量管理,提高朊病毒病实验室检测能力。     

Habitual physical activity (HPA) as a factor in sustained executive function in Alzheimer-type dementia: A cohort study

Evidence from studies on healthy older adults and mild cognitive impairment (MCI) populations suggests that physical activity interventions have a positive effect on executive function. In this study, we consider whether HPA is positively associated with executive function in Alzheimer's disease (AD). Eighty-two participants with a diagnosis of mild to moderate AD completed six measures of executive function. Objective measures of physical status were taken. In addition, informants completed questionnaires on the participants’ HPA and other lifestyle factors. A composite measure of executive function was the primary outcome. A multistage multiple regression was used to determine how much variance HPA accounted for. The final model comprised disease severity, cognitive reserve, cognitive activities, neuropsychiatric status and HPA status. The final model accounted for a total of 57% of the variance of executive performance, of which HPA itself accounted for 8% of the variance. HPA status is associated executive performance in an AD population even after controlling for key covariates. The findings encourage clinicians to recommend HPA and its cognitive benefits to AD patients and their carers.     

The role of cognitive event-related potentials in executive dysfunction

Frontal lobes are great and are a late-developing region of the neocortex that play a critical role in human behavior and executive function. The aim of this study was to clarify the role of event-related potentials (ERPs) in executive dysfunction and its relationship between generator mechanism and cognitive significance. We recruited 20 patients with frontal lobe lesion (FLL) and 27 age-matched controls. All patients submitted to comprehensive Frontal Test Battery and auditory ERPs measurement. In comparison with controls, the patients with FLL had significantly decreased executive function and manifested the delay of P300 latency, which reflected a delay of mental processing speed in these patients. Our findings suggest that patients with FLL may have prolonged P300 latency, which has a good correlation with executive dysfunction, poor performance, and longer P300 latencies. P300 ERPs are considered to be a useful method to identify the alteration of frontal-parietal connection.     

Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity

The aim of this study was to investigate the potential beneficial effects of dietary anserine and carnosine (CRC) supplementation on cognitive functioning and physical activity of the elderly. The fifty-six subjects (65+) were allocated to the CRC group or placebo group at a 1:1 ratio. The double-blind procedure was used. Data were collected at the baseline and after 13-weeks of supplementation. In the follow up procedure fifty one subjects took part. Chicken meat extract (CME) containing 40% of CRC components (2:1 ratio of anserine to carnosine) was administered 2.5 g per day which allowed to rich the level of 1 g CRC in dipeptides supplement. The cognitive function, physical capacity, body measurements, blood pressure and heart rate (HR) were assessed. After supplementation Body Mass Index (BMI) decreased significantly (p < 0.05) in the CRC group performance comparing the placebo group. In two of six Senior Fitness Test the scores increased significantly (p < 0.05) in CRC group comparing to the placebo group. The perceived exertion differed significantly (p < 0.05) at the baseline and after follow up at the CRC group. The mean values of the Short Test of Mental Status (STMS) scores showed the significant (p < 0.04) increase only in CRC group, in the subscores of construction/copying, abstraction and recall. Conducted anserine and carnosine supplementation in the elderly brings promising effects on cognitive functioning and physical capacity of participants. However, further studies are needed.     

Effect of anesthesia on cognitive status and MMP-2 expression in rats

Objective:To investigate the effect of anesthesia on the cognitive status damage and MMP-2expression in rats.Methods:A total of 120 healthy rats were selected and randomly divided into the control group,CF3-CH(OCH2F)-CF3(Sevoflurane)group and CF3-CH2-O-CHF-CF3group(Sevoflurane)(n=40).After training for 3 d by the Morris water maze,the control group were injected with fentanyl for analgesia,the CF3-CH(OCH2F)-CF3 group and the CF3-CH2-O-CHFCF3 group were anesthesia with CF3-CH(OCH2F)-CF3 and CF3-CH2-O-CHF-CF3 on the basis of fentanyl,then rats in three groups underwent open surgery and suture conventional incision.Morris water maze was used to measure the rats cognitive ability in three groups on the 1st d,3rd d,5th d and 7th d,and the brain tissue MMP-2 expression was detected.Results:After1 d/7 d of the surgery,Morris water maze performance and MMP-2 expression were not significantly different among three groups(P0.05);After 3 d/5 d of the surgery,compared with the control group,the Morris water maze test result was significantly worsened,MMP-2expression levels were significantly increased(P0.05);After 3 d/5 d of the surgery,compared with the CF3-CH2-O-CHF-CF3 group,Morris water maze test result of CF3-CH(OCH2F)-CF3group was significantly worsened,MMP-2 expression levels were significantly increased(P0.05).Conclusions:Anesthesia can cause some injury on cognitive status,different anesthetic drugs may cause different injury,and the cognitive status injury is related to the MMP-2 expression.     

Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Prnp-/-) mice

Cellular prion protein (PrPc) participates in the pathogenesis of prion diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Prnp−/− mice resulted in a higher number of circulating reticulocytes, hematocrits and spleen weights in WT mice than in Prnp−/− mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Ter119+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Ter119+ cells were going through apoptosis in Prnp−/− mice than in WT mice. Plasma erythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Prnp−/− (5500 pg/ml ) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Prnp−/− animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression.     

The impact of insomnia on cognitive functioning in older adults

OBJECTIVES: To examine whether self-reported symptoms of insomnia independently increase risk of cognitive decline in older adults. DESIGN: Longitudinal cohort study. SETTING: The four sites of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Six thousand four hundred forty-four community-dwelling men and women age 65 and older who had no more than one error on the Short Portable Mental Status Questionnaire (SPMSQ) at baseline and an in-person interview at the third annual follow-up (FU3). MEASUREMENTS: Insomnia was defined as report of trouble falling asleep or waking up too early most of the time. Cognitive decline was defined as two or more errors on the SPMSQ at FU3. Logistic regression was used to determine risk of cognitive decline associated with insomnia, controlling for demographic, behavioral, and health-related factors. Analyses were stratified by sex and depressed mood. RESULTS: Among nondepressed men, those reporting symptoms of insomnia at both baseline and FU3 had an adjusted odds ratio (OR) of 1.49 (95% CI = 1.03-2.14) for cognitive decline, relative to those with no insomnia at FU3. Men with insomnia at FU3 only were not at increased risk (OR = 1.16, 95% CI = 0.82-1.65). These relationships were not found in women. Men and women with depressive symptoms at FU3 were at increased risk for cognitive decline independent of insomnia. CONCLUSION: Chronic insomnia independently predicts incident cognitive decline in older men. More sensitive measures of cognitive performance may identify more subtle declines and may confirm whether insomnia is associated with cognitive decline in women.     

甲状腺功能异常对老年人认知功能的影响

甲状腺功能异常在老年人中较常见,它不仅影响老年人的躯体功能,还可能引起注意力、记忆、情感等认知功能障碍.已有研究从动物实验、神经电生理、神经影像等角度对甲状腺功能与认知功能之间的关系展开探讨.此外,在临床工作中,甲状腺功能异常引起的严重认知功能损害易与老年性痴呆相混淆.因此,医务人员需重视,避免误诊.及时、合理地纠正老年人甲状腺功能异常,可能有利于认知能力的恢复.     

Association of lung function with physical, mental and cognitive function in early old age

Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV(1)), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50-74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV(1) was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good 'summary' measure of overall functioning in early old age.     

Alcohol affects executive cognitive functioning differentially on the ascending versus descending limb of the blood alcohol concentration curve

BACKGROUND: Executive cognitive functioning (ECF), a construct that includes cognitive abilities such as planning, abstract reasoning, and the capacity to govern self-directed behavior, has been recently researched as an antecedent to many forms of psychopathology and has been implicated in alcohol-related aggression. This study was designed to examine whether differential ECF impairments can be noted on the ascending versus the descending limbs of the blood alcohol concentration curve. METHODS: Forty-one male university students participated in this study. Twenty-one subjects were given 1.32 ml of 95% alcohol per kilogram of body weight, mixed with orange juice, and the remaining 20 were given a placebo. Participants were randomly assigned to either an ascending or descending blood alcohol group and were tested on six tests of ECF on their assigned limb. Subjective mood data were also collected. RESULTS: Intoxicated participants on both limbs demonstrated ECF impairment; the descending-limb group showed greater impairment than their ascending-limb counterparts. Intoxicated subjects were significantly more anxious at baseline than placebo subjects. The introduction of this covariate nullified any significant differences in subjective mood found on either limb of the blood alcohol concentration curve, but ECF impairments remained robust. CONCLUSIONS: Our results support the conclusion that alcohol negatively affects cognitive performance and has a differential effect on the descending versus the ascending limb of the blood alcohol concentration curve. The latter finding may have important ramifications relating to the detrimental consequences of alcohol intoxication.     

Lower specific infectivity of protease-resistant prion protein generated in cell-free reactions

Prions are unconventional infectious agents that cause transmissible spongiform encephalopathy (TSE) diseases, or prion diseases. The biochemical nature of the prion infectious agent remains unclear. Previously, using a protein misfolding cyclic amplification (PMCA) reaction, infectivity and disease-associated protease-resistant prion protein (PrPres) were both generated under cell-free conditions, which supported a nonviral hypothesis for the agent. However, these studies lacked comparative quantitation of both infectivity titers and PrPres, which is important both for biological comparison with in vivo-derived infectivity and for excluding contamination to explain the results. Here during four to eight rounds of PMCA, end-point dilution titrations detected a >320-fold increase in infectivity versus that in controls. These results provide strong support for the hypothesis that the agent of prion infectivity is not a virus. PMCA-generated samples caused the same clinical disease and neuropathology with the same rapid incubation period as the input brain-derived scrapie samples, providing no evidence for generation of a new strain in PMCA. However, the ratio of the infectivity titer to the amount of PrPres (specific infectivity) was much lower in PMCA versus brain-derived samples, suggesting the possibility that a substantial portion of PrPres generated in PMCA might be noninfectious.     

Executive functioning in children with heavy prenatal alcohol exposure

BACKGROUND: Children with heavy prenatal alcohol exposure have well documented deficits in overall cognitive ability. Recently, attention has turned to the executive function (EF) domain in this population. Until recently, comprehensive measures of EF have not been available within one test battery. This study used a battery of tests to assess four domains of EF in alcohol-exposed children. METHODS: The Delis-Kaplan Executive Function Scale was used to evaluate EF in 18 children with heavy prenatal alcohol exposure, with and without a diagnosis of fetal alcohol syndrome (FAS), and 10 nonexposed controls. Children ranged in age from 8 to 15 years. Measures from four domains of executive functioning were analyzed: planning ability, cognitive flexibility, selective inhibition, and concept formation and reasoning. Tasks consisted of primary EF measures as well as measures of secondary component skills. RESULTS: Alcohol-exposed children were deficient on EF measures compared with nonexposed controls. Furthermore, in most cases, children with and without the FAS diagnosis did not differ from one another. These deficits were not entirely explainable by concomitant deficits on component skills. Specific impairments were identified within the domains of planning and response inhibition, with additional deficits in abstract thinking and flexibility. CONCLUSIONS: Deficits in executive functioning were observed in alcohol-exposed children with or without the diagnosis of FAS and in the absence of mental retardation. Performance on these EF tasks provides insight into the cognitive processes driving overall performance and has implications for adaptive and daily functions. These results are consistent with anecdotal and empirical reports of deficits in behavioral control and with neuroanatomical evidence of volumetric reductions in structures within the frontal-subcortical system in children with heavy prenatal alcohol exposure.