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1.
《Islets》2013,5(2)
Regenerative therapy in diabetes with the capacity to reconstitute a functional β-cell mass sufficient for glycemic control holds the promise to effectively prevent the development of devastating late complications due to the unique ability of the β-cell to sense and regulate blood-glucose levels. An ability that cannot be mimicked by insulin replacement therapy or any other means of current treatment regiments for very large patient populations. Recently, Douglas A. Melton’s group from Harvard University reported the identification of a circulating protein secreted from the liver under insulin resistant states which is sufficient to dramatically and specifically increase the replication rate of β-cells in the mouse resulting in an increased functional β-cell mass over time. They re-named the factor betatrophin and described a number of exciting features of this molecule which suggested that it could be a potential candidate for development as a regenerative medicine in diabetes.1 The official name of the gene encoding mouse betatrophin is Gm6484, but it has been annotated a number of times under different names: EG6242192,3, RIFL4, Lipasin5 and ANGPTL8.6 The official human gene name is C19orf80, but it has also been annotated as TD267, LOC559088, as well as RIFL, Lipasin, ANGPTL8 and betatrophin. 相似文献
2.
《Gut microbes》2013,4(3):267-271
Type IV pili (Tfp) play a primary role in mediating the adherence of pathogenic bacteria to their hosts. The pilus filament can retract with an immense force. However, the role of this activity in microbial pathogenesis has not been rigorously explored. Experiments performed on volunteers suggested that the retraction capacity of enteropathogenic Escherichia coli (EPEC) Tfp is required for full virulence. Here we review our recent study1 in which we showed that the retraction capacity of the EPEC Tfp facilitates tight-junction disruption and actin-rich pedestal formation by promoting efficient bacterial protein effector translocation into epithelial host cells. We also present new data using live imaging confocal microscopy suggesting that EPEC adheres to monolayers in microcolonies and that Tfp retraction facilitates significant changes in the microcolony shape, which may be critical for efficient effector delivery. Our studies hence suggest novel insights into the role of pili retraction in EPEC pathogenesis. 相似文献
3.
《Gut microbes》2013,4(4):485-493
Despite growing evidence for a causal role of environmental factors in autoimmune diseases including the rise in disease frequencies over the past several decades we lack an understanding of how particular environmental exposures modify disease risk. In addition, many autoimmune diseases display sex-biased incidence, with females being disproportionately affected but the mechanisms underlying this sex bias remain elusive. Emerging evidence suggests that both host metabolism and immune function is crucially regulated by the intestinal microbiome. Recently, we showed that in the non-obese diabetic (NOD) mouse model of Type 1 Diabetes (T1D), the gut commensal microbial community strongly impacts the pronounced sex bias in T1D risk by controlling serum testosterone and metabolic phenotypes1. Here we present new data in the NOD model that explores the correlations between microbial phylogeny, testosterone levels, and metabolic phenotypes, and discuss the future of microbiome-centered analysis and microbe-based therapeutic approaches in autoimmune diseases. 相似文献
4.
《Gut microbes》2013,4(5):474-475
Under normal conditions, the gut microbiota confers health benefits for the host. The microbiota aids in the nutrient processing and contributes to the construction of the intestinal epithelial barrier. Furthermore, animal models demonstrate the importance of stimulation from gut bacteria for a proper maturation of the immune system. In this addendum, we summarize our recent study1 in which we demonstrate that colonization with Escherichia coli and bifidobacteria in the first 2 months of life was related to higher numbers of CD27-positive memory B cells later in infancy. The numbers of total B cells or CD5+CD20+ B cells, on the other hand, were not related to the bacterial colonization pattern. Thus, the gut microbiota might affect the B cell maturation also in humans, and our study indicates that an early colonization pattern that includes E. coli and bifidobacteria might promote this maturation early in life. 相似文献
5.
《Gut microbes》2013,4(5):476-481
Recently, we demonstrated a novel role for gastrointestinal mast cells (MCs) in the early events that lead to the generation of Th2 immunity to helminth infection.1 Mice lacking MCs (KitW/KitW-v and KitW-Sh) showed a significant inhibition of Th2 cell priming following infection with the parasitic helminth Heligmosomoides polygyrus bakeri (Hp). We showed that MCs degranulate during the early stages of infection when the helminth larvae invade the small intestinal tissue. Furthermore, MC degranulation was required for the enhanced expression and production of the tissue-derived cytokines IL-25, IL-33 and TSLP, which are required for the optimal orchestration and priming of type 2 immunity. In this addendum we aim to address several questions raised by our findings — in particular, the mechanisms through which MCs may recognize helminth exposure in the early stages of infection and by which they may enhance expression of critical tissue cytokines thus, enabling Th2 priming. Furthermore, we will discuss these findings in the context of recently described novel innate immune cells, such as type 2 hematopoietic progenitors and type 2 innate lymphoid cells. 相似文献
6.
Giovanna E. Carpagnano Cinzia Ruggieri Giulia Scioscia Maria Maddalena Lo Storto Luigi Zoppo Maria P. Foschino-Barbaro 《COPD》2016,13(5):642-646
The smoking habit is accompanied by an acute inflammatory response which follows tissue injury. It would be desirable to find a non-invasive inflammatory marker that would simplify the task of studying and monitoring smokers more simply and allow us to identify populations at risk of contracting Chronic Obstructive Pulmonary Disease (COPD). Today's expectations regarding research focus on issues ranging from inflammatory markers to those of exhaled breath temperature (EBT) are considerable. That said, although the EBT has been largely studied in asthma and COPD, there have not been any studies thus far that have analysed the effect of cigarette smoking on the EBT.?Bearing this in mind, in this longitudinal study we aim to analyse the EBT in current smokers, monitor the effects both of cigarette smoking on EBT and of what happens after smoking cessation. Twenty-five (25) smokers (59.5 ± 3.1 yrs, 12 M) who participated in a multi-disciplinary smoking cessation programme and 25 healthy never-smokers (58.7 ± 2.9, 13 M) underwent EBT measurement. EBT values were higher in smokers before smoking (T0) than in never-smokers [34.6 (34.2–35) vs 33.2 (32.4–33.7)°C, p < 0.001. The smokers repeated measurement 5 minutes after smoking a cigarette (T1) and 2 hours after (T2). They repeated EBC measurement after 1 week (T3) and then after 3 months (T4) from smoking cessation. EBT is higher in smokers compared to controls. EBT increases after cigarette smoking and progressively decreases with the increase of time from when the last cigarette was smoked.?Thus, we can conclude that EBT is increased in smokers and also sensitive to the acute effect of cigarette smoke. 相似文献
7.
Over the last 20 years smoking has become the most common method of heroin use and increasing numbers of heroin smokers are presenting to local medical services, before the age of 40 years, with severe airway disease. To determine COPD prevalence we recruited 129 subjects from two local community drug services, of whom 107 were heroin smokers. We collected demographic, medical and treatment data, smoking history (including cannabis and opiates) and details of symptoms including MRC dyspnoea. Subjects completed the COPD Assessment Tool and spirometry. Thirty heroin smokers were identified as having COPD resulting in a COPD prevalence of 28%. Mean age was 43 (4) years and FEV1 was 2.71 (0.98) L; 70 (23) %predicted. Breathlessness and wheeze were more common in subjects with COPD (p < 0.04 and p < 0.05) but symptoms were common in all heroin smokers. MRC score was higher (3 vs. 2.4; p < 0.04) in those with COPD and health status appeared poorer (CAT 20.4 vs. 15.8; p < 0.07). Only 4 (11%) had previously been diagnosed with COPD and only 16 (53%) received any inhaled medication. Asthma prevalence was also high at 33% and asthmatic subjects had similar symptoms and health status compared with the COPD subjects, and were also significantly undertreated. COPD and asthma are common in current and former heroin smokers. They are often present at a young age and are underdiagnosed and undertreated. Awareness of this issue should be highlighted within drug services and in particular to heroin smokers. Screening this high-risk population with spirometry should be considered. 相似文献
8.
9.
Sarah W. Kennedy Alyssa A. Gamaldo Keith E. Whitfield 《Experimental aging research》2013,39(3):247-264
Background/Study Context: The current study examined the relationship between intellectual control and cognition and related the results to everyday problem solving in a mixed ethnicity sample of 35% African American and 65% Caucasian elders. Methods: Participants completed the Personality in Intellectual Aging Contexts Inventory (PIC; Lachman et al., 1982, Journal of Research in Personality, 16, 485–501), Everyday Cognition Battery (ECB; Allaire & Marsiske, 1999, Psychology & Aging, 14, 627–644; 2002, Psychology & Aging, 17, 101–115), and a battery of basic cognitive ability tests assessing memory, inductive reasoning, and verbal meaning. Results: Results indicated that African Americans had significantly lower intellectual control beliefs relative to Caucasian older adults. Regression models suggested that relationship between control beliefs and cognition was moderated by education and race. Decomposing the interactions with simple slope analysis revealed that across cognitive abilities, better cognitive performance was related to higher control beliefs in African Americans with at least 13 years of education. A similar relationship was also found in Caucasian elders with lower education. Conclusion: African American elders’ reaching a higher level of education may provide a basis for which individual differences in intellectual control beliefs are activated and thereby more strongly associated with cognitive performance. 相似文献
10.
Ted Tedrick 《Activities, Adaptation & Aging》2013,37(3):137-160
As the population of persons with intellectual disabilities continues to age and to increase, so, too, has Special Olympics witnessed the growth of numbers of adults who have remained involved for years and are now in their 40s, 50s, and beyond. Data from 2005 showed 44.9% of Special Olympians in North America to be age 22 or older (Lenox, 2007). Recent studies of motives and benefits of participation (Farrell, Crocker, McDonough, & Sedgwick, 2004; Goodwin, Fitzpatrick, Thurmeier, & Hall, 2006) have noted issues related to the maturing of athletes. Case studies of three adult Special Olympians were used to explore meaning and benefits (8 categories) of participation. Adult athletes were selected to represent different stages of adulthood and differing health conditions. Age-related changes for parents were also noted. Similar to previous research, athletes confirmed the importance of benefits such as fitness, sport skills, friendships, and competition. Practical implications for coaches and administrators are discussed. 相似文献
11.
Louis Bherer Arthur F. Kramer Matthew S. Peterson Stanley Colcombe Kirk Erickson Ensar Becic 《Experimental aging research》2013,39(3):188-219
Older adults' difficulties in performing two tasks concurrently have been well documented (Kramer & Madden, 2008). It has been observed that the age-related differences in dual-task performance are larger when the two tasks require similar motor responses (2001) and that in some conditions older adults also show greater susceptibility than younger adults to input interference (Hein & Schubert, 2004). The authors recently observed that even when the two tasks require motor responses, both older and younger adults can learn to perform a visual discrimination task and an auditory discrimination task faster and more accurately (Bherer et al., 2005). In the present study, the authors extended this finding to a dual-task condition that involves two visual tasks requiring two motor responses. Older and younger adults completed a dual-task training program in which continuous individualized adaptive feedback was provided to enhance performance. The results indicate that, even with similar motor responses and two visual stimuli, both older and younger adults showed substantial gains in performance after training and that the improvement generalized to new task combinations involving new stimuli. These results suggest that dual-task skills can be substantially improved in older adults and that cognitive plasticity in attentional control is still possible in old age. 相似文献
12.
The scientific community has recently come to appreciate that, rather than existing as independent organisms, multicellular hosts and their microbiota comprise a complex evolving superorganism or metaorganism, termed a holobiont. This point of view leads to a re-evaluation of our understanding of different physiological processes and diseases. In this paper we focus on experimental and computational approaches which, when combined in one study, allowed us to dissect mechanisms (traditionally named host-microbiota interactions) regulating holobiont physiology. Specifically, we discuss several approaches for microbiota perturbation, such as use of antibiotics and germ-free animals, including advantages and potential caveats of their usage. We briefly review computational approaches to characterize the microbiota and, more importantly, methods to infer specific components of microbiota (such as microbes or their genes) affecting host functions. One such approach called transkingdom network analysis has been recently developed and applied in our study.1 Finally, we also discuss common methods used to validate the computational predictions of host-microbiota interactions using in vitro and in vivo experimental systems. 相似文献
13.
Endobronchial valve (EBV) therapy has shown improvement in symptoms and lung function despite limited understanding of ideal patient selection. The impact of lobe selection on EBV therapy is unclear. We performed a retrospective analysis to determine the role of lobe selection and identify preprocedure predictors of response to EBV therapy. A total of 492 patients from the USA and Europe were randomized to EBV or control therapy. Spirometry and functional measurements were taken at baseline and 12 months later. At 365 days patients undergoing EBV therapy showed improvement in FEV1 change compared to control regardless of treatment to upper or lower. There was no difference in FEV1 change between the upper and lower lobe treatment groups (5.99, 7.04, p = 0.75). In addition lobe selection was not identified as a significant modifier of FEV1 change in multiple linear regression analysis. Complete lobe fissure was the only significant predictor of FEV1 change (OR 4.14 (2.29, 7.47)). Our results suggest that lobe selection does not play a major role in EBV therapy response. Complete fissure status preprocedure has the greatest influence on FEV1 improvement. These results have implications on patient selection for current treatment and in future EBV studies. 相似文献
14.
In the literature, there are few and conflicting reports regarding age-related changes in adult mentalizing abilities: whereas Happè et al. (1998, Developmental Psychology, 34, 358–362) showed better performances of elderly compared with young subjects in an advanced theory of mind (ToM) task, Mayor et al. (2002, British Journal of Psychology, 93, 465–485) and Sullivan and Ruffmann (2004, British Journal of Psychology, 95(Pt 1), 1–18) found an age-related decline. Former studies addressing the issue compared young to elderly subjects and did not investigate earlier changes in middle-aged adults. To shed light on changes in ToM skills along adulthood, the authors used the revised version of the “Reading the Mind in the Eyes Test” (Baron-Cohen et al., 2001, Journal of Child Psychology and Psychiatry, 42, 241–251) to compare four groups of people of different ages covering the whole span of adult life. The authors found aged-related decline in ToM skills as early as the fifth decade of life. Awareness of the age-related changes in adult mentalizing is important to differentiate normal aging effects from ToM impairments due to neuropsychiatric diseases. 相似文献
15.
Luciana Laganá PhD Therese Spellman BA Jennifer Wakefield BA Taylor Oliver MA 《Clinical gerontologist》2013,36(3):173-189
The authors investigated the relationship between marital adjustment and ethnic minority status, depressive symptomatology, and cognitive failures among 78 married, community-dwelling, and predominantly non-European-American older women (ages 57 to 89 years). Respondents were screened to rule out dementia. Level of depressive symptoms, self-report of cognitive failures, and marital adjustment scores were obtained. As hypothesized, higher depressive symptomatology and cognitive failures were associated with worse marital adjustment (p < .05 for both). The same was true for membership in a nondominant ethnic group, albeit only when ethnic status was considered outside the context of the other two independent variables. These results have clinical implications and fit within the theoretical framework of the socioemotional selectivity theory (Carstensen, 1992) applied to marriage in older age, a conceptualization formulated by Bookwala and Jacobs in 2004. 相似文献
16.
Social desirability is a multicomponent personality trait referring to the tendency of individuals to regulate their answers to establish a positive impression, avoid criticism, or satisfy a need for social approval (Johnson & Fendrich, 2002; Paulhus, 1984). This study investigated the role played by the socially desirable response style assessed with the Marlowe-Crowne Social Desirability Scale (Crowne & Marlowe, 1960) on self-rated measures of affect (i.e., Center of Epidemiological Studies of Depression Scale; Radloff, 1977), metacognitive efficiency (i.e., Sensitivity to Memory Questionnaire; Cornoldi & De Beni, 2003; and Cognitive Failures Questionnaire; Borella, Carretti, Cornoldi, & DeBeni, 2007), and self-perceived psychological wellness (Psychological Wellness and Aging Questionnaire; De Beni, Borella, Carretti, Marigo, & Nava, 2007) in a sample composed of young (M = 24.6 years), old (M = 69.4 years), and very old (M = 81.9 years) adults counterbalanced by gender and education (i.e., ≤ 8 years versus > 8 years). Results revealed that social desirability alone predicted measures of affect and emotional competencies and contributed to predicting personal satisfaction, general perceived wellness, and self-rated cognitive efficiency. Overall, the present outcomes suggest clinical psychologists should pay attention to the crucial interference of social desirability in assessing wellness even in late adulthood, that is, in a developmental phase thought to be mainly characterized by reduced control of physical and psychological functions. 相似文献
17.
Nikki M. Dudley 《Experimental aging research》2013,39(3):331-344
ABSTRACT Socioemotional selectivity theory (SST; Carstensen, 1995, Current Directions in Psychological Science, 4, 151–156) predicts that novel social partners are preferred in open-ended situations, whereas familiar social partners are preferred in future-limited situations. The authors attempted to generalize past research to new familiar and novel partner options. Studies 1 (N = 144; undergraduates, community-dwelling adults ages 65 to 95) and 2 (N = 336 community-dwelling participants ages 11 to 89) indicated that young and older participants in a future-limited situation preferred familiar partners. However, with different social partner options than have been used in previous research, young participants in an open-ended situation also preferred a familiar partner, contrary to the predictions of SST. 相似文献
18.
Thirty younger (mean age = 21 years) and 30 older (mean age = 73 years) adults were compared to determine if they had similar affective experiences to eight emotion films previously validated with young adults (Gross & Levenson, 1995). Participants rated their emotions, and heart rate was collected during two films of each emotion: amusement, anger, sadness, and fear. Older and younger adults were generally similar in their physiological and subjective responses to films, but with a few exceptions. Older adults reported more intense anger in response to one film and more intense nontarget negative emotions for both anger films compared with young adults. Some older adults also reported a negative response compared with young adults to one of the films designed to elicit amusement. Thus it is inappropriate to assume that emotional stimuli produce the same response across the adult life span. 相似文献
19.
Older adults generally experience high levels of life satisfaction (e.g., Charles & Carstensen, 2010) and participation in leisure activities may mediate some of their overall well-being. Frailty associated with biological aging may be related to reduced leisure activity engagement and loss of social belonging that may diminish life satisfaction (Charles, 2011). This study examined differences in leisure activity engagement by frailty status, and then tested a model evaluating the link between functional status and subjective well-being in a sample of 95 community-dwelling older adults. Participants completed self-report questionnaires that assessed leisure activity participation, life satisfaction, frailty, and mood. Leisure activities were coded as either social (e.g., taking classes) or solitary (e.g., reading) and summed across to create two composite scores. Results indicated there was a strong relationship between functional status and subjective well-being in older adults. High frailty and low social leisure engagement was associated with reduced subjective well-being. Implications for future research and clinical applications are discussed. 相似文献
20.
Roi Avraham 《Gut microbes》2016,7(6):518-525
The interface between immune cells and intracellular bacterial pathogens produces complex, diverse interactions. During individual encounters, highly adaptable and dynamic host cells and bacteria vary in their responses, thereby contributing to well-documented heterogeneous outcomes of infection. The challenge now is to break down the multidimensionality of these interactions into informative readouts of population physiology and predictors of responses to infection. We recently reported one approach to this challenge that couples single cell RNA-seq analysis with fluorescent markers to characterize infection phenotype.1 We detected bacterial subpopulations that elicit profoundly different host responses to infection in the specific host cells that they infect. Here we describe how heterogeneity might be maintained in populations of host and pathogens and discuss the advantages that heterogeneity confers to bacteria during infection and to host cells for eradicating a pathogen. We propose that single cell studies will allow the unraveling of host-pathogen biology and lead to an understanding of how the sum of individual encounters leads to the infection outcome of a whole organism. 相似文献