Rho GTPases are frequent targets of virulence factors as they are keystone signaling molecules. Herein, we demonstrate that AMPylation of Rho GTPases by VopS is a multifaceted virulence mechanism that counters several host immunity strategies. Activation of NFκB, Erk, and JNK kinase signaling pathways were inhibited in a VopS-dependent manner during infection with Vibrio parahaemolyticus. Phosphorylation and degradation of IKBα were inhibited in the presence of VopS as was nuclear translocation of the NFκB subunit p65. AMPylation also prevented the generation of superoxide by the phagocytic NADPH oxidase complex, potentially by inhibiting the interaction of Rac and p67. Furthermore, the interaction of GTPases with the E3 ubiquitin ligases cIAP1 and XIAP was hindered, leading to decreased degradation of Rac and RhoA during infection. Finally, we screened for novel Rac1 interactions using a nucleic acid programmable protein array and discovered that Rac1 binds to the protein C1QA, a protein known to promote immune signaling in the cytosol. Interestingly, this interaction was disrupted by AMPylation. We conclude that AMPylation of Rho Family GTPases by VopS results in diverse inhibitory consequences during infection beyond the most obvious phenotype, the collapse of the actin cytoskeleton.
The literature including social media shows that Mexican/Latino immigrants have attracted contempt and have been traditionally objected to as a minority in the U.S. The intent here is to search for historical and other factors that might explain the public antipathy and to identify reasons that could, either in isolation or in combination with others, explain anti-immigrant sentiments among people, many of whom are descendants of immigrants. The perusal of the challenges of Mexican immigrants to the U.S. through the decades will highlight some similarities related to discrimination against waves “peoples of color”, not only in the U.S. but in other parts of the world. The daily treatment within the society of immigrants of color as well as the frequent lower immigration quotas imposed on certain groups, including Mediterranean people, makes the topic quite relevant to today’s concerns.
This article presents an exploration of the relationship between community building and lifelong learning. Using a reflective style, the authors propose that the fusion of community building principles with lifelong learning practice can positively transform educational practice. Seven positive pursuits are highlighted regarding their potential to assist the implementation of community building into lifelong learning programs: (1) asset-based thinking; (2) critical reflection; (3) systems thinking; (4) cognitive vibrancy, (5) inclusiveness; (6) creative expression; and, (7) purpose in life. These pursuits draw upon the power of the community development field to bring about more positive transformative moments for individuals and communities participating in lifelong learning programs. The metaphor of bread making is used to illustrate how such transformative moments occur and why they are meaningful to individuals pursuing lifelong learning.
The increased interdependence and complexity of modern societies have increased the need to involve all members of a community into solving problems. In times of great uncertainty, when communities face threats of different kinds and magnitudes, the traditional top-down approach where government provides solely for community wellbeing is no longer plausible. Crowdsourcing has emerged as an effective means of empowering communities with the potential to engage individuals in innovation, self-organization activities, informal learning, mutual support, and political action that can all lead to resilience. However, there remains limited resource on the topic. In this paper, we outline the various forms of crowdsourcing, economic and community resilience, crowdsourcing and economic resilience, and a case study of the Nepal earthquake. his article presents an exploratory perspective on the link can be found between crowdsourcing and economic resilience. It introduces and describes a framework that can be used to study the impact of crowdsourcing initiatives for economic resilience by future research. An initial a set of indicators to be used to measure the change in the level of resilience is presented.
Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n = 1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI = 0.94, RMSEA = 0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management.
Many municipal governments have adopted affordable housing policies to benefit people whose socio-economic status is not commensurate with the price of housing. However, the effects and the functions of these policies in the city on sustainable development and living remains limited. Using a comparative case study, this study explores the characteristics and effects of affordable housing policies in three metropolitan cities in China: Beijing, Tianjin, and Guangshou. This study finds that these cities have their unique affordable housing policies and have experienced various challenges in implementing those policies. Conclusions and implications for other cities in China are addressed.
High proportions of autistic children suffer from gastrointestinal (GI) disorders, implying a link between autism and abnormalities in gut microbial functions. Increasing evidence from recent high-throughput sequencing analyses indicates that disturbances in composition and diversity of gut microbiome are associated with various disease conditions. However, microbiome-level studies on autism are limited and mostly focused on pathogenic bacteria. Therefore, here we aimed to define systemic changes in gut microbiome associated with autism and autism-related GI problems. We recruited 20 neurotypical and 20 autistic children accompanied by a survey of both autistic severity and GI symptoms. By pyrosequencing the V2/V3 regions in bacterial 16S rDNA from fecal DNA samples, we compared gut microbiomes of GI symptom-free neurotypical children with those of autistic children mostly presenting GI symptoms. Unexpectedly, the presence of autistic symptoms, rather than the severity of GI symptoms, was associated with less diverse gut microbiomes. Further, rigorous statistical tests with multiple testing corrections showed significantly lower abundances of the genera Prevotella, Coprococcus, and unclassified Veillonellaceae in autistic samples. These are intriguingly versatile carbohydrate-degrading and/or fermenting bacteria, suggesting a potential influence of unusual diet patterns observed in autistic children. However, multivariate analyses showed that autism-related changes in both overall diversity and individual genus abundances were correlated with the presence of autistic symptoms but not with their diet patterns. Taken together, autism and accompanying GI symptoms were characterized by distinct and less diverse gut microbial compositions with lower levels of Prevotella, Coprococcus, and unclassified Veillonellaceae.
on-cisgender identity, age of awareness, age of social transition, primary caregiver acceptance, secondary caregiver acceptance, and mental health. Hypotheses were partially supported for age of social transition with mental health, parental acceptance with mental health, and awareness-transition gap with parental acceptance. This study investigated under studied concepts of social transition and parental acceptance that appear to have an effect on the mental health of transgender adults.