Allergen-specific immunotherapy (IT) is widely used to treat allergic diseases. The molecular mechanisms have not been clarified yet completely. The present work was undertaken to analyze the effect of IT in the activation of NF-?B.
The Colorado Clinical and Translational Sciences Institute (CCTSI) aims to translate discovery into clinical practice. The Partnership of Academicians and Communities for Translation (PACT) represents a robust campus-community partnership.
Loss or duplication of chromosome segments can lead to further genomic changes associated with cancer. However, it is not known whether only a select subset of genes is responsible for driving further changes. To determine whether perturbation of any given gene in a genome suffices to drive subsequent genetic changes, we analyzed the yeast knockout collection for secondary mutations of functional consequence. Unlike wild-type, most gene knockout strains were found to have one additional mutant gene affecting nutrient responses and/or heat-stress-induced cell death. Moreover, independent knockouts of the same gene often evolved mutations in the same secondary gene. Genome sequencing identified acquired mutations in several human tumor suppressor homologs. Thus, mutation of any single gene may cause a genomic imbalance, with consequences sufficient to drive adaptive genetic changes. This complicates genetic analyses but is a logical consequence of losing a functional unit originally acquired under pressure during evolution.
Mammalian Bcl-x(L) protein localizes to the outer mitochondrial membrane, where it inhibits apoptosis by binding Bax and inhibiting Bax-induced outer membrane permeabilization. Contrary to expectation, we found by electron microscopy and biochemical approaches that endogenous Bcl-x(L) also localized to inner mitochondrial cristae. Two-photon microscopy of cultured neurons revealed large fluctuations in inner mitochondrial membrane potential when Bcl-x(L) was genetically deleted or pharmacologically inhibited, indicating increased total ion flux into and out of mitochondria. Computational, biochemical, and genetic evidence indicated that Bcl-x(L) reduces futile ion flux across the inner mitochondrial membrane to prevent a wasteful drain on cellular resources, thereby preventing an energetic crisis during stress. Given that F(1)F(O)-ATP synthase directly affects mitochondrial membrane potential and having identified the mitochondrial ATP synthase ? subunit in a screen for Bcl-x(L)-binding partners, we tested and found that Bcl-x(L) failed to protect ? subunit-deficient yeast. Thus, by bolstering mitochondrial energetic capacity, Bcl-x(L) may contribute importantly to cell survival independently of other Bcl-2 family proteins.
Peer review is fundamentally a cooperative process between scientists in a community who agree to review each others work in an unbiased fashion. Peer review is the foundation for decisions concerning publication in journals, awarding of grants, and academic promotion. Here we perform a laboratory study of open and closed peer review based on an online game. We show that when reviewer behavior was made public under open review, reviewers were rewarded for refereeing and formed significantly more cooperative interactions (13% increase in cooperation, P?=?0.018). We also show that referees and authors who participated in cooperative interactions had an 11% higher reviewing accuracy rate (P?=?0.016). Our results suggest that increasing cooperation in the peer review process can lead to a decreased risk of reviewing errors.
A common observation in tropical dry forests is the habitat preference of tree species along spatial soil water gradients. This pattern of habitat partitioning might be a result of species differentiation in their strategy for using water, along with competing functions such as maximizing water exploitation and tolerating soil water stress. We tested whether species from drier soil conditions exhibited a tolerance strategy compared with that of wet-habitat species. In a comparison of 12 morphophysiological traits in seedlings of 10 closely related dry and wet-habitat species pairs, we explored what trade-offs guide differentiation between habitats and species. Contrary to our expectations, dry-habitat species showed mostly traits associated with an exploitation strategy (higher carbon assimilation capacity, specific leaf area and leaf-specific conductivity and lower water-use efficiency). Strikingly, dry-habitat species tended to retain their leaves longer during drought. Additionally, we detected multiple strategies to live within each habitat, in part due to variation of strategies among lineages, as well as functional differentiation along the water storage capacity-stem density (xylem safety) trade-off. Our results suggest that fundamental trade-offs guide functional niche differentiation among tree species expressed both within and between soil water habitats in a tropical dry forest.
Anopheles arabiensis is a major vector of Plasmodium falciparum in southern Zambia. This study aimed to determine the rate of multiple human blood meals taken by An. arabiensis to more accurately estimate entomologic inoculation rates (EIRs). Mosquitoes were collected in four village areas over two seasons. DNA from human blood meals was extracted and amplified at four microsatellite loci. Using the three-allele method, which counts > or = 3 alleles at any microsatellite locus as a multiple blood meal, we determined that the overall frequency of multiple blood meals was 18.9%, which was higher than rates reported for An. gambiae in Kenya and An. funestus in Tanzania. Computer simulations showed that the three-allele method underestimates the true multiple blood meal proportion by 3-5%. Although P. falciparum infection status was not shown to influence the frequency of multiple blood feeding, the high multiple feeding rate found in this study increased predicted malaria risk by increasing EIR.
Asticot maggot (Blowfly, Calliphoridae family) is the most important live bait used for angling in our country. Prevalence of allergy to live fish bait in occupationally exposed workers has been described. The purpose of this study was to determine the prevalence of asticot allergy in amateur fishermen and the identification of marketed asticot species in Cáceres, Spain.
Mitochondrial fission and fusion are linked to synaptic activity in healthy neurons and are implicated in the regulation of apoptotic cell death in many cell types. We developed fluorescence microscopy and computational strategies to directly measure mitochondrial fission and fusion frequencies and their effects on mitochondrial morphology in cultured neurons. We found that the rate of fission exceeds the rate of fusion in healthy neuronal processes, and, therefore, the fission/fusion ratio alone is insufficient to explain mitochondrial morphology at steady state. This imbalance between fission and fusion is compensated by growth of mitochondrial organelles. Bcl-x(L) increases the rates of both fusion and fission, but more important for explaining the longer organelle morphology induced by Bcl-x(L) is its ability to increase mitochondrial biomass. Deficits in these Bcl-x(L)-dependent mechanisms may be critical in neuronal dysfunction during the earliest phases of neurodegeneration, long before commitment to cell death.
The mechanisms of drought resistance that allow plants to successfully establish at different stages of secondary succession in tropical dry forests are not well understood. We characterized mechanisms of drought resistance in early and late-successional species and tested whether risk of drought differs across sites at different successional stages, and whether early and late-successional species differ in resistance to experimentally imposed soil drought. The microenvironment in early successional sites was warmer and drier than in mature forest. Nevertheless, successional groups did not differ in resistance to soil drought. Late-successional species resisted drought through two independent mechanisms: high resistance of xylem to embolism, or reliance on high stem water storage capacity. High sapwood water reserves delayed the effects of soil drying by transiently decoupling plant and soil water status. Resistance to soil drought resulted from the interplay between variations in xylem vulnerability to embolism, reliance on sapwood water reserves and leaf area reduction, leading to a tradeoff of avoidance against tolerance of soil drought, along which successional groups were not differentiated. Overall, our data suggest that ranking species performance under soil drought based solely on xylem resistance to embolism may be misleading, especially for species with high sapwood water storage capacity.
In the last decade the use of different types of oral immunotherapy for food-allergic patients has increased with generally satisfactory outcomes. Cows milk and hens egg, a common element in the daily diet, have received the main interest. Most of these immunotherapy regimens are performed in the hospital, causing inconvenience for both children and their parents.
For underserved and disenfranchised communities in the United States, affordable, effective health care can be nearly inaccessible, which often leads to the exclusion of these communities from relevant medical information and care. Barriers to care are especially salient in minority communities, where language, traditions and customs, socioeconomics, and access to education can serve as additional roadblocks to accessing health care information and services. These factors have contributed to a national health disparity crisis that unnecessarily places some communities in a vulnerable position without adequate prevention and treatment opportunities. One solution to the exclusion some communities face in the health care system may be the promotores de salud (PdS)/community health worker (CHW), an approach to culturally competent health care delivery whose popularity in the mainstream health care system has been steadily growing in recent decades. Known by a wide variety of names and broad in the spectrum of health issues they address, the PdS/CHW serves as cultural brokers between their own community and the formal health care system and can play a crucial role in promoting health and wellness within their community. This annotated bibliography was created to educate the reader about the history, definition, key features, utility, outcomes, and broad potential of the CHW approach in a variety of populations. Intended to serve as a reference point to a vast body of information on the CHW/PdS approach, this document is a resource for those wishing to effect change in the disparities within the health care system, and to improve the access to, quality, and cost of health care for underserved patients and their communities. Promotores de Salud is a Spanish term that translates to Health Promoter. A female health worker may be referred to as a Promotora, a male as a Promotor, and the plural of both is Promotores. For the purposes of this bibliography, the terms community health worker and promotores de salud may be used interchangeably.
The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health disparities in populations.
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