Damage to the tissue and the ruining of functions characterize autoimmune syndromes. This review centers around leaky gut syndromes and how they stimulate autoimmune pathogenesis. Lymphoid tissue commonly associated with the gut, together with the neuroendocrine network, collaborates with the intestinal epithelial wall, with its paracellular tight junctions, to maintain the balance, tolerance, and resistance to foreign/neo-antigens. The physiological regulator of paracellular tight junctions plays a vital role in transferring macromolecules across the intestinal barrier and thereby maintains immune response equilibrium. A new paradigm has explained the intricacies of disease development and proposed that the processes can be prevented if the interaction between the genetic factor and environmental causes is barred by re-instituting the intestinal wall function. The latest clinical evidence and animal models reinforce this current thought and offer the basis for innovative methodologies to thwart and treat autoimmune syndromes.
The pink pigeon (Nesoenas mayeri ) is an endemic species of Mauritius that has made a remarkable recovery after a severe population bottleneck in the 1970s to early 1990s. Prior to this bottleneck, an ex situ population was established from which captive-bred individuals were released into free-living subpopulations to increase population size and genetic variation. This conservation rescue led to rapid population recovery to 400-480 individuals, and the species was twice downlisted on the International Union for the Conservation of Nature (IUCN) Red List. We analyzed the impacts of the bottleneck and genetic rescue on neutral genetic variation during and after population recovery (1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) with restriction site-associated sequencing, microsatellite analyses, and quantitative genetic analysis of studbook data of 1112 birds from zoos in Europe and the United States. We used computer simulations to study the predicted changes in genetic variation and population viability from the past into the future. Genetic variation declined rapidly, despite the population rebound, and the effective population size was approximately an order of magnitude smaller than census size. The species carried a high genetic load of circa 15 lethal equivalents for longevity. Our computer simulations predicted continued inbreeding will likely result in increased expression of deleterious mutations (i.e., a high realized load) and severe inbreeding depression. Without continued conservation actions, it is likely that the pink pigeon will go extinct in the wild within 100 years. Conservation rescue of the pink pigeon has been instrumental in the recovery of the free-living population. However, further genetic rescue with captive-bred birds from zoos is required to recover lost variation, reduce expression of harmful deleterious variation, and prevent extinction. The use of genomics and modeling data can inform IUCN assessments of the viability and extinction risk of species, and it helps in assessments of the conservation dependency of populations.
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