Opportunities For Diseases Research Articles

Acute Inflammatory Recovery-A Matter of Sophisticated Interaction of Two Cell Populations?

Acute Inflammatory Recovery-A Matter of Sophisticated Interaction of Two Cell Populations?

Tunicamycin Protects against LPS-Induced Lung Injury.

The pulmonary endothelium is a dynamic semipermeable barrier that orchestrates tissue-fluid homeostasis; regulating physiological and immunological responses. Endothelial abnormalities are caused by inflammatory stimuli interacting with intracellular messengers to remodel cytoskeletal junctions and adhesion proteins. Those phenomena are associated with sepsis, acute lung injury, and acute respiratory distress syndrome. The molecular processes beyond those responses are the main interest of our group. Unfolded protein response (UPR) is a highly conserved molecular pathway resolving protein-folding defects to counteract cellular threats. An emerging body of evidence suggests that UPR is a promising target against lung and cardiovascular disease. In the present study, we reveal that Tunicamycin (TM) (UPR inducer) protects against lipopolysaccharide (LPS)-induced injury. The barrier function of the inflamed endothelium was evaluated in vitro (transendothelial and paracellular permeability); as well as in mice exposed to TM after LPS. Our study demonstrates that TM supports vascular barrier function by modulating actomyosin remodeling. Moreover, it reduces the internalization of vascular endothelial cadherin (VE-cadherin), enhancing endothelial integrity. We suggest that UPR activation may deliver novel therapeutic opportunities in diseases related to endothelial dysregulation.

Dynamic nature of somatic chromosomal mosaicism, genetic-environmental interactions and therapeutic opportunities in disease and aging

BackgroundSomatic chromosomal mosaicism is the presence of cell populations differing with respect to the chromosome complements (e.g. normal and abnormal) in an individual. Chromosomal mosaicism is associated with a wide spectrum of disease conditions and aging. Studying somatic genome variations has indicated that amounts of chromosomally abnormal cells are likely to be unstable. As a result, dynamic changes of mosaicism rates occur through ontogeny. Additionally, a correlation between disease severity and mosaicism rates appears to exist. High mosaicism rates are usually associated with severe disease phenotypes, whereas low-level mosaicism is generally observed in milder disease phenotypes or in presumably unaffected individuals. Here, we hypothesize that dynamic nature of somatic chromosomal mosaicism may result from genetic-environmental interactions creating therapeutic opportunities in the associated diseases and aging.ConclusionGenetic-environmental interactions seem to contribute to the dynamic nature of somatic mosaicism. Accordingly, an external influence on cellular populations may shift the ratio of karyotypically normal and abnormal cells in favor of an increase in the amount of cells without chromosome rearrangements. Taking into account the role of somatic chromosomal mosaicism in health and disease, we have hypothesized that artificial changing of somatic mosaicism rates may be beneficial in individuals suffering from the associated diseases and/or behavioral or reproductive problems. In addition, such therapeutic procedures might be useful for anti-aging strategies (i.e. possible rejuvenation through a decrease in levels of chromosomal mosaicism) increasing the lifespan. Finally, the hypothesis appears to be applicable to any type of somatic mosacism.

Hypoxia: a double-edged sword of immunity

Hypoxia is a condition of low oxygen tension that characterizes virtually every site of inflammation, tissue damage, and neoplasia. Hypoxic environment attracts infiltrating immune cells that move against oxygen gradients and respond to these demanding conditions by switching to anaerobic metabolism to maintain their energy requirements. Several lines of evidence suggest that oxygen deprivation causes opposite effects on the innate or adaptive immune responses. We will review the evidence that the hypoxic environment promotes the recruitment, activation, and survival of innate immune cells while inhibiting the adaptive immunity through downregulation of effector lymphocyte functions. This divergent regulation of the innate and adaptive immunity appears to reflect evolutionary mechanisms aimed to both guarantee tissue homeostasis and provide safeguard mechanisms against autoimmunity. Selective inhibition of hypoxic signaling pathways in myeloid versus lymphoid cells may open new therapeutic opportunities in diseases characterized by low oxygen tension.

Monitoring Linked Epidemics: The Case of Tuberculosis and HIV

BackgroundThe tight epidemiological coupling between HIV and its associated opportunistic infections leads to challenges and opportunities for disease surveillance.Methodology/Principal FindingsWe review efforts of WHO and collaborating agencies to track and fight the TB/HIV co-epidemic, and discuss modeling—via mathematical, statistical, and computational approaches—as a means to identify disease indicators designed to integrate data from linked diseases in order to characterize how co-epidemics change in time and space. We present R TB/HIV, an index comparing changes in TB incidence relative to HIV prevalence, and use it to identify those sub-Saharan African countries with outlier TB/HIV dynamics. R TB/HIV can also be used to predict epidemiological trends, investigate the coherency of reported trends, and cross-check the anticipated impact of public health interventions. Identifying the cause(s) responsible for anomalous R TB/HIV values can reveal information crucial to the management of public health.Conclusions/SignificanceWe frame our suggestions for integrating and analyzing co-epidemic data within the context of global disease monitoring. Used routinely, joint disease indicators such as R TB/HIV could greatly enhance the monitoring and evaluation of public health programs.

A Tagging Study on Yellowtail Kingfish (Seriola Lalandi) and Samson Fish (S. Hippos) in South Australian Waters

SummaryWild yellowtail kingfish (Seriola lalandi Valenciennes, 1833) and Samson fish (S. hippos Günther, 1876) were tagged with nylon-headed, single-barbed dart tags between December 1, 2004 and December 31, 2006 in Spencer Gulf and offshore from the west coast of Eyre Peninsula, South Australia. Two-hundred and forty-one S. lalandi and 73 S. hippos were tagged. Twenty-four S. lalandi were recaptured and the maximum distance between capture points was 130 km and the maximum time at liberty was 442 days. Two S. hippos were recaptured, of which one was at liberty for a maximum of 378 days. Both S. hippos were recaptured at the original capture site. Recapture results indicate that large S. lalandi remain in, or return to, northern Spencer Gulf. This region may be important for aggregations of large, reproductively mature S. lalandi. One large S. lalandi tagged at Port Augusta was recaptured near Fitzgerald Bay, indicating that wild fish may move past S. lalandi sea-cage farms in this region. This course of movement may provide opportunities for disease and parasite interactions between wild and farmed fish. An additional outcome of this research was the residual impact that it has had on sustainable fishing practices in South Australia with increased recreational fisher participation in the tag and release of S. lalandi and S. hippos.