Volume 15 Issue 6, June 2009

Even with a recent influx of research money into biomedical research, competition for grants is unlikely to ease off any time soon. Otto Yang and Patrick Miller have experienced firsthand the challenges grant writing and both published books on the process. Yang and Miller shared some of their grant writing tips with Kirsten Dorans.

In recent years, research has continued to demonstrate that HIV wreaks terrible havoc in the gut. A few scientists believe that probiotic yogurt might help to counter some of the virus's devastating effects on the intestine. Melinda Wenner reports on a pilot project that is helping a Tanzanian community make its own probiotic yogurt for HIV-infected locals and empowering women in the process.

Platelets accumulate on the downstream face of a developing blood clot after local changes in blood flow. These findings offer new insights into how platelets pile up at sites of vascular injury (pages 665–673).

Blood vessels arise from progenitor cells, grow and branch by sprouting from preexisting vessels and remodel by splitting longitudinally. A new study proposes an additional mechanism. It seems that vascularization can proceed through the mechanical translocation and expansion of existing vessels, which loop into vascularising tissue (pages 657–664).

Calcium deficiency in the elderly is associated with low gastric acid secretion and bone loss. A new study linking defects in gastric acid secretion with bone destruction and impaired mineralization bolsters the view that calcium supplements can prevent these bone defects—but do they all work (pages 674–681)?

The cytokine interferon-α stimulates the turnover and proliferation of hematopoietic cells in vivo (pages 696–700). The findings hint at a new strategy to treat hematopoietic cancers.

Bariatric surgery is not only one of the most immediate and effective ways to slim down: recent clinical data show that certain procedures are also particularly good at quelling type 2 diabetes. In “Bedside to Bench,” Allison Goldfine, Steven Shoelson and Vincent Aguirre outline how researchers can better understand these new clinical findings at the mechanistic level. In the accompanying “Bench to Bedside,” Jorge Plutzky takes a look how proper regulation of the storage of fatty acids helps maintain their effectiveness as signaling molecules and reins in their potential pathological effects. Such research is leading to new ways of thinking about how to combat type 2 diabetes.

Neutrophils release neutrophil extracellular traps (NETs), chromatin fibers that can ensnare bacteria. In small-vessel vasculitis (SVV), a chronic inflammatory condition linked to antineutrophil autoantibodies, these NETs express SVV-associated autoantigens, accumulate in inflamed kidneys and promote the autoimmune response against neutrophils in people with SVV.

T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue.

Prostaglandins play a key role in inflammation in a variety of settings. Now, Shuh Narumiya and colleagues show that prostaglandin E2 drives the production of inflammatory T helper cells, and that this can be blocked by inhibiting its EP4 receptor subtype. EP4 inhibitors were also effective at inhibiting disease pathogenesis in animal models of two inflammatory diseases.

Staphylococcal superantigens are potent activators of T cells, causing toxic shock syndrome and death. But surprisingly few staphylococcal infections of humans are associated with TSS, even though the bacteria produce the superantigen toxins. Joaquin Madrenas and his colleagues report that other components of the bacteria can downregulate the superantigen-induced T cell activation, protecting the host from death by TSS.

The pathogenesis of aortic aneurysms involves inflammatory cell recruitment and increased levels of reactive oxygen species and matrix metalloproteases. Kimio Satoh et al. now mechanistically link the protein cyclophilin A—expressed in vascular smooth muscle cells—to these known mediators of aortic aneurysm formation and provide evidence in both mice and humans for the importance of cyclophilin A in aortic aneurysm formation.

In this report, Witold Kilarski et al. show that the rapid formation of new vessels in healing wound tissue does not depend on endothelial cell proliferation and sprouting, which typically have been presumed to be needed for the growth of new blood vessels. Instead, preexisting vessels enlarge and translocate, a process driven by the tension generated by contracting fibroblasts and/or myofibroblasts (pages 608–610).

Warwick Nesbitt, Erik Westein and coworkers describe a new mechanistic model for thrombus growth within a blood vessel, providing evidence that blood flow shear gradients—which can arise from vessel injury, stenosis or obstruction—are important in driving thrombus formation. Rapid changes in blood shear rates lead to dynamic restructuring of membranous structures, called 'tethers', on the platelet surface, facilitating stable platelet deposition onto a growing thrombus (pages 607–608).

Proper calcium levels are needed to maintain healthy bones. Michael Amling and his colleagues now show that gastric acidification is a key part of in this process. These findings have possible important clinical implications for patients with osteoporosis and/or those on proton-pump inhibitors, as well as those with a rare genetic disease that causes excess bone mass.

It has been well shown that NF-κB has a crucial role in promoting the maturation of bone-resorbing osteoclasts. Now, Cun-Yu Wang and his colleagues show that it also has a role in inhibiting the function of mature bone-forming osteoblasts. They go on to show that deficiency of NF-κB specifically in osteoblasts increases bone formation and protects against bone loss in experimentally-induced osteoporosis in mice.

In a new report, Satoru Noguchi and his colleagues have shown that oral administration of various sialic acid compounds helps improve the behavior of skeletal muscles in a mouse model of a severely debilitating human muscle disease—one with no current treatment option. Given the simplicity of their approach, it is possible these findings could have immediate clinical impact.

Although type I interferons such as interferon-α are well known to protect against viral infection, they may have other physiological effects in the uninfected state. Taku Sato et al. now show that type I interferon signaling in hematopoietic stem cells promotes their proliferation and impairs their ability to reconstitute the hematopoietic system (pages 696–700).

The development of a long-term intestinal culture system has, until recently, eluded researchers. Here the authors describe a method allowing long-term culture of both small intestine and colon that incorporates an air-liquid interface coupled with a three-dimensional matrix scaffold. The cultures show epithelial cell proliferation and multilineage differentiation to the major cell types and accurately recapitulate the Wnt- and Notch-dependent intestinal stem cell niche.