Be prepared - p585

doi:10.1038/nm0609-585

Pushing 'shovel-ready' technologies through the pipeline has the potential to substantially bolster defenses against the emerging flu strain and future pandemics.

Abstract - | Full Text - Be prepared | PDF (101 KB) - Be prepared

Computational tools evolve to reveal patterns in flu data - p587

Kirsten Dorans

doi:10.1038/nm0609-587

Full Text - Computational tools evolve to reveal patterns in flu data | PDF (180 KB) - Computational tools evolve to reveal patterns in flu data

Bone seems susceptible to range of drugs - p588

Charlotte Schubert

doi:10.1038/nm0609-588

Full Text - Bone seems susceptible to range of drugs | PDF (172 KB) - Bone seems susceptible to range of drugs

UK budget puts faith in biomedical sector - p589

Jon Evans

doi:10.1038/nm0609-589a

Full Text - UK budget puts faith in biomedical sector | PDF (77 KB) - UK budget puts faith in biomedical sector

NIH draft seen as 'working compromise' - p589

Stu Hutson

doi:10.1038/nm0609-589b

Full Text - NIH draft seen as 'working compromise' | PDF (77 KB) - NIH draft seen as 'working compromise'

Mind the skills gap - p589

Jon Evans

doi:10.1038/nm0609-589c

Full Text - Mind the skills gap | PDF (77 KB) - Mind the skills gap

News in brief - pp590 - 591

doi:10.1038/nm0609-590

Full Text - News in brief | PDF (761 KB) - News in brief

Straight talk with ... Otto Yang and Patrick Miller - pp592 - 593

Kirsten Dorans

doi:10.1038/nm0609-592

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.

Abstract - | Full Text - Straight talk with ... Otto Yang and Patrick Miller | PDF (597 KB) - Straight talk with ... Otto Yang and Patrick Miller

A cultured response to HIV - pp594 - 597

Melinda Wenner

doi:10.1038/nm0609-594

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.

Abstract - | Full Text - A cultured response to HIV | PDF (1,099 KB) - A cultured response to HIV

Publication of fake journals raises ethical questions - p598

Stu Hutson

doi:10.1038/nm0609-598a

Full Text - Publication of fake journals raises ethical questions | PDF (137 KB) - Publication of fake journals raises ethical questions

Malaria drug delivery program launches amid skepticism - p598

Nayanah Siva

doi:10.1038/nm0609-598b

Full Text - Malaria drug delivery program launches amid skepticism | PDF (137 KB) - Malaria drug delivery program launches amid skepticism

Worried about your memory? - p599

Howard Eichenbaum reviews Can't Remember What I Forgot: The Good News from the Front Lines of Memory Research by Sue Halpern

doi:10.1038/nm0609-599

Full Text - Worried about your memory? | PDF (106 KB) - Worried about your memory?

Mesenchymal stem cells: another anti-inflammatory treatment for sepsis? - pp601 - 602

Guillaume Monneret

doi:10.1038/nm0609-601

Full Text - Mesenchymal stem cells: another anti-inflammatory treatment for sepsis? | PDF (97 KB) - Mesenchymal stem cells: another anti-inflammatory treatment for sepsis?

Reply to 'Mesenchymal stem cells: another anti-inflammatory treatment for sepsis?' - p602

Krisztián Németh, Asada Leelahavanichkul, Peter S T Yuen, Balázs Mayer, Alissa Parmelee, Kent Doi, Pamela G Robey, Kantima Leelahavanichkul, Beverly H Koller, Jared M Brown, Xuzhen Hu, Ivett Jelinek, Robert A Star & Éva Mezey

doi:10.1038/nm0609-602a

Full Text - Reply to 'Mesenchymal stem cells: another anti-inflammatory treatment for sepsis?' | PDF (86 KB) - Reply to 'Mesenchymal stem cells: another anti-inflammatory treatment for sepsis?'

Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays - pp602 - 604

Thierry Bonnefoix & Mary Callanan

doi:10.1038/nm0609-602b

Full Text - Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays | PDF (206 KB) - Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays

Reply to 'Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays' - pp604 - 605

Peter Eirew, Miao Yu, Ryan Brinkman & Connie J Eaves

doi:10.1038/nm0609-604

Full Text - Reply to 'Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays' | PDF (140 KB) - Reply to 'Reassessing the human mammary stem cell concept by modeling limiting dilution transplantation assays'

In the shadow of the thrombus - pp607 - 608

Lawrence Brass

doi:10.1038/nm0609-607

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).

Abstract - | Full Text - In the shadow of the thrombus | PDF (1,874 KB) - In the shadow of the thrombus

See also: Article by Nesbitt et al.

Tension in the vasculature - pp608 - 610

Andrew V Benest & Hellmut G Augustin

doi:10.1038/nm0609-608

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).

Abstract - | Full Text - Tension in the vasculature | PDF (1,148 KB) - Tension in the vasculature

See also: Article by Kilarski et al.

Stomaching calcium for bone health - pp610 - 612

Brendan F Boyce

doi:10.1038/nm0609-610

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)?

Abstract - | Full Text - Stomaching calcium for bone health | PDF (1,188 KB) - Stomaching calcium for bone health

See also: Article by Schinke et al.

IFN- wakes up sleeping hematopoietic stem cells - pp612 - 613

Emmanuelle Passegué & Patricia Ernst

doi:10.1038/nm0609-612

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

Abstract - | Full Text - IFN- wakes up sleeping hematopoietic stem cells | PDF (968 KB) - IFN- wakes up sleeping hematopoietic stem cells

See also: Letter by Sato et al.

Compound clamps down on prostate cancer - p615

doi:10.1038/nm0609-615

Full Text - Compound clamps down on prostate cancer | PDF (127 KB) - Compound clamps down on prostate cancer

Expansion and contraction: treating diabetes with bariatric surgery - pp616 - 617

Allison B Goldfine, Steven E Shoelson & Vincent Aguirre

doi:10.1038/nm0609-616

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.

Abstract - | Full Text - Expansion and contraction: treating diabetes with bariatric surgery | PDF (632 KB) - Expansion and contraction: treating diabetes with bariatric surgery

Expansion and contraction: the mighty, mighty fatty acid - pp618 - 619

Jorge Plutzky

doi:10.1038/nm0609-618

Full Text - Expansion and contraction: the mighty, mighty fatty acid | PDF (2,545 KB) - Expansion and contraction: the mighty, mighty fatty acid

Research Highlights - pp620 - 621

doi:10.1038/nm0609-620

Full Text - Research Highlights | PDF (209 KB) - Research Highlights

Netting neutrophils in autoimmune small-vessel vasculitis - pp623 - 625

Kai Kessenbrock, Markus Krumbholz, Ulf Schönermarck, Walter Back, Wolfgang L Gross, Zena Werb, Hermann-Josef Gröne, Volker Brinkmann & Dieter E Jenne

doi:10.1038/nm.1959

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.

Abstract - | Full Text - Netting neutrophils in autoimmune small-vessel vasculitis | PDF (554 KB) - Netting neutrophils in autoimmune small-vessel vasculitis | Supplementary information

Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis - pp626 - 632

Gurumoorthy Krishnamoorthy, Amit Saxena, Lennart T Mars, Helena S Domingues, Reinhard Mentele, Avraham Ben-Nun, Hans Lassmann, Klaus Dornmair, Florian C Kurschus, Roland S Liblau & Hartmut Wekerle

doi:10.1038/nm.1975

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.

Abstract - | Full Text - Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis | PDF (526 KB) - Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis | Supplementary information

Prostaglandin E₂–EP4 signaling promotes immune inflammation through T_H1 cell differentiation and T_H17 cell expansion - pp633 - 640

Chengcan Yao, Daiji Sakata, Yoshiyasu Esaki, Youxian Li, Toshiyuki Matsuoka, Kenji Kuroiwa, Yukihiko Sugimoto & Shuh Narumiya

doi:10.1038/nm.1968

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.

Abstract - | Full Text - Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion | PDF (657 KB) - Prostaglandin E2–EP4 signaling promotes immune inflammation through TH1 cell differentiation and TH17 cell expansion | Supplementary information

Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome - pp641 - 648

Thu A Chau, Michelle L McCully, William Brintnell, Gary An, Katherine J Kasper, Enrique D Vinés, Paul Kubes, S M Mansour Haeryfar, John K McCormick, Ewa Cairns, David E Heinrichs & Joaquín Madrenas

doi:10.1038/nm.1965

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.

Abstract - | Full Text - Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome | PDF (486 KB) - Toll-like receptor 2 ligands on the staphylococcal cell wall downregulate superantigen-induced T cell activation and prevent toxic shock syndrome | Supplementary information

Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II–induced aortic aneurysms - pp649 - 656

Kimio Satoh, Patrizia Nigro, Tetsuya Matoba, Michael R O'Dell, Zhaoqiang Cui, Xi Shi, Amy Mohan, Chen Yan, Jun-ichi Abe, Karl A Illig & Bradford C Berk

doi:10.1038/nm.1958

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.

Abstract - | Full Text - Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II–induced aortic aneurysms | PDF (864 KB) - Cyclophilin A enhances vascular oxidative stress and the development of angiotensin II–induced aortic aneurysms | Supplementary information

Biomechanical regulation of blood vessel growth during tissue vascularization - pp657 - 664

Witold W Kilarski, Branka Samolov, Ludvig Petersson, Anders Kvanta & Pär Gerwins

doi:10.1038/nm.1985

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).

Abstract - | Full Text - Biomechanical regulation of blood vessel growth during tissue vascularization | PDF (1,065 KB) - Biomechanical regulation of blood vessel growth during tissue vascularization | Supplementary information

See also: News and Views by Benest & Augustin

A shear gradient–dependent platelet aggregation mechanism drives thrombus formation - pp665 - 673

Warwick S Nesbitt, Erik Westein, Francisco Javier Tovar-Lopez, Elham Tolouei, Arnan Mitchell, Jia Fu, Josie Carberry, Andreas Fouras & Shaun P Jackson

doi:10.1038/nm.1955

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).

Abstract - | Full Text - A shear gradient–dependent platelet aggregation mechanism drives thrombus formation | PDF (775 KB) - A shear gradient–dependent platelet aggregation mechanism drives thrombus formation | Supplementary information

See also: News and Views by Brass

Impaired gastric acidification negatively affects calcium homeostasis and bone mass - pp674 - 681

Thorsten Schinke, Arndt F Schilling, Anke Baranowsky, Sebastian Seitz, Robert P Marshall, Tilman Linn, Michael Blaeker, Antje K Huebner, Ansgar Schulz, Ronald Simon, Matthias Gebauer, Matthias Priemel, Uwe Kornak, Sandra Perkovic, Florian Barvencik, F Timo Beil, Andrea Del Fattore, Annalisa Frattini, Thomas Streichert, Klaus Pueschel, Anna Villa, Klaus-Michael Debatin, Johannes M Rueger, Anna Teti, Jozef Zustin, Guido Sauter & Michael Amling

doi:10.1038/nm.1963

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.

Abstract - | Full Text - Impaired gastric acidification negatively affects calcium homeostasis and bone mass | PDF (1,064 KB) - Impaired gastric acidification negatively affects calcium homeostasis and bone mass

See also: News and Views by Boyce

Inhibition of osteoblastic bone formation by nuclear factor-B - pp682 - 689

Jia Chang, Zhuo Wang, Eric Tang, Zhipeng Fan, Laurie McCauley, Renny Franceschi, Kunliang Guan, Paul H Krebsbach & Cun-Yu Wang

doi:10.1038/nm.1954

It has been well shown that NF-B 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-B specifically in osteoblasts increases bone formation and protects against bone loss in experimentally-induced osteoporosis in mice.

Abstract - | Full Text - Inhibition of osteoblastic bone formation by nuclear factor-B | PDF (1,000 KB) - Inhibition of osteoblastic bone formation by nuclear factor-B | Supplementary information

Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model - pp690 - 695

May Christine V Malicdan, Satoru Noguchi, Yukiko K Hayashi, Ikuya Nonaka & Ichizo Nishino

doi:10.1038/nm.1956

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.

First Paragraph - | Full Text - Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model | PDF (492 KB) - Prophylactic treatment with sialic acid metabolites precludes the development of the myopathic phenotype in the DMRV-hIBM mouse model | Supplementary information

Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion - pp696 - 700

Taku Sato, Nobuyuki Onai, Hiroki Yoshihara, Fumio Arai, Toshio Suda & Toshiaki Ohteki

doi:10.1038/nm.1973

Although type I interferons such as interferon- 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).

First Paragraph - | Full Text - Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion | PDF (398 KB) - Interferon regulatory factor-2 protects quiescent hematopoietic stem cells from type I interferon–dependent exhaustion | Supplementary information

See also: News and Views by Passegué & Ernst

Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche - pp701 - 706

Akifumi Ootani, Xingnan Li, Eugenio Sangiorgi, Quoc T Ho, Hiroo Ueno, Shuji Toda, Hajime Sugihara, Kazuma Fujimoto, Irving L Weissman, Mario R Capecchi & Calvin J Kuo

doi:10.1038/nm.1951

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.

Abstract - | Full Text - Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche | PDF (780 KB) - Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche | Supplementary information