Press release from Nature and the Nature Research Journals

Newswise — ****************************************************NATURE************************************************(http://www.nature.com/nature)

[1] Stem cell versatility questioned?

DOI: 10.1038/nature02069 (http://dx.doi.org/10.1038/nature02069)

Transplanted bone-marrow-derived cells (BMDCs) can fuse with other mature cell types in live mice, according to a study published online by Nature this week. This research questions the rationale of some stem cell transplants as a genuine replacement therapy.

In culture, bone marrow cells are able to generate liver, heart and brain cells. In vivo, the same also appears to be true. Although some researchers believe the transition to be a genuine transformation of one cell type to another, others think that the transplanted cells fuse with host tissue, thereby taking on the characteristics of the host cell. Fusion had been shown to occur in vitro, and a study published in Nature earlier this year showed that bone marrow cells could fuse with cells of a damaged liver in vivo.

Now Arturo Alvarez-Buylla and colleagues have shown that transplanted BMDCs from mouse can fuse with liver, brain and heart cells, even in a healthy animal. There was no evidence of authentic transdifferentiation — the ability of one cell type to turn into another.

The result hints that cell fusion might occur naturally. Under normal conditions, many heart and liver cells have two or more nuclei. This may be due to fusion, the authors speculate, although whether this represents a repair mechanism for damaged tissue is unknown. The rationale for clinical procedures based on the idea of transdifferentiation may also need rethinking. The team conclude that further animal studies are needed to assess the value of BMDC transplants as a useful replacement therapy.

***********************************************NATURE MEDICINE****************************************(http://www.nature.com/naturemedicine)

[2] Malaria parasite takes advantage of liver

DOI: 10.1038/nm947 (http://dx.doi.org/10.1038/nm947)

The parasite that causes malaria exploits one of the body's own chemicals to cause infection, according to a report in the November issue of Nature Medicine.Sporozoites of the parasite, Plasmodium berghei, infect a human host by traveling through the liver, wounding several liver cells along the way before settling down in one of them. Maria Mota and colleagues discovered that the wounded cells produce a protein called hepatocyte growth factor (HGF), which is normally involved in liver development and regeneration. When the secreted HGF activates receptors on a neighboring cell, it triggers a pathway that rearranges the internal skeleton of that cell and makes it more susceptible to Plasmodium infection.

Mota's findings might explain why malaria can be more severe in hepatitis B carriers, who have more HGF than normal. The researchers also found that blocking the HGF receptors prevented Plasmodium from infecting the liver. They suggest that interfering with the HGF pathway might be the key to developing new malaria treatments.

Other papers from Nature Medicine to be published online at the same time and with the same embargo:

[3] Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells(DOI: 10.1038/nm948) (http://dx.doi.org/10.1038/nm948)

*********************************************NATURE IMMUNOLOGY************************************(http://www.nature.com/natureimmunology)

[4] & [5] Balancing act

DOI: 10.1038/ni987 (http://dx.doi.org/10.1038/ni987) and DOI: 10.1038/ni988 (http://dx.doi.org/10.1038/ni988)

T cell responses must be finely balanced to avoid inflammatory tissue injury when fighting infection. In the November issue of Nature Immunology, scientists show that Tim-3, a molecule expressed by TH1 subset, is intimately involved in regulating this balance.

Two groups, headed by Terry Strom and Vijay Kuchroo respectively, showed that Tim-3 down-regulates TH1-mediated immune responses. Strom and colleagues looked at autoimmune diabetes in mice, a condition known to depend on a TH1 response. They found that blocking Tim-3 binding to its ligand accelerated diabetes onset. In a model of tissue transplants, mice with no Tim-3 rapidly rejected transplants despite receiving treatments that normally ensure transplant survival. Likewise, Kuchroo and colleagues also showed Tim-3 blockade or deficiency prevented mice from acquiring a state of 'immune tolerance,' which normally can be attained through administration of high doses of protein. Thus, Tim-3 dampens pro-inflammatory T cell responses and limits the associated tissue injury. The precise mechanism by which the Tim-3 pathway achieves this has yet to be elucidated.

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[6] TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway (DOI: 10.1038/ni986) (http://dx.doi.org/10.1038/ni986)

***************************************************************************************************************Items from other Nature journals to be published online at the same time and with the same embargo:

NATURE MATERIALS (http://www.nature.com/naturematerials)

[7] Liquid-liquid phase transition in supercooled silicon(DOI: 10.1038/nmat994) (http://dx.doi.org/10.1038/nmat994) [8] Interfacial heat flow in carbon nanotube suspensions(DOI: 10.1038/nmat996) (http://dx.doi.org/10.1038/nmat996)

NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology_

[9] E3 gene manipulations affect oncolytic adenovirus activity in immunocompetent tumor models(DOI: 10.1038/nbt887) (http://dx.doi.org/10.1038/nbt887)

[10] A genetic approach to inactivating chemokine receptors using a modified viral protein(DOI: 10.1038/nbt889) (http://dx.doi.org/10.1038/nbt889)

[11] Computational discovery of gene modules and regulatory networks (DOI: 10.1038/nbt890) (http://dx.doi.org/10.1038/nbt890)

[12] Human antibodies from immunized donors are protective against anthrax toxin in vivo(DOI: 10.1038/nbt891) (http://dx.doi.org/10.1038/nbt891)

NATURE GENETICS (http://www.nature.com/naturegenetics)

[13] Tat-binding protein-1, a component of the 26S proteasome, contributes to the E3 ubiquitin ligase function of the von Hippel-Lindau protein(DOI: 10.1038/ng1254) (http://dx.doi.org/10.1038/ng1254)

[14] Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse(DOI: 10.1038/ng1255) (http://dx.doi.org/10.1038/ng1255)

NATURE NEUROSCIENCE (http://www.nature.com/natureneuroscience)

[15] Activity-induced targeting of profilin and stabilization of dendritic spine morphology (DOI: 10.1038/nn1135) (http://dx.doi.org/10.1038/nn1135)

[16] EXP-1 is an excitatory GABA-gated cation channel (DOI: 10.1038/nn1136) (http://dx.doi.org/10.1038/nn1136)

[17] Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss (DOI: 10.1038/nn1139) (http://dx.doi.org/10.1038/nn1139)

[18] Language fMRI abnormalities associated with FOXP2 gene mutation (DOI: 10.1038/nn1138) (http://dx.doi.org/10.1038/nn1138)

[19] Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1 (DOI: 10.1038/nn1140) (http://dx.doi.org/10.1038/nn1140)

NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)

[20] Actin filament uncapping localizes to ruffling lamellae and rocketing vesicles(DOI: 10.1038/ncb1059) (http://dx.doi.org/10.1038/ncb1059)

[21] EB1 reveals mobile microtubule nucleation sites in Arabidopsis (DOI: 10.1038/ncb1057) (http://dx.doi.org/10.1038/ncb1057)

NATURE STRUCTURAL BIOLOGY (http://www.nature.com/naturestructuralbiology)

[22] Tandem PDZ repeats in glutamate receptor"interacting proteins have a novel mode of PDZ domain"mediated target binding (DOI: 10.1038/nsb992) (http://dx.doi.org/10.1038/nsb992)

[23] Structural correspondence between the alpha-helix and the random-flight chain resolves how unfolded proteins can have native-like properties (DOI: 10.1038/nsb995) (http://dx.doi.org/10.1038/nsb995)

[24] X-ray crystal structure of IRF-3 and its functional implications (DOI: 10.1038/nsb1001) (http://dx.doi.org/10.1038/nsb1001)

[25] Crystal structure of IRF-3 reveals mechanism of autoinhibition and virus-induced phosphoactivation (DOI: 10.1038/nsb1002) (http://dx.doi.org/10.1038/nsb1002)

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GEOGRAPHICAL LISTING OF AUTHORS

The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

CHINAHong Kong (Kowloon): 22

GERMANYBerlin: 4Dusseldorf: 1Frankfurt: 3Freiburg: 3

INDIABangalore: 7

ITALYTorino: 2

JAPANKanagawa: 6Osaka: 6, 24Sapporo: 24Tokyo: 24

PORTUGALOeiras: 2

SPAINMadrid: 2, 17

SWITZERLANDBasel: 15

UNITED KINGDOMCambridge: 19London: 4, 9, 18Norwich: 21Oxford: 9

UNITED STATES OF AMERICA

Arizona Tempe: 7California San Diego: 12 San Francisco: 1, 25 Stanford: 23District of Columbia Washington: 14Florida Miami: 14Illinois Urbana: 8Iowa Iowa City: 14Maryland Baltimore: 13 Bethesda: 18Massachusetts Boston: 4, 5, 17, 19, 20 Cambridge: 1, 4, 5, 11 Worcester: 25Michigan Ann Arbor: 1, 14Mississippi Jackson: 25New York New York: 2 Troy: 8North Carolina Chapel Hill: 10Pennsylvania Philadelphia: 13Texas Galveston: 17Utah Salt Lake City: 16

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