Summaries of papers From gorilla to human: a new immunodeficiency virus found, 'Trojan horse' deliveries by HIV, Recovery after spinal cord injury, Immune cells worsen brain damage after stroke, New genetic variants associated with cancer, Mice generated from reprogrammed cells, A new progenitor cell population in breast cancer
NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE
For papers that will be published online on 02 August 2009
This press release is copyrighted to the Nature journals mentioned below.
This press release contains:
· Summaries of newsworthy papers:
Neuroscience: How marijuana causes memory deficits
Medicine: From gorilla to human: a new immunodeficiency virus found
Immunology: ‘Trojan horse’ deliveries by HIV
Neuroscience: Recovery after spinal cord injury
Medicine: Immune cells worsen brain damage after stroke
Genetics: New genetic variants associated with cancer
Nature: Mice generated from reprogrammed cells
Chemical Biology: 800 million and counting
And finally…Medicine: A new progenitor cell population in breast cancer
· Mention of papers to be published at the same time with the same embargo
· Geographical listing of authors
PDFs of all the papers mentioned on this release can be found in the relevant journal’s section of http://press.nature.com. Press contacts for the Nature journals are listed at the end of this release.
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 Neuroscience: How marijuana causes memory deficits
Memory loss associated with marijuana use is caused by the drug’s interference with the brain’s natural protein synthesis machinery, according to a study published in Nature Neuroscience.
Though it has been documented that marijuana impairs memory, the precise mechanism for this memory impairment was previously unknown. Andrés Ozaita and colleagues focused on THC, the main psychoactive chemical compound in marijuana, which acts on a specific class of receptors known as cannabinoid receptors. These receptors are known to affect the connection strength between neurons.
The scientists found that THC increases the activity of a pathway that promotes protein synthesis in the mouse brain. This transient increase of protein synthesis was mediated specifically by cannabinoid receptors expressed on the brain’s inhibitory neurons, and correlated with long-term memory deficits in mice. Interestingly, the authors also found that inhibition of this signaling pathway by rapamycin, an immunosuppressant drug used to prevent organ rejection following transplantation, prevents THC-induced amnesia in mice.
Andrés Ozaita (Universitat Pompeu Fabra, Barcelona, Spain)
Tel: +34 93 316 0823; E-mail: email@example.com
 Medicine: From gorilla to human: a new immunodeficiency virus found
The existence of a new human immunodeficiency virus (HIV) derived from gorillas is reported in this week’s Nature Medicine.
Jean-Christophe Plantier identified a new form of HIV in a patient from Cameroon. The new virus is closely related to the known gorilla simian immunodeficiency virus (SIV). This gorilla strand shows no evidence of recombination with other HIV strains or with chimpanzee SIV. The human prevalence of this new form of HIV remains to be determined.
These findings indicate that gorillas, in addition to chimpanzees, are likely sources of HIV. The discovery of this novel HIV lineage highlights the need to better monitor the emergence of new HIV variants, particularly in western central Africa from where existing HIV groups have originated.
Jean-Christophe Plantier (Universite de Rouen, France)
Tel: +33 2 32 88 14 62; E-mail: Jean-Christophe.Plantier@univ-rouen.fr
 Immunology: ‘Trojan horse’ deliveries by HIV
Immune cells infected by HIV extend long thin tube-like structures that deliver virus-derived inhibitory proteins to disable non-infected immune cells. The report published online this week in Nature Immunology, sheds light on the processes that allow HIV to disrupt the immune system.
The Nef protein from HIV can block the generation of neutralizing antibodies against HIV; however, it was previously unclear how this occurs as antibody-producing B cells are not themselves infected by the virus. Andrea Cerutti and colleagues show that Nef triggers the formation of nanotubule-like structures to transport the protein to other immune cells, such as the B cells.
The new findings provide an explanation for how Nef protein is delivered to, and arrests B cell function, without becoming infected by HIV itself. The authors call this stealth delivery of immunosuppressive Nef protein the ‘Trojan horse’ of immune evasion.
Andrea Cerutti (Weill Medical College, Cornell University, New York, NY, USA)
Tel: +1 212 746 6396; E-mail: firstname.lastname@example.org
 Neuroscience: Recovery after spinal cord injury
Anatomical reconnection of severed nerves is possible in a rat model of spinal cord injury, reports a study published online in this week’s Nature Neuroscience.
Severe injuries to the spinal cord often lead to significant or complete loss of function of extremities. The lack of recovery is largely due to the loss of neuronal connections between the brain and other parts of the body since spontaneous regeneration is not possible. Previous efforts to restore neuronal connections between the body and the brain of rats have achieved limited success, often resulting in regeneration of nerves that failed to reach their correct target sites in the brain.
Mark Tuszynski and colleagues now report the re-growth of sensory nerves across an injury site in the spinal cord to the targeted region in the brainstem. Taking cues from normal brain development, the authors used a naturally occurring molecule that attracts growing nerves together with grafted bone marrow cells to act as a cellular “bridge” for regenerating nerve tract.
While full restoration of limb sensation was not achieved with this anatomical reconnection, this manipulation will impact the development of strategies to promote recovery after nerve injuries.
Mark Tuszynski (University of California, San Diego, CA, USA)
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 Medicine: Immune cells worsen brain damage after stroke
A class of immune cells has been implicated that have a harmful role in the late phase of ischemic brain injury, according to a study in this week’s Nature Medicine.
Immune cell recruitment and activation have been implicated in the progression of brain damage after stroke, but the relevant cell populations had remained unknown.
Akihiko Yoshimura and colleagues focused on an immune cell population known as gamma-delta-T, which initiates the production of interleukin-17 (IL-7) – an immune system signaling cell. They found that the infiltration of gamma-delta-T cells into the brain of mice, and the production of IL-17 by these cells, have a deleterious role on brain cells after a stroke.
Interestingly, the levels IL-17 peaked three days after stroke, pointing to a role for this cytokine in the late phase of brain injury. Moreover, keeping gamma-delta-T cells from entering the nervous system ameliorated the brain injury symptoms after stroke.
The authors propose that gamma-delta-T cells could be a therapeutic target against the inflammatory events that worsen the initial damage after a stroke.
Akihiko Yoshimura (Keio University School of Medicine, Tokyo, Japan)
Tel: +81 3 53 63 3483; E-mail: firstname.lastname@example.org
,  &  Genetics: New genetic variants associated with cancer
Common gene variants are associated with increased risk of 3 different types of cancer, according to studies published online in this week’s Nature Genetics.
Stephen Chanock and colleagues analyzed the genomes of thousands of pancreatic cancer patients and found that genetic variation at ABO, an important gene that regulates blood type, is associated with increased risk of pancreatic cancer. This finding provides an explanation for studies done in the 1950s and 1960s, which suggested that individuals with the A, AB, or B blood type have increased risk of pancreatic cancer, compared to individuals with blood group O. Pancreatic cancer is a highly fatal disease, leading to mortality in most cases.
Paul Pharoah and colleagues scanned the genomes of thousands of ovarian cancer cases and identified a genetic variant on chromosome 9p22 that is associated with increased risk of this disease. Ovarian cancer also has poor survival rates, with about half of diagnosed cases surviving 5 years past diagnosis.
Finally, Xifeng Wu and her team found that variation in the prostate stem cell antigen (PSCA) gene is associated with increased risk of urinary bladder cancer in US and European populations. Although urinary bladder cancer is more common in Western countries than pancreatic and ovarian cancers, urinary bladder cancer has a better survival rate, with approximately 80% of diagnosed cases surviving past 5 years of diagnosis.
Stephen Chanock (National Cancer Institute, Bethesda, MD, USA) Author paper 
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Paul Pharoah (University of Cambridge, UK) Author paper 
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Xifeng Wu (M. D. Anderson Cancer Center, Houston, TX, USA) Author paper 
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 Nature: Mice generated from reprogrammed cells
Following on from studies published last week, an independent team report the generation of fertile adult mice derived entirely from induced pluripotent stem (iPS) cells. A comparison of the different methods used by each team will reveal important information about the cellular state of pluripotency. The study, published online this week in Nature, serves to firmly establish that cells reprogrammed in the lab can be as pluripotent as embryonic stem cells.
Kristin Baldwin and colleagues generated 6 iPS cell lines from mouse fibroblasts, using different amounts of each of the four factors that are needed to reprogram the cells to a pluripotent embryo-like state. They then tested the ability of each of the lines to form an embryo by injection into a tetraploid blastocyst — groups of cells from fused embryos that form the placental tissue to support embryo growth, but cannot become part of the embryo itself. Live mice were successfully generated from 4 of the 6 lines, with similar efficiencies to that reported using embryonic stem cells in the same assay. Mice created from two of the lines also went on to produce offspring of their own, a final testament to the pluripotency of the original cells used.
With so many factors that can be tweaked in the recipe, research to identify the ‘right’ conditions for pluripotency is difficult and painstaking. Each study adds a bit more to this endeavour and allows researchers to refine their methods and improve efficiency.
Kristin Baldwin (The Scripps Research Institute, La Jolla, CA, USA)
Tel: +1 858 784 9466; E-mail: firstname.lastname@example.org
 Chemical Biology: 800 million and counting
A collection of 800 million chemicals, in which each chemical contains a unique DNA barcode, is used to identify new enzyme inhibitors as reported in a study published online this week in Nature Chemical Biology.
Attaching chemicals to small pieces of DNA is an attractive way of combining the power of molecular biology and chemical synthesis to identify potential drugs. However, this approach for creating “DNA-encoded” chemicals has typically been limited to relatively small collections of chemicals.
Barry Morgan and colleagues have developed a new approach for making DNA-encoded chemical libraries that uses double-stranded, rather than single-stranded, DNA. The authors synthesized chemical libraries nearly 10 times larger than any previous DNA-encoded library and about 5 orders of magnitude larger than typical libraries. In contrast with previous studies, which largely identified chemicals that bound to but did not necessarily inhibit a target, these libraries were used to identify highly effective new inhibitors of kinase enzymes.
With the achievement of library sizes exceeding those of the high-throughput screening libraries typically used at pharmaceutical companies, this method opens up a new and potentially more effective way to hunt for drug leads.
Barry Morgan, (GlaxoSmithKline, Waltham, MA, USA)
Tel: +1 781 795 4216; E-mail: email@example.com
 Medicine: A new progenitor cell population in breast cancer
Some breast cancers are thought to arise from mammary stem cells that mutate, but a study published in this week’s Nature Medicine indicates that luminal cells that line the mammary ducts may also be tumor progenitors.
Basal-like breast cancers arise in women carrying mutations in the gene encoding the tumor suppressor protein BRCA1. Jane Visvader and her colleagues isolated distinct cell populations from normal mammary tissue and pre-cancerous tissue from women who have one normal BRCA1 gene and one BRCA1 gene mutation. They found that breast tissue from BRCA1 mutation women harbors an expanded luminal progenitor population. Analysis of gene expression patterns showed that basal breast cancer tumor cells were more similar to the luminal progenitor cells than to any other cell type, including the stem cell population.
The discovery of an aberrant luminal progenitor population in pre-cancerous tissue from BRCA1 mutation carriers establishes these cells as a probable target population in the fight against such breast tumors.
Jane Visvader (The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia)
Tel: +61 3 9345 2494; E-mail: firstname.lastname@example.org
Items from other Nature journals to be published online at the same time and with the same embargo:
 Characterization of two classes of small molecule inhibitors of Arp2/3 complex
NATURE BIOTECHNOLOGY (http://www.nature.com/naturebiotechnology)
 Species-independent translational leaders facilitate cell-free expression
 Synthetic protein scaffolds provide modular control over metabolic flux
NATURE CELL BIOLOGY (http://www.nature.com/naturecellbiology)
 SADB phosphorylation of gamma-tubulin regulates centrosome duplication
NATURE CHEMICAL BIOLOGY (http://www.nature.com/nchembio)
 Redox-sensitive cysteines bridge p300/CBP-mediated acetylation and FoxO4 activity
 Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation
 Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation
NATURE CHEMISTRY (http://www.nature.com/nchem)
 Anion-tuning of supramolecular gel properties
NATURE GENETICS (http://www.nature.com/naturegenetics)
 Mutations in PYCR1 Cause Cutis Laxa with Progeroid Features
NATURE GEOSCIENCE (http://www.nature.com/ngeo)
 Storage and bioavailability of molybdenum in soils increased by organic matter complexation
 Hydrothermal alteration and microfossil artifacts of the 3,465-million-year-old Apex Chert
 Increasing Australian–Indonesian monsoon rainfall linked to early Holocene sea-level rise
NATURE IMMUNOLOGY (http://www.nature.com/natureimmunology)
 T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma
 Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells
Nature MEDICINE (http://www.nature.com/naturemedicine)
 Persistence of HIV-1 receptor–positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition
NATURE METHODS (http://www.nature.com/nmeth)
 Modular scanning FCS quantifies receptor-ligand interactions in living multicellular organisms
 Phymm and PhymmBL: Metagenomic Phylogenetic Classification with Interpolated Markov Models
NATURE NANOTECHNOLOGY (http://www.nature.com/nnano)
 Dynamic superlubricity and the elimination of wear on the nanoscale
 Molecular implementation of simple logic programs
 Structural transformations in graphene studied with high spatial and temporal resolution
Nature NEUROSCIENCE (http://www.nature.com/natureneuroscience)
 L-type voltage-dependent Ca2+ channels mediate expression of presynaptic LTP in amygdala
 Genetic address book for retinal cell types
 Kinetic basis of partial agonism at NMDA receptors
NATURE PHOTONICS (http://www.nature.com/nphoton)
 Frequency comb assisted diode laser spectroscopy for measurement of microcavity dispersion
Nature PHYSICS (http://www.nature.com/naturephysics)
 Elimination, reversal and directional bias of optical diffraction
 Testing the itinerancy of spin dynamics in superconducting Bi2Sr2CaCu2O8+delta
 Evidence for reversible control of magnetization in a ferromagnetic material by means of spin–orbit magnetic field
 Spin-injection Hall effect in a planar photovoltaic cell
Nature STRUCTURAL & MOLECULAR BIOLOGY (http://www.nature.com/natstructmolbiol)
 Structural and functional studies of the Ras-associating and pleckstrin-homology domains of Grb10 and Grb14
 Drosophila MSL complex globally acetylates H4K16 on the male X chromosome for dosage compensation
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.
Brisbane: 7, 11, 13, 23
Melbourne: 7, 11
New South Wales: 11, 19, 23
Parkville: 11, 19, 23
Montreal: 22, 25
Toronto: 6, 7
Copenhagen: 7, 10
Paris: 2, 22, 25
Dresden: 27, 31
Heidelberg: 6, 7, 8, 17, 19
Rehovot: 30, 36
Tokyo: 5, 8
Kuwait City: 19
Utrecht: 6, 16
Banska Bystrica: 8
Barcelona: 1, 6
Basel: 32, 33
UNITED ARAB EMIRATES
Al Ain: 19
Cambridge: 6, 7, 39
Didcot: 31, 37
London: 6, 7, 8, 31, 37
Oxford: 7, 31
UNITED STATES OF AMERICA
Foster City: 12
Irvine: 7, 24
La Jolla: 4, 9
Los Angeles: 4, 7, 8, 14, 19
Palo Alto: 5
San Diego: 4
San Francisco: 6, 12
New Haven: 6, 7, 12
Notre Dame: 38
West Lafayette: 38
Baltimore: 6, 24
Bethesda: 6, 8
College Park: 28
Boston: 6, 7, 10, 41
Cambridge: 10, 14
East Lansing: 6
Rochester: 6, 7
Buffalo: 6, 7, 34
New York: 3, 6, 10, 18, 33, 40
Chapel Hill: 7
Columbus: 6, 19
King of Prussia: 10
College Station: 39
Houston: 6, 7, 8
Seattle: 6, 7, 26
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