Seeing antigen-presenting cells in action

Summary of newsworthy papers appearing in Nature Journals on 11 March 2007: Seeing antigen-presenting cells in action, Multiferroics as the ultimate memory? How stress causes anxiety in adolescent mice, Bacteria-mediated immune system paralysis, Jumonji family removing the mark & A cheap alternative for large scale RNA interference screens.

NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 11 March 2007

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

* Summaries of newsworthy papers:

Seeing antigen-presenting cells in action - Nature Chemical Biology
Multiferroics as the ultimate memory? - Nature Materials
How stress causes anxiety in adolescent mice - Nature Neuroscience
Bacteria-mediated immune system paralysis - Nature Immunology
Jumonji family removing the mark - Nature Structural & Molecular Biology
A cheap alternative for large scale RNA interference screens - Nature Methods

* 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.

PICTURES: To obtain artwork from any of the journals, you must first obtain permission from the copyright holder (if named) or author of the research paper in question (if not).

NOTE: Once a paper is published, the digital object identifier (DOI) number can be used to retrieve the abstract and full text from the journal web site (abstracts are available to everyone, full text is available only to subscribers). To do this, add the DOI to the following URL: <http://dx.doi.org/> (For example, <http://dx.doi.org/10.1038/ng730>). For more information about DOIs and Advance Online Publication, see <http://www.nature.com/ng/aop/>.

PLEASE CITE THE SPECIFIC NATURE JOURNAL AND WEBSITE AS THE SOURCE OF THE FOLLOWING ITEMS. IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO THE APPROPRIATE JOURNAL’S WEBSITE.

***************** NATURE CHEMICAL BIOLOGY ***************

(<http://www.nature.com/nchembio >)

[1] Seeing antigen-presenting cells in action
DOI: 10.1038/nchembio868

Peptide binding by antigen-presenting cells, a critical step in generating an immune response, can now be seen in living cells using a method reported in the April issue of Nature Chemical Biology. During an immune response, antigenic peptides are loaded onto major histocompatibility complex (MHC) proteins. The MHC-bound peptides are then ‘displayed’ to T cells, which leads to the production of antibodies. Many questions remain about the biological mechanisms for regulating peptide loading onto MHCs.

Lawrence Stern, Barbara Imperiali, and colleagues have developed modified peptides that undergo a 1,000-fold increase in fluorescence when they bind to MHCs in vivo. Using this method, the authors investigated the ability of a type of antigen-presenting cell, the dendritic cell, to bind peptides during different developmental stages. Unexpectedly, they found that immature dendritic cells can efficiently display peptides.

Antigen presentation is a critical step in inducing an appropriate immune response and also in triggering inappropriate immune reactions in autoimmune diseases, such as rheumatoid arthritis. New methods for understanding the in vivo mechanisms of antigen presentation are therefore of importance.

Author contacts:

Lawrence J. Stern (University of Massachusetts Medical School, Worcester, MA, USA)
Tel: +1 508 856 1831; Email: [email protected]

Barbara Imperiali (Massachusetts Institute of Technology, Cambridge, MA, USA)
Tel: +1 617 253 1838; Email: [email protected]

**************** NATURE MATERIALS ******************

(<http://www.nature.com/naturematerials>)

[2] Multiferroics as the ultimate memory?
DOI: 10.1038/nmat1860

Multiferroic materials - a rare class of materials where electric and magnetic fields are coupled - could hold the key to achieve a memory device that is capable of storing large amounts of data within a very small amount of space, suggests a report to be published online this week in Nature Materials.

Manuel Bibes and colleagues investigated a device where electrons travel through a very thin multiferroic layer. Depending on the electric and magnetic fields in this layer, the electrical resistance across the film changes, which can be used as the fundamental element of a memory device. Crucially, the coupling of electric and magnetic fields in the multiferroic film means that the device could be electrically or magnetically written and electrically read. The present approach represents significant technological progress compared with commercial ferroelectric and magnetic memories, as it combines the advantages of both technologies, while avoiding their disadvantages.

An accompanying News & Views article by James Scott suggests that the advance achieved has the potential of a ‘disruptive technology’ that could overturn existing memory device concepts, and might lead to the widespread commercialization of multiferroics.

Author contacts:
Manuel Bibes (Universit� Paris-Sud, Orsay, France)
Tel: +33 1 69 15 40 41; E-mail: [email protected]

Martin Gajek (University of California, Berkeley, CA, USA)
E-mail: [email protected]

James Scott (Cambridge University, UK)
Tel: +44 1223 333 461; Email: [email protected]
N&V author

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

[3] Exploration of nanostructured channel systems with single-molecule probes
DOI: 10.1038/nmat1861

****************** NATURE NEUROSCIENCE ****************

(<http://www.nature.com/natureneuroscience>)

[4] How stress causes anxiety in adolescent mice
DOI: 10.1038/nn1868

Stress may cause anxiety in adolescents due to an atypical response to a neurosteroid, reports a paper to be published online this week in Nature Neuroscience. Tetrahydropregnanalone (THP) is produced in response to stress and normally acts to reduce anxiety, but in adolescent mice, THP acts on an unusual type of inhibitory receptor to increase it. If a similar mechanism occurs in humans, this may explain why stress causes so much anxiety in teenagers.

In adult mice, THP enhances inhibition through GABA receptors that contain the delta subunit, calming neural activity to reduce anxiety. Sheryl Smith and colleagues discovered that expression of a subtype of GABA receptor containing both delta and alpha4 subunits is markedly higher in adolescent mice. They also found that THP has the opposite effect on this type of receptor, reducing inhibition and thus making the brain more excitable. Thus, the release of THP triggered by stress made adolescent mice more anxious instead of more calm.

In many species, puberty is the time to leave the home environment and make one’s way among strangers. Anxiety under stressful circumstances during adolescence could contribute to caution, increasing the odds of survival. In humans, THP levels increase during adolescence, as does the risk of anxiety disorders, which often occur in response to stress. Further research is needed to determine whether THP has similar effects on GABA receptors and anxiety in human teenagers as in adolescent mice.

Author contact:
Sheryl Smith (SUNY Downstate Medical Center, Brooklyn, NY, USA)
Tel: +1 718 270 2226; E-mail: [email protected]

Additional contact for comment on paper:
Margaret McCarthy (University of Maryland, Baltimore, MD, USA)
Tel: +1 410 706 2655; E-mail: [email protected]

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

[5] Limits on the memory storage capacity of bounded synapses
DOI: 10.1038/nn1859

[6] Differential development of high-level visual cortex correlates with category-specific recognition memory
DOI: 10.1038/nn1865

[7] Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex
DOI: 10.1038/nn1866

[8] Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala
DOI: 10.1038/nn1871

[9] Musical experience shapes human brainstem encoding of linguistic pitch patterns
DOI: 10.1038/nn1872

******************* NATURE IMMUNOLOGY ****************

(<http://www.nature.com/natureimmunology>)

[10] Bacteria-mediated immune system paralysis
DOI: 10.1038/ni1450

How the pathogen Staphylococcus aureus, a leading cause of hospital-related infections, disables the immune system is described online this week in Nature Immunology.

Defence against S. aureus infection requires immune molecules called complement proteins, which circulate in the bloodstream as inactive precursors. After complement proteins recognize and attach to invading microbes, they are clipped to smaller subunits, ultimately releasing end products that recruit more immune cells and trigger other defence mechanisms.

S. aureus produces a protein called Efb, which can somehow suppress complement function. Brian Geisbrecht and colleagues have now solved the structure of Efb, both alone and when bound to a complement protein. Their findings indicate that Efb binding alters the shape of complement proteins, thereby blocking the activating cleavage steps and subsequent formation of the antimicrobial complement complexes and release of inflammatory mediators. This work might be useful in designing methods to inhibit complement activation, which may be used as therapy for diseases involving excessive inflammation.

Author contact:
Brian Geisbrecht (University of Missouri-Kansas City, MO, USA)
Tel: +1 816 235 2592; E-mail: [email protected]

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

[11] IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge
DOI: 10.1038/ni1449

******* NATURE STRUCTURAL AND MOLECULAR BIOLOGY *******

(<http://www.nature.com/natstructmolbiol>)

[12] & [13] Jumonji family removing the mark
DOI: 10.1038/nsmb1216
DOI: 10.1038/nsmb1217

DNA in the cell is wrapped around protein complexes to form chromatin, the structure of which is regulated by a panoply of factors which are still being identified. Two papers in the April issue of Nature Structural & Molecular Biology identify a sought-after regulator of 'marks' on the chromatin that are associated with whether the genes are switched on or off.

Researchers have found that a particular methylation mark, Histone H3K4me3, which is found on active genes, is under dynamic regulation. The elusive enzyme that removes this mark in the fruitfly Drosophila was identified by researchers led by Yi Zhang and Ali Shilatifard, a finding which builds on previous research in yeast. The enzyme belongs to the Jumonji domain family of proteins, a human member of which can also remove the gene-activating Histone H3K4me3 mark. These proteins may thus be one of the key players in stably altering gene expression across species.

Author contacts:
Yi Zhang (University of North Carolina/Howard Hughes Medical Institute, Chapel Hill, NC, USA)
Tel: +1 919 843 8225; E-mail: [email protected]
Author paper [12]

Ali Shilatifard (Stowers Institute for Medical Research, Kansas City, MO, USA)
Tel: +1 816 926 4465; E-mail: [email protected]
Author paper [13]

Other papers from Nature Structural & Molecular Biology to be published online at the same time and with the same embargo:

[14] Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions
DOI: 10.1038/nsmb1214

[15] Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea
DOI: 10.1038/nsmb1219

******************** NATURE METHODS ********************

(<http://www.nature.com/nmeth>)

[16] A cheap alternative for large scale RNA interference screens
DOI: 10.1038/nmeth1025

A cost-effective resource for RNA interference (RNAi) that allows the effective reduction of gene expression is presented online this week in Nature Methods.

RNAi is a process by which short stretches of RNA knock down the expression of specific genes. To trigger this process at will, scientists most commonly use synthetic ‘small interfering’ (si)RNAs. Their advantage is that they can be designed to precisely target a sequence of choice within a gene; their disadvantage is that they are expensive. A large RNAi screen that targets many genes is thus financially impossible for a lot of academic laboratories. Frank Buchholz and colleagues previously developed a method to generate siRNAs enzymatically - which makes them a lot cheaper but does not allow targeting of a particular sequence within a gene. Instead, the method creates a random pool of various siRNAs, some more effective than others, directed against a gene of interest. This presented a conundrum to many researchers who were intrigued by an easily accessible resource but doubted its efficacy in large screens.

The authors now introduce a selection step in their enzymatic synthesis process that makes the pool of enzymatically generated siRNAs more specific. The group shows that these enzymatically generated siRNAs work equally well, if not better, than synthetic siRNAs in a large RNAi screen, at a fraction of the cost.

Author contact:
Frank Buchholz, (Max Planck Institute, Dresden, Germany)

Tel: +49 351 210 2888; E-mail: [email protected] <mailto:[email protected]>

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

[17] Fluorescence imaging of amyloid formation in living cells by a functional, tetracysteine-tagged alpha-synuclein
DOI: 10.1038/nmeth1026

[18] Unitary permeability of gap junction channels to second messengers measured by FRET microscopy
DOI: 10.1038/nmeth1031

****************************************************************

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

Nature PHYSICS (<http://www.nature.com/naturephysics >)

[19] The possibility of an intrinsic spin lattice in high-mobility semiconductor heterostructures
DOI: 10.1038/nphys559

[20] Conditional statistics of electron transport in interacting nanoscale conductors
DOI: 10.1038/nphys564

[21] A metastable limit for compressed liquid water
DOI: 10.1038/nphys562

[22] A single-photon server with just one atom
DOI: 10.1038/nphys569

Nature MEDICINE (<http://www.nature.com/naturemedicine>)

[23] Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease
DOI: 10.1038/nm1555

[24] Bone marrow-specific Cap gene deletion protects against high-fat diet-induced insulin resistance
DOI: 10.1038/nm1550

[25] Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease
DOI: 10.1038/nm1548

[26] MRI detection of transcriptional regulation of gene expression in transgenic mice
DOI: 10.1038/nm1497

[27] Molecular imaging of VEGF receptors in angiogenic vasculature with single-chain VEGF-based probes
DOI: 10.1038/nm1522

Nature BIOTECHNOLOGY (<http://www.nature.com/naturebiotechnology>)

[28] An expression atlas of rice mRNAs and small RNAs
DOI: 10.1038/nbt1291

[29] Reporter proteins for in vivo fluorescence without oxygen
DOI: 10.1038/nbt1293

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

[30] Homozygous silencing of T-box transcription factor EOMES leads to microcephaly with polymicrogyria and corpus callosum agenesis
DOI: 10.1038/ng1993

[31] The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast
DOI: 10.1038/ng1994

[32] Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy
DOI: 10.1038/ng2000

[33] Genome-wide functional analysis of pathogenicity genes in the rice blast fungus
DOI: 10.1038/ng2002

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

[34] Rab27a regulates phagosomal pH and NADPH oxidase recruitment to dendritic cell phagosomes
DOI: 10.1038/ncb1552

[35] Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1
DOI: 10.1038/ncb1557

[36] Uncoupling proteins 2 and 3 are fundamental for mitochondrial Ca2+ uniport
DOI: 10.1038/ncb1556

[37] Normal epidermal differentiation but impaired skin-barrier formation on keratinocyte-restricted IKK1 ablation
DOI: 10.1038/ncb1560

*************************************************************

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.

ARGENTINA
Buenos Aires: 17

AUSTRIA
Graz: 36

BRAZIL
Rio de Janeiro: 32
Parana: 30

CANADA:
Montreal: 32
Toronto: 31

FRANCE
Orleans: 30
Orsay: 2, 8
Palaiseau: 2
Paris: 30, 32, 34
Pau: 3
Tours: 30

GERMANY
Bonn: 37
Cologne: 37
Dresden: 16
D�sseldorf: 29
Garching: 22
Goettingen: 17
Groningen: 35
Heidelberg: 16
Juelich: 29
Kiel: 25
Martinsried: 35
Mulheim an der Ruhr: 29
Munich: 3
Tubingen: 34

INDIA
Agra: 32
Bangalore: 19
Mumbai: 1
New Delhi: 32

ISRAEL
Rehovot: 26

ITALY
Monterotundo Scalo: 37
Padua: 18
Parma: 29

JAPAN
Okayama: 23
Tokyo: 15
Yokohama: 15

KOREA
Busan: 33
Seoul: 25, 33
Suwon: 33

MOROCCO
Rabat: 30

NETHERLANDS
Groningen: 35

SPAIN
Barcelona: 2

SWITZERLAND
Geneva: 20
Zurich: 20

UNITED KINGDOM
Bristol: 7
Cambridge: 19, 31
Liverpool: 35
London: 31, 34
Oxford: 22, 25

UNITED STATES OF AMERICA
California
Berkeley: 10
La Jolla: 24, 25
Los Angeles: 6, 24
Orange County: 25
Palo Alto: 27
San Diego: 24
San Francisco: 11
Stanford: 6
Connecticut
Farmington: 27
New Haven: 8
Newington: 27
Delaware
Newark: 28
Illinois
Chicago: 16, 23
Evanston: 9
Maryland
Bethesda: 7
Massachusetts
Boston: 23, 26
Cambridge: 1, 6
Charlestown: 23
Chestnut Hill: 25
Worcester: 1
Michigan
Ann Arbor: 24
Missouri
Kansas City: 10, 13
St Louis: 13
New Mexico
Albuquerque: 21
New York
Brooklyn: 4
Buffalo: 11
Cold Spring Harbor:
New York: 4, 5, 8, 12
Rochester: 20
North Carolina
Chapel Hill: 12
Ohio
Columbus: 28
Pennsylvania
Philadelphia: 10, 13, 25
University Park: 33
Texas
Dallas: 12
Houston: 14
Virginia
Ashburn: 25
Washington
Kirkland: 16

VIETNAM
Ho Chi Minh City: 32

PRESS CONTACTS…

For media inquiries relating to embargo policy for all the Nature Research Journals:

Katherine Anderson (Nature London)
Tel: +44 20 7843 4502; E-mail: [email protected]

Ruth Francis (Senior Press Officer, Nature, London)
Tel: +44 20 7843 4562; E-mail: [email protected]

For media inquiries relating to editorial content/policy for the Nature Research Journals, please contact the journals individually:

Nature Biotechnology (New York)
Peter Hare
Tel: +1 212 726 9284; E-mail: [email protected]

Nature Cell Biology (London)
Bernd Pulverer
Tel: +44 20 7843 4892; E-mail: [email protected]

Nature Chemical Biology (Boston)
Andrea Garvey
Tel: +1 617 475 9241, E-mail: [email protected]

Nature Genetics (New York)
Orli Bahcall
Tel: +1 212 726 9311; E-mail: [email protected]

Nature Immunology (New York)
Laurie Dempsey
Tel: +1 212 726 9372; E-mail: [email protected]

Nature Materials (London)
Maria Bellantone
Tel: +44 20 7843 4556; E-mail: [email protected]

Nature Medicine (New York)
Juan Carlos Lopez
Tel: +1 212 726 9325; E-mail: [email protected]

Nature Methods (New York)
Allison Doerr
Tel: +1 212 726 9393; E-mail: [email protected]

Nature Neuroscience (New York)
Sandra Aamodt (based in California)
Tel: +1 530 795 3256; E-mail: [email protected]

Nature Physics (London)
Alison Wright
Tel: +44 20 7843 4555; E-mail: [email protected]

Nature Structural & Molecular Biology (New York)
Michelle Montoya
Tel: +1 212 726 9326; E-mail: [email protected]

About Nature Publishing Group

Nature Publishing Group (NPG) is a division of Macmillan Publishers Ltd, dedicated to serving the academic, professional scientific and medical communities. NPG's flagship title, Nature, was first published in 1869. Other publications include Nature research journals, Nature Reviews, Nature Clinical Practice and a range of prestigious academic journals including society-owned publications. NPG also provides news content through [email protected] and scientific career information through Naturejobs.

NPG is a global company with headquarters in London and offices in New York, San Francisco, Washington DC, Boston, Tokyo, Paris, Munich, Hong Kong, Melbourne, Delhi, Mexico City and Basingstoke. For more information, please go to www.nature.com

Published: 11 Mar 2007

Contact details:

The Macmillan Building, 4 Crinan Street
London
N1 9XW
United Kingdom

+44 20 7833 4000
Country: 
Journal:
News topics: 
Content type: 
Websites: 

http://www.nature.com/nchembio Nature Chemical Biology http://www.nature.com/naturematerials Nature Materials http://www.nature.com/natureneuroscience Nature Neuroscience http://www.nature.com/natureimmunology Nature Immunology http://www.nature.com/natstructmolbiol Nature Structural & Molecular Biology http://www.nature.com/nmeth Nature Methods http://www.nature.com Nature Publishing Group

Reference: 

Cell
Medicine