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For life science research only. Not for use in diagnostic procedures. |  | | |  | TABLE OF CONTENTS
| March 2012 Volume 18, Issue 3 |  | | |  |  Editorial
News
Book Review
Correspondence
News and Views
Community Corner
Research Highlights
Review
Brief Communications
Articles
Letters
Technical Reports | | | Advertisement | | | | 
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 | | | | | Nature Medicine Podcast |  Top | |  | | On fertile ground
Ovarian stem cells could aid fertility treatment and resting-state brain scans promises to improve disease diagnosis.
Listen Now | | Editorial | Top | | | | The persistence of polio p323
doi:10.1038/nm.2708
Despite intense efforts to rid the world of poliovirus, it continues to persevere. Given the serious limitations of the existing vaccines, the feasibility of eradication must be reassessed.
Full Text | PDF | | News | Top | | | | NIH accused of being overly literal on stem cell approvals p325
Elie Dolgin
doi:10.1038/nm0312-325
Full Text | PDF | | | | Genomics contest underscores challenges of personalized medicine p326
Megan Scudellari
doi:10.1038/nm0312-326
Full Text | PDF | | | | Trial designs for vaccines adapt to the times p327
Elie Dolgin
doi:10.1038/nm0312-327
Full Text | PDF | | | | Limb-saving medicines sought to prevent amputations p328
Cassandra Willyard
doi:10.1038/nm0312-328
Full Text | PDF | | | | Korea okays stem cell therapies despite limited peer-reviewed data p329
D Yvette Wohn
doi:10.1038/nm0312-329a
Full Text | PDF | | | | Survey says: too many PhDs p329
Rebecca Hersher
doi:10.1038/nm0312-329b
Full Text | PDF | | | | Small biotechs raring to cash in on the orphan disease market pp330 - 331
Rebecca Hersher
doi:10.1038/nm0312-330
Full Text | PDF | | | | New blood-boosting drugs aim to staunch renal anemia p332
Melinda Wenner Moyer
doi:10.1038/nm0312-332a
Full Text | PDF | | | | India opens malaria vaccine center pp332 - 333
Killugudi Jayaraman
doi:10.1038/nm0312-332b
Full Text | PDF | | | | Indian TB cases highlight need for drug-resistance tests p333
Rebecca Hersher
doi:10.1038/nm0312-333
Full Text | PDF | | | | Nodding syndrome leaves baffled scientists shaking their heads p334
Sarah C P Williams
doi:10.1038/nm0312-334
Full Text | PDF | | | | | Q&A | | | | Straight talk with... Robert Beall p335
Elie Dolgin
doi:10.1038/nm0312-335
When Robert J. Beall joined the Cystic Fibrosis Foundation in 1980, he launched a program aimed at absorbing the early financial risk involved in drug development as a way to entice for-profit companies to get involved in cystic fibrosis research. That strategy was vindicated with the approval in January of the first small-molecule drug that directly interacts with the mutated protein responsible for cystic fibrosis. Elie Dolgin spoke with Beall to learn more about his organization’s pioneering approach to venture philanthropy.
Abstract | Full Text | PDF | | | | | News in Brief | | | | Biomedical briefing pp336 - 337
doi:10.1038/nm0312-336
Full Text | PDF | | | | Correction p337
doi:10.1038/nm0312-337
Full Text | PDF | | | | | News Feature | | | | Diagnosis by default pp338 - 340
Roxanne Khamsi
doi:10.1038/nm0312-338
Brain scans that map differences in how brain regions communicate while people lie idle in the imaging machine could one day provide clues about afflictions ranging from Alzheimer's disease to attention disorders. Roxanne Khamsi finds out why these so-called 'resting state' scans have made researchers and drug companies sit up and take notice.
Full Text | PDF | | | | | Opinion | | | | Public-private partnerships need honest brokering p341
Michel Goldman
doi:10.1038/nm0312-341
Given the current challenges in research and development, it's increasingly apparent that collaboration between large pharmaceutical companies, academic teams and biotechnology enterprises is essential for converting basic biomedical discoveries into lifesaving medicines. But these partnerships work best when a neutral third party helps foster them.
Full Text | PDF | | Book Review | Top | | | | The obscure targets of desire p343
Garret A. FitzGerald reviews The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines by Brent R. Stockwell
doi:10.1038/nm.2696
Full Text | PDF | | Correspondence | Top | | | | Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune system pp344 - 346
Metamia Ciampricotti, Cheei-Sing Hau, Chris W Doornebal, Jos Jonkers and Karin E de Visser
doi:10.1038/nm.2652
Full Text | PDF | | | | HIV-1 Env antibodies: are we in a bind or going blind? pp346 - 347
John P Moore
doi:10.1038/nm.2689
Full Text | PDF | | | | Reply to: Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune system p346
Laurence Zitvogel and Guido Kroemer
doi:10.1038/nm.2690
Full Text | PDF | | | | Reply to: HIV-1 Env antibodies: are we in a bind or going blind? pp347 - 348
Thomas J Hope
doi:10.1038/nm.2688
Full Text | PDF | | News and Views | Top | | | | | | Community Corner | Top | | | | At the heart of the benefits of bariatric surgery pp358 - 359
doi:10.1038/nm0312-358
Full Text | PDF | | Research Highlights | Top | | | | Brain: Strange bedfellows | Neurodegeneration: Prion escape to spleen | Cancer: Choked tumors bounce back | Metabolic disorders: FGF21 action in the fat | Immunity: Controlling commensals | Immunity: Infectious tolerance? | New from NPG | Review | Top | | | | The cellular and signaling networks linking the immune system and metabolism in disease pp363 - 374
Olivia Osborn and Jerrold M Olefsky
doi:10.1038/nm.2627
This review highlights the importance of immunometabolism to obesity and metabolic diseases such as diabetes. The authors describe recent advances in dissecting the cellular and signaling networks that link the immune and metabolic systems together, and how these insights could be translated to develop new therapeutic strategies to combat metabolic disease.
Abstract | Full Text | PDF | | Brief Communications | Top | | | | KIF5B-RET fusions in lung adenocarcinoma pp375 - 377
Takashi Kohno, Hitoshi Ichikawa, Yasushi Totoki, Kazuki Yasuda, Masaki Hiramoto, Takao Nammo, Hiromi Sakamoto, Koji Tsuta, Koh Furuta, Yoko Shimada, Reika Iwakawa, Hideaki Ogiwara, Takahiro Oike, Masato Enari, Aaron J Schetter, Hirokazu Okayama, Aage Haugen, Vidar Skaug, Suenori Chiku, Itaru Yamanaka, Yasuhito Arai, Shun-ichi Watanabe, Ikuo Sekine, Seishi Ogawa, Curtis C Harris, Hitoshi Tsuda, Teruhiko Yoshida, Jun Yokota and Tatsuhiro Shibata
doi:10.1038/nm.2644
The authors report a new type of genetic alteration in lung adenocarcinoma. Fusions of KIF5B with RET kinase are found in 1-2% of lung cancer patients, segregate from other known alterations and can potentially be targeted using RET kinase inhibitors.
First paragraph | Full Text | PDF
See also: News and Views by Pao & Hutchinson | | | | RET, ROS1 and ALK fusions in lung cancer pp378 - 381
Kengo Takeuchi, Manabu Soda, Yuki Togashi, Ritsuro Suzuki, Seiji Sakata, Satoko Hatano, Reimi Asaka, Wakako Hamanaka, Hironori Ninomiya, Hirofumi Uehara, Young Lim Choi, Yukitoshi Satoh, Sakae Okumura, Ken Nakagawa, Hiroyuki Mano and Yuichi Ishikawa
doi:10.1038/nm.2658
Through an integrated screening system, the authors catalog ALK and ROS1 fusions in lung cancer and identify a new class of fusions involving KIF5B and RET that may represent new therapeutic targets in adenocarcinoma.
First paragraph | Full Text | PDF
See also: News and Views by Pao & Hutchinson | | | | Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies pp382 - 384
Doron Lipson, Marzia Capelletti, Roman Yelensky, Geoff Otto, Alex Parker, Mirna Jarosz, John A Curran, Sohail Balasubramanian, Troy Bloom, Kristina W Brennan, Amy Donahue, Sean R Downing, Garrett M Frampton, Lazaro Garcia, Frank Juhn, Kathy C Mitchell, Emily White, Jared White, Zac Zwirko, Tamar Peretz, Hovav Nechushtan, Lior Soussan-Gutman, Jhingook Kim, Hidefumi Sasaki, Hyeong Ryul Kim, Seung-il Park, Dalia Ercan, Christine E Sheehan, Jeffrey S Ross, Maureen T Cronin, Pasi A Janne and Philip J Stephens
doi:10.1038/nm.2673
Using high-coverage targeted next-generation sequencing, this report provides a catalog of genetic alterations in colorectal and lung cancers, identifying previously unknown alterations, such as JAK2 mutations and KIF5B-RET fusions, that may represent druggable targets.
First paragraph | Full Text | PDF
See also: News and Views by Pao & Hutchinson | | | | Blockade of PDGFR-[beta] activation eliminates morphine analgesic tolerance pp385 - 387
Yan Wang, Katherine Barker, Shanping Shi, Miguel Diaz, Bing Mo and Howard B Gutstein
doi:10.1038/nm.2633
Morphine loses its ability to fight pain after chronic use. Now, Howard Gutstein and his colleagues report that morphine induces release of PDGF, and blockade of PDGFR signaling can reestablish morphine analgesic efficacy in rats that have become tolerant.
First paragraph | Full Text | PDF | | Articles | Top | | | | Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1 pp388 - 395
Mingjian Lu, Min Wan, Karla F Leavens, Qingwei Chu, Bobby R Monks, Sully Fernandez, Rexford S Ahima, Kohjiro Ueki, C Ronald Kahn and Morris J Birnbaum
doi:10.1038/nm.2686
The insulin signaling pathway regulating glucose homeostasis that has been well accepted is insulin-to-insulin receptor-to-IRS proteins-to-PI3K-to-Akt-to-Foxo1[mdash]a pathway that does not respond properly in states of insulin resistance, including type 2 diabetes. In a new study from Morris Birnbaum and colleagues, an alternative insulin signaling pathway has been uncovered, as mice with liver-specific deletion of Akt and Foxo1 still respond normally to nutritional cues and properly regulate glucose metabolism. Although the exact nature of this alternative pathway needs to be identified, the results should open many new avenues of exploration in the field of type 2 diabetes.
Abstract | Full Text | PDF
See also: News and Views by Cheng & White | | | | Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis pp396 - 404
Hikaru Sugimoto, Valerie S LeBleu, Dattatreyamurty Bosukonda, Peter Keck, Gangadhar Taduri, Wibke Bechtel, Hirokazu Okada, William Carlson, Philippe Bey, Mary Rusckowski, Bjorn Tampe, Desiree Tampe, Keizo Kanasaki, Michael Zeisberg and Raghu Kalluri
doi:10.1038/nm.2629
BMP7 has been previously shown to protect against renal fibrosis. Raghu Kalluri and his colleagues have now identified activin-like kinase 3 (Alk3) as the key co-receptor for BMP7 in the kidney and have identified an orally available, small-peptide agonist of Alk3 that reduces established fibrosis in five animal models of kidney injury.
Abstract | Full Text | PDF | | | | Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis pp405 - 412
Kazuhiro Maeda, Yasuhiro Kobayashi, Nobuyuki Udagawa, Shunsuke Uehara, Akihiro Ishihara, Toshihide Mizoguchi, Yuichiro Kikuchi, Ichiro Takada, Shigeaki Kato, Shuichi Kani, Michiru Nishita, Keishi Marumo, T John Martin, Yasuhiro Minami and Naoyuki Takahashi
doi:10.1038/nm.2653
In a new study, Yasuhiro Kobayashi and his colleagues show that noncanonical Wnt signaling regulates balanced osteoblast-induced osteoclastogenesis during normal physiology and that this pathway is perturbed in pathophysiological states, such as rheumatoid arthritis. These results explain further how osteoblasts cross-talk with preosteoclasts to ensure matched bone resorption with bone formation during skeletal homeostasis in the adult and also suggest a new target to treat arthritis.
Abstract | Full Text | PDF | | | | Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women pp413 - 421
Yvonne A R White, Dori C Woods, Yasushi Takai, Osamu Ishihara, Hiroyuki Seki and Jonathan L Tilly
doi:10.1038/nm.2669
In 2004, a team led by Jonathan Tilly reported that mice contained oogonial stem cells (OSCs), suggesting that females may be able to generate new oocytes in adulthood[mdash]a concept that was, and still is, quite controversial even though those findings have since been replicated by others. In a new report, Tilly and colleagues now perfect the purification of mouse OSCs and, using this technique, they show that similar cells exist in women of reproductive age. They also show that the mouse and human OSCs are able to give rise to oocytes in vivo (in the case of the human cells after xenotransplantation into NOD-SCID mice), while also showing that the mouse OSCs can give rise to embryos after in vitro fertilization.
Abstract | Full Text | PDF
See also: News and Views by Telfer & Albertini | | | | NKG2D signaling on CD8+ T cells represses T-bet and rescues CD4-unhelped CD8+ T cell memory recall but not effector responses pp422 - 428
Andrew Zloza, Frederick J Kohlhapp, Gretchen E Lyons, Jason M Schenkel, Tamson V Moore, Andrew T Lacek, Jeremy A O'Sullivan, Vineeth Varanasi, Jesse W Williams, Michael C Jagoda, Emily C Bellavance, Amanda L Marzo, Paul G Thomas, Biljana Zafirova, Bojan Polic, Lena Al-Harthi, Anne I Sperling and Jose A Guevara-Patino
doi:10.1038/nm.2683
CD8+ T cells primed in the absence of CD4+ T cell help fail to develop a robust memory cell response. Zloza et al. now report that these CD4-unhelped CD8+ T cells can be rescued by activating their cell surface receptor NKG2D, which restores CD8+ T cell expansion and cytolytic activity during a recall response and protection in a mouse model of influenza infection.
Abstract | Full Text | PDF | | | | USP15 stabilizes TGF-[beta] receptor I and promotes oncogenesis through the activation of TGF-[beta] signaling in glioblastoma pp429 - 435
Pieter J A Eichhorn, Laura Rodon, Alba Gonzalez-Junca, Annette Dirac, Magui Gili, Elena Martinez-Saez, Claudia Aura, Ignasi Barba, Vicente Peg, Aleix Prat, Isabel Cuartas, Jose Jimenez, David Garcia-Dorado, Juan Sahuquillo, Rene Bernards, Jose Baselga and Joan Seoane
doi:10.1038/nm.2619
TGF-[beta] signaling is commonly aberrantly activated in gliomas and other tumors and can exert a pro-oncogenic function. The authors identify a new mechanism for upregulation of TGF-[beta] signaling in cancer. The deubiquitinase USP15 is shown to be able to bind the TGF-[beta] receptor complex, counteract its degradation and potentiate its stimulation of downstream mediators. USP15 is amplified in human glioblastoma and could represent a therapeutic target, as its downregulation impairs the growth of glioblastoma cells in vivo.
Abstract | Full Text | PDF | | Letters | Top | | | | Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL pp436 - 440
Giusy Della Gatta, Teresa Palomero, Arianne Perez-Garcia, Alberto Ambesi-Impiombato, Mukesh Bansal, Zachary W Carpenter, Kim De Keersmaecker, Xavier Sole, Luyao Xu, Elisabeth Paietta, Janis Racevskis, Peter H Wiernik, Jacob M Rowe, Jules P Meijerink, Andrea Califano and Adolfo A Ferrando
doi:10.1038/nm.2610
The authors apply reverse engineering of transcriptional networks to identify the main functional drivers of the pro-leukemic transcriptional activity of TLX1 and TLX3, transcription factors usually altered in T-ALL. The network analysis uncovers RUNX1 as a key mediator of the effects of TLX factors and, consistently, mutations in RUNX1 are found in human T-ALL.
First paragraph | Full Text | PDF | | | | High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions pp441 - 445
Roberto Di Niro, Luka Mesin, Nai-Ying Zheng, Jorunn Stamnaes, Michael Morrissey, Jane-Hwei Lee, Min Huang, Rasmus Iversen, M Fleur du Pre, Shuo-Wang Qiao, Knut E A Lundin, Patrick C Wilson and Ludvig M Sollid
doi:10.1038/nm.2656
IgA antibodies directed against tissue transglutaminase 2 (TG2) are used as a serological marker of celiac disease. Ludvig M. Sollid and his colleagues provide an unbiased and thorough characterization of the mucosal antibody response directly from the effector compartment. They report that TG2-specific plasma cells are expanded in the duodenal mucosa of individuals with celiac disease. Antibodies cloned from these cells are of high affinity, show a restricted repertoire and minimal somatic hypermutation, and do not inhibit TG2 enzymatic activity.
First paragraph | Full Text | PDF | | | | A quantitative basis for antiretroviral therapy for HIV-1 infection pp446 - 451
Benjamin L Jilek, Melissa Zarr, Maame E Sampah, S Alireza Rabi, Cynthia K Bullen, Jun Lai, Lin Shen and Robert F Siliciano
doi:10.1038/nm.2649
Antiretroviral drug combinations for the treatment of HIV-1 infection have been determined on the basis of clinical trial outcomes, but without clear insight into why certain combinations are superior to others. Robert Siliciano and his colleagues present a quantitative basis for determining efficacious antiretroviral drug combinations.
First paragraph | Full Text | PDF
See also: News and Views by Ribeiro | | | | Activation of fast skeletal muscle troponin as a potential therapeutic approach for treating neuromuscular diseases pp452 - 455
Alan J Russell, James J Hartman, Aaron C Hinken, Alexander R Muci, Raja Kawas, Lena Driscoll, Guillermo Godinez, Kenneth H Lee, David Marquez, William F Browne IV, Michael M Chen, David Clarke, Scott E Collibee, Marc Garard, Richard Hansen, Zhiheng Jia, Pu-Ping Lu, Hector Rodriguez, Khalil G Saikali, Julia Schaletzky, Vipin Vijayakumar, Daniel L Albertus, Dennis R Claflin, David J Morgans, Bradley P Morgan and Fady I Malik
doi:10.1038/nm.2618
Neuromuscular disease is often marked by insufficient neural activation of muscle activity, resulting in muscle weakness. Fady Malik and colleagues have developed an orally available small molecule that sensitizes muscles to neural activity by reducing the off rate of calcium binding to troponin C. They validate the therapeutic potential of this drug in vivo in a rat model of myasthenia gravis and show that treatment improves grip strength by 50%.
First paragraph | Full Text | PDF | | Technical Reports | Top | | | | Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass pp456 - 462
Min Guan, Wei Yao, Ruiwu Liu, Kit S Lam, Jan Nolta, Junjing Jia, Brian Panganiban, Liping Meng, Ping Zhou, Mohammad Shahnazari, Robert O Ritchie and Nancy E Lane
doi:10.1038/nm.2665
Targeting mesenchymal stem cells (MSCs), progenitors of osteoblasts, to bone has been a long-standing goal but has had limited success so far. Here, Min Guan and her colleagues deliver a peptidomimetic integrin ligand against integrin [alpha]4[beta]1 conjugated to the bone-seeking agent bisphosphonate alendronate as a means of attracting infused and/or endogenous MSCs to the bone surface to stimulate bone formation. The approach was tested in both xenotransplantation and immunocompetent mice, as well as in mouse models of trabecular bone loss induced by aging and estrogen deficiency (ovariectomy).
Abstract | Full Text | PDF | | | | Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging pp463 - 467
Mya S Thu, L Henry Bryant, Tiziana Coppola, E Kay Jordan, Matthew D Budde, Bobbi K Lewis, Aneeka Chaudhry, Jiaqiang Ren, Nadimpalli Ravi S Varma, Ali S Arbab and Joseph A Frank
doi:10.1038/nm.2666
There are currently no good ways to track human cells in vivo in a clinical setting using magnetic resonance imaging (MRI) based on superparamagnetic iron-oxide nanoparticles. Mya Thu and colleagues have introduced a simple magnetic cell labeling approach that combines three currently US Food and Drug Administration-approved drugs[mdash]ferumoxytol, heparin and protamine[mdash]to form self-assembling nanocomplexes of about 150 nm in size that effectively label cells for MRI. The approach was shown to effectively label three types of stem cells and two types of immune cells.
Abstract | Full Text | PDF | | | Top | |  | | Advertisement | | Roche - Nature Medicine Translational Neuroscience Symposium 2012
Autism Spectrum Disorders: From Biological Understanding to Therapeutic Strategies
April 23-25, 2012 - Buonas, Switzerland
This symposium aims at bringing together the world's most distinguished scientists and academics in the areas of autism and neurodevelopmental disorders to share their latest work with each other and around 40 members of Roche's Neuroscience team.
Application deadline: March 12, 2012
www.nature.com/natureconferences/tns2012
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