abstract：:During fasting, induction of hepatic gluconeogenesis is crucial to ensure proper energy homeostasis. Such induction is dysregulated in type 2 diabetes, resulting in the development of fasting hyperglycemia. Hormonal and nutrient regulation of metabolic adaptation during fasting is mediated predominantly by the transcr...

journal_title：Nature medicine

authors： Sakai M,Matsumoto M,Tujimura T,Yongheng C,Noguchi T,Inagaki K,Inoue H,Hosooka T,Takazawa K,Kido Y,Yasuda K,Hiramatsu R,Matsuki Y,Kasuga M

更新日期：2012-03-18 00:00:00

abstract：:Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitami...

journal_title：Nature medicine

authors： Fujita K,Iwasaki M,Ochi H,Fukuda T,Ma C,Miyamoto T,Takitani K,Negishi-Koga T,Sunamura S,Kodama T,Takayanagi H,Tamai H,Kato S,Arai H,Shinomiya K,Itoh H,Okawa A,Takeda S

更新日期：2012-03-04 00:00:00

abstract：:CD4-unhelped CD8(+) T cells are functionally defective T cells primed in the absence of CD4(+) T cell help. Given the co-stimulatory role of natural-killer group 2, member D protein (NKG2D) on CD8(+) T cells, we investigated its ability to rescue these immunologically impotent cells. We demonstrate that augmented co-s...

journal_title：Nature medicine

authors： Zloza A,Kohlhapp FJ,Lyons GE,Schenkel JM,Moore TV,Lacek AT,O'Sullivan JA,Varanasi V,Williams JW,Jagoda MC,Bellavance EC,Marzo AL,Thomas PG,Zafirova B,Polić B,Al-Harthi L,Sperling AI,Guevara-Patiño JA

更新日期：2012-02-26 00:00:00

abstract：:Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a resu...

journal_title：Nature medicine

authors： Wang W,Lv N,Zhang S,Shui G,Qian H,Zhang J,Chen Y,Ye J,Xie Y,Shen Y,Wenk MR,Li P

更新日期：2012-01-15 00:00:00

abstract：:Congenital disorder of glycosylation-Ia (CDG-Ia, also known as PMM2-CDG) is caused by mutations in the gene that encodes phosphomannomutase 2 (PMM2, EC 5.4.2.8) leading to a multisystemic disease with severe psychomotor and mental retardation. In a hypomorphic Pmm2 mouse model, we were able to overcome embryonic letha...

journal_title：Nature medicine

authors： Schneider A,Thiel C,Rindermann J,DeRossi C,Popovici D,Hoffmann GF,Gröne HJ,Körner C

更新日期：2011-12-11 00:00:00

abstract：:High blood pressure, or hypertension, is a very common disorder with a substantial impact on public health because of its associated complications. Despite the high prevalence of essential hypertension and years of research, the basic causes remain obscure. Here I review recent advances in understanding the pathophysi...

journal_title：Nature medicine

authors： Coffman TM

更新日期：2011-11-07 00:00:00

abstract：:We report the involvement of an evolutionarily conserved set of mycobacterial genes, the esx-3 region, in evasion of bacterial killing by innate immunity. Whereas high-dose intravenous infections of mice with the rapidly growing mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were rapidly l...

journal_title：Nature medicine

authors： Sweeney KA,Dao DN,Goldberg MF,Hsu T,Venkataswamy MM,Henao-Tamayo M,Ordway D,Sellers RS,Jain P,Chen B,Chen M,Kim J,Lukose R,Chan J,Orme IM,Porcelli SA,Jacobs WR Jr

更新日期：2011-09-04 00:00:00

abstract：:Transcription factor FoxO1 promotes hepatic glucose production. Genetic inhibition of FoxO1 function prevents diabetes in experimental animal models, providing impetus to identify pharmacological approaches to modulate this function. Altered Notch signaling is evident in tumorigenesis, and Notch antagonists are in cli...

journal_title：Nature medicine

authors： Pajvani UB,Shawber CJ,Samuel VT,Birkenfeld AL,Shulman GI,Kitajewski J,Accili D

更新日期：2011-07-31 00:00:00

abstract：:Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal cen...

journal_title：Nature medicine

authors： Chung Y,Tanaka S,Chu F,Nurieva RI,Martinez GJ,Rawal S,Wang YH,Lim H,Reynolds JM,Zhou XH,Fan HM,Liu ZM,Neelapu SS,Dong C

更新日期：2011-07-24 00:00:00

abstract：:Cells that are deficient in homologous recombination, such as those that lack functional breast cancer-associated 1 (BRCA1) or BRCA2, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, BRCA-deficient tumors represent only a small fraction of adult cancers, which might restrict the therape...

journal_title：Nature medicine

authors： Johnson N,Li YC,Walton ZE,Cheng KA,Li D,Rodig SJ,Moreau LA,Unitt C,Bronson RT,Thomas HD,Newell DR,D'Andrea AD,Curtin NJ,Wong KK,Shapiro GI

更新日期：2011-06-26 00:00:00

abstract：:Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1...

journal_title：Nature medicine

authors： Ma C,Fan R,Ahmad H,Shi Q,Comin-Anduix B,Chodon T,Koya RC,Liu CC,Kwong GA,Radu CG,Ribas A,Heath JR

更新日期：2011-06-01 00:00:00

abstract：:How high salt intake increases blood pressure is a key question in the study of hypertension. Salt intake induces increased renal sympathetic activity resulting in sodium retention. However, the mechanisms underlying the sympathetic control of renal sodium excretion remain unclear. In this study, we found that β(2)-ad...

journal_title：Nature medicine

authors： Mu S,Shimosawa T,Ogura S,Wang H,Uetake Y,Kawakami-Mori F,Marumo T,Yatomi Y,Geller DS,Tanaka H,Fujita T

更新日期：2011-05-01 00:00:00

abstract：:Overwhelming evidence that relationships between universities, physicians and the medical products industry benefit patients explains the ubiquitous calls to encourage such relationships. Yet accumulating 'conflict of interest' regulations in academic health centers, government and industry have had the opposite effec...

journal_title：Nature medicine

authors： Stossel TP,Stell LK

更新日期：2011-04-01 00:00:00

abstract：:Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo. Tissue-...

journal_title：Nature medicine

authors： Bhang HE,Gabrielson KL,Laterra J,Fisher PB,Pomper MG

更新日期：2011-01-01 00:00:00

abstract：:Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2...

journal_title：Nature medicine

authors： Medici D,Shore EM,Lounev VY,Kaplan FS,Kalluri R,Olsen BR

更新日期：2010-12-01 00:00:00

abstract：:The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...

journal_title：Nature medicine

authors： Gold MS,Gebhart GF

更新日期：2010-11-01 00:00:00

abstract：:The lifetime prevalence (∼16%) and the economic burden ($100 billion annually) associated with major depressive disorder (MDD) make it one of the most common and debilitating neurobiological illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology of MDD have not been identified. ...

journal_title：Nature medicine

authors： Duric V,Banasr M,Licznerski P,Schmidt HD,Stockmeier CA,Simen AA,Newton SS,Duman RS

更新日期：2010-11-01 00:00:00

abstract：:Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of dono...

journal_title：Nature medicine

authors： Ryan MA,Nattamai KJ,Xing E,Schleimer D,Daria D,Sengupta A,Köhler A,Liu W,Gunzer M,Jansen M,Ratner N,Le Cras TD,Waterstrat A,Van Zant G,Cancelas JA,Zheng Y,Geiger H

更新日期：2010-10-01 00:00:00

abstract：:Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by compariso...

journal_title：Nature medicine

authors： Kotz KT,Xiao W,Miller-Graziano C,Qian WJ,Russom A,Warner EA,Moldawer LL,De A,Bankey PE,Petritis BO,Camp DG 2nd,Rosenbach AE,Goverman J,Fagan SP,Brownstein BH,Irimia D,Xu W,Wilhelmy J,Mindrinos MN,Smith RD,Davis RW

更新日期：2010-09-01 00:00:00

abstract：:Ethylmalonic encephalopathy is caused by mutations in ETHE1, a mitochondrial matrix sulfur dioxygenase, leading to failure to detoxify sulfide, a product of intestinal anaerobes and, in trace amounts, tissues. Metronidazole, a bactericide, or N-acetylcysteine, a precursor of sulfide-buffering glutathione, substantiall...

journal_title：Nature medicine

authors： Viscomi C,Burlina AB,Dweikat I,Savoiardo M,Lamperti C,Hildebrandt T,Tiranti V,Zeviani M

更新日期：2010-08-01 00:00:00

abstract：:Improved techniques to noninvasively image protein-protein interactions (PPIs) are essential. We molecularly engineered a positron emission tomography (PET)-based split reporter (herpes simplex virus type 1 thymidine kinase), cleaved between Thr265 and Ala266, and used this in a protein-fragment complementation assay ...

journal_title：Nature medicine

authors： Massoud TF,Paulmurugan R,Gambhir SS

更新日期：2010-08-01 00:00:00

abstract：:The notoriously drug-resistant bug MRSA has made headlines for years, but a whole other class of bacteria may prove even more troublesome. These microbes, Gram-negative bacteria, are increasingly a threat--and yet not a single late-stage drug in development specifically targets them. Christian Torres follows one man's...

journal_title：Nature medicine

authors： Torres C

更新日期：2010-06-01 00:00:00

abstract：:Chondrocyte hypertrophy followed by cartilage matrix degradation and vascular invasion, characterized by expression of type X collagen (COL10A1), matrix metalloproteinase-13 (MMP-13) and vascular endothelial growth factor (VEGF), respectively, are central steps of endochondral ossification during normal skeletal growt...

journal_title：Nature medicine

authors： Saito T,Fukai A,Mabuchi A,Ikeda T,Yano F,Ohba S,Nishida N,Akune T,Yoshimura N,Nakagawa T,Nakamura K,Tokunaga K,Chung UI,Kawaguchi H

更新日期：2010-06-01 00:00:00

abstract：:Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interaction...

journal_title：Nature medicine

authors： Said EA,Dupuy FP,Trautmann L,Zhang Y,Shi Y,El-Far M,Hill BJ,Noto A,Ancuta P,Peretz Y,Fonseca SG,Van Grevenynghe J,Boulassel MR,Bruneau J,Shoukry NH,Routy JP,Douek DC,Haddad EK,Sekaly RP

更新日期：2010-04-01 00:00:00

abstract：:Observational clinical and ex vivo studies have established a strong association between atrial fibrillation and inflammation. However, whether inflammation is the cause or the consequence of atrial fibrillation and which specific inflammatory mediators may increase the atria's susceptibility to fibrillation remain el...

journal_title：Nature medicine

authors： Rudolph V,Andrié RP,Rudolph TK,Friedrichs K,Klinke A,Hirsch-Hoffmann B,Schwoerer AP,Lau D,Fu X,Klingel K,Sydow K,Didié M,Seniuk A,von Leitner EC,Szoecs K,Schrickel JW,Treede H,Wenzel U,Lewalter T,Nickenig G,Zimmer

更新日期：2010-04-01 00:00:00

abstract：:New technology has provided methods for collecting large amounts of data reflecting gene expression, metabolite and protein abundance, and post-translational modification of proteins. Integration of these various data sets enable the genetic mapping of many new phenotypes and facilitates the creation of network models...

journal_title：Nature medicine

authors： Newgard CB,Attie AD

更新日期：2010-04-01 00:00:00

abstract：:Targeting the mammalian target of rapamycin (mTOR) protein is a promising strategy for cancer therapy. The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamyci...

journal_title：Nature medicine

authors： Janes MR,Limon JJ,So L,Chen J,Lim RJ,Chavez MA,Vu C,Lilly MB,Mallya S,Ong ST,Konopleva M,Martin MB,Ren P,Liu Y,Rommel C,Fruman DA

更新日期：2010-02-01 00:00:00

abstract：:How should clinical trials be improved? Ken Getz, a senior fellow at the Tufts Center for the Study of Drug Development, has been thinking up answers to this question for two decades. In 2003, Getz took on a new challenge when he launched the Center for Information & Study on Clinical Research, a nonprofit focused on ...

journal_title：Nature medicine

authors： Getz K

更新日期：2010-02-01 00:00:00

abstract：:Hypertension is one of the most frequent pathologies in the industrialized world. Although recognized to be dependent on a combination of genetic and environmental factors, its molecular basis remains elusive. Increased activity of the monomeric G protein RhoA in arteries is a common feature of hypertension. However, ...

journal_title：Nature medicine

authors： Guilluy C,Brégeon J,Toumaniantz G,Rolli-Derkinderen M,Retailleau K,Loufrani L,Henrion D,Scalbert E,Bril A,Torres RM,Offermanns S,Pacaud P,Loirand G

更新日期：2010-02-01 00:00:00

abstract：:The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis...

journal_title：Nature medicine

authors： Barlow JL,Drynan LF,Hewett DR,Holmes LR,Lorenzo-Abalde S,Lane AL,Jolin HE,Pannell R,Middleton AJ,Wong SH,Warren AJ,Wainscoat JS,Boultwood J,McKenzie AN

更新日期：2010-01-01 00:00:00

abstract：:Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons i...

journal_title：Nature medicine

authors： Taghibiglou C,Martin HG,Lai TW,Cho T,Prasad S,Kojic L,Lu J,Liu Y,Lo E,Zhang S,Wu JZ,Li YP,Wen YH,Imm JH,Cynader MS,Wang YT

更新日期：2009-12-01 00:00:00

abstract：:Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...

journal_title：Nature medicine

authors： Li X,Zhang X,Leathers R,Makino A,Huang C,Parsa P,Macias J,Yuan JX,Jamieson SW,Thistlethwaite PA

更新日期：2009-11-01 00:00:00

abstract：:With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive ...

journal_title：Nature medicine

authors： Oney S,Lam RT,Bompiani KM,Blake CM,Quick G,Heidel JD,Liu JY,Mack BC,Davis ME,Leong KW,Sullenger BA

更新日期：2009-10-01 00:00:00

abstract：:Here we show that ischemia induces sustained contraction of pericytes on microvessels in the intact mouse brain. Pericytes remain contracted despite successful reopening of the middle cerebral artery after 2 h of ischemia. Pericyte contraction causes capillary constriction and obstructs erythrocyte flow. Suppression o...

journal_title：Nature medicine

authors： Yemisci M,Gursoy-Ozdemir Y,Vural A,Can A,Topalkara K,Dalkara T

更新日期：2009-09-01 00:00:00

abstract：:To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and m...

journal_title：Nature medicine

authors： Zhu J,Hladik F,Woodward A,Klock A,Peng T,Johnston C,Remington M,Magaret A,Koelle DM,Wald A,Corey L

更新日期：2009-08-01 00:00:00

abstract：:Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...

journal_title：Nature medicine

authors： Binder NB,Niederreiter B,Hoffmann O,Stange R,Pap T,Stulnig TM,Mack M,Erben RG,Smolen JS,Redlich K

更新日期：2009-04-01 00:00:00

abstract：:Hypothalamic brain-derived neurotrophic factor (BDNF) is a key element in the regulation of energy balance. Here we investigated the therapeutic efficacy of BDNF by gene transfer in mouse models of obesity and diabetes. Gene transfer of BDNF led to marked weight loss and alleviation of obesity-associated insulin resis...

journal_title：Nature medicine

authors： Cao L,Lin EJ,Cahill MC,Wang C,Liu X,During MJ

更新日期：2009-04-01 00:00:00

abstract：:Immune sensing of a microbe occurs via multiple receptors. How signals from different receptors are coordinated to yield a specific immune response is poorly understood. We show that two pathogen recognition receptors, Toll-like receptor 2 (TLR2) and dectin-1, recognizing the same microbial stimulus, stimulate distinc...

journal_title：Nature medicine

authors： Manicassamy S,Ravindran R,Deng J,Oluoch H,Denning TL,Kasturi SP,Rosenthal KM,Evavold BD,Pulendran B

更新日期：2009-04-01 00:00:00

abstract：:Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteope...

journal_title：Nature medicine

authors： Malinin NL,Zhang L,Choi J,Ciocea A,Razorenova O,Ma YQ,Podrez EA,Tosi M,Lennon DP,Caplan AI,Shurin SB,Plow EF,Byzova TV

更新日期：2009-03-01 00:00:00

abstract：:Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish betw...

journal_title：Nature medicine

authors： Wu D,Vu Q,Nguyen A,Stone JR,Stubbs H,Kuhlmann G,Sholl LM,Iafrate AJ

更新日期：2009-02-01 00:00:00