The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure.

abstract：:Internalization of targeted therapeutics is often needed for efficacy, but also alters drug penetration of a tissue. A new model explores the trade-offs of intracellular drug trafficking. ...

journal_title：Nature medicine

authors： Stokes CL

更新日期：1995-11-01 00:00:00

abstract：:The BTB/POZ transcriptional repressor and candidate oncogene BCL6 is frequently misregulated in B-cell lymphomas. The interface through which the BCL6 BTB domain mediates recruitment of the SMRT, NCoR and BCoR corepressors was recently identified. To determine the contribution of this interface to BCL6 transcriptional...

journal_title：Nature medicine

authors： Polo JM,Dell'Oso T,Ranuncolo SM,Cerchietti L,Beck D,Da Silva GF,Prive GG,Licht JD,Melnick A

更新日期：2004-12-01 00:00:00

abstract：:Hedgehog signaling drives oncogenesis in several cancers, and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened (SMO). However, resistance to Smoothened inhibitors occurs by genetic changes of Smoothened or other downstream Hedgehog components. Here we overcome these ...

journal_title：Nature medicine

authors： Tang Y,Gholamin S,Schubert S,Willardson MI,Lee A,Bandopadhayay P,Bergthold G,Masoud S,Nguyen B,Vue N,Balansay B,Yu F,Oh S,Woo P,Chen S,Ponnuswami A,Monje M,Atwood SX,Whitson RJ,Mitra S,Cheshier SH,Qi J,Beroukh

更新日期：2014-07-01 00:00:00

abstract：:Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors....

journal_title：Nature medicine

authors： Davies H,Glodzik D,Morganella S,Yates LR,Staaf J,Zou X,Ramakrishna M,Martin S,Boyault S,Sieuwerts AM,Simpson PT,King TA,Raine K,Eyfjord JE,Kong G,Borg Å,Birney E,Stunnenberg HG,van de Vijver MJ,Børresen-Dale AL,Ma

更新日期：2017-04-01 00:00:00

abstract：:Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of ...

journal_title：Nature medicine

authors： Bhang HE,Ruddy DA,Krishnamurthy Radhakrishna V,Caushi JX,Zhao R,Hims MM,Singh AP,Kao I,Rakiec D,Shaw P,Balak M,Raza A,Ackley E,Keen N,Schlabach MR,Palmer M,Leary RJ,Chiang DY,Sellers WR,Michor F,Cooke VG,Korn JM

更新日期：2015-05-01 00:00:00

abstract：:The 55-kilodalton (kDa) protein from the E1B-region of adenovirus binds to and inactivates the p53 gene, which is mutated in half of human cancers. We have previously shown that the replication and cytopathogenicity of an E1B, 55-kDa gene-attenuated adenovirus, ONYX-015, is blocked by functional p53 in RKO and U20S ca...

journal_title：Nature medicine

authors： Heise C,Sampson-Johannes A,Williams A,McCormick F,Von Hoff DD,Kirn DH

更新日期：1997-06-01 00:00:00

abstract：:Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...

journal_title：Nature medicine

authors： Janes H,Herbeck JT,Tovanabutra S,Thomas R,Frahm N,Duerr A,Hural J,Corey L,Self SG,Buchbinder SP,McElrath MJ,O'Connell RJ,Paris RM,Rerks-Ngarm S,Nitayaphan S,Pitisuttihum P,Kaewkungwal J,Robb ML,Michael NL,Mullins JI

更新日期：2015-10-01 00:00:00

abstract：:Azoospermia or oligozoospermia due to disruption of spermatogenesis are common causes of human male infertility. We used the technique of spermatogonial transplantation in two infertile mouse strains, Steel (Sl) and dominant white spotting (W), to determine if stem cells from an infertile male were capable of generati...

journal_title：Nature medicine

authors： Ogawa T,Dobrinski I,Avarbock MR,Brinster RL

更新日期：2000-01-01 00:00:00

abstract：:Kidney transplantation has been one of the major medical advances of the past 30 years. However, tissue availability remains a major obstacle. This can potentially be overcome by the use of undifferentiated or partially developed kidney precursor cells derived from early embryos and fetal tissue. Here, transplantation...

journal_title：Nature medicine

authors： Dekel B,Burakova T,Arditti FD,Reich-Zeliger S,Milstein O,Aviel-Ronen S,Rechavi G,Friedman N,Kaminski N,Passwell JH,Reisner Y

更新日期：2003-01-01 00:00:00

abstract：:Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without ...

journal_title：Nature medicine

authors： Lee SH,Rho J,Jeong D,Sul JY,Kim T,Kim N,Kang JS,Miyamoto T,Suda T,Lee SK,Pignolo RJ,Koczon-Jaremko B,Lorenzo J,Choi Y

更新日期：2006-12-01 00:00:00

abstract：:Inflammation may underlie the metabolic disorders of insulin resistance and type 2 diabetes. IkappaB kinase beta (IKK-beta, encoded by Ikbkb) is a central coordinator of inflammatory responses through activation of NF-kappaB. To understand the role of IKK-beta in insulin resistance, we used mice lacking this enzyme in...

journal_title：Nature medicine

authors： Arkan MC,Hevener AL,Greten FR,Maeda S,Li ZW,Long JM,Wynshaw-Boris A,Poli G,Olefsky J,Karin M

更新日期：2005-02-01 00:00:00

abstract：:Natalizumab (NZM), a humanized monoclonal IgG4 antibody to α4 integrins, is used to treat patients with relapsing-remitting multiple sclerosis (MS)1,2, but in about 6% of the cases persistent neutralizing anti-drug antibodies (ADAs) are induced leading to therapy discontinuation3,4. To understand the basis of the ADA ...

journal_title：Nature medicine

authors： Cassotta A,Mikol V,Bertrand T,Pouzieux S,Le Parc J,Ferrari P,Dumas J,Auer M,Deisenhammer F,Gastaldi M,Franciotta D,Silacci-Fregni C,Fernandez Rodriguez B,Giacchetto-Sasselli I,Foglierini M,Jarrossay D,Geiger R,Sallusto

更新日期：2019-09-01 00:00:00

abstract：:De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...

journal_title：Nature medicine

authors： Breuss MW,Antaki D,George RD,Kleiber M,James KN,Ball LL,Hong O,Mitra I,Yang X,Wirth SA,Gu J,Garcia CAB,Gujral M,Brandler WM,Musaev D,Nguyen A,McEvoy-Venneri J,Knox R,Sticca E,Botello MCC,Uribe Fenner J,Pérez MC

更新日期：2020-01-01 00:00:00

abstract：: ...

journal_title：Nature medicine

authors： Hellmann MD,Snyder A

更新日期：2019-02-01 00:00:00

abstract：:Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with ins...

journal_title：Nature medicine

authors： Miyawaki K,Yamada Y,Ban N,Ihara Y,Tsukiyama K,Zhou H,Fujimoto S,Oku A,Tsuda K,Toyokuni S,Hiai H,Mizunoya W,Fushiki T,Holst JJ,Makino M,Tashita A,Kobara Y,Tsubamoto Y,Jinnouchi T,Jomori T,Seino Y

更新日期：2002-07-01 00:00:00

abstract：:One function of the glucocorticoid receptor (GR) in corticotroph cells is to suppress the transcription of the gene encoding proopiomelanocortin (POMC), the precursor of the stress hormone adrenocorticotropin (ACTH). Cushing disease is a neuroendocrine condition caused by partially glucocorticoid-resistant corticotrop...

journal_title：Nature medicine

authors： Riebold M,Kozany C,Freiburger L,Sattler M,Buchfelder M,Hausch F,Stalla GK,Paez-Pereda M

更新日期：2015-03-01 00:00:00

abstract：:Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a singl...

journal_title：Nature medicine

authors： Rapoport AP,Stadtmauer EA,Aqui N,Badros A,Cotte J,Chrisley L,Veloso E,Zheng Z,Westphal S,Mair R,Chi N,Ratterree B,Pochran MF,Natt S,Hinkle J,Sickles C,Sohal A,Ruehle K,Lynch C,Zhang L,Porter DL,Luger S,Guo C,

更新日期：2005-11-01 00:00:00

abstract：:Traumatic spinal cord injury often results in complete loss of voluntary motor and sensory function below the site of injury. The long-term neurological deficits after spinal cord trauma may be due in part to widespread apoptosis of neurons and oligodendroglia in regions distant from and relatively unaffected by the i...

journal_title：Nature medicine

authors： Springer JE,Azbill RD,Knapp PE

更新日期：1999-08-01 00:00:00

abstract：:The human CD4 molecule (hCD4) is expressed on T lymphocytes and macrophages and acts as a key component of the cellular receptor for HIV. At baseline, hCD4 transgenic mice expressed hCD4 on microglia, the resident mononuclear phagocytes of the brain, and showed no neuronal damage. Activation of brain microglia by peri...

journal_title：Nature medicine

authors： Buttini M,Westland CE,Masliah E,Yafeh AM,Wyss-Coray T,Mucke L

更新日期：1998-04-01 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：:Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal...

journal_title：Nature medicine

authors： Herzog RW,Yang EY,Couto LB,Hagstrom JN,Elwell D,Fields PA,Burton M,Bellinger DA,Read MS,Brinkhous KM,Podsakoff GM,Nichols TC,Kurtzman GJ,High KA

更新日期：1999-01-01 00:00:00

abstract：:The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ova...

journal_title：Nature medicine

authors： Wong GS,Zhou J,Liu JB,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,Jen

更新日期：2018-07-01 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：:Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to...

journal_title：Nature medicine

authors： Arunachalam PS,Charles TP,Joag V,Bollimpelli VS,Scott MKD,Wimmers F,Burton SL,Labranche CC,Petitdemange C,Gangadhara S,Styles TM,Quarnstrom CF,Walter KA,Ketas TJ,Legere T,Jagadeesh Reddy PB,Kasturi SP,Tsai A,Yeung BZ

更新日期：2020-06-01 00:00:00

abstract：:Atherosclerosis is a systemic disease of the large arteries, and activation of inflammatory pathways is important in its pathogenesis. Increasing evidence supports the importance of CD40-CD154 interactions in atherosclerosis, interactions originally known to be essential in major immune reactions and autoimmune diseas...

journal_title：Nature medicine

authors： Lutgens E,Gorelik L,Daemen MJ,de Muinck ED,Grewal IS,Koteliansky VE,Flavell RA

更新日期：1999-11-01 00:00:00

abstract：:Despite a more than 20-year experience of therapeutic benefit, the relevant molecular and cellular targets of intravenous immunoglobulin (IVIg) in autoimmune disease remain unclear. Contrary to the prevailing theories of IVIg action in autoimmunity, we show that IVIg drives signaling through activating Fc gamma recept...

journal_title：Nature medicine

authors： Siragam V,Crow AR,Brinc D,Song S,Freedman J,Lazarus AH

更新日期：2006-06-01 00:00:00

abstract：: ...

journal_title：Nature medicine

authors： Stower H

更新日期：2019-03-01 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：:Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymp...

journal_title：Nature medicine

authors： Wagar LE,Salahudeen A,Constantz CM,Wendel BS,Lyons MM,Mallajosyula V,Jatt LP,Adamska JZ,Blum LK,Gupta N,Jackson KJL,Yang F,Röltgen K,Roskin KM,Blaine KM,Meister KD,Ahmad IN,Cortese M,Dora EG,Tucker SN,Sperling AI

更新日期：2021-01-01 00:00:00

abstract：:Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta...

journal_title：Nature medicine

authors： Deane R,Du Yan S,Submamaryan RK,LaRue B,Jovanovic S,Hogg E,Welch D,Manness L,Lin C,Yu J,Zhu H,Ghiso J,Frangione B,Stern A,Schmidt AM,Armstrong DL,Arnold B,Liliensiek B,Nawroth P,Hofman F,Kindy M,Stern D,Zlokov

更新日期：2003-07-01 00:00:00