Researching genetic versus nongenetic determinants of disease: a comparison and proposed unification.

abstract：:Age is the most significant risk factor for atherosclerosis; however, the link between age and atherosclerosis is poorly understood. During both aging and atherosclerosis progression, the blood vessel wall stiffens owing to alterations in the extracellular matrix. Using in vitro and ex vivo models of vessel wall stiff...

journal_title：Science translational medicine

authors： Huynh J,Nishimura N,Rana K,Peloquin JM,Califano JP,Montague CR,King MR,Schaffer CB,Reinhart-King CA

更新日期：2011-12-07 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated wi...

journal_title：Science translational medicine

authors： Smith BN,Topp SD,Fallini C,Shibata H,Chen HJ,Troakes C,King A,Ticozzi N,Kenna KP,Soragia-Gkazi A,Miller JW,Sato A,Dias DM,Jeon M,Vance C,Wong CH,de Majo M,Kattuah W,Mitchell JC,Scotter EL,Parkin NW,Sapp PC,Nol

更新日期：2017-05-03 00:00:00

abstract：:Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte-specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-th...

journal_title：Science translational medicine

authors： Asimaki A,Kapoor S,Plovie E,Karin Arndt A,Adams E,Liu Z,James CA,Judge DP,Calkins H,Churko J,Wu JC,MacRae CA,Kléber AG,Saffitz JE

更新日期：2014-06-11 00:00:00

abstract：:Previous attempts to gain insight into the pathogenesis of psoriasis and eczema by comparing their molecular signatures were hampered by the high interindividual variability of those complex diseases. In patients affected by both psoriasis and nonatopic or atopic eczema simultaneously (n = 24), an intraindividual comp...

journal_title：Science translational medicine

authors： Quaranta M,Knapp B,Garzorz N,Mattii M,Pullabhatla V,Pennino D,Andres C,Traidl-Hoffmann C,Cavani A,Theis FJ,Ring J,Schmidt-Weber CB,Eyerich S,Eyerich K

更新日期：2014-07-09 00:00:00

abstract：:Clinical management of human cancer is dependent on the accurate monitoring of residual and recurrent tumors. The evaluation of patient-specific translocations in leukemias and lymphomas has revolutionized diagnostics for these diseases. We have developed a method, called personalized analysis of rearranged ends (PARE...

journal_title：Science translational medicine

authors： Leary RJ,Kinde I,Diehl F,Schmidt K,Clouser C,Duncan C,Antipova A,Lee C,McKernan K,De La Vega FM,Kinzler KW,Vogelstein B,Diaz LA Jr,Velculescu VE

更新日期：2010-02-24 00:00:00

abstract：:The invasive nature of glioblastoma (GBM) represents a major clinical challenge contributing to poor outcomes. Invasion of GBM into healthy tissue restricts chemotherapeutic access and complicates surgical resection. Here, we test the hypothesis that an effective anti-invasive agent can "contain" GBM and increase the ...

journal_title：Science translational medicine

authors： Munson JM,Fried L,Rowson SA,Bonner MY,Karumbaiah L,Diaz B,Courtneidge SA,Knaus UG,Brat DJ,Arbiser JL,Bellamkonda RV

更新日期：2012-03-28 00:00:00

abstract：:Trauma-induced critical illness is driven by acute inflammation, and elevated systemic interleukin-6 (IL-6) after trauma is a biomarker of adverse outcomes. We constructed a multicompartment, ordinary differential equation model that represents a virtual trauma patient. Individual-specific variants of this model repro...

journal_title：Science translational medicine

authors： Brown D,Namas RA,Almahmoud K,Zaaqoq A,Sarkar J,Barclay DA,Yin J,Ghuma A,Abboud A,Constantine G,Nieman G,Zamora R,Chang SC,Billiar TR,Vodovotz Y

更新日期：2015-04-29 00:00:00

abstract：:PTEN (phosphatase and tensin homolog) loss of function is the most common genetic aberration in endometrioid endometrial carcinomas. In addition to its well-described role in cell signaling, PTEN is involved in the maintenance of genomic stability. Loss of PTEN function causes defects in repair of DNA double-strand br...

journal_title：Science translational medicine

authors： Dedes KJ,Wetterskog D,Mendes-Pereira AM,Natrajan R,Lambros MB,Geyer FC,Vatcheva R,Savage K,Mackay A,Lord CJ,Ashworth A,Reis-Filho JS

更新日期：2010-10-13 00:00:00

abstract：:An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade significantly reduces tumor burden and improves survival in murine cancer models. ...

journal_title：Science translational medicine

authors： Jonas BA

更新日期：2017-04-19 00:00:00

abstract：:Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T cell activation. Although evidence for an active immune response, including infiltration with CD8(+) T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejecte...

journal_title：Science translational medicine

authors： Spranger S,Spaapen RM,Zha Y,Williams J,Meng Y,Ha TT,Gajewski TF

更新日期：2013-08-28 00:00:00

abstract：:Chemotherapy-induced cardiotoxicity (CIC) is a common clinical problem that compromises effective anticancer therapies. Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure. Althoug...

journal_title：Science translational medicine

authors： Saleme B,Gurtu V,Zhang Y,Kinnaird A,Boukouris AE,Gopal K,Ussher JR,Sutendra G

更新日期：2019-02-06 00:00:00

abstract：:Regular physical activity and especially aerobic exercise are associated with reduced risk of disease and enhanced longevity, but the molecular mechanisms of these health benefits remain obscure. A comprehensive metabolomic approach was used to characterize the changes in blood levels of >200 metabolites upon vigorous...

journal_title：Science translational medicine

authors： Burke MF,Dunbar RL,Rader DJ

更新日期：2010-07-21 00:00:00

abstract：:Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening, cutaneous adverse drug reactions that are accompanied by keratinocyte cell death. Dead keratinocytes from SJS/TEN lesions exhibited necrosis, by morphological criteria. Supernatant from peripheral blood mononuclear cells (PBMCs) ...

journal_title：Science translational medicine

authors： Saito N,Qiao H,Yanagi T,Shinkuma S,Nishimura K,Suto A,Fujita Y,Suzuki S,Nomura T,Nakamura H,Nagao K,Obuse C,Shimizu H,Abe R

更新日期：2014-07-16 00:00:00

abstract：:Myofibroblast-derived αvβ1 integrin has emerged as a critical mediator of transforming growth factor-β activation in experimental models of tissue fibrosis (Reed et al., this issue). ...

journal_title：Science translational medicine

authors： Dietz HC

更新日期：2015-05-20 00:00:00

abstract：:Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacok...

journal_title：Science translational medicine

authors： Andrews CD,Yueh YL,Spreen WR,St Bernard L,Boente-Carrera M,Rodriguez K,Gettie A,Russell-Lodrigue K,Blanchard J,Ford S,Mohri H,Cheng-Mayer C,Hong Z,Ho DD,Markowitz M

更新日期：2015-01-14 00:00:00

abstract：:Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations b...

journal_title：Science translational medicine

authors： Lipp MM,Batycky R,Moore J,Leinonen M,Freed MI

更新日期：2016-10-12 00:00:00

abstract：:Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomic analyses of clini...

journal_title：Science translational medicine

authors： Zhang L,Yao Y,Zhang S,Liu Y,Guo H,Ahmed M,Bell T,Zhang H,Han G,Lorence E,Badillo M,Zhou S,Sun Y,Di Francesco ME,Feng N,Haun R,Lan R,Mackintosh SG,Mao X,Song X,Zhang J,Pham LV,Lorenzi PL,Marszalek J,Heffern

更新日期：2019-05-08 00:00:00

abstract：:Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolom...

journal_title：Science translational medicine

authors： Zampieri M,Szappanos B,Buchieri MV,Trauner A,Piazza I,Picotti P,Gagneux S,Borrell S,Gicquel B,Lelievre J,Papp B,Sauer U

更新日期：2018-02-21 00:00:00

abstract：:Atherosclerosis is the cause of morbiditiy for 70% of patients with type 2 diabetes. In both of these diseases, a protein complex known as the inflammasome is stimulated to activate interleukin-1β (IL-1β) and IL-18, which are pathogenic inflammatory cytokines. Triggers for the inflammasome are obesity-related factors,...

journal_title：Science translational medicine

authors： Masters SL,Latz E,O'Neill LA

更新日期：2011-05-04 00:00:00

abstract：:Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and i...

journal_title：Science translational medicine

authors： Politis M,Wu K,Loane C,Quinn NP,Brooks DJ,Rehncrona S,Bjorklund A,Lindvall O,Piccini P

更新日期：2010-06-30 00:00:00

abstract：:Epithelial tissues line the organs of the body, providing an initial protective barrier as well as a surface for nutrient and drug absorption. Here, we identified enzymatic components present in the gastrointestinal epithelium that can serve as selective means for tissue-directed polymerization. We focused on the smal...

journal_title：Science translational medicine

authors： Li J,Wang T,Kirtane AR,Shi Y,Jones A,Moussa Z,Lopes A,Collins J,Tamang SM,Hess K,Shakur R,Karandikar P,Lee JS,Huang HW,Hayward A,Traverso G

更新日期：2020-08-26 00:00:00

abstract：:Vaccines against influenza viruses with pandemic potential, including H5N1, are under development. Because of a lack of preexisting immunity to these viruses, adjuvants (immune potentiators or enhancers) are needed to improve immune responses, to conserve scarce vaccine, and for cross-protection against strains that h...

journal_title：Science translational medicine

authors： Khurana S,Chearwae W,Castellino F,Manischewitz J,King LR,Honorkiewicz A,Rock MT,Edwards KM,Del Giudice G,Rappuoli R,Golding H

更新日期：2010-01-20 00:00:00

abstract：:A clinical trial evaluating HIV vaccine therapy teaches us much about optimal design (Sneller et al, this issue). ...

journal_title：Science translational medicine

authors： Michael NL

更新日期：2017-12-06 00:00:00

abstract：:Biomedical engineering tools can be harnessed to address some of the world's most challenging nondisease-focused problems. ...

journal_title：Science translational medicine

authors： LeDuc P,Agaba M,Cheng CM,Gracio J,Guzman A,Middelberg A

更新日期：2014-12-10 00:00:00

abstract：:Studies have suggested a role for the mammalian (or mechanistic) target of rapamycin (mTOR) in skeletal development and homeostasis, yet there is no evidence connecting mTOR with the key signaling pathways that regulate skeletogenesis. We identified a parathyroid hormone (PTH)/PTH-related peptide (PTHrP)-salt-inducibl...

journal_title：Science translational medicine

authors： Csukasi F,Duran I,Barad M,Barta T,Gudernova I,Trantirek L,Martin JH,Kuo CY,Woods J,Lee H,Cohn DH,Krejci P,Krakow D

更新日期：2018-09-19 00:00:00

abstract：:Advances in understanding the genetics and underlying pathology of the catastrophic childhood epilepsies are pointing toward treatments. ...

journal_title：Science translational medicine

authors： Katsnelson A,Buzsáki G,Swann JW

更新日期：2014-11-12 00:00:00

abstract：:Glucagon-like peptide-1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 inhibitors are widely prescribed diabetes drugs due to their ability to stimulate insulin secretion from remaining β cells and to reduce caloric intake. Unfortunately, they fail to increase human β cell proliferation. Small-molecule inhibitor...

journal_title：Science translational medicine

authors： Ackeifi C,Wang P,Karakose E,Manning Fox JE,González BJ,Liu H,Wilson J,Swartz E,Berrouet C,Li Y,Kumar K,MacDonald PE,Sanchez R,Thorens B,DeVita R,Homann D,Egli D,Scott DK,Garcia-Ocaña A,Stewart AF

更新日期：2020-02-12 00:00:00

abstract：:Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decrea...

journal_title：Science translational medicine

authors： Lim MM,Elkind J,Xiong G,Galante R,Zhu J,Zhang L,Lian J,Rodin J,Kuzma NN,Pack AI,Cohen AS

更新日期：2013-12-11 00:00:00

abstract：:Information provided to patients is thought to influence placebo and drug effects. In a prospective, within-subjects, repeated-measures study of 66 subjects with episodic migraine, we investigated how variations in medication labeling modified placebo and drug effects. An initial attack with no treatment served as a c...

journal_title：Science translational medicine

authors： Kam-Hansen S,Jakubowski M,Kelley JM,Kirsch I,Hoaglin DC,Kaptchuk TJ,Burstein R

更新日期：2014-01-08 00:00:00

abstract：:Hepatitis B virus (HBV)-induced hepatitis and carcinogen-induced hepatocellular carcinoma (HCC) are associated with serum androgen concentration. However, how androgen or the androgen receptor (AR) contributes to HBV-induced hepatocarcinogenesis remains unclear. We found that hepatic AR promotes HBV-induced hepatocarc...

journal_title：Science translational medicine

authors： Wu MH,Ma WL,Hsu CL,Chen YL,Ou JH,Ryan CK,Hung YC,Yeh S,Chang C

更新日期：2010-05-19 00:00:00