Simultaneous impairment of neuronal and metabolic function of mutated gephyrin in a patient with epileptic encephalopathy.

abstract：:In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are proliferating. However, this proportion increases dramatically following the angiogenic switch during tumor growth or wound healing. Recent evidence suggests that this angiogenic switch is accompanied by a metabolic switch. Here, we show th...

journal_title：EMBO molecular medicine

authors： Coutelle O,Hornig-Do HT,Witt A,Andree M,Schiffmann LM,Piekarek M,Brinkmann K,Seeger JM,Liwschitz M,Miwa S,Hallek M,Krönke M,Trifunovic A,Eming SA,Wiesner RJ,Hacker UT,Kashkar H

更新日期：2014-05-01 00:00:00

abstract：:Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with...

journal_title：EMBO molecular medicine

authors： Zhang J,He Y,Yan X,Chen S,He M,Lei Y,Zhang J,Gongol B,Gu M,Miao Y,Bai L,Cui X,Wang X,Zhang Y,Fan F,Li Z,Shen Y,Chou CH,Huang HD,Malhotra A,Rabinovitch M,Jing ZC,Shyy JY

更新日期：2020-05-08 00:00:00

abstract：:Sequence variations occurring in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) support an essential function of microglia and innate immunity in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. TREM2 matures within the secretory pathway, and its ectod...

journal_title：EMBO molecular medicine

authors： Schlepckow K,Kleinberger G,Fukumori A,Feederle R,Lichtenthaler SF,Steiner H,Haass C

更新日期：2017-10-01 00:00:00

abstract：:Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...

journal_title：EMBO molecular medicine

authors： Liang KX,Kristiansen CK,Mostafavi S,Vatne GH,Zantingh GA,Kianian A,Tzoulis C,Høyland LE,Ziegler M,Perez RM,Furriol J,Zhang Z,Balafkan N,Hong Y,Siller R,Sullivan GJ,Bindoff LA

更新日期：2020-10-07 00:00:00

abstract：:Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compoun...

journal_title：EMBO molecular medicine

authors： Hashemi P,Barreto K,Bernhard W,Lomness A,Honson N,Pfeifer TA,Harrigan PR,Sadowski I

更新日期：2018-02-01 00:00:00

abstract：:The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...

journal_title：EMBO molecular medicine

authors： Tosoni D,Pambianco S,Ekalle Soppo B,Zecchini S,Bertalot G,Pruneri G,Viale G,Di Fiore PP,Pece S

更新日期：2017-05-01 00:00:00

abstract：:The search for non-invasive systemic biomarkers of response to PD-L1/PD-1 blockade immunotherapy is currently a priority in oncoimmunology. In contrast to classical tumor biomarkers, the identification of clinically useful immunological biomarkers is certainly a challenge, as anti-cancer immune responses depend on the...

journal_title：EMBO molecular medicine

authors： Zuazo M,Arasanz H,Bocanegra A,Chocarro L,Vera R,Escors D,Kagamu H,Kochan G

更新日期：2020-09-07 00:00:00

abstract：:5'AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth...

journal_title：EMBO molecular medicine

authors： Zadra G,Photopoulos C,Tyekucheva S,Heidari P,Weng QP,Fedele G,Liu H,Scaglia N,Priolo C,Sicinska E,Mahmood U,Signoretti S,Birnberg N,Loda M

更新日期：2014-04-01 00:00:00

abstract：:On November 14 last year, the British Guardian published an account from an anonymous whistleblower at Google, accusing the company of misconduct in regard to handling sensitive health data. The whistleblower works for Project Nightingale, an attempt by Google to get into the lucrative US healthcare market, by storing...

journal_title：EMBO molecular medicine

authors： Schneble CO,Elger BS,Shaw DM

更新日期：2020-03-06 00:00:00

abstract：:Chimeric antigen receptor (CAR) T cell therapy, together with checkpoint inhibition, has been celebrated as a breakthrough technology due to the substantial benefit observed in clinical trials with patients suffering from relapsed or refractory B-cell malignancies. In this review, we provide a comprehensive overview o...

journal_title：EMBO molecular medicine

authors： Hartmann J,Schüßler-Lenz M,Bondanza A,Buchholz CJ

更新日期：2017-09-01 00:00:00

abstract：:Formation of pathogenic antibodies is a major problem in replacement therapies for inherited protein deficiencies. For example, antibodies to coagulation factors ('inhibitors') seriously complicate treatment of haemophilia. While immune tolerance induction (ITI) protocols have been developed, inhibitors against factor...

journal_title：EMBO molecular medicine

authors： Markusic DM,Hoffman BE,Perrin GQ,Nayak S,Wang X,LoDuca PA,High KA,Herzog RW

更新日期：2013-11-01 00:00:00

abstract：:Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...

journal_title：EMBO molecular medicine

authors： Molnár-Gábor F,Korbel JO

更新日期：2020-03-06 00:00:00

abstract：:The lack of actionable mutations in patients with non-small cell lung cancer (NSCLC) presents a significant hurdle in the design of targeted therapies for this disease. Here, we identify somatically mutated ABL1 as a genetic dependency that is required to maintain NSCLC cell survival. We demonstrate that NSCLC cells w...

journal_title：EMBO molecular medicine

authors： Testoni E,Stephenson NL,Torres-Ayuso P,Marusiak AA,Trotter EW,Hudson A,Hodgkinson CL,Morrow CJ,Dive C,Brognard J

更新日期：2016-02-01 00:00:00

abstract：:The insulin/insulin-like growth factor-1 signalling (IIS) pathway regulates cellular and organismal metabolism and controls the rate of aging. Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer. In contrast, loss-of-function mutations in p110α impa...

journal_title：EMBO molecular medicine

authors： Foukas LC,Bilanges B,Bettedi L,Pearce W,Ali K,Sancho S,Withers DJ,Vanhaesebroeck B

更新日期：2013-04-01 00:00:00

abstract：:Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defecti...

journal_title：EMBO molecular medicine

authors： Lahiguera Á,Hyroššová P,Figueras A,Garzón D,Moreno R,Soto-Cerrato V,McNeish I,Serra V,Lazaro C,Barretina P,Brunet J,Menéndez J,Matias-Guiu X,Vidal A,Villanueva A,Taylor-Harding B,Tanaka H,Orsulic S,Junza A,Yanes O,

更新日期：2020-06-08 00:00:00

abstract：:In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic ...

journal_title：EMBO molecular medicine

authors： Cronin T,Vandenberghe LH,Hantz P,Juttner J,Reimann A,Kacsó AE,Huckfeldt RM,Busskamp V,Kohler H,Lagali PS,Roska B,Bennett J

更新日期：2014-09-01 00:00:00

abstract：:Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastat...

journal_title：EMBO molecular medicine

authors： Xing F,Kobayashi A,Okuda H,Watabe M,Pai SK,Pandey PR,Hirota S,Wilber A,Mo YY,Moore BE,Liu W,Fukuda K,Iiizumi M,Sharma S,Liu Y,Wu K,Peralta E,Watabe K

更新日期：2013-03-01 00:00:00

abstract：:Organismal ageing is a complex process driving progressive impairment of functionality and regenerative potential of tissues. Cellular senescence is a state of stable cell cycle arrest occurring in response to damage and stress and is considered a hallmark of ageing. Senescent cells accumulate in multiple organs durin...

journal_title：EMBO molecular medicine

authors： Paez-Ribes M,González-Gualda E,Doherty GJ,Muñoz-Espín D

更新日期：2019-12-01 00:00:00

abstract：:The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogen...

journal_title：EMBO molecular medicine

authors： Carragher LA,Snell KR,Giblett SM,Aldridge VS,Patel B,Cook SJ,Winton DJ,Marais R,Pritchard CA

更新日期：2010-11-01 00:00:00

abstract：:Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally a...

journal_title：EMBO molecular medicine

authors： Wend P,Runke S,Wend K,Anchondo B,Yesayan M,Jardon M,Hardie N,Loddenkemper C,Ulasov I,Lesniak MS,Wolsky R,Bentolila LA,Grant SG,Elashoff D,Lehr S,Latimer JJ,Bose S,Sattar H,Krum SA,Miranda-Carboni GA

更新日期：2013-02-01 00:00:00

abstract：:Resistance to tamoxifen is a clinically major challenge in breast cancer treatment. Although downregulation of estrogen receptor-alpha (ERα) is the dominant mechanism of tamoxifen resistance, the reason for ERα decrease during tamoxifen therapy remains elusive. Herein, we reported that Spalt-like transcription factor ...

journal_title：EMBO molecular medicine

authors： Ye L,Lin C,Wang X,Li Q,Li Y,Wang M,Zhao Z,Wu X,Shi D,Xiao Y,Ren L,Jian Y,Yang M,Ou R,Deng G,Ouyang Y,Chen X,Li J,Song L

更新日期：2019-12-01 00:00:00

abstract：:Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in α2 Na(+),K(+) ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon ...

journal_title：EMBO molecular medicine

authors： Capuani C,Melone M,Tottene A,Bragina L,Crivellaro G,Santello M,Casari G,Conti F,Pietrobon D

更新日期：2016-08-01 00:00:00

abstract：:Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and...

journal_title：EMBO molecular medicine

authors： Xiang X,Werner G,Bohrmann B,Liesz A,Mazaheri F,Capell A,Feederle R,Knuesel I,Kleinberger G,Haass C

更新日期：2016-09-01 00:00:00

abstract：:In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2-3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine ...

journal_title：EMBO molecular medicine

authors： Delany I,Rappuoli R,De Gregorio E

更新日期：2014-06-01 00:00:00

abstract：:The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...

journal_title：EMBO molecular medicine

authors： Demminger DE,Walz L,Dietert K,Hoffmann H,Planz O,Gruber AD,von Messling V,Wolff T

更新日期：2020-05-08 00:00:00

abstract：:The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MM...

journal_title：EMBO molecular medicine

authors： Liu JC,Voisin V,Wang S,Wang DY,Jones RA,Datti A,Uehling D,Al-awar R,Egan SE,Bader GD,Tsao M,Mak TW,Zacksenhaus E

更新日期：2014-12-01 00:00:00

abstract：:High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...

journal_title：EMBO molecular medicine

authors： Germann M,Zangger N,Sauvain MO,Sempoux C,Bowler AD,Wirapati P,Kandalaft LE,Delorenzi M,Tejpar S,Coukos G,Radtke F

更新日期：2020-01-09 00:00:00

abstract：:Telomerase is expressed in the neonatal brain, in distinct regions of adult brain, and was shown to protect developing neurons from apoptosis. Telomerase reactivation by gene manipulation reverses neurodegeneration in aged telomerase-deficient mice. Hence, we and others hypothesized that increasing telomerase expressi...

journal_title：EMBO molecular medicine

authors： Eitan E,Tichon A,Gazit A,Gitler D,Slavin S,Priel E

更新日期：2012-04-01 00:00:00

abstract：:Germ-line mutations in the BRCA1 gene strongly predispose women to breast cancer (lifetime risk up to 80%). Furthermore, the BRCA1 protein is absent or present at very low levels in about one third of sporadic breast cancers. However, the mechanisms underlying BRCA1 somatic inactivation appear multiple and are still n...

journal_title：EMBO molecular medicine

authors： Garcia AI,Buisson M,Bertrand P,Rimokh R,Rouleau E,Lopez BS,Lidereau R,Mikaélian I,Mazoyer S

更新日期：2011-05-01 00:00:00

abstract：:Lipid droplets (LDs) are dynamic, cytosolic lipid-storage organelles found in nearly all cell types. Too many or too few LDs during excess or deficient fat storage lead to many different human diseases. Recent insights into LD biology and LD protein functions shed new light on mechanisms underlying those metabolic pat...

journal_title：EMBO molecular medicine

authors： Krahmer N,Farese RV Jr,Walther TC

更新日期：2013-07-01 00:00:00