The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells.

abstract：:Human memory B cells and plasma cells represent a rich source of antibodies that have been selected in response to human pathogens. In the last decade, different methods have been developed to interrogate the human memory repertoire and isolate monoclonal antibodies. I will discuss how a target-agnostic approach based...

journal_title：EMBO molecular medicine

authors： Lanzavecchia A

更新日期：2018-03-01 00:00:00

abstract：:Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies on loss of function and overexpression implicate PINK1 in apoptosis, abnormal mitochondrial morphology, impaired dopamine release and motor deficits. However,...

journal_title：EMBO molecular medicine

authors： Morais VA,Verstreken P,Roethig A,Smet J,Snellinx A,Vanbrabant M,Haddad D,Frezza C,Mandemakers W,Vogt-Weisenhorn D,Van Coster R,Wurst W,Scorrano L,De Strooper B

更新日期：2009-05-01 00:00:00

abstract：:Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...

journal_title：EMBO molecular medicine

authors： Christensen NR,De Luca M,Lever MB,Richner M,Hansen AB,Noes-Holt G,Jensen KL,Rathje M,Jensen DB,Erlendsson S,Bartling CR,Ammendrup-Johnsen I,Pedersen SE,Schönauer M,Nissen KB,Midtgaard SR,Teilum K,Arleth L,Sørensen AT

更新日期：2020-06-08 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：:The combinations of genetic alterations that cooperate with von Hippel-Lindau (VHL) mutation to cause clear cell renal cell carcinoma (ccRCC) remain poorly understood. We show that the TP53 tumour suppressor gene is mutated in approximately 9% of human ccRCCs. Combined deletion of Vhl and Trp53 in primary mouse embryo...

journal_title：EMBO molecular medicine

authors： Albers J,Rajski M,Schönenberger D,Harlander S,Schraml P,von Teichman A,Georgiev S,Wild PJ,Moch H,Krek W,Frew IJ

更新日期：2013-06-01 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：:Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system....

journal_title：EMBO molecular medicine

authors： Villa-Bellosta R

更新日期：2020-10-07 00:00:00

abstract：:Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose ...

journal_title：EMBO molecular medicine

authors： Albert V,Svensson K,Shimobayashi M,Colombi M,Muñoz S,Jimenez V,Handschin C,Bosch F,Hall MN

更新日期：2016-03-01 00:00:00

abstract：:Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. He...

journal_title：EMBO molecular medicine

authors： Canfrán-Duque A,Rotllan N,Zhang X,Fernández-Fuertes M,Ramírez-Hidalgo C,Araldi E,Daimiel L,Busto R,Fernández-Hernando C,Suárez Y

更新日期：2017-09-01 00:00:00

abstract：:Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to be useful for COVID-19 infection via proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. W...

journal_title：EMBO molecular medicine

authors： Stebbing J,Krishnan V,de Bono S,Ottaviani S,Casalini G,Richardson PJ,Monteil V,Lauschke VM,Mirazimi A,Youhanna S,Tan YJ,Baldanti F,Sarasini A,Terres JAR,Nickoloff BJ,Higgs RE,Rocha G,Byers NL,Schlichting DE,Nirula A

更新日期：2020-08-07 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：:Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. ...

journal_title：EMBO molecular medicine

authors： Alsina-Beauchamp D,Escós A,Fajardo P,González-Romero D,Díaz-Mora E,Risco A,Martín-Serrano MA,Del Fresno C,Dominguez-Andrés J,Aparicio N,Zur R,Shpiro N,Brown GD,Ardavín C,Netea MG,Alemany S,Sanz-Ezquerro JJ,Cuenda A

更新日期：2018-05-01 00:00:00

abstract：:The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with c...

journal_title：EMBO molecular medicine

authors： Surinova S,Radová L,Choi M,Srovnal J,Brenner H,Vitek O,Hajdúch M,Aebersold R

更新日期：2015-09-01 00:00:00

abstract：:Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain- and loss-of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary arteri...

journal_title：EMBO molecular medicine

authors： Kivelä R,Bry M,Robciuc MR,Räsänen M,Taavitsainen M,Silvola JM,Saraste A,Hulmi JJ,Anisimov A,Mäyränpää MI,Lindeman JH,Eklund L,Hellberg S,Hlushchuk R,Zhuang ZW,Simons M,Djonov V,Knuuti J,Mervaala E,Alitalo K

更新日期：2014-03-01 00:00:00

abstract：:Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. The related SMN2 gene expresses suboptimal levels of functional SMN protein, due to a splicing defect. Many SMA patients reach adulthood, and there is also adult-onset (type IV) SMA. There is currently ...

journal_title：EMBO molecular medicine

authors： Sahashi K,Ling KK,Hua Y,Wilkinson JE,Nomakuchi T,Rigo F,Hung G,Xu D,Jiang YP,Lin RZ,Ko CP,Bennett CF,Krainer AR

更新日期：2013-10-01 00:00:00

abstract：:Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...

journal_title：EMBO molecular medicine

authors： Moraes CT

更新日期：2009-11-01 00:00:00

abstract：:Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sust...

journal_title：EMBO molecular medicine

authors： Smith KM,Datti A,Fujitani M,Grinshtein N,Zhang L,Morozova O,Blakely KM,Rotenberg SA,Hansford LM,Miller FD,Yeger H,Irwin MS,Moffat J,Marra MA,Baruchel S,Wrana JL,Kaplan DR

更新日期：2010-09-01 00:00:00

abstract：:Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this con...

journal_title：EMBO molecular medicine

authors： Arnold C,Feldner A,Pfisterer L,Hödebeck M,Troidl K,Genové G,Wieland T,Hecker M,Korff T

更新日期：2014-08-01 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 tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplas...

journal_title：EMBO molecular medicine

authors： Ceder S,Eriksson SE,Cheteh EH,Dawar S,Corrales Benitez M,Bykov VJN,Fujihara KM,Grandin M,Li X,Ramm S,Behrenbruch C,Simpson KJ,Hollande F,Abrahmsen L,Clemons NJ,Wiman KG

更新日期：2020-12-14 00:00:00

abstract：:The prostate-specific membrane antigen (PSMA) has been demonstrated in numerous studies to be expressed specifically on prostate carcinoma cells and on the neovasculature of several other cancer entities. However, the simultaneous expression of PSMA on both, tumor cells as well as tumor vessels remains unclear, even i...

journal_title：EMBO molecular medicine

authors： Zekri L,Vogt F,Osburg L,Müller S,Kauer J,Manz T,Pflügler M,Maurer A,Heitmann JS,Hagelstein I,Märklin M,Hörner S,Todenhöfer T,Calaminus C,Stenzl A,Pichler B,la Fougère C,Schneider MA,Rammensee HG,Zender L,Sipos B,

更新日期：2020-12-29 00:00:00

abstract：:The tumour microenvironment is known to play an integral role in facilitating cancer progression at advanced stages, but its function in some pre-cancerous lesions remains elusive. We have used the (V600) (E)BRAF-driven mouse lung model that develop premalignant lesions to understand stroma-tumour interactions during ...

journal_title：EMBO molecular medicine

authors： Kamata T,Jin H,Giblett S,Patel B,Patel F,Foster C,Pritchard C

更新日期：2015-09-01 00:00:00

abstract：:Hearing relies on mechanically gated ion channels present in the actin-rich stereocilia bundles at the apical surface of cochlear hair cells. Our knowledge of the mechanisms underlying the formation and maintenance of the sound-receptive structure is limited. Utilizing a large-scale forward genetic screen in mice, gen...

journal_title：EMBO molecular medicine

authors： Dunbar LA,Patni P,Aguilar C,Mburu P,Corns L,Wells HR,Delmaghani S,Parker A,Johnson S,Williams D,Esapa CT,Simon MM,Chessum L,Newton S,Dorning J,Jeyarajan P,Morse S,Lelli A,Codner GF,Peineau T,Gopal SR,Alagramam K

更新日期：2019-09-01 00:00:00

abstract：:Mutations in genes affecting primary cilia cause ciliopathies, a diverse group of disorders often affecting skeletal development. This includes Jeune syndrome or asphyxiating thoracic dystrophy (ATD), an autosomal recessive skeletal disorder. Unraveling the responsible molecular pathology helps illuminate mechanisms r...

journal_title：EMBO molecular medicine

authors： Bosakova M,Abraham SP,Nita A,Hruba E,Buchtova M,Taylor SP,Duran I,Martin J,Svozilova K,Barta T,Varecha M,Balek L,Kohoutek J,Radaszkiewicz T,Pusapati GV,Bryja V,Rush ET,Thiffault I,Nickerson DA,Bamshad MJ,Universit

更新日期：2020-11-06 00:00:00

abstract：:Growing evidence supports that LKB1-deficient KRAS-driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL-G12D/+ ; Lkb1flox/flox (KL) model show strong plasticity, which...

journal_title：EMBO molecular medicine

authors： Tong X,Chen Y,Zhu X,Ye Y,Xue Y,Wang R,Gao Y,Zhang W,Gao W,Xiao L,Chen H,Zhang P,Ji H

更新日期：2021-01-13 00:00:00

abstract：:Shah et al have recently reported the first successful sequencing of the entire genome of a solid tumour (Shah et al, 2009). Philippe Bedard and Christos Sotiriou analyse their findings as well as the challenges of applying the study of cancer genomes to clinical cancer care. ...

journal_title：EMBO molecular medicine

authors： Bedard PL,Sotiriou C

更新日期：2010-01-01 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

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：:Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-c...

journal_title：EMBO molecular medicine

authors： Patel R,Fleming J,Mui E,Loveridge C,Repiscak P,Blomme A,Harle V,Salji M,Ahmad I,Teo K,Hamdy FC,Hedley A,van den Broek N,Mackay G,Edwards J,Sansom OJ,Leung HY

更新日期：2018-04-01 00:00:00

abstract：:Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease-modifying treatment strategies of neuropeptides represent promising candidate...

journal_title：EMBO molecular medicine

authors： Agostinho AS,Mietzsch M,Zangrandi L,Kmiec I,Mutti A,Kraus L,Fidzinski P,Schneider UC,Holtkamp M,Heilbronn R,Schwarzer C

更新日期：2019-10-01 00:00:00