Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy.

abstract：:Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the nove...

journal_title：EMBO molecular medicine

authors： Hankir MK,Kranz M,Gnad T,Weiner J,Wagner S,Deuther-Conrad W,Bronisch F,Steinhoff K,Luthardt J,Klöting N,Hesse S,Seibyl JP,Sabri O,Heiker JT,Blüher M,Pfeifer A,Brust P,Fenske WK

更新日期：2016-07-01 00:00:00

abstract：:KCNN3, encoding the small conductance calcium-activated potassium channel SK3, harbours a polymorphic CAG repeat in the amino-terminal coding region with yet unproven function. Hypothesizing that KCNN3 genotypes do not influence susceptibility to schizophrenia but modify its phenotype, we explored their contribution t...

journal_title：EMBO molecular medicine

authors： Grube S,Gerchen MF,Adamcio B,Pardo LA,Martin S,Malzahn D,Papiol S,Begemann M,Ribbe K,Friedrichs H,Radyushkin KA,Müller M,Benseler F,Riggert J,Falkai P,Bickeböller H,Nave KA,Brose N,Stühmer W,Ehrenreich H

更新日期：2011-06-01 00:00:00

abstract：:In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part of the cancer cachectic phenotype, particularly by reduced hepatic very-low-density-lipoprotein (VLDL) sec...

journal_title：EMBO molecular medicine

authors： Jones A,Friedrich K,Rohm M,Schäfer M,Algire C,Kulozik P,Seibert O,Müller-Decker K,Sijmonsma T,Strzoda D,Sticht C,Gretz N,Dallinga-Thie GM,Leuchs B,Kögl M,Stremmel W,Diaz MB,Herzig S

更新日期：2013-02-01 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：:Initiating neoplastic cell transformation events are of paramount importance for the comprehension of regeneration and vanguard oncogenic processes but are difficult to characterize and frequently clinically overlooked. In epithelia, pre-neoplastic transformation stages are often distinguished by the appearance of phe...

journal_title：EMBO molecular medicine

authors： Regalo G,Leutz A

更新日期：2013-08-01 00:00:00

abstract：:The first EMBO workshop on Emerging Themes in Infection Biology was held last June in the South of France. It gathered scientists working on various pathogens from viruses and bacteria to larger eukaryotic fungi and parasites. Topics included not only the crosstalk between pathogens and their hosts but also the tools ...

journal_title：EMBO molecular medicine

authors： Caldeira S,Dumenil G

更新日期：2010-09-01 00:00:00

abstract：:Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...

journal_title：EMBO molecular medicine

authors： Khan NA,Auranen M,Paetau I,Pirinen E,Euro L,Forsström S,Pasila L,Velagapudi V,Carroll CJ,Auwerx J,Suomalainen A

更新日期：2014-06-01 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：:Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...

journal_title：EMBO molecular medicine

authors： Perli E,Giordano C,Pisano A,Montanari A,Campese AF,Reyes A,Ghezzi D,Nasca A,Tuppen HA,Orlandi M,Di Micco P,Poser E,Taylor RW,Colotti G,Francisci S,Morea V,Frontali L,Zeviani M,d'Amati G

更新日期：2014-02-01 00:00:00

abstract：:EMBO Molecular Medicine is enriched by a number of innovative policies designed to enhance the editorial process: peer review process files, de-emphasis of confidential referee comments and cross-refereeing. ...

journal_title：EMBO molecular medicine

authors： Pulverer B

更新日期：2010-09-01 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：:Gene targeting constitutes a new step in the development of gene therapy for inherited diseases. Although previous studies have shown the feasibility of editing fibroblasts from Fanconi anemia (FA) patients, here we aimed at conducting therapeutic gene editing in clinically relevant cells, such as hematopoietic stem c...

journal_title：EMBO molecular medicine

authors： Diez B,Genovese P,Roman-Rodriguez FJ,Alvarez L,Schiroli G,Ugalde L,Rodriguez-Perales S,Sevilla J,Diaz de Heredia C,Holmes MC,Lombardo A,Naldini L,Bueren JA,Rio P

更新日期：2017-11-01 00:00:00

abstract：:The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in int...

journal_title：EMBO molecular medicine

authors： Zhang Z,Shen M,Gresch PJ,Ghamari-Langroudi M,Rabchevsky AG,Emeson RB,Stamm S

更新日期：2016-08-01 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：:Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area com...

journal_title：EMBO molecular medicine

authors： Maruyama S,Nakamura K,Papanicolaou KN,Sano S,Shimizu I,Asaumi Y,van den Hoff MJ,Ouchi N,Recchia FA,Walsh K

更新日期：2016-08-01 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：: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

abstract：:Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and prom...

journal_title：EMBO molecular medicine

authors： Lee SW,Jeong HK,Lee JY,Yang J,Lee EJ,Kim SY,Youn SW,Lee J,Kim WJ,Kim KW,Lim JM,Park JW,Park YB,Kim HS

更新日期：2012-09-01 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 zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mut...

journal_title：EMBO molecular medicine

authors： Bin BH,Hojyo S,Hosaka T,Bhin J,Kano H,Miyai T,Ikeda M,Kimura-Someya T,Shirouzu M,Cho EG,Fukue K,Kambe T,Ohashi W,Kim KH,Seo J,Choi DH,Nam YJ,Hwang D,Fukunaka A,Fujitani Y,Yokoyama S,Superti-Furga A,Ikegawa S,

更新日期：2014-08-01 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：: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：:Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FG...

journal_title：EMBO molecular medicine

authors： Maddaluno L,Urwyler C,Rauschendorfer T,Meyer M,Stefanova D,Spörri R,Wietecha M,Ferrarese L,Stoycheva D,Bender D,Li N,Strittmatter G,Nasirujjaman K,Beer HD,Staeheli P,Hildt E,Oxenius A,Werner S

更新日期：2020-09-07 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：:Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...

journal_title：EMBO molecular medicine

authors： Whidbey C,Vornhagen J,Gendrin C,Boldenow E,Samson JM,Doering K,Ngo L,Ezekwe EA Jr,Gundlach JH,Elovitz MA,Liggitt D,Duncan JA,Adams Waldorf KM,Rajagopal L

更新日期：2015-04-01 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：: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：: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 cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which l...

journal_title：EMBO molecular medicine

authors： Souffriau J,Timmermans S,Vanderhaeghen T,Wallaeys C,Van Looveren K,Aelbrecht L,Dewaele S,Vandewalle J,Goossens E,Verbanck S,Boyen F,Eggermont M,De Commer L,De Rycke R,De Bruyne M,Tito R,Ballegeer M,Vandevyver S,Velho

更新日期：2020-10-07 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