Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.

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：:Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. El...

journal_title：EMBO molecular medicine

authors： Liu T,Zhang J,Yang Y,Ma H,Li Z,Zhang J,Cheng J,Zhang X,Zhao Y,Xia Z,Zhang L,Wu G,Yi J

更新日期：2020-07-07 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：:Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...

journal_title：EMBO molecular medicine

authors： Goldmann T,Overlack N,Möller F,Belakhov V,van Wyk M,Baasov T,Wolfrum U,Nagel-Wolfrum K

更新日期：2012-11-01 00:00:00

abstract：:Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, is an autosomal dominant disorder caused by mutations in the gene encoding transcription factor p63. Here, we report the generation of a knock-in mouse model for AEC syndrome (p63(...

journal_title：EMBO molecular medicine

authors： Ferone G,Thomason HA,Antonini D,De Rosa L,Hu B,Gemei M,Zhou H,Ambrosio R,Rice DP,Acampora D,van Bokhoven H,Del Vecchio L,Koster MI,Tadini G,Spencer-Dene B,Dixon M,Dixon J,Missero C

更新日期：2012-03-01 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：: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：: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 disorders (MDs) are inherited multi-organ diseases with variable phenotypes. Inclusion body myositis (IBM), a sporadic inflammatory muscle disease, also shows mitochondrial dysfunction. We investigated whether primary and secondary MDs modify metabolism to reveal pathogenic pathways and biomarkers. We in...

journal_title：EMBO molecular medicine

authors： Buzkova J,Nikkanen J,Ahola S,Hakonen AH,Sevastianova K,Hovinen T,Yki-Järvinen H,Pietiläinen KH,Lönnqvist T,Velagapudi V,Carroll CJ,Suomalainen A

更新日期：2018-12-01 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：: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：:While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and...

journal_title：EMBO molecular medicine

authors： Marneros AG

更新日期：2016-03-01 00:00:00

abstract：:Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vas...

journal_title：EMBO molecular medicine

authors： Nurmi H,Saharinen P,Zarkada G,Zheng W,Robciuc MR,Alitalo K

更新日期：2015-11-01 00:00:00

abstract：:Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 muta...

journal_title：EMBO molecular medicine

authors： Inaguma Y,Hamada N,Tabata H,Iwamoto I,Mizuno M,Nishimura YV,Ito H,Morishita R,Suzuki M,Ohno K,Kumagai T,Nagata K

更新日期：2014-03-01 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：:The transcription factors of the MYC family play pivotal roles in the initiation and progression of human cancers. High oncogenic level of MYC invades low-affinity sites and enhancer sequences, which subsequently alters the transcriptome, causes metabolic imbalance, and induces stress response. The endoplasmic reticul...

journal_title：EMBO molecular medicine

authors： Zhang T,Li N,Sun C,Jin Y,Sheng X

更新日期：2020-05-08 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：:Clinical application of lentiviral vector (LV)-based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV-mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on th...

journal_title：EMBO molecular medicine

authors： Piras F,Riba M,Petrillo C,Lazarevic D,Cuccovillo I,Bartolaccini S,Stupka E,Gentner B,Cittaro D,Naldini L,Kajaste-Rudnitski A

更新日期：2017-09-01 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：: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：: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：:Conventional maximum-tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptiona...

journal_title：EMBO molecular medicine

authors： Schito L,Rey S,Xu P,Man S,Cruz-Muñoz W,Kerbel RS

更新日期：2020-09-07 00:00:00

abstract：:Familial Mediterranean fever (FMF) is the most frequent hereditary systemic autoinflammatory syndrome. FMF is usually caused by biallelic mutations in the MEFV gene, encoding Pyrin. Conclusive genetic evidence lacks for about 30% of patients diagnosed with clinical FMF. Pyrin is an inflammasome sensor maintained inact...

journal_title：EMBO molecular medicine

authors： Magnotti F,Lefeuvre L,Benezech S,Malsot T,Waeckel L,Martin A,Kerever S,Chirita D,Desjonqueres M,Duquesne A,Gerfaud-Valentin M,Laurent A,Sève P,Popoff MR,Walzer T,Belot A,Jamilloux Y,Henry T

更新日期：2019-11-07 00:00:00

abstract：:Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed th...

journal_title：EMBO molecular medicine

authors： Dedinszki D,Szeri F,Kozák E,Pomozi V,Tőkési N,Mezei TR,Merczel K,Letavernier E,Tang E,Le Saux O,Arányi T,van de Wetering K,Váradi A

更新日期：2017-11-01 00:00:00

abstract：:Alzheimer's disease (AD) is the most common cause of dementia. There are currently no effective treatments that may delay the onset, slow the progression or prevent the disease. Unless such treatments are developed, the number of AD cases is expected to double in the next 30 years. There is overwhelming genetic and bi...

journal_title：EMBO molecular medicine

authors： Holtzman DM

更新日期：2009-07-01 00:00:00

abstract：:Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition plays an important role in neurological disorders. Gephyrin is a central player at inhibitory postsynapses, directly binds and organizes GABAA and glycine receptors (GABAARs and GlyRs), and is thereby indispensable ...

journal_title：EMBO molecular medicine

authors： Dejanovic B,Djémié T,Grünewald N,Suls A,Kress V,Hetsch F,Craiu D,Zemel M,Gormley P,Lal D,EuroEPINOMICS Dravet working group.,Myers CT,Mefford HC,Palotie A,Helbig I,Meier JC,De Jonghe P,Weckhuysen S,Schwarz G

更新日期：2015-12-01 00:00:00

abstract：:Intellectual disability (ID) is a condition that affects approximately 1% of the population (Maulik et al, 2011). The numbers may differ across nations, owing to different systems and diagnosis entries or lack of such, but usually range between 0.6 and 3% (Stromme & Valvatne, 1998). Persons with ID are a heterogeneous...

journal_title：EMBO molecular medicine

authors： Kolset SO

更新日期：2020-10-07 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：:Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR act...

journal_title：EMBO molecular medicine

authors： Berthoux C,Hamieh AM,Rogliardo A,Doucet EL,Coudert C,Ango F,Grychowska K,Chaumont-Dubel S,Zajdel P,Maldonado R,Bockaert J,Marin P,Bécamel C

更新日期：2020-05-08 00:00:00

abstract：:Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogene...

journal_title：EMBO molecular medicine

authors： Hollingsworth EW,Vaughn JE,Orack JC,Skinner C,Khouri J,Lizarraga SB,Hester ME,Watanabe F,Kosik KS,Imitola J

更新日期：2017-12-01 00:00:00