Browsing Harvard Medical School by Title
Now showing items 10130-10149 of 18428
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Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis
(The Rockefeller University Press, 2016)Myeloproliferative neoplasm (MPN) patients frequently show co-occurrence of JAK2-V617F and mutations in epigenetic regulator genes, including EZH2. In this study, we show that JAK2-V617F and loss of Ezh2 in hematopoietic ... -
Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis
(Public Library of Science, 2014)Systemic Mastocytosis (SM) is a clonal disease characterized by abnormal accumulation of mast cells in multiple organs. Clinical presentations of the disease vary widely from indolent to aggressive forms, and to the ... -
Loss of HDAC-Mediated Repression and Gain of NF-?B Activation Underlie Cytokine Induction in ARID1A- and PIK3CA-Mutation-Driven Ovarian Cancer
(Elsevier BV, 2016)ARID1A is frequently mutated in ovarian clear cell carcinoma (OCCC) and often co-exists with activating mutations of PIK3CA. Although induction of pro-inflammatory cytokines has been observed in this cancer, the mechanism ... -
Loss of Ikaros DNA-binding function confers integrin-dependent survival on pre-B cells and progression to acute lymphoblastic leukemia
(Springer Nature, 2014)Deletion of the DNA-binding domain of the transcription factor Ikaros generates dominant-negative isoforms that interfere with its activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic ... -
Loss of Insulin Receptor in Osteoprogenitor Cells Impairs Structural Strength of Bone
(Hindawi Publishing Corporation, 2014)Type 1 diabetes mellitus (T1D) is associated with decreased bone mineral density, a deficit in bone structure, and subsequently an increased risk of fragility fracture. These clinical observations, paralleled by animal ... -
Loss of Leucine-rich Repeat Kinase 2 Causes Age-dependent Bi-phasic Alterations of the Autophagy Pathway
(BioMed Central, 2012)Background: Dominantly inherited missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, but its normal physiological function remains unclear. We previously ... -
Loss of Lkb1 and Pten Leads to Lung Squamous Cell Carcinoma with Elevated PD-L1 Expression
(Elsevier BV, 2014-05)Lung squamous cell carcinoma (SCC) is a deadly disease for which current treatments are inadequate. We demonstrate that biallelic inactivation of Lkb1 and Pten in the mouse lung leads to SCC that recapitulates the histology, ... -
Loss of Metabotropic Glutamate Receptor 5 Function on Peripheral Benzodiazepine Receptor in Mice Prenatally Exposed to LPS
(Public Library of Science, 2015)Parental microglial induced neuroinflammation, triggered by bacterial- or viral infections, can induce neuropsychiatric disorders like schizophrenia and autism to offspring in animal models. Recent investigations suggest ... -
Loss of p53 Attenuates the Contribution of IL-6 Deletion on Suppressed Tumor Progression and Extended Survival in Kras-Driven Murine Lung Cancer
(Public Library of Science, 2013)Interleukin-6 (IL-6) is involved in lung cancer tumorigenesis, tumor progression, metastasis, and drug resistance. Previous studies show that blockade of IL-6 signaling can inhibit tumor growth and increase drug sensitivity ... -
Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway
(Impact Journals LLC, 2015)Altered regulation of ER stress response has been implicated in a variety of human diseases, such as cancer and metabolic diseases. Excessive ER function contributes to malignant phenotypes, such as chemoresistance and ... -
Loss of PDZK1 Causes Coronary Artery Occlusion and Myocardial Infarction in Paigen Diet-Fed Apolipoprotein E Deficient Mice
(Public Library of Science, 2009)Background: PDZK1 is a four PDZ-domain containing protein that binds to the carboxy terminus of the HDL receptor, scavenger receptor class B type I (SR-BI), and regulates its expression, localization and function in a ... -
Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes
(National Academy of Sciences, 2002)Phosphorylation of proteins on serine/threonine residues preceding proline is a key signaling mechanism. The conformation and function of a subset of these phosphorylated proteins is regulated by the prolyl isomerase Pin ... -
Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon
(National Academy of Sciences, 2008)To examine the role of Rb1 in gastrointestinal (GI) tumors, we generated mice with an Apc(1638N) allele, Rb-tm2brn floxed alleles, and a villin-cre transgene (RBVCA). These animals had exon 19 deleted from Rb1 throughout ... -
Loss of Resting-State Posterior Cingulate Flexibility Is Associated with Memory Disturbance in Left Temporal Lobe Epilepsy
(Public Library of Science, 2015)The association between cognition and resting-state fMRI (rs-fMRI) has been the focus of many recent studies, most of which use stationary connectivity. The dynamics or flexibility of connectivity, however, may be seminal ... -
Loss of RNA expression and allele-specific expression associated with congenital heart disease
(Nature Publishing Group, 2016)Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, ... -
The loss of taste genes in cetaceans
(BioMed Central, 2014)Background: Five basic taste modalities, sour, sweet, bitter, salt and umami, can be distinguished by humans and are fundamental for physical and ecological adaptations in mammals. Molecular genetic studies of the receptor ... -
Loss of the Birt–Hogg–Dube Tumor Suppressor Results in Apoptotic Resistance due to Aberrant TGFb-Mediated Transcription
(Nature Publishing Group, 2011)Birt–Hogg–Dubé (BHD) syndrome is an inherited cancer susceptibility disease characterized by skin and kidney tumors, as well as cystic lung disease, which results from loss-of-function mutations in the BHD gene. BHD is ... -
Loss of the epigenetic mark, 5-Hydroxymethylcytosine, correlates with small cell/nevoid subpopulations and assists in microstaging of human melanoma
(Impact Journals LLC, 2015)Melanomas in the vertical growth phase (VGP) not infrequently demonstrate cellular heterogeneity. One commonly encountered subpopulation displays small cell/nevoid morphology. Although its significance remains unknown, ... -
Loss of the Epigenetic Tumor Suppressor SNF5 Leads to Cancer without Genomic Instability
(American Society for Microbiology, 2008)There is a growing appreciation of the role that epigenetic alterations can play in oncogenesis. However, given the large number of genetic anomalies present in most cancers, it has been difficult to evaluate the extent ... -
Loss of the Lupus Autoantigen Ro52/Trim21 Induces Tissue Inflammation and Systemic Autoimmunity by Disregulating the IL-23–Th17 Pathway
(The Rockefeller University Press, 2009)Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 ...