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Benjamin R Thiede et al.
Nature communications, 5, 3840-3840 (2014-05-23)
Precise frequency discrimination is a hallmark of auditory function in birds and mammals and is required for distinguishing similar sounding words, like 'bat,' 'cat' and 'hat.' In the cochlea, tuning and spectral separation result from longitudinal differences in basilar membrane
Yi Gong et al.
Molecular therapy : the journal of the American Society of Gene Therapy, 23(5), 824-834 (2015-01-17)
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1) responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. We used
James Hamilton et al.
Human molecular genetics, 24(17), 4862-4878 (2015-06-05)
Alterations in oxidative metabolism are considered to be one of the major contributors to Huntington's disease (HD) pathogenesis. However, existing data about oxidative metabolism in HD are contradictory. Here, we investigated the effect of mutant huntingtin (mHtt) on oxidative metabolism
Jérémy Rouillon et al.
Human molecular genetics, 24(17), 4916-4932 (2015-06-11)
Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the
Hiroko Mataki et al.
International journal of oncology, 46(3), 1039-1050 (2014-12-20)
Expression of the oncogene hepatocyte growth factor receptor (MET) and phosphorylation of the MET protein have been associated with both primary and acquired resistance to tyrosine kinase inhibitors (TKIs) used in therapy targeting the epidermal growth factor receptor (EGFR) in
Norbert Bencsik et al.
The Journal of cell biology, 210(5), 771-783 (2015-08-26)
Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro
Kristine H Kurtz et al.
Microcirculation (New York, N.Y. : 1994), 21(7), 593-605 (2014-04-08)
This study investigated the roles of the H1 and H2 histamine receptors, NO synthase, and sGC cyclase in histamine-induced modulation of rat mesenteric collecting lymphatic pumping. Isolated rat mesenteric collecting lymphatics were treated with 1- to 100-μM histamine. Histamine receptors
Antonio Di Meco et al.
Neurobiology of aging, 35(11), 2458-2464 (2014-06-29)
The enzyme 5-lipoxygenase (5LO) is upregulated in Alzheimer's disease (AD), and its pharmacologic blockade with zileuton slows down the development of the AD-like phenotype in young AD mice. However, its efficacy after the AD pathology is established is unknown. To
Roberta Squecco et al.
Experimental physiology, 100(6), 652-666 (2015-03-20)
What is the central question of this study? Fibroblast-to-myofibroblast transition is a key mechanism in the reparative response to tissue damage, but myofibroblast persistence in the wound leads to fibrosis and organ failure. The role of relaxin as an antifibrotic
Lili Pan et al.
Genes & development, 29(11), 1164-1174 (2015-06-13)
The conserved shelterin complex is critical for chromosome capping and maintaining telomere length homeostasis. In fission yeast, shelterin is comprised of five proteins. Taz1, Rap1, and Poz1 function as negative regulators of telomere elongation, whereas Pot1 and Tpz1 are critical
Steven C Tsai et al.
American journal of physiology. Cell physiology, 306(12), C1108-C1118 (2014-03-15)
Our knowledge of the molecular mechanisms underlying human embryonic stem cell (hESC) self-renewal and differentiation is incomplete. The level of octamer-binding transcription factor 4 (Oct4), a critical regulator of pluripotency, is precisely controlled in mouse embryonic stem cells. However, studies
Agata M Wasik et al.
Leukemia & lymphoma, 56(5), 1425-1431 (2014-08-15)
The differential diagnosis between mantle cell lymphoma (MCL) and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL) is essential, since MCL usually has a more aggressive clinical course. By flow cytometry both MCL and B-CLL are CD19, CD20 and usually CD5
Sreekanth Rajan et al.
Scientific reports, 5, 10609-10609 (2015-05-30)
Bcl-2 family proteins are key regulators for cellular homeostasis in response to apoptotic stimuli. Bcl-xL, an antiapoptotic Bcl-2 family member, undergoes conformational transitions, which leads to two conformational states: the cytoplasmic and membrane-bound. Here we present the crystal and small-angle
Sharon R Cooper et al.
The Journal of cell biology, 211(4), 807-814 (2015-11-26)
Cell-cell recognition guides the assembly of the vertebrate brain during development. δ-Protocadherins comprise a family of neural adhesion molecules that are differentially expressed and have been implicated in a range of neurodevelopmental disorders. Here we show that the expression of
Muhammad Saddiq Zahari et al.
Scientific reports, 5, 13660-13660 (2015-09-04)
Delays between tissue collection and tissue fixation result in ischemia and ischemia-associated changes in protein phosphorylation levels, which can misguide the examination of signaling pathway status. To identify a biomarker that serves as a reliable indicator of ischemic changes that
Peter S Fenwick et al.
PloS one, 10(6), e0128757-e0128757 (2015-06-20)
CD8+ T-cells are located in the small airways of COPD patients and may contribute to pathophysiology. CD8+ cells express the chemokine receptor, CXCR3 that binds CXCL9, CXCL10 and CXCL11, which are elevated in the airways of COPD patients. These chemokines
Anya Alayev et al.
Journal of cellular biochemistry, 116(3), 450-457 (2014-10-23)
Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) is a frequent event in breast cancer and current efforts are aimed at targeting the mTORC1 signaling pathway in combination with other targeted therapies. However, patients often develop drug resistance
Bing Xu et al.
American journal of physiology. Heart and circulatory physiology, 308(9), H980-H989 (2015-03-01)
Delivery of bone marrow-derived mesenchymal stem cells (MSCs) to myocardium protects ischemic tissue through the paracrine release of beneficial angiogenic and cytoprotective factors. Platelet-derived growth factor (PDGF)-BB, a potent mitogen of MSCs, is involved in the pathophysiology of ischemic heart
Yonglian Sun et al.
Science signaling, 8(405), ra122-ra122 (2015-12-03)
Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant
Bryan C Bergman et al.
American journal of physiology. Endocrinology and metabolism, 309(4), E398-E408 (2015-07-02)
Ceramides and sphingolipids are a family of lipid molecules that circulate in serum and accumulate in skeletal muscle, promoting insulin resistance. Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species.
Smrithi Rajendiran et al.
Molecular cancer, 13, 250-250 (2014-11-20)
MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have
Abhisek Ghosal et al.
American journal of physiology. Gastrointestinal and liver physiology, 307(3), G365-G373 (2014-06-07)
Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is
Anne Y Saiki et al.
Oncotarget, 6(10), 7701-7712 (2015-03-03)
Previous reports have provided evidence that p53 mutation is a strong negative predictor of response to MDM2 inhibitors. However, this correlation is not absolute, as many p53Mutant cell lines have been reported to respond to MDM2 inhibition, while many p53WT
Yi-Ping Li et al.
Journal of virology, 89(1), 811-823 (2014-10-31)
The first discovered and sequenced hepatitis C virus (HCV) genome and the first in vivo infectious HCV clones originated from the HCV prototype strains HCV-1 and H77, respectively, both widely used in research of this important human pathogen. In the
Sarmistha Bandyopadhyay et al.
PloS one, 9(10), e109525-e109525 (2014-10-09)
Francisella tularensis is a Gram-negative, facultative intracellular pathogen that replicates in the cytosol of macrophages and is the causative agent of the potentially fatal disease tularemia. A characteristic feature of F. tularensis is its limited proinflammatory capacity, but the mechanisms
Qianru Zhang et al.
Investigative ophthalmology & visual science, 55(12), 8153-8162 (2014-10-25)
Vitreous liquefaction and subsequent posterior vitreous detachment can lead to several sight-threatening diseases, including retinal detachment, macular hole and macular traction syndrome, nuclear cataracts, and possibly, open-angle glaucoma. In this study, we tested the ability of three novel synthetic chondroitin
Ousseynou Sarr et al.
PloS one, 9(6), e98433-e98433 (2014-06-14)
Uteroplacental insufficiency (UPI)-induced intrauterine growth restriction (IUGR) predisposes individuals to adult visceral obesity. We postulated that low birth weight (LBW) offspring, from UPI-induced IUGR pregnancies, would display a visceral adipose lipogenic molecular signature involving altered gene expression, phosphorylation status of
Ming-Li Chou et al.
PloS one, 9(6), e99145-e99145 (2014-06-20)
Clinical-grade ex vivo expansion of corneal endothelial cells can increase the availability of corneal tissues for transplantation and treatment of corneal blindness. However, these cells have very limited proliferative capacity. Successful propagation has required so far to use very complex
Do Hyun Lee et al.
Archives of virology, 160(9), 2197-2207 (2015-06-24)
Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine causing high mortality rates in piglets. PEDV outbreaks have occurred continuously in most swine-producing Asian countries and have recently emerged in the United States, leading to large
Aimen O Amer et al.
PloS one, 10(8), e0136173-e0136173 (2015-08-25)
Liver grafts donated after cardiac death are increasingly used to expand the donor pool but are prone to ischaemic-type biliary lesions. The anti-inflammatory effects of the activated pregnane X receptor have previously been shown to be beneficial in a number
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