361 results match your criteria CellBio


Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion.

Hum Genomics 2019 Apr 16;13(1):19. Epub 2019 Apr 16.

Center for Human Disease Modeling, Duke University Medical Center, Carmichael Building, 300 North Duke Street, Suite 48-118, Durham, NC, 27701, USA.

Background: Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases.

Results: We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Read More

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http://dx.doi.org/10.1186/s40246-019-0203-9DOI Listing
April 2019
1 Read

Flax tubulin and CesA superfamilies represent attractive and challenging targets for a variety of genome- and base-editing applications.

Funct Integr Genomics 2019 Mar 2. Epub 2019 Mar 2.

Istituto di Biologia e Biotecnologia Agraria IBBA-CNR, Via Alfonso Corti 12, 20133, Milan, Italy.

Flax is both a valuable resource and an interesting model crop. Despite a long history of flax genetic transformation only one transgenic linseed cultivar has been so far registered in Canada. Implementation and use of the genome-editing technologies that allow site-directed modification of endogenous genes without the introduction of foreign genes might improve this situation. Read More

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http://dx.doi.org/10.1007/s10142-019-00667-2DOI Listing

Molecular Pathogenesis in Huntington's Disease.

Biochemistry (Mosc) 2018 Sep;83(9):1030-1039

Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064, Russia.

Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. Read More

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http://dx.doi.org/10.1134/S0006297918090043DOI Listing
September 2018
21 Reads

Tissue self-organization underlies morphogenesis of the notochord.

Philos Trans R Soc Lond B Biol Sci 2018 Sep 24;373(1759). Epub 2018 Sep 24.

Department of Cell Biology, Duke University, Durham, NC 27710, USA

The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. Read More

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http://dx.doi.org/10.1098/rstb.2017.0320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158209PMC
September 2018
29 Reads

Transcriptome analysis supports viral infection and fluoride toxicity as contributors to chronic kidney disease of unknown etiology (CKDu) in Sri Lanka.

Int Urol Nephrol 2018 Sep 28;50(9):1667-1677. Epub 2018 May 28.

Molecular Microbiology and Human Diseases, National Institute of Fundamental Studies, Kandy, 20000, Sri Lanka.

Purpose: Chronic kidney disease of unknown etiology (CKDu), having epidemic characteristics, is being diagnosed increasingly in certain tropical regions of the world, mainly Latin America and Sri Lanka. They have been observed primarily in farming communities and current hypotheses point toward many environmental and occupational triggers. CKDu does not have common etiologies of chronic kidney disease (CKD) such as hypertension, diabetes, or autoimmune disease. Read More

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http://dx.doi.org/10.1007/s11255-018-1892-zDOI Listing
September 2018
5 Reads

The cell division protein MinD from dominates the assembly of the MinC-MinD copolymers.

J Biol Chem 2018 05 2;293(20):7786-7795. Epub 2018 Apr 2.

From the Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an, Shaanxi, China 710069 and

Cell division of rod-shaped bacteria requires the Z ring, a ring of FtsZ filaments associated with the inner-membrane wall. The MinCDE proteins help localize the Z ring to the center of the cell. MinC, which inhibits Z-ring assembly, is a passenger on MinD. Read More

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http://dx.doi.org/10.1074/jbc.RA117.001513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5961031PMC
May 2018
1 Read

Spine Patterning Is Guided by Segmentation of the Notochord Sheath.

Cell Rep 2018 02;22(8):2026-2038

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA. Electronic address:

The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord, the sheath, segments into alternating domains corresponding to the prospective centra and IVD areas. This process occurs sequentially in an anteroposterior direction via the activation of Notch signaling in alternating segments of the sheath, which transition from cartilaginous to mineralizing domains. Read More

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http://dx.doi.org/10.1016/j.celrep.2018.01.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860813PMC
February 2018
2 Reads

Myosin II sequences for Lethocerus indicus.

J Muscle Res Cell Motil 2017 04 13;38(2):193-200. Epub 2017 Jul 13.

Department of Cell Biology, Duke University, Box 3011, Durham, NC, 27705, USA.

We present the genomic and expressed myosin II sequences from the giant waterbug, Lethocerus indicus. The intron rich gene appears relatively ancient and contains six regions of mutually exclusive exons that are alternatively spliced. Alternatively spliced regions may be involved in the asymmetric myosin dimer structure known as the interacting heads motif, as well as stabilizing the interacting heads motif within the thick filament. Read More

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http://dx.doi.org/10.1007/s10974-017-9476-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5660136PMC
April 2017
11 Reads

Sheath Cell Invasion and Trans-differentiation Repair Mechanical Damage Caused by Loss of Caveolae in the Zebrafish Notochord.

Curr Biol 2017 Jul 22;27(13):1982-1989.e3. Epub 2017 Jun 22.

Department of Cell Biology, Duke University, Durham, NC 27710, USA. Electronic address:

The notochord, a conserved axial structure required for embryonic axis elongation and spine development, consists of giant vacuolated cells surrounded by an epithelial sheath [1-3]. During morphogenesis, vacuolated cells maintain their structural integrity despite being under constant mechanical stress [4]. We hypothesized that the high density of caveolae present in vacuolated cells [5, 6] could buffer mechanical tension. Read More

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http://dx.doi.org/10.1016/j.cub.2017.05.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526084PMC
July 2017
17 Reads

FtsZ Constriction Force - Curved Protofilaments Bending Membranes.

Subcell Biochem 2017;84:139-160

Department of Cell Biology, Duke University, Durham, NC, 27710, USA.

FtsZ assembles in vitro into protofilaments (pfs) that are one subunit thick and ~50 subunits long. In vivo these pfs assemble further into the Z ring, which, along with accessory division proteins, constricts to divide the cell. We have reconstituted Z rings in liposomes in vitro, using pure FtsZ that was modified with a membrane targeting sequence to directly bind the membrane. Read More

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http://dx.doi.org/10.1007/978-3-319-53047-5_5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733788PMC
January 2017
22 Reads

Mutations in TMEM260 Cause a Pediatric Neurodevelopmental, Cardiac, and Renal Syndrome.

Am J Hum Genet 2017 Apr 16;100(4):666-675. Epub 2017 Mar 16.

Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27701, USA.

Despite the accelerated discovery of genes associated with syndromic traits, the majority of families affected by such conditions remain undiagnosed. Here, we employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system (CNS), cardiac, renal, and digit abnormalities. We identified homozygous truncating mutations in TMEM260, a locus predicted to encode numerous splice isoforms. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00029297173007
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http://dx.doi.org/10.1016/j.ajhg.2017.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384036PMC
April 2017
24 Reads

The Chloroplast Tubulin Homologs FtsZA and FtsZB from the Red Alga Co-assemble into Dynamic Filaments.

J Biol Chem 2017 03 7;292(13):5207-5215. Epub 2017 Feb 7.

the Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina 27710-3709, and

FtsZ is a homolog of eukaryotic tubulin and is present in almost all bacteria and many archaea, where it is the major cytoskeletal protein in the Z ring, required for cell division. Unlike some other cell organelles of prokaryotic origin, chloroplasts have retained FtsZ as an essential component of the division machinery. However, chloroplast FtsZs have been challenging to study because they are difficult to express and purify. Read More

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http://dx.doi.org/10.1074/jbc.M116.767715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392668PMC
March 2017
5 Reads

The discovery of the prokaryotic cytoskeleton: 25th anniversary.

Mol Biol Cell 2017 Feb;28(3):357-358

Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710-3709

The year 2017 marks the 25th anniversary of the discovery of homologues of tubulin and actin in prokaryotes. Before 1992, it was largely accepted that tubulin and actin were unique to eukaryotes. Then three laboratories independently discovered that FtsZ, a protein already known as a key player in bacterial cytokinesis, had the "tubulin signature sequence" present in all α-, β-, and γ-tubulins. Read More

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http://dx.doi.org/10.1091/mbc.E16-03-0183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341718PMC
February 2017
4 Reads

Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains?

Curr Opin Struct Biol 2017 02 27;42:98-105. Epub 2016 Dec 27.

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. Read More

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http://dx.doi.org/10.1016/j.sbi.2016.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374013PMC
February 2017
4 Reads

Spontaneous Unfolding-Refolding of Fibronectin Type III Domains Assayed by Thiol Exchange: THERMODYNAMIC STABILITY CORRELATES WITH RATES OF UNFOLDING RATHER THAN FOLDING.

J Biol Chem 2017 01 30;292(3):955-966. Epub 2016 Nov 30.

From the Departments of Biochemistry and

Globular proteins are not permanently folded but spontaneously unfold and refold on time scales that can span orders of magnitude for different proteins. A longstanding debate in the protein-folding field is whether unfolding rates or folding rates correlate to the stability of a protein. In the present study, we have determined the unfolding and folding kinetics of 10 FNIII domains. Read More

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http://dx.doi.org/10.1074/jbc.M116.760371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247667PMC
January 2017
13 Reads
2 Citations
4.570 Impact Factor

Probing for Binding Regions of the FtsZ Protein Surface through Site-Directed Insertions: Discovery of Fully Functional FtsZ-Fluorescent Proteins.

J Bacteriol 2017 01 13;199(1). Epub 2016 Dec 13.

Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, USA

FtsZ, a bacterial tubulin homologue, is a cytoskeletal protein that assembles into protofilaments that are one subunit thick. These protofilaments assemble further to form a "Z ring" at the center of prokaryotic cells. The Z ring generates a constriction force on the inner membrane and also serves as a scaffold to recruit cell wall remodeling proteins for complete cell division in vivo One model of the Z ring proposes that protofilaments associate via lateral bonds to form ribbons; however, lateral bonds are still only hypothetical. Read More

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http://dx.doi.org/10.1128/JB.00553-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165096PMC
January 2017
6 Reads

Real time PCR for the rapid identification and drug susceptibility of Mycobacteria present in Bronchial washings.

BMC Infect Dis 2016 Oct 26;16(1):607. Epub 2016 Oct 26.

Department of Molecular Biology and Biotechnology, University of Peradeniya, Peradeniya, Sri Lanka.

Background: Mycobacteria have a spectrum of virulence and different susceptibilities to antibiotics. Distinguishing mycobacterial species is vital as patients with non-tuberculous mycobacterial (NTM) infections present clinical features that are similar to those of patients with tuberculosis. Thus, rapid differentiation of Mycobacterium tuberculosis complex from NTM is critical to administer appropriate treatment. Read More

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http://dx.doi.org/10.1186/s12879-016-1943-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080729PMC
October 2016
38 Reads

Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome.

Am J Hum Genet 2016 08;99(2):318-36

Center for Human Disease Modeling, Duke University School of Medicine, Durham, NC 27701, USA. Electronic address:

Bardet-Biedl syndrome (BBS) is a defining ciliopathy, notable for extensive allelic and genetic heterogeneity, almost all of which has been identified through sequencing. Recent data have suggested that copy-number variants (CNVs) also contribute to BBS. We used a custom oligonucleotide array comparative genomic hybridization (aCGH) covering 20 genes that encode intraflagellar transport (IFT) components and 74 ciliopathy loci to screen 92 unrelated individuals with BBS, irrespective of their known mutational burden. Read More

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http://dx.doi.org/10.1016/j.ajhg.2015.04.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974085PMC
August 2016
15 Reads

Mitochondrial Copy Number as a Biomarker for Autism?

Pediatrics 2016 04 31;137(4). Epub 2016 Mar 31.

Center for Human Disease Modeling, Duke University School of Medicine, Durham, North Carolina

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http://dx.doi.org/10.1542/peds.2016-0049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811322PMC
April 2016
11 Reads

Human Macrophages Utilize the Podosome Formin FMNL1 for Adhesion and Migration.

Cellbio (Irvine, Calif) 2015 Mar 4;4(1):1-11. Epub 2015 Mar 4.

Department of Cell & Developmental Biology, SUNY Upstate Medical University, New York, USA.

Macrophages play a crucial role in detecting, regulating, and resolving immune crises, requiring migration through complex extracellular matrices. Unwarranted macrophage inflammatory activity potentiates kidney disease, rheumatoid arthritis, and transplant rejection. Proper remodeling of the actin cytoskeleton, especially at adhesion structures, is essential to the translocation of macrophages. Read More

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http://dx.doi.org/10.4236/cellbio.2015.41001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772764PMC
March 2015
6 Reads

Human Umbilical Tissue-Derived Cells Promote Synapse Formation and Neurite Outgrowth via Thrombospondin Family Proteins.

J Neurosci 2015 Nov;35(47):15649-65

Departments of Cell Biology, Neurobiology, Duke Institute for Brain Sciences, Duke University, Durham, North Carolina 27710, and

Unlabelled: Cell therapy demonstrates great potential for the treatment of neurological disorders. Human umbilical tissue-derived cells (hUTCs) were previously shown to have protective and regenerative effects in animal models of stroke and retinal degeneration, but the underlying therapeutic mechanisms are unknown. Because synaptic dysfunction, synapse loss, degeneration of neuronal processes, and neuronal death are hallmarks of neurological diseases and retinal degenerations, we tested whether hUTCs contribute to tissue repair and regeneration by stimulating synapse formation, neurite outgrowth, and neuronal survival. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.1364-15.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659827PMC
November 2015
9 Reads

Newborn screening and the era of medical genomics.

Semin Perinatol 2015 Dec 21;39(8):617-22. Epub 2015 Oct 21.

Center for Human Disease Modeling, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701. Electronic address:

Across the span of the last 75+ years, technological and conceptual advances in genetics have found rapid implementation at the beginning of human life. From karyotype testing, to molecular cytogenetics, to gene panel testing, and now to whole exome and whole genome sequencing, each iterative expansion of our capability to acquire genetic data on the next generation has been implemented quickly in the clinical setting. In tandem, our continuously expanding ability to acquire large volumes of genetic data has generated its own challenges in terms of interpretation, clinical utility of the information, and concerns over privacy and discrimination; for the first time, we are faced with the possibility of having complete access to our genetic data from birth, if not shortly after conception. Read More

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http://dx.doi.org/10.1053/j.semperi.2015.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4644676PMC
December 2015
4 Reads

A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.

Am J Hum Genet 2015 May 30;96(5):784-96. Epub 2015 Apr 30.

Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland. Electronic address:

The 16p11.2 600 kb copy-number variants (CNVs) are associated with mirror phenotypes on BMI, head circumference, and brain volume and represent frequent genetic lesions in autism spectrum disorders (ASDs) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal 16p11. Read More

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http://dx.doi.org/10.1016/j.ajhg.2015.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570289PMC
May 2015
53 Reads

Stepping between membrane microdomains.

Biophys J 2015 Feb;108(4):783-784

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina. Electronic address:

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http://dx.doi.org/10.1016/j.bpj.2014.12.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336356PMC
February 2015
4 Reads

Chronic fluoxetine increases extra-hippocampal neurogenesis in adult mice.

Int J Neuropsychopharmacol 2014 Oct 31;18(4). Epub 2014 Oct 31.

Department of Cell Biology, Duke University Medical Center, Durham, NC (Drs Sachs and Caron); Department of Neurobiology, Duke University Medical Center, Durham, NC (Dr Caron).

Background: Chronic treatment with antidepressants has been shown to enhance neurogenesis in the adult mammalian brain. Although this effect was initially reported to be restricted to the hippocampus, recent work has suggested that fluoxetine, a selective serotonin reuptake inhibitor, also promotes neurogenesis in the cortex. However, whether antidepressants target neural progenitor cells in other brain regions has not been examined. Read More

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http://dx.doi.org/10.1093/ijnp/pyu029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360216PMC
October 2014
3 Reads
2 Citations
4.010 Impact Factor

Dissecting intraflagellar transport, one molecule at a time.

Dev Cell 2014 Nov 10;31(3):263-264. Epub 2014 Nov 10.

Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27701, USA. Electronic address:

Intraflagellar transport (IFT) is required for proper function of cilia, although many of the mechanistic details underlying this process are obscure. Two studies in this issue of Developmental Cell illuminate key functions of one IFT protein, IFT27, and offer clues into how IFT cargo is selected and transported. Read More

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http://dx.doi.org/10.1016/j.devcel.2014.10.021DOI Listing
November 2014
6 Reads

Expression of PKC iota affects neuronal differentiation of PC12 cells at least partly independent of kinase function.

Cellbio (Irvine, Calif) 2014 Mar;3(1):1-13

Department of Biology, Adelphi University, Garden City, NY, USA.

Atypical PKC (aPKC) plays a role in establishing cell polarity and has been indicated in neuronal differentiation and polarization, including neurite formation in rat pheochromocytoma PC12 cells, albeit by unclear mechanisms. Here, the role of the aPKC isoform, PKC iota (PKCι), in the early neuronal differentiation of PC12 cells was investigated. NGF-treated PC12 cells with stably expressed exogenous wild-type PKCι showed decreased expression of a neuroendocrine marker, increased expression of a neuronal marker, and increased neurite formation. Read More

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http://dx.doi.org/10.4236/cellbio.2014.31001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045628PMC
March 2014
7 Reads

Interpreting human genetic variation with in vivo zebrafish assays.

Biochim Biophys Acta 2014 Oct 2;1842(10):1960-1970. Epub 2014 Jun 2.

Center for Human Disease Modeling, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Rapid advances and cost erosion in exome and genome analysis of patients with both rare and common genetic disorders have accelerated gene discovery and illuminated fundamental biological mechanisms. The thrill of discovery has been accompanied, however, with the sobering appreciation that human genomes are burdened with a large number of rare and ultra rare variants, thereby posing a significant challenge in dissecting both the effect of such alleles on protein function and also the biological relevance of these events to patient pathology. In an effort to develop model systems that are able to generate surrogates of human pathologies, a powerful suite of tools have been developed in zebrafish, taking advantage of the relatively small (compared to invertebrate models) evolutionary distance of that genome to humans, the orthology of several organs and signaling processes, and the suitability of this organism for medium and high throughput phenotypic screening. Read More

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http://dx.doi.org/10.1016/j.bbadis.2014.05.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382103PMC
October 2014
10 Reads

Integrated approaches to understanding antipsychotic drug action at GPCRs.

Curr Opin Cell Biol 2014 Apr 14;27:56-62. Epub 2013 Dec 14.

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, United States; Department of Medicine, Neurobiology, Duke University Medical Center, Durham, NC 27710, United States. Electronic address:

The G-protein coupled receptor (GPCR) family of genes represents one of the largest druggable families of genes in the human genome. This is evident by the fact that approximately 30% of currently marketed drugs target GPCRs. However, many of these drugs are limited in their clinical potential as they are associated with debilitating side effects-a consequence of our incomplete understanding of their pharmacology and the signaling pathways regulated by GPCRs. Read More

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http://dx.doi.org/10.1016/j.ceb.2013.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702556PMC
April 2014
3 Reads

Sex differences in response to chronic mild stress and congenital serotonin deficiency.

Psychoneuroendocrinology 2014 Feb 19;40:123-9. Epub 2013 Nov 19.

Department of Cell Biology, Duke University, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Women exhibit a nearly twofold increased risk of developing depression and anxiety disorders when compared to men, a fact that has been hypothesized to result in part from increased stress susceptibility. Here, we used the tryptophan hydroxylase-2 R439H knock-in mouse (Tph2KI) and the chronic unpredictable mild stress (CMS) model to examine sex differences in response to congenital 5-HT deficiency and chronic stress. Our results demonstrate that female mice, but not 5-HT-deficient animals, exhibit significantly increased susceptibility to CMS-induced despair-like behavior in the forced swim test. Read More

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http://dx.doi.org/10.1016/j.psyneuen.2013.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918518PMC
February 2014
4 Reads
5 Citations
4.940 Impact Factor

Calcium Integrin Binding Protein Associates with Integrins αβ and αβ Independent of β Activation Motifs.

Cellbio (Irvine, Calif) 2012 Dec;1(2):30-37

Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, USA.

The Calcium Integrin Binding protein (CIB) has been identified as interacting specifically with the cytoplasmic tail of the integrin α domain to induce receptor activation and integrin αβ mediated cell adhesion to extracellular proteins. In K562 cells stably expressing mutated integrin αβ, or chimeric αβ carrying α cytoplasmic tail, we report that the interaction of CIB with β integrins is not αβ specific but binds α as well as α cytoplasmic tail domains. A double mutation of two proline residues to alanine residues in the α cytoplasmic domain, previously shown to disturb its conformation, inhibits chimeric α/αβ-CIB interaction. Read More

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http://dx.doi.org/10.4236/cellbio.2012.12004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807131PMC
December 2012
5 Reads

Congenital brain serotonin deficiency leads to reduced ethanol sensitivity and increased ethanol consumption in mice.

Neuropharmacology 2014 Feb 22;77:177-84. Epub 2013 Sep 22.

Department of Cell Biology, Duke University, Durham, NC 27710, USA; Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Serotonergic dysfunction has been hypothesized to play an important role in the pathophysiology of alcoholism. However, whether congenital serotonin (5-HT) deficiency leads to increased alcohol consumption or affects ethanol-related behaviors has not been established. Here, we use a transgenic mouse line that expresses a hypofunctional variant of the 5-HT synthesis enzyme, tryptophan hydroxylase 2, to examine the impact of 5-HT deficiency on responses to alcohol. Read More

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http://dx.doi.org/10.1016/j.neuropharm.2013.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874885PMC
February 2014
7 Reads
2 Citations
5.110 Impact Factor

Triphenylmethane dye activation of beta-arrestin.

Biochemistry 2013 Aug 1;52(32):5403-14. Epub 2013 Aug 1.

Departments of Cell Biology, Duke University, Durham, NC 27710, USA.

β-Arrestins regulate G protein-coupled receptor signaling as competitive inhibitors and protein adaptors. Low molecular weight biased ligands that bind receptors and discriminate between the G protein dependent arm and β-arrestin, clathrin-associated arm of receptor signaling are considered therapeutically valuable as a result of this distinctive pharmacological behavior. Other than receptor agonists, compounds that activate β-arrestins are not available. Read More

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http://dx.doi.org/10.1021/bi400217rDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744129PMC
August 2013
19 Reads

Liposome division by a simple bacterial division machinery.

Proc Natl Acad Sci U S A 2013 Jul 17;110(27):11000-4. Epub 2013 Jun 17.

Department of Cell Biology, Duke University Medical Center, Durham, NC 27710-3709, USA.

We previously reconstituted Z rings in tubular multilamellar liposomes with FtsZ-YFP-mts, where mts is a membrane-targeting amphiphilic helix. These reconstituted Z rings generated a constriction force but did not divide the thick-walled liposomes. Here we developed a unique system to observe Z rings in unilamellar liposomes. Read More

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http://dx.doi.org/10.1073/pnas.1222254110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703997PMC
July 2013
11 Reads

The troponin I: inhibitory peptide uncouples force generation and the cooperativity of contractile activation in mammalian skeletal muscle.

J Muscle Res Cell Motil 2013 May 23;34(2):83-92. Epub 2013 Jan 23.

Division of Physiology, Department of Cell Biology, Duke University Medical School, Box 3011, Durham, NC, 27710, USA.

Hodges and his colleagues identified a 12 amino acid fragment of troponin I (TnI-ip) that inhibits Ca(2+)-activated force and reduces the effectiveness Ca(2+) as an activator. To understand the role of troponin C (TnC) in the extended cooperative interactions of thin filament activation, we compared the effect of TnI-ip with that of partial troponin TnC extraction. Both methods reduce maximal Ca(2+)-activated force and increase [Ca(2+)] required for activation. Read More

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http://dx.doi.org/10.1007/s10974-013-9336-yDOI Listing
May 2013
2 Reads

Elimination of GRK2 from cholinergic neurons reduces behavioral sensitivity to muscarinic receptor activation.

J Neurosci 2012 Aug;32(33):11461-6

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Although G-protein-coupled receptor kinase 2 (GRK2) is the most widely studied member of a family of kinases that has been shown to exert powerful influences on a variety of G-protein-coupled receptors, its role in the brain remains largely unknown. Here we report the localization of GRK2 in the mouse brain and generate novel conditional knock-out (KO) mice to assess the physiological importance of this kinase in cholinergic neurons. Mice with the selective deletion of GRK2 in this cell population (ChAT(IRES-cre)Grk2(f/f) KO mice) exhibit reduced behavioral responsiveness to challenge with oxotremorine-M (Oxo-M), a nonselective muscarinic acetylcholine receptor agonist. Read More

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http://dx.doi.org/10.1523/JNEUROSCI.2234-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428034PMC
August 2012
6 Reads

Bacterial actin homolog ParM: arguments for an apolar, antiparallel double helix.

J Mol Biol 2012 Sep 28;422(4):461-3. Epub 2012 May 28.

Departments of Cell Biology, Biochemistry, and Biomedical Engineering, Duke University, Durham, NC 27710-3709, USA.

The bacterial actin homolog ParM has always been modeled as a polar filament, comprising two parallel helical strands, like actin itself. I present arguments here that ParM may be an apolar filament, in which the two helical strands are antiparallel. Read More

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http://dx.doi.org/10.1016/j.jmb.2012.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428494PMC
September 2012
5 Reads

Diverse ubiquitin signaling in NF-κB activation.

Authors:
Kazuhiro Iwai

Trends Cell Biol 2012 Jul 28;22(7):355-64. Epub 2012 Apr 28.

Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.

Nuclear factor-kappa B (NF-κB) is a transcription factor involved in a wide variety of phenomena including inflammation, immune responses, and cell survival. Abnormal activation of NF-κB occurs in many pathological conditions, such as allergic and auto-inflammatory diseases and malignancies. As a result, the signal-induced NF-κB activation pathway has been extensively studied and revealed to be regulated by ubiquitination. Read More

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http://dx.doi.org/10.1016/j.tcb.2012.04.001DOI Listing
July 2012
9 Reads

Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs.

PLoS One 2012 23;7(2):e32436. Epub 2012 Feb 23.

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, United States of America.

Surfactant protein-A (SP-A) has well-established functions in reducing bacterial and viral infections but its role in chronic lung diseases such as asthma is unclear. Mycoplasma pneumoniae (Mp) frequently colonizes the airways of chronic asthmatics and is thought to contribute to exacerbations of asthma. Our lab has previously reported that during Mp infection of non-allergic airways, SP-A aides in maintaining airway homeostasis by inhibiting an overzealous TNF-alpha mediated response and, in allergic mice, SP-A regulates eosinophilic infiltration and inflammation of the airway. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0032436PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285686PMC
August 2012
4 Reads

Synthesis and analysis of linear ubiquitin chains.

Authors:
Kazuhiro Iwai

Methods Mol Biol 2012 ;832:229-38

Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan.

Previously, polyubiquitin chains have been believed to be generated through isopeptide linkages between C-terminal of carboxyl group of ubiquitin and ε-amino group of one of the seven lysine residues in another ubiquitin. In 2006, a new type of polyubiquitin chain was identified in which the C-terminal carboxyl group of one ubiquitin is conjugated to α-amino group of the N-terminal methionine of another ubiquitin. The new type of polyubiquitin was named as the linear polyubiquitin chain. Read More

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http://dx.doi.org/10.1007/978-1-61779-474-2_16DOI Listing
July 2012
1 Read

Effect of intraperitoneal administration of bacterial lipopolysaccharide on synthesis of pro-opiomelanocortin mRNA in rat tanycytes.

Bull Exp Biol Med 2011 Feb;150(4):443-5

Department of Immunology and Cell Biology, Udmurt State University, Izhevsk, Russia.

Intensity of pro-opiomelanocortin mRNA synthesis in tanycytes of adrenalectomied and sham-operated rats was studied by in situ hybridization 4 h after intraperitoneal injection of bacterial LPS. The results were compared with pro-opiomelanocortin mRNA expression in rats subjected to immobilization stress. Immobilization and LPS injection to adrenalectomied and sham-operated animals sharply reduced pro-opiomelanocortin mRNA expression in tanycytes. Read More

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February 2011
3 Reads

Modeling of bias for the analysis of receptor signaling in biochemical systems.

Biochemistry 2012 Feb 2;51(6):1114-25. Epub 2012 Feb 2.

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, United States.

Ligand bias is a recently introduced concept in the receptor signaling field that underlies innovative strategies for targeted drug design. Ligands, as a consequence of conformational selectivity, produce signaling bias in which some downstream biochemical pathways are favored over others, and this contributes to variability in physiological responsiveness. Though the concept of bias and its implications for receptor signaling have become more important, its working definition in biochemical signaling is sufficiently imprecise as to impede the use of bias as an analytical tool. Read More

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http://dx.doi.org/10.1021/bi201308sDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278972PMC
February 2012
4 Reads

Opposite function of dopamine D1 and N-methyl-D-aspartate receptors in striatal cannabinoid-mediated signaling.

Eur J Neurosci 2011 Nov;34(9):1378-89

Department of Cell Biology, Duke University Medical Center, Durham, NC, USA.

It is well established that the cannabinoid and dopamine systems interact at various levels to regulate basal ganglia function. Although it is well known that acute administration of cannabinoids to mice can modify dopamine-dependent behaviors, the intraneuronal signaling pathways employed by these agents in the striatum are not well understood. Here we used knockout mouse models to examine the regulation of striatal extracellular-signal-regulated kinases 1 and 2 (ERK1/2) signaling by behaviorally relevant doses of cannabinoids. Read More

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http://dx.doi.org/10.1111/j.1460-9568.2011.07874.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225005PMC
November 2011
5 Reads

Fibronectin aggregation and assembly: the unfolding of the second fibronectin type III domain.

J Biol Chem 2011 Nov 23;286(45):39188-99. Epub 2011 Sep 23.

Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

The mechanism of fibronectin (FN) assembly and the self-association sites are still unclear and contradictory, although the N-terminal 70-kDa region ((I)1-9) is commonly accepted as one of the assembly sites. We previously found that (I)1-9 binds to superfibronectin, which is an artificial FN aggregate induced by anastellin. In the present study, we found that (I)1-9 bound to the aggregate formed by anastellin and a small FN fragment, (III)1-2. Read More

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http://dx.doi.org/10.1074/jbc.M111.262337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234744PMC
November 2011
3 Reads

Linear polyubiquitin chains: a new modifier involved in NFκB activation and chronic inflammation, including dermatitis.

Authors:
Kazuhiro Iwai

Cell Cycle 2011 Sep 15;10(18):3095-104. Epub 2011 Sep 15.

Department of Biophysics and Biochemistry, Graduate School of Medicine, Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

The ubiquitin conjugation system regulates a wide variety of biological phenomena, including protein degradation and signal transduction, by regulating protein function via polyubiquitin conjugation in most cases. Several types of polyubiquitin chains exist in cells, and the type of polyubiquitin chain conjugated to a protein seems to determine how that protein is regulated. We identified a novel linear polyubiquitin chain and the ubiquitin-protein ligase complex that assembles it, designated LUBAC. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218620PMC
http://dx.doi.org/10.4161/cc.10.18.17437DOI Listing
September 2011
3 Reads

Electron microscopy and x-ray diffraction evidence for two Z-band structural states.

Biophys J 2011 Aug;101(3):709-17

Department of Cell Biology, Duke University, Durham, North Carolina, USA.

In vertebrate muscles, Z-bands connect adjacent sarcomeres, incorporate several cell signaling proteins, and may act as strain sensors. Previous electron microscopy (EM) showed Z-bands reversibly switch between a relaxed, "small-square" structure, and an active, "basketweave" structure, but the mechanism of this transition is unknown. Here, we found the ratio of small-square to basketweave in relaxed rabbit psoas muscle varied with temperature, osmotic pressure, or ionic strength, independent of activation. Read More

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http://dx.doi.org/10.1016/j.bpj.2011.06.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3145273PMC
August 2011
1 Read

Regulation of asymmetric cell division in the epidermis.

Cell Div 2011 Jun 6;6(1):12. Epub 2011 Jun 6.

Department of Cell Biology, Duke University Medical Center, Durham, USA.

For proper tissue morphogenesis, cell divisions and cell fate decisions must be tightly and coordinately regulated. One elegant way to accomplish this is to couple them with asymmetric cell divisions. Progenitor cells in the developing epidermis undergo both symmetric and asymmetric cell divisions to balance surface area growth with the generation of differentiated cell layers. Read More

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http://dx.doi.org/10.1186/1747-1028-6-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123617PMC
June 2011
4 Reads

Inside-out Z rings--constriction with and without GTP hydrolysis.

Mol Microbiol 2011 Jul 16;81(2):571-9. Epub 2011 Jun 16.

Department of Cell Biology, 3079, Duke University Medical Center, Durham, NC 27710-3709, USA.

The bacterial tubulin homologue FtsZ forms a ring-like structure called the Z ring that drives cytokinesis. We showed previously that FtsZ-YFP-mts, which has a short amphipathic helix (mts) on its C terminus that inserts into the membrane, can assemble contractile Z rings in tubular liposomes without any other protein. Here we study mts-FtsZ-YFP, where the membrane tether is switched to the opposite side of the protofilament. Read More

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http://dx.doi.org/10.1111/j.1365-2958.2011.07716.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3229917PMC
July 2011
6 Reads

A screen for conditional growth suppressor genes identifies the Drosophila homolog of HD-PTP as a regulator of the oncoprotein Yorkie.

Dev Cell 2011 May;20(5):700-12

Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Mammalian cancers depend on "multiple hits," some of which promote growth and some of which block apoptosis. We screened for mutations that require a synergistic block in apoptosis to promote tissue overgrowth and identified myopic (mop), the Drosophila homolog of the candidate tumor-suppressor and endosomal regulator His-domain protein tyrosine phosphatase (HD-PTP). We find that Myopic regulates the Salvador/Warts/Hippo (SWH) tumor suppressor pathway: Myopic PPxY motifs bind conserved residues in the WW domains of the transcriptional coactivator Yorkie, and Myopic colocalizes with Yorkie at endosomes. Read More

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http://dx.doi.org/10.1016/j.devcel.2011.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386645PMC
May 2011
5 Reads

X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle.

Proc Natl Acad Sci U S A 2011 Jan 9;108(1):120-5. Epub 2010 Dec 9.

Department of Cell Biology, Box 3011, Duke University, Durham, NC 27710, USA.

Stretch activation is important in the mechanical properties of vertebrate cardiac muscle and essential to the flight muscles of most insects. Despite decades of investigation, the underlying molecular mechanism of stretch activation is unknown. We investigated the role of recently observed connections between myosin and troponin, called "troponin bridges," by analyzing real-time X-ray diffraction "movies" from sinusoidally stretch-activated Lethocerus muscles. Read More

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http://dx.doi.org/10.1073/pnas.1014599107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3017141PMC
January 2011
5 Reads