Heparan sulfate facilitates Rift Valley fever virus entry into the cell.
Authorsde Boer SM, Kortekaas J, de Haan CA, Rottier PJ, Moormann RJ, Bosch BJ,
JournalJ Virol
PubMed ID23015725
Rift Valley fever virus (RVFV), an emerging arthropod-borne pathogen, has a broad host and cell tropism. Here we report that the glycosaminoglycan heparan sulfate, abundantly present on the surface of most animal cells, is required for efficient entry of RVFV. Entry was significantly reduced by preincubating the virus inoculum with ... More
'Pseudogout is an autoinflammatory condition triggered by calcium pyrophosphate dehydrate (CPPD) crystal deposition in the joints. The innate immune system is irritated by and responds to the presence of the crystals with an inflammatory response. The synovial fluid contains activated inflammatory macrophages and neutrophil granulocytes. Several details of crystal-induced macrophage ... More
Preclinical activity profile and therapeutic efficacy of the HSP90 inhibitor ganetespib in triple-negative breast cancer.
AuthorsProia DA, Zhang C, Sequeira M, Jimenez JP, He S, Spector N, Shapiro GI, Tolaney S, Nagai M, Acquaviva J, Smith DL, Sang J, Bates RC, El-Hariry I,
Journal
PubMed ID24173541
'Treatment options for patients with triple-negative breast cancer (TNBC) are largely limited to systemic chemotherapies, which have shown disappointing efficacy in the metastatic setting. Here, we undertook a comprehensive evaluation of the activity of ganetespib, a potent inhibitor of HSP90, in this malignancy. The antitumor and antimetastatic activity of ganetespib ... More
Secreted meningeal chemokines, but not VEGFA, modulate the migratory properties of medulloblastoma cells.
'Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the understanding of molecular mechanisms driving this process is nascent. In this study, we examined the secretory chemokine profile of medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned media (CM) of meningothelial cells increased adhesion, spreading ... More
Hepatitis C virus core protein inhibits interferon production by a human plasmacytoid dendritic cell line and dysregulates interferon regulatory factor-7 and signal transducer and activator of transcription (STAT) 1 protein expression.
AuthorsStone AE, Mitchell A, Brownell J, Miklin DJ, Golden-Mason L, Polyak SJ, Gale MJ, Rosen HR,
Journal
PubMed ID24788809
'Plasmacytoid Dendritic Cells (pDCs) represent a key immune cell population in the defense against viruses. pDCs detect viral pathogen associated molecular patterns (PAMPs) through pattern recognition receptors (PRR). PRR/PAMP interactions trigger signaling events that induce interferon (IFN) production to initiate local and systemic responses. pDCs produce Type I and Type ... More
Oncolytic therapy of a recombinant Newcastle disease virus D90 strain for lung cancer.
AuthorsChai Z, Zhang P, Fu F, Zhang X, Liu Y, Hu L, Li X,
Journal
PubMed ID24885546
'Lung cancer is one of the leading causes of deaths from cancer worldwide. Tumor virotherapy using naturally oncolytic Newcastle disease virus (NDV) has been shown to be safe and effective in preclinical studies and clinical trials. Previously, we have reported the NDV D90 strain that was isolated from natural source ... More
220D-F2 from Rubus ulmifolius kills Streptococcus pneumoniae planktonic cells and pneumococcal biofilms.
AuthorsTalekar SJ, Chochua S, Nelson K, Klugman KP, Quave CL, Vidal JE,
Journal
PubMed ID24823499
'Streptococcus pneumoniae (pneumococcus) forms organized biofilms to persist in the human nasopharynx. This persistence allows the pneumococcus to produce severe diseases such as pneumonia, otitis media, bacteremia and meningitis that kill nearly a million children every year. While bacteremia and meningitis are mediated by planktonic pneumococci, biofilm structures are present ... More
Chronic inflammation and angiogenic signaling axis impairs differentiation of dental-pulp stem cells.
AuthorsBoyle M, Chun C, Strojny C, Narayanan R, Bartholomew A, Sundivakkam P, Alapati S,
Journal
PubMed ID25427002
'Dental-pulp tissue is often exposed to inflammatory injury. Sequested growth factors or angiogenic signaling proteins that are released following inflammatory injury play a pivotal role in the formation of reparative dentin. While limited or moderate angiogenesis may be helpful for dental pulp maintenance, the induction of significant level of angiogenesis ... More
Disruption of endogenous perlecan function improves differentiation of rat articular chondrocytes in vitro.
AuthorsNakamura R, Nakamura F, Fukunaga S,
Journal
PubMed ID25410015
'Heparan sulfate (HS) and heparan sulfate proteoglycans (HSPG) are necessary for normal cartilage development and chondrocyte differentiation. However, recent studies demonstrated that HSPG accelerate dedifferentiation and catabolism in chondrocytes from degenerative cartilage. In this study, we investigated the inhibitory effect of HSPG on chondrocyte differentiation in vitro. Rat articular chondrocytes ... More
Cytotoxicity, DNA damage, and apoptosis induced by titanium dioxide nanoparticles in human non-small cell lung cancer A549 cells.
AuthorsWang Y, Cui H, Zhou J, Li F, Wang J, Chen M, Liu Q,
Journal
PubMed ID25339530
'Concerns about the risk of titanium dioxide nanoparticles (TiO2 NPs) to human health and environment are gradually increasing due to their wide range of applications. In this study, cytotoxicity, DNA damage, and apoptosis induced by TiO2 NPs (5 nm) in A549 cells were investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays revealed the ... More
Expression of protease-activated receptor 1 and 2 and anti-tubulogenic activity of protease-activated receptor 1 in human endothelial colony-forming cells.
AuthorsFortunato TM, Vara DS, Wheeler-Jones CP, Pula G,
Journal
PubMed ID25289673
'Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface ... More
Transcriptional activation of Fsp27 by the liver-enriched transcription factor CREBH promotes lipid droplet growth and hepatic steatosis.
AuthorsXu X, Park JG, So JS, Lee AH,
Journal
PubMed ID25125366
'Fat-specific protein 27 (Fsp27) is a lipid droplet-associated protein that promotes lipid droplet (LD) growth and triglyceride (TG) storage in white adipocytes. Fsp27 is also highly expressed in the steatotic liver and contributes to TG accumulation. In this study we discovered that the liver produces Fsp27ß, an alternative Fsp27 isoform, ... More
RAGE, receptor of advanced glycation endoproducts, negatively regulates chondrocytes differentiation.
AuthorsKosaka T, Fukui R, Matsui M, Kurosaka Y, Nishimura H, Tanabe M, Takakura Y, Iwai K, Waki T, Fujita T,
Journal
PubMed ID25275461
'RAGE, receptor for advanced glycation endoproducts (AGE), has been characterized as an activator of osteoclastgenesis. However, whether RAGE directly regulates chondrocyte proliferation and differentiation is unclear. Here, we show that RAGE has an inhibitory role in chondrocyte differentiation. RAGE expression was observed in chondrocytes from the prehypertrophic to hypertrophic regions. ... More
Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells.
AuthorsSobol A, Galluzzo P, Liang S, Rambo B, Skucha S, Weber MJ, Alani S, Bocchetta M,
Journal
PubMed ID25283437
'Hypoxic non-small cell lung cancer (NSCLC) is dependent on Notch-1 signaling for survival. Targeting Notch-1 by means of ?-secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post-mortem analysis of GSI-treated, NSCLC-burdened mice suggested enhanced phosphorylation of 4E-BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this ... More
Adenovirus-mediated FKHRL1/TM sensitizes melanoma cells to apoptosis induced by temozolomide.
AuthorsEgger ME, McNally LR, Nitz J, McMasters KM, Gomez-Gutierrez JG,
Journal
PubMed ID25238278
'Melanoma exhibits variable resistance to the alkylating agent temozolomide (TMZ). We evaluated the potential of adenovirus expressing forkhead human transcription factor like 1 triple mutant (Ad-FKHRL1/TM) to sensitize melanoma cells to TMZ. Four melanoma cell lines were treated with Ad-FKHRL1/TM and TMZ, alone or in combination. Apoptosis was assessed by ... More
A nucleolytic lupus autoantibody is toxic to BRCA2-deficient cancer cells.
AuthorsNoble PW, Young MR, Bernatsky S, Weisbart RH, Hansen JE,
Journal
PubMed ID25091037
'Cancer cells with defects in DNA repair are highly susceptible to DNA-damaging agents, but delivery of therapeutic agents into cell nuclei can be challenging. A subset of lupus autoantibodies is associated with nucleolytic activity, and some of these antibodies are capable of nuclear penetration. We hypothesized that such antibodies might ... More
FUS is phosphorylated by DNA-PK and accumulates in the cytoplasm after DNA damage.
AuthorsDeng Q, Holler CJ, Taylor G, Hudson KF, Watkins W, Gearing M, Ito D, Murray ME, Dickson DW, Seyfried NT, Kukar T,
Journal
PubMed ID24899704
'Abnormal cytoplasmic accumulation of Fused in Sarcoma (FUS) in neurons defines subtypes of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). FUS is a member of the FET protein family that includes Ewing''s sarcoma (EWS) and TATA-binding protein-associated factor 2N (TAF15). FET proteins are predominantly localized to the nucleus, ... More
BCL-xL/MCL-1 inhibition and RAR? antagonism work cooperatively in human HL60 leukemia cells.
AuthorsPerri M, Yap JL, Yu J, Cione E, Fletcher S, Kane MA,
Journal
PubMed ID25088254
'The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia-retinoic acid receptor, alpha fusion protein (PML-RARa). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates > 80% by activating ... More
Amyloid-beta (Aß(1-42))-induced paralysis in Caenorhabditis elegans is inhibited by the polyphenol quercetin through activation of protein degradation pathways.
AuthorsRegitz C, Dußling LM, Wenzel U,
Journal
PubMed ID25066301
'Dietary polyphenols are suggested to play a role in the prevention of Alzheimer''s disease, of which accumulation of aggregated beta amyloid (Aß) is a key histopathological hallmark. We used the transgenic Caenorhabditis elegans strain CL2006, which expresses human Aß(1-42) under control of a muscle-specific promoter and responds to Aß(1-42) aggregation ... More
Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK-CHOP signaling pathways.
AuthorsDo MT, Na M, Kim HG, Khanal T, Choi JH, Jin SW, Oh SH, Hwang IH, Chung YC, Kim HS, Jeong TC, Jeong HG,
Journal
PubMed ID24930757
'TRAIL induces apoptosis in a variety of tumor cells. However, development of resistance to TRAIL is a major obstacle to more effective cancer treatment. Therefore, novel pharmacological agents that enhance sensitivity to TRAIL are necessary. In the present study, we investigated the molecular mechanisms by which ilimaquinone isolated from a ... More
Sequential administration of carbon nanotubes and near-infrared radiation for the treatment of gliomas.
AuthorsSantos T, Fang X, Chen MT, Wang W, Ferreira R, Jhaveri N, Gundersen M, Zhou C, Pagnini P, Hofman FM, Chen TC,
Journal
PubMed ID25077069
'The objective was to use carbon nanotubes (CNT) coupled with near-infrared radiation (NIR) to induce hyperthermia as a novel non-ionizing radiation treatment for primary brain tumors, glioblastoma multiforme (GBM). In this study, we report the therapeutic potential of hyperthermia-induced thermal ablation using the sequential administration of carbon nanotubes (CNT) and ... More
Dual contribution of MAPK and PI3K in epidermal growth factor-induced destabilization of thyroid follicular integrity and invasion of cells into extracellular matrix.
AuthorsIngeson-Carlsson C, Nilsson M,
Journal
PubMed ID24726885
'Normal thyrocytes grown as reconstituted follicles in collagen gel were evaluated for drug effects of small molecule kinase inhibitors on growth factor-induced cell migration in a 3D context. MEK inhibition by U0126 only partially antagonized EGF/serum-induced cell migration from the basal follicular surface into the matrix. Combined treatment with U0126 ... More
Functional analysis of Fenneropenaeus chinensis anti-lipopolysaccharide factor promoter regulated by lipopolysaccharide and (1,3)-ß-D-glucan.
AuthorsTang T, Li L, Sun L, Bu J, Xie S, Liu F,
Journal
PubMed ID24704418
'Current knowledge on cis-regulatory elements of immune genes of shrimp is poor. In this study, the genomic sequence of the Fenneropenaeus chinensis anti-lipopolysaccharide factor (ALFFc) gene was obtained by using PCR and genome walking techniques, and the promoter was identified. The ALFFc gene contained three exons interrupted by two introns. ... More
Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.
AuthorsBeaumont PE, McHugh B, Gwyer Findlay E, Mackellar A, Mackenzie KJ, Gallo RL, Govan JR, Simpson AJ, Davidson DJ,
Journal
PubMed ID24887410
'Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides) and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role ... More
Facile electrochemical synthesis of antimicrobial TiO2 nanotube arrays.
AuthorsZhao Y, Xing Q, Janjanam J, He K, Long F, Low KB, Tiwari A, Zhao F, Shahbazian-Yassar R, Friedrich C, Shokuhfar T,
Journal
PubMed ID25429214
'Infection-related complications have been a critical issue for the application of titanium orthopedic implants. The use of Ag nanoparticles offers a potential approach to incorporate antimicrobial properties into the titanium implants. In this work, a novel and simple method was developed for synthesis of Ag (II) oxide deposited TiO2 nanotubes ... More
Generation of induced pluripotent stem cells without genetic defects by small molecules.
AuthorsPark HS, Hwang I, Choi KA, Jeong H, Lee JY, Hong S,
Journal
PubMed ID25477171
'The generation of induced pluripotent stem cells (iPSCs) often causes genetic and epigenetic defects, which may limit their clinical applications. Here, we show that reprogramming in the presence of small molecules preserved the genomic stability of iPSCs by inhibiting DNA double-strand breaks (DSBs) and activating Zscan4 gene. Surprisingly, the small ... More
Neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.
AuthorsStankowska DL, Minton AZ, Rutledge MD, Mueller BH, Phatak NR, He S, Ma HY, Forster MJ, Yorio T, Krishnamoorthy RR,
Journal
PubMed ID25587060
'Purpose: Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP), leading to optic nerve head (ONH) cupping, axon loss and apoptosis of retinal ganglion cells (RGCs) which could ultimately result in blindness. Brn3b is a class-4 POU domain transcription factor that plays a key role in RGC ... More
Manipulation of cellular spheroid composition and the effects on vascular tissue fusion.
AuthorsOlsen TR, Mattix B, Casco M, Herbst A, Williams C, Tarasidis A, Simionescu D, Visconti RP, Alexis F,
Journal
PubMed ID25463485
'Cellular spheroids were investigated as tissue-engineered building blocks that can be fused to form functional tissue constructs. While spheroids can be assembled using passive contacts for the fusion of complex tissues, physical forces can be used to promote active contacts to improve tissue homogeneity and accelerate tissue fusion. Understanding the ... More
Combined efficacy of cediranib and quinacrine in glioma is enhanced by hypoxia and causally linked to autophagic vacuole accumulation.
AuthorsLobo MR, Wang X, Gillespie GY, Woltjer RL, Pike MM,
Journal
PubMed ID25490024
'We have previously reported that the in vivo anti-glioma efficacy of the anti-angiogenic receptor tyrosine kinase inhibitor cediranib is substantially enhanced via combination with the late-stage autophagy inhibitor quinacrine. The current study investigates the role of hypoxia and autophagy in combined cediranib/quinacrine efficacy. EF5 immunostaining revealed a prevalence of hypoxia ... More
Genotoxic and immunotoxic effects of cellulose nanocrystals in vitro.
AuthorsCatalán J, Ilves M, Järventaus H, Hannukainen KS, Kontturi E, Vanhala E, Alenius H, Savolainen KM, Norppa H,
Journal
PubMed ID25257801
'Nanocellulosics are among the most promising innovations for a wide-variety of applications in materials science. Although nanocellulose is presently produced only on a small scale, its possible toxic effects should be investigated at this early stage. The aim of the present study was to examine the potential genotoxicity and immunotoxicity ... More
An intravaginal ring for the sustained delivery of antibodies.
AuthorsGunawardana M, Baum MM, Smith TJ, Moss JA,
Journal
PubMed ID25231193
'Human monoclonal antibodies (mAbs) based on IgG and IgA have shown promise as topical microbicide candidates to protect women from HIV infection. Application of mAbs has been limited, however, by the inability of vaginal gels and conventional intravaginal ring (IVR) designs, the predominant vaginal product formulations, to effectively deliver biomolecules ... More
Use of zinc-finger nucleases to knock out the WAS gene in K562 cells: a human cellular model for Wiskott-Aldrich syndrome.
AuthorsToscano MG, Anderson P, Muñoz P, Lucena G, Cobo M, Benabdellah K, Gregory PD, Holmes MC, Martin F,
JournalDis Model Mech
PubMed ID23324327
'Mutations in the WAS gene cause Wiskott-Aldrich syndrome (WAS), which is characterized by eczema, immunodeficiency and microthrombocytopenia. Although the role of WASP in lymphocytes and myeloid cells is well characterized, its role on megakaryocyte (MK) development is poorly understood. In order to develop a human cellular model that mimics the ... More
Loss of Igfbp7 causes precocious involution in lactating mouse mammary gland.
AuthorsChatterjee S, Bacopulos S, Yang W, Amemiya Y, Spyropoulos D, Raouf A, Seth A,
Journal
PubMed ID24505323
'Insulin like growth factors (IGFs) and their binding proteins (IGFBPs) are secreted peptides that play major roles in regulating the normal development and maturation of mammary gland. While Igfbp7 has been shown to decrease breast tumor growth, its role in regulating the normal mammary gland development has not been studied. ... More
Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds.
AuthorsSims-Mourtada J, Niamat RA, Samuel S, Eskridge C, Kmiec EB,
Journal
PubMed ID24570583
'A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture ... More
Application of a cell-based protease assay for testing inhibitors of picornavirus 3C proteases.
Authorsvan der Linden L, Ulferts R, Nabuurs SB, Kusov Y, Liu H, George S, Lacroix C, Goris N, Lefebvre D, Lanke KH, De Clercq K, Hilgenfeld R, Neyts J, van Kuppeveld FJ,
Journal
PubMed ID24393668
'Proteolytical cleavage of the picornaviral polyprotein is essential for viral replication. Therefore, viral proteases are attractive targets for anti-viral therapy. Most assays available for testing proteolytical activity of proteases are performed in vitro, using heterologously expressed proteases and peptide substrates. To deal with the disadvantages associated with in vitro assays, ... More
Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity.
AuthorsKrajewska M, You Z, Rong J, Kress C, Huang X, Yang J, Kyoda T, Leyva R, Banares S, Hu Y, Sze CH, Whalen MJ, Salmena L, Hakem R, Head BP, Reed JC, Krajewski S,
JournalPLoS One
PubMed ID21957448
'Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8(-/-)), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. Caspase 8 deletion reduced rates ... More
PARK9-associated ATP13A2 localizes to intracellular acidic vesicles and regulates cation homeostasis and neuronal integrity.
AuthorsRamonet D, Podhajska A, Stafa K, Sonnay S, Trancikova A, Tsika E, Pletnikova O, Troncoso JC, Glauser L, Moore DJ,
JournalHum Mol Genet
PubMed ID22186024
'Mutations in the ATP13A2 gene (PARK9, OMIM 610513) cause autosomal recessive, juvenile-onset Kufor-Rakeb syndrome and early-onset parkinsonism. ATP13A2 is an uncharacterized protein belonging to the P(5)-type ATPase subfamily that is predicted to regulate the membrane transport of cations. The physiological function of ATP13A2 in the mammalian brain is poorly understood. ... More
Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling system.
AuthorsBaetz NW, Goldenring JR,
JournalMol Biol Cell
PubMed ID23283983
'The Rab11-family interacting proteins (Rab11-FIPs) facilitate Rab11-dependent vesicle recycling. We hypothesized that Rab11-FIPs define discrete subdomains and carry out temporally distinct roles within the recycling system. We used live-cell deconvolution microscopy of HeLa cells expressing chimeric fluorescent Rab11-FIPs to examine Rab11-FIP localization, transferrin passage through Rab11-FIP-containing compartments, and overlap among ... More
The Ubiquitin-CXCR4 Axis Plays an Important Role in Acute Lung Infection-Enhanced Lung Tumor Metastasis.
AuthorsYan L, Cai Q, Xu Y,
Journal
PubMed ID23690484
'Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms. We combined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms ... More
Cofilin nuclear-cytoplasmic shuttling affects cofilin-actin rod formation during stress.
AuthorsMunsie LN, Desmond CR, Truant R,
JournalJ Cell Sci
PubMed ID22623727
'Cofilin protein is involved in regulating the actin cytoskeleton during typical steady state conditions, as well as during cell stress conditions where cofilin saturates F-actin, forming cofilin-actin rods. Cofilin can enter the nucleus through an active nuclear localization signal (NLS), accumulating in nuclear actin rods during stress. Here, we characterize ... More
The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus.
AuthorsHofmann H, Logue EC, Bloch N, Daddacha W, Polsky SB, Schultz ML, Kim B, Landau NR,
JournalJ Virol
PubMed ID22973040
'Sterile alpha motif domain- and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase that restricts the replication of lentiviruses in myeloid cells by hydrolyzing the cellular deoxynucleotide triphosphates to a level below that which is required for reverse transcription. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency ... More
Metastatic bladder cancer cells distinctively sense and respond to physical cues of collagen fibril-mimetic nanotopography.
AuthorsIuliano JN, Kutscha PD, Biderman N, Subbaram S, Groves TR, Tenenbaum SA, Hempel N,
Journal
PubMed ID25465204
'Tumor metastasis is characterized by enhanced invasiveness and migration of tumor cells through the extracellular matrix (ECM), resulting in extravasation into the blood and lymph and colonization at secondary sites. The ECM provides a physical scaffold consisting of components such as collagen fibrils, which have distinct dimensions at the nanoscale. ... More
Rapid neurogenesis through transcriptional activation in human stem cells.
AuthorsBusskamp V, Lewis NE, Guye P, Ng AH, Shipman SL, Byrne SM, Sanjana NE, Murn J, Li Y, Li S, Stadler M, Weiss R, Church GM,
Journal
PubMed ID25403753
'Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem ... More
Experimental approaches to investigating the vaginal biofilm microbiome.
AuthorsBaum MM, Gunawardana M, Webster P,
Journal
PubMed ID24664828
'Unraveling the complex ecology of the vaginal biofilm microbiome relies on a number of complementary techniques. Here, we describe the experimental approaches for studying vaginal microbial biofilm samples with a focus on specimen preparation for subsequent analysis. The techniques include fluorescence microscopy, fluorescence in situ hybridization, and scanning and transmission ... More
Caspase 1 Activation Is Protective against Hepatocyte Cell Death by Up-regulating Beclin 1 Protein and Mitochondrial Autophagy in the Setting of Redox Stress.
AuthorsSun Q, Gao W, Loughran P, Shapiro R, Fan J, Billiar TR, Scott MJ,
JournalJ Biol Chem
PubMed ID23589298
'Caspase 1 activation can be induced by oxidative stress, which leads to the release of the proinflammatory cytokines IL1ß and IL18 in myeloid cells and a potentially damaging inflammatory response. However, little is known about the role of caspase 1 in non-immune cells, such as hepatocytes, that express and activate ... More
Phosphate starvation in fungi induces the replacement of phosphatidylcholine with the phosphorus-free betaine lipid diacylglyceryl-n,n,n-trimethylhomoserine.
'Diacylglyceryl-N,N,N-trimethylhomoserine (DGTS) is a phosphorus-free betaine-lipid analog of phosphatidylcholine (PtdCho) synthesized by many soil bacteria, algae, and nonvascular plants. Synthesis of DGTS and other phosphorus-free lipids in bacteria occurs in response to phosphorus (P) deprivation and results in the replacement of phospholipids by nonphosphorous lipids. The genes encoding DGTS biosynthetic ... More
Targeting c-MYC by antagonizing PP2A inhibitors in breast cancer.
AuthorsJanghorban M, Farrell AS, Allen-Petersen BL, Pelz C, Daniel CJ, Oddo J, Langer EM, Christensen DJ, Sears RC,
Journal
PubMed ID24927563
'The transcription factor c-MYC is stabilized and activated by phosphorylation at serine 62 (S62) in breast cancer. Protein phosphatase 2A (PP2A) is a critical negative regulator of c-MYC through its ability to dephosphorylate S62. By inactivating c-MYC and other key signaling pathways, PP2A plays an important tumor suppressor function. Two ... More
Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis.
AuthorsDixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS, Stockwell BR,
Journal
PubMed ID24844246
'Exchange of extracellular cystine for intracellular glutamate by the antiporter system xc (-) is implicated in numerous pathologies. Pharmacological agents that inhibit system xc (-) activity with high potency have long been sought, but have remained elusive. In this study, we report that the small molecule erastin is a potent, ... More
Creation of Rift Valley fever viruses with four-segmented genomes reveals flexibility in bunyavirus genome packaging.
AuthorsWichgers Schreur PJ, Oreshkova N, Moormann RJ, Kortekaas J,
Journal
PubMed ID25008937
'Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into ... More
CD47 functions as a molecular switch for erythrocyte phagocytosis.
AuthorsBurger P, Hilarius-Stokman P, de Korte D, van den Berg TK, van Bruggen R,
JournalBlood
PubMed ID22427202
'CD47 on erythrocytes inhibits phagocytosis through interaction with the inhibitory immunoreceptor SIRPa expressed by macrophages. Thus, the CD47-SIRPa interaction constitutes a negative signal for erythrocyte phagocytosis. However, we report here that CD47 does not only function as a ' ... More
The TLR9 ligand, CpG-ODN, induces protection against cerebral ischemia/reperfusion injury via activation of PI3K/Akt signaling.
AuthorsLu C, Ha T, Wang X, Liu L, Zhang X, Kimbrough EO, Sha Z, Guan M, Schweitzer J, Kalbfleisch J, Williams D, Li C,
Journal
PubMed ID24721797
'Toll-like receptors (TLRs) have been shown to be involved in cerebral ischemia/reperfusion (I/R) injury. TLR9 is located in intracellular compartments and recognizes CpG-DNA. This study examined the effect of CpG-ODN on cerebral I/R injury. C57BL/6 mice were treated with CpG-ODN by i.p. injection 1 hour before the mice were subjected ... More
Block-Cell-Printing for live single-cell printing.
AuthorsZhang K, Chou CK, Xia X, Hung MC, Qin L,
Journal
PubMed ID24516129
A unique live-cell printing technique, termed
Induction of C-X-C Chemokine Receptor Type 7 (CXCR7) Switches Stromal Cell-derived Factor-1 (SDF-1) Signaling and Phagocytic Activity in Macrophages Linked to Atherosclerosis.
AuthorsMa W, Liu Y, Ellison N, Shen J,
JournalJ Biol Chem
PubMed ID23599431
The discovery of CXCR7 as a new receptor for SDF-1 places many previously described SDF-1 functions attributed to CXCR4 in question, though whether CXCR7 acts as a signaling or ... More
Induction of cholesterol biosynthesis by archazolid B in T24 bladder cancer cells.
AuthorsHamm R, Chen YR, Seo EJ, Zeino M, Wu CF, Müller R, Yang NS, Efferth T,
Journal
PubMed ID24976507
Resistance of cancer cells towards chemotherapeutics represents a major cause of therapy failure. The objective of our study was to evaluate cellular defense strategies in response to the novel vacuolar H(+)-ATPase inhibitor, archazolid B. The effects of archazolid B on T24 bladder carcinoma cells were investigated by combining ... More
Recruitment of galectin-3 during cell invasion and intracellular trafficking of Trypanosoma cruzi extracellular amastigotes.
AuthorsMachado FC, Cruz L, da Silva AA, Cruz MC, Mortara RA, Roque-Barreira MC, da Silva CV,
Journal
PubMed ID24225883
The invasion of host cells by the intracellular protozoan Trypanosoma cruzi requires interactions with host cell molecules, and the replication of the parasite requires escape from a parasitophorous vacuole into the host cell cytosol. Galectin-3, a member of ß-galactosidase-binding lectin family, has numerous extracellular and intracellular functions. In this study, ... More
Evaluation of in vitro properties of predicted kinases that phosphorylate serine residues within nuclear localization signal 1 of high mobility group box?1.
AuthorsTaira J, Higashimoto Y,
Journal
PubMed ID24863048
Phosphorylation of high mobility group box?1 (HMGB1) is involved in the subcellular translocation of this protein and its subsequent secretion. Two nuclear localization signals (NLSs), NLS1 and NLS2, in this protein regulate its nucleocytoplasmic relocation, and phosphorylation of both NLSs strongly promotes HMGB1 mobilization. However, the phosphorylation properties of serine ... More
Lipid binding promotes oligomerization and focal adhesion activity of vinculin.
AuthorsChinthalapudi K, Rangarajan ES, Patil DN, George EM, Brown DT, Izard T,
Journal
PubMed ID25488920
Adherens junctions (AJs) and focal adhesion (FA) complexes are necessary for cell migration and morphogenesis, and for the development, growth, and survival of all metazoans. Vinculin is an essential regulator of both AJs and FAs, where it provides links to the actin cytoskeleton. Phosphatidylinositol 4,5-bisphosphate (PIP2) affects the functions of ... More
Specific Phosphorylations Transmit Signals from Leukocyte ß2 to ß1 Integrins and Regulate Adhesion.
AuthorsUotila LM, Jahan F, Soto Hinojosa L, Melandri E, Grönholm M, Gahmberg CG,
Journal
PubMed ID25278023
The regulation of integrins expressed on leukocytes must be controlled precisely, and members of different integrin subfamilies have to act in concert to ensure the proper traffic of immune cells to sites of inflammation. The activation of ß2 family integrins through the T cell receptor or by chemokines leads to ... More
Molecular mechanisms of neutrophil dysfunction in glycogen storage disease type Ib.
AuthorsJun HS, Weinstein DA, Lee YM, Mansfield BC, Chou JY,
Journal
PubMed ID24565827
Glycogen storage disease type Ib (GSD-Ib) is an autosomal-recessive syndrome characterized by neutropenia and impaired glucose homeostasis resulting from a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT). The underlying cause of GSD-Ib neutropenia is an enhanced neutrophil apoptosis, but patients also manifest neutrophil dysfunction of unknown etiology. Previously, we showed ... More
Temozolomide induces the production of epidermal growth factor to regulate MDR1 expression in glioblastoma cells.
Glioblastoma multiforme (GBM) commonly resists the frontline chemotherapy treatment temozolomide. The multidrug resistance gene (MDR1) and its protein, P-glycoprotein (P-gp), are associated with chemoresistance. This study investigated the mechanisms underlying MDR1-mediated resistance by GBM to temozolomide. P-gp trafficking was studied by flow cytometry and Western blot analysis. MDR1 expression was ... More
A preclinical assay for chemosensitivity in multiple myeloma.
Accurate preclinical predictions of the clinical efficacy of experimental cancer drugs are highly desired but often haphazard. Such predictions might be improved by incorporating elements of the tumor microenvironment in preclinical models by providing a more physiological setting. In generating improved xenograft models, it is generally accepted that the use ... More
Hypoxic stress facilitates acute activation and chronic downregulation of fanconi anemia proteins.
AuthorsScanlon SE, Glazer PM,
Journal
PubMed ID24688021
Hypoxia induces genomic instability through replication stress and dysregulation of vital DNA repair pathways. The Fanconi anemia (FA) proteins, FANCD2 and FANCI, are key members of a DNA repair pathway that responds to replicative stress, suggesting that they undergo regulation by hypoxic conditions. Here acute hypoxic stress activates the FA ... More
The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal.
AuthorsRosas M, Davies LC, Giles PJ, Liao CT, Kharfan B, Stone TC, O'Donnell VB, Fraser DJ, Jones SA, Taylor PR,
Journal
PubMed ID24762537
Tissue-resident macrophages are heterogeneous as a consequence of anatomical niche-specific functions. Many populations self-renew independently of bone marrow in the adult, but the molecular mechanisms of this are poorly understood. We determined a transcriptional profile for the major self-renewing population of peritoneal macrophages in mice. These cells specifically expressed the ... More
Proteolytic activation of the porcine epidemic diarrhea coronavirus spike fusion protein by trypsin in cell culture.
AuthorsWicht O, Li W, Willems L, Meuleman TJ, Wubbolts RW, van Kuppeveld FJ, Rottier PJ, Bosch BJ,
Journal
PubMed ID24807723
Isolation of porcine epidemic diarrhea coronavirus (PEDV) from clinical material in cell culture requires supplementation of trypsin. This may relate to the confinement of PEDV natural infection to the protease-rich small intestine of pigs. Our study focused on the role of protease activity on infection by investigating the spike protein ... More
Stenotrophomonas maltophilia Encodes a Type II Protein Secretion System That Promotes Detrimental Effects on Lung Epithelial Cells.
AuthorsKaraba SM, White RC, Cianciotto NP,
Journal
PubMed ID23774603
The Gram-negative bacterium Stenotrophomonas maltophilia is increasingly identified as a multidrug-resistant pathogen, being associated with pneumonia, among other infections. Despite this increasing clinical problem, the genetic and molecular basis of S. maltophilia virulence is quite minimally defined. We now report that strain K279a, the first clinical isolate of S. maltophilia ... More
Loss of TGF-ß adaptor ß2SP activates notch signaling and SOX9 expression in esophageal adenocarcinoma.
AuthorsSong S, Maru DM, Ajani JA, Chan CH, Honjo S, Lin HK, Correa A, Hofstetter WL, Davila M, Stroehlein J, Mishra L,
JournalCancer Res
PubMed ID23536563
TGF-ß and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-ß signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-ß adapter ß2SP (SPNB2) activates Notch signaling ... More
Metabolomic profiling reveals a role for caspase-2 in lipoapoptosis.
The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed to play an important role in the pathogenesis of several metabolic diseases, including non-alcoholic fatty liver disease, diabetes mellitus, and cardiovascular disease. In this report, we demonstrate a novel role ... More
Sequential delivery of immunomodulatory cytokines to facilitate the M1-to-M2 transition of macrophages and enhance vascularization of bone scaffolds.
AuthorsSpiller KL, Nassiri S, Witherel CE, Anfang RR, Ng J, Nakazawa KR, Yu T, Vunjak-Novakovic G,
Journal
PubMed ID25453950
In normal tissue repair, macrophages exhibit a pro-inflammatory phenotype (M1) at early stages and a pro-healing phenotype (M2) at later stages. We have previously shown that M1 macrophages initiate angiogenesis while M2 macrophages promote vessel maturation. Therefore, we reasoned that scaffolds that promote sequential M1 and M2 polarization of infiltrating ... More
Actin cytoskeletal disruption following cryopreservation alters the biodistribution of human mesenchymal stromal cells in vivo.
Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawing defect also impacts the postinfusion biodistribution properties of MSCs. Under both static and physiologic flow, compared with live ... More
Systemic Staphylococcus aureus infection mediated by Candida albicans hyphal invasion of mucosal tissue.
Candida albicans and Staphylococcus aureus are often co-isolated in cases of biofilm-associated infections. C. albicans can cause systemic disease through morphological switch from the rounded yeast to the invasive hyphal form. Alternatively, systemic S. aureus infections arise from seeding through breaks in host epithelial layers although many patients have no ... More
Bactericidal effect of bovine lactoferrin and synthetic peptide lactoferrin chimera in Streptococcus pneumoniae and the decrease in luxS gene expression by lactoferrin.
AuthorsLeón-Sicairos N, Angulo-Zamudio UA, Vidal JE, López-Torres CA, Bolscher JG, Nazmi K, Reyes-Cortes R, Reyes-López M, de la Garza M, Canizalez-Román A,
Journal
PubMed ID25053107
Streptococcus pneumoniae (pneumococcus) is responsible for nearly one million child deaths annually. Pneumococcus causes infections such as pneumonia, otitis media, meningitis, and sepsis. The human immune system includes antibacterial peptides and proteins such as lactoferrin (LF), but its activity against pneumococcus is not fully understood. The aim of this work ... More
Evidence for SH2 domain-containing 5'-inositol phosphatase-2 (SHIP2) contributing to a lymphatic dysfunction.
The lymphatic vasculature plays a critical role in a number of disease conditions of increasing prevalence, such as autoimmune disorders, obesity, blood vascular diseases, and cancer metastases. Yet, unlike the blood vasculature, the tools available to interrogate the molecular basis of lymphatic dysfunction/disease have been lacking. More recently, investigators have ... More
Inhibition of mTOR Prevents ROS Production Initiated by Ethidium Bromide-Induced Mitochondrial DNA Depletion.
AuthorsNacarelli T, Azar A, Sell C,
Journal
PubMed ID25104948
The regulation of mitochondrial mass and DNA content involves a complex interaction between mitochondrial DNA replication machinery, functional components of the electron transport chain, selective clearance of mitochondria, and nuclear gene expression. In order to gain insight into cellular responses to mitochondrial stress, we treated human diploid fibroblasts with ethidium ... More
Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue.
AuthorsKauppila JH, Korvala J, Siirilä K, Manni M, Mäkinen LK, Hagström J, Atula T, Haglund C, Selander KS, Saarnio J, Karttunen TJ, Lehenkari PP, Salo T,
Journal
PubMed ID25338738
Toll-like receptor 9 (TLR9) is a cellular receptor, which recognizes bacterial and host-derived DNA. Stimulation of TLR9 induces cellular invasion via matrix metalloproteinase 13 (MMP-13). The aim of this study was to evaluate the role of TLR9 in invasion of oral tongue squamous cell carcinoma (OTSCC). The effects of TLR9 ... More
Benzimidazole analogs as potent hypoxia inducible factor inhibitors: synthesis, biological evaluation, and profiling drug-like properties.
AuthorsChen J, Wang J, Schwab LP, Park KT, Seagroves TN, Jennings LK, Miller DD, Li W,
Journal
PubMed ID25075010
To develop potent HIF-1a inhibitors for potential treatment of cancer. Chemical synthesis, HIF-luciferase assay, cytotoxic assay, platelet aggregation assay, western blot analysis, quantitative real-time PCR, aqueous solubility, protein binding, metabolic stability, and metabolic pathways. Thirteen novel benzimidazole analogs were synthesized. Compounds 3a and 3k showed the highest anti-HIF-1a activity. They ... More
Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds.
AuthorsMulley G, Jenkins AT, Waterfield NR,
Journal
PubMed ID24728271
There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are ... More
Cytotoxicity and genotoxicity caused by yttrium oxide nanoparticles in HEK293 cells.
AuthorsSelvaraj V, Bodapati S, Murray E, Rice KM, Winston N, Shokuhfar T, Zhao Y, Blough E,
Journal
PubMed ID24648735
The increased use of engineered nanoparticles (NPs) has caused new concerns about the potential exposure to biological systems and the potential risk that these materials may pose on human health. Here, we examined the effects of exposure to different concentrations (0-50 µg/mL) and incubation times (10 hours, 24 hours, or ... More
Thermoresponsive worms for expansion and release of human embryonic stem cells.
The development of robust suspension cultures of human embryonic stem cells (hESCs) without the use of cell membrane disrupting enzymes or inhibitors is critical for future clinical applications in regenerative medicine. We have achieved this by using long, flexible, and thermoresponsive polymer worms decorated with a recombinant vitronectin subdomain that ... More
Boosting accumulation of neutral lipids in Rhodosporidium kratochvilovae HIMPA1 grown on hemp (Cannabis sativa Linn) seed aqueous extract as feedstock for biodiesel production.
AuthorsPatel A, Pravez M, Deeba F, Pruthi V, Singh RP, Pruthi PA,
Journal
PubMed ID24746767
Hemp seeds aqueous extract (HSAE) was used as cheap renewable feedstocks to grow novel oleaginous yeast Rhodosporidium kratochvilovae HIMPA1 isolated from Himalayan permafrost soil. The yeast showed boosted triglyceride (TAG) accumulation in the lipid droplets (LDs) which were transesterified to biodiesel. The sonicated HSAE prepared lacked toxic inhibitors and showed ... More
Identification and purification of human induced pluripotent stem cell-derived atrial-like cardiomyocytes based on sarcolipin expression.
AuthorsJosowitz R, Lu J, Falce C, D'Souza SL, Wu M, Cohen N, Dubois NC, Zhao Y, Sobie EA, Fishman GI, Gelb BD,
Journal
PubMed ID25010565
The use of human stem cell-derived cardiomyocytes to study atrial biology and disease has been restricted by the lack of a reliable method for stem cell-derived atrial cell labeling and purification. The goal of this study was to generate an atrial-specific reporter construct to identify and purify human stem cell-derived ... More
The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells.
Cell adhesion and migration play important roles in physiological and pathological states, including embryonic development and cancer invasion and metastasis. The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is expressed mainly in brain and prostate and its expression is deregulated in prostate cancer. ... More
A multidisciplinary study using in vivo tumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells.
AuthorsMattei F, Schiavoni G, De Ninno A, Lucarini V, Sestili P, Sistigu A, Fragale A, Sanchez M, Spada M, Gerardino A, Belardelli F, Businaro L, Gabriele L,
Journal
PubMed ID24597645
A full elucidation of events occurring inside the cancer microenvironment is fundamental for the optimization of more effective therapies. In the present study, the cross-talk between cancer and immune cells was examined by employing mice deficient (KO) in interferon regulatory factor (IRF)-8, a transcription factor essential for induction of competent ... More
Neuregulin-3 regulates epithelial progenitor cell positioning and specifies mammary phenotype.
AuthorsKogata N, Oliemuller E, Wansbury O, Howard BA,
Journal
PubMed ID24936779
Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland development. Here, we investigate functions of Nrg3 signaling in embryonic mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis. Basal and suprabasal epithelial cells are significantly smaller within the hypoplastic ... More
Thymoquinone induces cell death in human squamous carcinoma cells via caspase activation-dependent apoptosis and LC3-II activation-dependent autophagy.
AuthorsChu SC, Hsieh YS, Yu CC, Lai YY, Chen PN,
Journal
PubMed ID25000169
Thymoquinone (TQ), an active component of Nigella sativa or black cumin, elicits cytotoxic effects on various cancer cell lines. However, the anti-cancer effects of TQ on head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, TQ elicited a strong cytotoxic effect on SASVO3, a highly malignant HNSCC ... More
Oral administration of soy peptides suppresses cognitive decline by induction of neurotrophic factors in SAMP8 mice.
SAMP8 mice have a shorter lifespan and show the dysfunction of the central nervous system. We here investigated whether soy peptides (SP) composed mainly of di- and tripeptides has the potential to prevent age-dependent cognitive impairment. SAMP8 and normal aging mice, SAMR1, were fed a diet supplemented with SP or ... More
Maintenance of ischemic ß cell viability through delivery of lipids and ATP by targeted liposomes.
AuthorsAtchison N, Swindlehurst G, Papas KK, Tsapatsis M, Kokkoli E,
Journal
PubMed ID24653833
Islet transplantation is a promising treatment for type 1 diabetes, but despite the successes, existing challenges prevent widespread application. Ischemia, occurring during pancreas preservation and isolation, as well as after islet transplantation, decreases islet viability and function. We hypothesized that the liposomal delivery of adenosine triphosphate (ATP) could prevent the ... More
Argonaute-2 promotes miR-18a entry in human brain endothelial cells.
AuthorsFerreira R, Santos T, Amar A, Gong A, Chen TC, Tahara SM, Giannotta SL, Hofman FM,
Journal
PubMed ID24837588
Cerebral arteriovenous malformation (AVM) is a vascular disease exhibiting abnormal blood vessel morphology and function. miR-18a ameliorates the abnormal characteristics of AVM-derived brain endothelial cells (AVM-BEC) without the use of transfection reagents. Hence, our aim was to identify the mechanisms by which miR-18a is internalized by AVM-BEC. Since AVM-BEC overexpress ... More
The polyphenol quercetin protects the mev-1 mutant of Caenorhabditis elegans from glucose-induced reduction of survival under heat-stress depending on SIR-2.1, DAF-12, and proteasomal activity.
AuthorsFitzenberger E, Deusing DJ, Marx C, Boll M, Lüersen K, Wenzel U,
Journal
PubMed ID24407905
Hyperglycemia is a hallmark of diabetes mellitus but slighter increases of blood glucose levels are observed also during ageing. Using the Caenorhabditis elegans mev-1 mutant, we identified molecular mechanisms underlying the protection from glucose toxicity by the polyphenol quercetin. We fed C. elegans mev-1 mutants on a liquid medium supplemented ... More
Combinatorial gene editing in mammalian cells using ssODNs and TALENs.
AuthorsStrouse B, Bialk P, Niamat RA, Rivera-Torres N, Kmiec EB,
Journal
PubMed ID24445749
The regulation of gene editing is being elucidated in mammalian cells and its potential as well as its limitations are becoming evident. ssODNs carry out gene editing by annealing to their complimentary sequence at the target site and acting as primers for replication fork extension. To effect a genetic change, ... More
Involvement of conserved tryptophan residues for secretion of TIMP-2.
AuthorsUkaji T, Sasazawa Y, Umezawa K, Simizu S,
Journal
PubMed ID24527068
Tissue inhibitor of metalloproteinases (TIMPs) are endogenous inhibitor proteins of matrix metalloproteinases and contain 12 cysteine residues that are conserved among TIMPs, and which are important for their activity and structure. In the present study, three tryptophan residues conserved among TIMPs were revealed to be important for the secretion of ... More
Janus magnetic cellular spheroids for vascular tissue engineering.
AuthorsMattix BM, Olsen TR, Casco M, Reese L, Poole JT, Zhang J, Visconti RP, Simionescu A, Simionescu DT, Alexis F,
Journal
PubMed ID24183699
Cell aggregates, or spheroids, have been used as building blocks to fabricate scaffold-free tissues that can closely mimic the native three-dimensional in vivo environment for broad applications including regenerative medicine and high throughput testing of drugs. The incorporation of magnetic nanoparticles (MNPs) into spheroids permits the manipulation of spheroids into ... More
Expression of green fluorescent protein in human foreskin fibroblasts for use in 2D and 3D culture models.
The availability of fibroblasts that express green fluorescent protein (GFP) would be of interest for the monitoring of cell growth, migration, contraction, and other processes within the fibroblast-populated collagen matrix and other culture systems. A plasmid lentiviral vector-GFP (pLV-GFP) was utilized for gene delivery to produce primary human foreskin fibroblasts ... More
Role of the EphB2 receptor in autophagy, apoptosis and invasion in human breast cancer cells.
AuthorsChukkapalli S, Amessou M, Dilly AK, Dekhil H, Zhao J, Liu Q, Bejna A, Thomas RD, Bandyopadhyay S, Bismar TA, Neill D, Azoulay L, Batist G, Kandouz M,
Journal
PubMed ID24211352
The Eph and Ephrin proteins, which constitute the largest family of receptor tyrosine kinases, are involved in normal tissue development and cancer progression. Here, we examined the expression and role of the B-type Eph receptor EphB2 in breast cancers. By immunohistochemistry using a progression tissue microarray of human clinical samples, ... More
Crystal structure of the avian astrovirus capsid spike.
AuthorsDubois RM, Freiden P, Marvin S, Reddivari M, Heath RJ, White SW, Schultz-Cherry S,
JournalJ Virol
PubMed ID23658448
Astroviruses are small, nonenveloped, single-stranded RNA viruses that cause diarrhea in a wide variety of mammals and birds. On the surface of the viral capsid are globular spikes that are thought to be involved in attachment to host cells. To understand the basis of species specificity, we investigated the structure ... More
Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.
AuthorsFazly A, Jain C, Dehner AC, Issi L, Lilly EA, Ali A, Cao H, Fidel PL, P Rao R, Kaufman PD,
Journal
PubMed ID23904484
Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans ... More
Novel recombinant hepatitis B virus vectors efficiently deliver protein and RNA encoding genes into primary hepatocytes.
AuthorsHong R, Bai W, Zhai J, Liu W, Li X, Zhang J, Cui X, Zhao X, Ye X, Deng Q, Tiollais P, Wen Y, Liu J, Xie Y,
JournalJ Virol
PubMed ID23552416
Hepatitis B virus (HBV) has extremely restricted host and hepatocyte tropism. HBV-based vectors could form the basis of novel therapies for chronic hepatitis B and other liver diseases and would also be invaluable for the study of HBV infection. Previous attempts at developing HBV-based vectors encountered low yields of recombinant ... More
Critical roles for multiple formins during cardiac myofibril development and repair.
Cardiac and skeletal muscle function depends on the proper formation of myofibrils, which are tandem arrays of highly organized actomyosin contractile units called sarcomeres. How the architecture of these colossal molecular assemblages is established during development and maintained over the lifetime of an animal is poorly understood. We investigate the ... More
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
AuthorsDrewniak A, Gazendam RP, Tool AT, van Houdt M, Jansen MH, van Hamme JL, van Leeuwen EM, Roos D, Scalais E, de Beaufort C, Janssen H, van den Berg TK, Kuijpers TW,
JournalBlood
PubMed ID23335372
Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the ... More
Kaposi's sarcoma-associated herpesvirus induces rapid release of angiopoietin-2 from endothelial cells.
Kaposi sarcoma-associated herpesvirus (KSHV) stimulates proliferation, angiogenesis, and inflammation to promote Kaposi sarcoma (KS) tumor growth, which involves various growth factors and cytokines. Previously, we found that KSHV infection of human umbilical vein endothelial cells (HUVECs) induces a transcriptional induction of the proangiogenic and proinflammatory cytokine angiopoietin-2 (Ang-2). Here, we ... More
Mammalian target of rapamycin complex 1 (mTORC1) plays a role in Pasteurella multocida toxin (PMT)-induced protein synthesis and proliferation in Swiss 3T3 cells.
AuthorsOubrahim H, Wong A, Wilson BA, Chock PB,
JournalJ Biol Chem
PubMed ID23223576
Pasteurella multocida toxin (PMT) is a potent mitogen known to activate several signaling pathways via deamidation of a conserved glutamine residue in the a subunit of heterotrimeric G-proteins. However, the detailed mechanism behind mitogenic properties of PMT is unknown. Herein, we show that PMT induces protein synthesis, cell migration, and ... More