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Johanna Myllyharju
University of Oulu, Uleoborg, Oulu, Finland
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Available from: Karl-Heinz Herzig
HIF prolyl 4-hydroxylase-2 inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction.
Lea Rahtu-Korpela
Sara Karsikas
Sohvi Hörkkö
Roberto Blanco Sequeiros
Eveliina Lammentausta
Kari A Mäkelä
Karl-Heinz Herzig
Gail Walkinshaw
Kari I Kivirikko
, Johanna Myllyharju,
Raisa Serpi
Peppi Koivunen
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Obesity is a major public health problem predisposing subjects to metabolic syndrome, type 2 diabetes and cardiovascular diseases. Specific prolyl 4-hydroxylases (P4Hs) regulate the stability of the hypoxia-inducible factor (HIF), a potent governor of metabolism, isoenzyme 2 being the main regulator. We investigated here whether HIF-P4H-2 inhibition could be used to treat obesity and its consequences. Hif-p4h-2-deficient mice, whether fed normal chow or a high-fat diet, had less adipose tissue, smaller adipocytes and less adipose tissue inflammation than their littermates. They also had improved glucose tolerance and insulin sensitivity. The mRNA levels of the HIF-1 targets glucose transporters, glycolytic enzymes and pyruvate dehydrogenase kinase-1 were increased in their tissues, while acetyl-CoA concentration was decreased. The hepatic mRNA level of the HIF-2 target insulin receptor substrate-2 was higher, while those of two key enzymes of fatty acid synthesis were lowered. Serum cholesterol levels and de novo lipid synthesis were decreased and the mice were protected against hepatic steatosis. Oral administration of a HIF-P4H inhibitor, FG-4497, to wild-type mice with a metabolic dysfunction phenocopied these beneficial effects. HIF-P4H-2 inhibition may be a novel therapy that not only protects against the development of obesity and its consequences but also reverses these conditions.
Diabetes 05/2014;
· 7.90 Impact Factor
Clinical characterization, genetic mapping and whole-genome sequence analysis of a novel autosomal recessive intellectual disability syndrome
Eevi Kaasinen
Elisa Rahikkala
Peppi Koivunen
Sirpa Miettinen
Mirjam M.C. Wamelink
Mervi Aavikko
Kimmo Palin
, Johanna Myllyharju,
Jukka S. Moilanen
Leila Pajunen
Auli Karhu
Lauri A. Aaltonen
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We identified six patients presenting with a strikingly similar clinical phenotype of profound syndromic intellectual disability of unknown etiology. All patients lived in the same village. Extensive genealogical work revealed that the healthy parents of the patients were all distantly related to a common ancestor from the 17th century, suggesting autosomal recessive inheritance. In addition to intellectual disability, the clinical features included hypotonia, strabismus, difficulty to fix the eyes to an object, planovalgus in the feet, mild contractures in elbow joints, interphalangeal joint hypermobility and coarse facial features that develop gradually during childhood. The clinical phenotype did not fit any known syndrome. Genome-wide SNP genotyping of the patients and genetic mapping revealed the longest shared homozygosity at 3p22.1-3p21.1 encompassing 11.5Mb, with no other credible candidate loci emerging. Single point parametric linkage analysis showed logarithm of the odds score of 11 for the homozygous region, thus identifying a novel intellectual disability predisposition locus. Whole-genome sequencing of one affected individual pinpointed three genes with potentially protein damaging homozygous sequence changes within the predisposition locus: transketolase (TKT), prolyl 4-hydroxylase transmembrane (P4HTM), and ubiquitin specific peptidase 4 (USP4). The changes were found in heterozygous form with 0.3-0.7% allele frequencies in 402 whole-genome sequenced controls from the north-east of Finland. No homozygotes were found in this nor additional control data sets. Our study facilitates clinical and molecular diagnosis of patients with this novel autosomal recessive intellectual disability syndrome. However, further studies are needed to unambiguously identify the underlying genetic defect.
European Journal of Medical Genetics. 01/2014;
The Structural Motifs for Substrate Binding and Dimerization of the α Subunit of Collagen Prolyl 4-Hydroxylase.
Jothi Anantharajan
M Kristian Koski
Petri Kursula
Reija Hieta
Ulrich Bergmann
, Johanna Myllyharju,
Rik K Wierenga
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Collagen prolyl 4-hydroxylase (C-P4H) catalyzes the proline hydroxylation of procollagen, an essential modification in the maturation of collagens. C-P4H consists of two catalytic α subunits and two protein disulfide isomerase β subunits. The assembly of these subunits is unknown. The α subunit contains an N domain (1-143), a peptide-substrate-binding-domain (PSB, 144-244) and a catalytic domain (245-517). Here, we report the dimeric structure of the N-terminal region (1-244) of the α subunit. It is shown that the N domain has an important role in the assembly of the C-P4H tetramer, by forming an extended four-helix bundle that includes an antiparallel coiled-coil dimerization motif between the two α subunits. Complexes of this construct with a C-P4H inhibitor and substrate show the mode of peptide-binding to the PSB domain. Both peptides adopt a poly-(L)-proline-type-II helix conformation and bind in a curved, asymmetric groove lined by conserved tyrosines and an Arg-Asp salt bridge.
Structure 10/2013;
· 5.99 Impact Factor
Available from: Andrey Anisimov
Activation of Hypoxia Response in Endothelial Cells Contributes to Ischemic Cardioprotection.
Risto Kerkelä
Sara Karsikas
Zoltan Szabo
Raisa Serpi
Johanna Magga
Erhe Gao
Kari Alitalo
Andrey Anisimov
Raija Sormunen
Ilkka Pietilä
Laura Vainio
Walter J Koch
Kari I Kivirikko
, Johanna Myllyharju,
Peppi Koivunen
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Small molecule inhibition of HIF-P4Hs is being explored for treatment of anemia. Previous studies suggest that HIF-P4H-2 inhibition may also protect heart from ischemic insult. Hif-p4h-2(gt/gt) mice, which have 76-93% knock-down of Hif-p4h-2 mRNA in endothelial cells, fibroblasts and cardiomyocytes, and normoxic stabilization of Hif-α, were subjected to ligation of left anterior descending coronary artery (LAD). Hif-p4h-2 deficiency resulted in increased survival, better preserved left ventricular (LV) systolic function and smaller infarct size. Surprisingly, a significantly larger area of LV remained perfused in Hif-p4h-2(gt/gt) hearts during LAD ligation compared to wild-type. However, no difference was observed in collateral vessels, while the size of capillaries, but not their number, was significantly increased in Hif-p4h-2(gt/gt) hearts relative to wild type. Hif-p4h-2(gt/gt) mice showed increased cardiac expression of endothelial Hif target genes Tie-2, Apelin, APJ and eNOS, and increased serum nitric oxide concentrations. Remarkably, blockage of Tie-2 signaling was sufficient to normalize cardiac apelin and APJ expression, and resulted in reversal of the enlarged capillary phenotype and ischemic cardioprotection in Hif-p4h-2(gt/gt) hearts. Activation of the hypoxia response by HIF-P4H-2 inhibition in endothelial cells appears a major determinant of ischemic cardioprotection and justifies exploration of systemic small molecular HIF-P4H-2 inhibitors for ischemic heart disease.
Molecular and cellular biology 06/2013;
· 6.06 Impact Factor
Prolyl 4-hydroxylases, master regulators of the hypoxia response.
Johanna Myllyharju
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A decrease in oxygenation is a life-threatening situation for most organisms. An evolutionarily conserved efficient and rapid hypoxia response mechanism activated by a hypoxia-inducible transcription factor (HIF) is present in animals ranging from the simplest multicellular phylum Placozoa to humans. In humans, HIF induces the expression of more than 100 genes that are required to increase oxygen delivery and to reduce oxygen consumption. As its name indicates HIF is found at protein level only in hypoxic cells, whereas in normoxia it is degraded by the proteasome pathway. Prolyl 4-hydroxylases, enzymes that require oxygen in their reaction, are the cellular oxygen sensors regulating the stability of HIF. In normoxia, 4-hydroxyproline residues formed in the α subunit of HIF by these enzymes lead to its ubiquitination by the Von Hippel Lindau E3 ubiquitin ligase and immediate destruction in proteasomes thus preventing the formation of a functional HIF αβ dimer. Prolyl 4-hydroxylation is inhibited in hypoxia, facilitating formation of the HIF dimer and activation of its target genes, such as those for erythropoietin and vascular endothelial growth factor. This review starts with a summary of the molecular and catalytic properties and individual functions of the four HIF prolyl 4-hydroxylase isoenzymes. Induction of the hypoxia response via inhibition of the HIF prolyl 4-hydroxylases may provide a novel therapeutic target in the treatment of hypoxia associated diseases. The current status of studies aiming at such therapeutic approaches is introduced in the final part of this review. Acta Physiologica © 2013 Scandinavian Physiological Society.
Acta Physiologica 03/2013;
· 4.38 Impact Factor
Hypoxia-inducible factor prolyl 4-hydroxylases, common and specific roles.
Johanna Myllyharju,
Peppi Koivunen
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Abstract Hypoxia-inducible transcription factor (HIF), an αβ dimer, is the key inducer of hypoxia responsive genes that operate both during normal development and pathological processes in association with decreased oxygen availability. The products of HIF target genes function in e.g. hematopoesis, angiogenesis, iron transport, glucose utilization, resistance to oxidative stress, cell proliferation, survival and apoptosis, extracellular matrix homeostasis, and tumorigenesis and metastasis. HIF is accumulated in hypoxia, whereas it is rapidly degraded in normoxic cells. The oxygen sensing mechanism behind this phenomenon is provided by HIF prolyl 4-hydroxylases (HIF-P4Hs, commonly known as PHDs and EglNs) that require oxygen in their reaction. In normoxia two prolines in the oxygen-dependent degradation domain of the HIFα subunit become hydroxylated by the HIF-P4Hs. The 4-hydroxyproline residues formed serve as recognition sites for the von Hippel-Lindau E3 ubiquitin ligase complex, and result in subsequent ubiquitination and instant proteasomal degradation of HIFα in normoxia. The HIF-P4H reaction is inhibited in hypoxia, HIFα evades degradation and forms a functional dimer with HIFβ leading to activation of the HIF target genes. The central role of HIF-P4Hs in the regulation of the hypoxia response pathway has provided an attractive possibility as a drug candidate for treatment of e.g. severe anemias and ischemic conditions and several companies are currently carrying out clinical studies on the use of HIF-P4H inhibitors to treat anemia in patients suffering from a kidney disease. Therefore, it is important to understand the effects of individual HIF-P4H isoenzymes on the hypoxia response and potential other pathways in vivo. Common and specific functions of the HIF-P4H isoenzymes are discussed in this review based on available data from cell biological studies and gene-modified animals.
Biological Chemistry 01/2013;
· 2.68 Impact Factor
Available from: Antony P Page
Prolyl 4-hydroxlase activity is essential for development and cuticle formation in the human infective parasitic nematode Brugia malayi.
Alan D Winter
Gillian McCormack
, Johanna Myllyharju,
Antony P Page
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Collagen prolyl 4-hydroxylases (C-P4H) are required for formation of extracellular matrices in higher eukaryotes. These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4-hydroxyproline, a modification essential for the stability of the triple helix. C-P4Hs are most often oligomeric complexes, with enzymatic activity contributed by the α subunits, and the β subunits formed by protein disulfide isomerase (PDI). Here we characterise this enzyme class in the important human parasitic nematode Brugia malayi. All potential C-P4H subunits were identified by detailed bioinformatic analysis of sequence databases, function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans, while biochemical activity and complex formation were examined via co-expression in insect cells. Simultaneous RNAi of two B. malayi C-P4H α subunit-like genes resulted in a striking, highly penetrant body morphology phenotype in parasite larvae. This was replicated by single RNAi of a B. malayi C-P4H β subunit-like PDI. Surprisingly however, the B. malayi proteins were not capable of rescuing a C. elegans α subunit mutant, whereas the human enzymes could. In contrast, the B. malayi PDI did functionally complement the lethal phenotype of a C. elegans β subunit mutant. Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non-reducible, inter-subunit cross-link, present only in the parasite. We therefore demonstrate that C-P4H activity is essential for development of B. malayi and uncover a novel parasite-specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control.
Journal of Biological Chemistry 12/2012;
· 4.65 Impact Factor
The expression and role of Lysyl oxidase (LOX) in dentinogenesis.
L Tjäderhane
M Vered
V Pääkkönen
A Peteri
J M Mäki
, J Myllyharju,
D Dayan
T Salo
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AIM: To establish whether eliminating Lysyl oxidase (LOX) gene would affect dentine formation. METHODOLOGY: Newborn wild-type (wt) and homo- and heterozygous LOX knock-out (Lox(-/-) and Lox(+/-) , respectively) mice were used to study developing tooth morphology and dentine formation. Collagen aggregation in the developing dentine was examined histochemically with picrosirius red (PSR) staining followed by polarized microscopy. Because Lox(-/-) die at birth, adult wt and Lox(+/-) mouse tooth morphologies were examined with FESEM. Human odontoblasts and pulp tissue were used to study the expression of LOX and its isoenzymes with Affymetrix cDNA microarray. RESULTS: No differences between Lox(-/-) , Lox(+/-) and wt mice developing tooth morphology were seen by light microscopy. Histochemically, however, teeth in wt mice demonstrated yellow-orange and orange-red polarization colours with PSR staining, indicating thick and more densely packed collagen fibres, whilst in Lox(-/-) and Lox(+/-) mice, most of the polarization colours were green to green-yellow, indicating thinner, less aggregated collagen fibres. Fully developed teeth did not show any differences between Lox(+/-) and wt mice with FESEM. Human odontoblasts expressed LOX and three of four of its isoenzymes. CONCLUSIONS: The data indicate that LOX is not essential in dentinogenesis, even though LOX deletion may affect dentine matrix collagen thickness and packing. The absence of functional LOX may be compensated by LOX isoenzymes.
International Endodontic Journal 10/2012;
· 2.05 Impact Factor
Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.
Anu Laitala
Ellinoora Aro
Gail Walkinshaw
Joni M Mäki
Maarit Rossi
Minna Heikkilä
Eeva-Riitta Savolainen
Michael Arend
Kari I Kivirikko
Peppi Koivunen
, Johanna Myllyharju
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An endoplasmic reticulum transmembrane prolyl 4-hydroxylase (P4H-TM) is able to hydroxylate the α subunit of the hypoxia-inducible factor (HIF) in vitro and in cultured cells, but nothing is known about its roles in mammalian erythropoiesis. We studied such roles here by administering a HIF-P4H inhibitor, FG-4497, to P4h-tm(-/-) mice. This caused larger increases in serum Epo concentration and kidney but not liver Hif-1α and Hif-2α protein and Epo mRNA levels than in wild-type mice, while the liver Hepcidin mRNA level was lower in the P4h-tm(-/-) mice than in the wild-type. Similar, but not identical, differences were also seen between FG-4497-treated Hif-p4h-2 hypomorphic (Hif-p4h-2(gt/gt)) and Hif-p4h-3(-/-) mice versus wild-type mice. FG-4497 administration increased hemoglobin and hematocrit values similarly in the P4h-tm(-/-) and wild-type mice, but caused higher increases in both values in the Hif-p4h-2(gt/gt) mice and in hematocrit value in the Hif-p4h-3(-/-) mice than in the wild-type. Hif-p4h-2(gt/gt)/P4h-tm(-/-) double gene-modified mice nevertheless had increased hemoglobin and hematocrit values without any FG-4497 administration, although no such abnormalities were seen in the Hif-p4h-2(gt/gt) or P4h-tm(-/-) mice. Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis.
Blood 09/2012; 120(16):3336-44.
· 9.78 Impact Factor
Hypoxia-inducible factor-1 (HIF-1) but not HIF-2 is essential for hypoxic induction of collagen prolyl 4-hydroxylases in primary newborn mouse epiphyseal growth plate chondrocytes.
Ellinoora Aro
Richa Khatri
Rita Gerard-O'Riley
Laura Mangiavini
, Johanna Myllyharju,
Ernestina Schipani
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Hypoxia-inducible factors (HIFs) are the master regulators of hypoxia-responsive genes. They play a critical role in the survival, development and differentiation of chondrocytes in the avascular hypoxic fetal growth plate, which is rich in extracellular matrix (ECM) and in its main component, collagens. Several genes involved in the synthesis, maintenance and degradation of ECM are regulated by HIFs. Collagen prolyl 4-hydroxylases (C-P4Hs) are key enzymes in collagen synthesis, as the resulting 4-hydroxyprolines are necessary for the stability of all collagen molecules. The vertebrate C-P4Hs are α(2)β](2) tetramers with three isoforms of the catalytic α subunit, yielding C-P4Hs of types I-III. C-P4H-I is the main form in most cells, but C-P4H-II is the major form in chondrocytes. We postulated here that post-translational modification of collagens, particularly 4-hydroxylation of proline residues, could be one of the modalities by which HIF regulates the adaptive responses of chondrocytes in fetal growth plates. To address this hypothesis, we used primary epiphyseal growth plate chondrocytes isolated from newborn mice with conditionally inactivated genes for HIF-1α, HIF-2α or the von Hippel-Lindau (VHL) protein. The data obtained showed that C-P4H α(I) and α(II) mRNA levels were increased in hypoxic chondrocytes in a manner dependent on HIF-1 but not on HIF-2. Furthermore, the increases in the C-P4H mRNA levels were associated with both increased amounts of the C-P4H tetramers and augmented C-P4H activity in hypoxia. The hypoxia-inducibility of the C-P4H isoenzymes is thus likely to ensure sufficient C-P4H activity for collagen synthesis occurring in chondrocytes in a hypoxic environment.
Journal of Biological Chemistry 08/2012;
· 4.65 Impact Factor
Available from: Tova Lifshitz
High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2.
Shikma Mordechai
Libe Gradstein
Annika Pasanen
Rivka Ofir
Khalil El Amour
Jaime Levy
Nadav Belfair
Tova Lifshitz
Sara Joshua
Ginat Narkis
Khalil Elbedour
, Johanna Myllyharju,
Ohad S Birk
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Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli consanguineous kindred. Some affected individuals also had variable expressivity of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary sight loss due to severe retinal detachments. Through genome-wide linkage analysis, the disease-associated gene was mapped to ∼1.7 Mb on chromosome 3q28 (the maximum LOD score was 11.5 at θ = 0 for marker D3S1314). Sequencing of the entire coding regions and intron-exon boundaries of the six genes within the defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1, encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase that hydroxylates collagens. The mutation affects a glycine that is conserved within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant recombinant P3H2 polypeptides expressed in insect cells showed that the mutation led to complete inactivation of P3H2.
The American Journal of Human Genetics 09/2011; 89(3):438-45.
· 11.20 Impact Factor
Available from: Kathrin H Kirsch
The Ras signaling inhibitor LOX-PP interacts with Hsp70 and c-Raf to reduce Erk activation and transformed phenotype of breast cancer cells.
Seiichi Sato
Philip C Trackman
Joni M Mäki
, Johanna Myllyharju,
Kathrin H Kirsch
Gail E Sonenshein
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The lysyl oxidase gene (LOX) inhibits Ras signaling in transformed fibroblasts and breast cancer cells. Its activity was mapped to the 162-amino-acid propeptide domain (LOX-PP) of the lysyl oxidase precursor protein. LOX-PP inhibits Erk signaling, motility, and tumor formation in a breast cancer xenograft model; however, its mechanism of action is largely unknown. Here, a copurification-mass spectrometry approach was taken using ectopically expressed LOX-PP in HEK293T cells and the heat shock/chaperone protein Hsp70 identified. Hsp70 interaction with LOX-PP was confirmed using coimmunoprecipitation of intracellularly and bacterially expressed and endogenous proteins. The interaction was mapped to the Hsp70 peptide-binding domain and to LOX-PP amino acids 26 to 100. LOX-PP association reduced Hsp70 chaperone activities of protein refolding and survival after heat shock. LOX-PP interacted with the Hsp70 chaperoned protein c-Raf. With the use of ectopic expression of LOX-PP wild-type and deletion proteins, small interfering RNA (siRNA) knockdown, and Lox(-/-) mouse embryo fibroblasts, LOX-PP interaction with c-Raf was shown to decrease downstream activation of MEK and NF-κB, migration, and anchorage-independent growth and reduce its mitochondrial localization. Thus, the interaction of LOX-PP with Hsp70 and c-Raf inhibits a critical intermediate in Ras-induced MEK signaling and plays an important role in the function of this tumor suppressor.
Molecular and cellular biology 07/2011; 31(13):2683-95.
· 6.06 Impact Factor
Available from: Xiang Wang
A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases.
Xuelai Luo
Yongxiang Liu
Stefan Kubicek
, Johanna Myllyharju,
Anthony Tumber
Stanley Ng
Ka Hing Che
Jessica Podoll
Tom D Heightman
Udo Oppermann
Stuart L Schreiber
Xiang Wang
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Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.
Journal of the American Chemical Society 06/2011; 133(24):9451-6.
· 10.68 Impact Factor
Roles of the human hypoxia-inducible factor (HIF)-3α variants in the hypoxia response.
Minna Heikkilä
Annika Pasanen
Kari I Kivirikko
, Johanna Myllyharju
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The hypoxia-inducible transcription factor (HIF) controls (in an oxygen-dependent manner) the expression of a large number of genes whose products are involved in the response of cells to hypoxia. HIF is an αβ dimer that binds to hypoxia response elements (HREs) in its target genes. Human HIF-α has three isoforms, HIF-1α, HIF-2α and HIF-3α, of which the roles of HIF-3α are largely unknown, although it is usually regarded as a negative regulator of HIF-1α and HIF-2α. The human HIF-3α locus is subject to extensive alternative splicing, leading to at least seven variants. We analyzed here the effects of the long variants and the short variant HIF-3α4 on the hypoxia response. All these variants were found to interact with HIF-β, HIF-1α and HIF-2α. The long HIF-3α variants were localized in the nucleus in hypoxia, while HIF-3α4 was cytoplasmic. Interaction of the HIF-3α variants with HIF-1α inhibited the nuclear translocation of both. None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2. Unexpectedly, siRNA knock-down of the endogenous HIF-3α variants led to downregulation of certain HIF target genes, while overexpression of individual long HIF-3α variants upregulated certain HIF target genes in a variant and target gene-specific manner under conditions in which HIF-β was not a limiting factor. These data indicate that the HIF-3α variants may have more versatile and specific roles in the regulation of the hypoxia response than previously anticipated.
Cellular and Molecular Life Sciences CMLS 04/2011; 68(23):3885-901.
· 5.62 Impact Factor
Deficiency of a Transmembrane Prolyl 4-Hydroxylase in the Zebrafish Leads to Basement Membrane Defects and Compromised Kidney Function
Jaana Hyvärinen
Mataleena Parikka
Raija Sormunen
Mika Rämet
Karl Tryggvason
Kari I. Kivirikko
, Johanna Myllyharju,
Peppi Koivunen
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Prolyl 4-hydroxylases (P4Hs) catalyze the hydroxylation of collagens and hypoxia-inducible factor (HIF)-α subunits. We studied the zebrafish homologue of the recently characterized human transmembrane P4H (P4H-TM) that can hydroxylate HIF-α, but not collagens, in vitro and influence HIF-α levels in cellulo. The zebrafish P4H-TM mRNA had its highest expression in the eye and brain and lower levels in other tissues, including the kidney. Morpholino knockdown of P4H-TM in embryos resulted in a reduction in the size of the eye and head and morphological alterations in the head from 2 days postfertilization onward. In addition, pericardial edema, regarded as a sign of kidney dysfunction, developed from 3 days postfertilization onward. The phenotype was dependent on the P4H-TM catalytic activity because similar results were obtained with morpholinos targeting either translation initiation or catalytic residues of the enzyme. Structural and functional analyses of the morphant pronephric kidneys revealed fragmented glomerular basement membranes (BMs), disorganized podocyte foot processes, and severely compromised pronephric kidney function leading to proteinuria. The opacity of the eye lens was increased due to the presence of extra nuclei and deposits, and the structure of the lens capsule BM was altered. Our data suggest that P4H-TM catalytic activity is required for the proper development of the glomerular and lens capsule BMs. Many HIF target genes were induced in the P4H-TM-deficient morphants, but the observed phenotype is not likely to be mediated at least solely via the HIF pathway, and thus P4H-TM probably has additional, as yet unknown, substrates.
Journal of Biological Chemistry 12/2010; 285(53):42023-42032.
· 4.65 Impact Factor
Characterization of two carnation petal prolyl 4 hydroxylases.
Florina Vlad
Päivi Tiainen
Carolyn Owen
Thodhoraq Spano
Firas Bou Daher
Fatiha Oualid
Namik Ozer Senol
Daniela Vlad
, Johanna Myllyharju,
Panagiotis Kalaitzis
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Prolyl 4-hydroxylases (P4Hs) catalyze the proline hydroxylation, a major post-translational modification, of hydroxyproline-rich glycoproteins. Two carnation petal P4H cDNAs, (Dianthus caryophyllus prolyl 4-hydroxylase) DcP4H1 and DcP4H2, were identified and characterized at the gene expression and biochemical level in order to investigate their role in flower senescence. Both mRNAs showed similar patterns of expression with stable transcript abundance during senescence progression and differential tissue-specific expression with DcP4H1 and DcP4H2 strongly expressed in ovaries and stems, respectively. Recombinant DcP4H1 and DcP4H2 proteins were produced and their catalytic properties were determined. Pyridine 2,4-dicarboxylate (PDCA) was identified as a potent inhibitor of the in vitro enzyme activity of both P4Hs and used to determine whether inhibition of proline hydroxylation in petals is involved in senescence progression of cut carnation flowers. PDCA suppressed the climacteric ethylene production indicating a strong correlation between the inhibition of DcP4H1 and DcP4H2 activity in vitro by PDCA and the suppression of climacteric ethylene production in cut carnation flowers.
Physiologia Plantarum 10/2010; 140(2):199-207.
· 3.66 Impact Factor
Deficiency of a transmembrane prolyl 4-hydroxylase in the zebrafish leads to basement membrane defects and compromised kidney function.
Jaana Hyvärinen
Mataleena Parikka
Raija Sormunen
Mika Rämet
Karl Tryggvason
Kari I Kivirikko
, Johanna Myllyharju,
Peppi Koivunen
[Show abstract]
[Hide abstract]
Prolyl 4-hydroxylases (P4Hs) catalyze the hydroxylation of collagens and hypoxia-inducible factor (HIF)-α subunits. We studied the zebrafish homologue of the recently characterized human transmembrane P4H (P4H-TM) that can hydroxylate HIF-α, but not collagens, in vitro and influence HIF-α levels in cellulo. The zebrafish P4H-TM mRNA had its highest expression in the eye and brain and lower levels in other tissues, including the kidney. Morpholino knockdown of P4H-TM in embryos resulted in a reduction in the size of the eye and head and morphological alterations in the head from 2 days postfertilization onward. In addition, pericardial edema, regarded as a sign of kidney dysfunction, developed from 3 days postfertilization onward. The phenotype was dependent on the P4H-TM catalytic activity because similar results were obtained with morpholinos targeting either translation initiation or catalytic residues of the enzyme. Structural and functional analyses of the morphant pronephric kidneys revealed fragmented glomerular basement membranes (BMs), disorganized podocyte foot processes, and severely compromised pronephric kidney function leading to proteinuria. The opacity of the eye lens was increased due to the presence of extra nuclei and deposits, and the structure of the lens capsule BM was altered. Our data suggest that P4H-TM catalytic activity is required for the proper development of the glomerular and lens capsule BMs. Many HIF target genes were induced in the P4H-TM-deficient morphants, but the observed phenotype is not likely to be mediated at least solely via the HIF pathway, and thus P4H-TM probably has additional, as yet unknown, substrates.
Journal of Biological Chemistry 10/2010; 285(53):42023-32.
· 4.65 Impact Factor
Available from: PubMed Central
Collagen binding specificity of the discoidin domain receptors: binding sites on collagens II and III and molecular determinants for collagen IV recognition by DDR1.
Huifang Xu
Nicolas Raynal
Stavros Stathopoulos
, Johanna Myllyharju,
Richard W Farndale
Birgit Leitinger
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The discoidin domain receptors, DDR1 and DDR2 are cell surface receptor tyrosine kinases that are activated by triple-helical collagen. While normal DDR signalling regulates fundamental cellular processes, aberrant DDR signalling is associated with several human diseases. We previously identified GVMGFO (O is hydroxyproline) as a major DDR2 binding site in collagens I-III, and located two additional DDR2 binding sites in collagen II. Here we extend these studies to the homologous DDR1 and the identification of DDR binding sites on collagen III. Using sets of overlapping triple-helical peptides, the Collagen II and Collagen III Toolkits, we located several DDR2 binding sites on both collagens. The interaction of DDR1 with Toolkit peptides was more restricted, with DDR1 mainly binding to peptides containing the GVMGFO motif. Triple-helical peptides containing the GVMGFO motif induced DDR1 transmembrane signalling, and DDR1 binding and receptor activation occurred with the same amino acid requirements as previously defined for DDR2. While both DDRs exhibit the same specificity for binding the GVMGFO motif, which is present only in fibrillar collagens, the two receptors display distinct preferences for certain non-fibrillar collagens, with the basement membrane collagen IV being exclusively recognised by DDR1. Based on our recent crystal structure of a DDR2-collagen complex, we designed mutations to identify the molecular determinants for DDR1 binding to collagen IV. By replacing five amino acids in DDR2 with the corresponding DDR1 residues we were able to create a DDR2 construct that could function as a collagen IV receptor.
Matrix biology: journal of the International Society for Matrix Biology 10/2010; 30(1):16-26.
· 3.56 Impact Factor
Hypoxia-inducible factor (HIF)-3alpha is subject to extensive alternative splicing in human tissues and cancer cells and is regulated by HIF-1 but not HIF-2.
Annika Pasanen
Minna Heikkilä
Kati Rautavuoma
Maija Hirsilä
Kari I Kivirikko
, Johanna Myllyharju
[Show abstract]
[Hide abstract]
The hypoxia-inducible transcription factors (HIFs) play a central role in the response of cells to hypoxia. HIFs are alphabeta dimers, the human alpha subunit having three isoforms. HIF-3alpha is unique among the HIF-alpha isoforms in that its gene is subject to extensive alternative splicing. Database analyses have predicted the generation of six HIF-3alpha splice variants that utilize three alternative transcription initiation sites. None of these variants is likely to act as an efficient transcription factor, but some of them have been reported to inhibit HIF-1 and HIF-2 functions. We analyzed here for the first time in detail whether these six variants are indeed generated in various human tissues and cell lines. We identified four novel variants, named here HIF-3alpha7 to HIF-3alpha10, whereas we obtained no evidence for the predicted HIF-3alpha3 and HIF-3alpha5. Distinct differences in the expression patterns of the variants were found between human tissues, the levels being particularly low in many cancer cell lines. Hypoxia upregulated transcription from all three alternative HIF-3alpha promoters. siRNA experiments showed that this induction is mediated specifically by HIF-1 and not by HIF-2. The tissue-specific differences in the expression patterns and levels of the HIF-3alpha variants can be expected to modulate the hypoxia response of various tissues and cell types to different extents during development and in pathological situations. A further level of regulation is brought about by the fact that the levels of the HIF-3alpha transcripts themselves are regulated by hypoxia and by changes in HIF-1 levels.
The international journal of biochemistry & cell biology 04/2010; 42(7):1189-200.
· 4.89 Impact Factor
Hearts of hypoxia-inducible factor prolyl 4-hydroxylase-2 hypomorphic mice show protection against acute ischemia-reperfusion injury.
Jaana Hyvärinen
Ilmo E Hassinen
Raija Sormunen
Joni M Mäki
Kari I Kivirikko
Peppi Koivunen
, Johanna Myllyharju
[Show abstract]
[Hide abstract]
Hypoxia-inducible factor (HIF) has a pivotal role in oxygen homeostasis and cardioprotection mediated by ischemic preconditioning. Its stability is regulated by HIF prolyl 4-hydroxylases (HIF-P4Hs), the inhibition of which is regarded as a promising strategy for treating diseases such as anemia and ischemia. We generated a viable Hif-p4h-2 hypomorph mouse line (Hif-p4h-2(gt/gt)) that expresses decreased amounts of wild-type Hif-p4h-2 mRNA: 8% in the heart; 15% in the skeletal muscle; 34-47% in the kidney, spleen, lung, and bladder; 60% in the brain; and 85% in the liver. These mice have no polycythemia and show no signs of the dilated cardiomyopathy or hyperactive angiogenesis observed in mice with broad spectrum conditional Hif-p4h-2 inactivation. We focused here on the effects of chronic Hif-p4h-2 deficiency in the heart. Hif-1 and Hif-2 were stabilized, and the mRNA levels of glucose transporter-1, several enzymes of glycolysis, pyruvate dehydrogenase kinase 1, angiopoietin-2, and adrenomedullin were increased in the Hif-p4h-2(gt/gt) hearts. When isolated Hif-p4h-2(gt/gt) hearts were subjected to ischemia-reperfusion, the recovery of mechanical function and coronary flow rate was significantly better than in wild type, while cumulative release of lactate dehydrogenase reflecting the infarct size was reduced. The preischemic amount of lactate was increased, and the ischemic versus preischemic [CrP]/[Cr] and [ATP] remained at higher levels in Hif-p4h-2(gt/gt) hearts, indicating enhanced glycolysis and an improved cellular energy state. Our data suggest that chronic stabilization of Hif-1alpha and Hif-2alpha by genetic knockdown of Hif-p4h-2 promotes cardioprotection by induction of many genes involved in glucose metabolism, cardiac function, and blood pressure.
Journal of Biological Chemistry 02/2010; 285(18):13646-57.
· 4.65 Impact Factor
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Peppi Koivunen
University of Oulu
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text: River Kidz VBS View full-size image < previous next > Is this photo a winner? "June 8-12 Vacation Bible school! We loved the bright safety orange color and our kids loved the bright fun design!" - http://Www.oldriverbaptist.com - River Kidz (Jun 12, 2014) Share this photo on: Twitter Facebook Pinterest Similar Photos: vacation bible school | religious | camps retreats bible school | vbs | large group | safety orange Feeling inspired? Visit the CustomInk Design Lab to start your own group order. Design Your Own

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text:
|Posted By:
|Richard Helm
|Re: Isaac Fonda, Saratoga Dist., Albany Co., NY 1779
|Post Date:
|May 19, 2002 at 12:23:43
|Message URL:
|Fonda Family Genealogy Forum
|Forum URL:
I read with interest your message about the early Fondas. My wife has the Fonda line in her ancestry. I have researched the line back to Douw Fonda of Amsterdam b. ca. 1580. Your message is the first I have seen that refers to him as Douwe Evertse and has any earlier generations. I would appreciate anything you could send on these earlier Fondas. What is your source(s) for this information? You can reach me at email@example.com. If you need a postal address, let me know by e-mail and I will reply. I also appreciated the info on 'name of records'. Looking forward to hearing from you.


text:
Fri, Dec 19, 2003
CMC Electronics has been selected by
the Dubai Air Wing as the avionics systems integrator for their
C-130 Hercules, L100-30 cockpit upgrade. CMC Electronics is teamed
with Gulf Aircraft Maintenance Company (GAMCO), the prime
contractor for the project.
CMC Electronics will supply its CMA-900 Flight Management System
(FMS) as the core of the upgrade, while GAMCO is responsible for
all Program Depot Maintenance (PDM) inspection requirements, a new
cargo handling system, aircraft painting and the installation of
the cockpit upgrade systems in full coordination with CMC
The Dubai Air Wing configuration is a multi-sensor system based
on a fully integrated dual CMA-900 FMS, providing effectively 100
per cent dispatch reliability anywhere in the world, and seamless
navigation from take-off to final approach. This upgrade will allow
the Dubai Air Wing's aircraft to meet all P-RNAV (precision area
navigation), flight data recording and TAWS (Terrain Avoidance
Warning System) requirements. The CMA-900 features a color,
liquid-crystal multi-function display and includes CMC Electronics'
GPS sensor.
"We look forward to working closely with the Dubai Air Wing and
GAMCO on this very important modernization program," said Mr. Bruce
Bailey, CMC Electronics' vice president, commercial aviation.
GAMCO General Manager Mr. Saif Al Mughairy said, "We are
delighted to be working with CMC Electronics and are confident that
our reputation for quality and service will be reinforced by this
upgrade program for the Dubai Air Wing."
According to Dubai Air Wing Commander Col. Rashid K. Balhaul,
"We are looking forward to realizing the many economic, operational
and, in particular, safety-related benefits provided by the upgrade
of our C-130 aircraft."
Aero-TV: Potential Energy -- Aero Electric Aircraft Corporation
Airborne 11.26.14: Island Air 'Scrooges' Pilots, DC's NextGen, EAA On Stadium Flights
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text:
After discovering my sons issues, I found ALOT of supporting info re celiac and me.. I made an appt with my family dr in 8 days~ do I HAVE to stay on gluten until then? if so, how much is the minimum?
I have concluded nearly 95% that wheat IS causing my horrible hives, that includes my face/eyes/lips and tongue swelling. I was gluten-free for about a week with my son with subsiding of my hives, and then binged this weekend on pizza. I have horrible muscle aches/severe joint pain to the point I don't want to move. My hives are back full force, and the antihistamines aren't helping. I have an upset tummy. I have sharp pains in my stomach area. I don't want to do this for another week if I don't have to, but if I must, for proper blood work, how much is the minimum to consume?
Share this page:
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Started by cherie012, Jan 01 2006 09:15 AM
1 reply to this topic
Posted 01 January 2006 - 09:15 AM
- 0
Posted 01 January 2006 - 10:48 AM
In order to find out if your body produces antibodies to something, you have to be "getting" that something for it to react to. So yes, you have to continue eating plenty of gluten - the recommendation, I believe, before testing, is a minimum of the equivalent of three slices of wheat bread a day.
- 0
Tiffany aka "Have I Mentioned Chocolate Lately?"
Inconclusive Blood Tests, Positive Dietary Results, No Endoscopy
G.F. - September 2003; C.F. - July 2004
Hiker, Yoga Teacher, Engineer, Painter, Be-er of Me
Bellevue, WA
Inconclusive Blood Tests, Positive Dietary Results, No Endoscopy
G.F. - September 2003; C.F. - July 2004
Hiker, Yoga Teacher, Engineer, Painter, Be-er of Me
Bellevue, WA
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The high cost of war hangs in the air of Moon Molsen's tale of two army casualty-notification officers who travel to the Harlem projects to deliver some news to a Sayeeda Porter about her son serving in the war overseas. It's news that Sayeeda isn't ready to hear.
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39 year old woman | Long Island City, NY, USA | Seeking men 35-45 within 20 miles
Looking forward to our paths crossing
As a native New Yorker, I love this city but try to escape whenever I can, whether to a far off land or a trip to Jones beach or upstate to go hiking. I have an easygoing nature and an up-for-anything attitude so am always ready for a day/night out to explore the fun city events and parks, check out a new restaurant, or see an exhibit or some live music. Spending time with family and friends is very important to me and I also enjoy my downtime being a homebody—watching Netflix, trying a new recipe, or dancing around my living room to old favorites. Life is a balancing act and I try to appreciate the simple things with a little adventure mixed in to keep it interesting... and having someone to share it with makes it all the better. As for you... I don't have a perfect description of the type of guy I'm looking for, but twist my arm and I'll tell you that the qualities important to me and that I maintain are kindness, respect, honesty, affection, humor, and smarts. Basically I'd like to meet someone with an overall zest for life, who likes himself, and is looking for someone to share his days with.... and having a cute smile certainly doesn't hurt either :) I can go on about myself and who I'm looking for in this profile, but it sure is a lot more fun to find out for ourselves over a glass of wine or a coffee... do you agree? And if there's that spark, we can discover the things that go beyond what's written in this box. Maybe we'll be the elusive someone special to each other that we're on here hoping to find.
Coffee and conversation , Cooking , Dining out , Movies/Videos , Museums and art , Music and concerts , Exploring new areas , Performing arts , Travel/Sightseeing , Volunteering , Watching sports , Wine tasting
Bowling, Cycling, Dancing, Other types of exercise, Tennis / Racquet sports, Walking / Hiking, Yoga
I exercise 3-4 times per week.
I like Cats, Dogs
Any place that has great food and a good wine or beer list! Gantry Park. I love to travel and always looking to add to the list of places to explore—some favorites are Spain, Argentina, Holland,Costa Rica, New Orleans
Planning things (trips, parties, projects...), cooking for people, someone cooking for me ;), old fashioneds, morning walks, old school hip hop (I was raised in BK!), mani-pedis, days or nights so great you lose track of time
Going to see live music, particularly jazz, (badly) playing tennis, checking out an exhibit or show, taking a day trip upstate…really anything can be fun with good company.
I am a graduate candidate so lately what's assigned, which now includes the Omnivore's Dilemma and the Meat Racket. Also lots of blogs (McSweeney's, 99U, Eater, etc)
Z{{Cta}} {{#if HasMoreInfo}} ?{{CtaSecondary}} {{/if}}
|What she is looking for
|5'7" (170cms)
|5'9" (175cms) to 6'11" (210cms)
|Body type:
|Athletic and toned
|Slender, About average, Athletic and toned
|No preference
|Dark brown
|No preference
|No Way
|No Way
|Social Drinker
|Social Drinker
|Other profession
|No preference
Transitioning careers - still freelance in branding/advertising while I go to grad school to become a dietician. But you can only check one box!
|I'll tell you later
|No preference
|Never Married
|No preference
|Have kids:
|No preference
|Wants kids:
|Definitely, Someday, Not sure
|Background / Values
|Latino / Hispanic, White / Caucasian
|Latino / Hispanic, White / Caucasian, Other
|Spiritual but not religious
|No preference
Culturally Catholic but really just try to live by the Golden Rule
|Graduate degree
|Bachelors degree, Graduate degree, PhD / Post Doctoral
I am working towards a master's degree in nutrition


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text:
- Report: #137318
Report - Rebuttal - Arbitrate
Complaint Review: Annita Phengsavath AKA Khamphone Phengsavath
Annita Phengsavath AKA Khamphone PhengsavathSan Diego, CA San Diego, California United States of America
Annita Phengsavath - Khamphone Phengsavath Homewrecking W**** Annita Phengsavath of San Diego, CA LOVES to mess with married men. But beware.. one of her married customers has GENITAL WARTS!!! behaving like a prostitute Jokes on you w**** San Diego California
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If you fall into one of the following categories, you should definitely keep reading this:
*Husband or live in boyfriend of Annita (I believe his name is *Bounlonh Savaty) *Annita's Family *Annita's Friends *Annita's co workers at SPAWAR in San Diego *any one else that Annita has or currently is f*****/s******...
Annita Phengsavath is a woman with three children and is in a committed relationship (not sure if the tramp is married or just living with the father of her kids).
My friend (who used to live in San Diego, CA with her ex-husband MARK W MILLER) found out in Nov. 2003 that her ex husband was cheating on her after 1 year of marriage (for the second time). He was cheating on his beautiful wife with this nasty ghetto w**** that he works with (both are government contractors for SPAWAR in San Diego, CA).
I am a believer that it takes two to hold a marriage together, but it is impossible if only 1 person wants to make it work. My friend was a good wife to Mark (doted on him, was loving, faithful etc.) but he is someone with major major issues (pathological liar and porn addict). She discovered hard evidence of Mark's sexual relationship with Annita and left him. Good for you girl!!! Of course like a typical liar and cheater, he tried to blame her for his affair...funny how that works right!
Anyways, my friend (the ex wife) has moved on with her life but I still think there is some unfinished business to take care of. I wish I'd seen this website earlier but at least I found it!
I think it is extremely important that ALL of Annita's sexual partners AND Husband/live in boyfriend/Father of her children know of her activities at work/lunchtime. The reason is because that married man she was f****** (MARK W MILLER) has an incurable STD (genital warts). He (or they, most likely) have a right to know!!! What if it were worse than warts??? The hilarous part of it is that Mark didn't bother to inform Annita of this fact (apparently he didn't have too much respect for her either...but why would he?)
Annita told my friend (when confronted) that "it takes two to tango". You're right, w****, it does! So what's your excuse for messing around with a married man? You knew he was married!!!
Yes, he was the one who made the commitment but you KNEW he was married and still did what you wanted. My friend is so much better off with out him (and she knows it) but that doesn't excuse your role in the BREAKUP of this marriage.
Annita (and Mark) really screwed things up for my friend for a while; she made many many sacrifices for him. So my view is that Annita needs to feel the heat a little as well. Why should she go on with her life as if nothing ever happened? Perhaps she should focus on her current relationship and her children instead of behaving like a prostitute.
Max San diego, California
This report was posted on Ripoff Report on 04/02/2005 01:55 PM and is a permanent record located here: http://www.ripoffreport.com/r/Annita-Phengsavath-AKA-Khamphone-Phengsavath/San-Diego-California/Annita-Phengsavath-Khamphone-Phengsavath-Homewrecking-W-Annita-Phengsavath-of-San-Di-137318. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
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- Paralegal (5)
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Hotel Executive Suites
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Wednesday in New York
... happen. Runners run, cyclists cycle, and roads run through it - everyone and everything co-exists in that massive green lung. We started the day with a workout in the gym. I burned of all of a 100 calries and then had breakfast at Le Pain Quotidien. Janine had Brown Rice Pudding, I had a Belgian waffle with cream and jam. I know that's more than a 100 calories worth but hey, when in New York ... Today we've sat ...
New York day 3
... by pretty mews and featured buildings. We finally found our destination 'Washington Square Park' which had a big archway (like arc de triumph) and a lovely big fountain with water jets also coming out of the sides, nestled in a lovely large beautiful park area. It was very busy being a Saturday. We walked on down through to 'Soho' (& no nothing like london's soho!) ! It looked a respectable residential area with locals around, as there was not a lot to see ...
Arrived in the New York City
... cab to our hotel Four Points Mid-Town 40th Street. Driving in New York is crazy the taxi drivers going in and out almost hitting people walking across the street. The cost of the taxi was $60.00.
The hotel room was small but we knew this ahead of time as most New York City hotel rooms are just like Europe. However you are not in New York to stay in your hotel room anyways.
We decided to walk around and see ...
Day 21 - Downtown Brooklyn and Transit Museum
... is made especially for Shake Shack by Brooklyn Brewery. That's probably why people love this place so much. I did not have any of that because I did not want to be in a food coma so early in the day. My next stop was just a block away at the NYC Transit Museum. This was a super cool museum that is in an old subway station. You go down underground through the old subway entrance to get in. There is an detailed exhibit on how ...
Moma, Times Square, Macy's, 110th street Central P
... some others.
After that we headed to Times Square which was amazing in the day time as well. We bought ourselves some comedy tickets for tomorrow night after the 4th of July fireworks off some street salesman. Fingers crossed that pays off!
Then we went to the M & M factory.
3 stories of M & M stuff and chocolate tubes of color. Though it's so bloody hot we didn't dare buy any cause it would have ...


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Mary Alice Black
May 14, 2013
Services for Mary Alice Black, 79, were May 17, 2013, at Coleman Funeral Home in Ackerman. Burial was in Mt. Nebo Cemetery near Ackerman.
She was born Feb. 20, 1934, in Payne. Mrs. Black … Read more
Mary Alice Black
May 14, 2013
Services for Mary Alice Black, 79, were May 17, 2013, at Coleman Funeral Home in Ackerman. Burial was in Mt. Nebo Cemetery near Ackerman.
She was born Feb. 20, 1934, in Payne. Mrs. Black … Read more
Billy 'B.R.' Forbes
April 28, 2013
Services for Billy "B.R." Forbes, 74, of Stewart were May 1, 2013, at Oliver Funeral Home Chapel in Eupora. Burial was in Greensboro Cemetery.
Mr. Forbes was a member of Union Baptist Church, and … Read more
Charlene Senter Glasgow
April 18, 2013
Services for Charlene Senter Glasgow , 96, were April 24, 2013, at
Coleman Funeral Home in Ackerman.
She was born in Fulton to the late Alfred Richard and Maudena
Sheffield Senter. Mrs. Glasgow established … Read more
James Thomas Croft
April 8, 2013
Graveside services for James Thomas Croft, 67, of Eupora were April
13, 2013, at Greensboro Cemetery with the Rev. James Caffey officiating.
He was born June 30, 1945, in Tupelo to the late Tommie … Read more
Jerry D. Ferguson Sr.
April 7, 2013
Services for Jerry D. Ferguson Sr. were April 10, 2013, at Morgan
Chapel Baptist Church. Burial was in the church cemetery.
He was born April 14, 1944, to the late Rufus and Myrtle … Read more
S.C. Thomas
'Bussie' Fulgham
March 26, 2013
Services for S.C. Thomas Fulgham, 83, of Maben were March 29, 2013,
at Wise Funeral Home Chapel in Eupora with the Revs. Jimmy Vance and
Josh Buford officiating. Burial was in Double Springs … Read more
Clarice Ila
Trull Boykin
March 12, 2013
Services for Clarice Ila Trull Boykin, 93, were March 14, 2013, at
Welch Funeral Home in Starkville with the Rev. Randall Poss
officiating. Burial was in Adaton United Methodist Church Cemetery.
Born June … Read more
Aubrey Lamar Hood
Feb. 21, 2013
Services with full military honors for Aubrey Lamar Hood, 75, of
Goose Creek, S.C., were Feb . 24, 2013, at Carolina Memorial Funeral
Home in North Charleston, S.C., with the Rev. Jeff Price officiating.… Read more
Ruby Faye Dean
Feb. 23, 2013
Services for Ruby Faye Dean, 72, of Eupora were Feb. 25, 2013, at
Coleman Funeral Home in Ackerman with the Revs. Michael Mann and Coy
Fulgham officiating. Burial was in Mt. Pisgah Cemetery.
She … Read more
William Pat Gibson Feb. 4, 2013 Services for William Pat Gibson, 50, of Studio City, Calif., were Feb. 16, 2013, at Mantee Baptist Church with the Rev. William Carpenter officiating. Burial was in Mt. Pleasant Cemetery.
He was born July … Read more
Weather forecast by WP Wunderground & Denver Snow Service


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A classic cut off the Geto Boys' 1991 We Can't Be Stopped LP, Mind Playing Tricks On Me gets a high-rolling makeover on Settle 4 Le$' similarly-titled Booth debut, Mind Playin Tricks. Here, DJ Mr. Rogers (the beatsmith behind Gerald Walker's recently-released Um, Excuse Me video) serves up a tweaked version of John Okuribido's original boardwork to back the headliner and fellow Houston natives Slim Thug and Killa Kyleon as they paint a paranoid, yet luxurious lyrical picture of the paper chase. For more, check out Le$' Les$ Is More street album, released today and available now for digital download.
Le$Killa KyleonSlim Thug Downloads
Written by richard on 04/23/12
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First DJ Booth Appearance:
"Houston Astro (Remix)" (2012)
Total DJ Booth Features:
5 Songs
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