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1

Profiling of apoptosis genes identifies distinct types of primary cutaneous large B cell lymphoma  

Microsoft Academic Search

Two distinct primary cutaneous large B cell lymphomas are recognized: primary cutaneous follicle centre lymphoma (PCFCL), characterized by an excellent prognosis, and primary cutaneous large B cell lymphoma, leg-type (PCLBCL leg-type), with an unfavourable prognosis. To determine whether inhibition of the apoptosis pathways may underlie the difference in clinical outcome between PCFCL and PCLBCL leg-type, we investigated the expression of

J. C. van Galen; J. J. Hoefnagel; M. H. Vermeer; R. Willemze; R. Dijkman; C. P. Tensen; WPH de Boer; C. J. W. Meijer; J. J. Oudejans

2008-01-01

2

DNA affinity labeling of adenovirus type 2 upstream promoter sequence-binding factors identifies two distinct proteins  

SciTech Connect

A rapid affinity labeling procedure with enhanced specificity was developed to identify DNA-binding proteins. /sup 32/P was first introduced at unique phosphodiester bonds within the DNA recognition sequence. UV light-dependent cross-linking of pyrimidines to amino acid residues in direct contact at the binding site, followed by micrococcal nuclease digestion, resulted in the transfer of /sup 32/P to only those specific protein(s) which recognized the binding sequence. This method was applied to the detection and characterization of proteins that bound to the upstream promoter sequence (-50 to -66) of the human adenovirus type 2 major late promoter. We detected two distinct proteins with molecular weights of 45,000 and 116,000 that interacted with this promoter element. The two proteins differed significantly in their chromatographic and cross-linking behaviors.

Safer, B.; Cohen, R.B.; Garfinkel, S.; Thompson, J.A.

1988-01-01

3

High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children  

Microsoft Academic Search

BACKGROUND: Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. METHODS: We recently defined the population structure of S. Typhi, using new sequencing technologies to identify

Kathryn E Holt; Stephen Baker; Sabina Dongol; Buddha Basnyat; Neelam Adhikari; Stephen Thorson; Anoop S Pulickal; Yajun Song; Julian Parkhill; Jeremy J Farrar; David R Murdoch; Dominic F Kelly; Andrew J Pollard; Gordon Dougan

2010-01-01

4

Gene Expression Profiling of Liposarcoma Identifies Distinct Biological Types\\/Subtypes and Potential Therapeutic Targets in Well-Differentiated and Dedifferentiated Liposarcoma  

Microsoft Academic Search

Classification of liposarcoma into three biological types encompassing five subtypes, (a) well-differentiated\\/dediffer- entiated, (b) myxoid\\/round cell, and (c) pleomorphic, based on morphologic features and cytogenetic aberrations, is widely accepted. However, diagnostic discordance remains even among expert sarcoma pathologists. We sought to develop a more systematic approach to liposarcoma classification based on gene expression analysis and to identify subtype-specific differentially expressed

Nicholas D. Socci; Grazia Ambrosini; Elliot Sambol; Penelope Decarolis; Yuhsin Wu; Rachael O'Connor; Robert Maki; Chris Sander; Gary K. Schwartz; Cristina R. Antonescu

2007-01-01

5

Stability in controlling viral replication identifies long-term nonprogressors as a distinct subgroup among human immunodeficiency virus type 1-infected persons.  

PubMed Central

Long-term nonprogressors (LTNPs) of human immunodeficiency virus type 1 (HIV-1) infection are characterized by low levels of HIV-1 replication and viral load. However, it has not been established whether they differ in this regard from progressors from the very early stage of infection. By studying peripheral blood mononuclear cell (PBMC) specimens from a longitudinally monitored cohort of HIV-1-infected men, we found that HIV-1 proviral copy numbers and HIV-1 mRNA expression levels as low or lower than those seen in seven carefully selected LTNPs were commonly observed in specimens collected soon after seroconversion from 28 subjects who became infected while under observation. However, only the LTNPs were able to stably maintain such an efficient viral control over time. Because of the instability of the early control of HIV-1 replication, the predictive value of HIV-1 mRNA expression in PBMCs at postseroconversion was found to be limited but significantly increased during the first year of infection. Besides their diagnostic implications, these data support the idea that LTNPs may be a pathophysiologically distinct subgroup among persons infected with HIV-1.

Vesanen, M; Stevens, C E; Taylor, P E; Rubinstein, P; Saksela, K

1996-01-01

6

ADHD Combined Type and ADHD Predominantly Inattentive Type Are Distinct and Unrelated Disorders  

Microsoft Academic Search

We comprehensively reviewed research assessing differences in attention-deficit hyperactivity disorder (ADHD) subtypes to examine the possibility that ADHD\\/ combined type (ADHD\\/Q and ADHD\\/predominantly inattentive type (ADHD\\/I) are distinct and unrelated disorders. Differences among subtypes were examined along dimensions identified as being important in documenting the distinctiveness of two disorders. These include essential and associated features, demographics, measures of cognitive and

Richard Milich; Amy C. Balentine; Donald R. Lynam

2001-01-01

7

Propionibacterium acnes Types I and II Represent Phylogenetically Distinct Groups  

PubMed Central

Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported. Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P. acnes isolates. Analysis of isolates from failed prosthetic hip implants (n = 40) revealed approximately equal numbers of type I and II organisms. Isolates from failed prosthetic hip-associated bone (n = 6) and tissue (n = 38) samples, as well as isolates from acne (n = 22), dental infections (n = 8), and skin removed during surgical incision (n = 18) were predominately of type I. A total of 11 (8%) isolates showed atypical MAb labeling and could not be conclusively identified. Phylogenetic analysis of P. acnes by nucleotide sequencing revealed the 16S rRNA gene to be highly conserved between types I and II. In contrast, sequence analysis of recA and a putative hemolysin gene (tly) revealed significantly greater type-specific polymorphisms that corresponded to phylogenetically distinct cluster groups. All 11 isolates with atypical MAb labeling were identified as type I by sequencing. Within the recA and tly phylogenetic trees, nine of these isolates formed a cluster distinct from other type I organisms, suggesting a further phylogenetic subdivision within type I. Our study therefore demonstrates that the phenotypic differences between P. acnes types I and II reflect deeper differences in their phylogeny. Furthermore, nucleotide sequencing provides an accurate method for identifying the type status of P. acnes isolates.

McDowell, Andrew; Valanne, Susanna; Ramage, Gordon; Tunney, Michael M.; Glenn, Josephine V.; McLorinan, Gregory C.; Bhatia, Ajay; Maisonneuve, Jean-Francois; Lodes, Michael; Persing, David H.; Patrick, Sheila

2005-01-01

8

Evidence for distinct types of ``perfect pitch.''  

Microsoft Academic Search

The ability to identify and reproduce sounds of specific frequencies, typically called ``perfect pitch,'' is remarkable and uncommon. Whether this skill is learned early in life or inherited has been a matter of great controversy. Further, a substantial literature suggests that ``perfect pitch'' may be heterogeneous. Previously, we proposed a model to account for heterogeneity. The model subdivides individuals capable

David A. Ross; John C. Gore; Lawrence E. Marks

2003-01-01

9

Characterization of Distinct Immunophenotypes across Pediatric Brain Tumor Types.  

PubMed

Despite increasing evidence that antitumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors' microenvironment has not been defined. To address this, the current study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common pediatric brain tumor types. The initial study cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5 glioblastoma (GBM), 6 medulloblastoma (MED), and 5 nontumor brain (NT) control samples obtained from epilepsy surgery. Immune cell types analyzed included both myeloid and T cell lineages and respective markers of activated or suppressed functional phenotypes. Immune parameters that distinguished each of the tumor types were identified. PA and EPN demonstrated significantly higher infiltrating myeloid and lymphoid cells compared with GBM, MED, or NT. Additionally, PA and EPN conveyed a comparatively activated/classically activated myeloid cell-skewed functional phenotype denoted in particular by HLA-DR and CD64 expression. In contrast, GBM and MED contained progressively fewer infiltrating leukocytes and more muted functional phenotypes similar to that of NT. These findings were recapitulated using whole tumor expression of corresponding immune marker genes in a large gene expression microarray cohort of pediatric brain tumors. The results of this cross-tumor comparative analysis demonstrate that different pediatric brain tumor types exhibit distinct immunophenotypes, implying that specific immunotherapeutic approaches may be most effective for each tumor type. PMID:24078694

Griesinger, Andrea M; Birks, Diane K; Donson, Andrew M; Amani, Vladimir; Hoffman, Lindsey M; Waziri, Allen; Wang, Michael; Handler, Michael H; Foreman, Nicholas K

2013-09-27

10

Principal Component Analysis of Dynamically distinct D-Type Asteroids  

Microsoft Academic Search

Principal Component Analysis (PCA), a common statistically based classification technique, has been used to classify asteroids into broad spectral categories. In some cases, a spectral superclass considered in isolation may undergo sub-classification (e.g. S-type subclasses). Since D-type asteroids populate at least three distinct dynamical regions in the asteroid belt -- namely Hilda, L4 Trojans and L5 Trojans, and since the

Sanja Nedic; J. Ziffer; H. Campins; Y. R. Fernandez; M. Walker

2008-01-01

11

Identifying Clinically Distinct Subgroups of Self-Injurers among Young Adults: A Latent Class Analysis  

ERIC Educational Resources Information Center

|High rates of nonsuicidal self-injury (NSSI; 14%-17%) in adolescents and young adults suggest that some self-injurers may exhibit more or different psychiatric problems than others. In the present study, the authors utilized a latent class analysis to identify clinically distinct subgroups of self-injurers. Participants were 205 young adults with…

Klonsky, E. David; Olino, Thomas M.

2008-01-01

12

Identifying Clinically Distinct Subgroups of Self-Injurers Among Young Adults: A Latent Class Analysis  

Microsoft Academic Search

High rates of nonsuicidal self-injury (NSSI; 14%–17%) in adolescents and young adults suggest that some self-injurers may exhibit more or different psychiatric problems than others. In the present study, the authors utilized a latent class analysis to identify clinically distinct subgroups of self-injurers. Participants were 205 young adults with a history of 1 or more NSSI behaviors. Latent classes were

E. David Klonsky; Thomas M. Olino

2008-01-01

13

A Framework for Identifying Distinct Multipollutant Profiles in Air Pollution Data  

PubMed Central

BACKGROUND The importance of describing, understanding and regulating multi-pollutant mixtures has been highlighted by the US National Academy of Science and the Environmental Protection Agency. Furthering our understanding of the health effects associated with exposure to mixtures of pollutants will lead to the development of new multi-pollutant National Air Quality Standards. OBJECTIVES Introduce a framework within which diagnostic methods that are based on our understanding of air pollution mixtures are used to validate the distinct air pollutant mixtures identified using cluster analysis. METHODS: S ix years of daily gaseous and particulate air pollution data collected in Boston, MA were classified solely on their concentration profiles. Classification was performed using k-means partitioning and hierarchical clustering. Diagnostic strategies were developed to identify the most optimal clustering. RESULTS The optimal solution used k-means analysis and contained five distinct groups of days. Pollutant concentrations and elemental ratios were computed in order to characterize the differences between clusters. Time-series regression confirmed that the groups differed in their chemical compositions. The mean values of meteorological parameters were estimated for each group and air mass origin between clusters was examined using back-trajectory analysis. This allowed us to link the distinct physico-chemical characteristics of each cluster to characteristic weather patterns and show that different clusters were associated with distinct air mass origins. CONCLUSIONS This analysis yielded a solution that was robust to outlier points and interpretable based on chemical, physical and meteorological characteristics. This novel method provides an exciting tool with which to identify and further investigate multi-pollutant mixtures and link them directly to health effects studies.

Austin, Elena; Coull, Brent; Thomas, Dylan; Koutrakis, Petros

2013-01-01

14

Whole-genome screening identifies proteins localized to distinct nuclear bodies.  

PubMed

The nucleus is a unique organelle that contains essential genetic materials in chromosome territories. The interchromatin space is composed of nuclear subcompartments, which are defined by several distinctive nuclear bodies believed to be factories of DNA or RNA processing and sites of transcriptional and/or posttranscriptional regulation. In this paper, we performed a genome-wide microscopy-based screening for proteins that form nuclear foci and characterized their localizations using markers of known nuclear bodies. In total, we identified 325 proteins localized to distinct nuclear bodies, including nucleoli (148), promyelocytic leukemia nuclear bodies (38), nuclear speckles (27), paraspeckles (24), Cajal bodies (17), Sam68 nuclear bodies (5), Polycomb bodies (2), and uncharacterized nuclear bodies (64). Functional validation revealed several proteins potentially involved in the assembly of Cajal bodies and paraspeckles. Together, these data establish the first atlas of human proteins in different nuclear bodies and provide key information for research on nuclear bodies. PMID:24127217

Fong, Ka-Wing; Li, Yujing; Wang, Wenqi; Ma, Wenbin; Li, Kunpeng; Qi, Robert Z; Liu, Dan; Songyang, Zhou; Chen, Junjie

2013-10-14

15

DNA Methylome of Familial Breast Cancer Identifies Distinct Profiles Defined by Mutation Status  

PubMed Central

It is now understood that epigenetic alterations occur frequently in sporadic breast carcinogenesis, but little is known about the epigenetic alterations associated with familial breast tumors. We performed genome-wide DNA-methylation profiling on familial breast cancers (n = 33) to identify patterns of methylation specific to the different mutation groups (BRCA1, BRCA2, and BRCAx) or intrinsic subtypes of breast cancer (basal, luminal A, luminal B, HER2-amplified, and normal-like). We used methylated DNA immunoprecipitation (MeDIP) on Affymetrix promoter chips to interrogate methylation profiles across 25,500 distinct transcripts. Using a support vector machine classification algorithm, we demonstrated that genome-wide methylation profiles predicted tumor mutation status with estimated error rates of 19% (BRCA1), 31% (BRCA2), and 36% (BRCAx) but did not accurately predict the intrinsic subtypes defined by gene expression. Furthermore, using unsupervised hierarchical clustering, we identified a distinct subgroup of BRCAx tumors defined by methylation profiles. We validated these findings in the 33 tumors in the test set, as well as in an independent validation set of 47 formalin-fixed, paraffin-embedded familial breast tumors, by pyrosequencing and Epityper. Finally, gene-expression profiling and SNP CGH array previously performed on the same samples allowed full integration of methylation, gene-expression, and copy-number data sets, revealing frequent hypermethylation of genes that also displayed loss of heterozygosity, as well as of genes that show copy-number gains, providing a potential mechanism for expression dosage compensation. Together, these data show that methylation profiles for familial breast cancers are defined by the mutation status and are distinct from the intrinsic subtypes.

Flanagan, James M.; Cocciardi, Sibylle; Waddell, Nic; Johnstone, Cameron N.; Marsh, Anna; Henderson, Stephen; Simpson, Peter; da Silva, Leonard; Khanna, Kumkum; Lakhani, Sunil; Boshoff, Chris; Chenevix-Trench, Georgia

2010-01-01

16

TLR4 and TLR5 induce distinct types of vasculitis  

PubMed Central

Large vessel vasculitides, such as Takayasu arteritis and giant cell arteritis (GCA), affect vital arteries and cause clinical complications by either luminal occlusion or vessel wall destruction. Inflammatory infiltrates, often with granulomatous arrangements, are distributed as a panarteritis throughout all of the artery’s wall layers or cluster in the adventitia as a perivasculitis. Factors determining the architecture and compartmentalization of vasculitis are unknown. Human macrovessels are populated by indigenous dendritic cells (DC) positioned in the adventitia. Herein, we report that these vascular DC sense bacterial pathogens and regulate the patterning of the emerging arteritis. In human temporal artery-SCID chimeras, lipopolysaccharides stimulating Toll-like receptor (TLR) 4 and flagellin stimulating TLR5 trigger vascular DC and induce T-cell recruitment and activation. However, the architecture of the evolving inflammation is ligand specific; TLR4 ligands cause transmural panarteritis and TLR5 ligands promote adventitial perivasculitis. Underlying mechanisms involve selective recruitment of functional T cell subsets. Specifically, TLR4-mediated DC stimulation markedly enhances production of the chemokine CCL20, biasing recruitment towards CCL20-responsive CCR6+ T cells. In adoptive transfer experiments,CCR6+ T cells produce an arteritis pattern with media-invasive T cells damaging vascular smooth muscle cells. Also, CCR6+ T cells dominate the vasculitic infiltrates in patients with panarteritic GCA. Thus, depending on the original danger signal, vascular DC edit the emerging immune response by differentially recruiting specialized T effector cells and direct the disease process toward distinct types of vasculitis.

Deng, Jiusheng; Ma-Krupa, Wei; Gewirtz, Andrew T.; Younge, Brian R.; Goronzy, Jorg J.; Weyand, Cornelia M.

2009-01-01

17

Novel and Distinct Metabolites Identified Following a Single Oral Dose of ?- or ?-Hexabromocyclododecane in Mice  

PubMed Central

The metabolism of ?- and ?-hexabromocyclododecane (HBCD) was investigated in adult C57BL/6 female mice. ?- or ?-[14C]HBCD (3 mg/kg bw) was orally administered with subsequent urine and feces collection for 4 consecutive days; a separate group of mice were dosed and sacrificed 3 hours post-exposure to investigate tissue metabolite levels. Extractable and non-extractable HBCD metabolites were quantitated in liver, blood, fat, brain, bile, urine and feces and characterized by LC/MS (ESI-). Metabolites identified were distinct between the two stereoisomers. In mice exposed to ?-HBCD, four hydroxylated metabolites were detected in fecal extracts, and one of these metabolite isomers was consistently characterized in liver, brain, and adipose tissue extracts. In contrast, mice exposed to ?-HBCD contained multiple isomers of monohydroxy-pentabromocyclododecene, dihydroxy-pentabromocyclododecene, and dihydroxy-pentabromocyclododecadiene in the feces while only a single monohydroxy-pentabromocyclododecane metabolite was measured in liver and adipose tissue. Both stereoisomers were transformed to metabolites which formed covalent bonds to proteins and/or lipids in the gut as evidenced by high fecal non-extractables. Although the potential toxicity of these free and bound metabolites remains to be determined, the presence of distinct metabolic products from the two main HBCD stereoisomers should allow biomarkers to be selected that may aid in characterizing sources of HBCD exposure.

Szabo, David T.; Huwe, Janice; Diliberto, Janet; Birnbaum, Linda S.

2013-01-01

18

OFF bipolar cells express distinct types of dendritic glutamate receptors in the mouse retina.  

PubMed

Parallel representations of the visual world are already established at the very first synapse of the visual system. Cone photoreceptors, which hyperpolarize in response to light, forward the visual signal onto distinct types of ON and OFF cone bipolar cells (BCs). In the case of OFF BCs, the glutamatergic cone input is integrated by ionotropic glutamate receptors, giving rise to a sign-preserving mode of synaptic transmission. The combination of glutamate receptor (GluR) subunits, i.e. AMPA or kainate subunits, importantly contributes to shaping the OFF bipolar cells' distinct response properties. The mouse is one of the few mammals in which the (most likely) complete set of (five) retinal OFF BC types is identified. However, it is not clear which GluR subtypes are expressed by the different mouse OFF BC types. We addressed this question by combining immunolabeling, electrical whole-cell recordings and pharmacology, and present evidence that the different types of OFF BCs express distinct types of glutamate receptors: Type 1 BCs exclusively expressed AMPA receptors, whereas type 2 and type 3a BCs expressed kainate receptors of different subunit compositions. Additionally, we found that two OFF BC types (3b and 4) very likely express both AMPA and kainate receptors but, interestingly, the two receptor subunits were not co-localized at the same dendritic site. The complex, BC type-specific expression pattern of GluRs we describe here supports their essential role in establishing parallel pathways at the first synapse of the mouse visual system. PMID:23567811

Puller, C; Ivanova, E; Euler, T; Haverkamp, S; Schubert, T

2013-04-06

19

Automated image analysis identifies signaling pathways regulating distinct signatures of cardiac myocyte hypertrophy  

PubMed Central

Cardiac hypertrophy is controlled by a complex signal transduction and gene regulatory network, containing multiple layers of crosstalk and feedback. While numerous individual components of this network have been identified, understanding how these elements are coordinated to regulate heart growth remains a challenge. Past approaches to measure cardiac myocyte hypertrophy have been manual and often qualitative, hindering the ability to systematically characterize the network's higher-order control structure and identify therapeutic targets. Here, we develop and validate an automated image analysis approach for objectively quantifying multiple hypertrophic phenotypes from immunofluorescence images. This approach incorporates cardiac myocyte-specific optimizations and provides quantitative measures of myocyte size, elongation, circularity, sarcomeric organization, and cell-cell contact. As a proof-of-concept, we examined the hypertrophic response to ?-adrenergic, ?-adrenergic, tumor necrosis factor (TNF?), insulin-like growth factor-1 (IGF-1), and fetal bovine serum pathways. While all five hypertrophic pathways increased myocyte size, other hypertrophic metrics were differentially regulated, forming a distinct phenotype signature for each pathway. Sarcomeric organization was uniquely enhanced by ?-adrenergic signaling. TNF? and ?-adrenergic pathways markedly decreased cell circularity due to increased myocyte protrusion. Surprisingly, adrenergic and IGF-1 pathways differentially regulated myocyte-myocyte contact, potentially forming a feed-forward loop that regulates hypertrophy. Automated image analysis unlocks a range of new quantitative phenotypic data, aiding dissection of the complex hypertrophic signaling network and enabling myocyte-based high-content drug screening.

Bass, Gregory T.; Ryall, Karen A.; Katikapalli, Ashwin; Taylor, Brooks E.; Dang, Stephen T.; Acton, Scott T.; Saucerman, Jeffrey J.

2011-01-01

20

Distinct subtypes of cholecystokinin (CCK)-containing interneurons of the basolateral amygdala identified using a CCK promoter-specific lentivirus.  

PubMed

The basolateral amygdala (BLA) is critical for the formation of emotional memories. Little is known about the physiological properties of BLA interneurons, which can be divided into four subtypes based on their immunocytochemical profiles. Cholecystokinin (CCK) interneurons play critical roles in feedforward inhibition and behavioral fear responses. Evidence suggests that interneurons within a subgroup can display heterogeneous physiological properties. However, little is known about the physiological properties of CCK interneurons in the BLA and/or whether they represent a homogeneous or heterogeneous population. To address this question, we generated a lentivirus-expressing GFP under the control of the CCK promoter to identify CCK neurons in vivo. We combined this with whole cell patch-clamp recording techniques to examine the physiological properties of CCK-containing interneurons of the rat BLA. Here, we describe the physiological properties of 57 cells recorded in current-clamp mode; we used hierarchical cluster and discriminant function analysis to demonstrate that CCK interneurons can be segregated into three distinct subtypes (I, II, III) based on their passive and active membrane properties. Additionally, Type II neurons could be further separated into adapting and nonadapting types based on their rates of spike frequency adaptation. These data suggest that CCK interneurons of the BLA are a heterogeneous population and may be functionally distinct subpopulations that differentially contribute to the processing of emotionally salient stimuli. PMID:19164102

Jasnow, Aaron M; Ressler, Kerry J; Hammack, Sayamwong E; Chhatwal, Jasmeer P; Rainnie, Donald G

2009-01-21

21

Distinct Subtypes of Cholecystokinin (CCK)-Containing Interneurons of the Basolateral Amygdala Identified Using a CCK Promoter-Specific Lentivirus  

PubMed Central

The basolateral amygdala (BLA) is critical for the formation of emotional memories. Little is known about the physiological properties of BLA interneurons, which can be divided into four subtypes based on their immunocytochemical profiles. Cholecystokinin (CCK) interneurons play critical roles in feedforward inhibition and behavioral fear responses. Evidence suggests that interneurons within a subgroup can display heterogeneous physiological properties. However, little is known about the physiological properties of CCK interneurons in the BLA and/or whether they represent a homogeneous or heterogeneous population. To address this question, we generated a lentivirus-expressing GFP under the control of the CCK promoter to identify CCK neurons in vivo. We combined this with whole cell patch-clamp recording techniques to examine the physiological properties of CCK-containing interneurons of the rat BLA. Here, we describe the physiological properties of 57 cells recorded in current-clamp mode; we used hierarchical cluster and discriminant function analysis to demonstrate that CCK interneurons can be segregated into three distinct subtypes (I, II, III) based on their passive and active membrane properties. Additionally, Type II neurons could be further separated into adapting and nonadapting types based on their rates of spike frequency adaptation. These data suggest that CCK interneurons of the BLA are a heterogeneous population and may be functionally distinct subpopulations that differentially contribute to the processing of emotionally salient stimuli.

Jasnow, Aaron M.; Ressler, Kerry J.; Hammack, Sayamwong E.; Chhatwal, Jasmeer P.; Rainnie, Donald G.

2009-01-01

22

Distinct Stability States of Disease-Associated Human Prion Protein Identified by Conformation-Dependent Immunoassay?  

PubMed Central

The phenotypic and strain-related properties of human prion diseases are, according to the prion hypothesis, proposed to reside in the physicochemical properties of the conformationally altered, disease-associated isoform of the prion protein (PrPSc), which accumulates in the brains of patients suffering from Creutzfeldt-Jakob disease and related conditions, such as Gerstmann-Straussler-Scheinker disease. Molecular strain typing of human prion diseases has focused extensively on differences in the fragment size and glycosylation site occupancy of the protease-resistant prion protein (PrPres) in conjunction with the presence of mutations and polymorphisms in the prion protein gene (PRNP). Here we report the results of employing an alternative strategy that specifically addresses the conformational stability of PrPSc and that has been used previously to characterize animal prion strains transmitted to rodents. The results show that there are at least two distinct conformation stability states in human prion diseases, neither of which appears to correlate fully with the PrPres type, as judged by fragment size or glycosylation, the PRNP codon 129 status, or the presence or absence of mutations in PRNP. These results suggest that conformational stability represents a further dimension to a complete description of potentially phenotype-related properties of PrPSc in human prion diseases.

Choi, Young Pyo; Peden, Alexander H.; Groner, Albrecht; Ironside, James W.; Head, Mark W.

2010-01-01

23

Coronal type II bursts and interplanetary type II bursts: Distinct shock drivers  

NASA Astrophysics Data System (ADS)

We study solar radio type II bursts combining with Wind/WAVES type II bursts and coronal mass ejections (CMEs). The aim of the present work is to investigate the effectiveness of shocks to cause type II bursts in the solar corona and the interplanetary space. We consider the following findings. The distribution of the cessation heights of type II emission is confined to a rather narrow range of height than the distribution of the heights of start frequencies. This is suggestive of the presence of a gradient for the Alfvén speed from the heliocentric height of ˜1.4 solar radii. The range of the kinetic energy of CMEs associated with coronal type II emission taken together with the suggested computation method and the Alfvén speed gradient, indicates the limit to the height up to which type II emission could be expected. This height is ˜2 solar radii from the center of the Sun. Further, the large time gap between the cessation time and heights of coronal type II emission and the commencement time and heights of most of the IP type II bursts do not account for the difference between the two heights and the average shock speed. Also, there is clear difference in the magnitude of the kinetic energies and the distinct characteristics of the CMEs associated with coronal and IP type II bursts. Hence, we suggest that in most instances the coronal type II bursts and IP type II bursts occur due to distinct shocks. We also address the question of the origin of type II bursts and discuss the possible explanation of observed results.

Suryanarayana, G. S.

2012-02-01

24

A Focused Small-Molecule Screen Identifies 14 Compounds with Distinct Effects on Toxoplasma gondii  

PubMed Central

Toxoplasma gondii is a globally ubiquitous pathogen that can cause severe disease in immunocompromised humans and the developing fetus. Given the proven role of Toxoplasma-secreted kinases in the interaction of Toxoplasma with its host cell, identification of novel kinase inhibitors could precipitate the development of new anti-Toxoplasma drugs and define new pathways important for parasite survival. We selected a small (n = 527) but diverse set of putative kinase inhibitors and screened them for effects on the growth of Toxoplasma in vitro. We identified and validated 14 noncytotoxic compounds, all of which had 50% effective concentrations in the nanomolar to micromolar range. We further characterized eight of these compounds, four inhibitors and four enhancers, by determining their effects on parasite motility, invasion, and the likely cellular target (parasite or host cell). Only two compounds had an effect on parasite motility and invasion. All the inhibitors appeared to target the parasite, and interestingly, two of the enhancers appeared to rather target the host cell, suggesting modulation of host cell pathways beneficial for parasite growth. For the four inhibitors, we also tested their efficacy in a mouse model, where one compound proved potent. Overall, these 14 compounds represent a new and diverse set of small molecules that are likely targeting distinct parasite and host cell pathways. Future work will aim to characterize their molecular targets in both the host and parasite.

Kamau, Edwin T.; Srinivasan, Ananth R.; Brown, Mark J.; Fair, Matthew G.; Caraher, Erin J.

2012-01-01

25

Propionibacterium acnes Types I and II Represent Phylogenetically Distinct Groups  

Microsoft Academic Search

Although two phenotypes of the opportunistic pathogen Propionibacterium acnes (types I and II) have been described, epidemiological investigations of their roles in different infections have not been widely reported. Using immunofluorescence microscopy with monoclonal antibodies (MAbs) QUBPa1 and QUBPa2, specific for types I and II, respectively, we investigated the prevalences of the two types among 132 P. acnes isolates. Analysis

Andrew McDowell; Susanna Valanne; Gordon Ramage; Michael M. Tunney; Josephine V. Glenn; Gregory C. McLorinan; Ajay Bhatia; Jean-Francois Maisonneuve; Michael Lodes; David H. Persing; Sheila Patrick

2005-01-01

26

Cluster analysis of the national weight control registry to identify distinct subgroups maintaining successful weight loss.  

PubMed

The National Weight Control Registry (NWCR) is the largest ongoing study of individuals successful at maintaining weight loss; the registry enrolls individuals maintaining a weight loss of at least 13.6 kg (30 lb) for a minimum of 1 year. The current report uses multivariate latent class cluster analysis to identify unique clusters of individuals within the NWCR that have distinct experiences, strategies, and attitudes with respect to weight loss and weight loss maintenance. The cluster analysis considers weight and health history, weight control behaviors and strategies, effort and satisfaction with maintaining weight, and psychological and demographic characteristics. The analysis includes 2,228 participants enrolled between 1998 and 2002. Cluster 1 (50.5%) represents a weight-stable, healthy, exercise conscious group who are very satisfied with their current weight. Cluster 2 (26.9%) has continuously struggled with weight since childhood; they rely on the greatest number of resources and strategies to lose and maintain weight, and report higher levels of stress and depression. Cluster 3 (12.7%) represents a group successful at weight reduction on the first attempt; they were least likely to be overweight as children, are maintaining the longest duration of weight loss, and report the least difficulty maintaining weight. Cluster 4 (9.9%) represents a group less likely to use exercise to control weight; they tend to be older, eat fewer meals, and report more health problems. Further exploration of the unique characteristics of these clusters could be useful for tailoring future weight loss and weight maintenance programs to the specific characteristics of an individual. PMID:22469954

Ogden, Lorraine G; Stroebele, Nanette; Wyatt, Holly R; Catenacci, Victoria A; Peters, John C; Stuht, Jennifer; Wing, Rena R; Hill, James O

2012-04-03

27

Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages  

PubMed Central

Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4+ CCR5+ cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.

Peters, Paul J.; Bhattacharya, Jayanta; Hibbitts, Samantha; Dittmar, Matthias T.; Simmons, Graham; Bell, Jeanne; Simmonds, Peter; Clapham, Paul R.

2004-01-01

28

Dome-Type: A Distinctive Variant of Colonic Adenocarcinoma  

PubMed Central

Introduction. Ten cases of dome-type adenocarcinoma of the colon have been reported so far. Most of them were presented as early lesions, with endoscopic and microscopic distinguishing features. Methods and Results. A raised plaque was removed from the right colon during colonoscopy in a 56-year-old man. Histopathological examination showed a cancerized adenoma invading the submucosa with several typical features of dome-type adenocarcinoma, in particular the associated prominent lymphoid tissue. Immunohistochemistry showed retention of the mismatch repair proteins MLH-1, MSH-2, MLH-6, and PMS-2. Conclusion. We report an additional case of dome-type adenocarcinoma of the colon as an early, low-risk, and microsatellite stable tumor, indicating that this particular histotype may deserve specific consideration for both classification and management.

Puppa, Giacomo; Molaro, Mariella

2012-01-01

29

Functional cell types in taste buds have distinct longevities.  

PubMed

Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU) to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor) taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic) taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells. PMID:23320081

Perea-Martinez, Isabel; Nagai, Takatoshi; Chaudhari, Nirupa

2013-01-08

30

Functional Cell Types in Taste Buds Have Distinct Longevities  

PubMed Central

Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8–12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2?-deoxyuridine (EdU) to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor) taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic) taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

Perea-Martinez, Isabel; Nagai, Takatoshi; Chaudhari, Nirupa

2013-01-01

31

Single-Cell Quantitative HER2 Measurement Identifies Heterogeneity and Distinct Subgroups within Traditionally Defined HER2-Positive Patients.  

PubMed

Human epidermal growth factor receptor 2 (HER2) is an important biomarker for breast and gastric cancer prognosis and patient treatment decisions. HER2 positivity, as defined by IHC or fluorescent in situ hybridization testing, remains an imprecise predictor of patient response to HER2-targeted therapies. Challenges to correct HER2 assessment and patient stratification include intratumoral heterogeneity, lack of quantitative and/or objective assays, and differences between measuring HER2 amplification at the protein versus gene level. We developed a novel immunofluorescence method for quantitation of HER2 protein expression at the single-cell level on FFPE patient samples. Our assay uses automated image analysis to identify and classify tumor versus non-tumor cells, as well as quantitate the HER2 staining for each tumor cell. The HER2 staining level is converted to HER2 protein expression using a standard cell pellet array stained in parallel with the tissue sample. This approach allows assessment of HER2 expression and heterogeneity within a tissue section at the single-cell level. By using this assay, we identified distinct subgroups of HER2 heterogeneity within traditional definitions of HER2 positivity in both breast and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity may offer an opportunity to improve the identification of patients likely to respond to HER2-targeted therapies. The broad applicability of the assay was demonstrated by measuring HER2 expression profiles on multiple tumor types, and on normal and diseased heart tissues. PMID:24035511

Onsum, Matthew D; Geretti, Elena; Paragas, Violette; Kudla, Arthur J; Moulis, Sharon P; Luus, Lia; Wickham, Thomas J; McDonagh, Charlotte F; Macbeath, Gavin; Hendriks, Bart S

2013-09-11

32

Does TDP-43 type confer a distinct pattern of atrophy in frontotemporal lobar degeneration?  

PubMed Central

Objective: To determine whether TDP-43 type is associated with distinct patterns of brain atrophy on MRI in subjects with pathologically confirmed frontotemporal lobar degeneration (FTLD). Methods: In this case-control study, we identified all subjects with a pathologic diagnosis of FTLD with TDP-43 immunoreactive inclusions (FTLD-TDP) and at least one volumetric head MRI scan (n = 42). In each case we applied published criteria for subclassification of FTLD-TDP into FTLD-TDP types 1-3. Voxel-based morphometry was used to compare subjects with each of the different FTLD-TDP types to age- and gender-matched normal controls (n = 30). We also assessed different pathologic and genetic variants within, and across, the different types. Results: Twenty-two subjects were classified as FTLD-TDP type 1, 9 as type 2, and 11 as type 3. We identified different patterns of atrophy across the types with type 1 showing frontotemporal and parietal atrophy, type 2 predominantly anterior temporal lobe atrophy, and type 3 predominantly posterior frontal atrophy. Within the FTLD-TDP type 1 group, those with a progranulin mutation had significantly more lateral temporal lobe atrophy than those without. All type 2 subjects were diagnosed with semantic dementia. Subjects with a pathologic diagnosis of FTLD with motor neuron degeneration had a similar pattern of atrophy, regardless of whether they were type 1 or type 3. Conclusions: Although there are different patterns of atrophy across the different FTLD-TDP types, it appears that genetic and pathologic factors may also affect the patterns of atrophy. GLOSSARY AD = Alzheimer disease; ADRC = Alzheimer's Disease Research Center; bvFTD = behavioral variant frontotemporal dementia; CBS = corticobasal syndrome; CDR-SB = Clinical Dementia Rating scale sum of boxes; FTLD = frontotemporal lobar degeneration; FTLD-MND = frontotemporal lobar degeneration with motor neuron degeneration; FTLD-TDP = frontotemporal lobar degeneration with TDP-43 immunoreactive inclusions; MMSE = Mini-Mental State Examination; NCI = neuronal cytoplasmic inclusion; PNFA = progressive nonfluent aphasia; SMD = semantic dementia; STMS = Short Test of Mental Status; VBM = voxel-based morphometry.

Whitwell, J.L.; Jack, C.R.; Parisi, J.E.; Senjem, M.L.; Knopman, D.S.; Boeve, B.F.; Rademakers, R.; Baker, M.; Petersen, R.C.; Dickson, D.W.; Josephs, K.A.

2010-01-01

33

Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells  

Microsoft Academic Search

Distinct structural forms of type I collagen modulate cell cycle regulatory proteins in mesangial cells.BackgroundExtracellular matrix molecules profoundly regulate cell behavior, including proliferation. In glomerulonephritis, type I collagen accumulates in the mesangium and is constantly structurally modified and degraded during the course of the disease.MethodsWe studied how two structurally distinct forms of type I collagen, monomer versus polymerized fibrils, affect

Harald O Schöcklmann; Stefan Lang; Martina Kralewski; Andrea Hartner; Andrea Lüdke; R Bernd Sterzel

2000-01-01

34

Familial colorectal cancer type X syndrome: two distinct molecular entities?  

PubMed

In a fraction of families fulfilling the Amsterdam criteria for hereditary non-polyposis colorectal cancer, colorectal cancers are microsatellite stable and DNA mismatch repair gene (MMR) mutations are not found. These families were designated as familial colorectal cancer type X (FCCTX). We aimed to characterise a group of FCCTX families defined by the Amsterdam criteria and MSS tumours at clinical and molecular level. Twenty-four tumours from 15 FCCTX families were analysed for loss of known tumour suppressor gene (TSG) loci (APC, TP53, SMAD4 and DCC), MGMT and MMR genes promoter methylation, and also APC and KRAS somatic mutations. FCCTX families presented specific clinical features: absence of endometrial tumours, high adenoma/carcinoma ratio (1.91) and prevalence of rectal cancers (13/27, 48%). New molecular features were found: the majority of FCCTX tumours (13/18; 72%) presented TSG loss. TSG loss positive tumours presented frequent APC and KRAS somatic mutations and MGMT methylation [10/13 (77%), 7/13 (54%) and 6/11 (54%), respectively]. In TSG loss negative tumours (5/18; 28%), the same molecular events were found in 2/5 (40%), 2/5 (40%) and 1/3 (33%) tumours, respectively. Transition mutations in KRAS were more frequent among MGMT methylated tumours than in unmethylated [5/8 (63%) vs. 1/10 (10%), P = 0.03]. Although sharing similar clinical features, at least two different molecular entities should exist among FCCTX families, one whose tumours present frequent TSG loss, APC and KRAS somatic mutations, and MGMT promoter methylation, and a second, lesser predominant, with no evidence of TSG loss and rarely presenting promoter methylation. PMID:21837511

Francisco, Inês; Albuquerque, Cristina; Lage, Pedro; Belo, Hélio; Vitoriano, Inês; Filipe, Bruno; Claro, Isabel; Ferreira, Sara; Rodrigues, Paula; Chaves, Paula; Leitão, Carlos Nobre; Pereira, António Dias

2011-12-01

35

Characterization of the Proteomes Associating with Three Distinct Membrane Raft Sub-types in Murine Sperm  

PubMed Central

Mammalian sperm are transcriptionally and translationally inactive. To meet changing needs in the epididymis and female tract, they rely heavily on post-translational modifications and protein acquisition/degradation. Membrane rafts are sterol and sphingolipid-enriched micro-domains that organize and regulate various pathways. Rafts have significance in sperm by transducing the stimulus of sterol efflux into changes in intracellular signaling that confer fertilization competence. We recently characterized 3 biochemically distinct sub-types of sperm rafts, and now present profiles for proteins targeting to and associating with these sub-types, along with a fraction largely comprised of “non-raft” domains. Proteomics analysis using a gel-based LC-MS/MS approach identified 190 strictly validated proteins in the raft sub-types. Interestingly, many of these are known to be expressed in the epididymis, where sperm membrane composition matures. To investigate potential roles for rafts in epididymal protein acquisition, we compared the expression and localization of 2 different sterol-interacting proteins, apolipoprotein-A1 and prominin-1 in sperm from different zones. We found that apolipoprotein-A1 was gradually added to the plasma membrane overlying the acrosome, whereas prominin-1 was not, suggesting different mechanisms for raft protein acquisition. Our results define raft-associating proteins, demonstrate functional similarities and differences among raft sub-types, and provide insights into raft-mediated epididymal protein acquisition.

Asano, Atsushi; Nelson, Jacquelyn L.; Zhang, Sheng; Travis, Alexander J.

2010-01-01

36

Double H-type tracheoesophageal fistulas identified and repaired in 1 operation.  

PubMed

Isolated tracheoesophageal ("H-type") fistula is a relatively uncommon congenital anomaly that can be difficult to identify and, at times, challenging to repair. We present a very unusual case of an infant with 2 distinct H-type tracheoesophageal fistulas (TEFs) identified and repaired in 1 operation. A newborn male infant presented with coughing with feeds. Contrast esophagram demonstrated an intrathoracic H-type fistula without esophageal atresia. In the operating room, rigid bronchoscopy was performed, and a second TEF was identified in the cervical region. A separate balloon catheter was placed in each fistula. The intrathoracic fistula was repaired through a thoracotomy incision, and the more proximal fistula was repaired through a cervical incision. Each repair was uncomplicated, and recovery was uneventful. Double H-type tracheoesophageal appears to be extremely rare. This case underscores the importance of searching for a second fistula by bronchoscopy before undertaking definitive repair of a TEF. PMID:23164022

Mattei, Peter

2012-11-01

37

Porcine Skin-Derived Progenitor (SKP) Spheres and Neurospheres: Distinct "Stemness" Identified by Microarray Analysis  

PubMed Central

Abstract Skin-derived progenitors (SKP) are neural crest derived and can generate neural and mesodermal progeny in vitro, corresponding to the multipotency of neural crest stem cells. Likewise, neural stem/progenitor cells (displaying as neurospheres) have the capacity of self-renewing, and can produce most phenotypes in the nervous system. Both form spheres when cultured with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Although the “stemness” of neural stem/progenitor cells has been extensively investigated, the molecular comparison of SKP spheres and neurospheres has not been elucidated. Here, SKP spheres and neurospheres from the same individual porcine fetuses were isolated with the same culture medium, and the multipotency was tested by in vitro differentiation assays. Microarray analysis was used to illustrate the “stemness” of SKP spheres and neurospheres. The upregulated genes that were in common in the SKP spheres and neurospheres are involved in ribosome, tight junction, gap junction, cell communication, calcium signaling, ErbB signaling, JAK–STAT signaling, MAPK signaling, etc. The differentially expressed genes between SKP spheres and neurospheres are mainly involved in ECM–receptor interaction and the transforming growth factor-beta (TGF-?) signaling pathway. Finally, treatment with leukemia inhibitory factor (LIF) or MEK inhibitor results in a distinctive impact on the “stemness” and differentiation genes of SKP spheres and neurospheres. Thus, the cell-intrinsic genetic program may contribute to the innate “stemness” of SKP spheres and neurospheres in a similar local microenvironment.

Zhao, Ming-Tao; Whitworth, Kristin M.; Lin, Hui; Zhang, Xia; Isom, S. Clay; Dobbs, Kyle B.; Bauer, Bethany; Zhang, Yong

2010-01-01

38

A novel split kinesin assay identifies motor proteins that interact with distinct vesicle populations  

PubMed Central

Identifying the kinesin motors that interact with different vesicle populations is a longstanding and challenging problem with implications for many aspects of cell biology. Here we introduce a new live-cell assay to assess kinesin–vesicle interactions and use it to identify kinesins that bind to vesicles undergoing dendrite-selective transport in cultured hippocampal neurons. We prepared a library of “split kinesins,” comprising an axon-selective kinesin motor domain and a series of kinesin tail domains that can attach to their native vesicles; when the split kinesins were assembled by chemical dimerization, bound vesicles were misdirected into the axon. This method provided highly specific results, showing that three Kinesin-3 family members—KIF1A, KIF13A, and KIF13B—interacted with dendritic vesicle populations. This experimental paradigm allows a systematic approach to evaluate motor–vesicle interactions in living cells.

Jenkins, Brian; Decker, Helena; Bentley, Marvin; Luisi, Julie

2012-01-01

39

Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma  

Microsoft Academic Search

Osteosarcoma is the most common primary malignant bone tumour. Currently osteosarcoma classification is based on histological\\u000a appearance. It was the aim of this study to use a more systematic approach to osteosarcoma classification based on gene expression\\u000a analysis and to identify subtype specific differentially expressed genes. We analysed the global gene expression profiles\\u000a of ten osteosarcoma samples using Affymetrix U133A

Bernd Kubista; Florian Klinglmueller; Martin Bilban; Martin Pfeiffer; Richard Lass; Alexander Giurea; Phillipp T. Funovics; Cyril Toma; Martin Dominkus; Rainer Kotz; Theresia Thalhammer; Klemens Trieb; Teresa Zettl; Christian F. Singer

2011-01-01

40

Identifying land cover variability distinct from land cover change: Cheatgrass in the Great Basin  

Microsoft Academic Search

An understanding of land use\\/land cover change at local, regional, and global scales is important in an increasingly human-dominated biosphere. Here, we report on an under-appreciated complexity in the analysis of land cover change important in arid and semi-arid environments. In these environments, some land cover types show a high degree of inter-annual variability in productivity. In this study, we

Bethany A. Bradley; John F. Mustard

2005-01-01

41

A Comparative Genome Analysis Identifies Distinct Sorting Pathways in Gram-Positive Bacteria  

Microsoft Academic Search

Surface proteins in gram-positive bacteria are frequently required for virulence, and many are attached to the cell wall by sortase enzymes. Bacteria frequently encode more than one sortase enzyme and an even larger number of potential sortase substrates that possess an LPXTG-type cell wall sorting signal. In order to elucidate the sorting pathways present in gram-positive bacteria, we performed a

David Comfort; Robert T. Clubb

2004-01-01

42

'Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns  

PubMed Central

Background: Large gene expression studies, such as those conducted using DNA arrays, often provide millions of different pieces of data. To address the problem of analyzing such data, we describe a statistical method, which we have called 'gene shaving'. The method identifies subsets of genes with coherent expression patterns and large variation across conditions. Gene shaving differs from hierarchical clustering and other widely used methods for analyzing gene expression studies in that genes may belong to more than one cluster, and the clustering may be supervised by an outcome measure. The technique can be 'unsupervised', that is, the genes and samples are treated as unlabeled, or partially or fully supervised by using known properties of the genes or samples to assist in finding meaningful groupings. Results: We illustrate the use of the gene shaving method to analyze gene expression measurements made on samples from patients with diffuse large B-cell lymphoma. The method identifies a small cluster of genes whose expression is highly predictive of survival. Conclusions: The gene shaving method is a potentially useful tool for exploration of gene expression data and identification of interesting clusters of genes worth further investigation.

Hastie, Trevor; Tibshirani, Robert; Eisen, Michael B; Alizadeh, Ash; Levy, Ronald; Staudt, Louis; Chan, Wing C; Botstein, David; Brown, Patrick

2000-01-01

43

Maternal Glutaric Acidemia, Type I Identified by Newborn Screening*  

PubMed Central

We report two women with glutaric acidemia type I in whom the diagnosis was unsuspected until a low carnitine level was found in their newborn children. Both mothers had low carnitine in plasma. In the first, organic acid analysis was only done after fibroblast studies revealed normal carnitine uptake. Having learned from the first family, organic acid analysis was done immediately in the mother of family 2. In both, the plasma acylcarnitine profile was normal but both excreted the metabolites typical of their disorder. One of the women was a compound heterozygote for distinct mutations in the glutaric acid dehydrogenase gene, whereas the second was either homozygous or hemizygous for a mutation in Exon 6 of the gene.

Crombez, Eric A.; Cederbaum, Stephen D.; Spector, Elaine; Chan, Erica; Salazar, Denise; Neidich, Julie; Goodman, Stephen

2008-01-01

44

Ancient, independent evolution and distinct molecular features of the novel human T-lymphotropic virus type 4  

Microsoft Academic Search

BACKGROUND: Human T-lymphotropic virus type 4 (HTLV-4) is a new deltaretrovirus recently identified in a primate hunter in Cameroon. Limited sequence analysis previously showed that HTLV-4 may be distinct from HTLV-1, HTLV-2, and HTLV-3, and their simian counterparts, STLV-1, STLV-2, and STLV-3, respectively. Analysis of full-length genomes can provide basic information on the evolutionary history and replication and pathogenic potential

William M Switzer; Marco Salemi; Shoukat H Qari; Hongwei Jia; Rebecca R Gray; Aris Katzourakis; Susan J Marriott; Kendle N Pryor; Nathan D Wolfe; Donald S Burke; Thomas M Folks; Walid Heneine

2009-01-01

45

Morphologically distinct plaque types differentially affect dendritic structure and organisation in the early and late stages of Alzheimer's disease  

Microsoft Academic Search

We have investigated the effects of the deposition of insoluble #-amyloid plaques on dendritic morphology within the neocortex. Labelling for #-amyloid identified three morphologically distinct plaque types present both within the brains of preclinical Alzheimer's disease (AD) and end-stage AD cases. In both preclinical and end-stage AD, the percentage area occupied by diffuse plaques contained a greater density of labelling

Paul A. Adlard; James C. Vickers

2002-01-01

46

Polymerase chain reaction analyses identify two distinct classes of Borrelia burgdorferi.  

PubMed Central

We sequenced homologous chromosomal loci from several North American and European isolates of the Lyme disease spirochete Borrelia burgdorferi, as well as from the relapsing fever spirochete Borrelia hermsii. Inter- and intraspecies sequence comparisons permitted the design of B. burgdorferi-specific polymerase chain reaction primers that detected all strains tested (n = 31) from diverse geographical and biological origins. Polymerase chain reaction "typing" with other unique sets of primers subdivided B. burgdorferi isolates into two groups: all North American isolates and a few European isolates made up one group, while the majority of the European and Asian isolates made up the second group. This classification may have a clinical correlate reflected in differences between "typical" Lyme borreliosis in North America and Europe. Images

Rosa, P A; Hogan, D; Schwan, T G

1991-01-01

47

A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival.  

PubMed

With the advent of high-throughput sequencing technologies, much progress has been made in the identification of somatic structural rearrangements in cancer genomes. However, characterization of the complex alterations and their associated mechanisms remains inadequate. Here, we report a comprehensive analysis of whole-genome sequencing and DNA copy number data sets from The Cancer Genome Atlas to relate chromosomal alterations to imbalances in DNA dosage and describe the landscape of intragenic breakpoints in glioblastoma multiforme (GBM). Gene length, guanine-cytosine (GC) content, and local presence of a copy number alteration were closely associated with breakpoint susceptibility. A dense pattern of repeated focal amplifications involving the murine double minute 2 (MDM2)/cyclin-dependent kinase 4 (CDK4) oncogenes and associated with poor survival was identified in 5% of GBMs. Gene fusions and rearrangements were detected concomitant within the breakpoint-enriched region. At the gene level, we noted recurrent breakpoints in genes such as apoptosis regulator FAF1. Structural alterations of the FAF1 gene disrupted expression and led to protein depletion. Restoration of the FAF1 protein in glioma cell lines significantly increased the FAS-mediated apoptosis response. Our study uncovered a previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM. PMID:23796897

Zheng, Siyuan; Fu, Jun; Vegesna, Rahulsimham; Mao, Yong; Heathcock, Lindsey E; Torres-Garcia, Wandaliz; Ezhilarasan, Ravesanker; Wang, Shuzhen; McKenna, Aaron; Chin, Lynda; Brennan, Cameron W; Yung, W K Alfred; Weinstein, John N; Aldape, Kenneth D; Sulman, Erik P; Chen, Ken; Koul, Dimpy; Verhaak, Roel G W

2013-06-24

48

Two Types of Alpha Satellite DNA in Distinct Chromosomal Locations in Azara's Owl Monkey  

PubMed Central

Alpha satellite DNA is a repetitive sequence known to be a major DNA component of centromeres in primates (order Primates). New World monkeys form one major taxon (parvorder Platyrrhini) of primates, and their alpha satellite DNA is known to comprise repeat units of around 340 bp. In one species (Azara's owl monkey Aotus azarae) of this taxon, we identified two types of alpha satellite DNA consisting of 185- and 344-bp repeat units that we designated as OwlAlp1 and OwlAlp2, respectively. OwlAlp2 exhibits similarity throughout its entire sequence to the alpha satellite DNA of other New World monkeys. The chromosomal locations of the two types of sequence are markedly distinct: OwlAlp1 was observed at the centromeric constrictions, whereas OwlAlp2 was found in the pericentric regions. From these results, we inferred that OwlAlp1 was derived from OwlAlp2 and rapidly replaced OwlAlp2 as the principal alpha satellite DNA on a short time scale at the speciation level. A less likely alternative explanation is also discussed.

Prakhongcheep, Ornjira; Hirai, Yuriko; Hara, Toru; Srikulnath, Kornsorn; Hirai, Hirohisa; Koga, Akihiko

2013-01-01

49

Identifying aquifer type in fractured rock aquifers using harmonic analysis.  

PubMed

Determining aquifer type, unconfined, semi-confined, or confined, by drilling or performing pumping tests has inherent problems (i.e., cost and complex field issues) while sometimes yielding inconclusive results. An improved method to cost-effectively determine aquifer type would be beneficial for hydraulic mapping of complex aquifer systems like fractured rock aquifers. Earth tides are known to influence water levels in wells penetrating confined aquifers or unconfined thick, low-porosity aquifers. Water-level fluctuations in wells tapping confined and unconfined aquifers are also influenced by changes in barometric pressure. Harmonic analyses of water-level fluctuations of a thick (~1000 m) carbonate aquifer located in south-central Oklahoma (Arbuckle-Simpson aquifer) were utilized in nine wells to identify aquifer type by evaluating the influence of earth tides and barometric-pressure variations using signal identification. On the basis of the results, portions of the aquifer responded hydraulically as each type of aquifer even though there was no significant variation in lithostratigraphy. The aquifer type was depth dependent with confined conditions becoming more prevalent with depth. The results demonstrate that harmonic analysis is an accurate and low-cost method to determine aquifer type. PMID:22463080

Rahi, Khayyun A; Halihan, Todd

2012-03-28

50

Biological Analysis of Human Immunodeficiency Virus Type 1 R5 Envelopes Amplified from Brain and Lymph Node Tissues of AIDS Patients with Neuropathology Reveals Two Distinct Tropism Phenotypes and Identifies Envelopes in the Brain That Confer an Enhanced Tropism and Fusigenicity for Macrophages  

Microsoft Academic Search

Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen dif- ferent envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4 CCR5 cells. Infectivity

Paul J. Peters; Jayanta Bhattacharya; Samantha Hibbitts; Matthias T. Dittmar; Graham Simmons; Jeanne Bell; Peter Simmonds; Paul R. Clapham

2004-01-01

51

Discovery of two distinct types of equatorial 150 km radar echoes  

NASA Astrophysics Data System (ADS)

We show here that VHF signals scattered from the 150 km region above Jicamaca exhibit two distinct types of features. In one type (type A), the Doppler spectral width increases with the echo strength and the corresponding signal-to-noise ratio (SNR). A second type (type B) of higher SNR echoes exhibits SNR-independent Doppler spectral widths that are much narrower than those observed in the first type. The type A echo population is by far the dominant population. Comparisons with earlier data sets collected at Jicamarca and elsewhere suggest that the type A and type B are likely to be associated with a naturally enhanced incoherent scattering (NEIS) process and the unstable growth of field-aligned irregularities (FAIs), respectively. We conjecture that small radar systems operated near the geomagnetic equator that have reported 150 km echo observations detected FAI echoes and that the NEIS echoes can only be seen by high sensitivity systems.

Chau, J. L.; Kudeki, E.

2013-09-01

52

ON IDENTIFYING THE PROGENITORS OF Type Ia SUPERNOVAE  

SciTech Connect

We propose two new means of identifying the main class of progenitors of Type Ia supernovae-single or double degenerate: (1) if the range of supernova properties is significantly determined by the range of viewing angles of non-spherically symmetric explosions, then the nature of the correlation between polarization and another property (for example, the velocity gradient) can be used to determine the geometry of the asymmetry and hence the nature of the progenitor, and (2) in the double- but not in the single-degenerate case, the range in the observed properties (e.g., velocity gradients) is likely to increase with the amount of carbon seen in the ejecta.

Livio, Mario; Pringle, J. E., E-mail: mlivio@stsci.edu [Space Telescope Science Institute, Baltimore, MD (United States)

2011-10-10

53

Pseudomonas Chromosomal Replication Origins: A Bacterial Class Distinct From Escherichia coli-Type Origins  

Microsoft Academic Search

The bacterial origins of DNA replication have been isolated from Pseudomonas aeruginosa and Pseudomonas putida. These origins comprise a second class of bacterial origins distinct from enteric-type origins: both origins function in both Pseudomonas species, and neither functions in Escherichia coli; enteric origins do not function in either pseudomonad. Both cloned sequences hybridize to chromosomal fragments that show properties expected

Thomas W. Yee; Douglas W. Smith

1990-01-01

54

A bacterial pathogen uses distinct type III secretion systems to alternate between host kingdoms  

Technology Transfer Automated Retrieval System (TEKTRAN)

Plant and animal-pathogenic bacteria utilize phylogenetically distinct type III secretion systems (T3SS) that produce needle-like injectisomes or pili for the delivery of effector proteins into host cells. Pantoea stewartii subsp. stewartii (Pnss), the causative agent of Stewart’s bacterial wilt and...

55

A Bacterial Pathogen uses Distinct Type III Secretion Systems to Alternate between Host Kingdom  

Technology Transfer Automated Retrieval System (TEKTRAN)

Gram-negative bacterial pathogens of eukaryotes often secrete proteins directly into host cells via a needle-like protein channel called a ‘type III secretion system’ (T3SS). Bacteria that are adapted to either animal or plant hosts use phylogenetically distinct T3SSs for secreting proteins. Here, ...

56

Obesogenic Family Types Identified through Latent Profile Analysis  

PubMed Central

Background Obesity may cluster in families due to shared physical and social environments. Purpose This study aims to identify family typologies of obesity risk based on family environments. Methods Using 2007–2008 data from 706 parent/youth dyads in Minnesota, we applied latent profile analysis and general linear models to evaluate associations between family typologies and body mass index (BMI) of youth and parents. Results Three typologies described most families with 18.8% “Unenriched/Obesogenic,” 16.9% “Risky Consumer,” and 64.3% “Healthy Consumer/Salutogenic.” After adjustment for demographic and socioeconomic factors, parent BMI and youth BMI Z-scores were higher in unenriched/obesogenic families (BMI difference=2.7, p<0.01 and BMI Z-score difference=0.51, p<0.01, respectively) relative to the healthy consumer/salutogenic typology. In contrast, parent BMI and youth BMI Z-scores were similar in the risky consumer families relative to those in healthy consumer/salutogenic type. Conclusions We can identify family types differing in obesity risks with implications for public health interventions.

VazquezBenitez, Gabriela; Patnode, Carrie D.; Hearst, Mary O.; Sherwood, Nancy E.; Parker, Emily D.; Sirard, John; Pasch, Keryn E.; Lytle, Leslie

2011-01-01

57

Analysis of GT-3a identifies a distinct subgroup of trihelix DNA-binding transcription factors in Arabidopsis.  

PubMed

Trihelix DNA-binding factors (or GT factors) bind to GT elements found in the promoters of many plant genes. Although the binding specificity and the transcriptional activity of some members (e.g. GT-1 and GT-2) have been studied, the regulatory function of this family of transcription factors remains largely unknown. In this work, we have characterised a new GT factor, namely GT-3a, and a closely related member, GT-3b. We show that (1) they can form either homo- or heterodimers but do not interact with GT-1; (2) they are predominantly expressed in floral buds and roots; (3) GT-3a cannot bind to the binding sites of GT-1 or GT-2, but binds to the cab2 and rbcS-1A gene promoters via the 5'-GTTAC sequence, which has been previously shown to be the core of the Site 1 type of GT elements. These results suggest that GT-3a and GT-3b belong to a distinct subgroup of GT factors and that each subgroup of GT factors binds to a functionally distinct type of cis-acting GT elements. PMID:15044016

Ayadi, Mira; Delaporte, Virginie; Li, You-Fang; Zhou, Dao-Xiu

2004-03-26

58

Distinctive structure in dynamic spectra of type V solar radio bursts  

SciTech Connect

Observations of type V solar radio bursts obtained with a 45--90 MHz radio spectrograph at the Institute of Terrestrial Magnetism are discussed. The dynamic spectra of type V events are highly diversified and complex. Categories of bursts are discriminated, depending on the behavior of the radiation at the leading and trailing edges. Various types of fine structure are encountered in the dynamic spectra of many bursts. An analysis is made of type V bursts that distinctly exhibit radio emission at the frequencies of the fundamental and the second harmonic.

Bakunin, L.M.; Markeev, A.K.; Fomichev, V.V.; Chertok, I.M.

1979-05-01

59

Clonal Complexes of Campylobacter jejuni Identified by Multilocus Sequence Typing Correlate with Strain Associations Identified by Multilocus Enzyme Electrophoresis  

PubMed Central

Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) with SmaI were used to subtype 55 isolates of Campylobacter jejuni from a diverse range of human and animal sources previously characterized by multilocus enzyme electrophoresis (MEE). MEE and MLST targeted 11 and 7 loci, respectively, and all loci were unique to each method. MEE, MLST, and PFGE identified 40, 37, and 48 discrete subtypes, respectively, with many of the subtypes occurring only once within the data set. Simpson's indices of diversity were calculated to be 0.979, 0.966, and 0.994 for MEE, MLST, and PFGE, respectively, demonstrating that MEE and MLST had similar discriminatory powers but that PFGE was more discriminatory. Allele diversity was higher in the MLST loci; individual single-locus diversities for the 11 MEE loci and the 7 MLST loci were 0.491 and 0.854, respectively. The clonal complexes recognized by MLST correlated with the strain associations previously recognized by MEE and contained some isolates indistinguishable by PFGE. Many clusters contained isolates from diverse geographical regions and from both humans and animals. These results demonstrate the usefulness of MLST for investigation of the global epidemiology of this important pathogen and illustrate its potential to identify indistinguishable strains or clones in geographically distinct regions.

Sails, Andrew D.; Swaminathan, Bala; Fields, Patricia I.

2003-01-01

60

Burkholderia Type VI Secretion Systems Have Distinct Roles in Eukaryotic and Bacterial Cell Interactions  

PubMed Central

Bacteria that live in the environment have evolved pathways specialized to defend against eukaryotic organisms or other bacteria. In this manuscript, we systematically examined the role of the five type VI secretion systems (T6SSs) of Burkholderia thailandensis (B. thai) in eukaryotic and bacterial cell interactions. Consistent with phylogenetic analyses comparing the distribution of the B. thai T6SSs with well-characterized bacterial and eukaryotic cell-targeting T6SSs, we found that T6SS-5 plays a critical role in the virulence of the organism in a murine melioidosis model, while a strain lacking the other four T6SSs remained as virulent as the wild-type. The function of T6SS-5 appeared to be specialized to the host and not related to an in vivo growth defect, as ?T6SS-5 was fully virulent in mice lacking MyD88. Next we probed the role of the five systems in interbacterial interactions. From a group of 31 diverse bacteria, we identified several organisms that competed less effectively against wild-type B. thai than a strain lacking T6SS-1 function. Inactivation of T6SS-1 renders B. thai greatly more susceptible to cell contact-induced stasis by Pseudomonas putida, Pseudomonas fluorescens and Serratia proteamaculans—leaving it 100- to 1000-fold less fit than the wild-type in competition experiments with these organisms. Flow cell biofilm assays showed that T6S-dependent interbacterial interactions are likely relevant in the environment. B. thai cells lacking T6SS-1 were rapidly displaced in mixed biofilms with P. putida, whereas wild-type cells persisted and overran the competitor. Our data show that T6SSs within a single organism can have distinct functions in eukaryotic versus bacterial cell interactions. These systems are likely to be a decisive factor in the survival of bacterial cells of one species in intimate association with those of another, such as in polymicrobial communities present both in the environment and in many infections.

Schwarz, Sandra; West, T. Eoin; Boyer, Frederic; Chiang, Wen-Chi; Carl, Mike A.; Hood, Rachel D.; Rohmer, Laurence; Tolker-Nielsen, Tim; Skerrett, Shawn J.; Mougous, Joseph D.

2010-01-01

61

Distinct transcriptional regulatory modules underlie STAT3's cell type-independent and cell type-specific functions  

PubMed Central

Transcription factors (TFs) regulate gene expression by binding to short DNA sequence motifs, yet their binding specificities alone cannot explain how certain TFs drive a diversity of biological processes. In order to investigate the factors that control the functions of the pleiotropic TF STAT3, we studied its genome-wide binding patterns in four different cell types: embryonic stem cells, CD4+ T cells, macrophages and AtT-20 cells. We describe for the first time two distinct modes of STAT3 binding. First, a small cell type-independent mode represented by a set of 35 evolutionarily conserved STAT3-binding sites that collectively regulate STAT3’s own functions and cell growth. We show that STAT3 is recruited to sites with E2F1 already pre-bound before STAT3 activation. Second, a series of different transcriptional regulatory modules (TRMs) assemble around STAT3 to drive distinct transcriptional programs in the four cell types. These modules recognize cell type-specific binding sites and are associated with factors particular to each cell type. Our study illustrates the versatility of STAT3 to regulate both universal- and cell type-specific functions by means of distinct TRMs, a mechanism that might be common to other pleiotropic TFs.

Hutchins, Andrew Paul; Diez, Diego; Takahashi, Yoshiko; Ahmad, Shandar; Jauch, Ralf; Tremblay, Michel Lucien; Miranda-Saavedra, Diego

2013-01-01

62

Fiber type composition of the architecturally distinct regions of human supraspinatus muscle: a cadaveric study.  

PubMed

The human supraspinatus muscle is clinically important as it is frequently injured in older adults and the elderly. We have previously shown that the supraspinatus has a complex architecture with two distinct regions each consisting of three parts. Further we have found dynamic changes in architectural parameters such as fiber bundle length markedly vary between these regions. Fiber types of the supraspinatus have not been thoroughly investigated throughout its volume and are of interest to clinicians treating supraspinatus pathologies. In this study we investigated the distribution of fiber types within the distinct regions and parts of supraspinatus. Samples of supraspinatus were excised from six distinct parts of each muscle from five formalin embalmed specimens (one male, four female; mean age 77±11.1 years) free of tendon pathology. Samples were frozen in liquid nitrogen and then cryosectioned. Serial sections were labeled using immunohistochemical techniques and antibodies against fast or slow myosin heavy chain isoforms. The mean percentage of Type I (slow) fibers ranged from 56.73% to 63.97%. Results demonstrated significant variations in fiber type distribution. The middle part of the anterior region has a significantly greater percentage of Type I fibers compared to that of the posterior. The superficial part of the anterior region has a greater percentage of Type II (fast) fibers compared to the middle and deep parts. Findings aid in highlighting the distinct functions of the anterior and posterior regions, and prompt the need to re-evaluate assessment and treatment techniques established on a limited understanding of the fiber type distribution. PMID:23463598

Kim, S Y; Lunn, D D; Dyck, R J; Kirkpatrick, L J; Rosser, B W C

2013-03-06

63

Animal Models of GWAS-Identified Type 2 Diabetes Genes  

PubMed Central

More than 65 loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notably TCF7L2 and ZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics.

da Silva Xavier, Gabriela; Bellomo, Elisa A.; McGinty, James A.; French, Paul M.; Rutter, Guy A.

2013-01-01

64

Animal models of GWAS-identified type 2 diabetes genes.  

PubMed

More than 65 loci, encoding up to 500 different genes, have been implicated by genome-wide association studies (GWAS) as conferring an increased risk of developing type 2 diabetes (T2D). Whilst mouse models have in the past been central to understanding the mechanisms through which more penetrant risk genes for T2D, for example, those responsible for neonatal or maturity-onset diabetes of the young, only a few of those identified by GWAS, notably TCF7L2 and ZnT8/SLC30A8, have to date been examined in mouse models. We discuss here the animal models available for the latter genes and provide perspectives for future, higher throughput approaches towards efficiently mining the information provided by human genetics. PMID:23710470

da Silva Xavier, Gabriela; Bellomo, Elisa A; McGinty, James A; French, Paul M; Rutter, Guy A

2013-04-11

65

Identifying Fracture Types and Relative Ages Using Fluid Inclusion Stratigraphy  

SciTech Connect

Enhanced Geothermal Systems (EGS) are designed to recover heat from the subsurface by mechanically creating fractures in subsurface rocks. Understanding the life cycle of a fracture in a geothermal system is fundamental to the development of techniques for creating fractures. Recognizing the stage of a fracture, whether it is currently open and transmitting fluids; if it recently has closed; or if it is an ancient fracture would assist in targeting areas for further fracture stimulation. Identifying dense fracture areas as well as large open fractures from small fracture systems will also assist in fracture stimulation selection. Geothermal systems are constantly generating fractures, and fluids and gases passing through rocks in these systems leave small fluid and gas samples trapped in healed microfractures. Fluid inclusions trapped in minerals as the fractures heal are characteristic of the fluids that formed them, and this signature can be seen in fluid inclusion gas analysis. Our hypothesis is that fractures over their life cycle have different chemical signatures that we can see in fluid inclusion gas analysis and by using the new method of fluid inclusion stratigraphy (FIS) the different stages of fractures, along with an estimate of fracture size can be identified during the well drilling process. We have shown with this study that it is possible to identify fracture locations using FIS and that different fractures have different chemical signatures however that signature is somewhat dependent upon rock type. Open, active fractures correlate with increase concentrations of CO2, N2, Ar, and to a lesser extent H2O. These fractures would be targets for further enhancement. The usefulness of this method is that it is low cost alternative to current well logging techniques and can be done as a well is being drilled.

Dilley, Lorie M.; Norman, David; Owens, Lara

2008-06-30

66

Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human  

PubMed Central

Summary Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of “beige” cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we show that deposits of brown fat previously observed in adult humans are composed of beige adipose cells. These data illustrate a new cell type with therapeutic potential in mouse and human.

Wu, Jun; Bostrom, Pontus; Sparks, Lauren M.; Ye, Li; Choi, Jang Hyun; Giang, An-Hoa; Khandekar, Melin; Nuutila, Pirjo; Schaart, Gert; Huang, Kexin; Tu, Hua; van Marken Lichtenbelt, Wouter D.; Hoeks, Joris; Enerback, Sven; Schrauwen, Patrick; Spiegelman, Bruce M.

2012-01-01

67

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3  

PubMed Central

Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1?Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21–q24.3, 6p25.1–p21.2, 21q21.2–q21.3 and 21q22.13–q22.3 and loss of 1p36.33–p34.3, 1p31.1–p21.2, 6q16.2–q25.3 and 8p23.3–p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3–p22.3 and 8q23.2–q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM.

Hughes, S; Damato, B E; Giddings, I; Hiscott, P S; Humphreys, J; Houlston, R S

2005-01-01

68

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.  

PubMed

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic steatosis is heritable (?26%-27%) in family-based Amish, Family Heart, and Framingham Heart Studies (n?=?880 to 3,070). By carrying out a fixed-effects meta-analysis of genome-wide association (GWA) results between CT hepatic steatosis and ?2.4 million imputed or genotyped SNPs in 7,176 individuals from the Old Order Amish, Age, Gene/Environment Susceptibility-Reykjavik study (AGES), Family Heart, and Framingham Heart Studies, we identify variants associated at genome-wide significant levels (p<5×10(-8)) in or near PNPLA3, NCAN, and PPP1R3B. We genotype these and 42 other top CT hepatic steatosis-associated SNPs in 592 subjects with biopsy-proven NAFLD from the NASH Clinical Research Network (NASH CRN). In comparisons with 1,405 healthy controls from the Myocardial Genetics Consortium (MIGen), we observe significant associations with histologic NAFLD at variants in or near NCAN, GCKR, LYPLAL1, and PNPLA3, but not PPP1R3B. Variants at these five loci exhibit distinct patterns of association with serum lipids, as well as glycemic and anthropometric traits. We identify common genetic variants influencing CT-assessed steatosis and risk of NAFLD. Hepatic steatosis associated variants are not uniformly associated with NASH/fibrosis or result in abnormalities in serum lipids or glycemic and anthropometric traits, suggesting genetic heterogeneity in the pathways influencing these traits. PMID:21423719

Speliotes, Elizabeth K; Yerges-Armstrong, Laura M; Wu, Jun; Hernaez, Ruben; Kim, Lauren J; Palmer, Cameron D; Gudnason, Vilmundur; Eiriksdottir, Gudny; Garcia, Melissa E; Launer, Lenore J; Nalls, Michael A; Clark, Jeanne M; Mitchell, Braxton D; Shuldiner, Alan R; Butler, Johannah L; Tomas, Marta; Hoffmann, Udo; Hwang, Shih-Jen; Massaro, Joseph M; O'Donnell, Christopher J; Sahani, Dushyant V; Salomaa, Veikko; Schadt, Eric E; Schwartz, Stephen M; Siscovick, David S; Voight, Benjamin F; Carr, J Jeffrey; Feitosa, Mary F; Harris, Tamara B; Fox, Caroline S; Smith, Albert V; Kao, W H Linda; Hirschhorn, Joel N; Borecki, Ingrid B

2011-03-10

69

The effect of temperature stress on coral- Symbiodinium associations containing distinct symbiont types  

NASA Astrophysics Data System (ADS)

Several studies have demonstrated that the temperature tolerance of scleractinian reef-building corals is controlled, in part, by hosting physiologically distinct symbiotic algae. We investigated the thermal tolerance of coral-algal associations within seven common species of reef-building corals hosting distinct Symbiodinium sub-clades collected from Heron Island during experimentally induced bleaching conditions. During experimental heating, photosynthetic fitness was assessed by the dark-adapted yield of PSII ( F v/ F m), and excitation pressure across PSII ( Q m) of each coral-algal association using pulse amplitude modulation fluorometry. The onset of bleaching was determined by the measurement of Symbiodinium cell density. Using the ribosomal internal transcribed spacer 2 (ITS-2) region, we showed that Symbiodinium type-coral host associations were temporally and spatially conserved in a high proportion of the colonies sampled within each species. Generally, the species Acropora millepora, Platygyra daedalea, Acropora aspera and Acropora formosa contained Symbiodinium ITS-2 type C3, whereas the species Montipora digitata, Porites cylindrica and Porites lutea contained Symbiodinium type C15. Bleaching susceptibility showed some association with Symbiodinium type, but further research is required to confirm this. Corals hosting C3 Symbiodinium displayed higher reductions in F v/ F m during heating compared to their C15 counterparts, irrespective of host species. However, a corresponding reduction in Symbiodinium density was not observed. Nonetheless, A. aspera and A. formosa showed significant reductions in Symbiodinium density relative to controls. This correlated with large increases in Q m and decreases in F v/ F m in heated explants. Our results suggest a range of bleaching susceptibilities for the coral species investigated, with A. aspera and A. formosa showing the greatest susceptibility to bleaching and M. digitata showing the lowest bleaching susceptibility. The data provide strong evidence for distinct differences in temperature tolerance between C3 and C15 Symbiodinium types when in- hospite; however, future studies addressing the confounding effect of host species would help to confirm this.

Fisher, P. L.; Malme, M. K.; Dove, S.

2012-06-01

70

A novel supervised trajectory segmentation algorithm identifies distinct types of human adenovirus motion in host cells.  

PubMed

Biological trajectories can be characterized by transient patterns that may provide insight into the interactions of the moving object with its immediate environment. The accurate and automated identification of trajectory motifs is important for the understanding of the underlying mechanisms. In this work, we develop a novel trajectory segmentation algorithm based on supervised support vector classification. The algorithm is validated on synthetic data and applied to the identification of trajectory fingerprints of fluorescently tagged human adenovirus particles in live cells. In virus trajectories on the cell surface, periods of confined motion, slow drift, and fast drift are efficiently detected. Additionally, directed motion is found for viruses in the cytoplasm. The algorithm enables the linking of microscopic observations to molecular phenomena that are critical in many biological processes, including infectious pathogen entry and signal transduction. PMID:17532228

Helmuth, Jo A; Burckhardt, Christoph J; Koumoutsakos, Petros; Greber, Urs F; Sbalzarini, Ivo F

2007-04-14

71

A Novel Approach to Identify Two Distinct Receptor Binding Surfaces of Insulin-like Growth Factor II*S?  

PubMed Central

Very little is known about the residues important for the interaction of insulin-like growth factor II (IGF-II) with the type 1 IGF receptor (IGF-1R) and the insulin receptor (IR). Insulin, to which IGF-II is homologous, is proposed to cross-link opposite halves of the IR dimer through two receptor binding surfaces, site 1 and site 2. In the present study we have analyzed the contribution of IGF-II residues equivalent to insulin's two binding surfaces toward the interaction of IGF-II with the IGF-1R and IR. Four “site 1” and six “site 2” analogues were produced and analyzed in terms of IGF-1R and IR binding and activation. The results show that Val43, Phe28, and Val14 (equivalent to site 1) are critical to IGF-1R and IR binding, whereas mutation to alanine of Gln18 affects only IGF-1R and not IR binding. Alanine substitutions at Glu12, Asp15, Phe19, Leu53, and Glu57 analogues resulted in significant (>2-fold) decreases in affinity for both the IGF-1R and IR. Furthermore, taking a novel approach using a monomeric, single-chain minimized IGF-1R we have defined a distinct second binding surface formed by Glu12, Phe19, Leu53, and Glu57 that potentially engages the IGF-1R at one or more of the FnIII domains.

Alvino, Clair L.; McNeil, Kerrie A.; Ong, Shee Chee; Delaine, Carlie; Booker, Grant W.; Wallace, John C.; Whittaker, Jonathan; Forbes, Briony E.

2009-01-01

72

Differential gene expression analysis identifies murine Cacnb3 as strongly upregulated in distinct dendritic cell populations upon stimulation.  

PubMed

Langerhans cells (LCs) represent the dendritic cell (DC) population in the epidermis. Among the set of genes induced in primary mouse LCs in response to stimulation, both isoforms of the voltage-dependent Ca²(+) channel (VDCC) regulatory subunit Cacnb3 as well as the DC maturation marker Fscn1 were upregulated most strongly. Comparable results were obtained for a recently described myeloid DC line (SP37A3). Other antigen presenting cell populations, namely, bone marrow-derived DCs, macrophages and primary B cells, showed no stimulation-associated upregulation of Cacnb3 expression. Pharmacological inhibition of Ca²(+) channel activity during the stimulation of SP37A3 cells enhanced their T cell stimulatory capacity, while selective inhibition of L-type VDCC had no effect. Both Cacnb3 isoforms, similar to Fscn1, required JNK and p38 kinase activity for stimulation-associated upregulation, and this process was inhibited by ERK and PI(3)K. The putative promoter region of Cacnb3 isoform 2, which we found to be less ubiquitously expressed than Cacnb3 isoform 1, exerted reporter activity in LC-like cell lines. Our findings suggest that Cacnb3 exerts its function in distinct activated DC populations. Further analysis of the regulatory region(s) facilitating stimulation-induced upregulation of Cacnb3 expression in these DC subsets will help to gain better insight into DC subset specific gene regulation. PMID:21040760

Bros, Matthias; Dexheimer, Nadine; Ross, Ralf; Trojandt, Stefanie; Höhn, Yvette; Tampe, Jens; Sutter, Arne; Jährling, Frank; Grabbe, Stephan; Reske-Kunz, Angelika B

2010-10-30

73

Improvement of the Owner Distinction Method for Healing-Type Pet Robots  

NASA Astrophysics Data System (ADS)

In order to decrease human stress, Animal Assisted Therapy which applies pets to heal humans is attracted. However, since animals are insanitary and unsafe, it is difficult to practically apply animal pets in hospitals. For the reason, on behalf of animal pets, pet robots have been attracted. Since pet robots would have no problems in sanitation and safety, they are able to be applied as a substitute for animal pets in the therapy. In our previous study where pet robots distinguish their owners like an animal pet, we used a puppet type pet robot which has pressure type touch sensors. However, the accuracy of our method was not sufficient to practical use. In this paper, we propose a method to improve the accuracy of the distinction. The proposed method can be applied for capacitive touch sensors such as installed in AIBO in addition to pressure type touch sensors. Besides, this paper shows performance of the proposed method from experimental results and confirms the proposed method has improved performance of the distinction in the conventional method.

Nambo, Hidetaka; Kimura, Haruhiko; Hara, Mirai; Abe, Koji; Tajima, Takuya

74

Distinct functional properties of isoamylase-type starch debranching enzymes in monocot and dicot leaves.  

PubMed

Isoamylase-type starch debranching enzymes (ISA) play important roles in starch biosynthesis in chloroplast-containing organisms, as shown by the strict conservation of both catalytically active ISA1 and the noncatalytic homolog ISA2. Functional distinctions exist between species, although they are not understood yet. Numerous plant tissues require both ISA1 and ISA2 for normal starch biosynthesis, whereas monocot endosperm and leaf exhibit nearly normal starch metabolism without ISA2. This study took in vivo and in vitro approaches to determine whether organism-specific physiology or evolutionary divergence between monocots and dicots is responsible for distinctions in ISA function. Maize (Zea mays) ISA1 was expressed in Arabidopsis (Arabidopsis thaliana) lacking endogenous ISA1 or lacking both native ISA1 and ISA2. The maize protein functioned in Arabidopsis leaves to support nearly normal starch metabolism in the absence of any native ISA1 or ISA2. Analysis of recombinant enzymes showed that Arabidopsis ISA1 requires ISA2 as a partner for enzymatic function, whereas maize ISA1 was active by itself. The electrophoretic mobility of recombinant and native maize ISA differed, suggestive of posttranslational modifications in vivo. Sedimentation equilibrium measurements showed recombinant maize ISA1 to be a dimer, in contrast to previous gel permeation data that estimated the molecular mass as a tetramer. These data demonstrate that evolutionary divergence between monocots and dicots is responsible for the distinctions in ISA1 function. PMID:24027240

Facon, Maud; Lin, Qiaohui; Azzaz, Abdelhamid M; Hennen-Bierwagen, Tracie A; Myers, Alan M; Putaux, Jean-Luc; Roussel, Xavier; D'Hulst, Christophe; Wattebled, Fabrice

2013-09-11

75

Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord  

PubMed Central

Background Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted ~7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in ~6% of GABAergic boutons in laminae I-IIo, and ~1% of those in laminae IIi-III. Conclusions These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina II.

2011-01-01

76

The Actinomycete Thermobispora bispora Contains Two Distinct Types of Transcriptionally Active 16S rRNA Genes  

Microsoft Academic Search

Here we present the first description of the presence of two distinct types of 16S rRNA genes in the genome of a (eu)bacterium, Thermobispora bispora. We cloned and determined the nucleotide sequences of all four rRNA operons of T. bispora. Sequence comparisons revealed that the genome of T. bispora contains two distinct types of 16S rRNA genes, each type consisting

YUE WANG; ZHENSHUI ZHANG; NARENDRAKUMAR RAMANAN

1997-01-01

77

Foraging Blainville's beaked whales (Mesoplodon densirostris) produce distinct click types matched to different phases of echolocation.  

PubMed

Blainville's beaked whales (Mesoplodon densirostris Blainville) echolocate for prey during deep foraging dives. Here we use acoustic tags to demonstrate that these whales, in contrast to other toothed whales studied, produce two distinct types of click sounds during different phases in biosonar-based foraging. Search clicks are emitted during foraging dives with inter-click intervals typically between 0.2 and 0.4 s. They have the distinctive form of an FM upsweep (modulation rate of about 110 kHz ms(-1)) with a -10 dB bandwidth from 26 to 51 kHz and a pulse length of 270 micros, somewhat similar to chirp signals in bats and Cuvier's beaked whales (Ziphius cavirostris Cuvier), but quite different from clicks of other toothed whales studied. In comparison, the buzz clicks, produced in short bursts during the final stage of prey capture, are short (105 micros) transients with no FM structure and a -10 dB bandwidth from 25 to 80 kHz or higher. Buzz clicks have properties similar to clicks reported from large delphinids and hold the potential for higher temporal resolution than the FM clicks. It is suggested that the two click types are adapted to the separate problems of target detection and classification versus capture of low target strength prey in a cluttered acoustic environment. PMID:17142692

Johnson, M; Madsen, P T; Zimmer, W M X; de Soto, N Aguilar; Tyack, P L

2006-12-01

78

Molecular cloning and expression analysis of two distinct F-type lectins from the rock bream, Oplegnathus fasciatus.  

PubMed

Several lectin families characterized by distinct signature sequence motifs and structural folds, such as C-type, peptidoglycan recognition protein, ficolin, pentraxins, and most recently galectins, have been implicated in immune surveillance. In this study, two distinct F-type lectins RbFTL-1 and RbFTL-2, from the rock bream (Oplegnathus fasciatus), were identified and their expression was analyzed. The full-length cDNA of RbFTL-1 was composed of 1204 bp with a 945-bp open reading frame (ORF) that encoded a 314 amino-acid protein, while that of RbFTL-2 consisted of 1614 bp with a 951-bp ORF encoding a 316 amino-acid protein. RbFTL-1 and RbFTL-2 mRNAs were predominately expressed in the head-kidney and in the liver, respectively. Levels of the RbFTL-1 mRNA transcript increased up to 5.0- and 2.8-fold in the head-kidney and trunk-kidney compared to the muscle, respectively, while those of the RbFTL-2 mRNA transcript increased up to 12.0-fold in liver. The expression of RbFTL-1 and RbFTL-2 were differentially up-regulated in rock bream challenged with Edwardsiella tarda, Streptococcus iniae, and RSIV, with significant increases at 1 and 3h post-challenge compared to the controls. PMID:21683734

Park, Hyung-Jun; Kim, Ju-Won; Kim, Eun-Gyeong; Kim, Ha-Na; Chae, Young-Sun; Jeong, Ji-Min; Kim, Do-Hyung; Park, Chan-Il

2011-06-12

79

IS3 profiling identifies the enterohaemorrhagic Escherichia coli O-island 62 in a distinct enteroaggregative E. coli lineage  

PubMed Central

Background Enteroaggregative Escherichia coli (EAEC) are important diarrhoeal pathogens that are defined by a HEp-2 adherence assay performed in specialist laboratories. Multilocus sequence typing (MLST) has revealed that aggregative adherence is convergent, providing an explanation for why not all EAEC hybridize with the plasmid-derived probe for this category, designated CVD432. Some EAEC lineages are globally disseminated or more closely associated with disease. Results To identify genetic loci conserved within significant EAEC lineages, but absent from non-EAEC, IS3-based PCR profiles were generated for 22 well-characterised EAEC strains. Six bands that were conserved among, or missing from, specific EAEC lineages were cloned and sequenced. One band corresponded to the aggR gene, a plasmid-encoded regulator that has been used as a diagnostic target but predominantly detects EAEC bearing the plasmid already marked by CVD432. The sequence from a second band was homologous to an open-reading frame within the cryptic enterohaemorrhagic E. coli (EHEC) O157 genomic island, designated O-island 62. Screening of an additional 46 EAEC strains revealed that the EHEC O-island 62 was only present in those EAEC strains belonging to the ECOR phylogenetic group D, largely comprised of sequence type (ST) complexes 31, 38 and 394. Conclusions The EAEC 042 gene orf1600, which lies within the EAEC equivalent of O-island 62 island, can be used as a marker for EAEC strains belonging to the ECOR phylogenetic group D. The discovery of EHEC O-island 62 in EAEC validates the genetic profiling approach for identifying conserved loci among phylogenetically related strains.

2011-01-01

80

Method for identifying type I diabetes mellitus in humans  

SciTech Connect

A method and system for classifying subject populations utilizing predictive and diagnostic biomarkers for type I diabetes mellitus. The method including determining the levels of a variety of markers within the serum or plasma of a target organism and correlating this level to general populations as a screen for predisposition or progressive monitoring of disease presence or predisposition.

Metz, Thomas O [Kennewick, WA; Qian, Weijun [Richland, WA; Jacobs, Jon M [Pasco, WA

2011-04-12

81

Golgi stain identifies three types of fibres in fish muscle  

Microsoft Academic Search

Summary Using Golgi infiltration we have studied the structure and disposition of tranverse tubules in muscle fibres from the sand dab fin musculature. Three types of fibres differ significantly from each other in the extent and disposition of junctions between transverse tubules and the sarcoplasmic reticulum. These correlate with the three groups of fibres having different relaxation times shown in

Clara Franzini-Armstrong; William F. Gilly; Eva Aladjem; Denah Appelt

1987-01-01

82

Array CGH identifies distinct DNA copy number profiles of oncogenes and tumor suppressor genes in chromosomal- and microsatellite-unstable sporadic colorectal carcinomas.  

PubMed

DNA copy number changes represent molecular fingerprints of solid tumors and are as such relevant for better understanding of tumor development and progression. In this study, we applied genome-wide array comparative genomic hybridization (aCGH) to identify gene-specific DNA copy number changes in chromosomal (CIN)- and microsatellite (MIN)-unstable sporadic colorectal cancers (sCRC). Genomic DNA was extracted from microdissected, matching normal colorectal epithelium and invasive tumor cells of formalin-fixed and paraffin-embedded tissues of 22 cases with colorectal cancer (CIN = 11, MIN = 11). DNA copy number changes were determined by aCGH for 287 target sequences in tumor cell DNAs, using pooled normal DNAs as reference. aCGH data of tumor cell DNAs was confirmed by fluorescence in situ hybridization (FISH) for three genes on serial tissues as those used for aCGH. aCGH revealed DNA copy number changes previously described by metaphase CGH (gains 7, 8q, 13q, and 20q; losses 8p, 15q, 18q, and 17p). However, chromosomal regions 20q, 13q, 7, and 17p were preferentially altered in CIN-type tumors and included DNA amplifications of eight genes on chromosome 20q (TOP1, AIB1, MYBL2, CAS, PTPN1, STK15, ZNF217, and CYP24), two genes on chromosome 13q (BRCA2 and D13S25), and three genes on chromosome 7 (IL6, CYLN2, and MET) as well as DNA deletions of two genes on chromosome 17p (HIC1 and LLGL1). Finally, additional CIN-tumor-associated DNA amplifications were identified for EXT1 (8q24.11) and MYC (8q24.12) as well as DNA deletions for MAP2K5 (15q23) and LAMA3 (18q11.2). In contrast, distinct MIN-tumor-associated DNA amplifications were detected for E2F5 (8p22-q21.3), GARP (11q13.5-q14), ATM (11q22.3), KAL (Xp22.3), and XIST (Xq13.2) as well as DNA deletions for RAF1 (3p25), DCC (18q21.3), and KEN (21q tel). aCGH revealed distinct DNA copy number changes of oncogenes and tumor suppressor genes in CIN- and MIN-type sporadic colorectal carcinomas. The identified candidate genes are likely to have distinct functional roles in the carcinogenesis and progression of CIN- and MIN-type sporadic CRCs and may be involved in the differential response of CIN- and MIN-type tumor cells to (adjuvant) therapy, such as 5-fluorouracil. PMID:17143621

Lassmann, Silke; Weis, Roland; Makowiec, Frank; Roth, Jasmine; Danciu, Mihai; Hopt, Ulrich; Werner, Martin

2006-12-02

83

New mutations identified in the ocular albinism type 1 gene  

Microsoft Academic Search

As the most common form of ocular albinism, ocular albinism type I (OA1) is an X-linked disorder that has an estimated prevalence of about 1:50,000. We searched for mutations through the human genome sequence draft by direct sequencing on eighteen patients with OA1, both within the coding region and in a thousand base pairs upstream of its start site. Here,

Cristin Roma; Paola Ferrante; Ombretta Guardiola; Andrea Ballabio; Massimo Zollo

2007-01-01

84

A Visual Screen of a Gfp-Fusion Library Identifies a New Type of Nuclear Envelope Membrane Protein  

PubMed Central

The nuclear envelope (NE) is a distinct subdomain of the ER, but few membrane components have been described that are specific to it. We performed a visual screen in tissue culture cells to identify proteins targeted to the NE. This approach does not require assumptions about the nature of the association with the NE or the physical separation of NE and ER. We confirmed that screening a library of fusions to the green fluorescent protein can be used to identify proteins targeted to various subcompartments of mammalian cells, including the NE. With this approach, we identified a new NE membrane protein, named nurim. Nurim is a multispanning membrane protein without large hydrophilic domains that is very tightly associated with the nucleus. Unlike the known NE membrane proteins, it is neither associated with nuclear pores, nor targeted like lamin-associated membrane proteins. Thus, nurim is a new type of NE membrane protein that is localized to the NE by a distinct mechanism.

Rolls, Melissa M.; Stein, Pascal A.; Taylor, Stephen S.; Ha, Edward; McKeon, Frank; Rapoport, Tom A.

1999-01-01

85

Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities  

Microsoft Academic Search

Glioblastoma is classified into two subtypes on the basis of clinical history: ''primary glioblastoma'' arising de novo without detectable antecedent disease and ''secondary glio- blastoma'' evolving from a low-grade astrocytoma. Despite their distinctive clinical courses, they arrive at an indistin- guishable clinical and pathologic end point highlighted by widespread invasion and resistance to therapy and, as such, are managed clinically

Elizabeth A. Maher; Cameron Brennan; Patrick Y. Wen; Laura Durso; Keith L. Ligon; Aaron Richardson; Deepak Khatry; Raktim Sinha; David N. Louis; John Quackenbush; Lynda Chin; Ronald A. DePinho

2006-01-01

86

Different central nervous system cell types display distinct and nonrandom arrangements of satellite DNA sequences.  

PubMed Central

Paraformaldehyde-fixed tissue from mouse cerebellum was hybridized with biotin-labeled satellite DNA for identification of centromeres. By using avidin-peroxidase conjugates, it was possible to define the nuclear position of centromeres at the ultrastructural level. Three-dimensional analysis of well-resolved centromere arrays were aided by computer reconstruction of serial sections. Different cell types displayed distinct, nonrandom centromere locations. In Purkinje neurons, the majority of detected sequences were clustered together around the central nucleolus, whereas in granule neurons, more numerous, dispersed centromere clusters were associated with the nuclear membrane. In Purkinje cells, peroxidase-labeled regions corresponded to dense heterochromatic aggregates were detected in Purkinje cells of several different species. These observations suggest that in these highly differentiated cells, the nuclear position of centromeres is maintained in evolution despite species differences in centromeric DNA sequence. Such defined ordering of centromeres may be integral to specific functional capacities. Images

Manuelidis, L

1984-01-01

87

Duck Hepatitis A Virus Possesses a Distinct Type IV Internal Ribosome Entry Site Element of Picornavirus  

PubMed Central

Sequence analysis of duck hepatitis virus type 1 (DHV-1) led to its classification as the only member of a new genus, Avihepatovirus, of the family Picornaviridae, and so was renamed duck hepatitis A virus (DHAV). The 5? untranslated region (5? UTR) plays an important role in translation initiation and RNA synthesis of the picornavirus. Here, we provide evidence that the 651-nucleotide (nt)-long 5? UTR of DHAV genome contains an internal ribosome entry site (IRES) element that functions efficiently in vitro and within BHK cells. Comparative sequence analysis showed that the 3? part of the DHAV 5? UTR is similar to the porcine teschovirus 1 (PTV-1) IRES in sequence and predicted secondary structure. Further mutational analyses of the predicted domain IIId, domain IIIe, and pseudoknot structure at the 3? end of the DHAV IRES support our predicted secondary structure. However, unlike the case for the PTV-1 IRES element, analysis of various deletion mutants demonstrated that the optimally functional DHAV IRES element with a size of approximately 420 nt is larger than that of PTV-1 and contains other peripheral domains (Id and Ie) that do not exist within the type IV IRES elements. The domain Ie, however, could be removed without significant loss of activity. Surprisingly, like the hepatitis A virus (HAV) IRES element, the activity of DHAV IRES could be eliminated by expression of enterovirus 2A protease. These findings indicate that the DHAV IRES shares common features with type IV picornavirus IRES elements, whereas it exhibits significant differences from type IV IRESs. Therefore, we propose that DHAV possesses a distinct type IV IRES element of picornavirus.

Pan, Meng; Yang, Xiaorong; Zhou, Lei; Ge, Xinna; Guo, Xin; Liu, Jinhua

2012-01-01

88

Mucinous carcinoma of the breast is genomically distinct from invasive ductal carcinomas of no special type.  

PubMed

Mucinous carcinomas are a rare entity accounting for up to 2% of all breast cancers, which have been shown to display a gene expression profile distinct from that of invasive ductal carcinomas of no special type (IDC-NSTs). Here, we have defined the genomic aberrations that are characteristic of this special type of breast cancer and have investigated whether mucinous carcinomas might constitute a genomic entity distinct from IDC-NSTs. Thirty-five pure and 11 mixed mucinous breast carcinomas were assessed by immunohistochemistry using antibodies against oestrogen receptor (ER), progesterone receptor, HER2, Ki67, cyclin D1, cortactin, Bcl-2, p53, E-cadherin, basal markers, neuroendocrine markers, and WT1. Fifteen pure mucinous carcinomas and 30 grade- and ER-matched IDC-NSTs were microdissected and subjected to high-resolution microarray-based comparative genomic hybridization (aCGH). In addition, the distinct components of seven mixed mucinous carcinomas were microdissected separately and subjected to aCGH. Pure mucinous carcinomas consistently expressed ER (100%), lacked HER2 expression (97.1%), and showed a relatively low level of genetic instability. Unsupervised hierarchical cluster analysis revealed that pure mucinous carcinomas were homogeneous and preferentially clustered together, separately from IDC-NSTs. They less frequently harboured gains of 1q and 16p and losses of 16q and 22q than grade- and ER-matched IDC-NSTs, and no pure mucinous carcinoma displayed concurrent 1q gain and 16q loss, a hallmark genetic feature of low-grade IDC-NSTs. Finally, both components of all but one mixed mucinous carcinoma displayed similar patterns of genetic aberrations and preferentially clustered together with pure mucinous carcinomas on unsupervised clustering analysis. Our results demonstrate that mucinous carcinomas are more homogeneous between themselves at the genetic level than IDC-NSTs. Both components of mixed mucinous tumours are remarkably similar at the molecular level to pure mucinous cancers, suggesting that mixed mucinous carcinomas may be best classified as variants of mucinous cancers rather than of IDC-NSTs. PMID:20815046

Lacroix-Triki, Magali; Suarez, Paula H; MacKay, Alan; Lambros, Maryou B; Natrajan, Rachael; Savage, Kay; Geyer, Felipe C; Weigelt, Britta; Ashworth, Alan; Reis-Filho, Jorge S

2010-11-01

89

A newly identified hepatitis B type virus in tree squirrels.  

PubMed

Virus-associated particles have been isolated from the livers of three common gray tree squirrels (Sciurus carolinensis pennsylvanicus) that have histological evidence of hepatitis. Two of these livers were also positive by orcein staining, suggesting the presence of surface antigen in the cytoplasm of hepatocytes. Fractionation of these particles by CsCl density equilibrium gradient centrifugation and assay of the fractions for surface antigen, core antigen, and DNA polymerase activities demonstrate the presence of all three at an approximate density peak of 1.27. Electron microscopic examination of purified virus preparations showed spherical particles with a mean diameter of 25 nm. Initial characterization of the DNA polymerase product by gel electrophoresis showed a single DNase I sensitive band, migrating slightly faster than the woodchuck hepatitis virus DNA polymerase product. The presence of apparently cross-reacting antibodies was demonstrated by purified hepatitis B surface and/or core antigens binding to some squirrel sera in solid phase assays. Infected tree squirrels appear to lack detectable antigen in their sera. These results suggest that the tree squirrels studied are chronic carriers of a hepatitis B type virus. The host-virus interaction described herein may be useful in understanding the chronic carrier state associated with hepatitis B in man. PMID:3457384

Feitelson, M A; Millman, I; Halbherr, T; Simmons, H; Blumberg, B S

1986-04-01

90

Two Distinct Types of ON Directionally Selective Ganglion Cells in the Rabbit Retina  

PubMed Central

Mammalian retinas contain about 20 types of ganglion cells that respond to different aspects of the visual scene, including the direction of motion of objects in the visual field. The rabbit retina has long been thought to contain two distinct types of directionally selective (DS) ganglion cell: a bistratified ON-OFF DS ganglion cell that responds to onset and termination of light, and an ON DS ganglion cell, which stratifies only in the ON layer and responds only to light onset. This division is challenged by targeted recordings from rabbit retina, which indicate that ON DS ganglion cells occur in two discriminably different types. One of these is strongly tracer-coupled to amacrine cells; the other is never tracer-coupled. These two types also differ in branching pattern, stratification depth, relative latency, and transience of spiking. The sustained, uncoupled ON DS cell ramifies completely within the lower cholinergic band and responds to nicotine with continuous firing. In contrast, the transient, coupled ON DS ganglion cell stratifies above the cholinergic band and is not positioned to receive major input from cholinergic amacrine cells, consistent with its modest response to the cholinergic agonist nicotine. Much data have accrued that directional responses in the mammalian retina originate via gamma-aminobutyric acid (GABA) release from the dendrites of starburst amacrine cells (Euler et al., 2002). If there is an ON DS ganglion cell that does not stratify in the starburst band, this suggests that its GABA-dependent directional signals may be generated by a mechanism independent of starburst amacrine cells.

Hoshi, Hideo; Tian, Lian-Ming; Massey, Stephen C.; Mills, Stephen L.

2012-01-01

91

Comparison of odor-active compounds from six distinctly different rice flavor types.  

PubMed

Using a dynamic headspace system with Tenax trap, GC-MS, GC-olfactometry (GC-O), and multivariate analysis, the aroma chemistry of six distinctly different rice flavor types (basmati, jasmine, two Korean japonica cultivars, black rice, and a nonaromatic rice) was analyzed. A total of 36 odorants from cooked samples were characterized by trained assessors. Twenty-five odorants had an intermediate or greater intensity (odor intensity >or= 3) and were considered to be major odor-active compounds. Their odor thresholds in air were determined using GC-O. 2-Acetyl-1-pyrroline (2-AP) had the lowest odor threshold (0.02 ng/L) followed by 11 aldehydes (ranging from 0.09 to 3.1 ng/L), guaiacol (1.5 ng/L), and 1-octen-3-ol (2.7 ng/L). On the basis of odor thresholds and odor activity values (OAVs), the importance of each major odor-active compound was assessed. OAVs for 2-AP, hexanal, ( E)-2-nonenal, octanal, heptanal, and nonanal comprised >97% of the relative proportion of OAVs from each rice flavor type, even though the relative proportion varied among samples. Thirteen odor-active compounds [2-AP, hexanal, ( E)-2-nonenal, octanal, heptanal, nonanal, 1-octen-3-ol, ( E)-2-octenal, ( E, E)-2,4-nonadienal, 2-heptanone, ( E, E)-2,4-decadienal, decanal, and guaiacol] among the six flavor types were the primary compounds explaining the differences in aroma. Multivariate analysis demonstrated that the individual rice flavor types could be separated and characterized using these compounds, which may be of potential use in rice-breeding programs focusing on flavor. PMID:18363355

Yang, Dong Sik; Shewfelt, Robert L; Lee, Kyu-Seong; Kays, Stanley J

2008-03-26

92

Two distinct types of ON directionally selective ganglion cells in the rabbit retina.  

PubMed

Mammalian retinas contain about 20 types of ganglion cells that respond to different aspects of the visual scene, including the direction of motion of objects in the visual field. The rabbit retina has long been thought to contain two distinct types of directionally selective (DS) ganglion cell: a bistratified ON-OFF DS ganglion cell that responds to onset and termination of light, and an ON DS ganglion cell, which stratifies only in the ON layer and responds only to light onset. This division is challenged by targeted recordings from rabbit retina, which indicate that ON DS ganglion cells occur in two discriminably different types. One of these is strongly tracer-coupled to amacrine cells; the other is never tracer-coupled. These two types also differ in branching pattern, stratification depth, relative latency, and transience of spiking. The sustained, uncoupled ON DS cell ramifies completely within the lower cholinergic band and responds to nicotine with continuous firing. In contrast, the transient, coupled ON DS ganglion cell stratifies above the cholinergic band and is not positioned to receive major input from cholinergic amacrine cells, consistent with its modest response to the cholinergic agonist nicotine. Much data have accrued that directional responses in the mammalian retina originate via gamma-aminobutyric acid (GABA) release from the dendrites of starburst amacrine cells (Euler et al., 2002). If there is an ON DS ganglion cell that does not stratify in the starburst band, this suggests that its GABA-dependent directional signals may be generated by a mechanism independent of starburst amacrine cells. PMID:21618235

Hoshi, Hideo; Tian, Lian-Ming; Massey, Stephen C; Mills, Stephen L

2011-09-01

93

Spatial firing correlates of physiologically distinct cell types of the rat dentate gyrus.  

PubMed

The dentate gyrus (DG) occupies a key position in information flow through the hippocampus. Its principal cell, the granule cell, has spatially selective place fields. However, the behavioral correlates of cells located in the hilus of the rat dentate gyrus are unknown. We report here that cells below the granule layer show spatially selective firing that consists of multiple subfields. Other cells recorded from the DG had single place fields. Compared with cells with multiple fields, cells with single fields fired at lower rates during sleep were less bursty, and were more likely to be recorded simultaneously with large populations of neurons that were active during sleep and silent during behavior. We propose that cells with single fields are likely to be mature granule cells that use sparse encoding to potentially disambiguate input patterns. Furthermore, we hypothesize that cells with multiple fields might be cells of the hilus or newborn granule cells. These data are the first demonstration, based on physiological criteria, that single- and multiple-field cells constitute at least two distinct cell classes in the DG. Because of the heterogeneity of firing correlates and cell types in the DG, understanding which cell types correspond to which firing patterns, and how these correlates change with behavioral state and between different environments, are critical questions for testing long-standing computational theories that the DG performs a pattern separation function using a very sparse coding strategy. PMID:22423105

Neunuebel, Joshua P; Knierim, James J

2012-03-14

94

Identification of a Distinct, Cryptic Heparosan Synthase from Pasteurella multocida Types A, D, and F  

PubMed Central

The extracellular polysaccharide capsules of Pasteurella multocida types A, D, and F are composed of hyaluronan, N-acetylheparosan (heparosan or unsulfated, unepimerized heparin), and unsulfated chondroitin, respectively. Previously, a type D heparosan synthase, a glycosyltransferase that forms the repeating disaccharide heparosan backbone, was identified. Here, a ?73% identical gene product that is encoded outside of the capsule biosynthesis locus was also shown to be a functional heparosan synthase. Unlike PmHS1, the PmHS2 enzyme was not stimulated greatly by the addition of an exogenous polymer acceptor and yielded smaller- molecular-weight-product size distributions. Virtually identical hssB genes are found in most type A, D, and F isolates. The occurrence of multiple polysaccharide synthases in a single strain invokes the potential for capsular variation.

DeAngelis, Paul L.; White, Carissa L.

2004-01-01

95

Identification of a distinct, cryptic heparosan synthase from Pasteurella multocida types A, D, and F.  

PubMed

The extracellular polysaccharide capsules of Pasteurella multocida types A, D, and F are composed of hyaluronan, N-acetylheparosan (heparosan or unsulfated, unepimerized heparin), and unsulfated chondroitin, respectively. Previously, a type D heparosan synthase, a glycosyltransferase that forms the repeating disaccharide heparosan backbone, was identified. Here, a approximately 73% identical gene product that is encoded outside of the capsule biosynthesis locus was also shown to be a functional heparosan synthase. Unlike PmHS1, the PmHS2 enzyme was not stimulated greatly by the addition of an exogenous polymer acceptor and yielded smaller- molecular-weight-product size distributions. Virtually identical hssB genes are found in most type A, D, and F isolates. The occurrence of multiple polysaccharide synthases in a single strain invokes the potential for capsular variation. PMID:15576804

Deangelis, Paul L; White, Carissa L

2004-12-01

96

Two distinct types of fatty acid-binding protein are expressed in heart ventricle of Antarctic teleost fishes.  

PubMed

This report provides the first evidence for the existence of two distinct types of fatty acid-binding protein (FABP) in cardiac tissue of vertebrates. Four species of Antarctic teleost fish (Chaenocephalus aceratus, Cryodraco antarcticus, Gobionotothen gibberifrons and Notothenia coriiceps) exhibited two FABP mRNAs of 1. 0 kb and 0.8 kb, which we have termed Hh-FABP and Had-FABP (isolated from Heart tissue, with similarity to mammalian heart-type FABP or mammalian adipose-type FABP respectively). These FABP types appear to be products of distinct genes. Both FABP transcripts were abundant in cardiac and aerobic pectoral muscle. However, relative abundance of the two types varied distinctly among other tissues such as kidney, brain, spleen and white muscle. Neither FABP type was expressed in liver or intestine. The coding regions of Hh-FABP and Had-FABP cDNAs from the same species are only approximately 60% identical with one another. However, homologues of each FABP species, which exhibit >98% identity to their respective types, were isolated from three other Antarctic teleosts. Phylogenetic analysis of aligned amino-acid sequences places Hh-FABP with other vertebrate heart-type FABPs, and Had with adipose/cutaneous FABPs. Expression of two distinct FABPs in cardiac tissue of Antarctic teleosts may be related to their ability to both utilize fatty acid as the primary metabolic fuel and to store lipid intracellularly. PMID:9461533

Vayda, M E; Londraville, R L; Cashon, R E; Costello, L; Sidell, B D

1998-02-15

97

Two distinct types of fatty acid-binding protein are expressed in heart ventricle of Antarctic teleost fishes.  

PubMed Central

This report provides the first evidence for the existence of two distinct types of fatty acid-binding protein (FABP) in cardiac tissue of vertebrates. Four species of Antarctic teleost fish (Chaenocephalus aceratus, Cryodraco antarcticus, Gobionotothen gibberifrons and Notothenia coriiceps) exhibited two FABP mRNAs of 1. 0 kb and 0.8 kb, which we have termed Hh-FABP and Had-FABP (isolated from Heart tissue, with similarity to mammalian heart-type FABP or mammalian adipose-type FABP respectively). These FABP types appear to be products of distinct genes. Both FABP transcripts were abundant in cardiac and aerobic pectoral muscle. However, relative abundance of the two types varied distinctly among other tissues such as kidney, brain, spleen and white muscle. Neither FABP type was expressed in liver or intestine. The coding regions of Hh-FABP and Had-FABP cDNAs from the same species are only approximately 60% identical with one another. However, homologues of each FABP species, which exhibit >98% identity to their respective types, were isolated from three other Antarctic teleosts. Phylogenetic analysis of aligned amino-acid sequences places Hh-FABP with other vertebrate heart-type FABPs, and Had with adipose/cutaneous FABPs. Expression of two distinct FABPs in cardiac tissue of Antarctic teleosts may be related to their ability to both utilize fatty acid as the primary metabolic fuel and to store lipid intracellularly.

Vayda, M E; Londraville, R L; Cashon, R E; Costello, L; Sidell, B D

1998-01-01

98

Bent Bone Dysplasia-FGFR2 type, a Distinct Skeletal Disorder, Has Deficient Canonical FGF Signaling  

PubMed Central

Fibroblast growth factor receptor 2 (FGFR2) is a crucial regulator of bone formation during embryonic development. Both gain and loss-of-function studies in mice have shown that FGFR2 maintains a critical balance between the proliferation and differentiation of osteoprogenitor cells. We have identified de novo FGFR2 mutations in a sporadically occurring perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones. Histological analysis of the long bones revealed that the growth plate contained smaller hypertrophic chondrocytes and a thickened hypercellular periosteum. Four unrelated affected individuals were found to be heterozygous for missense mutations that introduce a polar amino acid into the hydrophobic transmembrane domain of FGFR2. Using diseased chondrocytes and a cell-based assay, we determined that these mutations selectively reduced plasma-membrane levels of FGFR2 and markedly diminished the receptor's responsiveness to extracellular FGF. All together, these clinical and molecular findings are separate from previously characterized FGFR2 disorders and represent a distinct skeletal dysplasia.

Merrill, Amy E.; Sarukhanov, Anna; Krejci, Pavel; Idoni, Brian; Camacho, Natalia; Estrada, Kristine D.; Lyons, Karen M.; Deixler, Hannah; Robinson, Haynes; Chitayat, David; Curry, Cynthia J.; Lachman, Ralph S.; Wilcox, William R.; Krakow, Deborah

2012-01-01

99

Digital morphometry of rat cerebellar climbing fibers reveals distinct branch and bouton types.  

PubMed

Cerebellar climbing fibers (CFs) provide powerful excitatory input to Purkinje cells (PCs), which represent the sole output of the cerebellar cortex. Recent discoveries suggest that CFs have information-rich signaling properties important for cerebellar function, beyond eliciting the well known all-or-none PC complex spike. CF morphology has not been quantitatively analyzed at the same level of detail as its biophysical properties. Because morphology can greatly influence function, including the capacity for information processing, it is important to understand CF branching structure in detail, as well as its variability across and within arbors. We have digitally reconstructed 68 rat CFs labeled using biotinylated dextran amine injected into the inferior olive and comprehensively quantified their morphology. CF structure was considerably diverse even within the same anatomical regions. Distinctly identifiable primary, tendril, and distal branches could be operationally differentiated by the relative size of the subtrees at their initial bifurcations. Additionally, primary branches were more directed toward the cortical surface and had fewer and less pronounced synaptic boutons, suggesting they prioritize efficient and reliable signal propagation. Tendril and distal branches were spatially segregated and bouton dense, indicating specialization in signal transmission. Furthermore, CFs systematically targeted molecular layer interneuron cell bodies, especially at terminal boutons, potentially instantiating feedforward inhibition on PCs. This study offers the most detailed and comprehensive characterization of CF morphology to date. The reconstruction files and metadata are publicly distributed at NeuroMorpho.org. PMID:23077053

Brown, Kerry M; Sugihara, Izumi; Shinoda, Yoshikazu; Ascoli, Giorgio A

2012-10-17

100

Distinct Structural Elements Dictate the Specificity of the Type III Pentaketide Synthase from Neurospora crassa  

SciTech Connect

The fungal type III polyketide synthase 2'-oxoalkylresorcyclic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C{sub 4}--C{sub 20}) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 {angstrom} resolution, the Phe-252{yields}Gly site-directed mutant to 2.1 {angstrom} resolution, and a binary conplex of ORAS with eicosanoic acid to 2.0 {angstrom} resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accomodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.

Rubin-Pitel, Sheryl B.; Zhang, Houjin; Vu, Trang; Brunzelle, Joseph S.; Zhao, Huimin; Nair, Satish K. (UIUC); (NWU)

2009-01-15

101

Discovery of a Distinct Superfamily of Kunitz-Type Toxin (KTT) from Tarantulas  

PubMed Central

Background Kuntiz-type toxins (KTTs) have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking) were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. Principal Findings Here we report the presence of a new superfamily of KTTs in spiders (Tarantulas: Ornithoctonus huwena and Ornithoctonus hainana), which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI) as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (?) for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins) derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications. Conclusions/Significance These finding illustrate that the two activity sites of Kunitz-type toxins are functionally and evolutionally independent and provide new insights into effects of Darwinian selection pressures on KTT evolution, and mechanisms by which new functions can be grafted onto old protein scaffolds.

Diao, Jian-Bo; Jiang, Li-Ping; Tang, Xing; Liang, Song-Ping

2008-01-01

102

Distinct behavioural and network correlates of two interneuron types in prefrontal cortex.  

PubMed

Neurons in the prefrontal cortex exhibit diverse behavioural correlates, an observation that has been attributed to cell-type diversity. To link identified neuron types with network and behavioural functions, we recorded from the two largest genetically defined inhibitory interneuron classes, the perisomatically targeting parvalbumin (PV) and the dendritically targeting somatostatin (SOM) neurons in anterior cingulate cortex of mice performing a reward foraging task. Here we show that PV and a subtype of SOM neurons form functionally homogeneous populations showing a double dissociation between both their inhibitory effects and behavioural correlates. Out of several events pertaining to behaviour, a subtype of SOM neurons selectively responded at reward approach, whereas PV neurons responded at reward leaving and encoded preceding stay duration. These behavioural correlates of PV and SOM neurons defined a behavioural epoch and a decision variable important for foraging (whether to stay or to leave), a crucial function attributed to the anterior cingulate cortex. Furthermore, PV neurons could fire in millisecond synchrony, exerting fast and powerful inhibition on principal cell firing, whereas the inhibitory effect of SOM neurons on firing output was weak and more variable, consistent with the idea that they respectively control the outputs of, and inputs to, principal neurons. These results suggest a connection between the circuit-level function of different interneuron types in regulating the flow of information and the behavioural functions served by the cortical circuits. Moreover, these observations bolster the hope that functional response diversity during behaviour can in part be explained by cell-type diversity. PMID:23708967

Kvitsiani, D; Ranade, S; Hangya, B; Taniguchi, H; Huang, J Z; Kepecs, A

2013-05-26

103

Sources and Types of Confidence Identified by World Class Sport Performers  

Microsoft Academic Search

This study identified the sources and types of confidence salient to 14 (7 male, 7 female) successful World Class athletes. Nine sources of confidence were identified: Preparation, performance accomplishments, coaching, innate factors, social support, experience, competitive advantage, self-awareness, and trust. A testament to the multi-dimensional nature of sport confidence, six types of sport confidence were also identified: skill execution, achievement,

Kate Hays; Ian Maynard; Owen Thomas; Mark Bawden

2007-01-01

104

Mucinous and neuroendocrine breast carcinomas are transcriptionally distinct from invasive ductal carcinomas of no special type  

Microsoft Academic Search

Mucinous carcinoma is considered a distinct pathological entity. However, mucinous tumours can be divided into a least two groups: mucinous A (or paucicellular) and mucinous B (or hypercellular). Mucinous B cancers display histological features that significantly overlap with those of neuroendocrine carcinomas. We investigate using genome-wide oligonucleotide microarrays whether mucinous A, mucinous B and neuroendocrine carcinomas are entities distinct from

Britta Weigelt; Felipe C Geyer; Hugo M Horlings; Bas Kreike; Hans Halfwerk; Jorge S Reis-Filho

2009-01-01

105

Acidification of morphologically distinct endosomes in mutant and wild- type Chinese hamster ovary cells  

PubMed Central

In the preceding paper (Yamashiro, D. J., and F. R. Maxfield. 1987. J. Cell Biol. 105:2713-2721), we have shown that there is rapid acidification of endosomal compartments to pH 6.3 by 3 min in wild-type Chinese hamster ovary (CHO) cells. In contrast, early acidification of endosomes is markedly reduced in the CHO mutants, DTF 1-5-4 and DTF 1-5- 1. Since these CHO mutants are pleiotropically defective in endocytosis (Robbins, A. R., S. S. Peng, and J. L. Marshall. 1983. J. Cell Biol. 96:1064-1071; Robbins, A. R., C. Oliver, J. L. Bateman, S. S. Krag, C. J. Galloway, and I. Mellman. 1984. J. Cell Biol. 99:1296-1308), our results are consistent with a requirement for proper acidification of early endocytic compartments in many pH-regulated endocytic processes. In this paper, by measuring the pH of morphologically distinct endosomes using fluorescence microscopy and digital image analysis, we have determined in which of the endocytic compartments the defective acidification occurs. We found that the acidification of both the para- Golgi recycling endosomes and lysosomes was normal in the CHO mutants DTG 1-5-4 and DTF 1-5-1. The mean pH of large endosomes containing either fluorescein-labeled alpha 2-macroglobulin or fluorescein- isothiocyanate dextran was only slightly less acidic in the mutant cells than in wild-type cells. However, when we examined the pH of individual large (150-250 nm) endosomes, we found that there was an increased number of endosomes with a pH greater than 6.5 in the CHO mutants when compared with wild-type cells. Heterogeneity in the acidification of large endosomes was also seen in DTF 1-5-1 by a combined null point pH method and digital image analysis technique. In addition, both CHO mutants showed a marked decrease in the acidification of the earliest endosomal compartment, a diffusely fluorescent compartment comprised of small vesicles and tubules. We suggest that the defect in endosome acidification is most pronounced in the early, small vesicular, and tubular endosomes and that this defect partially carries over to the large endosomes that are involved in the sorting and processing of ligands. The proper step-wise acidification of the different endosomes along the endocytic pathway may have an important role in the regulation of endocytic processes.

1987-01-01

106

Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome  

PubMed Central

Background Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. Methods We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. Results We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.

2012-01-01

107

Lung Adenocarcinoma Global Profiling Identifies Type II Transforming Growth Factor Receptor as a Repressor of Invasiveness  

Microsoft Academic Search

Rationale: Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness. Objectives: We hypothesized that invasiveness is associated with a distinct mo- lecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrixremodelingpathwaysassociatedwiththeacquisitionofinva- siveness in lung adenocarcinoma. Main Results: Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and

Alain C. Borczuk; Han K. Kim; Hilary A. Yegen; Richard A. Friedman; Charles A. Powell

2005-01-01

108

Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits  

Microsoft Academic Search

Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of computed tomography (CT) measured hepatic steatosis, a non-invasive measure of NAFLD, in large population based samples. Using variance components methods, we show that CT hepatic

Elizabeth K. Speliotes; Laura M. Yerges-Armstrong; Jun Wu; Ruben Hernaez; Lauren J. Kim; Cameron D. Palmer; Vilmundur Gudnason; Gudny Eiriksdottir; Melissa E. Garcia; Lenore J. Launer; Michael A. Nalls; Jeanne M. Clark; Braxton D. Mitchell; Alan R. Shuldiner; Johannah L. Butler; Marta Tomas; Udo Hoffmann; Shih-Jen Hwang; Joseph M. Massaro; Christopher J. ODonnell; Dushyant V. Sahani; Veikko Salomaa; Eric E. Schadt; Stephen M. Schwartz; David S. Siscovick; Benjamin F. Voight; J. Jeffrey Carr; Mary F. Feitosa; Tamara B. Harris; Caroline S. Fox; Albert V. Smith; W. H. Linda Kao; Joel N. Hirschhorn; Ingrid B. Borecki; M. den Heijer; J. J. Hottenga; G. Willemsen; Geus de E. J. C; D. I. Boomsma

2011-01-01

109

Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm.  

PubMed

Thyroid carcinoma has been described as occurring more frequently than expected in association with familial adenomatous polyposis. The histology of these cases has not been described in detail, although the reported cases were usually diagnosed as papillary carcinoma. We now report the pathological features of four cases of thyroid carcinoma associated with familial adenomatous polyposis, and review the findings in the literature. The tumours in these four cases were all of follicular cell origin as shown by thyroglobulin immunohistochemistry. In three they were multifocal. The tumours showed some features of papillary carcinoma--grooved nuclei and papillary architecture, but these were not consistent. They also showed features that were unusual for papillary carcinoma--a cribriform pattern and solid areas with spindle cell component. Commonly the tumours combined both patterns. A review of the reported cases of thyroid cancer associated with familial adenomatous polyposis showed that they also were commonly multifocal and occurred predominantly in young women. When the histology was adequately reported or illustrated it was, in most instances, consistent with the findings in our own cases. We therefore suggest that these thyroid tumours form a distinct type with some unusual features. Clearly it is likely that the APC gene is associated with their pathogenesis, and that other factors contribute to the predominantly female incidence in this as in sporadic tumours. Six of 63 reported cases showed metastasis or died from thyroid carcinoma. In a number of cases the tumours presented before the familial adenomatous polyposis was recognized. The findings of these unusual histological features in a thyroid tumour, and particularly of multicentricity, should alert the pathologist to the possibility of familial adenomatous polyposis with its implications for family screening. The tumours are often well demarcated but, because of the multicentricity, total thyroidectomy should be advocated. PMID:7698732

Harach, H R; Williams, G T; Williams, E D

1994-12-01

110

A major human immunodeficiency virus type 1-initiated killing pathway distinct from apoptosis.  

PubMed Central

We have investigated the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with T-cell-tropic, cytopathic human immunodeficiency virus type 1 (HIV-1), by employing diverse strategies to inhibit PCD or to detect its common end-stage sequelae. When Bcl-2-transfected cell lines were infected with HIV-1, their viability was only slightly higher than that of control infections. Although the adenovirus E1B 19-kDa protein has been reported to be a stronger competitor of apoptosis than Bcl-2, it did not inhibit HIV-mediated cell death better than Bcl-2 protein. Competition for Fas ligand or inactivation of the Fas pathway secondary to intracellular mutation (MOLT-4 T cells) also had modest effects on overall cell death during acute HIV infection. In contrast to these observations with HIV infection or with HIV envelope-initiated cell death, Tat-expressing cell lines were much more susceptible (200% enhancement) to Fas-induced apoptosis than controls and Bcl-2 overexpression strongly (75%) inhibited this apoptotic T-cell death. PCD associated with FasR ligation resulted in the cleavage of common interleukin-1beta-converting enzyme (ICE)-protease targets, poly(ADP-ribose) polymerase (PARP) and pro-ICE, whereas cleaved products were not readily detected during HIV infection of peripheral blood mononuclear cells or T-cell lines even during periods of extensive cell death. These results indicate that one important form of HIV-mediated cell killing proceeds by a pathway that lacks the characteristics of T-cell apoptosis. Our observations support the conclusion that at least two HIV genes (env and tat) can kill T cells by distinct pathways and that an envelope-initiated process of T-cell death can be discriminated from apoptosis by many of the properties most closely associated with apoptotic cell death.

Kolesnitchenko, V; King, L; Riva, A; Tani, Y; Korsmeyer, S J; Cohen, D I

1997-01-01

111

Tectonically Undulating Terrestrial Geospheres and Concordant Development of Two Distinct Somatic Types of Man  

NASA Astrophysics Data System (ADS)

The human organisms in microgravity conditions loss Ca or become less dense. But variously dense men also develop on Earth due to varying tectonics. As any celestial body, Earth is not a billiard-ball but is complexly warped by a number of standing waves imprinted in the geoid shape. The fundamental wave (long 2? R, R- planet radius) makes tectonic dichotomy (an opposition of the eastern and western oceanic hemispheres), the first overtone (? R) makes sectoring: on the continental eastern hemisphere, for example, around the Pamirs-Hindukush converge 4 sectors. They are 2 opposed differently uplifted (African ++, Asian +) separated by 2 opposed differently subsided (Eurasian -, Indoceanic - -). In rotating Earth the alternating uplifts (++, +) and subsidences (- -, -) require materials of different densities: less dense for uplifts and denser for subsidences. This requirement concerns all geospheres including anthroposphere. The long development of Homo sapiens adapting to graviconditions of uplifting and subsiding blocks produced two distinct somatic types of man: long and narrow (slim) leptosomes and short and broad eirisomes. As shows F. Weidenreich [1], this fundamental division appeared very early in the human history and is observed in all great human races and even in apes. A block uplifting (an increase of the planetary radius) requires diminishing density. This is achieved by distributing the man's weight by the longer stature. Thus appears long and slim leptosome. On the contrary, a block subsidence (diminishing radius) requires increasing density: man is shorter and broader (eirisome). A long existence on intensively moving (up or down) blocks makes these somatic types characteristic of races. Thus, many African tribes developing on intensively moving up continent (more than one kilometer in a few mln. y. ) are leptosomatic; on the contrary, Indians of subsiding western hemisphere are typically eirisomatic with high Rohrer's index; Polynesians of Pacific are high but corpulent, the Rohrer' index is also high. Short in time cosmic experiments (abrupt uplifting) with a sharp drop in gravity produce noticeable effect of Ca leaching out of organism making it less dense. Sure, changing gravity influences not only bones but also flesh, blood, hairs and eventually genes. The frequencies of genetic markers of Rh-system in blood of inhabitants of 4 variously leveled sectors and subsided western hemisphere are clearly different. References: [1] F. Weidenreich. Rasse und Körperbau (in Russian translation, State Publishing House, Moscow-Leningrad, 1929, 271 pp.).

Kochemasov, G. G.

112

Heterologous Expression Studies of Saccharomyces cerevisiae Reveal Two Distinct Trypanosomatid CaaX Protease Activities and Identify Their Potential Targets? †  

PubMed Central

The CaaX tetrapeptide motif typically directs three sequential posttranslational modifications, namely, isoprenylation, proteolysis, and carboxyl methylation. In all eukaryotic systems evaluated to date, two CaaX proteases (Rce1 and Ste24/Afc1) have been identified. Although the Trypanosoma brucei genome also encodes two putative CaaX proteases, the lack of detectable T. brucei Ste24 activity in trypanosome cell extracts has suggested that CaaX proteolytic activity within this organism is solely attributed to T. brucei Rce1 (J. R. Gillespie et al., Mol. Biochem. Parasitol. 153:115-124. 2007). In this study, we demonstrate that both T. brucei Rce1 and T. brucei Ste24 are enzymatically active when heterologously expressed in yeast. Using a-factor and GTPase reporters, we demonstrate that T. brucei Rce1 and T. brucei Ste24 possess partially overlapping specificities much like, but not identical to, their fungal and human counterparts. Of interest, a CaaX motif found on a trypanosomal Hsp40 protein was not cleaved by either T. brucei CaaX protease when examined in the context of the yeast a-factor reporter but was cleaved by both in the context of the Hsp40 protein itself when evaluated using an in vitro radiolabeling assay. We further demonstrate that T. brucei Rce1 is sensitive to small molecules previously identified as inhibitors of the yeast and human CaaX proteases and that a subset of these compounds disrupt T. brucei Rce1-dependent localization of our GTPase reporter in yeast. Together, our results suggest the conserved presence of two CaaX proteases in trypanosomatids, identify an Hsp40 protein as a substrate of both T. brucei CaaX proteases, support the potential use of small molecule CaaX protease inhibitors as tools for cell biological studies on the trafficking of CaaX proteins, and provide evidence that protein context influences T. brucei CaaX protease specificity.

Mokry, David Z.; Manandhar, Surya P.; Chicola, Kristen A.; Santangelo, George M.; Schmidt, Walter K.

2009-01-01

113

Distinct deregulation of the hypoxia inducible factor by PHD2 mutants identified in germline DNA of patients with polycythemia  

PubMed Central

Background Congenital secondary erythrocytoses are due to deregulation of hypoxia inducible factor resulting in overproduction of erythropoietin. The most common germline mutation identified in the hypoxia signaling pathway is the Arginine 200-Tryptophan mutant of the von Hippel-Lindau tumor suppressor gene, resulting in Chuvash polycythemia. This mutant displays a weak deficiency in hypoxia inducible factor ? regulation and does not promote tumorigenesis. Other von Hippel-Lindau mutants with more deleterious effects are responsible for von Hippel-Lindau disease, which is characterized by the development of multiple tumors. Recently, a few mutations in gene for the prolyl hydroxylase domain 2 protein (PHD2) have been reported in cases of congenital erythrocytosis not associated with tumor formation with the exception of one patient with a recurrent extra-adrenal paraganglioma. Design and Methods Five PHD2 variants, four of which were novel, were identified in patients with erythrocytosis. These PHD2 variants were functionally analyzed and compared with the PHD2 mutant previously identified in a patient with polycythemia and paraganglioma. The capacity of PHD2 to regulate the activity, stability and hydroxylation of hypoxia inducible factor ? was assessed using hypoxia-inducible reporter gene, one-hybrid and in vitro hydroxylation assays, respectively. Results This functional comparative study showed that two categories of PHD2 mutants could be distinguished: one category with a weak deficiency in hypoxia inducible factor ? regulation and a second one with a deleterious effect; the mutant implicated in tumor occurrence belongs to the second category. Conclusions As observed with germline von Hippel-Lindau mutations, there are functional differences between the PHD2 mutants with regards to hypoxia inducible factor regulation. PHD2 mutation carriers do, therefore, need careful medical follow-up, since some mutations must be considered as potential candidates for tumor predisposition.

Ladroue, Charline; Hoogewijs, David; Gad, Sophie; Carcenac, Romain; Storti, Federica; Barrois, Michel; Gimenez-Roqueplo, Anne-Paule; Leporrier, Michel; Casadevall, Nicole; Hermine, Olivier; Kiladjian, Jean-Jacques; Baruchel, Andre; Fakhoury, Fadi; Bressac-de Paillerets, Brigitte; Feunteun, Jean; Mazure, Nathalie; Pouyssegur, Jacques; Wenger, Roland H.; Richard, Stephane; Gardie, Betty

2012-01-01

114

Evidence that two distinct crypt cell types secrete chloride and potassium in human colon.  

PubMed

BACKGROUND: Human colon may secrete substantial amounts of water secondary to chloride (Cl(-)) and/or potassium (K(+)) secretion in a variety of diarrhoeal diseases. Ion secretion occurs via Cl(-) and K(+) channels, which are generally assumed to be co-located in the colonocyte apical membrane, although their exact cellular sites remain unclear. OBJECTIVE:  To investigate the location of apical Cl(-) (CFTR) and apical K(+) (large conductance; BK) channels within human colonic epithelium. DESIGN: Whole-cell patch clamp recordings were obtained from intact human colonic crypts. Specific blockers of K(+) channels and CFTR identified different types of K(+) channel and CFTR under resting conditions and after stimulating intracellular cAMP with forskolin. The BK channel ?3-subunit was localised by immunostaining. RESULTS: Two types of crypt cells were identified. One (73% of cells) had whole-cell currents dominated by intermediate conductance (IK) K(+) channels under resting conditions, which developed large CFTR-mediated currents in response to increasing intracellular cAMP. The other (27% of cells) had resting currents dominated by BK channels inhibited by the BK channel blocker penitrem A, but insensitive to both forskolin and the IK channel blocker clotrimazole. Immunostaining showed co-localisation of the BK channel ?3-subunit and the goblet cell marker, MUC2. CONCLUSIONS: In human colon, Cl(-) secretion originates from the dominant population of colonocytes expressing apical CFTR, whereas K(+) secretion is derived from a smaller population of goblet cells expressing apical BK channels. These findings provide new insights into the pathophysiology of secretory diarrhoea and should be taken into account during the development of anti-diarrhoeal drugs. PMID:23740188

Linley, John; Loganathan, Arun; Kopanati, Shashikala; Sandle, Geoffrey I; Hunter, Malcolm

2013-06-01

115

Progression and Regression: Distinct Developmental Patterns of Diabetic Retinopathy in Patients With Type 2 Diabetes Treated in the Diabetes Care System West-Friesland, the Netherlands  

PubMed Central

OBJECTIVE To identify distinct developmental patterns of diabetic retinopathy (DR) and assess the risk factor levels of patients in these clusters. RESEARCH DESIGN AND METHODS A cohort of 3,343 patients with type 2 diabetes mellitus (T2DM) monitored and treated in the Diabetes Care System West-Friesland, the Netherlands, was followed from 2 to 6 years. Risk factors were measured, and two-field fundus photographs were taken annually and graded according to the EURODIAB study group. Latent class growth modeling was used to identify distinct developmental patterns of DR over time. RESULTS Five clusters of patients with distinct developmental patterns of DR were identified: A, patients without any signs of DR (88.9%); B, patients with a slow regression from minimal background to no DR (4.9%); C, patients with a slow progression from minimal background to moderate nonproliferative DR (4.0%); D, patients with a fast progression from minimal or moderate nonproliferative to (pre)proliferative or treated DR (1.4%); and E, patients with persistent proliferative DR (0.8%). Patients in clusters A and B were characterized by lower risk factor levels, such as diabetes duration, HbA1c, and systolic blood pressure compared with patients in progressive clusters (C–E). CONCLUSIONS Clusters of patients with T2DM with markedly different patterns of DR development were identified, including a cluster with regression of DR. These clusters enable a more detailed examination of the influence of various risk factors on DR.

Zavrelova, Hata; Hoekstra, Trynke; Alssema, Marjan; Welschen, Laura M.C.; Nijpels, Giel; Moll, Annette C.; de Vet, Henrica C.W.; Polak, Bettine C.P.; Dekker, Jacqueline M.

2011-01-01

116

HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor ? on genetically distinct surfaces.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) requires the cellular transcription factor core binding factor subunit ? (CBF?) to stabilize its viral infectivity factor (Vif) protein and neutralize the APOBEC3 restriction factors. CBF? normally heterodimerizes with the RUNX family of transcription factors, enhancing their stability and DNA-binding affinity. To test the hypothesis that Vif may act as a RUNX mimic to bind CBF?, we generated a series of CBF? mutants at the RUNX/CBF? interface and tested their ability to stabilize Vif and impact transcription at a RUNX-dependent promoter. While several CBF? amino acid substitutions disrupted promoter activity, none of these impacted the ability of CBF? to stabilize Vif or enhance degradation of APOBEC3G. A mutagenesis screen of CBF? surface residues identified a single amino acid change, F68D, that disrupted Vif binding and its ability to degrade APOBEC3G. This mutant still bound RUNX and stimulated RUNX-dependent transcription. These separation-of-function mutants demonstrate that HIV-1 Vif and the RUNX transcription factors interact with cellular CBF? on genetically distinct surfaces. PMID:22725134

Hultquist, Judd F; McDougle, Rebecca M; Anderson, Brett D; Harris, Reuben S

2012-08-13

117

Gene Expression Identifies Distinct Ascending Glutamatergic Pathways to Frequency-Organized Auditory Cortex in the Rat Brain  

PubMed Central

A conserved feature of sound processing across species is the presence of multiple auditory cortical fields with topographically organized responses to sound frequency. Current organizational schemes propose that the ventral division of the medial geniculate body (MGBv) is a single functionally homogenous structure that provides the primary source of input to all neighboring frequency-organized cortical fields. These schemes fail to account for the contribution of MGBv to functional diversity between frequency-organized cortical fields. Here, we report response property differences for two auditory fields in the rat, and find they have nonoverlapping sources of thalamic input from the MGBv that are distinguished by the gene expression for type 1 vesicular glutamate transporter. These data challenge widely accepted organizational schemes and demonstrate a genetic plurality in the ascending glutamatergic pathways to frequency-organized auditory cortex.

Storace, Douglas A.; Higgins, Nathan C.; Chikar, Jennifer A.; Oliver, Douglas L.

2012-01-01

118

An EST-based analysis identifies new genes and reveals distinctive gene expression features of Coffea arabica and Coffea canephora  

PubMed Central

Background Coffee is one of the world's most important crops; it is consumed worldwide and plays a significant role in the economy of producing countries. Coffea arabica and C. canephora are responsible for 70 and 30% of commercial production, respectively. C. arabica is an allotetraploid from a recent hybridization of the diploid species, C. canephora and C. eugenioides. C. arabica has lower genetic diversity and results in a higher quality beverage than C. canephora. Research initiatives have been launched to produce genomic and transcriptomic data about Coffea spp. as a strategy to improve breeding efficiency. Results Assembling the expressed sequence tags (ESTs) of C. arabica and C. canephora produced by the Brazilian Coffee Genome Project and the Nestlé-Cornell Consortium revealed 32,007 clusters of C. arabica and 16,665 clusters of C. canephora. We detected different GC3 profiles between these species that are related to their genome structure and mating system. BLAST analysis revealed similarities between coffee and grape (Vitis vinifera) genes. Using KA/KS analysis, we identified coffee genes under purifying and positive selection. Protein domain and gene ontology analyses suggested differences between Coffea spp. data, mainly in relation to complex sugar synthases and nucleotide binding proteins. OrthoMCL was used to identify specific and prevalent coffee protein families when compared to five other plant species. Among the interesting families annotated are new cystatins, glycine-rich proteins and RALF-like peptides. Hierarchical clustering was used to independently group C. arabica and C. canephora expression clusters according to expression data extracted from EST libraries, resulting in the identification of differentially expressed genes. Based on these results, we emphasize gene annotation and discuss plant defenses, abiotic stress and cup quality-related functional categories. Conclusion We present the first comprehensive genome-wide transcript profile study of C. arabica and C. canephora, which can be freely assessed by the scientific community at http://www.lge.ibi.unicamp.br/coffea. Our data reveal the presence of species-specific/prevalent genes in coffee that may help to explain particular characteristics of these two crops. The identification of differentially expressed transcripts offers a starting point for the correlation between gene expression profiles and Coffea spp. developmental traits, providing valuable insights for coffee breeding and biotechnology, especially concerning sugar metabolism and stress tolerance.

2011-01-01

119

A Distinct Class of Inducible Murine Type-C Viruses that Replicates in the Rabbit SIRC Cell Line  

Microsoft Academic Search

The existence of the selectively permissive rabbit cell line SIRC allows definition of a new class of endogenous murine type-C virus. Continuous clonal lines of transformed cells derived from the BALB\\/c mouseembryo cell line BALB\\/3T3 contain at least two distinct classes of endogenous type-C viral genomes. Spontaneously released endogenous viruses grow well on the mouse cell line NIH\\/3T3 (N-tropic viruses)

Raoul E. Benveniste; Michael M. Lieber; George J. Todaro

1974-01-01

120

Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism  

Microsoft Academic Search

Growth\\/differentiation factor 5 (GDF5) is a secreted growth factor that plays a key regulatory role in embryonic skeletal\\u000a and joint development. Mutations in the GDF5 gene can cause different types of skeletal dysplasia, including brachydactyly\\u000a type C (BDC) and proximal symphalangism (SYM1). We report two novel mutations in the GDF5 gene in Chinese families with distinct limb malformations. In one

Wei Yang; Lihua Cao; Wenli Liu; Li Jiang; Miao Sun; Dai Zhang; Shusen Wang; Wilson H. Y. Lo; Yang Luo; Xue Zhang

2008-01-01

121

Differential display reverse transcription PCR applied to male Mytilus edulis mussels with two distinct mitochondrial DNA types  

Microsoft Academic Search

Differential display reverse transcriptase PCR (DD-RT-PCR) was used to test for differences in gene expression in gonad tissue of 12 male blue mussels (Mytilus edulis) containing one of two distinct types of mitochondrial DNA. These two male mitotypes, referred to as the “standard” and “recently-masculinized” M-types, respectively, exhibit ?16.5% uncorrected sequence divergence and ?8.7% amino acid sequence divergence. Pairwise comparisons

Erin H. Knock; Stephen D. Petersen; Donald T. Stewart

2005-01-01

122

Cross-Species Analyses Identify the BNIP-2 and Cdc42GAP Homology (BCH) Domain as a Distinct Functional Subclass of the CRAL_TRIO/Sec14 Superfamily  

PubMed Central

The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ?100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs (‘h’ is large and hydrophobic residue and ‘s’ is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding ‘BCH-only’ domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, ‘BCH-like’ and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases.

Gupta, Anjali Bansal; Wee, Liang En; Zhou, Yi Ting; Hortsch, Michael; Low, Boon Chuan

2012-01-01

123

Heat-induced antigen retrieval: an effective method to detect and identify progenitor cell types during adult hippocampal neurogenesis.  

PubMed

Traditional methods of immunohistochemistry (IHC) following tissue fixation allow visualization of various cell types. These typically proceed with the application of antibodies to bind antigens and identify cells with characteristics that are a function of the inherent biology and development. Adult hippocampal neurogenesis is a sequential process wherein a quiescent neural stem cell can become activated and proceed through stages of proliferation, differentiation, maturation and functional integration. Each phase is distinct with a characteristic morphology and upregulation of genes. Identification of these phases is important to understand the regulatory mechanisms at play and any alterations in this process that underlie the pathophysiology of debilitating disorders. Our heat-induced antigen retrieval approach improves the intensity of the signal that is detected and allows correct identification of the progenitor cell type. As discussed in this paper, it especially allows us to circumvent current problems in detection of certain progenitor cell types. PMID:24022759

Hussaini, Syed M Q; Jun, Heechul; Cho, Chang Hoon; Kim, Hyo Jin; Kim, Woon Ryoung; Jang, Mi-Hyeon

2013-08-30

124

Parameter estimation of a monod-type model. Part I: Theoretical identifiability and sensitivity analysis  

Microsoft Academic Search

Parameter estimation of a Monod-type model based on the study of the theoretical identifiability of the model followed by the sensitivity analysis of the state variables with respect to parameters is presented. Theorerical identifiability allows to establish the unicity of the solution. On the other hand, sensitivity analysis throws light on the conditions that make parameters identifiable. Thus, the introduction

N. Chouakri; C. Fonteix; I. Marc; J. P. Corriou

1994-01-01

125

Pascal-Type Triangle for the Number of Topologically Distinct Many-Electron Feynman Graphs.  

National Technical Information Service (NTIS)

Expressing the Green's function for a many body system by means of a perturbative expansion written as a sum over all connected and topologically distinct Feynman graphs, it is shown that the number of such diagrams can be iteratively obtained from a Pasc...

F. Battaglia T. F. George

1987-01-01

126

Two traditions of happiness research, not two distinct types of happiness  

Microsoft Academic Search

In an earlier paper (Kashdan, Biswas-Diener, & King, 2008), we outlined a critique of the distinction being made between eudaimonic and hedonic forms of happiness. That paper seems to have had the desired effect in stimulating discourse on this important subject as evidenced by a number of responses from our colleagues. In this paper, we address these responses collectively. In

Robert Biswas-Diener; Todd B. Kashdan; Laura A. King

2009-01-01

127

Essential role of EBF1 in the generation and function of distinct mature B cell types  

PubMed Central

The transcription factor EBF1 is essential for lineage specification in early B cell development. In this study, we demonstrate by conditional mutagenesis that EBF1 is required for B cell commitment, pro–B cell development, and subsequent transition to the pre–B cell stage. Later in B cell development, EBF1 was essential for the generation and maintenance of several mature B cell types. Marginal zone and B-1 B cells were lost, whereas follicular (FO) and germinal center (GC) B cells were reduced in the absence of EBF1. Activation of the B cell receptor resulted in impaired intracellular signaling, proliferation and survival of EBF1-deficient FO B cells. Immune responses were severely reduced upon Ebf1 inactivation, as GCs were formed but not maintained. ChIP- and RNA-sequencing of FO B cells identified EBF1-activated genes that encode receptors, signal transducers, and transcriptional regulators implicated in B cell signaling. Notably, ectopic expression of EBF1 efficiently induced the development of B-1 cells at the expense of conventional B cells. These gain- and loss-of-function analyses uncovered novel important functions of EBF1 in controlling B cell immunity.

Vilagos, Bojan; Hoffmann, Mareike; Souabni, Abdallah; Sun, Qiong; Werner, Barbara; Medvedovic, Jasna; Bilic, Ivan; Minnich, Martina; Axelsson, Elin; Jaritz, Markus

2012-01-01

128

Meta-analysis of microarray-derived data from PACAP-deficient adrenal gland in vivo and PACAP-treated chromaffin cells identifies distinct classes of PACAP-regulated genes  

PubMed Central

Initial PACAP-regulated transcriptomes of PACAP-treated cultured chromaffin cells, and the adrenal gland of wild-type versus PACAP-deficient mice, have been assembled using microarray analysis. These were compared to previously acquired PACAP-regulated transcriptome sets from PC12 cells and mouse central nervous system, using the same microarray platform. The Ingenuity Pathways Knowledge Base was then employed to group regulated transcripts into common first and second messenger regulatory clusters. The purpose of our meta-analysis was to identify sets of genes regulated distinctly or in common by the neurotransmitter/neurotrophin PACAP in specific physiological contexts. Results suggest that PACAP participates in both the basal differentiated expression, and the induction upon physiological stimulation, of distinct sets of transcripts in neuronal and endocrine cells. PACAP in both developmental and acute regulatory paradigms acts on target genes regulated by either TNF? or TGF?, two first messengers acting on transcription mainly through NF?B and Smads, respectively.

Samal, Babru; Gerdin, Matthew J.; Huddleston, David; Hsu, Chang-Mei; Elkahloun, Abdel G.; Stroth, Nikolas; Hamelink, Carol; Eiden, Lee E.

2007-01-01

129

Occurrence of two distinct types of tissue inhibitors of metallo-proteinases-2 in Fugu rubripes  

NASA Astrophysics Data System (ADS)

In this study, genes of two distinct tissue inhibitors of metalloproteinases-2 (TIMP-2) from Japanese puffer fish Fugu rubripes, Fugu TIMP-2a and TIMP-2b, were cloned. The open reading frames of Fugu TIMP-2a and TIMP-2b cDNAs are composed of 660 and 657 nucleotides and 220 and 219 amino acids, respectively. Both Fugu TIMP-2s contain 12 cysteine residues, which might form six disulfide bonds as in other animals’ TIMP-2s. Reverse-transcribed polymerase chain reaction analysis showed the mRNAs of Fugu TIMP-2a and TIMP-2b to be expressed in some tissues examined with different expression patterns. These findings suggest that the two distinct Fugu TIMP-2s might perform different functions in Fugu tissues.

Yokoyama, Yoshihiro; Tsukamoto, Hiroshi; Suzuki, Tohru; Mizuta, Shohshi; Yoshinaka, Reiji

2005-07-01

130

Reciprocal phosphorylation of yeast glycerol-3-phosphate dehydrogenases in adaptation to distinct types of stress.  

PubMed

Eukaryotic cells have evolved mechanisms for ensuring growth and survival in the face of stress caused by a fluctuating environment. Saccharomyces cerevisiae has two homologous glycerol-3-phosphate dehydrogenases, Gpd1 and Gpd2, that are required to endure various stresses, including hyperosmotic shock and hypoxia. These enzymes are only partially redundant, and their unique functions were attributed previously to differential transcriptional regulation and localization. We find that Gpd1 and Gpd2 are negatively regulated through phosphorylation by distinct kinases under reciprocal conditions. Gpd2 is phosphorylated by the AMP-activated protein kinase Snf1 to curtail glycerol production when nutrients are limiting. Gpd1, in contrast, is a target of TORC2-dependent kinases Ypk1 and Ypk2. Inactivation of Ypk1 by hyperosmotic shock results in dephosphorylation and activation of Gpd1, accelerating recovery through increased glycerol production. Gpd1 dephosphorylation acts synergistically with its transcriptional upregulation, enabling long-term growth at high osmolarity. Phosphorylation of Gpd1 and Gpd2 by distinct kinases thereby enables rapid adaptation to specific stress conditions. Introduction of phosphorylation motifs targeted by distinct kinases provides a general mechanism for functional specialization of duplicated genes during evolution. PMID:22988299

Lee, Yong Jae; Jeschke, Grace R; Roelants, Françoise M; Thorner, Jeremy; Turk, Benjamin E

2012-09-17

131

Connectivity from OR37 expressing olfactory sensory neurons to distinct cell types in the hypothalamus  

PubMed Central

Olfactory sensory neurons (OSNs) which express a member from the OR37 subfamily of odorant receptor (OR) genes are wired to the main olfactory bulb (MOB) in a unique monoglomerular fashion; from these glomeruli an untypical connectivity into higher brain centers exists. In the present study we have investigated by DiI and transsynaptic tracing approaches how the connection pattern from these glomeruli into distinct hypothalamic nuclei is organized. The application of DiI onto the ventral domain of the bulb which harbors the OR37 glomeruli resulted in the labeling of fibers within the paraventricular nucleus (PVN) and supraoptic nucleus (SO) of the hypothalamus; some of these fibers were covered with varicose-like structures. No DiI-labeled cell somata were detectable in these nuclei. The data indicate that projection neurons which originate in the OR37 region of the MOB form direct connections into these nuclei. The cells that were labeled by the transsynaptic tracer WGA in these nuclei were further characterized. Their distribution pattern in the paraventricular nucleus was reminiscent of cells which produce distinct neuropeptides. Double labeling experiments confirmed that they contained vasopressin, but not the related neuropeptide oxytocin. Morphological analysis revealed that they comprise of magno- and parvocellular cells. A comparative investigation of the WGA-positive cells in the SO demonstrated that these were vasopressin-positive, as well, whereas oxytocin-producing cells of this nucleus also contained no transsynaptic tracer. Together, the data demonstrates a connectivity from OR37 expressing sensory neurons to distinct hypothalamic neurons with the same neuropeptide content.

Bader, Andrea; Klein, Bettina; Breer, Heinz; Strotmann, Jorg

2012-01-01

132

Implement of the Owner Distinction Function for Healing-Type Pet Robots  

NASA Astrophysics Data System (ADS)

In recent years, a robotics technology is extremely progressive, and robots are widely applied in many fields. One of the most typical robots is a pet robot. The pet robot is based on an animal pet, such as a dog or a cat. Also, it is known that an animal pet has a healing effect. Therefore, the study to apply pet robots to Animal Assisted Therapy instead of an animal pet has begun to be investigated. We, also, have investigated a method of an owner distinction for pet robot, to emphasize a healing effect of pet robots. In this paper, taking account of implementation into pet robots, a real-time owner distinction method is proposed. In the concrete, the method provides a real-time matching algorithm and an oblivion mechanism. The real-time matching means that a matching and a data acquisition are processed simultaneously. The oblivion mechanism is deleting features of owners in the database of the pet robots. Additionally, the mechanism enables to reduce matching costs or size of database and it enables to follow a change of owners. Furthermore, effectivity and a practicality of the method are evaluated by experiments.

Nambo, Hidetaka; Kimura, Haruhiko; Hirose, Sadaki

133

The culture of olfactory ensheathing cells (OECs)--a distinct glial cell type  

PubMed Central

Olfactory ensheathing cells (OECs) have become a popular candidate for the transplant-mediated repair of the damaged CNS. In this review a description is made of the origins of these cells and a historical development of their purification and maintenance in culture. In addition, we illustrate the cellular and molecular characteristics of OECs and emphasise that although they share many properties with Schwann cells, they possess several inherent differences which may allow them to be more beneficial for CNS repair. In summary, OECs are distinct glial cells and the detailed understanding of their biological and molecular properties is essential in ensuring their clinical efficacy after cell transplantation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

Higginson, Jennifer R.; Barnett, Susan C.

2011-01-01

134

Effect of Two Distinct Stressors on Gene Expression of the Type 1 IP3 Receptors  

Microsoft Academic Search

Inositol 1,4,5-trisphosphate (IP3) is one of the second messengers, which triggers calcium release from intracellular pools via IP3 receptors. Previously we have shown that single immobilization stress increased gene expression of both, the type 1 and type 2 IP3 receptors (IP3R1 and IP3R2, respectively). In this study we evaluated whether long-term exposure to softer stressor (cold exposure to 4 ?C)

O. Krizanova; R. Kvetnansky; D. Jurkovicova

2005-01-01

135

L1Type Cell Adhesion Molecules: Distinct Roles in Synaptic Targeting, Organization, and Function  

Microsoft Academic Search

\\u000a L1-type cell adhesion molecules are known to be involved in several early developmental processes such as neurite outgrowth,\\u000a axon guidance, fasciculation, and cell migration. In this chapter, we review their less well-studied roles in synaptogenesis.\\u000a Despite the limited number of studies that has been conducted to assay the cellular mechanisms involving L1-type CAMs at the\\u000a synapse, the breadth and scope

Smitha Babu Uthaman; Tanja Angela Godenschwege

136

Human Immunodeficiency Virus Type 1 Clade B Superinfection: Evidence for Differential Immune Containment of Distinct Clade B Strains  

Microsoft Academic Search

Sequential infection with different strains of human immunodeficiency virus type 1 (HIV-1) is a rarely identified phenomenon with important implications for immunopathogenesis and vaccine development. Here, we identify an individual whose good initial control of viremia was lost in association with reduced containment of a superinfecting strain. Subject 2030 presented with acute symptoms of HIV-1 infection with high viremia and

Otto O. Yang; Eric S. Daar; Beth D. Jamieson; Arumugam Balamurugan; Davey M. Smith; Jacqueline A. Pitt; Christos J. Petropoulos; Douglas D. Richman; Susan J. Little; Andrew J. Leigh Brown

2005-01-01

137

The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types in a diet-independent and fiber-type unrelated way  

Microsoft Academic Search

BACKGROUND: The mouse skeletal muscle is composed of four distinct fiber types that differ in contractile function, number of mitochondria and metabolism. Every muscle type has a specific composition and distribution of the four fiber types. To find novel genes involved in specifying muscle types, we used microarray analysis to compare the gastrocnemius with the quadriceps from mice fed a

Janneke de Wilde; Martijn FM Hulshof; Mark V Boekschoten; Philip de Groot; Egbert Smit; Edwin CM Mariman

2010-01-01

138

A de novo interstitial deletion of 8p11.2 including ANK1 identified in a patient with spherocytosis, psychomotor developmental delay, and distinctive facial features.  

PubMed

The contiguous gene syndrome involving 8p11.2 is recognized as a combined phenotype of both Kallmann syndrome and hereditary spherocytosis, because the genes responsible for these 2 clinical entities, the fibroblast growth factor receptor 1 (FGFR1) and ankyrin 1 (ANK1) genes, respectively, are located in this region within a distance of 3.2Mb. We identified a 3.7Mb deletion of 8p11.2 in a 19-month-old female patient with hereditary spherocytosis. The identified deletion included ANK1, but not FGFR1, which is consistent with the absence of any phenotype or laboratory findings of Kallmann syndrome. Compared with the previous studies, the deletion identified in this study was located on the proximal end of 8p, indicating a pure interstitial deletion of 8p11.21. This patient exhibited mild developmental delay and distinctive facial findings in addition to hereditary spherocytosis. Thus, some of the genes included in the deleted region would be related to these symptoms. PMID:22771917

Miya, Kazushi; Shimojima, Keiko; Sugawara, Midori; Shimada, Shino; Tsuri, Hiroyuki; Harai-Tanaka, Tomomi; Nakaoka, Sachiko; Kanegane, Hirokazu; Miyawaki, Toshio; Yamamoto, Toshiyuki

2012-07-04

139

Phacomatosis pigmentokeratotica: another epidermal nevus syndrome and a distinctive type of twin spotting.  

PubMed

The name epidermal nevus syndrome could be applied to a group of clinically and histopathologically different entities as has been pointed out by Happle. Phacomatosis pigmentokeratotica is a further type of epidermal nevus syndrome distinguished by the presence of a sebaceous nevus and a contralateral speckled lentiginous nevus of the papular type, associated with skeletal or neurological abnormalities. Three new cases of this recently delineated syndrome are presented. A common origin may account for the temporal and spatial relationship between the epidermal and the speckled lentiginous nevus. The concept of melanocytic-epidermal twin spotting similar to the interpretation of vascular twin spotting could explain the pathogenesis of this entity. PMID:10725816

Boente, M C; Pizzi de Parra, N; Larralde de Luna, M; Bonet, H B; Santos Muñoz, A; Parra, V; Gramajo, P; Moreno, S; Asial, R A

140

The distinct mechanisms of the antitumor activity of emodin in different types of cancer (Review).  

PubMed

Emodin, a tyrosine kinase inhibitor, is a natural anthraquinone derivative found in the roots and rhizomes of numerous plants. The inhibitory effect of emodin on mammalian cell cycle modulation in specific oncogene-overexpressing cells has formed the basis for using this compound as an anticancer drug. Previous reviews have summarized the antitumor properties of emodin. However, the specific molecular mechanisms of emodin-mediated tumor inhibition have not been completely elucidated over the last 5 years. Recently, there has been great progress in the preclinical study of the anticancer mechanisms of emodin. Our recent study revealed that emodin has therapeutic effects on pancreatic cancer through various antitumor mechanisms. Notably, the therapeutic efficacy of emodin in combination with chemotherapy was found to be higher than the comparable single chemotherapeutic regime, and the combination therapy also exhibited fewer side-effects. Despite these encouraging results, further investigation is warranted as emodin has been shown to modulate one or more key regulators of cancer growth. This review provides an overview of the distinct mechanisms of anticancer action of emodin in different body systems identi?ed over the past 5 years. These new breakthrough ?ndings may have important implications for targeted cancer therapy and for the future clinical use of emodin. PMID:24065213

Wei, Wei-Tian; Lin, Sheng-Zhang; Liu, Dian-Lei; Wang, Zhao-Hong

2013-09-19

141

Distinct types of disorder in the human proteome: functional implications for alternative splicing.  

PubMed

Intrinsically disordered regions have been associated with various cellular processes and are implicated in several human diseases, but their exact roles remain unclear. We previously defined two classes of conserved disordered regions in budding yeast, referred to as "flexible" and "constrained" conserved disorder. In flexible disorder, the property of disorder has been positionally conserved during evolution, whereas in constrained disorder, both the amino acid sequence and the property of disorder have been conserved. Here, we show that flexible and constrained disorder are widespread in the human proteome, and are particularly common in proteins with regulatory functions. Both classes of disordered sequences are highly enriched in regions of proteins that undergo tissue-specific (TS) alternative splicing (AS), but not in regions of proteins that undergo general (i.e., not tissue-regulated) AS. Flexible disorder is more highly enriched in TS alternative exons, whereas constrained disorder is more highly enriched in exons that flank TS alternative exons. These latter regions are also significantly more enriched in potential phosphosites and other short linear motifs associated with cell signaling. We further show that cancer driver mutations are significantly enriched in regions of proteins associated with TS and general AS. Collectively, our results point to distinct roles for TS alternative exons and flanking exons in the dynamic regulation of protein interaction networks in response to signaling activity, and they further suggest that alternatively spliced regions of proteins are often functionally altered by mutations responsible for cancer. PMID:23633940

Colak, Recep; Kim, TaeHyung; Michaut, Magali; Sun, Mark; Irimia, Manuel; Bellay, Jeremy; Myers, Chad L; Blencowe, Benjamin J; Kim, Philip M

2013-04-25

142

Production scheduling in a semiconductor wafer fabrication facility producing multiple product types with distinct due dates  

Microsoft Academic Search

Focuses on production scheduling in a semiconductor wafer fab producing multiple product types that have different due dates and different process flows. In the wafer fab, wafer lots are processed on serial and batch processing workstations, each of which consists of parallel identical machines. Machines in serial processing workstations process wafer lots one by one, while those in batch processing

Yeong-Dae Kim; Jae-Gon Kim; Bum Choi; Hyung-Un Kim

2001-01-01

143

Distinctions between islet neogenesis and ?-cell replication: implications for reversal of Type 1 and 2 diabetes.  

PubMed

The terms "islet" and "?-cell" are often used interchangeably, yet islets are highly complex multicellular organelles that contain the insulin-producing ?-cells and four other cells types, all of which play a role in maintaining glucose homeostasis within a very narrow range. Although the formation of new islets in adults is rare, occurring primarily in response to pancreatic injury and major stress to the pancreas, ?-cell replication from existing cells occurs throughout adulthood. An understanding of the regulatory factors controlling pancreatic development has more clearly defined the differences between new islet formation from progenitor cells located throughout the adult pancreas and ?-cell replication occurring within existing islets. The present review sets forth to more clearly distinguish the differences between the postnatal pathways of islet neogenesis and ?-cell replication with a discussion of the potential implications for reversal of Type 1 and 2 diabetic patients using islet neogenesis agents that are now in development. For Type 1 diabetic patients, an immune tolerance agent in conjunction with an islet neogenesis agent may allow achievement of adequate islet mass, perhaps with subsequent potential to withdraw medications. For Type 2 diabetic patients, lifestyle changes and/or medications may sustain the production of new islets and limit the accelerated ?-cell apoptosis characteristic of the condition. PMID:20923488

Levetan, Claresa

2010-03-25

144

Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB  

Microsoft Academic Search

Pseudohypoparathyroidism type IB (PHPIB) is associated with abnormal imprinting of GNAS, the gene encoding the heterotrimeric G protein Gsa and other alternative products. The gene contains three differen- tially methylated regions (DMRs) located upstream of the Gsa promoter (from upstream to downstream): the paternally methylated NESP55 promoter region, the maternally methylated NESP antisense (NESPAS)\\/XLas promoter region and the maternally methylated

Jie Liu; Julie G. Nealon; Lee S. Weinstein

2005-01-01

145

Distinct Th1- and Th2-Type Prenatal Cytokine Responses to Plasmodium falciparum Erythrocyte Invasion Ligands  

PubMed Central

Prenatal immunity to Plasmodium falciparum merozoite proteins involved in erythrocyte invasion may contribute to the partial protection against malaria that is acquired during infancy in areas of stable malaria transmission. We examined newborn and maternal cytokine and antibody responses to merozoite surface protein-1 (MSP-1), ribosomal phosphoprotein P0 (PfP0), and region II of erythrocyte binding antigen-175 (EBA-175) in infant-mother pairs in Kenya. Overall, 82 of 167 (50%), 106 of 176 (60%), and 38 of 84 (45%) cord blood lymphocytes (CBL) from newborns produced one or more cytokines in response to MSP-1, PfP0, and EBA-175, respectively. Newborns of primigravid and/or malaria-infected women were more likely to have antigen-responsive CBL than were newborns of multigravid and/or uninfected women at delivery. Newborn cytokine responses did not match those of their mothers and fell into three distinct categories, Th1 (21 of 55 CBL donors produced only gamma interferon and/or interleukin 2 [IL-2]), Th2 (21 of 55 produced only IL-5 and/or IL-13), and mixed Th1/Th2 (13 of 55). Newborns produced more IL-10 than adults. High and low levels of cord blood IL-12 p70 production induced by anti-CD40 activation were associated with malaria-specific Th1 and Th2 responses, respectively. Antigen-responsive CBL in some newborns were detected only after depletion of IL-10-secreting CD8 cells with enrichment for CD4 cells. These data indicate that prenatal sensitization to blood-stage Plasmodium falciparum occurs frequently in areas where malaria is holoendemic. Modulation of this immunity, possibly by maternal parity and malaria, may affect the acquisition of protective immunity against malaria during infancy.

Malhotra, Indu; Mungai, Peter; Muchiri, Eric; Ouma, John; Sharma, Shobhona; Kazura, James W.; King, Christopher L.

2005-01-01

146

Distinct Microbial Communities within the Endosphere and Rhizosphere of Populus deltoides Roots across Contrasting Soil Types.  

SciTech Connect

The root-rhizosphere interface of Populus is the nexus of a variety of associations between bacteria, fungi, and the host plant and an ideal model for studying interactions between plants and microorganisms. However, such studies have generally been confined to greenhouse and plantation systems. Here we analyze microbial communities from the root endophytic and rhizospheric habitats of Populus deltoides in mature natural trees from both upland and bottomland sites in central Tennessee. Community profiling utilized 454 pyrosequencing with separate primers targeting the V4 region for bacterial 16S rRNA and the D1/D2 region for fungal 28S rRNA genes. Rhizosphere bacteria were dominated by Acidobacteria (31%) and Alphaproteobacteria (30%), whereas most endophytes were from the Gammaproteobacteria (54%) as well as Alphaproteobacteria (23%). A single Pseudomonas-like operational taxonomic unit (OTU) accounted for 34% of endophytic bacterial sequences. Endophytic bacterial richness was also highly variable and 10-fold lower than in rhizosphere samples originating from the same roots. Fungal rhizosphere and endophyte samples had approximately equal amounts of the Pezizomycotina (40%), while the Agaricomycotina were more abundant in the rhizosphere (34%) than endosphere (17%). Both fungal and bacterial rhizosphere samples were highly clustered compared to the more variable endophyte samples in a UniFrac principal coordinates analysis, regardless of upland or bottomland site origin. Hierarchical clustering of OTU relative abundance patterns also showed that the most abundant bacterial and fungal OTUs tended to be dominant in either the endophyte or rhizosphere samples but not both. Together, these findings demonstrate that root endophytic communities are distinct assemblages rather than opportunistic subsets of the rhizosphere.

Gottel, Neil R [ORNL; Castro Gonzalez, Hector F [ORNL; Kerley, Marilyn K [ORNL; Yang, Zamin [ORNL; Pelletier, Dale A [ORNL; Podar, Mircea [ORNL; Karpinets, Tatiana V [ORNL; Uberbacher, Edward C [ORNL; Tuskan, Gerald A [ORNL; Vilgalys, Rytas [Duke University; Doktycz, Mitchel John [ORNL; Schadt, Christopher Warren [ORNL

2011-01-01

147

Using wearable cameras to categorise type and context of accelerometer-identified episodes of physical activity  

PubMed Central

Background Accelerometers can identify certain physical activity behaviours, but not the context in which they take place. This study investigates the feasibility of wearable cameras to objectively categorise the behaviour type and context of participants’ accelerometer-identified episodes of activity. Methods Adults were given an Actical hip-mounted accelerometer and a SenseCam wearable camera (worn via lanyard). The onboard clocks on both devices were time-synchronised. Participants engaged in free-living activities for 3 days. Actical data were cleaned and episodes of sedentary, lifestyle-light, lifestyle-moderate, and moderate-to-vigorous physical activity (MVPA) were identified. Actical episodes were categorised according to their social and environmental context and Physical Activity (PA) compendium category as identified from time-matched SenseCam images. Results There were 212 days considered from 49 participants from whom SenseCam images and associated Actical data were captured. Using SenseCam images, behaviour type and context attributes were annotated for 386 (out of 3017) randomly selected episodes (such as walking/transportation, social/not-social, domestic/leisure). Across the episodes, 12 categories that aligned with the PA Compendium were identified, and 114 subcategory types were identified. Nineteen percent of episodes could not have their behaviour type and context categorized; 59% were outdoors versus 39% indoors; 33% of episodes were recorded as leisure time activities, with 33% transport, 18% domestic, and 15% occupational. 33% of the randomly selected episodes contained direct social interaction and 22% were in social situations where the participant wasn’t involved in direct engagement. Conclusion Wearable camera images offer an objective method to capture a spectrum of activity behaviour types and context across 81% of accelerometer-identified episodes of activity. Wearable cameras represent the best objective method currently available to categorise the social and environmental context of accelerometer-defined episodes of activity in free-living conditions.

2013-01-01

148

Myosin IIB isoform plays an essential role in the formation of two distinct types of macropinosomes  

PubMed Central

The function and mechanism of macropinocytosis in cells outside of the immune system remain poorly understood. We used a neuroblastoma cell line, Neuro-2a, to study macropinocytosis in neuronal cells. We found phorbol 12-myristate 13-acetate (PMA) and insulin-like growth factor 1 (IGF-1) induced two dinstinct types of macropinocytosis in the Neuro-2a cells. IGF-1-induced macropinocytosis occurs mostly around the cell bodies and requires phosphoinositide 3-kinase (PI3K), while PMA-induced macropinocytosis occurs predominantly in the neurites and is independent of PI3K. Both types of macropinocytosis were inhibited by a specific inhibitor of non-muscle myosin II, blebbistatin. siRNA knock-down of nonmuscle myosin II isoforms, -IIA and –IIB, resulted in opposite effects on macropinocytosis induced by PMA or IGF. Myosin IIA knock-down significantly increased, whereas myosin IIB knock-down significantly decreased, macropinocytosis with correlating changes in membrane ruffle formation.

Jiang, Jun; Kolpak, Adrianne L.; Bao, Zheng-Zheng

2009-01-01

149

CALTECH CORE-COLLAPSE PROJECT (CCCP) OBSERVATIONS OF TYPE II SUPERNOVAE: EVIDENCE FOR THREE DISTINCT PHOTOMETRIC SUBTYPES  

SciTech Connect

We present R-band light curves of Type II supernovae (SNe) from the Caltech Core-Collapse Project (CCCP). With the exception of interacting (Type IIn) SNe and rare events with long rise times, we find that most light curve shapes belong to one of three apparently distinct classes: plateau, slowly declining, and rapidly declining events. The last class is composed solely of Type IIb SNe which present similar light curve shapes to those of SNe Ib, suggesting, perhaps, similar progenitor channels. We do not find any intermediate light curves, implying that these subclasses are unlikely to reflect variance of continuous parameters, but rather might result from physically distinct progenitor systems, strengthening the suggestion of a binary origin for at least some stripped SNe. We find a large plateau luminosity range for SNe IIP, while the plateau lengths seem rather uniform at approximately 100 days. As analysis of additional CCCP data goes on and larger samples are collected, demographic studies of core-collapse SNe will likely continue to provide new constraints on progenitor scenarios.

Arcavi, Iair; Gal-Yam, Avishay; Yaron, Ofer [Department of Particle Physics and Astrophysics, Weizmann Institute of Science, Rehovot 76100 (Israel); Cenko, S. Bradley; Becker, Adam B. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Fox, Derek B. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Leonard, Douglas C. [Department of Astronomy, San Diego State University, San Diego, CA 92182 (United States); Moon, Dae-Sik [Department of Astronomy and Astrophysics, University of Toronto, Toronto, ON M5S 3H4 (Canada); Sand, David J. [Las Cumbres Observatory Global Telescope Network, Santa Barbara, CA 93117 (United States); Soderberg, Alicia M. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Kiewe, Michael [Department of Physics, University of Wisconsin, Madison, WI 53706 (United States); Scheps, Raphael [King's College, University of Cambridge, Cambridge CB2 1ST (United Kingdom); Birenbaum, Gali [12 Amos St, Ramat Chen, Ramat Gan 52233 (Israel); Chamudot, Daniel [20 Chen St, Petach Tikvah 49520 (Israel); Zhou, Jonathan, E-mail: iair.arcavi@weizmann.ac.il [101 Dunster Street, Box 398, Cambridge, MA 02138 (United States)

2012-09-10

150

Distinctive Higgs signals of a type II two-Higgs-doublet model at the LHC  

SciTech Connect

We perform a numerical analysis of Higgs-to-Higgs decays within a type II two-Higgs-doublet model (2HDM), highlighting several channels that cannot occur in its supersymmetric version, thereby allowing one to possibly distinguish between these two scenarios. Our results are compliant with all available experimental bounds from both direct and indirect Higgs searches and with theoretical constraints from vacuum stability and perturbative unitarity.

Kanemura, Shinya; Mukai, Yuki; Yagyu, Kei [Department of Physics, University of Toyama, 3190 Gofuku, Toyama 930-8555 (Japan); Moretti, Stefano; Santos, Rui [School of Physics and Astronomy, University of Southampton, Highfield, Southampton SO17 1BJ (United Kingdom)

2009-03-01

151

Foot-and-mouth disease type O viruses exhibit genetically and geographically distinct evolutionary lineages (topotypes)  

Microsoft Academic Search

Serotype O is the most prevalent of the seven serotypes of foot-and-mouth disease (FMD) virus and occurs in many parts of the world. The UPGMA method was used to construct a phylogenetic tree based on nucleotide sequences at the 3« end of the VP1 gene from 105 FMD type O viruses obtained from samples submitted to the OIE\\/FAO World Reference

A. R. Samuel; N. J. Knowles

2001-01-01

152

Distinction Between Envelope Antigens of Murine Xenotropic and Ecotropic Type C Viruses by Immunoelectron Microscopy  

Microsoft Academic Search

SUMMARY The indirect ferritin-labelled antibody technique was used to determine the reactivity of an antiserum prepared against the NZB xenotropic virus with three murine xenotropic viruses, a feline xenotropic virus and a murine ecotropic virus. The envelope antigens of the xenotropic type C viruses isolated from the NZB, NIH Swiss and C57L mice were tagged with ferritin. The feline RD114

L. S. Oshiro; J. A. Levy; J. L. Riggs; E. H. Lennette

1977-01-01

153

Phenotypic Variation of Helicobacter pylori Isolates from Geographically Distinct Regions Detected by Lectin Typing  

PubMed Central

A total of 309 Helicobacter pylori isolates from 18 different countries were analyzed with a previously developed lectin typing system. The system was developed by using a proteolytic pretreatment to enhance the carbohydrate fraction of the sample. Four lectins from Ulex europaeus, Lotus tetragonolobus, Erythrina cristigali, and Triticum vulgaris were used to type the strains. The lectins were chosen for their specificities for sugars commonly encountered in the lipopolysaccharide of H. pylori. The isolates were received from their parent institutions as pellets of biomass and were typed at one of three centers (in Ireland, Sweden, and Estonia). All 16 possible lectin reaction patterns were observed in the study, with the isolates with the predominant pattern exhibiting reactions with all the lectins in the panel. For European patients suffering from gastritis, an association was noted between lectin reaction pattern MH4 and atrophic chronic gastritis; isolates with lectin reaction pattern MH4 were isolated from patients with atrophic chronic gastritis, whereas isolates with this pattern were not isolated from patients with chronic gastritis (P = 0.0006). In addition, statistically significant relationships were noted between the lectin reaction pattern and the associated pathology of isolates from the Swedish population. Isolates with patterns MH13 and MH16, which had low lectin reactivities, correlated with nonulcer disease (P = 0.0025 and P = 0.0002, respectively), and all four isolates from adenocarcinoma patients were characterized as possessing reaction pattern MH16. In contrast, isolates with lectin reaction patterns MH1 and MH10, which had high lectin reactivities, were associated with ulcer disease (P = 0.046 and P = 0.0022, respectively).

Hynes, Sean O.; Broutet, Nathalie; Wadstrom, Torkel; Mikelsaar, Marika; O'Toole, Paul W.; Telford, John; Engstrand, Lars; Kamiya, Shigeru; Mentis, Andreas F.; Moran, Anthony P.

2002-01-01

154

Phenotypic variation of Helicobacter pylori isolates from geographically distinct regions detected by lectin typing.  

PubMed

A total of 309 Helicobacter pylori isolates from 18 different countries were analyzed with a previously developed lectin typing system. The system was developed by using a proteolytic pretreatment to enhance the carbohydrate fraction of the sample. Four lectins from Ulex europaeus, Lotus tetragonolobus, Erythrina cristigali, and Triticum vulgaris were used to type the strains. The lectins were chosen for their specificities for sugars commonly encountered in the lipopolysaccharide of H. pylori. The isolates were received from their parent institutions as pellets of biomass and were typed at one of three centers (in Ireland, Sweden, and Estonia). All 16 possible lectin reaction patterns were observed in the study, with the isolates with the predominant pattern exhibiting reactions with all the lectins in the panel. For European patients suffering from gastritis, an association was noted between lectin reaction pattern MH4 and atrophic chronic gastritis; isolates with lectin reaction pattern MH4 were isolated from patients with atrophic chronic gastritis, whereas isolates with this pattern were not isolated from patients with chronic gastritis (P = 0.0006). In addition, statistically significant relationships were noted between the lectin reaction pattern and the associated pathology of isolates from the Swedish population. Isolates with patterns MH13 and MH16, which had low lectin reactivities, correlated with nonulcer disease (P = 0.0025 and P = 0.0002, respectively), and all four isolates from adenocarcinoma patients were characterized as possessing reaction pattern MH16. In contrast, isolates with lectin reaction patterns MH1 and MH10, which had high lectin reactivities, were associated with ulcer disease (P = 0.046 and P = 0.0022, respectively). PMID:11773120

Hynes, Sean O; Broutet, Nathalie; Wadström, Torkel; Mikelsaar, Marika; O'Toole, Paul W; Telford, John; Engstrand, Lars; Kamiya, Shigeru; Mentis, Andreas F; Moran, Anthony P

2002-01-01

155

Satellite tracking reveals distinct movement patterns for Type B and Type C killer whales in the southern Ross Sea, Antarctica  

Microsoft Academic Search

During January\\/February 2006, we satellite-tracked two different ecotypes of killer whales (Orcinus orca) in McMurdo Sound, Ross Sea, Antarctica, using surface-mounted tags attached with sub-dermal darts. A single Type B whale\\u000a (pinniped prey specialist), tracked for 27 days, traveled an average net distance of 56.8 ± 32.8 km day?1, a maximum of 114 km day?1, and covered an estimated area of 49,351 km2. It spent several days near

Russel D. Andrews; Robert L. Pitman; Lisa T. Ballance

2008-01-01

156

Identifying the Types of Student and Teacher Behaviours Associated with Teacher Stress  

ERIC Educational Resources Information Center

|The objectives of this study were to identify the student behaviours associated with teacher stress and determine the types of teacher behaviours that may elicit these stressful student behaviours. Student teachers (n = 186) and their supervising teachers (n = 77) completed a stressful student behaviour questionnaire, a teacher behaviour…

Geving, Allison M.

2007-01-01

157

Two distinct subgroups of senile dementia of Alzheimer type: quantitative study of neurofibrillary tangles.  

PubMed

The heterogeneity of senile dementia of Alzheimer type (SDAT) has been suggested by some authors clinically and neuropathologically. The heterogeneity of SDAT was investigated based on quantification of NFT combining Braak and Braak's neuropathological staging and the density of NFT in various areas of the cerebral cortex. Brain tissues were examined from 16 autopsy cases with clinically late onset dementia (> age 65) and neuropathologically diagnosed dementia of Alzheimer type (DAT). Gallyas-Braak staining was used for the quantification of NFT. The density of NFT was examined in the precentral gyrus, middle temporal gyrus (T2), parahippocampal gyrus and the amygdaloid nucleus. The 16 cases studied were divided into two groups depending on the number of NFT in the cortex (cut-off score: 5/mm2): the AD-like group (NFT > or = 5/mm2) and the common group (NFT < 5/mm2). The density of NFT in the precentral gyrus (t(3.225) = -9.007, P = 0.002) and T2 (t(3.365) = -3.774, P = 0.027) in the AD-like group was significantly higher than those in the common group. However, no significant difference was observed in the parahippocampal gyrus between the two groups (t(14) = -0.318, NS). Moreover, there were no significant differences between the two groups as regards age at onset and the duration of the illness. The present study revealed the possible existence of two subgroups in SDAT having significantly different NFT densities in various areas of the cerebral cortex without any significant difference in their duration of illness. This classification has no relationship to Braak and Braak's staging, which depends only on the distribution of NFT, irrespective of their density. Arai et al. revealed that the NFT density in AD was significantly higher than in SDAT. We suggest that the neuropathological findings of the AD-like group in SDAT resemble those of presenile AD. PMID:14719543

Mizuno, Yutaka; Ikeda, Kenji; Tsuchiya, Kuniaki; Ishihara, Ryoko; Shibayama, Hiroto

2003-12-01

158

Distinct localizations of urokinase-type plasminogen activator and its type 1 inhibitor under cultured human fibroblasts and sarcoma cells  

PubMed Central

We studied the immunocytochemical localization of urokinase-type plasminogen activator (u-PA) and the type 1 plasminogen activator inhibitor (PAI-1) in human fibroblasts and sarcoma cells, using both polyclonal and monoclonal antibodies. The u-PA was found to be located at discrete cell-substratum contact sites, and also at areas of cell- cell contacts, whereas PAI-1 was distributed as a homogeneous carpet excluding strialike areas on the substrate under the cells. To confirm the extracellular localization of u-PA and PAI-1, we stained the cells live at 0 degree C before fixation. A double-labeling experiment showed different distribution of u-PA and PAI-1 under the cells, and especially their peripheral parts. The staining pattern of u-PA and PAI- 1 resisted treatment with 0.2% saponin followed by mechanical removal of cells, a method previously reported to isolate focal contact membranes of fibroblasts. We further demonstrated the deposition of u- PA to the contact areas of cells obtained by saponin treatment by zymography, and that of PAI-1 by metabolic labeling, reverse zymography, immunoblotting, and immunoprecipitation. Fibronectin was also present in the preparations. The deposition of both PAI-1 and fibronectin by the sarcoma cells was enhanced, after treating the cells with 10(-6) M dexamethasone. The confinement of u-PA to discrete contact sites and the more uniform distribution of PAI-1 on the cell substratum may explain how cells producing large amounts of enzyme inhibitors can produce PA-mediated focal proteolysis.

1987-01-01

159

Use of Genomic DNA as an Indirect Reference for Identifying Gender-Associated Transcripts in Morphologically Identical, but Chromosomally Distinct, Schistosoma mansoni Cercariae  

PubMed Central

Background The use of DNA microarray technology to study global Schistosoma gene expression has led to the rapid identification of novel biological processes, pathways or associations. Implementation of standardized DNA microarray protocols across laboratories would assist maximal interpretation of generated datasets and extend productive application of this technology. Methodology/Principal Findings Utilizing a new Schistosoma mansoni oligonucleotide DNA microarray composed of 37,632 elements, we show that schistosome genomic DNA (gDNA) hybridizes with less variation compared to complex mixed pools of S. mansoni cDNA material (R?=?0.993 for gDNA compared to R?=?0.956 for cDNA during ‘self versus self’ hybridizations). Furthermore, these effects are species-specific, with S. japonicum or Mus musculus gDNA failing to bind significantly to S. mansoni oligonucleotide DNA microarrays (e.g R?=?0.350 when S. mansoni gDNA is co-hybridized with S. japonicum gDNA). Increased median fluorescent intensities (209.9) were also observed for DNA microarray elements hybridized with S. mansoni gDNA compared to complex mixed pools of S. mansoni cDNA (112.2). Exploiting these valuable characteristics, S. mansoni gDNA was used in two-channel DNA microarray hybridization experiments as a common reference for indirect identification of gender-associated transcripts in cercariae, a schistosome life-stage in which there is no overt sexual dimorphism. This led to the identification of 2,648 gender-associated transcripts. When compared to the 780 gender-associated transcripts identified by hybridization experiments utilizing a two-channel direct method (co-hybridization of male and female cercariae cDNA), indirect methods using gDNA were far superior in identifying greater quantities of differentially expressed transcripts. Interestingly, both methods identified a concordant subset of 188 male-associated and 156 female-associated cercarial transcripts, respectively. Gene ontology classification of these differentially expressed transcripts revealed a greater diversity of categories in male cercariae. Quantitative real-time PCR analysis confirmed the DNA microarray results and supported the reliability of this platform for identifying gender-associated transcripts. Conclusions/Significance Schistosome gDNA displays characteristics highly suitable for the comparison of two-channel DNA microarray results obtained from experiments conducted independently across laboratories. The schistosome transcripts identified here demonstrate, for the first time, that gender-associated patterns of expression are already well established in the morphologically identical, but chromosomally distinct, cercariae stage.

Fitzpatrick, Jennifer M.; Protasio, Anna V.; McArdle, Andrew J.; Williams, Gary A.; Johnston, David A.; Hoffmann, Karl F.

2008-01-01

160

Calcium-permeable AMPA receptors provide a common mechanism for LTP in glutamatergic synapses of distinct hippocampal interneuron types  

PubMed Central

Glutamatergic synapses on some hippocampal GABAergic interneurons exhibit activity-induced long-term potentiation (LTP). Interneuron types within the CA1 area expressing mutually exclusive molecular markers differ in LTP responses. Potentiation that depends on calcium-permeable (CP-) AMPA receptors has been characterized in oriens-lacunosum moleculare (O-LM) interneurons, which express parvalbumin (PV) and somatostatin (SM). However, it is unknown how widely CP-AMPAR-dependent plasticity is expressed among different GABAergic interneuron types. Here we examine synaptic plasticity in rat hippocampal O-LM cells and two other interneuron types expressing either nitric oxide synthase (NOS) or cholecystokinin (CCK), which are known to be physiologically and developmentally distinct. We report similar CP-AMPAR–dependent LTP in NOS-immunopositive ivy cells and SM-expressing O-LM cells to afferent fiber theta burst stimulation. The potentiation in both cell types is induced at postsynaptic membrane potentials below firing threshold, and induction is blocked by intense spiking simultaneously with afferent stimulation. The strong inward rectification and calcium permeability of AMPARs is explained by a low level of GluA2 subunit mRNA expression. LTP is not elicited in CCK-expressing Schaffer collateral-associated (SCA) cells, which lack CP-AMPARs and express high levels of the GluA2 subunit. The results show that CP-AMPAR-mediated synaptic potentiation is common in hippocampal interneuron types and occurs in interneurons of both feedforward and feedback inhibitory pathways.

Szabo, Andras; Somogyi, Jozsef; Cauli, Bruno; Lambolez, Bertrand; Somogyi, Peter; Lamsa, Karri P.

2012-01-01

161

Analysis of T cell hybridomas. II. Comparisons among three distinct types of monoclonal suppressor factors  

PubMed Central

Five hybridoma T cell lines were prepared by fusion of Ts3 cells with the BW 5147 thymoma. The culture supernatants from these T cell hybrids contained a factor, TsF3, which specifically suppressed 4-hydroxy-3- nitrophenyl acetyl hapten (NP(-hapten cutaneous sensitivity responses. The properties of this new series of hybridoma factors was compared with those of two previously characterized types of NP-specific suppressor factors (TsF1 and TsF2). TsF3 activity was only observed if the factor was administered during the effector phases of the immune response. TsF3 bears I-J and C57BL anti-NP antibody idiotypic determinants and has binding specificity for the NP hapten. Furthermore, TsF3 does not suppress H-2 (I-J)-incompatible mice. In addition to this H-2 restriction, the monoclonal TsF3 factors also demonstrated an Igh genetic restriction. Finally, the TsF3 factors could be distinguished by their ability to suppress cyclophosphamide- treated recipients.

1981-01-01

162

Decomposition of satellite-derived images for the distinction of cloud types' features  

NASA Astrophysics Data System (ADS)

Linear filtering methods using convolution techniques are applied in computer vision, to detect spatial discontinuities in the intensity of luminance of photograph images. These techniques are based on the following principal: a pixel's neighborhood contains information about its intensity. The variation of this intensity provides some information about the distribution and the possible decomposition of the image in various features. This decomposition relies on the relative position of the pixel (edge or not) on the image. These principals, integrated into remote sensing analyses, are applied in this study to differentiate cloud morphological features representing cloud types from a thermal image product (the Cloud top temperatures) derived from polar orbit satellites' observations. This approach contrast with that of other techniques commonly used in satellite cloud classification, and based on optical or thermodynamic properties of the clouds. The interpretation of the distribution of these cloud morphological features, and their frequency is evaluated against another cloud classification method relying on cloud optical properties. The results show a relatively good match between the two classifications. Implications of these results, on the estimation of the impact of cloud shapes' variations on the recent climate are discussed.

Dim, Jules R.; Murakami, Hiroshi

2013-02-01

163

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?  

PubMed

Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions. PMID:21317917

Uibo, Raivo; Panarina, Marina; Teesalu, Kaupo; Talja, Ija; Sepp, Epp; Utt, Meeme; Mikelsaar, Marika; Heilman, Kaire; Uibo, Oivi; Vorobjova, Tamara

2011-02-14

164

Mercury dynamics in groundwater across three distinct riparian zone types of the US Midwest.  

PubMed

Although the intense biogeochemical gradients present in riparian zones have the potential to affect mercury (Hg) cycling, Hg dynamics in riparian zones has received relatively little attention in the literature. Our study investigated groundwater filtered total mercury (THg) and methylmercury (MeHg) dynamics in three riparian zones with contrasting hydrogeomorphic (HGM) characteristics (till, alluvium, outwash) in the US Midwest. Despite high Hg deposition rates (>16 ?g m(-2)) in the region, median THg (<1.05 ng L(-1)) and MeHg (<0.05 ng L(-1)) concentrations were low at the study sites. Methylmercury concentrations were significantly (p < 0.05) correlated to THg (R = 0.82), temperature (R = 0.55), and dissolved organic carbon (DOC) (R = 0.62). THg also correlated with groundwater DOC (R = 0.59). The proportion of MeHg in THg (%MeHg) was significantly correlated to temperature (R = 0.58) and MeHg (R = 0.50). Results suggest that HGM characteristics, the presence of tile drains, and the propensity for overbank flooding at a riparian site determined the extent to which stream water Hg concentrations influenced riparian groundwater Hg levels or vice versa. Differences in hydrogeomorphic characteristics between sites did not translate however in significant differences in groundwater MeHg or %MeHg. Overall, widespread Hg contamination in the most common riparian hydrogeomorphic types of the US Midwest is unlikely to be a major concern. However, for frequently flooded riparian zones located downstream from a potentially large source of Hg (e.g., concentrated urban development), Hg concentrations are likely to be higher than at other sites. PMID:24113840

Vidon, Philippe G; Mitchell, Carl P J; Jacinthe, Pierre-André; Baker, Matthew E; Liu, Xiaoqiang; Fisher, Katelin R

2013-10-23

165

Two distinct types of inhibition mediated by cartwheel cells in the dorsal cochlear nucleus.  

PubMed

Individual neurons have been shown to exhibit target cell-specific synaptic function in several brain areas. The time course of the postsynaptic conductances (PSCs) strongly influences the dynamics of local neural networks. Cartwheel cells (CWCs) are the most numerous inhibitory interneurons in the dorsal cochlear nucleus (DCN). They are excited by parallel fiber synapses, which carry polysensory information, and in turn inhibit other CWCs and the main projection neurons of the DCN, pyramidal cells (PCs). CWCs have been implicated in "context-dependent" inhibition, producing either depolarizing (other CWCs) or hyperpolarizing (PCs) post synaptic potentials. In the present study, we used paired whole cell recordings to examine target-dependent inhibition from CWCs in neonatal rat DCN slices. We found that CWC inhibitory postsynaptic potentials (IPSPs) onto PCs are large (1.3 mV) and brief (half-width = 11.8 ms), whereas CWC IPSPs onto other CWCs are small (0.2 mV) and slow (half-width = 36.8 ms). Evoked IPSPs between CWCs exhibit paired-pulse facilitation, while CWC IPSPs onto PCs exhibit paired-pulse depression. Perforated-patch recordings showed that spontaneous IPSPs in CWCs are hyperpolarizing at rest with a mean estimated reversal potential of -67 mV. Spontaneous IPSCs were smaller and lasted longer in CWCs than in PCs, suggesting that the kinetics of the receptors are different in the two cell types. These results reveal that CWCs play a dual role in the DCN. The CWC-CWC network interactions are slow and sensitive to the average rate of CWC firing, whereas the CWC-PC network is fast and sensitive to transient changes in CWC firing. PMID:19474167

Mancilla, Jaime G; Manis, Paul B

2009-05-27

166

Analysis of Gene Expression Data from Non-Small Cell Lung Carcinoma Cell Lines Reveals Distinct Sub-Classes from Those Identified at the Phenotype Level  

PubMed Central

Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC) can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

Dalby, Andrew R.; Emam, Ibrahim; Franke, Raimo

2012-01-01

167

Melanocytes derived from patients with Hermansky-Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking.  

PubMed

Hermansky-Pudlak Syndrome (HPS) is a genetically heterogeneous disorder in which mutations in one of several genes interrupts biogenesis of melanosomes, platelet dense bodies, and lysosomes. Affected patients have oculocutaneous albinism, a bleeding diathesis, and sometimes develop granulomatous colitis or pulmonary fibrosis. In order to assess the role of HPS genes in melanosome biogenesis, melanocytes cultured from patients with HPS subtypes 1, 2, or 3 were assessed for the localization of various melanocyte proteins. Tyrosinase, Tyrp1, and Dct/Tyrp2 were atypically and distinctly expressed in HPS-1 and HPS-3 melanocytes, whereas only tyrosinase showed an atypical distribution in HPS-2 melanocytes. The HPS1 and AP3B1 (i.e., HPS-2) gene products showed no expression in HPS-1 and HPS-2 melanocytes, respectively, whereas HPS-3 melanocytes exhibited normal expression for both proteins. In normal human melanocytes, the HPS1 protein was expressed as an approximately 80 kDa molecule with both granular and reticular intracellular profiles. In HPS-1, lysosome associated membrane protein 1 (LAMP1), and LAMP3 were localized to abnormal large granules; in HPS-2, all LAMPs exhibited a normal granular expression; and in HPS-3, LAMP1, and LAMP3 exhibited a distinct less granular and more floccular pattern. In contrast, the expressions of Rab 27, transferrin, and cKit were unaffected in all three HPS genotypes. These data demonstrate that the three initially identified subtypes of human HPS exhibit distinct defects in the trafficking of various melanocyte-specific proteins. PMID:15675963

Richmond, Bonnie; Huizing, Marjan; Knapp, Jill; Koshoffer, Amy; Zhao, Yang; Gahl, William A; Boissy, Raymond E

2005-02-01

168

Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type.  

PubMed

Poly I:C, a synthetic dsRNA analogue, has been used extensively for decades to study innate responses in vivo and in different cell types. We have found substantial variability while using poly I:C from different sources. In this study we found that poly I:C from 2 commercial sources induced sharply opposite responses in myeloid and fibroblasts, depending on the length of the poly I:C. Although short poly I:C (?1-1.5 kb) induced greater amounts of TNF-?, IL-8, and IFN-? and a stronger antiviral response in myeloid cells, it was a poor inducer in fibroblasts. By contrast, long poly I:C (>5 kb) preferentially elicited higher cytokine and antiviral responses in fibroblasts and showed diminished responses in myeloid cells. Poly I:C activated NF-?B and STAT-1 signaling in a length- and cell-type-dependent fashion. Mechanistically, short poly I:C was better internalized in the myeloid cells and long poly I:C in the fibroblasts. Finally, long poly I:C required SR-A, whereas short poly I:C required RIG-I and Raftlin. We provide evidence that the length of dsRNA drives distinct innate responses in different cell lineages. These findings may augment in selecting the appropriate poly I:C type to design cell-type-specific potent adjuvants for vaccines against infectious diseases or cancers. PMID:23911868

Mian, M Firoz; Ahmed, Amna N; Rad, Mehrnaz; Babaian, Artem; Bowdish, Dawn; Ashkar, Ali A

2013-08-02

169

Co-existence of Distinct Prion Types Enables Conformational Evolution of Human PrPSc by Competitive Selection.  

PubMed

The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation of pathogenic prion proteins (PrP(Sc)). The molecular mechanism responsible for the adaptation, mutation, and evolution of prions observed in cloned cells and upon crossing the species barrier remains unsolved. Using biophysical techniques and conformation-dependent immunoassays in tandem, we isolated two distinct populations of PrP(Sc) particles with different conformational stabilities and aggregate sizes, which frequently co-exist in the most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein misfolding cyclic amplification replicates each of the PrP(Sc) particle types independently and leads to the competitive selection of those with lower initial conformational stability. In serial propagation with a nonglycosylated mutant PrP(C) substrate, the dominant PrP(Sc) conformers are subject to further evolution by natural selection of the subpopulation with the highest replication rate due to its lowest stability. Cumulatively, the data show that sporadic Creutzfeldt-Jakob disease PrP(Sc) is not a single conformational entity but a dynamic collection of two distinct populations of particles. This implies the co-existence of different prions, whose adaptation and evolution are governed by the selection of progressively less stable, faster replicating PrP(Sc) conformers. PMID:23974118

Haldiman, Tracy; Kim, Chae; Cohen, Yvonne; Chen, Wei; Blevins, Janis; Qing, Liuting; Cohen, Mark L; Langeveld, Jan; Telling, Glenn C; Kong, Qingzhong; Safar, Jiri G

2013-08-23

170

The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes  

Microsoft Academic Search

BACKGROUND: The aim of the study was to optimize protocols for finding and identifying serum proteins that are differentially expressed in persons with normal glucose tolerance (NGT) compared to individuals with type 2 diabetes mellitus (T2DM). Serum from persons with NGT and persons with T2DM was profiled using ProteinChip arrays and time-of-flight mass spectra were generated by surface enhanced laser

Tea Sundsten; Michael Eberhardson; Michael Göransson; Peter Bergsten

2006-01-01

171

A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene  

Microsoft Academic Search

Type 1 diabetes (T1D) in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin. A number of genetic determinants of T1D have already been established through candidate gene studies, primarily within the major histocompatibility complex but also within other loci. To identify new genetic factors that increase the risk of T1D, we performed a

Hakon Hakonarson; Struan F. A. Grant; Jonathan P. Bradfield; Luc Marchand; Cecilia E. Kim; Joseph T. Glessner; Rosemarie Grabs; Tracy Casalunovo; Shayne P. Taback; Edward C. Frackelton; Margaret L. Lawson; Luke J. Robinson; Robert Skraban; Yang Lu; Rosetta M. Chiavacci; Charles A. Stanley; Susan E. Kirsch; Eric F. Rappaport; Jordan S. Orange; Dimitri S. Monos; Marcella Devoto; Hui-Qi Qu; Constantin Polychronakos

2007-01-01

172

Phase diagrams of binary mixtures of patchy colloids with distinct numbers and types of patches: The empty fluid regime  

NASA Astrophysics Data System (ADS)

We investigate the effect of distinct bonding energies on the onset of criticality of low functionality fluid mixtures. We focus on mixtures of particles with two and three patches as this includes the mixture where ``empty'' fluids were originally reported. In addition to the number of patches, the species differ in the type of patches or bonding sites. For simplicity, we consider that the patches on each species are identical: one species has three patches of type A and the other has two patches of type B. We have found a rich phase behavior with closed miscibility gaps, liquid-liquid demixing, and negative azeotropes. Liquid-liquid demixing was found to pre-empt the ``empty'' fluid regime, of these mixtures, when the AB bonds are weaker than the AA or BB bonds. By contrast, mixtures in this class exhibit ``empty'' fluid behavior when the AB bonds are stronger than at least one of the other two. Mixtures with bonding energies ?BB = ?AB and ?AA < ?BB, were found to exhibit an unusual negative azeotrope.

Heras, Daniel de las; Tavares, José Maria; da Gama, Margarida M. Telo

2011-03-01

173

Phase diagrams of binary mixtures of patchy colloids with distinct numbers and types of patches: the empty fluid regime.  

PubMed

We investigate the effect of distinct bonding energies on the onset of criticality of low functionality fluid mixtures. We focus on mixtures of particles with two and three patches as this includes the mixture where "empty" fluids were originally reported. In addition to the number of patches, the species differ in the type of patches or bonding sites. For simplicity, we consider that the patches on each species are identical: one species has three patches of type A and the other has two patches of type B. We have found a rich phase behavior with closed miscibility gaps, liquid-liquid demixing, and negative azeotropes. Liquid-liquid demixing was found to pre-empt the "empty" fluid regime, of these mixtures, when the AB bonds are weaker than the AA or BB bonds. By contrast, mixtures in this class exhibit "empty" fluid behavior when the AB bonds are stronger than at least one of the other two. Mixtures with bonding energies ?(BB) = ?(AB) and ?(AA) < ?(BB), were found to exhibit an unusual negative azeotrope. PMID:21405190

de las Heras, Daniel; Tavares, José Maria; da Gama, Margarida M Telo

2011-03-14

174

Transcriptome Profiling Identifies Candidate Genes Associated with the Accumulation of Distinct Sulfur ?-Glutamyl Dipeptides in Phaseolus vulgaris and Vigna mungo Seeds  

PubMed Central

Common bean (Phaseolus vulgaris) and black gram (Vigna mungo) accumulate ?-Glutamyl-S-methylcysteine and ?-Glutamyl-methionine in seed, respectively. Transcripts were profiled by 454 pyrosequencing data at a similar developmental stage coinciding with the beginning of the accumulation of these metabolites. Expressed sequence tags were assembled into Unigenes, which were assigned to specific genes in the early release chromosomal assembly of the P. vulgaris genome. Genes involved in multiple sulfur metabolic processes were expressed in both species. Expression of Sultr3 members was predominant in P. vulgaris, whereas expression of Sultr5 members predominated in V. mungo. Expression of the cytosolic SERAT1;1 and -1;2 was approximately fourfold higher in P. vulgaris while expression of the plastidic SERAT2;1 was twofold higher in V. mungo. Among BSAS family members, BSAS4;1, encoding a cytosolic cysteine desulfhydrase, and BSAS1;1, encoding a cytosolic O-acetylserine sulphydrylase were most highly expressed in both species. This was followed by BSAS3;1 encoding a plastidic ?-cyanoalanine synthase which was more highly expressed by 10-fold in P. vulgaris. The data identify BSAS3;1 as a candidate enzyme for the biosynthesis of S-methylcysteine through the use of methanethiol as substrate instead of cyanide. Expression of GLC1 would provide a complete sequence leading to the biosynthesis of ?-Glutamyl-S-methylcysteine in plastids. The detection of S-methylhomoglutathione in P. vulgaris suggested that homoglutathione synthetase may accept, to some extent, ?-Glutamyl-S-methylcysteine as substrate, which might lead to the formation of S-methylated phytochelatins. In conclusion, 454 sequencing was effective at revealing differences in the expression of sulfur metabolic genes, providing information on candidate genes for the biosynthesis of distinct sulfur amino acid ?-Glutamyl dipeptides between P. vulgaris and V. mungo.

Liao, Dengqun; Cram, Dustin; Sharpe, Andrew G.; Marsolais, Frederic

2013-01-01

175

Unique functions of the type II interleukin 4 receptor identified in mice lacking the interleukin 13 receptor ?1 chain  

PubMed Central

The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2 (TH2)–mediated disease and associates with either the common ?-chain to form the type I IL-4R or with the IL-13R ?1 chain (IL-13R?1) to form the type II IL-4R. Here we used Il13ra1?/? mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to Il4ra?/? mice, which have weak TH2 responses, Il13ra1?/? mice had exacerbated TH2 responses. Il13ra1?/? mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13R?1 was essential for allergen-induced airway hyperreactivity and mucus hypersecretion but not for fibroblast or alternative macrophage activation. Thus, type I and II IL-4 receptors exert distinct effects on immune responses.

Ramalingam, Thirumalai R; Pesce, John T; Sheikh, Faruk; Cheever, Allen W; Mentink-Kane, Margaret M; Wilson, Mark S; Stevens, Sean; Valenzuela, David M; Murphy, Andrew J; Yancopoulos, George D; Urban, Joseph F; Donnelly, Raymond P; Wynn, Thomas A

2009-01-01

176

Distinct association of serum FGF21 or adiponectin levels with clinical parameters in patients with type 2 diabetes  

Microsoft Academic Search

Fibroblast growth factor 21 (FGF21) has been identified as a novel metabolic regulator. This cross-sectional study was performed to clarify how serum FGF21 levels were associated with clinical parameters in Japanese subjects with type 2 diabetes (n=139). Anthropometric and blood biochemical parameters, uses of drugs for diabetes, hypertension and dyslipidemia were examined regarding associations with fasting serum FGF21 concentrations. FGF21

Kazuhiro Eto; Bayasgalan Tumenbayar; Shu-ichi Nagashima; Fumiko Tazoe; Michiaki Miyamoto; Manabu Takahashi; Akihiko Ando; Kenta Okada; Hiroaki Yagyu; Shun Ishibashi

2010-01-01

177

Distinctive modulatory effects of five human auxiliary beta2 subunit splice variants on L-type calcium channel gating.  

PubMed

Sequence analysis of the human genome permitted cloning of five Ca(2+)-channel beta(2) splice variants (beta(2a)-beta(2e)) that differed only in their proximal amino-termini. The functional consequences of such beta(2)-subunit diversity were explored in recombinant L-type channels reconstituted in HEK 293 cells. Beta(2a) and beta(2e) targeted autonomously to the plasma membrane, whereas beta(2b)-beta(2d) localized to the cytosol when expressed in HEK 293 cells. The pattern of modulation of L-type channel voltage-dependent inactivation gating correlated with the subcellular localization of the component beta(2) variant-membrane-bound beta(2a) and beta(2e) subunits conferred slow(er) channel inactivation kinetics and displayed a smaller fraction of channels recovering from inactivation with fast kinetics, compared to beta(2b)-beta(2d) channels. The varying effects of beta(2) subunits on inactivation gating were accounted for by a quantitative model in which L-type channels reversibly distributed between fast and slow forms of voltage-dependent inactivation-membrane-bound beta(2) subunits substantially decreased the steady-state fraction of fast inactivating channels. Finally, the beta(2) variants also had distinctive effects on L-type channel steady-state activation gating, as revealed by differences in the waveforms of tail-activation (G-V) curves, and conferred differing degrees of prepulse facilitation to the channel. Our results predict important physiological consequences arising from subtle changes in Ca(2+)-channel beta(2)-subunit structure due to alternative splicing and emphasize the utility of splice variants in probing structure-function mechanisms. PMID:12719232

Takahashi, Shoji X; Mittman, Scott; Colecraft, Henry M

2003-05-01

178

Characterization of the N-ATPase, a distinct, laterally transferred Na+-translocating form of the bacterial F-type membrane ATPase.  

PubMed

An analysis of the distribution of the Na(+)-translocating ATPases/ATP synthases among microbial genomes identified an atypical form of the F(1)F(o)-type ATPase that is present in the archaea Methanosarcina barkeri and M. acetivorans, in a number of phylogenetically diverse marine and halotolerant bacteria and in pathogens Burkholderia spp. In complete genomes, representatives of this form (referred to here as N-ATPase) are always present as second copies, in addition to the typical proton-translocating ATP synthases. The N-ATPase is encoded by a highly conserved atpDCQRBEFAG operon and its subunits cluster separately from the equivalent subunits of the typical F-type ATPases. N-ATPase c subunits carry a full set of sodium-binding residues, indicating that most of these enzymes are Na(+)-translocating ATPases that likely confer on their hosts the ability to extrude Na(+) ions. Other distinctive properties of the N-ATPase operons include the absence of the delta subunit from its cytoplasmic sector and the presence of two additional membrane subunits, AtpQ (formerly gene 1) and AtpR (formerly gene X). We argue that N-ATPases are an early-diverging branch of membrane ATPases that, similarly to the eukaryotic V-type ATPases, do not synthesize ATP. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20472544

Dibrova, Daria V; Galperin, Michael Y; Mulkidjanian, Armen Y

2010-05-13

179

Sequence homology between the subunits of two immunologically and functionally distinct types of fimbriae of Actinomyces spp.  

PubMed Central

Nucleotide sequencing of the type 1 fimbrial subunit gene of Actinomyces viscosus T14V revealed a consensus ribosome-binding site followed by an open reading frame of 1,599 nucleotides. The encoded protein of 533 amino acids (Mr = 56,899) was predominantly hydrophilic except for an amino-terminal signal peptide and a carboxy-terminal region identified as a potential membrane-spanning segment. Edman degradation of the cloned protein expressed in Escherichia coli and the type 1 fimbriae of A. viscosus T14V showed that both began with alanine at position 31 of the deduced amino acid sequence. The amino acid compositions of the cloned protein and fimbriae also were comparable and in close agreement with the composition of the deduced protein. The amino acid sequence of the A. viscosus T14V type 1 fimbrial subunit showed no significant global homology with various other proteins, including the pilins of gram-negative bacteria. However, 34% amino acid sequence identity was noted between the type 1 fimbrial subunit of strain T14V and the type 2 fimbrial subunit of Actinomyces naeslundii WVU45 (M. K. Yeung and J. O. Cisar, J. Bacteriol. 170:3803-3809, 1988). This homology included several different conserved sequences of up to eight identical amino acids that were distributed in both the amino- and carboxy-terminal thirds of each Actinomyces fimbrial subunit. These findings indicate that the different types of fimbriae on these gram-positive bacteria share a common ancestry.

Yeung, M K; Cisar, J O

1990-01-01

180

Amplified Fragment Length Polymorphism Reveals Specific Epigenetic Distinctions between Mycobacterium avium Subspecies paratuberculosis Isolates of Various Isolation Types?  

PubMed Central

Amplified fragment length polymorphism (AFLP) was employed as a genetic analysis tool for the study of the genetic relatedness of Mycobacterium avium subsp. paratuberculosis isolates harvested from bovine fecal samples and from bovine or human tissues. This analysis revealed genetic differences between these two isolate types that were confirmed through cluster analysis. Dendrogram analysis separated these two isolate types based on the isolation scheme (tissue-associated versus fecal M. avium subsp. paratuberculosis isolates). Further sequence analysis of unique genetic regions from each isolation type revealed no genetic sequence differences. However, Clustal DNA alignments identified AFLP restriction enzyme sites that were undigested in the tissue-associated isolates. AFLP analysis also disclosed that the same AFLP restriction sites were digested in all of the fecal isolates. Sequence analysis further revealed a consensus sequence upstream of the undigested restriction sites for possible methyltransferase recognition in the tissue-associated M. avium subsp. paratuberculosis isolates.

O'Shea, B.; Khare, S.; Klein, P.; Roussel, A.; Adams, L. G.; Ficht, T. A.; Rice-Ficht, A. C.

2011-01-01

181

Comparative Functional Genomic Analysis Identifies Distinct and Overlapping Sets of Genes Required for Resistance to Monomethylarsonous Acid (MMAIII) and Arsenite (AsIII) in Yeast  

PubMed Central

Arsenic is a human toxin and carcinogen commonly found as a contaminant in drinking water. Arsenite (AsIII) is the most toxic inorganic form, but recent evidence indicates that the metabolite monomethylarsonous acid (MMAIII) is even more toxic. We have used a chemical genomics approach to identify the genes that modulate the cellular toxicity of MMAIII and AsIII in the yeast Saccharomyces cerevisiae. Functional profiling using homozygous deletion mutants provided evidence of the requirement of highly conserved biological processes in the response against both arsenicals including tubulin folding, DNA double-strand break repair, and chromatin modification. At the equitoxic doses of 150?M MMAIII and 300?M AsIII, genes related to glutathione metabolism were essential only for resistance to the former, suggesting a higher potency of MMAIII to disrupt glutathione metabolism than AsIII. Treatments with MMAIII induced a significant increase in glutathione levels in the wild-type strain, which correlated to the requirement of genes from the sulfur and methionine metabolic pathways and was consistent with the induction of oxidative stress. Based on the relative sensitivity of deletion strains deficient in GSH metabolism and tubulin folding processes, oxidative stress appeared to be the primary mechanism of MMAIII toxicity whereas secondary to tubulin disruption in the case of AsIII. Many of the identified yeast genes have orthologs in humans that could potentially modulate arsenic toxicity in a similar manner as their yeast counterparts.

Jo, William J.; Loguinov, Alex; Wintz, Henri; Chang, Michelle; Smith, Allan H.; Kalman, Dave; Zhang, Luoping; Smith, Martyn T.; Vulpe, Chris D.

2009-01-01

182

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis  

PubMed Central

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combinedP < 5 × 10?8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josee; Qi, Lu; Segre, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Bostrom, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisel P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; J?rgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proenca, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Spars?, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Ines; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

2011-01-01

183

Multilocus Sequence Typing Supports the Hypothesis that Cow- and Human-Associated Salmonella Isolates Represent Distinct and Overlapping Populations? †  

PubMed Central

A collection of 179 human and 156 bovine clinical Salmonella isolates obtained from across New York state over the course of 1 year was characterized using serotyping and a multilocus sequence typing (MLST) scheme based on the sequencing of three genes (fimA, manB, and mdh). The 335 isolates were differentiated into 52 serotypes and 72 sequence types (STs). Analyses of bovine isolates collected on different farms over time indicated that specific subtypes can persist over time on a given farm; in particular, a number of farms showed evidence for the persistence of a specific Salmonella enterica serotype Newport sequence type. Serotypes and STs were not randomly distributed among human and bovine isolates, and selected serotypes and STs were associated exclusively with either human or bovine sources. A number of common STs were geographically widespread. For example, ST6, which includes isolates representing serotype Typhimurium as well as the emerging serotype 4,5,12:i:-, was found among human and bovine isolates in a number of counties in New York state. Phylogenetic analyses supported the possibility that serotype 4,5,12:i:- is closely related to Salmonella serotype Typhimurium. Salmonella serotype Newport was found to represent two distinct evolutionary lineages that differ in their frequencies among human and bovine isolates. A number of Salmonella isolates carried two copies of manB (33 isolates) or showed small deletion events in fimA (nine isolates); these duplication and deletion events may provide mechanisms for the rapid diversification of Salmonella surface molecules. We conclude that the combined use of an economical three-gene MLST scheme and serotyping can provide considerable new insights into the evolution and transmission of Salmonella.

Alcaine, S. D.; Soyer, Y.; Warnick, L. D.; Su, W.-L.; Sukhnanand, S.; Richards, J.; Fortes, E. D.; McDonough, P.; Root, T. P.; Dumas, N. B.; Grohn, Y.; Wiedmann, M.

2006-01-01

184

Identifying nearby, Young, Late-type Stars by Means of their Circumstellar Disks  

NASA Astrophysics Data System (ADS)

It has recently been shown that a significant fraction of late-type members of nearby, very young associations (age lsim10 Myr) display excess emission at mid-IR wavelengths indicative of dusty circumstellar disks. We demonstrate that the detection of mid-IR excess emission can be utilized to identify new nearby, young, late-type stars including two definite new members ("TWA 33" and "TWA 34") of the TW Hydrae Association (TWA). Both new TWA members display mid-IR excess emission in the Wide-field Infrared Survey Explorer catalog and they show proper motion and youthful spectroscopic characteristics—namely, H? emission, strong lithium absorption, and low surface gravity features consistent with known TWA members. We also detect mid-IR excess—the first unambiguous evidence of a dusty circumstellar disk—around a previously identified UV-bright, young, accreting star (2M1337) that is a likely member of the Lower-Centaurus Crux region of the Scorpius-Centaurus Complex.

Schneider, Adam; Song, Inseok; Melis, Carl; Zuckerman, B.; Bessell, Mike

2012-10-01

185

IDENTIFYING NEARBY, YOUNG, LATE-TYPE STARS BY MEANS OF THEIR CIRCUMSTELLAR DISKS  

SciTech Connect

It has recently been shown that a significant fraction of late-type members of nearby, very young associations (age {approx}<10 Myr) display excess emission at mid-IR wavelengths indicative of dusty circumstellar disks. We demonstrate that the detection of mid-IR excess emission can be utilized to identify new nearby, young, late-type stars including two definite new members ('TWA 33' and 'TWA 34') of the TW Hydrae Association (TWA). Both new TWA members display mid-IR excess emission in the Wide-field Infrared Survey Explorer catalog and they show proper motion and youthful spectroscopic characteristics-namely, H{alpha} emission, strong lithium absorption, and low surface gravity features consistent with known TWA members. We also detect mid-IR excess-the first unambiguous evidence of a dusty circumstellar disk-around a previously identified UV-bright, young, accreting star (2M1337) that is a likely member of the Lower-Centaurus Crux region of the Scorpius-Centaurus Complex.

Schneider, Adam; Song, Inseok [Department of Physics and Astronomy, University of Georgia, Athens, GA 30602 (United States); Melis, Carl [Center for Astrophysics and Space Sciences, University of California, San Diego, CA 92093 (United States); Zuckerman, B. [Department of Physics and Astronomy, University of California, Los Angeles, CA, 90095 (United States); Bessell, Mike, E-mail: aschneid@physast.uga.edu, E-mail: song@physast.uga.edu, E-mail: cmelis@ucsd.edu, E-mail: ben@astro.ucla.edu, E-mail: bessell@mso.anu.edu.au [Research School of Astronomy and Astrophysics, The Australian National University, Weston Creek, ACT 2611 (Australia)

2012-10-01

186

Identifying different types of de-differentiated microspores from indica-japonica F(1) hybrids with subspecies-differentiating RFLP probes in rice.  

PubMed

The indica, japonica and intermediary types of de-differentiated microspores from indica-japonica F(1) hybrids were identified with 11 subspecies-differentiating RELP probes in rice (Oryza sativa L.). The results showed that the distribution of indica, japonica and intermediary types of de-differentiated microspores could be easily detected in a simple and quick way using the RFLP method. Moreover, the microspores from the same F(1) hybrid but inoculated onto different media, or microspores from different F(1) hybrids when inoculated onto the same medium, often displayed distinctive distribution curves of de-differentiated microspores types, indicating that the media employed in this experiment had high selectivity for the de-differentiation of certain types of microspores. The application of the RELP method to de-differentiated microspore identification is of great theoretical and practical significance in rice doubled-haploid breeding. PMID:19352742

Xie, J H; Gao, M W; Lu, J; Zhuang, J Y; Lin, H X; Qian, H R; Zheng, K L

1997-01-01

187

The Boggy Plain Supersuite: A distinctive belt of I?type igneous rocks of potential economic significance in the Lachlan Fold Belt  

Microsoft Academic Search

The Early Devonian Boggy Plain Supersuite is a belt of I?type granitic and volcanic rocks extending for over 500 km in the central Lachlan Fold Belt. It has a distinctive composition and origin. Compared with other Lachlan Fold Belt I?types, rocks of the supersuite are high in Cu and incompatible elements (K, Ba, Sr, Rb, La, Ce, U, and Th).

D. Wyborn; B. S. Turner; B. W. Chappell

1987-01-01

188

The plasmid R64 thin pilus identified as a type IV pilus.  

PubMed Central

The entire nucleotide sequence of the pil region of the IncI1 plasmid R64 was determined. Analysis of the sequence indicated that 14 genes, designated pilI through pilV, are involved in the formation of the R64 thin pilus. Protein products of eight pil genes were identified by the maxicell procedure. The pilN product was shown to be a lipoprotein by an experiment using globomycin. A computer search revealed that several R64 pil genes have amino acid sequence homology with proteins involved in type IV pilus biogenesis, protein secretion, and transformation competence. The pilS and pilV products were suggested to be prepilins for the R64 thin pilus, and the pilU product appears to be a prepilin peptidase. These results suggest that the R64 thin pilus belongs to the type IV family, specifically group IVB, of pili. The requirement of the pilR and pilU genes for R64 liquid mating was demonstrated by constructing their frameshift mutations. Comparison of three type IVB pilus biogenesis systems, the pil system of R64, the toxin-coregulated pilus (tcp) system of Vibrio cholerae, and the bundle-forming pilus (bfp) system of enteropathogenic Escherichia coli, suggests that they have evolved from a common ancestral gene system.

Kim, S R; Komano, T

1997-01-01

189

Constrained Evolution of Human Immunodeficiency Virus Type 1 Protease during Sequential Therapy with Two Distinct Protease Inhibitors  

PubMed Central

Human immunodeficiency virus type 1 (HIV-1) variants that have developed protease (PR) inhibitor resistance most often display cross-resistance to several molecules within this class of antiretroviral agents. The clinical benefit of the switch to a second PR inhibitor in the presence of such resistant viruses may be questionable. We have examined the evolution of HIV-1 PR genotypes and phenotypes in individuals having failed sequential treatment with two distinct PR inhibitors: saquinavir (SQV) followed by indinavir (IDV). In viruses where typical SQV resistance mutations were detected before the change to IDV, the corresponding mutations were maintained under IDV, while few additional mutations emerged. In viruses where no SQV resistance mutations were detected before the switch to IDV, typical SQV resistance profiles emerged following the introduction of IDV. We conclude that following suboptimal exposure to a first PR inhibitor, the introduction of a second molecule of this class can lead to rapid selection of cross-resistant virus variants that may not be detectable by current genotyping methods at the time of the inhibitor switch. Viruses committed to resistance to the first inhibitor appear to bear the “imprint” of this initial selection and can further adapt to the selective pressure exerted by the second inhibitor following a pathway that preserves most of the initially selected mutations.

Dulioust, Anne; Paulous, Sylvie; Guillemot, Laurent; Delavalle, Anne-Marie; Boue, Francois; Clavel, Francois

1999-01-01

190

Distinct Mechanisms Trigger Apoptosis in Human Immunodeficiency Virus Type 1-Infected and in Uninfected Bystander T Lymphocytes  

PubMed Central

Apoptosis is a main feature of AIDS pathogenesis and is thought to play a role in the progressive decrease of CD4+ T lymphocytes in infected individuals. To determine whether apoptosis occurs in infected and/or in uninfected peripheral blood T lymphocytes, we have used a recombinant human immunodeficiency virus type 1 (HIV-1) infectious clone expressing the green fluorescent protein (GFP). Using flow cytometry, we have determined the incidence of apoptosis by either terminal transferase dUTP nick end labeling or annexin-V assays in different cell subpopulations, i.e., in CD4+ or CD8+ T cells that were GFP positive or negative. After HIV-1 infection of purified peripheral blood lymphocytes, we observed that apoptosis occurred mostly in infected CD4+ peripheral blood lymphocytes. Remarkably, the presence of monocyte-derived macrophages in the culture increased dramatically the apoptosis of uninfected bystander T lymphocytes, while apoptosis in HIV-infected T lymphocytes was not changed. We therefore demonstrate that HIV-induced apoptosis results from at least two distinct mechanisms: (i) direct apoptosis in HIV-infected CD4+ T lymphocytes and (ii) indirect apoptosis in uninfected T cells mediated by antigen-presenting cells.

Herbein, Georges; Van Lint, Carine; Lovett, Jennie L.; Verdin, Eric

1998-01-01

191

Distinctions between bovine herpesvirus 1 and herpes simplex virus type 1 VP22 tegument protein subcellular associations.  

PubMed

The alphaherpesvirus tegument protein VP22 has been characterized with multiple traits including microtubule reorganization, nuclear localization, and nonclassical intercellular trafficking. However, all these data were derived from studies using herpes simplex virus type 1 (HSV-1) and may not apply to VP22 homologs of other alphaherpesviruses. We compared subcellular attributes of HSV-1 VP22 (HVP22) with bovine herpesvirus 1 (BHV-1) VP22 (BVP22) using green fluorescent protein (GFP)-fused VP22 expression vectors. Fluorescence microscopy of cell lines transfected with these constructs revealed differences as well as similarities between the two VP22 homologs. Compared to that of HVP22, the BVP22 microtubule interaction was much less pronounced. The VP22 nuclear interaction varied, with a marbled or halo appearance for BVP22 and a speckled or nucleolus-bound appearance for HVP22. Both VP22 homologs associated with chromatin at various stages of mitosis and could traffic from expressing cells to the nuclei of nonexpressing cells. However, distinct qualitative differences in microtubule, nuclear, and chromatin association as well as trafficking were observed. The differences in VP22 homolog characteristics revealed in this study will help define VP22 function within HSV-1 and BHV-1 infection. PMID:10708447

Harms, J S; Ren, X; Oliveira, S C; Splitter, G A

2000-04-01

192

Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain  

PubMed Central

To characterize gene expression patterns in the regional subdivisions of the mammalian brain, we integrated spatial gene expression patterns from the Allen Brain Atlas for the adult mouse with panels of cell type-specific genes for neurons, astrocytes, and oligodendrocytes from previously published transcriptome profiling experiments. We found that the combined spatial expression patterns of 170 neuron-specific transcripts revealed strikingly clear and symmetrical signatures for most of the brain’s major subdivisions. Moreover, the brain expression spatial signatures correspond to anatomical structures and may even reflect developmental ontogeny. Spatial expression profiles of astrocyte- and oligodendrocyte-specific genes also revealed regional differences; these defined fewer regions and were less distinct but still symmetrical in the coronal plane. Follow-up analysis suggested that region-based clustering of neuron-specific genes was related to (i) a combination of individual genes with restricted expression patterns, (ii) region-specific differences in the relative expression of functional groups of genes, and (iii) regional differences in neuronal density. Products from some of these neuron-specific genes are present in peripheral blood, raising the possibility that they could reflect the activities of disease- or injury-perturbed networks and collectively function as biomarkers for clinical disease diagnostics.

Ko, Younhee; Ament, Seth A.; Eddy, James A.; Caballero, Juan; Earls, John C.; Hood, Leroy; Price, Nathan D.

2013-01-01

193

Genetically Distinct Populations in an Asian Soldier-Producing Aphid, Pseudoregma bambucicola (Homoptera: Aphididae), Identified by DNA Fingerprinting and Molecular Phylogenetic Analysis  

Microsoft Academic Search

To estimate genetic structure of a soldier-producing aphid, Pseudoregma bambucicola, samples from natural populations throughout southeastern Asia were analyzed by a DNA fingerprinting technique. We unexpectedly found that P. bambucicola comprises two geographic groups, the northern group and the southern group, which are genetically distinct from each other but morphologically almost indistinguishable. Molecular phylogenetic and statistical analyses based on mitochondrial

Takema Fukatsu; Harunobu Shibao; Naruo Nikoh; Shigeyuki Aoki

2001-01-01

194

Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations  

NSDL National Science Digital Library

Glucose sensing in the brain has been proposed to be involved in regulating food intake, but the mechanism is not known. Glucose transporter type 2 (GLUT2)-null mice fail to control their food intake in response to glucose, suggesting a potential role for this transporter as a glucose sensor in the brain. Here we show that individuals with a genetic variation in GLUT2 (Thr110Ile) have a higher daily intake of sugars in two distinct populations. In the first population, compared with individuals with the Thr/Thr genotype, carriers of the Ile allele had a significantly higher intake of sugars as assessed from 3-day food records administered on two separate visits (visit 1: 112 ñ 9 vs. 86 ñ 4 g/day, P = 0.01; visit 2: 111 ñ 8 vs. 82 ñ 4 g/day, P = 0.003), demonstrating within-population reproducibility. In a second population, carriers of the Ile allele also reported consuming a significantly greater intake of sugars (131 ñ 5 vs. 115 ñ 3 g/day, P = 0.007) over a 1-mo period as measured from a food frequency questionnaire. GLUT2 genotypes were not associated with fat, protein, or alcohol intake in either population. These observations were consistent across older and younger adults as well as among subjects with early Type 2 diabetes and healthy individuals. Taken together, our findings show that a genetic variation in GLUT2 is associated with habitual consumption of sugars, suggesting an underlying glucose-sensing mechanism that regulates food intake.

Karen M Eny (University of Toronto Nutritional Sciences); Thomas MS Wolever (University of Toronto/St. Michael's Hospital Nutritional Science); Benedicte Fontaine-Bisson (University of Toronto Nutritional Sciences); Ahmed El-Sohemy (University of Toronto Nutritional Sciences)

2008-03-18

195

The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes  

PubMed Central

Background The aim of the study was to optimize protocols for finding and identifying serum proteins that are differentially expressed in persons with normal glucose tolerance (NGT) compared to individuals with type 2 diabetes mellitus (T2DM). Serum from persons with NGT and persons with T2DM was profiled using ProteinChip arrays and time-of-flight mass spectra were generated by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Results Mass spectra from NGT- and T2DM-groups were compared. Fifteen proteins ranging from 5 to 79 kDa were differentially expressed (p < 0.05). Five of these proteins showed decreased and ten showed increased serum levels in individuals with T2DM. To be able to identify the proteins, the complexity of the sample was reduced by fractionation approaches. Subsequently, the purified fractions containing biomarkers were separated by one-dimensional SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in two identical lanes. Protein bands of the first lane were excised and subjected to passive elution to recapture the biomarkers on ProteinChip arrays. The corresponding bands of the second lane were subjected to peptide-mass fingerprinting (PMF). Using this approach four of the differentially expressed proteins were identified as apolipoprotein C3 (9.4 kDa), transthyretin (13.9 kDa), albumin (66 kDa) and transferrin (79 kDa). Whereas apolipoprotein C3 and transthyretin were up-regulated, albumin and transferrin were down-regulated in T2DM. Conclusion Protocols for protein profiling by SELDI-TOF MS and protein identification by fractionation, SDS-PAGE and PMF were optimized for serum from humans with T2DM. With these protocols differentially expressed proteins were discovered and identified when serum from NGT- and T2DM-individuals was analyzed.

Sundsten, Tea; Eberhardson, Michael; Goransson, Michael; Bergsten, Peter

2006-01-01

196

Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle.  

PubMed

The activities of type 1 protein phosphatase (PP1) and 2A (PP2A) have distinct, essential roles in cell cycle control. Two previously identified PP1 genes (dis2+ and sds21+) and two PP2A genes (ppa1+ and ppa2+), highly homologous to mammalian PP2A, have been isolated from fission yeast. Only double gene disruption of both PP2A genes results in lethality, as is the case for PP1 genes. By fractionating and assaying PPases in wild-type, various deletion, and point mutant strains, the decrease of PP1 or PP2A activity is shown to cause mitotic defects, exhibiting strikingly different cell cycle phenotypes: cold-sensitive mutations in the same amino acid lesion of PP1 and PP2A produce chromosome nondisjunction and premature mitosis, respectively. Consistently, PP1 and PP2A genes cannot be functionally substituted. Although the overall levels of PP1 and PP2A activities do not fluctuate during the cell cycle, subpopulations might be regulated. PMID:2170029

Kinoshita, N; Ohkura, H; Yanagida, M

1990-10-19

197

Significant Deregulated Pathways in Diabetes Type II Complications Identified through Expression Based Network Biology  

NASA Astrophysics Data System (ADS)

Type 2 Diabetes is a complex multifactorial disease, which alters several signaling cascades giving rise to serious complications. It is one of the major risk factors for cardiovascular diseases. The present research work describes an integrated functional network biology approach to identify pathways that get transcriptionally altered and lead to complex complications thereby amplifying the phenotypic effect of the impaired disease state. We have identified two sub-network modules, which could be activated under abnormal circumstances in diabetes. Present work describes key proteins such as P85A and SRC serving as important nodes to mediate alternate signaling routes during diseased condition. P85A has been shown to be an important link between stress responsive MAPK and CVD markers involved in fibrosis. MAPK8 has been shown to interact with P85A and further activate CTGF through VEGF signaling. We have traced a novel and unique route correlating inflammation and fibrosis by considering P85A as a key mediator of signals. The next sub-network module shows SRC as a junction for various signaling processes, which results in interaction between NF-kB and beta catenin to cause cell death. The powerful interaction between these important genes in response to transcriptionally altered lipid metabolism and impaired inflammatory response via SRC causes apoptosis of cells. The crosstalk between inflammation, lipid homeostasis and stress, and their serious effects downstream have been explained in the present analyses.

Ukil, Sanchaita; Sinha, Meenakshee; Varshney, Lavneesh; Agrawal, Shipra

198

Tests of two methods for identifying founder effects in metapopulations reveal substantial type II error.  

PubMed

Genetic analysis has been promoted as a way to reconstruct recent historical dynamics ("historical demography") by screening for signatures of events, such as bottlenecks, that disrupt equilibrium patterns of variation. Such analyses might also identify "metapopulation" processes like extinction and recolonization or source-sink dynamics, but this potential remains largely unrealized. Here we use simulations to test the ability of two currently used strategies to distinguish between a set of interconnected subpopulations (demes) that have undergone bottlenecks or extinction and recolonization events (metapopulation dynamics) from a set of static demes. The first strategy, decomposed pairwise regression, provides a holistic test for heterogeneity among demes in their patterns of isolation-by-distance. This method suffered from a type II error rate of 59-100 %, depending on parameter conditions. The second strategy tests for deviations from mutation-drift equilibrium on a deme-by-deme basis to identify sites likely to have experienced recent bottlenecks or founder effects. Although bottleneck tests have good statistical power for single populations with recent population declines, their validity in structured populations has been called into question, and they have not been tested in a metapopulation context with immigration (or colonization) and population recovery. Our simulations of hypothetical metapopulations show that population recovery can rapidly eliminate the statistical signature of a bottleneck, and that moderate levels of gene flow can generate a false signal of recent population growth for demes in equilibrium. Although we did not cover all possible metapopulation scenarios, the performance of the tests was disappointing. Our results indicate that these methods might often fail to identify population bottlenecks and founder effects if population recovery and/or gene flow are influential demographic features of the study system. PMID:23504127

Reynolds, R Graham; Fitzpatrick, Benjamin M

2013-03-17

199

The evolution of three types of indoleamine 2,3 dioxygenases in fungi with distinct molecular and biochemical characteristics.  

PubMed

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme and known as a mammalian immunosuppressive molecule. In fungi, the primary role of IDO is to supply nicotinamide adenine dinucleotide (NAD(+)) via the kynurenine pathway. We previously reported that the koji-mold, Aspergillus oryzae has two IDO genes, IDO? and IDO?. In the present study, we found that A. oryzae also has the third IDO, IDO?. These three-types of IDOs are widely distributed among the Pezizomycotina fungi, although the black truffle, Tuber melanosporum has only one corresponding gene to IDO?/IDO?. The yeast, Saccharomyces cerevisiae has a single IDO gene. Generally, Pezizomycotina IDO? showed similar enzymatic properties to the yeast IDO, suggesting that the IDO? is a functional homologue of the S. cerevisiae IDO. In contrast to IDO?, the K(m) value of IDO? is higher. However, the reaction velocity of IDO? is very fast, resulting in comparable or higher catalytic efficiency than IDO?. Thus IDO? may functionally substitute for IDO? in fungal L-Trp metabolism. The enzymatic activity of IDO? was comparatively very low with the values of enzymatic parameters comparable to vertebrate IDO2 enzymes. IDO? and IDO? have similar gene structures, suggesting that they were generated by gene duplication which occurred rather early in Pezizomycotina evolution, although the timing of the duplication remains debatable. In contrast, the phylogenetic trees suggest that IDO?s form an evolutionarily distinct group of IDO enzymes, with a closer relationship to group I bacterial IDOs than other fungal IDOs. The ancestor of the IDO? family is likely to have diverged from other eukaryotic IDOs at a very early stage of eukaryotic evolution. PMID:22564706

Yuasa, Hajime J; Ball, Helen J

2012-05-05

200

Type 1 Gaucher Disease: Significant disease manifestations in "asymptomatic" homozygotes identified by prenatal carrier screening  

PubMed Central

Background Type 1 Gaucher Disease (GD), an autosomal recessive lysosomal storage disease, is most prevalent in the Ashkenazi Jewish (AJ) population. Experts have suggested that up to two-thirds of AJ homozygotes for the common mutation (N370S) are asymptomatic throughout life and never come to medical attention. However, there are no systematic studies of N370S homozygotes to support this presumption. Methods Prenatal carrier screening of 8069 AJ adults for six common GD mutations was performed. GD manifestations in 37 previously unrecognized homozygotes were assessed by clinical, laboratory and imaging studies. Results Among the 8069 AJ screenees, 524 GD carriers (1:15.4) and nine previously unrecognized GD homozygotes (1:897) were identified, consistent with that expected (1:949, p=1.0). Six of these homozygotes, and 31 AJ GD homozygotes identified by other prenatal carrier screening programs in the New York metropolitan area were evaluated (aged 17-40 years). Of these, 84% were N370S homozygotes, others being heteroallelic for N370S and V394L, L444P or R496H. Notably, 65% reported no GD medical complaints. However, 49% had anemia and/or thrombocytopenia. Among the 29 who had imaging studies, 97% had mild to moderate splenomegaly and 55% had hepatomegaly; skeletal imaging revealed marrow infiltration (100%), Erlenmeyer flask deformities (43%), lucencies (22%) and bone infarcts (14%). DEXA studies of 25 homozygotes found 60% osteopenic or osteoporotic. Conclusions Contrary to previous discussions, almost all asymptomatic GD homozygotes serendipitously diagnosed by prenatal carrier screening had disease manifestations and should be followed for disease progression and institution of appropriate medical management.

Balwani, Manisha; Fuerstman, Laura; Kornreich, Ruth; Edelmann, Lisa; Desnick, Robert J.

2011-01-01

201

Identifying obesity indicators which best correlate with type 2 diabetes in a Chinese population  

PubMed Central

Background Obesity has been shown to be a prognostic indicator of type 2 diabetes (T2D); however, the power of different obesity indicators in the detection of T2D remains controversial. This study evaluates the detecting power of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHTR) for the presence of T2D in undiagnosed diabetics among the Chinese population. Methods Individuals were selected from an ongoing large-scale population-based Beijing Community Pre-Diabetes (BCPD) study cohort. The oral glucose tolerance tests (OGTT) were performed to diagnose diabetes. A total of 220 new cases of T2D and 1,868 normal blood glucose subjects were analyzed. ROC curve analyses were used to compare the association of different obesity indicators with T2D and determine the optimal cut-off points of the best predictor for identifying T2D in men and women. Results All indicators positively correlated with presence of T2D in both men and women. In women, WC, WHR and WHTR were similar, but were better in identifying T2D when compared to BMI (P?

2012-01-01

202

A Machine Learning Approach for Identifying Novel Cell Type-Specific Transcriptional Regulators of Myogenesis  

PubMed Central

Transcriptional enhancers integrate the contributions of multiple classes of transcription factors (TFs) to orchestrate the myriad spatio-temporal gene expression programs that occur during development. A molecular understanding of enhancers with similar activities requires the identification of both their unique and their shared sequence features. To address this problem, we combined phylogenetic profiling with a DNA–based enhancer sequence classifier that analyzes the TF binding sites (TFBSs) governing the transcription of a co-expressed gene set. We first assembled a small number of enhancers that are active in Drosophila melanogaster muscle founder cells (FCs) and other mesodermal cell types. Using phylogenetic profiling, we increased the number of enhancers by incorporating orthologous but divergent sequences from other Drosophila species. Functional assays revealed that the diverged enhancer orthologs were active in largely similar patterns as their D. melanogaster counterparts, although there was extensive evolutionary shuffling of known TFBSs. We then built and trained a classifier using this enhancer set and identified additional related enhancers based on the presence or absence of known and putative TFBSs. Predicted FC enhancers were over-represented in proximity to known FC genes; and many of the TFBSs learned by the classifier were found to be critical for enhancer activity, including POU homeodomain, Myb, Ets, Forkhead, and T-box motifs. Empirical testing also revealed that the T-box TF encoded by org-1 is a previously uncharacterized regulator of muscle cell identity. Finally, we found extensive diversity in the composition of TFBSs within known FC enhancers, suggesting that motif combinatorics plays an essential role in the cellular specificity exhibited by such enhancers. In summary, machine learning combined with evolutionary sequence analysis is useful for recognizing novel TFBSs and for facilitating the identification of cognate TFs that coordinate cell type–specific developmental gene expression patterns.

Kim, Yongsok; Tansey, Terese; Bloom, Molly J.; Ovcharenko, Ivan; Michelson, Alan M.

2012-01-01

203

Insertion element IS 1296 in Mycoplasma mycoides subsp. mycoides small colony identifies a European clonal line distinct from African and Australian strains  

Microsoft Academic Search

Strains of Mycoplasma mycoides subsp. mycoides small colony (SC) type, the agent of contagious bovine pleuropneumonia (CBPP), were analysed with respect to the polymorphism of distribution of a newly discovered insertion element, lS1296, on the chromosome. Analysis of 64 strains isolated from Europe, Africa and Australia, including four vaccine strains and the type strain PG1, revealed ten different IS patterns,

Xiaoxing Cheng; Jacques Nicolet; F. Poumarat; Jose Regalla; Franqois Thiaucourt; J. Frey

1995-01-01

204

EDAM: an ontology of bioinformatics operations, types of data and identifiers, topics and formats  

PubMed Central

Motivation: Advancing the search, publication and integration of bioinformatics tools and resources demands consistent machine-understandable descriptions. A comprehensive ontology allowing such descriptions is therefore required. Results: EDAM is an ontology of bioinformatics operations (tool or workflow functions), types of data and identifiers, application domains and data formats. EDAM supports semantic annotation of diverse entities such as Web services, databases, programmatic libraries, standalone tools, interactive applications, data schemas, datasets and publications within bioinformatics. EDAM applies to organizing and finding suitable tools and data and to automating their integration into complex applications or workflows. It includes over 2200 defined concepts and has successfully been used for annotations and implementations. Availability: The latest stable version of EDAM is available in OWL format from http://edamontology.org/EDAM.owl and in OBO format from http://edamontology.org/EDAM.obo. It can be viewed online at the NCBO BioPortal and the EBI Ontology Lookup Service. For documentation and license please refer to http://edamontology.org. This article describes version 1.2 available at http://edamontology.org/EDAM_1.2.owl. Contact: jison@ebi.ac.uk

Ison, Jon; Kalas, Matus; Jonassen, Inge; Bolser, Dan; Uludag, Mahmut; McWilliam, Hamish; Malone, James; Lopez, Rodrigo; Pettifer, Steve; Rice, Peter

2013-01-01

205

Targeting Tn5 Transposase Identifies Human Immunodeficiency Virus Type 1 Inhibitors  

PubMed Central

Human immunodeficiency virus (HIV) type 1 (HIV-1) integrase is an underutilized drug target for the treatment of HIV infection. One limiting factor is the lack of costructural data for use in the rational design or modification of integrase inhibitors. Tn5 transposase is a structurally well characterized, related protein that may serve as a useful surrogate. However, little data exist on inhibitor cross-reactivity. Here we screened 16,000 compounds using Tn5 transposase as the target and identified 20 compounds that appear to specifically inhibit complex assembly. Six were found to also inhibit HIV-1 integrase. These compounds likely interact with a highly conserved region presumably within the catalytic core. Most promising, several cinnamoyl derivatives were found to inhibit HIV transduction in cells. The identification of integrase inhibitors from a screen using Tn5 transposase as the target illustrates the utility of Tn5 as a surrogate for HIV-1 integration even though the relationship between the two systems is limited to the active site architecture and catalytic mechanism.

Ason, Brandon; Knauss, Daniel J.; Balke, Allison M.; Merkel, George; Skalka, Anna Marie; Reznikoff, William S.

2005-01-01

206

Genetic diversity of human immunodeficiency virus type 2: evidence for distinct sequence subtypes with differences in virus biology.  

PubMed Central

The virulence properties of human immunodeficiency virus type 2 (HIV-2) are known to vary significantly and to range from relative attenuation in certain individuals to high-level pathogenicity in others. These differences in clinical manifestations may, at least in part, be determined by genetic differences among infecting virus strains. Evaluation of the full spectrum of HIV-2 genetic diversity is thus a necessary first step towards understanding its molecular epidemiology, natural history of infection, and biological diversity. In this study, we have used nested PCR techniques to amplify viral sequences from the DNA of uncultured peripheral blood mononuclear cells from 12 patients with HIV-2 seroreactivity. Sequence analysis of four nonoverlapping genomic regions allowed a comprehensive analysis of HIV-2 phylogeny. The results revealed (i) the existence of five distinct and roughly equidistant evolutionary lineages of HIV-2 which, by analogy with HIV-1, have been termed sequence subtypes A to E; (ii) evidence for a mosaic HIV-2 genome, indicating that coinfection with genetically divergent strains and recombination can occur in HIV-2-infected individuals; and (iii) evidence supporting the conclusion that some of the HIV-2 subtypes may have arisen from independent introductions of genetically diverse sooty mangabey viruses into the human population. Importantly, only a subset of HIV-2 strains replicated in culture: all subtype A viruses grew to high titers, but attempts to isolate representatives of subtypes C, D, and E, as well as the majority of subtype B viruses, remained unsuccessful. Infection with all five viral subtypes was detectable by commercially available serological (Western immunoblot) assays, despite intersubtype sequence differences of up to 25% in the gag, pol, and env regions. These results indicate that the genetic and biological diversity of HIV-2 is far greater than previously appreciated and suggest that there may be subtype-specific differences in virus biology. Systematic natural history studies are needed to determine whether this heterogeneity has clinical relevance and whether the various HIV-2 subtypes differ in their in vivo pathogenicity. Images

Gao, F; Yue, L; Robertson, D L; Hill, S C; Hui, H; Biggar, R J; Neequaye, A E; Whelan, T M; Ho, D D; Shaw, G M

1994-01-01

207

Functionally different AMPA-type glutamate receptors in morphologically identified neurons in rat superficial superior colliculus  

Microsoft Academic Search

In the superficial superior colliculus, a center of sensory processing related to visual salience, glutamate is used as a major excitatory neurotransmitter. ?-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors include a Ca2+-impermeable, outwardly rectifying type (type I) and a Ca2+-permeable, inwardly rectifying type (type II). To study the contribution of these AMPA receptor subtypes to visual sensory processing in the superior

T Endo; T Isa

2001-01-01

208

Enhanced malignant transformation induced by expression of a distinct protein domain of ribonucleotide reductase large subunit from herpes simplex virus type 2.  

PubMed Central

The 1.3-kilobase (kb) Pst I DNA fragment C (Pst I-C) of herpes simplex virus type 2 (HSV-2) morphological transforming region III (mtrIII; map unit 0.562-0.570) encodes part of the N-terminal half of the large subunit of ribonucleotide reductase (RR1; amino acid residues 71-502) and induces the neoplastic transformation of immortalized cell lines. To assess directly the role of these RR1 protein sequences in cell transformation, the Pst I-C fragment was cloned in an expression vector (p91023) containing an adenovirus-simian virus 40 promoter-enhancer to generate recombinant plasmid p9-C. Expression of a protein domain (approximately 65 kDa) was observed in p9-C-transfected COS-7 and Rat2 cells but not in those transfected with plasmid pHC-14 (Pst I-C in a promoterless vector). In Rat2 cells, p9-C induced highly transformed foci at an elevated frequency compared with that of pHC-14. Introduction of translation termination (TAG) condons within the RR1 coding sequence and within all three reading frames inactivated RR1 protein expression from p9-C and reduced its transforming activity to the level seen with the standard pHC-14 construct. Wild-type p9-C specified a protein kinase capable of autophosphorylation. Computer-assisted analysis further revealed significant similarity between regions of mtrIII-specific RR1 and amino acid patterns conserved within the proinsulin precursor family and DNA transposition proteins. These results identify a distinct domain of the HSV-2 RR1 protein involved in the induction of enhanced malignant transformation. In addition, the data indicate that the mtrIII DNA itself can induce basal-level transformation in the absence of protein expression. Images

Ali, M A; McWeeney, D; Milosavljevic, A; Jurka, J; Jariwalla, R J

1991-01-01

209

Isolation and characterization of epithelial and myogenic cells by "fishing" for the morphologically distinct cell types in rat primary periodontal ligament cultures.  

PubMed

The periodontal ligament (PDL) contains various cell populations and plays a central role in the maintenance, repair, and regeneration of the periodontium, i.e., tooth-supporting structures. Because primary cells isolated from PDL tissue are heterogeneous, the establishment of an effective isolation method for cells of interest is desired. In the present study, two morphologically distinct cell types were identified in confluent primary cultures derived from rat PDL. To isolate these cell populations, a small piece of filter paper soaked with trypsin-EDTA was placed directly onto the target cell population, enabling the cells to detach from the culture dish. The filter papers were then transferred into fresh culture dishes to establish outgrowth cultures; these two steps constitute the "cell fishing" method. The "fished" cell types were propagated and subcultured for further analyses. In morphological evaluation, immunocytochemical analyses, and reverse transcription-polymerase chain reaction, the isolated cells exhibited a polygonal appearance or a mono- or multinucleated appearance, with a high cytoplasm-to-nucleus ratio, leading to their being characterized as epithelial or myogenic cell populations, respectively. Surprisingly, a notable proportion of the multinuclear cells in the primary and subsequent isolated cultures demonstrated dramatic, spontaneous contractions, a feature typical of skeletal muscle cells. Finally, the isolated cell populations maintained a normal karyotype with a diploid chromosomal number. These results demonstrated that physiological epithelial and skeletal muscle cells can be obtained from primary PDL cultures without artificial induction using growth factors or chemicals, and can be propagated as individual lineage-committed cell populations; the populations consisted of differentiated and progenitor cells that maintained chromosomal stability. This simple, classical culture procedure provides new insights into the biological properties of PDL cells, which are potentially important for the differentiation of tissue or somatic stem cells and for the development of future cell-based therapies for dental and muscular diseases. PMID:23649106

Tominaga, Noriko; Nakahara, Taka; Nasu, Masanori; Satoh, Tazuko

2013-05-04

210

Virus Isolates during Acute and Chronic Human Immunodeficiency Virus Type 1 Infection Show Distinct Patterns of Sensitivity to Entry Inhibitors  

PubMed Central

We studied the effect of entry inhibitors on 58 virus isolates derived during acute and chronic infection to validate these inhibitors in vitro and to probe whether viruses at early and chronic disease stages exhibit general differences in the interaction with entry receptors. We included members of all types of inhibitors currently identified: (i) agents that block gp120 binding to CD4 (CD4-IgG2 and monoclonal antibody [MAb] IgG1b12), (ii) compounds that block the interaction with CCR5 (the chemokine RANTES/CCL5, the small-molecule inhibitor AD101, and the anti-CCR5 antibody PRO 140), (iii) the fusion inhibitor enfuvirtide (T-20), and (iv) neutralizing antibodies directed against gp120 (MAb 2G12) and gp41 (MAbs 2F5 and 4E10). No differences between viruses from acute and chronic infections in the susceptibility to inhibitors targeting the CD4 binding site, CCR5, or fusion or to MAb 2G12 were apparent, rendering treatment with entry inhibitors feasible across disease stages. The notable exceptions were antibodies 2F5 and 4E10, which were more potent in inhibiting viruses from acute infection (P = 0.0088 and 0.0005, respectively), although epitopes of these MAbs were equally well preserved in both groups. Activities of these MAbs correlated significantly with each other, suggesting that common features of the viral envelope modulate their potencies.

Rusert, Peter; Kuster, Herbert; Joos, Beda; Misselwitz, Benjamin; Gujer, Cornelia; Leemann, Christine; Fischer, Marek; Stiegler, Gabriela; Katinger, Hermann; Olson, William C.; Weber, Rainer; Aceto, Leonardo; Gunthard, Huldrych F.; Trkola, Alexandra

2005-01-01

211

Differences in Cortical Actin Structure and Dynamics Document That Different Types of Blebs Are Formed by Distinct Mechanisms  

Microsoft Academic Search

Bleb formation has been studied by specifically targeting major factors controlling this process, such as microtubule disassembly, local actin depolymerization, and increased pressure. At least two different types of blebs (types 1 and 2) formed by different mechanisms and possibly a third type (type 3) can be documented at the front of living polarized cells expressing green fluorescent protein-actin and\\/or

Hansuli Keller; Patrick Rentsch; Jörg Hagmann

2002-01-01

212

Clinical, pathological and antigenic aspects of bovine viral diarrhea virus (BVDV) type 2 isolates identified in Brazil  

Microsoft Academic Search

Nucleotide sequencing and phylogenetic analysis of Brazilian bovine viral diarrhea virus (BVDV) field isolates identified four viruses belonging to the genotype 2. Comparison of 5? UTR sequences from these isolates to those of North American BVDV type 2 revealed genomic variations that correlated with the geographic origins of the isolates. Two of the Brazilian type 2 viruses were isolated from

E. F Flores; L. H. G. V Gil; S. A Botton; R Weiblen; J. F Ridpath; L. C Kreutz; C Pilati; D Driemeyer; V Moojen; A. C Wendelstein

2000-01-01

213

Using functional data analysis to identify physician decision strategies which lead to better type 2 diabetes patient outcomes  

Microsoft Academic Search

An approach was developed and tested to identify strategies used by physicians treating patients with type 2 diabetes. In a previously published study 19 physicians treated 3 simulated type 2 diabetes patients to a standard blood glucose (A1c) goal. A1c trajectories of physicians treating each patient were analyzed using functional data analysis (FDA). Two characteristic patterns were observed. One pattern

Gregory W. Ramsey; Paul E. Johnson; Patrick J. O'Connor; JoAnn M. Sperl-Hillen; William A. Rush

2010-01-01

214

Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci  

PubMed Central

Background Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late onset CRC. Integration of genome and transcriptome data identifies seven novel candidate genes with the potential to identify an increased risk for CRC.

2010-01-01

215

Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages.  

PubMed

We have analyzed publicly available K562 Hi-C data, which enable genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model and a power-law decay background to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 45 transcription factors and 9 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into two types of chromatin linkages. The different clusters of loci display very different relationships with transcription factor-binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 9, which is distinguished by marks of open chromatin but not by active enhancer or promoter marks, was not bound by most transcription factors but was highly enriched for three transcription factors (GATA1, GATA2 and c-Jun) and three chromatin modifiers (BRG1, INI1 and SIRT6). To investigate the impact of chromatin organization on gene regulation, we performed ribonucleicacid-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors not only alters the expression of genes having a nearby bound GATA but also affects expression of genes in interacting loci. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provides genome-wide evidence that Hi-C data identify sets of biologically relevant interacting loci. PMID:22675074

Lan, Xun; Witt, Heather; Katsumura, Koichi; Ye, Zhenqing; Wang, Qianben; Bresnick, Emery H; Farnham, Peggy J; Jin, Victor X

2012-06-06

216

A method of identifying the type of grain boundaries in condensed films by decoration with metals  

SciTech Connect

The authors developed a method of determining the type of grain boundaries in condensed films of semimetals and semiconductors based on the nature and magnitude of the relative variation of electrical resistivity in the initial period of deposition of these films on metals. The method was checked on condensed films of lead telluride in which the grain boundaries act as powerful potential barriers in respect of the electrons and on condensed bismuth films in which the grain boundaries are of the scattering type. The films were produced and their resistivity measured in type UVN-74P equipment. This method makes it possible to estimate the contribution of the barrier-type grain boundaries to the total electrical resistivity of films, and to determine the type of grain boundaries in films of antimony, tellurium, and bismuth telluride.

Vigdorovich, V.N.; Markov, F.V.; Vkhlinov, G.A.; Zheredov, V.Y.

1986-03-01

217

Distinct Types of rRNA Operons Exist in the Genome of the Actinomycete Thermomonospora chromogena and Evidence for Horizontal Transfer of an Entire rRNA Operon  

Microsoft Academic Search

We describe here the presence of two distinct types of rRNA operons in the genome of a thermophilic actinomycete Thermomonospora chromogena. The genome of T. chromogena contains six rRNA operons (rrn), of which four complete and two incomplete ones were cloned and sequenced. Comparative analysis revealed that the operon rrnB exhibits high levels of sequence variations to the other five

WAI HO YAP; ZHENSHUI ZHANG; YUE WANG

1999-01-01

218

Genealogical concordance between the mating type locus and seven other nuclear genes supports formal recognition of nine phylogenetically distinct species within the Fusarium graminearum clade  

Microsoft Academic Search

Species limits were investigated within the Fusarium graminearum clade (Fg clade) through phylogenetic analyses of DNA sequences from portions of 11 nuclear genes including the mating-type (MAT) locus. Nine phylogenetically distinct species were resolved within the Fg clade, and they all possess contiguous MAT1-1 and MAT1-2 idiomorphs consistent with a homothallic reproductive mode. In contrast, only one of the two

Kerry O’Donnell; Todd J. Ward; David M. Geiser; H. Corby Kistler; Takayuki Aoki

2004-01-01

219

Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle  

PubMed Central

Background Using oligonucleotide microarrays, we compared transcriptional profiles corresponding to the initial cell cycle stages of mouse fibroblasts lacking the small GTPases H-Ras and/or N-Ras with those of matching, wild-type controls. Results Serum-starved wild-type and knockout ras fibroblasts had very similar transcriptional profiles, indicating that H-Ras and N-Ras do not significantly control transcriptional responses to serum deprivation stress. In contrast, genomic disruption of H-ras or N-ras, individually or in combination, determined specific differential gene expression profiles in response to post-starvation stimulation with serum for 1 hour (G0/G1 transition) or 8 hours (mid-G1 progression). The absence of N-Ras caused significantly higher changes than the absence of H-Ras in the wave of transcriptional activation linked to G0/G1 transition. In contrast, the absence of H-Ras affected the profile of the transcriptional wave detected during G1 progression more strongly than did the absence of N-Ras. H-Ras was predominantly functionally associated with growth and proliferation, whereas N-Ras had a closer link to the regulation of development, the cell cycle, immunomodulation and apoptosis. Mechanistic analysis indicated that extracellular signal-regulated kinase (ERK)-dependent activation of signal transducer and activator of transcription 1 (Stat1) mediates the regulatory effect of N-Ras on defense and immunity, whereas the pro-apoptotic effects of N-Ras are mediated through ERK and p38 mitogen-activated protein kinase signaling. Conclusions Our observations confirm the notion of an absolute requirement for different peaks of Ras activity during the initial stages of the cell cycle and document the functional specificity of H-Ras and N-Ras during those processes.

2009-01-01

220

Types of callosally projecting nonpyramidal neurons in rat visual cortex identified by lysosomal HRP retrograde labeling  

Microsoft Academic Search

Callosally projecting neurons, labeled following injection of horseradish peroxidase (HRP) into the 17\\/18a border of the contralateral hemisphere, have been examined by light and electron microscopy. These neurons exhibit two types of horseradish peroxidase labeling: either a diffuse, Golgi-like labeling, or a granular, punctate labeling. The punctate type of HRP-labeling is the predominant form in nonpyramidal neurons, while pyramidal neurons

Candice M. Hughes; Alan Peters

1992-01-01

221

YspM, a Newly Identified Ysa Type III Secreted Protein of Yersinia enterocolitica  

Microsoft Academic Search

Yersinia enterocolitica has three type three secretion systems, the flagellar, the plasmid Ysc type III secretion system (T3SS), and the chromosomal Ysa T3SS. The Ysc T3SS, through the proteins it secretes (Yops), prevents phagocytosis of Y. enterocolitica and is required for disease processes in the mouse host. Recent data demonstrate a role for the Ysa T3SS during initial colonization of

Sarah E. Witowski; Kimberly A. Walker; Virginia L. Miller

2008-01-01

222

Analysis of the Arabidopsis Shoot Meristem Transcriptome during Floral Transition Identifies Distinct Regulatory Patterns and a Leucine-Rich Repeat Protein That Promotes Flowering[C][W][OA  

PubMed Central

Flowering of Arabidopsis thaliana is induced by exposure to long days (LDs). During this process, the shoot apical meristem is converted to an inflorescence meristem that forms flowers, and this transition is maintained even if plants are returned to short days (SDs). We show that exposure to five LDs is sufficient to commit the meristem of SD-grown plants to flower as if they were exposed to continuous LDs. The MADS box proteins SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and FRUITFULL (FUL) play essential roles in this commitment process and in the induction of flowering downstream of the transmissible FLOWERING LOCUS T (FT) signal. We exploited laser microdissection and Solexa sequencing to identify 202 genes whose transcripts increase in the meristem during floral commitment. Expression of six of these transcripts was tested in different mutants, allowing them to be assigned to FT-dependent or FT-independent pathways. Most, but not all, of those dependent on FT and its paralog TWIN SISTER OF FT (TSF) also relied on SOC1 and FUL. However, this dependency on FT and TSF or SOC1 and FUL was often bypassed in the presence of the short vegetative phase mutation. FLOR1, which encodes a leucine-rich repeat protein, was induced in the early inflorescence meristem, and flor1 mutations delayed flowering. Our data contribute to the definition of LD-dependent pathways downstream and in parallel to FT.

Torti, Stefano; Fornara, Fabio; Vincent, Coral; Andres, Fernando; Nordstrom, Karl; Gobel, Ulrike; Knoll, Daniela; Schoof, Heiko; Coupland, George

2012-01-01

223

Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation  

PubMed Central

In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels.

Hoehenwarter, Wolfgang; Brzobohaty, Bretislav

2013-01-01

224

Hepatosplenic and hepatocytotropic T-cell lymphoma: two distinct types of T-cell lymphoma in dogs.  

PubMed

The clinical, clinicopathologic, and pathological findings of 9 dogs with T-cell lymphoma that involved the liver in the absence of peripheral lymphadenopathy were assessed. Seven dogs had hepatosplenic T-cell lymphoma (HS-TCL). Dogs with HS-TCL presented with hepato- and/or splenomegaly, regenerative anemia, thrombocytopenia, and hypoproteinemia. The clinical course was rapidly progressive with all dogs but 1 dead within 24 days of initial presentation. Neoplastic lymphocytes were centered on hepatic and splenic sinusoids and had a CD3+ (5/7), TCR??- (5/5), TCR??+ (3/5), CD11d+ (6/7), granzyme B+ (5/7) immunophenotype. Bone marrow and lungs were consistently but variably involved. These findings closely resemble the human disease and support the classification of HS-TCL as a distinct World Health Organization entity in dogs. The remaining 2 dogs markedly differed in the pattern of hepatic involvement by neoplastic lymphocytes, which were not confined to hepatic sinusoids but invaded hepatic cords. In addition, neoplastic cells had a CD11d- immunophenotype, and clinicopathologic data indicated marked cholestasis and mild to absent anemia. Based on the distinct tropism of neoplastic lymphocytes for hepatocytes, the name hepatocytotropic T-cell lymphoma (HC-TCL) is proposed. Given the histomorphologic, clinicopathologic, and immunophenotypic differences, HC-TCL likely represents a separate biological entity rather than a histomorphologic variant of HS-TCL. PMID:22711745

Keller, S M; Vernau, W; Hodges, J; Kass, P H; Vilches-Moure, J G; McElliot, V; Moore, P F

2012-06-18

225

Proteome and metabolome profiling of cytokinin action in Arabidopsis identifying both distinct and similar responses to cytokinin down- and up-regulation.  

PubMed

In plants, numerous developmental processes are controlled by cytokinin (CK) levels and their ratios to levels of other hormones. While molecular mechanisms underlying the regulatory roles of CKs have been intensely researched, proteomic and metabolomic responses to CK deficiency are unknown. Transgenic Arabidopsis seedlings carrying inducible barley cytokinin oxidase/dehydrogenase (CaMV35S>GR>HvCKX2) and agrobacterial isopentenyl transferase (CaMV35S>GR>ipt) constructs were profiled to elucidate proteome- and metabolome-wide responses to down- and up-regulation of CK levels, respectively. Proteome profiling identified >1100 proteins, 155 of which responded to HvCKX2 and/or ipt activation, mostly involved in growth, development, and/or hormone and light signalling. The metabolome profiling covered 79 metabolites, 33 of which responded to HvCKX2 and/or ipt activation, mostly amino acids, carbohydrates, and organic acids. Comparison of the data sets obtained from activated CaMV35S>GR>HvCKX2 and CaMV35S>GR>ipt plants revealed unexpectedly extensive overlaps. Integration of the proteomic and metabolomic data sets revealed: (i) novel components of molecular circuits involved in CK action (e.g. ribosomal proteins); (ii) previously unrecognized links to redox regulation and stress hormone signalling networks; and (iii) CK content markers. The striking overlaps in profiles observed in CK-deficient and CK-overproducing seedlings might explain surprising previously reported similarities between plants with down- and up-regulated CK levels. PMID:24064926

Cerny, Martin; Kuklová, Alena; Hoehenwarter, Wolfgang; Fragner, Lena; Novák, Ondrej; Rotková, Gabriela; Jedelsky, Petr L; Záková, Katerina; Smehilová, Mária; Strnad, Miroslav; Weckwerth, Wolfram; Brzobohaty, Bretislav

2013-09-24

226

Single and coexpression of CXCR4 and CXCR5 identifies CD4 T helper cells in distinct lymph node niches during influenza virus infection.  

PubMed

Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide lifelong humoral immunity against the homotypic virus strain. Follicular T helper cells (T(FH)) are key regulators of humoral immunity. Questions remain regarding the presence, identity, and function of T(FH) subsets regulating early extrafollicular and later germinal center B cell responses. This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity induced by influenza virus infection and identifies germinal center T cells (T(GC)) as lymph node-resident CD4(+) ICOS(+) CXCR4(+) CXCR5(+) PSGL-1(lo) PD-1(hi) cells. The CXCR4 expression intensity further distinguished their germinal center light and dark zone locations. This population emerged strongly in regional lymph nodes and with kinetics similar to those of germinal center B cells and were the only T(FH) subsets missing in influenza virus-infected, germinal center-deficient SAP(-/-) mice, mice which were shown previously to lack protective memory responses after a secondary influenza virus challenge, thus indicting the nonredundant functions of CXCR4- and CXCR5-coexpressing CD4 helper cells in antiviral B cell immunity. CXCR4-single-positive T cells, present in B cell-mediated autoimmunity and regarded as "extrafollicular" helper T cells, were rare throughout the response, despite prominent extrafollicular B cell responses, revealing fundamental differences in autoimmune- and infection-induced T-dependent B cell responses. While all ICOS(+) subsets induced similar antibody levels in vitro, CXCR5-single-positive T cells were superior in inducing B cell proliferation. The regulation of T cell localization, marked by the single and coexpression of CXCR4 and CXCR5, might be an important determinant of T(FH) function. PMID:22532671

Elsner, Rebecca A; Ernst, David N; Baumgarth, Nicole

2012-04-24

227

Single and Coexpression of CXCR4 and CXCR5 Identifies CD4 T Helper Cells in Distinct Lymph Node Niches during Influenza Virus Infection  

PubMed Central

Influenza virus infection results in strong, mainly T-dependent, extrafollicular and germinal center B cell responses, which provide lifelong humoral immunity against the homotypic virus strain. Follicular T helper cells (TFH) are key regulators of humoral immunity. Questions remain regarding the presence, identity, and function of TFH subsets regulating early extrafollicular and later germinal center B cell responses. This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity induced by influenza virus infection and identifies germinal center T cells (TGC) as lymph node-resident CD4+ ICOS+ CXCR4+ CXCR5+ PSGL-1lo PD-1hi cells. The CXCR4 expression intensity further distinguished their germinal center light and dark zone locations. This population emerged strongly in regional lymph nodes and with kinetics similar to those of germinal center B cells and were the only TFH subsets missing in influenza virus-infected, germinal center-deficient SAP?/? mice, mice which were shown previously to lack protective memory responses after a secondary influenza virus challenge, thus indicting the nonredundant functions of CXCR4- and CXCR5-coexpressing CD4 helper cells in antiviral B cell immunity. CXCR4-single-positive T cells, present in B cell-mediated autoimmunity and regarded as “extrafollicular” helper T cells, were rare throughout the response, despite prominent extrafollicular B cell responses, revealing fundamental differences in autoimmune- and infection-induced T-dependent B cell responses. While all ICOS+ subsets induced similar antibody levels in vitro, CXCR5-single-positive T cells were superior in inducing B cell proliferation. The regulation of T cell localization, marked by the single and coexpression of CXCR4 and CXCR5, might be an important determinant of TFH function.

Elsner, Rebecca A.; Ernst, David N.

2012-01-01

228

NK1 Receptor Immunoreactivity in Distinct Morphological Types of Lamina I Neurons of the Primate Spinal Cord  

Microsoft Academic Search

In cat and monkey, lamina I cells can be classified into three basic morphological types (fusiform, pyramidal, and multipolar), and recent intracellular labeling evidence in the cat indicates that fusiform and multipolar lamina I cells are two different types of nociceptive cells, whereas pyramidal cells are innocuous thermoreceptive-specific. Because earlier observations indi- cated that only nociceptive dorsal horn neurons respond

X. H. Yu; E.-T. Zhang; A. D. Craig; R. Shigemoto; A. Ribeiro-da-Silva; Y. De Koninck

1999-01-01

229

Multilocus Sequence Typing Supports the Hypothesis that Cow and Human-Associated Salmonella Isolates Represent Distinct and Overlapping Populations  

Microsoft Academic Search

A collection of 179 human and 156 bovine clinical Salmonella isolates obtained from across New York state over the course of 1 year was characterized using serotyping and a multilocus sequence typing (MLST) scheme based on the sequencing of three genes (fimA, manB, and mdh). The 335 isolates were differentiated into 52 serotypes and 72 sequence types (STs). Analyses of

S. D. Alcaine; Y. Soyer; L. D. Warnick; W.-L. Su; S. Sukhnanand; J. Richards; E. D. Fortes; P. McDonough; T. P. Root; N. B. Dumas; Y. Grohn; M. Wiedmann

2006-01-01

230

A GIS APPROACH TO IDENTIFY AND CLASSIFY HYDROGEOMORPHIC TYPES OF COASTAL WETLANDS  

EPA Science Inventory

Description of the georeferenced digital database produced by the U.S. EPA/MED along with the U.S. FWS for a R-EMAP project funded by EPA/ORD for Region 5 that produced an inventory of the coastal wetlands of the Great Lakes was described. The process used to identify and classif...

231

Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity  

PubMed Central

The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements active in seven cell lines representative of diverse human cell types, we used DNase-seq and FAIRE-seq (Formaldehyde Assisted Isolation of Regulatory Elements) to map “open chromatin.” Over 870,000 DNaseI or FAIRE sites, which correspond tightly to nucleosome-depleted regions, were identified across the seven cell lines, covering nearly 9% of the genome. The combination of DNaseI and FAIRE is more effective than either assay alone in identifying likely regulatory elements, as judged by coincidence with transcription factor binding locations determined in the same cells. Open chromatin common to all seven cell types tended to be at or near transcription start sites and to be coincident with CTCF binding sites, while open chromatin sites found in only one cell type were typically located away from transcription start sites and contained DNA motifs recognized by regulators of cell-type identity. We show that open chromatin regions bound by CTCF are potent insulators. We identified clusters of open regulatory elements (COREs) that were physically near each other and whose appearance was coordinated among one or more cell types. Gene expression and RNA Pol II binding data support the hypothesis that COREs control gene activity required for the maintenance of cell-type identity. This publicly available atlas of regulatory elements may prove valuable in identifying noncoding DNA sequence variants that are causally linked to human disease.

Song, Lingyun; Zhang, Zhancheng; Grasfeder, Linda L.; Boyle, Alan P.; Giresi, Paul G.; Lee, Bum-Kyu; Sheffield, Nathan C.; Graf, Stefan; Huss, Mikael; Keefe, Damian; Liu, Zheng; London, Darin; McDaniell, Ryan M.; Shibata, Yoichiro; Showers, Kimberly A.; Simon, Jeremy M.; Vales, Teresa; Wang, Tianyuan; Winter, Deborah; Zhang, Zhuzhu; Clarke, Neil D.; Birney, Ewan; Iyer, Vishwanath R.; Crawford, Gregory E.; Lieb, Jason D.; Furey, Terrence S.

2011-01-01

232

Identifying related cancer types based on their incidence among people with multiple cancers  

Microsoft Academic Search

BACKGROUND: There are several reasons that someone might be diagnosed with more than one primary cancer. The aim of this analysis was to determine combinations of cancer types that occur more often than expected. The expected values in previous analyses are based on age-and-gender-adjusted risks in the population. However, if cancer in people with multiple primaries is somehow different than

Chris D Bajdik; Zenaida U Abanto; John J Spinelli; Angela Brooks-Wilson; Richard P Gallagher

2006-01-01

233

Using genome-context data to identify specific types of functional associations in pathway\\/genome databases  

Microsoft Academic Search

Background: Hundreds of genes lacking homology to any protein of known function are sequenced every day. Genome-context methods have proved useful in providing clues about functional annotations for many proteins. However, genome-context methods detect many biological types of functional associations, and do not identify which type of functional association they have found. Results: We have developed two new genome-context-based algorithms.

Michelle L. Green; Peter D. Karp

2007-01-01

234

Exclusion of chromosome 9 helps to identify mild variants of acromesomelic dysplasia Maroteaux type  

PubMed Central

Acromesomelic dysplasia Maroteaux type (AMDM) is an autosomal recessive disorder belonging to the group of acromesomelic dysplasias. AMDM is characterised by severe dwarfism with shortening of the middle and distal segments of the limbs. An AMDM gene has recently been mapped to human chromosome 9p13-q12 by homozygosity mapping in four consanguineous families. Here, we show linkage of the disease gene to chromosome 9p13-q12 in four of five consanguineous AMDM families and its exclusion in a fifth family with two children affected with a mild form of the disease. This study suggests that genetic heterogeneity accounts for the variable clinical and radiological severity of AMDM.???Keywords: acromesomelic dysplasia Maroteaux type; acromesomelic dysplasias; homozygosity mapping; chromosome 9

Faivre, L.; Le Merrer, M.; Megarbane, A.; Gilbert, B.; Mortier, G.; Cusin, V.; Munnich, A.; Maroteaux, P.; Cormier-Daire, V.

2000-01-01

235

A genome-wide association study identifies novel risk loci for type 2 diabetes  

Microsoft Academic Search

Type 2 diabetes mellitus results from the interaction of environmental factors with a combination of genetic variants, most of which were hitherto unknown. A systematic search for these variants was recently made possible by the development of high-density arrays that permit the genotyping of hundreds of thousands of polymorphisms. We tested 392,935 single-nucleotide polymorphisms in a French case-control cohort. Markers

Robert Sladek; Ghislain Rocheleau; Johan Rung; Christian Dina; Lishuang Shen; David Serre; Philippe Boutin; Daniel Vincent; Alexandre Belisle; Samy Hadjadj; Beverley Balkau; Barbara Heude; Guillaume Charpentier; Thomas J. Hudson; Alexandre Montpetit; Alexey V. Pshezhetsky; Marc Prentki; Barry I. Posner; David J. Balding; David Meyre; Constantin Polychronakos; Philippe Froguel

2007-01-01

236

Innate immune sensing of cancer: clues from an identified role for type I IFNs.  

PubMed

A subset of patients with a variety of cancers shows evidence of a natural adaptive immune response against their tumor, as evidenced by spontaneous T-cell infiltration, circulating anti-tumor T cells, or antibody responses. Evidence has indicated that such natural immune responses have positive prognostic import in early stage disease and may be predictive of clinical response to immunotherapeutics in advanced disease. However, these observations raise a new critical fundamental question-what innate immune signals might be generated in the context of non-pathogen-induced cancers that drive productive antigen presentation toward induction of an adaptive immune response? Gene expression profiling in melanoma revealed that tumors having high expression of T-cell markers also show evidence of a type I IFN transcriptional signature. Mechanistic experiments in mice have revealed that a spontaneous CD8(+) T-cell response against transplantable tumors depends on host type I IFN signaling, through a mechanism dependent upon CD8?(+) dendritic cells (DCs). The requirement for type I IFN production by host DCs has suggested a subset of innate immune sensing receptors and signaling pathways that might be involved with initiating this process. Elucidating further these innate immune mechanisms should provide new insights into cancer immunotherapy. PMID:22722449

Gajewski, Thomas F; Fuertes, Mercedes B; Woo, Seng-Ryong

2012-06-22

237

Three novel ZBTB24 mutations identified in Japanese and Cape Verdean type 2 ICF syndrome patients.  

PubMed

Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive disorder that shows DNA hypomethylation at pericentromeric satellite-2 and -3 repeats in chromosomes 1, 9 and 16. ICF syndrome is classified into two groups: type 1 (ICF1) patients have mutations in the DNMT3B gene and about half of type 2 (ICF2) patients have mutations in the ZBTB24 gene. Besides satellite-2 and -3 repeats, ?-satellite repeats are also hypomethylated in ICF2. In this study, we report three novel ZBTB24 mutations in ICF2. A Japanese patient was homozygous for a missense mutation (C383Y), and a Cape Verdean patient was compound heterozygous for a nonsense mutation (K263X) and a frame-shift mutation (C327W fsX54). In addition, the second Japanese patient was homozygous for a previously reported nonsense mutation (R320X). The C383Y mutation abolished a C2H2 motif in one of the eight zinc-finger domains, and the other three mutations caused a complete or large loss of the zinc-finger domains. Our immunofluorescence analysis revealed that mouse Zbtb24 proteins possessing a mutation corresponding to either C383Y or R320X are mislocalized from pericentrometic heterochromatin, suggesting the importance of the zinc-finger domains in proper intranuclear localization of this protein. We further revealed that the proper localization of wild-type Zbtb24 protein does not require DNA methylation. PMID:23739126

Nitta, Hirohisa; Unoki, Motoko; Ichiyanagi, Kenji; Kosho, Tomoki; Shigemura, Tomonari; Takahashi, Hiroshi; Velasco, Guillaume; Francastel, Claire; Picard, Capucine; Kubota, Takeo; Sasaki, Hiroyuki

2013-06-06

238

IL10 and the Dangers of Immune Polarization: Excessive Type 1 and Type 2 Cytokine Responses Induce Distinct Forms of Lethal Immunopathology in Murine Schistosomiasis  

Microsoft Academic Search

To dissect the controversial roles of type 1 and type 2 cytokines to the pathogenesis of schistosomiasis, we generated IL-10\\/IL-4- and IL-10\\/IL-12-deficient mice that develop highly polarized type 1 and type 2 cytokine responses, respectively. Interestingly, the Th1-polarized IL-10\\/IL-4-deficient mice rapidly lost weight at the onset of egg-laying and displayed 100% mortality by wk 9 postinfection. This acute mortality was

Karl F. Hoffmann; Allen W. Cheever; Thomas A. Wynn

239

Markers typed in genome-wide analysis identify regions showing deviation from Hardy-Weinberg equilibrium  

PubMed Central

Background Deviations from Hardy-Weinberg equilibrium (HWE) are commonly thought of as indicating genotyping errors, population stratification or some other artefact. However they could also arise through important biological mechanisms. In particular, genetic variants having a recessive effect on the successful fertilisation and/or development of an embryo might be manifest through such deviations in an unselected sample of "control" subjects. Findings We investigated genotypes from 463842 autosomal markers from 1504 British subjects. We identified regions in which several neighbouring markers exhibited deviation from HWE in the same direction by considering "heterozygosity scores" in windows of 10 markers. The heterozygosity score for each marker was defined as -log(p) or log(p) according to whether the marker demonstrated increased heterozygosity or homozygosity. In each window the marker with the highest absolute score was ignored and the positive and negative scores were summed for the other nine markers. Windows were selected on the basis of this sum exceeding a given threshold, for which we used values of 50 or 15. For the threshold of 50, we identified 7 regions with increased heterozygosity and for the threshold of 15 we identified 22 regions with increased heterozygosity, 23 with increased homozygosity and 2 containing both kinds of window. The most impressive of these results came from a group of 6 markers at 17q21, each of which showed increased heterozygosity significant at p < 10-190. Conclusion The human genome contains regions which deviate markedly from HWE and these might harbour genes influencing embryonic survival.

Vine, Anna E; Curtis, David

2009-01-01

240

A new point mutation in the ND1 mitochondrial gene identified in a type II diabetic patient  

SciTech Connect

A novel mutation in a mitochondrial gene was identified in a patient with type II diabetes mellitus. G-to-A transition was localized at the nt3316 position of gene ND1 and resulted in alanine threonine replacement at position 4 of mitochondrial NAD-H-dehydrogenase. 6 refs., 2 figs.

Kalinin, V.N. [Research Center of Medical Genetics, Moscow (Russian Federation); Schmidt, W.; Olek, K. [Institut fuer Molekularbiologische Diagnostik, Bonn (Germany)] [and others

1995-08-01

241

The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color  

Technology Transfer Automated Retrieval System (TEKTRAN)

Background: Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. Results: We describe the sequencing and assembly of...

242

Identifying individual n- and p-type ZnO nanowires by the output voltage sign of piezoelectric nanogenerator.  

PubMed

Based on a comparative study between the piezoelectric outputs of n-type nanowires (NWs) and n-core/p-shell NWs along with the previous study (Lu et al 2009 Nano. Lett. 9 1223), we demonstrate a one-step technique for identifying the conductivity type of individual ZnO nanowires (NWs) based on the output of a piezoelectric nanogenerator without destroying the sample. A negative piezoelectric output voltage indicates an NW is n-type and it appears after the tip scans across the center of the NW, while a positive output voltage reveals p-type conductivity and it appears before the tip scans across the central line of the NW. This atomic force microscopy based technique is reliable for statistically mapping the majority carrier type in ZnO NWs arrays. The technique may also be applied to other wurtzite semiconductors, such as GaN, CdS and ZnS. PMID:19687547

Lin, S S; Song, J H; Lu, Y F; Wang, Z L

2009-08-18

243

Short and Long-term memory in Drosophila require cAMP signaling in distinct neuron types  

PubMed Central

Summary Background A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuro-anatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Results We have investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca++ responsive adenylyl cyclase rutabaga is believed to be a coincidence detector in ? neurons, one of the three principle classes of MB Kenyon cells. We are able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Conclusions Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB ? neurons, and a long-lived trace in ?/? neurons.

Blum, Allison L.; Li, Wanhe; Cressy, Mike; Dubnau, Josh

2009-01-01

244

Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses  

Microsoft Academic Search

THE molecular basis of recognition and target cell killing by cytotoxic T cells is still unknown. Doherty and Zinkernagel showed that mouse cells infected with lymphocytic choriomeningitis virus can be lysed by immune cytotoxic T cells but only if both cell types share at least part of the major histocompatibility (H-2) region (see ref. 1). H-2 compatibility is also required

H. J. Zweerink; S. A. Courtneidge; J. J. Skehel; M. J. Crumpton; Brigitte A. Askonas

1977-01-01

245

Characterizing the successful student in general chemistry and physical science classes in terms of Jung's personality types as identified by the Myers-Briggs Type Indicator  

NASA Astrophysics Data System (ADS)

A student's success in a science class can depend upon previous experiences, motivation, and the level of interest in the subject. Since psychological type is intrinsic to a person's whole being, it can be influential upon the student's motivation and interests. Thus, a study of student psychological types versus the level of success in a class, as measured by a percentage, has potential to uncover certain personality characteristics which may be helpful to or which may hinder a student's learning environment. This study was initiated, using the Myers-Briggs Type Indicator, to evaluate any correlation between a student's personality type and his/her performance in a science class. A total of 1041 students from three classes: Chemistry 121/122, Chemistry 112, Physical Science 100, volunteered for the study. An analysis of variance (ANOVA) was used to determine the levels of significance among sixteen personality types' averages. The results reveal that for the Chemistry 1121/122 course, the average score of the INTJ personality type was 5.1 to 12.6 points higher than every other personality type. The ANOVA identifies 3 personality types with averages significantly below the INTJ at the p < 0.05 significance level. The ANOVA analysis for the Chemistry 112 course identified significances between student scores at p = 0.08. The significance level for the differences among scores for the Physical Science 100 course was determined at a level of p = 0.02. Significance levels for p < 0.05 and <0.01 were identified between several groups in this course. The data suggest, that although personality type may not predict a particular student's success in a science class, students with certain personality traits may be favored in a chemistry class due the structure of the instruction and the presentation of the subject matter.

Riley, Wayne David

1998-11-01

246

Three distinct types of quantum phase transitions in a (2+1)-dimensional array of dissipative Josephson junctions  

NASA Astrophysics Data System (ADS)

We have performed large-scale Monte Carlo simulations on a model describing a (2+1)-dimensional array of dissipative Josephson junctions. We find three distinct stable quantum phases of the system. The most ordered state features long-range spatial ordering in the phase ? of the superconducting order parameter, but temporal ordering only in spatial gradients ??, not in ?. Significantly, the most ordered state therefore does not have three-dimensional (3D) XY ordering. Rather, it features two-dimensional (2D) spin waves coexisting with temporally disordered phases ?. There is also an intermediate phase featuring quasi-long-range spatial order in ? coexisting with a gas of instantons in ??. We briefly discuss possible experimental signatures of such a state, which may be viewed as a local metal and a global superconductor. The most disordered state has phase disorder in all spatio-temporal directions, and may be characterized as a gas of proliferated vortices coexisting with a gas of ?? instantons. The phase transitions between these phases are discussed. The transition from the most ordered state to the intermediate state is driven by proliferation of instantons in ??. The transition from the intermediate state to the most disordered state is driven by the proliferation of spatial point vortices in the background of a proliferated ??-instanton gas, and constitutes a Berezinskii-Kosterlitz-Thouless phase transition. The model also features a direct phase transition from the most ordered state to the most disordered state, and this transition is neither in the 2D XY nor in the 3D XY universality class. It comes about via a simultaneous proliferation of point vortices in two spatial dimensions and ?? instantons, with a complicated interplay between them. The results are compared to, and differ in a fundamental way from, the results that are found in dissipative quantum rotor systems. The difference originates with the difference in the values that the fundamental degrees of freedom can take in the latter systems compared to dissipative Josephson junction arrays.

Stiansen, Einar B.; Sperstad, Iver Bakken; Sudbø, Asle

2012-06-01

247

Two phenotypically distinct T cells are involved in ultraviolet-irradiated urocanic acid-induced suppression of the efferent delayed-type hypersensitivity response to herpes simplex virus, type 1 in vivo  

SciTech Connect

When UVB-irradiated urocanic acid, the putative photoreceptor/mediator for UVB suppression, is administered to mice it induces a dose-dependent suppression of the delayed-type hypersensitivity response to herpes simplex virus, type 1 (HSV-1), of similar magnitude to that induced by UV irradiation of mice. In this study, the efferent suppression of delayed-type hypersensitivity by UV-irradiated urocanic acid is demonstrated to be due to 2 phenotypically distinct T cells, (Thy1+, L3T4-, Ly2+) and (Thy1+, L3T4+, Ly2-). The suppression is specific for HSV-1. This situation parallels the generation of 2 distinct T-suppressor cells for HSV-1 by UV irradiation of mice and provides further evidence for the involvement of urocanic acid in the generation of UVB suppression.

Ross, J.A.; Howie, S.E.; Norval, M.; Maingay, J.

1987-09-01

248

Conditional IFNAR1 ablation reveals distinct requirements of Type I IFN signaling for NK cell maturation and tumor surveillance  

PubMed Central

Mice with an impaired Type I interferon (IFN) signaling (IFNAR1- and IFN?-deficient mice) display an increased susceptibility toward v-ABL-induced B-cell leukemia/lymphoma. The enhanced leukemogenesis in the absence of an intact Type I IFN signaling is caused by alterations within the tumor environment. Deletion of Ifnar1 in tumor cells (as obtained in Ifnar1f/f CD19-Cre mice) failed to impact on disease latency or type. In line with this observation, the initial transformation and proliferative capacity of tumor cells were unaltered irrespective of whether the cells expressed IFNAR1 or not. v-ABL-induced leukemogenesis is mainly subjected to natural killer (NK) cell-mediated tumor surveillance. Thus, we concentrated on NK cell functions in IFNAR1 deficient animals. Ifnar1-/- NK cells displayed maturation defects as well as an impaired cytolytic activity. When we deleted Ifnar1 selectively in mature NK cells (by crossing Ncr1-iCre mice to Ifnar1f/f animals), maturation was not altered. However, NK cells derived from Ifnar1f/f Ncr1-iCre mice showed a significant cytolytic defect in vitro against the hematopoietic cell lines YAC-1 and RMA-S, but not against the melanoma cell line B16F10. Interestingly, this defect was not related to an in vivo phenotype as v-ABL-induced leukemogenesis was unaltered in Ifnar1f/f Ncr1-iCre compared with Ifnar1f/f control mice. Moreover, the ability of Ifnar1f/f Ncr1-iCre NK cells to kill B16F10 melanoma cells was unaltered, both in vitro and in vivo. Our data reveal that despite the necessity for Type I IFN in NK cell maturation the expression of IFNAR1 on mature murine NK cells is not required for efficient tumor surveillance.

Mizutani, Tatsuaki; Neugebauer, Nina; Putz, Eva M.; Moritz, Nadine; Simma, Olivia; Zebedin-Brandl, Eva; Gotthardt, Dagmar; Warsch, Wolfgang; Eckelhart, Eva; Kantner, Hans-Peter; Kalinke, Ulrich; Lienenklaus, Stefan; Weiss, Siegfried; Strobl, Birgit; Muller, Mathias; Sexl, Veronika; Stoiber, Dagmar

2012-01-01

249

Identification and Characterization of a New and Distinct Molecular Subtype of Human T-Cell Lymphotropic Virus Type 2  

Microsoft Academic Search

Molecular studies have demonstrated the existence of at least two major subtypes of human T-cell lympho- tropic virus type 2 (HTLV-2), designated HTLV-2a and HTLV-2b. To further investigate the heterogeneity of this family of viruses, we have characterized the HTLV-2 subtypes present in several urban areas in Brazil. DNAsfromperipheralbloodmononuclearcellsofalargenumberofinfectedindividuals,themajorityofwhom were intravenous drug abusers, were analyzed by using PCR with restriction

NOBUTAKA EIRAKU; PATRICIA NOVOA; MARIZETE DACOSTA FERREIRA; CLAUDE MONKEN; RICARDO ISHAK; ORLANDO DACOSTA FERREIRA; SHI WEI ZHU; ROSEMARIE LORENCO; MARLUISA ISHAK; VANIA AZVEDO; JOAO GUERREIRO; MARIA POMBO DEOLIVEIRA; PAULA LOUREIRO; NELSON HAMMERSCHLAK; SHINJI IJICHI; W. HALL; Emilo Ribas

1996-01-01

250

Pheochromocytomas in von Hippel-Lindau Syndrome and Multiple Endocrine Neoplasia Type 2 Display Distinct Biochemical and Clinical Phenotypes  

Microsoft Academic Search

This study examined the mechanisms linking different biochemical and clinical phenotypes of pheochromocytoma in multiple endocrine neoplasia type 2 (MEN 2) and von Hippel-Lindau (VHL) syndrome to underlying differences in the expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, and of phe- nylethanolamine N-methyltransferase (PNMT), the enzyme that con- verts norepinephrine to epinephrine. Signs and symptoms of

GRAEME EISENHOFER; MCCLELLAN M. WALTHER; THANH-TRUC HUYNH; SHENG-TING LI; STEFAN R. BORNSTEIN; ALEXANDER VORTMEYER; MASSIMO MANNELLI; DAVID S. GOLDSTEIN; W. MARSTON LINEHAN; JACQUES W. M. LENDERS; KAREL PACAK

251

Ticking Stellar Time Bomb Identified - Astronomers find prime suspect for a Type Ia supernova  

NASA Astrophysics Data System (ADS)

Using ESO's Very Large Telescope and its ability to obtain images as sharp as if taken from space, astronomers have made the first time-lapse movie of a rather unusual shell ejected by a "vampire star", which in November 2000 underwent an outburst after gulping down part of its companion's matter. This enabled astronomers to determine the distance and intrinsic brightness of the outbursting object. It appears that this double star system is a prime candidate to be one of the long-sought progenitors of the exploding stars known as Type Ia supernovae, critical for studies of dark energy. "One of the major problems in modern astrophysics is the fact that we still do not know exactly what kinds of stellar system explode as a Type Ia supernova," says Patrick Woudt, from the University of Cape Town and lead author of the paper reporting the results. "As these supernovae play a crucial role in showing that the Universe's expansion is currently accelerating, pushed by a mysterious dark energy, it is rather embarrassing." The astronomers studied the object known as V445 in the constellation of Puppis ("the Stern") in great detail. V445 Puppis is the first, and so far only, nova showing no evidence at all for hydrogen. It provides the first evidence for an outburst on the surface of a white dwarf [1] dominated by helium. "This is critical, as we know that Type Ia supernovae lack hydrogen," says co-author Danny Steeghs, from the University of Warwick, UK, "and the companion star in V445 Pup fits this nicely by also lacking hydrogen, instead dumping mainly helium gas onto the white dwarf." In November 2000, this system underwent a nova outburst, becoming 250 times brighter than before and ejecting a large quantity of matter into space. The team of astronomers used the NACO adaptive optics instrument [2] on ESO's Very Large Telescope (VLT) to obtain very sharp images of V445 Puppis over a time span of two years. The images show a bipolar shell, initially with a very narrow waist, with lobes on each side. Two knots are also seen at both the extreme ends of the shell, which appear to move at about 30 million kilometres per hour. The shell - unlike any previously observed for a nova - is itself moving at about 24 million kilometres per hour. A thick disc of dust, which must have been produced during the last outburst, obscures the two central stars. "The incredible detail that we can see on such small scales - about hundred milliarcseconds, which is the apparent size of a one euro coin seen from about forty kilometres - is only possible thanks to the adaptive optics technology available on large ground-based telescopes such as ESO's VLT," says Steeghs. A supernova is one way that a star can end its life, exploding in a display of grandiose fireworks. One family of supernovae, called Type Ia supernovae, are of particular interest in cosmology as they can be used as "standard candles" to measure distances in the Universe [3] and so can be used to calibrate the accelerating expansion that is driven by dark energy. One defining characteristic of Type Ia supernovae is the lack of hydrogen in their spectrum. Yet hydrogen is the most common chemical element in the Universe. Such supernovae most likely arise in systems composed of two stars, one of them being the end product of the life of sun-like stars, or white dwarfs. When such white dwarfs, acting as stellar vampires that suck matter from their companion, become heavier than a given limit, they become unstable and explode [4]. The build-up is not a simple process. As the white dwarf cannibalises its prey, matter accumulates on its surface. If this layer becomes too dense, it becomes unstable and erupts as a nova. These controlled, mini-explosions eject part of the accumulated matter back into space. The crucial question is thus to know whether the white dwarf can manage to gain weight despite the outburst, that is, if some of the matter taken from the companion stays on the white dwarf, so that it will eventual

2009-11-01

252

Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells  

PubMed Central

Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2?, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors.

Hertwig, Falk; Meyer, Katharina; Braun, Sebastian; Ek, Sara; Spang, Rainer; Pfenninger, Cosima V.; Artner, Isabella; Prost, Gaelle; Chen, Xinbin; Biegel, Jaclyn A.; Judkins, Alexander R.; Englund, Elisabet; Nuber, Ulrike A.

2012-01-01

253

Definition of genetic events directing the development of distinct types of brain tumors from postnatal neural stem/progenitor cells.  

PubMed

Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2?, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. PMID:22719073

Hertwig, Falk; Meyer, Katharina; Braun, Sebastian; Ek, Sara; Spang, Rainer; Pfenninger, Cosima V; Artner, Isabella; Prost, Gaëlle; Chen, Xinbin; Biegel, Jaclyn A; Judkins, Alexander R; Englund, Elisabet; Nuber, Ulrike A

2012-06-20

254

A multiplex real-time PCR for identifying and differentiating B. anthracis virulent types.  

PubMed

Bacillus anthracis is closely related to the endospore forming bacteria Bacillus cereus and Bacillus thuringiensis. For accurate detection of the life threatening pathogen B. anthracis, it is essential to distinguish between these three species. Here we present a novel multiplex real-time PCR for simultaneous specific identification of B. anthracis and discrimination of different B. anthracis virulence types. Specific B. anthracis markers were selected by whole genome comparison and different sets of primers and probes with optimal characteristic for multiplex detection of the B. anthracis chromosome, the B. anthracis pXO1 and pXO2 plasmids and an internal control (IC) were designed. The primer sets were evaluated using a panel of B. anthracis strains and exclusivity was tested using genetically closely related B. cereus strains. The robustness of final primer design was evaluated by laboratories in three different countries using five different real-time PCR thermocyclers. Testing of a panel of more than 20 anthrax strains originating from different locations around the globe, including the recent Swedish anthrax outbreak strain, showed that all strains were detected correctly. PMID:20826037

Wielinga, Peter R; Hamidjaja, Raditijo A; Agren, Joakim; Knutsson, Rickard; Segerman, Bo; Fricker, Martina; Ehling-Schulz, Monika; de Groot, Astrid; Burton, Jane; Brooks, Tim; Janse, Ingmar; van Rotterdam, Bart

2010-08-10

255

DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients  

PubMed Central

In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors. We uncovered 276 CpG loci affiliated to promoters of 254 genes displaying significant differential DNA methylation in diabetic islets. These methylation changes were not present in blood cells from T2D individuals nor were they experimentally induced in non-diabetic islets by exposure to high glucose. For a subgroup of the differentially methylated genes, concordant transcriptional changes were present. Functional annotation of the aberrantly methylated genes and RNAi experiments highlighted pathways implicated in ?-cell survival and function; some are implicated in cellular dysfunction while others facilitate adaptation to stressors. Together, our findings offer new insights into the intricate mechanisms of T2D pathogenesis, underscore the important involvement of epigenetic dysregulation in diabetic islets and may advance our understanding of T2D aetiology.

Volkmar, Michael; Dedeurwaerder, Sarah; Cunha, Daniel A; Ndlovu, Matladi N; Defrance, Matthieu; Deplus, Rachel; Calonne, Emilie; Volkmar, Ute; Igoillo-Esteve, Mariana; Naamane, Najib; Del Guerra, Silvia; Masini, Matilde; Bugliani, Marco; Marchetti, Piero; Cnop, Miriam; Eizirik, Decio L; Fuks, Francois

2012-01-01

256

Isolates of Burkholderia pseudomallei from Northern Australia Are Distinct by Multilocus Sequence Typing, but Strain Types Do Not Correlate with Clinical Presentation  

Microsoft Academic Search

Melioidosis is the disease caused by the saprophytic organism Burkholderia pseudomallei. Previous studies have suggested some strain tropism and differential virulence. In this study, we defined strains by multilocus sequence typing (MLST) of isolates taken from the Top End of Australia's Northern Territory and compared the results with those of other strains typed worldwide. We specifically sought clinical and geographical

Allen C. Cheng; Daniel Godoy; Mark Mayo; Daniel Gal; Brian G. Spratt; Bart J. Currie

2004-01-01

257

Endometrial Glandular Dysplasia (EmGD): morphologically and biologically distinctive putative precursor lesions of Type II endometrial cancers  

PubMed Central

In this article, the authors briefly review the historical evolution of the various putative precursor lesions for Type II endometrial cancers, with an emphasis on the newly defined "Endometrial Glandular Dysplasia (EmGD)". The evidentiary basis for delineating serous EmGD as the most probable precursor lesions to endometrial serous carcinoma is reviewed in detail. An argument is advanced for the discontinuation of the term serous "endometrial intraepithelial carcinoma (EIC)" as a descriptor for a supposedly intraepithelial, precancerous lesion. Preliminary evidence is also presented that suggests that there is a morphologically recognizable "clear cell EmGD" that probably represents a precancerous lesion to endometrial clear cell carcinomas.

Fadare, Oluwole; Zheng, Wenxin

2008-01-01

258

Particular Candida albicans Strains in the Digestive Tract of Dyspeptic Patients, Identified by Multilocus Sequence Typing  

PubMed Central

Background Candida albicans is a human commensal that is also responsible for chronic gastritis and peptic ulcerous disease. Little is known about the genetic profiles of the C. albicans strains in the digestive tract of dyspeptic patients. The aim of this study was to evaluate the prevalence, diversity, and genetic profiles among C. albicans isolates recovered from natural colonization of the digestive tract in the dyspeptic patients. Methods and Findings Oral swab samples (n?=?111) and gastric mucosa samples (n?=?102) were obtained from a group of patients who presented dyspeptic symptoms or ulcer complaints. Oral swab samples (n?=?162) were also obtained from healthy volunteers. C. albicans isolates were characterized and analyzed by multilocus sequence typing. The prevalence of Candida spp. in the oral samples was not significantly different between the dyspeptic group and the healthy group (36.0%, 40/111 vs. 29.6%, 48/162; P > 0.05). However, there were significant differences between the groups in the distribution of species isolated and the genotypes of the C. albicans isolates. C. albicans was isolated from 97.8% of the Candida-positive subjects in the dyspeptic group, but from only 56.3% in the healthy group (P < 0.001). DST1593 was the dominant C. albicans genotype from the digestive tract of the dyspeptic group (60%, 27/45), but not the healthy group (14.8%, 4/27) (P < 0.001). Conclusions Our data suggest a possible link between particular C. albicans strain genotypes and the host microenvironment. Positivity for particular C. albicans genotypes could signify susceptibility to dyspepsia.

Gong, Yan-Bing; Zheng, Jian-Ling; Jin, Bo; Zhuo, De-Xiang; Huang, Zhu-Qing; Qi, He; Zhang, Wei; Duan, Wei; Fu, Ji-Ting; Wang, Chui-Jie; Mao, Ze-Bin

2012-01-01

259

B-type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors  

PubMed Central

Objective To test the hypothesis that B?type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. Methods 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. Results In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r??=???0.475, p?

Wong, K Y K; McSwiggan, S; Kennedy, N S J; MacWalter, R S; Struthers, A D

2006-01-01

260

Distinct hydration properties of wild-type and familial point mutant A53T of ?-synuclein associated with Parkinson's disease.  

PubMed

The propensity of ?-synuclein to form amyloid plays an important role in Parkinson's disease. Three familial mutations, A30P, E46K, and A53T, correlate with Parkinson's disease. Therefore, unraveling the structural effects of these mutations has basic implications in understanding the molecular basis of the disease. Here, we address this issue through comparing details of the hydration of wild-type ?-synuclein and its A53T mutant by a combination of wide-line NMR, differential scanning calorimetry, and molecular dynamics simulations. All three approaches suggest a hydrate shell compatible with a largely disordered state of both proteins. Its fine details, however, are different, with the mutant displaying a somewhat higher level of hydration, suggesting a bias to more open structures, favorable for protein-protein interactions leading to amyloid formation. These differences disappear in the amyloid state, suggesting basically the same surface topology, irrespective of the initial monomeric state. PMID:22067166

Hazy, E; Bokor, M; Kalmar, L; Gelencser, A; Kamasa, P; Han, K-H; Tompa, K; Tompa, P

2011-11-01

261

Distinct Hydration Properties of Wild-Type and Familial Point Mutant A53T of ?-Synuclein Associated with Parkinson's Disease  

PubMed Central

The propensity of ?-synuclein to form amyloid plays an important role in Parkinson's disease. Three familial mutations, A30P, E46K, and A53T, correlate with Parkinson's disease. Therefore, unraveling the structural effects of these mutations has basic implications in understanding the molecular basis of the disease. Here, we address this issue through comparing details of the hydration of wild-type ?-synuclein and its A53T mutant by a combination of wide-line NMR, differential scanning calorimetry, and molecular dynamics simulations. All three approaches suggest a hydrate shell compatible with a largely disordered state of both proteins. Its fine details, however, are different, with the mutant displaying a somewhat higher level of hydration, suggesting a bias to more open structures, favorable for protein-protein interactions leading to amyloid formation. These differences disappear in the amyloid state, suggesting basically the same surface topology, irrespective of the initial monomeric state.

Hazy, E.; Bokor, M.; Kalmar, L.; Gelencser, A.; Kamasa, P.; Han, K.-H.; Tompa, K.; Tompa, P.

2011-01-01

262

Multi-Virulence-Locus Sequence Typing Identifies Single Nucleotide Polymorphisms Which Differentiate Epidemic Clones and Outbreak Strains of Listeria monocytogenes  

Microsoft Academic Search

A recently developed multi-virulence-locus sequence typing (MVLST) method showed improved discrimi- natory power for subtyping genetically diverse Listeria monocytogenes isolates and identified epidemic clone II isolates associated with two recent U.S. multistate listeriosis outbreaks. To evaluate the ability of MVLST to distinguish other epidemic clones and outbreak strains of L. monocytogenes, 58 outbreak-related isolates from 14 outbreaks and 49 unrelated

Yi Chen; Wei Zhang; Stephen J. Knabel

2007-01-01

263

Extended-spectrum ?-lactamases in Enterobacteriaceae isolated in Brazil carry distinct types of plasmid-mediated quinolone resistance genes.  

PubMed

One hundred and six nalidixic acid-resistant Enterobacteriaceae isolates from two Brazilian hospitals isolated from June to October 2010 were evaluated to characterize the co-existence of plasmid-mediated quinolone resistant (PMQR) and extended-spectrum ?-lactamase (ESBL) determinants. The qnr genetic environment was determined by PCR and sequencing. Conjugation and hybridization experiments determined whether qnr-carrying plasmids were self-transferable. The aac(6')-Ib-cr and qepA genes were also screened. Thirteen qnr-like genes (12.3?%) were identified, with qnrB1 the most common, followed by qnrS1, qnrB2 and qnrB19. No qnrA, qnrC, qnrD or qepA determinant was detected. All qnr-positive strains possessed chromosomal substitutions in gyrase- and topoisomerase-encoding genes and four harboured a aac(6')-Ib-cr gene. The co-production of blaCTX-M was observed in ten qnr-positive strains. These results indicate the dissemination of PMQR genes shown in clinical isolates from Brazil, and their co-existence with ESBL genes emphasizes the complexity of plasmid-mediated resistance determinants among Enterobacteriaceae. PMID:23741024

Viana, André L M; Cayô, Rodrigo; Avelino, Cassia C; Gales, Ana C; Franco, Marília C; Minarini, Luciene A R

2013-06-05

264

A novel C-type lectin identified by EST analysis in tissue migratory larvae of Ascaris suum.  

PubMed

C-type lectins (CTLs) are a group of proteins which bind to carbohydrate epitopes in the presence of Ca(2+), which have been described in a wide range of species. In this study, a cDNA sequence coding a putative CTL has been identified from the cDNA library constructed from the pig round worm Ascaris suum lung L3 (LL3) larvae, which was designated as A. suum C-type lectin-1 (As-CTL-1). The 510 nucleotide open reading frame of As-CTL-1 cDNA encoded the predicted 169 amino acid protein including a putative signal peptide of 23 residues and C-type lectin/C-type lectin-like domain (CLECT) at residue 26 to 167. As-CTL-1 was most similar to Toxocara canis C-type lectin-1 and 4 (Tc-CTL-1 and 4), and highly homologous to namatode CTLs and mammalian CTLs as well, such as human C-type lectin domain family 4 member G (CLECG4). In addition, As-CTL-1 was strongly expressed in tissue migrating LL3 and the L4 larvae, which were developmental larvae stages within the mammalian host. These results suggest that A. suum larvae might utilize As-CTL-1 to avoid pathogen recognition mechanisms in mammalian hosts due to it is similarity to host immune cell receptors. PMID:22006188

Yoshida, Ayako; Nagayasu, Eiji; Horii, Yoichiro; Maruyama, Haruhiko

2011-10-18

265

CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from ?-Defensin-1 HIV Inhibition  

PubMed Central

CD8+ T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8+ T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that ?-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether ?-defensins, particularly ?-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant ?-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8+ cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with ?-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, ?-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, ?-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8+ cells with potent HIV-1 inhibitory activity and a neutralizing antibody against ?-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that ?-defensin-1 inhibits HIV-1 infection following viral entry but that ?-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.

Chang, Theresa Li-Yun; Francois, Fleur; Mosoian, Arevik; Klotman, Mary E.

2003-01-01

266

Novel sequences encoding venom C-type lectins are conserved in phylogenetically and geographically distinct Echis and Bitis viper species.  

PubMed

Envenoming by Echis saw scaled vipers and Bitis arietans puff adders is the leading cause of death and morbidity in Africa due to snake bite. Despite their medical importance, the composition and constituent functionality of venoms from these vipers remains poorly understood. Here, we report the cloning of cDNA sequences encoding seven clusters or isoforms of the haemostasis-disruptive C-type lectin (CTL) proteins from the venom glands of Echis ocellatus, E. pyramidum leakeyi, E. carinatus sochureki and B. arietans. All these CTL sequences encoded the cysteine scaffold that defines the carbohydrate-recognition domain of mammalian CTLs. All but one of the Echis and Bitis CTL sequences showed greater sequence similarity to the beta than alpha CTL subunits in venoms of related Asian and American vipers. Four of the new CTL clusters showed marked inter-cluster sequence conservation across all four viper species which were significantly different from that of previously published viper CTLs. The other three Echis and Bitis CTL clusters showed varying degrees of sequence similarity to published viper venom CTLs. Because viper venom CTLs exhibit a high degree of sequence similarity and yet exert profoundly different effects on the mammalian haemostatic system, no attempt was made to assign functionality to the new Echis and Bitis CTLs on the basis of sequence alone. The extraordinary level of inter-specific and inter-generic sequence conservation exhibited by the Echis and Bitis CTLs leads us to speculate that antibodies to representative molecules should neutralise the biological function of this important group of venom toxins in vipers that are distributed throughout Africa, the Middle East and the Indian subcontinent. PMID:14557069

Harrison, R A; Oliver, J; Hasson, S S; Bharati, K; Theakston, R D G

2003-10-01

267

Genome Wide DNA Copy Number Analysis of Serous Type Ovarian Carcinomas Identifies Genetic Markers Predictive of Clinical Outcome  

PubMed Central

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups.

Growdon, Whitfield B.; Drapkin, Ronny I.; Nitta, Mai; Sergent, Petra A.; Allred, Serena F.; Gross, Jenny; Deavers, Michael T.; Kuo, Wen-Lin; Karlan, Beth Y.; Rueda, Bo R.; Orsulic, Sandra; Gershenson, David M.; Birrer, Michael J.; Gray, Joe W.; Mohapatra, Gayatry

2012-01-01

268

Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome.  

PubMed

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups. PMID:22355333

Engler, David A; Gupta, Sumeet; Growdon, Whitfield B; Drapkin, Ronny I; Nitta, Mai; Sergent, Petra A; Allred, Serena F; Gross, Jenny; Deavers, Michael T; Kuo, Wen-Lin; Karlan, Beth Y; Rueda, Bo R; Orsulic, Sandra; Gershenson, David M; Birrer, Michael J; Gray, Joe W; Mohapatra, Gayatry

2012-02-15

269

Envelope Variants from Women Recently Infected with Clade A Human Immunodeficiency Virus Type 1 Confer Distinct Phenotypes That Are Discerned by Competition and Neutralization Experiments  

Microsoft Academic Search

Women infected with clade A human immunodeficiency virus type 1 harbor a virus population that is genetically diverse in the envelope gene, a fact that contrasts with the homogeneous virus population identified in newly infected men. It is not known whether viral genetic diversity at this early stage of infection is manifested as phenotypic diversity. This is a significant question

Sally L. Painter; Roman Biek; David C. Holley; Mary Poss

2003-01-01

270

Automatically Identifying Tag Types  

Microsoft Academic Search

Web 2.0 applications such as delicious, flickr or lastfm have recently become extremely popular and as a result, a large amount of semantically rich metadata produced by users becomes\\u000a available and exploitable. Tag information can be used for many purposes (e.g. user profiling, recommendations, clustering etc), though the benefit of tags for search is by far the most discussed usage.

Kerstin Bischoff; Claudiu S. Firan; Cristina Kadar; Wolfgang Nejdl; Raluca Paiu

2009-01-01

271

Two mechanistically distinct effects of dihydropyridine nifedipine on CaV1.2 L-type Ca²? channels revealed by Timothy syndrome mutation.  

PubMed

Dihydropyridine Ca(2+) channel antagonists (DHPs) block Ca(V)1.2 L-type Ca(2+) channels (LTCCs) by stabilizing their voltage-dependent inactivation (VDI); however, it is still not clear how DHPs allosterically interact with the kinetically distinct (fast and slow) VDI. Thus, we analyzed the effect of a prototypical DHP, nifedipine on LTCCs with or without the Timothy syndrome mutation that resides in the I-II linker (L(I)-(II)) of Ca(V)1.2 subunits and impairs VDI. Whole-cell Ba(2+) currents mediated by rabbit Ca(V)1.2 with or without the Timothy mutation (G436R) (analogous to the human G406R mutation) were analyzed in the presence and absence of nifedipine. In the absence of nifedipine, the mutation significantly impaired fast closed- and open-state VDI (CSI and OSI) at -40 and 0 mV, respectively, but did not affect channels' kinetics at -100 mV. Nifedipine equipotently blocked these channels at -80 mV. In wild-type LTCCs, nifedipine promoted fast CSI and OSI at -40 and 0 mV and promoted or stabilized slow CSI at -40 and -100 mV, respectively. In LTCCs with the mutation, nifedipine resumed the impaired fast CSI and OSI at -40 and 0 mV, respectively, and had the same effect on slow CSI as in wild-type LTCCs. Therefore, nifedipine has two mechanistically distinct effects on LTCCs: the promotion of fast CSI/OSI caused by L(I-II) at potentials positive to the sub-threshold potential and the promotion or stabilization of slow CSI caused by different mechanisms at potentials negative to the sub-threshold potential. PMID:22554770

Sheng, Xiaona; Nakada, Tsutomu; Kobayashi, Motohiro; Kashihara, Toshihide; Shibazaki, Toshihide; Horiuchi-Hirose, Miwa; Gomi, Simmon; Hirose, Masamichi; Aoyama, Toshifumi; Yamada, Mitsuhiko

2012-04-23

272

The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite  

PubMed Central

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called ‘serine repeat antigens’ (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical active site serine residue instead of a catalytic cysteine. Members of this SERAser subfamily are abundantly expressed in asexual blood stages, rendering them attractive drug and vaccine targets. In this study, we show by antibody localization and in vivo fluorescent tagging with the red fluorescent protein mCherry that the two P. berghei serine-type family members, PbSERA1 and PbSERA2, display differential expression towards the final stages of merozoite formation. Via targeted gene replacement, we generated single and double gene knockouts of the P. berghei SERAser genes. These loss-of-function lines progressed normally through the parasite life cycle, suggesting a specialized, non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed increased expression of the cysteine-type PbSERA3. Compensatory mechanisms between distinct SERA subfamilies may thus explain the absence of phenotypical defect in SERAser disruptants, and challenge the suitability to develop potent antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

Putrianti, Elyzana D; Schmidt-Christensen, Anja; Arnold, Iris; Heussler, Volker T; Matuschewski, Kai; Silvie, Olivier

2010-01-01

273

Potentiation of the Cardiac L-Type Ca2+ Channel (?1C) by Dihydropyridine Agonist and Strong Depolarization Occur via Distinct Mechanisms  

PubMed Central

A defining property of L-type Ca2+ channels is their potentiation by both 1,4-dihydropyridine agonists and strong depolarization. In contrast, non–L-type channels are potentiated by neither agonist nor depolarization, suggesting that these two processes may by linked. In this study, we have tested whether the mechanisms of agonist- and depolarization-induced potentiation in the cardiac L-type channel (?1C) are linked. We found that the mutant L-type channel GFP-?1C(TQ?YM), bearing the mutations T1066Y and Q1070M, was able to undergo depolarization-induced potentiation but not potentiation by agonist. Conversely, the chimeric channel GFP-CACC was potentiated by agonist but not by strong depolarization. These data indicate that the mechanisms of agonist- and depolarization-induced potentiation of ?1C are distinct. Since neither GFP-CACC nor GFP-CCAA was potentiated significantly by depolarization, no single repeat of ?1C appears to be responsible for depolarization-induced potentiation. Surprisingly, GFP-CACC displayed a low estimated open probability similar to that of the ?1C, but could not support depolarization-induced potentiation, demonstrating that a relatively low open probability alone is not sufficient for depolarization-induced potentiation to occur. Thus, depolarization-induced potentiation may be a global channel property requiring participation from all four homologous repeats.

Wilkens, Christina M.; Grabner, Manfred; Beam, Kurt G.

2001-01-01

274

Homozygosity of the Polymorphism MICA5.1 Identifies Extreme Risk of Progression to Overt Adrenal Insufficiency among 21-Hydroxylase Antibody-Positive Patients with Type 1 Diabetes  

PubMed Central

Context: Autoimmunity associated with Addison’s disease (AD) can be detected by measuring 21-hydroxylase (21OH) autoantibodies. Subjects with type 1 diabetes (T1D) are at increased risk for AD. Genetic factors including HLA-DRB1*0404 and MICA have been associated with AD in populations with and without T1D. Objective: The objective of the study was to examine the effect of the MICA5.1 allele in subjects with 21OH autoantibodies on progression to AD. Design: Two components were used: 1) a cross-sectional study with subjects with AD identified and enrolled from September 1993 to November 2008 and 2) a cohort study prospectively following up patients with T1D who screened positive for 21OH autoantibodies. Setting: Subjects were identified from the Barbara Davis Center and through the National Adrenal Diseases Foundation. Patients: Sixty-three subjects with AD were referred through the National Adrenal Diseases Foundation (AD referrals). Sixty-three subjects with positive 21OH antibodies from the Barbara Davis Center were followed up for progression to AD, and 11 were diagnosed with AD (progressors). Results: Seventy-three percent of progressors (eight of 11) and 57% of AD referrals (36 of 63) were MICA5.1 homozygous (P = ns). Overall, 59% of patients with AD (44 of 74) were MICA5.1/5.1 compared with 17% of nonprogressors (nine of 52) (P < 0.0001) and 19% of normal DR3/4-DQB1*0302 controls (64 of 336) (P < 0.0001). Conclusions: Identifying extreme risk should facilitate monitoring of progression from 21OH antibody positivity to overt AD. The HLA-DR3/0404 genotype defines high-risk subjects for adrenal autoimmunity. MICA5.1/5.1 may define those at highest risk for progression to overt AD, a feature unique to AD and distinct from T1D.

Triolo, Taylor M.; Baschal, Erin E.; Armstrong, Taylor K.; Toews, Carrie S.; Fain, Pamela R.; Rewers, Marian J.; Yu, Liping; Miao, Dongmei; Eisenbarth, George S.; Gottlieb, Peter A.; Barker, Jennifer M.

2009-01-01

275

In vitro inhibition of SKOV-3 cell migration as a distinctive feature of progesterone receptor membrane component type 2 versus type 1.  

PubMed

Progesterone receptor membrane component type 2 (PGRMC2) is strongly homologous to PGRMC1 which is highly expressed in ovarian cancer and other cancer cells and was claimed to play an important role in chemotherapy resistance. Whereas PGRMC1 has been extensively characterized in in vitro studies, comparably little is known about PGRMC2. To determine PGRMC2's role in ovarian cancer cell proliferation and mobility PGRMC1- and 2-depleted and -overexpressing SKOV-3 cells were generated. In electric cell-substrate impedance sensing studies, PGRMC2 negatively affects SKOV-3 migration rate if overexpressed; oppositely, depletion was associated with an increased migration rate. PGRMC1 had no effect in this assay. These effects were not associated with f-actin regulation or actin cytoskeleton reorganization. Yet, these highly homologous proteins share many properties. Both PGRMC1 and 2 are localized to the endoplasmic reticulum. As PGRMC1 was reported to interact with cytochrome P450 proteins (CYP) binding of two different CYPs to PGRMC2 was tested; a stable interaction of PGRMC2 with CYP3A4 and CYP21A2 was found in human embryonic kidney cells. For both PGRMC types, cell viability assays revealed no significant differences of SKOV-3 survival in overexpressing and depleted cells. PGRMC2 also does not seem to have any influence on the apoptotic effect of cisplatin or the antiapoptotic effect of progesterone which had been reported for PGRMC1. In contrast to PGRMC1, protein levels of PGRMC2 in SKOV-3 cells are reduced by treatment with cisplatin (30-60?M). In conclusion, we show for the first time that PGRMC2 inhibits migration of SKOV-3 ovarian cancer cells in vitro. PMID:23064006

Albrecht, Christian; Huck, Volker; Wehling, Martin; Wendler, Alexandra

2012-10-12

276

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.  

PubMed

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10??). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10?¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D. PMID:23209189

Tabassum, Rubina; Chauhan, Ganesh; Dwivedi, Om Prakash; Mahajan, Anubha; Jaiswal, Alok; Kaur, Ismeet; Bandesh, Khushdeep; Singh, Tejbir; Mathai, Benan John; Pandey, Yogesh; Chidambaram, Manickam; Sharma, Amitabh; Chavali, Sreenivas; Sengupta, Shantanu; Ramakrishnan, Lakshmi; Venkatesh, Pradeep; Aggarwal, Sanjay K; Ghosh, Saurabh; Prabhakaran, Dorairaj; Srinath, Reddy K; Saxena, Madhukar; Banerjee, Monisha; Mathur, Sandeep; Bhansali, Anil; Shah, Viral N; Madhu, Sri Venkata; Marwaha, Raman K; Basu, Analabha; Scaria, Vinod; McCarthy, Mark I; Venkatesan, Radha; Mohan, Viswanathan; Tandon, Nikhil; Bharadwaj, Dwaipayan

2012-12-03

277

Non-susceptibility genes to Bombyx densovirus type 1, Nid- 1 and nsd- 1, affect distinct steps of the viral infection pathway  

Microsoft Academic Search

In the silkworm Bombyx mori, densovirus type 1 (BmDNV-1) replicates only in the midgut and causes fatal disease. Resistance to BmDNV-1 is determined by two genes, nsd-1 and Nid-1, respectively. Neither of them has been identified yet. We investigated the viral transcript by RT-PCR in inoculated silkworms carrying different sets of nsd-1 and Nid-1 genotype. BmDNV-1 transcript was not detected

Kurako Kidokoro; Katsuhiko Ito; Dorington O. Ogoyi; Hiroaki Abe; Kazuei Mita; Keiko Kadono-Okuda

2010-01-01

278

Urinary fetuin-a is a novel marker for diabetic nephropathy in type 2 diabetes identified by lectin microarray.  

PubMed

We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n?=?17) and measured urinary excretion of fetuin-A (n?=?85). The increased signals of urine samples were observed in Sia?2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40±0.43; A2, 0.60±0.53; A3 1.57±1.13 ng/gCr; p?=?7.29×10(-8)) and of GFR stages (G1, 0.39±0.39; G2, 0.49±0.45; G3, 1.25±1.18; G4, 1.34±0.80 ng/gCr; p?=?3.89×10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881-11.844) and 3.739 (1.785-7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy. PMID:24143207

Inoue, Kentaro; Wada, Jun; Eguchi, Jun; Nakatsuka, Atsuko; Teshigawara, Sanae; Murakami, Kazutoshi; Ogawa, Daisuke; Terami, Takahiro; Katayama, Akihiro; Tone, Atsuhito; Iseda, Izumi; Hida, Kazuyuki; Yamada, Masao; Ogawa, Tomohisa; Makino, Hirofumi

2013-10-15

279

Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray  

PubMed Central

We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n?=?17) and measured urinary excretion of fetuin-A (n?=?85). The increased signals of urine samples were observed in Sia?2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography–tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40±0.43; A2, 0.60±0.53; A3 1.57±1.13 ng/gCr; p?=?7.29×10?8) and of GFR stages (G1, 0.39±0.39; G2, 0.49±0.45; G3, 1.25±1.18; G4, 1.34±0.80 ng/gCr; p?=?3.89×10?4). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881–11.844) and 3.739 (1.785–7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy.

Inoue, Kentaro; Wada, Jun; Eguchi, Jun; Nakatsuka, Atsuko; Teshigawara, Sanae; Murakami, Kazutoshi; Ogawa, Daisuke; Terami, Takahiro; Katayama, Akihiro; Tone, Atsuhito; Iseda, Izumi; Hida, Kazuyuki; Yamada, Masao; Ogawa, Tomohisa; Makino, Hirofumi

2013-01-01

280

A unique enhancer element for the trans activator (p40 sup tax ) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphobol-13-acetate-responsive elements  

SciTech Connect

The trans activator (p40{sup tax}) of human T-cell leukemia virus type I (HTLV-I) is a transcriptional factor that activates the long terminal repeat (LTR) of HTLV-I and interleukin-2 receptor {alpha}. The authors examined the HTLV-I enhancer responsible for tax-mediated trans activation and identified (A/T)(G/C)(G/C)CNNTGACG(T/A) as a plausible tax-responsive element (TRE). The putative TRE in the LTR was found to be different from the elements required for activation by cyclic AMP and 12-O-tetradecanoylphorbol-13-acetate, although these elements overlapped each other. The TRE was also different from a binding site of N-{kappa}B-like factor that was identified was identified in the interleukin-2 receptor {alpha} promoter and human immunodeficiency virus LTR as a TRE. The latter result was further demonstrated by the failure of the NF-{kappa}B sequence to compete with the TRE of the LTR in a protein-binding assay. These findings indicate that tax function and its cascade can modulate activities of various enhancer sequences, which are probably regulated by distinct DNA-binding factors.

Fujisawa, Junichi; Toita, Masami; Yoshida, Mitsuaki (Cancer Institute, Tokyo (Japan))

1989-08-01

281

Low-Altitude and Land-Based Infrared Thermography to Identify Types of Groundwater Discharge in NWT Streams  

NASA Astrophysics Data System (ADS)

In tributaries of the Mackenzie River in the Northwest Territories (NWT), Canada, groundwater discharge provides critical fish habitat for Dolly Varden and bull trout populations by maintaining base flows, creating thermal refugia in winter, and providing stable riverbed temperatures for spawning. Where temperature contrasts exist between surface water and groundwater, infrared thermography can use heat as a tracer to locate groundwater discharge areas. Thermal images acquired from satellites and high altitude airplanes tend to be expensive, lack the resolution necessary to identify small discharge locations, and do not allow real time decisions to investigate and ground truth identified temperature anomalies. Therefore, a system was developed using a handheld FLIR ThermaCam P25 infrared camera, visual video camera, infrared video capture system, and GPS in a low flying helicopter and on the ground. The advantage of the system was its ability to inexpensively and efficiently characterize several kilometer long reaches of river and identify springs and seeps on a sub-meter scale and in real time. The different types of groundwater discharge that can occur in these streams include: deep geothermally heated groundwater; shallow groundwater; and active zone water, but differentiating them can be difficult because observed thermal anomalies can be non-unique functions of the initial groundwater temperature, magnitude of discharge, air and surface water temperatures, and temporal variations. Work performed in March and September easily detected spring and seeps of deep groundwater (8 to 13 ° C) at Smith Creek, Gibson Creek, Gayna River, and Little Fish Creek. Shallow groundwater discharge was detected (1 to 3 ° C) at White Sand Creek, Canyon Creek, and Fish Creek, but was more difficult to identify. Subtle variations from surrounding temperatures (<1 ° C) at some sites suggested seeps from the hyporheic zone or possibly the active zone. The limitations of infrared thermography include only being able to measure temperatures of surfaces and difficulty differentiating spatial anomalies from possible temporal influences. Overall, the handheld system was a useful reconnaissance tool for identifying surficial expressions of different types of ground water discharge.

Conant, B.; Mochnacz, N. J.

2009-05-01

282

Discrete typing units of Trypanosoma cruzi identified in rural dogs and cats in the humid Argentinean Chaco.  

PubMed

The discrete typing units (DTUs) of Trypanosoma cruzi that infect domestic dogs and cats have rarely been studied. With this purpose we conducted a cross-sectional xenodiagnostic survey of dog and cat populations residing in 2 infested rural villages in Pampa del Indio, in the humid Argentine Chaco. Parasites were isolated by culture from 44 dogs and 12 cats with a positive xenodiagnosis. DTUs were identified from parasite culture samples using a strategy based on multiple polymerase-chain reactions. TcVI was identified in 37 of 44 dogs and in 10 of 12 cats, whereas TcV was identified in 5 dogs and in 2 cats -a new finding for cats. No mixed infections were detected. The occurrence of 2 dogs infected with TcIII -classically found in armadillos- suggests a probable link with the local sylvatic transmission cycle involving Dasypus novemcinctus armadillos and a potential risk of human infection with TcIII. Our study reinforces the importance of dogs and cats as domestic reservoir hosts and sources of various DTUs infecting humans, and suggests a link between dogs and the sylvatic transmission cycle of TcIII. PMID:23058180

Enriquez, G F; Cardinal, M V; Orozco, M M; Lanati, L; Schijman, A G; Gürtler, R E

2012-10-12

283

Discrete typing units of Trypanosoma cruzi identified in rural dogs and cats in the humid Argentinean Chaco  

PubMed Central

SUMMARY The discrete typing units (DTUs) of Trypanosoma cruzi that infect domestic dogs and cats have rarely been studied. With this purpose we conducted a cross-sectional xenodiagnostic survey of dog and cat populations residing in two infested rural villages in Pampa del Indio, in the humid Argentine Chaco. Parasites were isolated by culture from 44 dogs and 12 cats with a positive xenodiagnosis. DTUs were identified from parasite culture samples using a strategy based on multiple polymerase-chain reactions. TcVI was identified in 37 of 44 dogs and in 10 of 12 cats, whereas TcV was identified in five dogs and in two cats –a new finding for cats. No mixed infections were detected. The occurrence of two dogs infected with TcIII –classically found in armadillos– suggests a probable link with the local sylvatic transmission cycle involving Dasypus novemcinctus armadillos and a potential risk of human infection with TcIII. Our study reinforces the importance of dogs and cats as domestic reservoir hosts and sources of various DTUs infecting humans, and suggests a link between dogs and the sylvatic transmission cycle of TcIII.

ENRIQUEZ, G.F.; CARDINAL, M.V.; OROZCO, M.M.; LANATI, L.; SCHIJMAN, A.G.; GURTLER, R.E.

2013-01-01

284

Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina.  

PubMed

X-linked CSNB patients may exhibit myopia, nystagmus, strabismus and ERG abnormalities of the Schubert-Bornschein type. We recently identified the retina-specific L-type calcium channel alpha1 subunit gene CACNA1F localised to the Xp11.23 region, which is mutated in families showing the incomplete type (CSNB2). Here, we report comprehensive mutation analyses in the 48 CACNA1F exons in 36 families, most of them from Germany. All families were initially diagnosed as having the incomplete type of CSNB, except for two which have been designated as Aland Island eye disease (AIED)-like. Out of 33 families, a total of 30 different mutations were identified, of which 24 appear to be unique for the German population. The mutations, 20 of which are published here for the first time, were found to be equally distributed over the entire gene sequence. No mutation could be found in a classic AIED family previously shown to map to the CSNB2 interval. Cacna1f expression in photoreceptor-negative mice strains indicate that the gene is expressed in the outer nuclear, the inner nuclear, and the ganglion cell layer. Such a distribution points to the central role of calcium regulation in the interaction of retinal cells that mediate signal transmission. PMID:12111638

Wutz, Krisztina; Sauer, Christian; Zrenner, Eberhart; Lorenz, Birgit; Alitalo, Tiina; Broghammer, Martina; Hergersberg, Martin; de la Chapelle, Albert; Weber, Bernhard H F; Wissinger, Bernd; Meindl, Alfons; Pusch, Carsten M

2002-08-01

285

Monoclonal Antibodies Identify Individual Determinants on Mouse Mammary Tumor Virus Glycoprotein gp52 with Group, Class, or Type Specificity  

PubMed Central

Hybrid cell lines producing monoclonal antibodies against the C3H strain of mouse mammary tumor virus (C3H MMTV) were prepared by the fusion of mouse myeloma cells with the lymphocytes of BALB/c mice that were immunized with C3H MMTV. Approximately 10% of the hybrid cells initially plated after cell fusion produced immunoglobulins that reacted in antibody-binding assays with C3H MMTV; 40 of these cells were cloned, and 6 eventually yielded stable cell lines. High concentrations of monoclonal antibodies (5 to 20 mg/ml) were obtained from serum and ascites fluid of syngeneic mice inoculated with the hybrid cells. All of the monoclonal antibodies were directed against the envelope glycoprotein gp52. Three of the hybrid cell lines produced immunoglobulins of the immunoglobulin M subclass and three produced immunoglobulin G2a. The monoclonal antibodies showed limited charge heterogeneity in light and heavy chains when analyzed by high-resolution, two-dimensional gel electrophoresis. Three serologically distinct specificities were observed when these ascites fluids were tested against different strains of MMTV. The antigenic determinants detected were the following: (i) a type-specific determinant unique to the C3H strain of MMTV; (ii) class-specific determinants shared between C3H and GR MMTVs; and (iii) a group-specific determinant found on C3H, GR, RIII, and the endogenous C3H (C3Hf) MMTVs. Because monoclonal antibodies recognize single antigenic determinants, these results demonstrate for the first time that the three patterns of antigenic reactivity for MMTV are related to individual determinants on the gp52 molecule and also clearly show that one strain of MMTV can be distinguished from other strains. Images

Massey, Richard J.; Arthur, Larry O.; Nowinski, Robert C.; Schochetman, Gerald

1980-01-01

286

The Application of the Diabetes Prevention Trial-Type 1 Risk Score for Identifying a Preclinical State of Type 1 Diabetes  

PubMed Central

OBJECTIVE We assessed the utility of the Diabetes Prevention Trial–Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T1D) within 2 years. RESEARCH DESIGN AND METHODS The DPTRS was previously developed from Diabetes Prevention Trial–Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS). DPTRS components included C-peptide and glucose indexes from oral glucose tolerance testing, along with age and BMI. The cumulative incidence of T1D was determined after DPTRS thresholds were first exceeded and after the first occurrences of glucose abnormalities. RESULTS The 2-year risks after the 9.00 DPTRS threshold was exceeded were 0.88 and 0.77 in DPT-1 (n = 90) and the TNNHS (n = 69), respectively. In DPT-1, the 2-year risks were much lower after dysglycemia first occurred (0.37; n = 306) and after a 2-h glucose value between 190 and 199 mg/dL was first reached (0.64; n = 59). Among those who developed T1D in DPT-1, the 9.00 threshold was exceeded 0.81 ± 0.53 years prior to the conventional diagnosis. Postchallenge C-peptide levels were substantially higher (P = 0.001 for 30 min; P < 0.001 for other time points) when the 9.00 threshold was first exceeded compared with the levels at diagnosis. CONCLUSIONS A DPTRS threshold of 9.00 identifies individuals who are very highly likely to progress to the conventional diagnosis of T1D within 2 years and, thus, are essentially in a preclinical diabetic state. The 9.00 threshold is exceeded well before diagnosis, when stimulated C-peptide levels are substantially higher.

Sosenko, Jay M.; Skyler, Jay S.; Mahon, Jeffrey; Krischer, Jeffrey P.; Beam, Craig A.; Boulware, David C.; Greenbaum, Carla J.; Rafkin, Lisa E.; Cowie, Catherine; Cuthbertson, David; Palmer, Jerry P.

2012-01-01

287

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.  

PubMed

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D. PMID:22158537

Cho, Yoon Shin; Chen, Chien-Hsiun; Hu, Cheng; Long, Jirong; Ong, Rick Twee Hee; Sim, Xueling; Takeuchi, Fumihiko; Wu, Ying; Go, Min Jin; Yamauchi, Toshimasa; Chang, Yi-Cheng; Kwak, Soo Heon; Ma, Ronald C W; Yamamoto, Ken; Adair, Linda S; Aung, Tin; Cai, Qiuyin; Chang, Li-Ching; Chen, Yuan-Tsong; Gao, Yutang; Hu, Frank B; Kim, Hyung-Lae; Kim, Sangsoo; Kim, Young Jin; Lee, Jeannette Jen-Mai; Lee, Nanette R; Li, Yun; Liu, Jian Jun; Lu, Wei; Nakamura, Jiro; Nakashima, Eitaro; Ng, Daniel Peng-Keat; Tay, Wan Ting; Tsai, Fuu-Jen; Wong, Tien Yin; Yokota, Mitsuhiro; Zheng, Wei; Zhang, Rong; Wang, Congrong; So, Wing Yee; Ohnaka, Keizo; Ikegami, Hiroshi; Hara, Kazuo; Cho, Young Min; Cho, Nam H; Chang, Tien-Jyun; Bao, Yuqian; Hedman, Åsa K; Morris, Andrew P; McCarthy, Mark I; Takayanagi, Ryoichi; Park, Kyong Soo; Jia, Weiping; Chuang, Lee-Ming; Chan, Juliana C N; Maeda, Shiro; Kadowaki, Takashi; Lee, Jong-Young; Wu, Jer-Yuarn; Teo, Yik Ying; Tai, E Shyong; Shu, Xiao Ou; Mohlke, Karen L; Kato, Norihiro; Han, Bok-Ghee; Seielstad, Mark

2011-12-11

288

The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color.  

PubMed

BACKGROUND: Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. RESULTS: We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina 1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation. CONCLUSIONS: We report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits. PMID:23731509

Motamayor, Juan C; Mockaitis, Keithanne; Schmutz, Jeremy; Haiminen, Niina; Livingstone, Donald; Cornejo, Omar; Findley, Seth D; Zheng, Ping; Utro, Filippo; Royaert, Stefan; Saski, Christopher; Jenkins, Jerry; Podicheti, Ram; Zhao, Meixia; Scheffler, Brian E; Stack, Joseph C; Feltus, Frank A; Mustiga, Guiliana M; Amores, Freddy; Phillips, Wilbert; Marelli, Jean Philippe; May, Gregory D; Shapiro, Howard; Ma, Jianxin; Bustamante, Carlos D; Schnell, Raymond J; Main, Dorrie; Gilbert, Don; Parida, Laxmi; Kuhn, David N

2013-06-01

289

Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus  

PubMed Central

Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D), focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip) and absolute methylation values were estimated using a Bayesian algorithm (BATMAN). Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p?=?9.40×10?4, permutation p?=?1.0×10?3). Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p?=?1.13×10?7). Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM), encapsulates a Highly Conserved Non-Coding Element (HCNE) that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA) SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

Wilson, Gareth A.; Rakyan, Vardhman K.; Teschendorff, Andrew E.; Akan, Pelin; Stupka, Elia; Down, Thomas A.; Prokopenko, Inga; Morison, Ian M.; Mill, Jonathan; Pidsley, Ruth; Deloukas, Panos; Frayling, Timothy M.; Hattersley, Andrew T.; McCarthy, Mark I.; Beck, Stephan; Hitman, Graham A.

2010-01-01

290

Identifying postpartum intervention approaches to prevent type 2 diabetes in women with a history of gestational diabetes  

PubMed Central

Background Women who develop gestational diabetes mellitus (GDM) have an increased risk for the development of type 2 diabetes. Despite this "window of opportunity," few intervention studies have targeted postpartum women with a history of GDM. We sought perspectives of women with a history of GDM to identify a) barriers and facilitators to healthy lifestyle changes postpartum, and b) specific intervention approaches that would facilitate participation in a postpartum lifestyle intervention program. Methods We used mixed methods to gather data from women with a prior history of GDM, including focus groups and informant interviews. Analysis of focus groups relied on grounded theory and used open-coding to categorize data by themes, while frequency distributions were used for the informant interviews. Results Of 38 women eligible to participate in focus groups, only ten women were able to accommodate their schedules to attend a focus group and 15 completed informant interviews by phone. We analyzed data from 25 women (mean age 35, mean pre-pregnancy BMI 28, 52% Caucasian, 20% African American, 12% Asian, 8% American Indian, 8% refused to specify). Themes from the focus groups included concern about developing type 2 diabetes, barriers to changing diet, and barriers to increasing physical activity. In one focus group, women expressed frustration about feeling judged by their physicians during their GDM pregnancy. Cited barriers to lifestyle change were identified from both methods, and included time and financial constraints, childcare duties, lack of motivation, fatigue, and obstacles at work. Informants suggested facilitators for lifestyle change, including nutrition education, accountability, exercise partners/groups, access to gyms with childcare, and home exercise equipment. All focus group and informant interview participants reported access to the internet, and the majority expressed interest in an intervention program delivered primarily via the internet that would include the opportunity to work with a lifestyle coach. Conclusion Time constraints were a major barrier. Our findings suggest that an internet-based lifestyle intervention program should be tested as a novel approach to prevent type 2 diabetes in postpartum women with a history of GDM. Trial Registration ClinicalTrials.gov: NCT01102530

2011-01-01

291

Comparison of infection-neutralizing and -enhancing antibody balance induced by two distinct genotype strains of dengue virus type 1 or 3 DNA vaccines in mice.  

PubMed

Dengue viruses have spread throughout tropical and subtropical countries, and vaccine development is urgently needed. However, one concern is that induction of insufficient levels of neutralizing antibodies in vaccines may increase disease severity because of a hypothetical mechanism termed antibody-dependent enhancement of infection. This study used two distinct genotype strains of dengue virus types 1 and 3 (DENV1 and DENV3, respectively) to compare antibody responses in a mouse-DNA vaccine model. As expected, a conventional neutralization test using Vero cells showed higher antibody titers in homologous rather than heterologous combinations of genotype strains used for mouse immunization and the neutralization test, for each of DENV1 and DENV3. However, our assay system using K562 cells to measure the balance of neutralizing and enhancing antibodies indicated that Vero cell-neutralizing antibody titers did not always correlate with enhancing activities observed at subneutralizing doses. Rather, induction of enhancing activities depended on the genotype strain used for mouse immunization. The genotype/strain difference also affected IgG subclass profiles and potentially the composition of antibody species induced in mice. This study suggests that enhancing activities of dengue virus-induced neutralizing antibodies may vary according to the genotype and has implications for vaccine antigen development. PMID:23911844

Sjatha, Fithriyah; Takizawa, Yamato; Kotaki, Tomohiro; Yamanaka, Atsushi; Konishi, Eiji

2013-08-02

292

Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97.  

PubMed

Stardust (Sdt) and Discs-Large (Dlg) are membrane-associated guanylate kinases (MAGUKs) involved in the organization of supramolecular protein complexes at distinct epithelial membrane compartments in Drosophila. Loss of either Sdt or Dlg affects epithelial development with severe effects on apico-basal polarity. Moreover, Dlg is required for the structural and functional integrity of synaptic junctions. Recent biochemical and cell culture studies have revealed that various mammalian MAGUKs can interact with mLin-7/Veli/MALS, a small PDZ-domain protein. To substantiate these findings for their in vivo significance with regard to Sdt- and Dlg-based protein complexes, we analyzed the subcellular distribution of Drosophila Lin-7 (DLin-7) and performed genetic and biochemical assays to characterize its interaction with either of the two MAGUKs. In epithelia, Sdt mediates the recruitment of DLin-7 to the subapical region, while at larval neuromuscular junctions, a particular isoform of Dlg, Dlg-S97, is required for postsynaptic localization of DLin-7. Ectopic expression of Dlg-S97 in epithelia, however, was not sufficient to induce a redistribution of DLin-7. These results imply that the recruitment of DLin-7 to MAGUK-based protein complexes is defined by cell-type specific mechanisms and that DLin-7 acts downstream of Sdt in epithelia and downstream of Dlg at synapses. PMID:15039455

Bachmann, André; Timmer, Marco; Sierralta, Jimena; Pietrini, Grazia; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

2004-03-23

293

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci  

PubMed Central

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ?50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ?2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10?9) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10?6). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10?7) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10?15). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10?8). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups.

Saxena, Richa; Elbers, Clara C.; Guo, Yiran; Peter, Inga; Gaunt, Tom R.; Mega, Jessica L.; Lanktree, Matthew B.; Tare, Archana; Castillo, Berta Almoguera; Li, Yun R.; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F.; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Bohm, Bernhard O.; Braund, Peter S.; Burton, Paul R.; Chandrupatla, Hareesh R.; Clarke, Robert; Cooper-DeHoff, Rhonda M.; Crook, Errol D.; Davey-Smith, George; Day, Ian N.; de Boer, Anthonius; de Groot, Mark C.H.; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S.; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A.; Glessner, Joseph T.; Goel, Anuj; Gong, Yan; Grant, Struan F.A.; Grobbee, Diederick E.; Hastie, Claire; Humphries, Steve E.; Kim, Cecilia E.; Kivimaki, Mika; Kleber, Marcus; Meisinger, Christa; Kumari, Meena; Langaee, Taimour Y.; Lawlor, Debbie A.; Li, Mingyao; Lobmeyer, Maximilian T.; Maitland-van der Zee, Anke-Hilse; Meijs, Matthijs F.L.; Molony, Cliona M.; Morrow, David A.; Murugesan, Gurunathan; Musani, Solomon K.; Nelson, Christopher P.; Newhouse, Stephen J.; O'Connell, Jeffery R.; Padmanabhan, Sandosh; Palmen, Jutta; Patel, Sanjey R.; Pepine, Carl J.; Pettinger, Mary; Price, Thomas S.; Rafelt, Suzanne; Ranchalis, Jane; Rasheed, Asif; Rosenthal, Elisabeth; Ruczinski, Ingo; Shah, Sonia; Shen, Haiqing; Silbernagel, Gunther; Smith, Erin N.; Spijkerman, Annemieke W.M.; Stanton, Alice; Steffes, Michael W.; Thorand, Barbara; Trip, Mieke; van der Harst, Pim; van der A, Daphne L.; van Iperen, Erik P.A.; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Wolffenbuttel, Bruce H.R.; Young, Taylor; Zafarmand, M. Hadi; Zmuda, Joseph M.; Boehnke, Michael; Altshuler, David; McCarthy, Mark; Kao, W.H. Linda; Pankow, James S.; Cappola, Thomas P.; Sever, Peter; Poulter, Neil; Caulfield, Mark; Dominiczak, Anna; Shields, Denis C.; Bhatt, Deepak L.; Zhang, Li; Curtis, Sean P.; Danesh, John; Casas, Juan P.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Doevendans, Pieter A.; Dorn, Gerald W.; Farrall, Martin; FitzGerald, Garret A.; Hamsten, Anders; Hegele, Robert; Hingorani, Aroon D.; Hofker, Marten H.; Huggins, Gordon S.; Illig, Thomas; Jarvik, Gail P.; Johnson, Julie A.; Klungel, Olaf H.; Knowler, William C.; Koenig, Wolfgang; Marz, Winfried; Meigs, James B.; Melander, Olle; Munroe, Patricia B.; Mitchell, Braxton D.; Bielinski, Susan J.; Rader, Daniel J.; Reilly, Muredach P.; Rich, Stephen S.; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schadt, Eric E.; Shuldiner, Alan R.; Silverstein, Roy; Kottke-Marchant, Kandice; Talmud, Philippa J.; Watkins, Hugh; Asselbergs, Folkert W.; de Bakker, Paul I.W.; McCaffery, Jeanne; Wijmenga, Cisca; Sabatine, Marc S.; Wilson, James G.; Reiner, Alex; Bowden, Donald W.; Hakonarson, Hakon; Siscovick, David S.; Keating, Brendan J.

2012-01-01

294

Distinct transformation tropism exhibited by human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 is the result of postinfection T cell clonal expansion.  

PubMed

Human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 are related but pathogenically distinct viruses. HTLV-1 mainly causes adult T cell leukemia, while HTLV-2 is not associated with leukemia. In vitro, HTLV-1 and HTLV-2 predominantly transform CD4(+) and CD8(+) T cells, respectively: the genetic determinant maps to the viral envelope. Herein, we investigate whether this transformation tropism occurs during initial infection or subsequently during the cellular transformation process. Since most individuals are chronically infected at the time of detection, we utilized an established rabbit model to longitudinally measure the early HTLV-1 and HTLV-2 infection and replication kinetics in purified CD4(+) and CD8(+) T cells. HTLV-1 and HTLV-2 were detected in both CD4(+) and CD8(+) T cells within 1 week postinoculation. In HTLV-1-infected rabbit CD4(+) T cells, proviral burden and tax/rex mRNA expression peaked early, and expression levels were directly proportional to each other. The late expression of the antisense transcript (Hbz or Aph-2) correlated directly with a late proviral burden peak in HTLV-1- or HTLV-2-infected rabbit CD8(+) T cells, respectively. This study provides the first in vivo evidence that these viruses do not exhibit cellular preference during initial infection. We further evaluated the transformation tropism of HTLV-1 and HTLV-2 over a 9-week period using in vitro cell growth/immortalization assays. At the early weeks, both HTLV-1 and HTLV-2 showed proportionate growth of CD4(+) and CD8(+) T cells. However, beyond week 5, the predominance of one particular T cell type emerged, supporting the conclusion that transformation tropism is a postinfection event due to selective clonal expansion over time. PMID:22278223

Kannian, Priya; Yin, Han; Doueiri, Rami; Lairmore, Michael D; Fernandez, Soledad; Green, Patrick L

2012-01-25

295

Distinct Transformation Tropism Exhibited by Human T Lymphotropic Virus Type 1 (HTLV-1) and HTLV-2 Is the Result of Postinfection T Cell Clonal Expansion  

PubMed Central

Human T lymphotropic virus type 1 (HTLV-1) and HTLV-2 are related but pathogenically distinct viruses. HTLV-1 mainly causes adult T cell leukemia, while HTLV-2 is not associated with leukemia. In vitro, HTLV-1 and HTLV-2 predominantly transform CD4+ and CD8+ T cells, respectively: the genetic determinant maps to the viral envelope. Herein, we investigate whether this transformation tropism occurs during initial infection or subsequently during the cellular transformation process. Since most individuals are chronically infected at the time of detection, we utilized an established rabbit model to longitudinally measure the early HTLV-1 and HTLV-2 infection and replication kinetics in purified CD4+ and CD8+ T cells. HTLV-1 and HTLV-2 were detected in both CD4+ and CD8+ T cells within 1 week postinoculation. In HTLV-1-infected rabbit CD4+ T cells, proviral burden and tax/rex mRNA expression peaked early, and expression levels were directly proportional to each other. The late expression of the antisense transcript (Hbz or Aph-2) correlated directly with a late proviral burden peak in HTLV-1- or HTLV-2-infected rabbit CD8+ T cells, respectively. This study provides the first in vivo evidence that these viruses do not exhibit cellular preference during initial infection. We further evaluated the transformation tropism of HTLV-1 and HTLV-2 over a 9-week period using in vitro cell growth/immortalization assays. At the early weeks, both HTLV-1 and HTLV-2 showed proportionate growth of CD4+ and CD8+ T cells. However, beyond week 5, the predominance of one particular T cell type emerged, supporting the conclusion that transformation tropism is a postinfection event due to selective clonal expansion over time.

Kannian, Priya; Yin, Han; Doueiri, Rami; Lairmore, Michael D.; Fernandez, Soledad

2012-01-01

296

Identifying the Influence of Variable Ice Types on Passive and Active Microwave Measurements for the Purpose of SWE Retrieval  

NASA Astrophysics Data System (ADS)

Dual polarized airborne passive microwave (PM) brightness temperatures (Tbs) at 6.9, 19 and 37 GHz H/V and satellite X-band (9.65 GHz VV/VH) active microwave backscatter measurements were combined with coincident in-situ measurements of snow and ice characteristics to determine the potential of unique emission/interaction caused by variable ice properties. Algorithms designed to estimate snow water equivalent (SWE) using the common brightness temperature difference approach (37GHz - 19 GHz) continually underestimate in-situ levels when applied to pure-ice pixels in the Canadian subarctic. Ice thickness measurements were positively correlated with 19 GHz vertically polarised (V pol) passive microwave emissions (R= 0.67), and negatively with 19 GHz horizontally polarised (H pol) emissions (R = -0.79), indicating that surface conditions at the ice/snow interface affect the emissivity at H pol. This study examines the effect of ice types on coincident passive and active microwave measurements for free-floating ice in two lakes (Sitidgi, Husky Lakes). Ice types are delineated using the SAR segmentation program MAGIC (MAp Guided Ice Classification) that has previously been used to characterize sea ice types. Based on output ice types produced by MAGIC, the relationship between active and passive microwave measurements is examined. Output ice classes corresponded well to those measured at coincident in-situ sampling sites. Emissions at 19 GHz H and cross-polarised X-band backscatter (9.65 GHz) increase coincident to ice types that exhibit more scattering potential. Clear ice exhibits the lowest return, followed by a transition zone between clear ice and grey ice. Grey ice exhibits higher returns as a result of the inclusion of spherical air bubbles, followed by rafted ice, which exhibits an excess of scattering potential. Concurrently, transects of dual polarized 6.9 and 19 GHz PM Tbs exhibited a positive relationship with cross-polarized active microwave backscatter (VH) over freshwater ice (Sitidgi Lake) with the highest R coefficient noticed in the H pol for 6.9 and 19 GHz emissions (R = 0.84 and 0.58 respectively). In brackish water, 6.9 and 19 GHz PM Tbs exhibited a negative relationship as a result of a high concentration of bubbles at the ice/water interface, and the incorporation of lossy brine pockets into the ice medium. This study identifies congruency between passive and active microwave measurements over lake ice for the purpose of improving SWE retrieval algorithms. Further quantification of passive microwave emission is needed for unique ice types, however it has been established that cross-polarised X-band backscatter can be utilized as a priori information for spaceborne PM algorithms, providing information on ice type, characteristics (floating, frozen to bed), and the presence of bubbles at the ice/water interface.

Gunn, G. E.; Duguay, C. R.; Derksen, C.

2010-12-01

297

Distinct mechanisms of axonal globule formation in mice expressing human wild type ?-synuclein or dementia with Lewy bodies-linked P123H ss-synuclein  

PubMed Central

Background Axonopathy is critical in the early pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Axonal swellings such as globules and spheroids are a distinct feature of axonopathy and our recent study showed that transgenic (tg) mice expressing DLB-linked P123H ?-synuclein (P123H ?S) were characterized by P123H ?S-immunoreactive axonal swellings (P123H ?S-globules). Therefore, the objectives of this study were to evaluate ?-synuclein (?S)-immunoreactive axonal swellings (?S-globules) in the brains of tg mice expressing human wild-type ?S and to compare them with the globules in P123H ?S tg mice. Results In ?S tg mice, ?S-globules were formed in an age-dependent manner in various brain regions, including the thalamus and basal ganglia. These globules were composed of autophagosome-like membranous structures and were reminiscent of P123H ?S-globules in P123H ?S tg mice. In the ?S-globules, frequent clustering and deformation of mitochondria were observed. These changes were associated with oxidative stress, based on staining of nitrated ?S and 4-hydroxy-2-nonenal (4-HNE). In accord with the absence of mitochondria in the P123H ?S-globules, staining of nitrated ?S and 4-HNE in these globules was weaker than that for ?S-globules. Leucine-rich repeat kinase 2 (LRRK2), the PARK8 of familial PD, was detected exclusively in ?S-globules, suggesting a specific role of this molecule in these globules. Conclusions Lysosomal pathology was similarly observed for both ?S- and P123H ?S-globules, while oxidative stress was associated with the ?S-globules, and to a lesser extent with the P123H ?S-globules. Other pathologies, such as mitochondrial alteration and LRRK2 accumulation, were exclusively detected for ?S-globules. Collectively, both ?S- and P123H ?S-globules were formed through similar but distinct pathogenic mechanisms. Our findings suggest that synuclein family members might contribute to diverse axonal pathologies.

2012-01-01

298

Distribution of calretinin-containing neurons relative to other neurochemically-identified cell types in the medial septum of the rat  

Microsoft Academic Search

The topographic distribution of calretinin-immunoreactive neurons was studied in the medial septum–diagonal band of Broca complex of the rat, in relation to the localization of other neurochemically identified cell groups containing choline acetyltransferase, parvalbumin or calbindin D28k. Double-labelling experiments revealed that these four antigen-containing cells formed distinct dorsoventrally running lamellae overlayed on top of each other similar to onion leaves.

J. KISS; Z Maglóczky; J. SOMOGYI; T. F. FREUND

1997-01-01

299

Genome-wide association study in people of South Asian ancestry identifies six novel susceptibility loci for type 2 diabetes  

PubMed Central

We carried out a genome wide association study of type-2 diabetes (T2D) amongst 20,119 people of South Asian ancestry (5,561 with T2D); we identified 20 independent SNPs associated with T2D at P<10?4 for testing amongst a further 38,568 South Asians (13,170 with T2D). In combined analysis, common genetic variants at six novel loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) were associated with T2D (P=4.1×10?8 to P=1.9×10?11); SNPs at GRB14 were also associated with insulin sensitivity, and at ST6GAL1 and HNF4A with pancreatic beta-cell function respectively. Our findings provide additional insight into mechanisms underlying T2D, and demonstrate the potential for new discovery from genetic association studies in South Asians who have increased susceptibility to T2D.

Kooner, Jaspal S; Saleheen, Danish; Sim, Xueling; Sehmi, Joban; Zhang, Weihua; Frossard, Philippe; Been, Latonya F; Chia, Kee-Seng; Dimas, Antigone S; Hassanali, Neelam; Jafar, Tazeen; Jowett, Jeremy BM; Li, Xinzhing; Radha, Venkatesan; Rees, Simon D; Takeuchi, Fumihiko; Young, Robin; Aung, Tin; Basit, Abdul; Chidambaram, Manickam; Das, Debashish; Grunberg, Elin; Hedman, Asa K; Hydrie, Zafar I; Islam, Muhammed; Khor, Chiea-Chuen; Kowlessur, Sudhir; Kristensen, Malene M; Liju, Samuel; Lim, Wei-Yen; Matthews, David R; Liu, Jianjun; Morris, Andrew P; Nica, Alexandra C; Pinidiyapathirage, Janani M; Prokopenko, Inga; Rasheed, Asif; Samuel, Maria; Shah, Nabi; Shera, A Samad; Small, Kerrin S; Suo, Chen; Wickremasinghe, Ananda R; Wong, Tien Yin; Yang, Mingyu; Zhang, Fan; Abecasis, Goncalo R; Barnett, Anthony H; Caulfield, Mark; Deloukas, Panos; Frayling, Tim; Froguel, Philippe; Kato, Norihiro; Katulanda, Prasad; Kelly, M Ann; Liang, Junbin; Mohan, Viswanathan; Sanghera, Dharambir K; Scott, James; Seielstad, Mark; Zimmet, Paul Z; Elliott, Paul; Teo, Yik Ying; McCarthy, Mark I; Danesh, John; Tai, E Shyong; Chambers, John C

2013-01-01

300

Lipid level and type alter stearoyl CoA desaturase mRNA abundance differently in mice with distinct susceptibilities to diet-influenced diseases.  

PubMed

Chronic diseases develop in susceptible individuals following exposure to environmental conditions including high fat diets. Inbred strains of mice differing in susceptibility to atherosclerosis, diabetes, obesity and certain cancers are models for understanding the genetic basis and molecular mechanisms whereby diet influences these polygenic and multifactorial disorders. Expression sequence tags (EST) and disease quantitative trait loci (QTL) are also being identified with these strains. Reported here are comparisons of food intake, growth, nonfasting serum lipids and expression of mRNA for hepatic apolipoprotein E (ApoE), hepatic stearoyl CoA desaturase (Scd1) and heart lipoprotein lipase (Lpl) in a 2 x 2 x 2 design with C57BL/6J and BALB/cByJ mice fed semipurified diets with 4 or 20% saturated (coconut) or unsaturated (corn) oils for 4 mo. Histological studies of aortas and coronary arteries are also reported for these animals. After 4 mo, BALB/cByJ mice were significantly heavier and had significantly higher total serum cholesterol, HDL cholesterol and triglyceride concentrations in the fed state than C57BL/6J mice. Efficiency of utilizing dietary energy did not differ consistently between strains. Oil level affected serum total cholesterol, triglycerides and HDL cholesterol, which were significantly greater in mice fed high fat diets. Lpl and ApoE mRNA expression levels were not significantly affected by mouse strain, oil source or oil level. Scd1 mRNA expression, however, was significantly higher in C57BL/6J than in BALB/cByJ mice and was lower in all mice fed 20% compared with those fed 4% fat diets. Genes regulated differently by diet among strains with distinct susceptibility to diet-influenced disease may be associated with molecular pathways contributing to incidence or severity. PMID:9109606

Park, E I; Paisley, E A; Mangian, H J; Swartz, D A; Wu, M X; O'Morchoe, P J; Behr, S R; Visek, W J; Kaput, J

1997-04-01

301

A Quantitative Affinity-Profiling System That Reveals Distinct CD4/CCR5 Usage Patterns among Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Strains ?  

PubMed Central

The affinity of human immunodeficiency virus (HIV) envelope for CD4 and CCR5 appears to be associated with aspects of R5 virus (virus using the CCR5 coreceptor) pathogenicity. However, entry efficiency results from complex interactions between the viral envelope glycoprotein and both CD4 and CCR5, which limits attempts to correlate viral pathogenicity with surrogate measures of envelope CD4 and CCR5 affinities. Here, we present a system that provides a quantitative and comprehensive characterization of viral entry efficiency as a direct interdependent function of both CD4 and CCR5 levels. This receptor affinity profiling system also revealed heretofore unappreciated complexities underlying CD4/CCR5 usage. We first developed a dually inducible cell line in which CD4 and CCR5 could be simultaneously and independently regulated within a physiologic range of surface expression. Infection by multiple HIV type 1 (HIV-1) and simian immunodeficiency virus isolates could be examined simultaneously for up to 48 different combinations of CD4/CCR5 expression levels, resulting in a distinct usage pattern for each virus. Thus, each virus generated a unique three-dimensional surface plot in which viral infectivity varied as a function of both CD4 and CCR5 expression. From this functional form, we obtained a sensitivity vector along with corresponding metrics that quantified an isolate's overall efficiency of CD4/CCR5 usage. When applied to viral isolates with well-characterized sensitivities to entry/fusion inhibitors, the vector metrics were able to encapsulate their known biological phenotypes. The application of the vector metrics also indicated that envelopes derived from elite suppressors had overall-reduced entry efficiencies compared to those of envelopes derived from chronically infected viremic progressors. Our affinity-profiling system may help to refine studies of R5 virus tropism and pathogenesis.

Johnston, Samantha. H.; Lobritz, Michael A.; Nguyen, Sandra; Lassen, Kara; Delair, Shirley; Posta, Filippo; Bryson, Yvonne J.; Arts, Eric J.; Chou, Tom; Lee, Benhur

2009-01-01

302

Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis.  

PubMed

IL-13 and IL-4 are central T helper 2 (Th2) cytokines in the immune system and potent activators of inflammatory responses and fibrosis during Th2 inflammation. Recent studies using Il13ra1(-/-) mice have demonstrated a critical role for IL-13 receptor (IL-13R) alpha1 in allergen-induced airway responses. However, these observations require further attention especially because IL-4 can induce similar lung pathology to IL-13, independent of IL-13, and is still present in the allergic lung. Thus, we hypothesized that IL-13Ralpha1 regulates IL-4-induced responses in the lung. To dissect the role of IL-13Ralpha1 and the type I and II IL-4Rs in experimental asthma, we examined lung pathology induced by allergen, IL-4, and IL-13 challenge in Il13ra1(-/-) mice. We report that IL-13Ralpha1 is essential for baseline IgE production, but Th2 and IgE responses to T cell-dependent antigens are IL-13Ralpha1-independent. Furthermore, we demonstrate that increased airway resistance, mucus, TGF-beta, and eotaxin(s) production, but not cellular infiltration, are critically dependent on IL-13Ralpha1. Surprisingly, our results identify a CCR3- and IL-13Ralpha1-independent pathway for lung eosinophilia. Global expression profiling of lungs from mice stimulated with allergen or IL-4 demonstrated that marker genes of alternatively activated macrophages are differentially regulated by the type I and type II IL-4R. Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Ralpha1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R. PMID:18480254

Munitz, A; Brandt, E B; Mingler, M; Finkelman, F D; Rothenberg, M E

2008-05-14

303

Non-susceptibility genes to Bombyx densovirus type 1, Nid-1 and nsd-1, affect distinct steps of the viral infection pathway.  

PubMed

In the silkworm Bombyx mori, densovirus type 1 (BmDNV-1) replicates only in the midgut and causes fatal disease. Resistance to BmDNV-1 is determined by two genes, nsd-1 and Nid-1, respectively. Neither of them has been identified yet. We investigated the viral transcript by RT-PCR in inoculated silkworms carrying different sets of nsd-1 and Nid-1 genotype. BmDNV-1 transcript was not detected in nsd-1-carrying strains irrespective of existence of Nid-1 but clearly detected in strains carrying Nid-1 without nsd-1. The result suggests that nsd-1 blocks early step of infection. On the other hand, Nid-1 does not block cell and nucleus entry and viral transcription in nuclei but blocks later step in the viral infection cycle. PMID:19836396

Kidokoro, Kurako; Ito, Katsuhiko; Ogoyi, Dorington O; Abe, Hiroaki; Mita, Kazuei; Kadono-Okuda, Keiko

2009-10-27

304

A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.  

PubMed

Substantial progress has been made in identification of type 2 diabetes (T2D) risk loci in the past few years, but our understanding of the genetic basis of T2D in ethnically diverse populations remains limited. We performed a genome-wide association study and a replication study in Chinese Hans comprising 8,569 T2D case subjects and 8,923 control subjects in total, from which 10 single nucleotide polymorphisms were selected for further follow-up in a de novo replication sample of 3,410 T2D case and 3,412 control subjects and an in silico replication sample of 6,952 T2D case and 11,865 control subjects. Besides confirming seven established T2D loci (CDKAL1, CDKN2A/B, KCNQ1, CDC123, GLIS3, HNF1B, and DUSP9) at genome-wide significance, we identified two novel T2D loci, including G-protein-coupled receptor kinase 5 (GRK5) (rs10886471: P = 7.1 × 10(-9)) and RASGRP1 (rs7403531: P = 3.9 × 10(-9)), of which the association signal at GRK5 seems to be specific to East Asians. In nondiabetic individuals, the T2D risk-increasing allele of RASGRP1-rs7403531 was also associated with higher HbA(1c) and lower homeostasis model assessment of ?-cell function (P = 0.03 and 0.0209, respectively), whereas the T2D risk-increasing allele of GRK5-rs10886471 was also associated with higher fasting insulin (P = 0.0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. PMID:22961080

Li, Huaixing; Gan, Wei; Lu, Ling; Dong, Xiao; Han, Xueyao; Hu, Cheng; Yang, Zhen; Sun, Liang; Bao, Wei; Li, Pengtao; He, Meian; Sun, Liangdan; Wang, Yiqin; Zhu, Jingwen; Ning, Qianqian; Tang, Yong; Zhang, Rong; Wen, Jie; Wang, Di; Zhu, Xilin; Guo, Kunquan; Zuo, Xianbo; Guo, Xiaohui; Yang, Handong; Zhou, Xianghai; Zhang, Xuejun; Qi, Lu; Loos, Ruth J F; Hu, Frank B; Wu, Tangchun; Liu, Ying; Liu, Liegang; Yang, Ze; Hu, Renming; Jia, Weiping; Ji, Linong; Li, Yixue; Lin, Xu

2012-09-06

305

Identifying harms.  

PubMed

Moral disagreements often revolve around the issue of harm to others. Identifying harms, however, is a contested enterprise. This paper provides a conceptual toolbox for identifying harms, and so possible wrongdoing, by drawing several distinctions. First, I distinguish between four modes of human vulnerability, forming four ways in which one can be in a harmed state. Second, I argue for the intrinsic disvalue of harm and so distinguish the presence of harm from the fact that it is instrumental to or constitutive of a valued act, practice or way of life. Finally, I distinguish between harm and wrongdoing, arguing that while harm is a normative concept requiring justification, not all harmed states are automatically unjustified. The advantage of this view is that it refocuses the moral debate on the normative issues involved while establishing a common basis to which both sides can agree: the presence of harm to others. PMID:21434956

Harrosh, Shlomit

2011-03-25

306

Distinct Roles of Lymphotoxin ? and the Type I Tumor Necrosis Factor (TNF) Receptor in the Establishment of Follicular Dendritic Cells from Non-Bone Marrow-derived Cells  

PubMed Central

In mice deficient in either lymphotoxin ? (LT-?) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen. We investigated the role of LT-? and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LT-?–deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-?–expressing cells required to establish organized FDC are derived from BM. The role of LT-? in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)–deficient BM cells into LT-?–deficient mice. Organized FDC were identified with both the FDC-M1 and anti-CR1 monoclonal antibodies in these BM-chimeric mice, indicating that these cells were derived from the LT-?–deficient recipient. Thus, expression of LT-? in the BM-derived cells, but not in the non–BM-derived cells, is required for the maturation of FDC from non-BM precursor cells. In contrast, when TNFR-I–deficient mice were reconstituted with wild-type BM, they showed no detectable FDC clusters or GC formation. This indicates that TNFR-I expression on non–BM-derived cellular components is necessary for the establishment of these lymphoid structures. TNFR-I–deficient BM was able to restore FDC organization and GC formation in LT-?–deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM-derived cells. The data in this study demonstrate that FDC organization and GC formation are controlled by both LT-?–expressing BM-derived cells and by TNFR-I-expressing non–BM-derived cells.

Matsumoto, Mitsuru; Fu, Yang-Xin; Molina, Hector; Huang, Guangming; Kim, Jinho; Thomas, Dori A.; Nahm, Moon H.; Chaplin, David D.

1997-01-01

307

Two Distinct Antigenic Types of the Polysaccharide Chains of Helicobacter pylori Lipopolysaccharides Characterized by Reactivity with Sera from Humans with Natural Infection  

PubMed Central

We have purified lipopolysaccharides (LPS) from 10 Helicobacter pylori clinical isolates which were selected on the basis of chemotype and antigenic variation. Data from immunoblotting of the purified LPS with sera from humans with H. pylori infection and from absorption of the sera with LPS indicated the presence of two distinct epitopes, termed the highly antigenic and the weakly antigenic epitopes, on the polysaccharide chains. Among 68 H. pylori clinical isolates, all smooth strains possessed either epitope; the epitopes were each carried by about 50% of the smooth strains. Thus, H. pylori strains can be classified into three types on the basis of their antigenicity in humans: those with smooth LPS carrying the highly antigenic epitope, those with smooth LPS carrying the weakly antigenic epitope, and those with rough LPS. Sera from humans with H. pylori infection could be grouped into three categories: those containing immunoglobulin G (IgG) antibodies against the highly antigenic epitope, those containing IgG against the weakly antigenic epitope, and those containing both specific IgGs; these groups made up about 50%, less than 10%, and about 40%, respectively, of all infected sera tested. In other words, IgG against the highly antigenic epitope were detected in more than 90% of H. pylori-infected individuals with high titers. IgG against the weakly antigenic epitope were detected in about 50% of the sera tested; however, the antibody titers were low. The two human epitopes existed independently from the mimic structures of Lewis antigens, which are known to be an important epitope of H. pylori LPS. No significant relationship between the reactivities toward purified LPS of human sera and a panel of anti-Lewis antigen antibodies was found. Moreover, the reactivities of the anti-Lewis antigen antibodies, but not human sera, were sensitive to particular ?-l-fucosidases. The human epitopes appeared to be located on O-polysaccharide chains containing endo-?-galactosidase-sensitive galactose residues as the backbone. Data from chemical analyses indicated that all LPS commonly contained galactose, glucosamine, glucose, and fucose (except one rough strain) as probable polysaccharide components, together with typical components of inner core and lipid A. We were not able to distinguish between the differences of antigenicity in humans by on the basis of the chemical composition of the LPS.

Yokota, Shin-Ichi; Amano, Ken-Ichi; Shibata, Yoshiko; Nakajima, Mizuho; Suzuki, Miyuki; Hayashi, Shunji; Fujii, Nobuhiro; Yokochi, Takashi

2000-01-01

308

Complexes between tissue-type plasminogen activator and proteinase inhibitors in human plasma, identified with an immunoradiometric assay  

SciTech Connect

Extrinsic (tissue-type) plasminogen activator antigen in human plasma, as measured by a two-site immunoradiometric assay, is composed of a fibrin-adsorbable and a nonadsorbable fraction. Gel filtration on Ultrogel AcA 44 in 1.6M KSCN of the fibrin-adsorbable fraction showed a peak with M/sub r/ approx. =70,000, which contained plasminogen activator activity and was assumed to represent free extrinsic plasminogen activator. The nonadsorbable fraction showed a broad peak with M/sub r/ approx. =140,000 without plasminogen activator activity. Overnight incubation at 37/sup 0/C of postexercise plasma revealed a shift of the M/sub r/ approx. =70,000 peak to the M/sub r/ approx. =140,000 position, suggesting that the M/sub r/ approx. =140,000 peak consists of extrinsic plasminogen activator-protease inhibitor complex(es). ..cap alpha../sub 2/-Antiplasmin is the main inhibitor of extrinsic plasminogen activator in plasma and is probably responsible for the generation of the M/sub r/ approx. =140,000 component. A possible involvement of other plasma proteinase inhibitors was explored by incubation of /sup 125/I-labeled extrinsic plasminogen activator in ..cap alpha../sub 2/-antiplasmin-depleted plasma. A complex was formed with a t1/2 of about 1 hr, which was identified by immunoprecipitation as extrinsic plasminogen activator-..cap alpha../sub 2/-antiplasmin complex. Additional evidence for the presence of extrinsic plasminogen activator complexes with ..cap alpha../sub 2/-antiplasmin and ..cap alpha../sub 1/-antitrypsin in plasma was obtained from two-site immunoradiometric assays. It was concluded that plasma contains both free extrinsic plasminogen activator and plasminogen activator complexes with ..cap alpha../sub 2/-antiplasmin and ..cap alpha../sub 1/-antitrypsin. These complexes are also present in plasma collected on the active site inhibitor, D-Phe-Pro-Arg-CH/sub 2/Cl, at rest and after exercise and are therefore assumed to circulate in vivo. (JMT)

Rijken, D.C. (Univ. of Leuven, Belgium); Juhan-Vague, I.; Collen, D.

1983-02-01

309

High frequency of abnormal glucose tolerance in DQA1 * 0102\\/DQB1 * 0602 relatives identified as part of the Diabetes Prevention Trial—Type 1 Diabetes  

Microsoft Academic Search

Aims\\/hypothesis  Immunological and genetic markers can be used to assess risk of developing type 1 diabetes prior to the onset of clinical symptoms. Autoantibody-positive relatives of patients with type 1 diabetes are at increased risk for disease, while the presence of HLA DQA1*0102\\/DQB1*0602 is thought to confer protection. Using the unique population identified by the Diabetes Prevention Trial—Type Diabetes (DPT-1), our

C. J. Greenbaum; G. Eisenbarth; M. Atkinson; L. Yu; S. Babu; D. Schatz; A. Zeidler; T. Orban; C. Wasserfall; D. Cuthbertson; J. Krischer

2005-01-01

310

Axon contacts and acetylcholinesterase activity on chicken intrafusal muscle fiber types identified by their myosin heavy chain composition  

Microsoft Academic Search

Summary Muscle spindles of 8-week old chicken tibialis anterior muscles were examined to determine if specific intrafusal fiber types were also characterized by differences in motor innervation. Incubation with a monoclonal antibody against myosin heavy chains permitted the identification of strongly reactive, moderately reactive and unreactive intrafusal fibers. The innervation of each fiber type was evaluated in silver-impregnated sections, and

Alfred Maier

1991-01-01

311

Computer-aided design of chiral ligands. Part I. Database search methods to identify chiral ligand types for asymmetric reactions.  

PubMed

The utility of database searching to identify chiral ligand motifs is outlined. The key elements of three known chiral ligands have been described as bond vectors. The CAVEAT program was then used to screen the Cambridge Structural Database (CSD), portions of the Chemical Abstracts Services three-dimensional database (CAS-3D), and the TRIAD tricyclic structure database for scaffolds containing these elements. Scaffolds corresponding to the known starting points were identified indicating that this method can be used to identify chiral ligand structural motifs. In addition, alternate structural motifs were found that suggested alternative possible ligands. PMID:11885961

Kozlowski, Marisa C; Panda, Manoranjan

2002-03-01

312

Characterizing the successful student in general chemistry and physical science classes in terms of Jung's personality types as identified by the Myers-Briggs Type Indicator  

Microsoft Academic Search

A student's success in a science class can depend upon previous experiences, motivation, and the level of interest in the subject. Since psychological type is intrinsic to a person's whole being, it can be influential upon the student's motivation and interests. Thus, a study of student psychological types versus the level of success in a class, as measured by a

Wayne David Riley

1998-01-01

313

Follow-up analysis of genome-wide association data identifies novel loci for type 1 diabetes  

Microsoft Academic Search

OBJECTIVE: Two recent genome-wide association (GWA) studies have revealed novel loci for type 1 diabetes, a common multifactorial disease with a strong genetic component. To fully utilize the GWA data that we had obtained by genotyping 563 type 1 diabetes probands and 1,146 control subjects, as well as 483 case subject-parent trios, using the Illumina HumanHap550 BeadChip, we designed a

S. F. Grant; H. Q. Qu; J. P. Bradfield; L. Marchand; C. E. Kim; J. T. Glessner; R. Grabs; S. P. Taback; E. C. Frackelton; A. W. Eckert; K. Annaiah; M. L. Lawson; F. G. Otieno; E. Santa; J. L. Shaner; R. M. Smith; R. Skraban; M. Imielinski; R. M. Chiavacci; R. W. Grundmeier; C. A. Stanley; S. E. Kirsch; D. Waggott; A. D. Paterson; D. S. Monos; C. Polychronakos; H. Hakonarson

2009-01-01

314

Flanking proline residues identify the L-type Ca2+ channel binding site of calciseptine and FS2.  

PubMed

Calciseptine and FS2 are 60-amino acid polypeptides, isolated from venom of the black mamba (Dendroaspis polylepis polylepis), that block voltage-dependent L-type Ca2+ channels. We predicted that these polypeptides contain an identical functional site between residues 43 and 46 by searching for proline residues that mark the flanks of protein-protein interaction sites [Kini, R. M., and Evans, H. J. (1966) FEBS Lett. 385, 81-86]. The predicted Ca2+ channel binding site also occurs in closely related toxins, C10S2C2 and S4C8. Therefore, it is likely that these toxins also will block L-type Ca2+ channels. To test the proposed binding site on calciseptine and FS2, an eight-residue peptide, named L-calchin (L-type calcium channel inhibitor), was synthesized and examined for biological activity. As expected for an L-type Ca2+ channel blocker, L-calchin reduced peak systolic and developed pressure in isolated rat heart Langendorff preparations without affecting diastolic pressure or heart rate. Furthermore, L-calchin caused a voltage-independent block of L-type Ca2+ channel currents in whole-cell patch-clamped rabbit ventricular myocytes. Thus the synthetic peptide exhibits the L-type Ca2+ channel blocking properties of the parent molecules, calciseptine and FS2, but with a lower potency. These results strongly support the identification of a site in calciseptine and FS2 that is important for binding to L-type Ca2+ channels and reinforce the importance of proline brackets flanking protein-protein interaction sites. PMID:9636051

Kini, R M; Caldwell, R A; Wu, Q Y; Baumgarten, C M; Feher, J J; Evans, H J

1998-06-23

315

Rate of leaf expansion: A criterion for identifying oil palm ( Elaeis guineensis Jacq.) types suitable for planting at high densities  

Microsoft Academic Search

The aim of the present study, carried out in South Sumatra under conditions of high solar radiation and a rainfall of about 2500mm per year, was to identify oil palm material suitable for planting at high densities. To that end, we monitored leaf expansion of tenera progenies descending from the pisifera male parent origins Ekona, Nigeria and Calabar, by fitting

C. J. Breure

2010-01-01

316

Tumour-related enzyme alterations in the clear cell type of human renal cell carcinoma identified by two-dimensional gel electrophoresis.  

PubMed

To identify tumour-related enzyme alterations we have used 2D-gels to analyse the proteome from dissected malignant and benign kidney areas from patients with clear-cell-type renal carcinoma. The expression of 12 proteins was diminished in tumour. Four proteins were characterized by mass spectrometry and were identified as enoyl-CoA hydratase, alpha-glycerol-3-phosphate dehydrogenase, aldehyde dehydrogenase 1 and aminoacylase-I. PMID:11722587

Balabanov, S; Zimmermann, U; Protzel, C; Scharf, C; Klebingat, K J; Walther, R

2001-11-01

317

The ability of quantitative ultrasound at the calcaneus to identify postmenopausal women with different types of nontraumatic fractures  

Microsoft Academic Search

The aim of the cross-sectional study was to determine if ultrasound (US) measurements of the calcaneus have the ability to predict the risk for fractures and to discriminate between postmenopausal women with and without different types of nontraumatic fractures. All women (n = 1129, age range 40 to 87 years) were divided into group 1, created by 656 women with

Bogna Drozdzowska; Wojciech Pluskiewicz

2002-01-01

318

A mutation unique in serine protease inhibitors (serpins) identified in a family with type II hereditary angioneurotic edema.  

PubMed Central

BACKGROUND: Hereditary angioneurotic edema (HANE) is an autosomal dominant disease due to genetic alterations at the C1 inhibitor gene. Mutations within the C1 inhibitor gene are responsible for the molecular defect in type II HANE. Most of the dysfunctional proteins result from mutations involving the Arg-444 (the P-1 site of the reactive center) or amino acids NH2-terminal to the reactive center. MATERIALS AND METHODS: We have studied a Spanish family with type II HANE by using polymerase chain reaction (PCR) to amplify the exon eight of the C1 inhibitor gene. The purified 338-bp PCR product was subcloned and transformed into competent cells. After overnight cultures, we extracted the cloning vector from the positive colonies and sequenced both strands of the PCR product from each patient and healthy members of the family. RESULTS: We show that affected individuals in this family have a missense mutation, changing an adenine to cytosine in the codon 445. This substitution changes threonine at the P-1' site of the reactive center to a proline. This mutation generates a new restriction site, recognized by Bsi YI. CONCLUSIONS: To our knowledge, this is the first molecular defect characterized in a Spanish family with type II HANE, and to date, this is the first reported mutation at the P-1' site of the reactive center in individuals with type II HANE. This new mutation located at the reactive center emphasizes once more time the enormous heterogeneity of this gene. Images FIG. 1 FIG. 2 FIG. 3

Ocejo-Vinyals, J. G.; Leyva-CobiA?n, F.; FernA?ndez-Luna, J. L.

1995-01-01

319

Identifying different types of de-differentiated microspores from indica-japonica F 1 hybrids with subspecies-differentiating RFLP probes in rice  

Microsoft Academic Search

The indica, japonica and intermediary types of de-differentiated microspores from indica-japonica F1 hybrids were identified with 11 subspecies-differentiating RELP probes in rice (Oryza sativa L.). The results showed that the distribution of indica, japonica and intermediary types of de-differentiated microspores could be easily detected in a simple and quick way using the RFLP\\u000a method. Moreover, the microspores from the same

J.-H. Xie; M.-W. Gao; J. Lu; J.-Y. Zhuang; H.-X. Lin; H.-R. Qian; K.-L. Zheng

1997-01-01

320

Inhibitors of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] identified by in silico molecular docking.  

PubMed

AAC(6')-Ib is an important aminoglycoside resistance enzyme to target with enzymatic inhibitors. An in silico screening approach was used to identify potential inhibitors from the ChemBridge library. Several compounds were identified, of which two of them, 4-[(2-{[1-(3-methylphenyl)-4,6-dioxo-2-thioxotetrahydro-5(2H)-pyrimidinylidene]methyl}phenoxy)methyl]benzoic acid and 2-{5-[(4,6-dioxo-1,3-diphenyl-2-thioxotetrahydro-5(2H)-pyrimidinylidene)methyl]-2-furyl}benzoic acid, showed micromolar activity in inhibiting acetylation of kanamycin A. These compounds are predicted to bind the aminoglycoside binding site of AAC(6')-Ib and exhibited competitive inhibition against kanamycin A. PMID:24011645

Lin, David L; Tran, Tung; Adams, Christina; Alam, Jamal Y; Herron, Steven R; Tolmasky, Marcelo E

2013-08-12

321

The social construction of ability and disability: I. Profile types of Latino children identified as language learning disabled.  

PubMed

During the course of an ethnographic study of a bilingual special education classroom, three profile types of students emerged, ranging from students with severe language learning disabilities to students with normal abilities. The study points out the inadequacy of a medical model view of student abilities and disabilities--a view that underestimates the communicative and academic competence of bilingual students. Concurrently, the results support a contextual performance view--a view that acknowledges the role of instructional context in revealing the upper or lower range of students' communicative and academic competence. The study further suggests some contextual features of instruction that are associated with students from all profile types showing their best in terms of language and literacy skills. PMID:7595039

Ruiz, N T

1995-10-01

322

71 A genome-wide association study in Indian Asians identifies four susceptibility loci for type-2 diabetes  

Microsoft Academic Search

BackgroundType-2 diabetes (T2D) is a major risk factor for cardiovascular disease, and a leading causing of mortality worldwide. T2D is 2–4 fold more common among Indian Asians than Europeans, and contributes to higher cardiovascular disease mortality in Asians. Little is known of the genetic basis of T2D in Indian Asians.MethodsWe carried out a genome-wide association (GWA) study of T2D in

J Sehmi; D Salaheen; Y Yeo; W Zhang; D Das; M I McCarthy; E S Tai; J Danesh; J Kooner; J Chambers

2011-01-01

323

A single-gene biomarker identifies breast cancers associated with immature cell type and short duration of prior breastfeeding  

Microsoft Academic Search

The pathogenesis of breast cancers that do not express estrogen receptors or Her-2\\/neu receptors (ERx\\/HER2x phenotype) is incompletely understood. We had observed markedly elevated gene expression of gamma-aminobutyric acid type A (GABAA) receptor subunit p (GABAp, GABRP) in some breast cancers with ERx\\/HER2x phenotype. In this study, transcriptional profiles (TxPs) were obtained from 82 primary invasive breast cancers by oligonucleotide

W F Symmans; D J Fiterman; S K Anderson; M Ayers; R Rouzier; V Dunmire; J Stec; V Valero; N Sneige; C Albarracin; J S Ross; P Wagner; R L Theriault; B Arun; H Kuerer; K R Hess; W Zhang; G N Hortobagyi; L Pusztai

2005-01-01

324

Mutation analysis of peroxisome proliferator-activated receptor-? coactivator-1 (PGC1) and relationships of identified amino acid polymorphisms to Type II diabetes mellitus  

Microsoft Academic Search

.\\u000a Aim\\/hypothesis:   This study aimed to investigate if variability in the peroxisome proliferator-activated receptor-? coactivator-1 (PGC-1) gene is associated with Type II (non-insulin-dependent) diabetes mellitus. \\u000a \\u000a \\u000a \\u000a Methods:   The PGC-1 gene was examined in 53 Type II diabetic patients applying single strand conformational polymorphism analysis followed by\\u000a nucleotide sequencing. Identified variants were genotyped in an association study comprising 483 Type II diabetic

J. Ek; G. Andersen; S. A. Urhammer; P. H. Gæde; T. Drivsholm; K. Borch-Johnsen; T. Hansen; O. Pedersen

2001-01-01

325

Comparison of B-type natriuretic peptide assays for identifying heart failure in stable elderly patients with a clinical diagnosis of chronic obstructive pulmonary disease  

Microsoft Academic Search

Aims: To compare the ability of different B-type natriuretic peptide (BNP) assays to identify heart failure in stable elderly patients with a diagnosis of chronic obstructive pulmonary disease (COPD). Methods: 200 patients aged ?65 years with COPD according to their general practitioner and without known heart failure, underwent a diagnostic work-up. The final diagnosis of heart failure was established by

Frans H. Rutten; Maarten-Jan M. Cramer; Nicolaas P. A. Zuithoff; Jan-Willem J. Lammers; Wim Verweij; Diederick E. Grobbee; Arno W. Hoes

2007-01-01

326

Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci  

Microsoft Academic Search

We carried out a meta-analysis of data from three genome-wide association (GWA) studies of type 1 diabetes (T1D), testing 305,090 SNPs in 3,561 T1D cases and 4,646 controls of European ancestry. We obtained further support for 4q27 (IL2-IL21, P = 1.9 × 10?8) and, after genotyping an additional 6,225 cases, 6,946 controls and 2,828 families, convincing evidence for four previously

Deborah J Smyth; Adam M Smiles; Vincent Plagnol; Neil M Walker; James E Allen; Kate Downes; Jeffrey C Barrett; Barry C Healy; Josyf C Mychaleckyj; James H Warram; John A Todd; Jason D Cooper

2008-01-01

327

A novel means of identifying the neuraminidase type of currently circulating human A(H1) influenza viruses  

Microsoft Academic Search

With the recent emergence and spread of influenza A(H1N2) viruses which appear to have arisen by reassortment of circulating A(H1N1) and A(H3N2) strains, there is a need in epidemiological studies to determine the neuraminidase type in order to differentiate between influenza A(H1N2) and A(H1N1) strains. A fluorescence-based neuraminidase enzyme inhibition assay that has been developed to screen influenza viruses for

Aeron C Hurt; Ian G Barr; Naomi Komadina; Alan W Hampson

2004-01-01

328

A novel means of identifying the neuraminidase type of currently circulating human A(H1) influenza viruses.  

PubMed

With the recent emergence and spread of influenza A(H1N2) viruses which appear to have arisen by reassortment of circulating A(H1N1) and A(H3N2) strains, there is a need in epidemiological studies to determine the neuraminidase type in order to differentiate between influenza A(H1N2) and A(H1N1) strains. A fluorescence-based neuraminidase enzyme inhibition assay that has been developed to screen influenza viruses for potential resistance to the neuraminidase inhibitor drugs appears to be suitable for this purpose. When used with the neuraminidase inhibitor zanamivir the assay was able to provide a positive predictive value of 93.5% for the identification of neuraminidase type N1 or N2. This assay enables a large number of influenza A viruses to be screened at low cost to determine relative levels of A(H1N2) or A(H1N1) viruses circulating in the population. PMID:15163493

Hurt, Aeron C; Barr, Ian G; Komadina, Naomi; Hampson, Alan W

2004-07-01

329

Inactive proenzyme to tissue-type plasminogen activator from human melanoma cells, identified after affinity purification with a monoclonal antibody.  

PubMed Central

The human 66 000 mol. wt. plasminogen activator (HPA66; tissue-type plasminogen activator) has been purified from melanoma cells by a one-step affinity method with a monoclonal antibody. HPA66 purified in this way consists mainly of a one-polypeptide chain form with small amounts (15%) of a form containing two polypeptide chains held together by one or more disulphide bridges. The one-chain form was converted to the two-chain form by catalytic amounts of plasmin. During the conversion, the enzyme activity of HPA66, as measured by an [125I]plasminogen conversion assay and with a chromogenic substrate, increased linearly with the percentage of the two-chain form. A linear regression analysis showed that all enzyme activity could be accounted for by the two-chain form, while the one-chain form had no measurable enzyme activity (detection limit approximately 5% of the activity of the two-chain form). Together with previous findings of inactive proenzymes to murine and human approximately 50 000 mol. wt. (urokinase-type) plasminogen activators, these findings indicate that plasminogen activators are generally formed from inactive one-chain proenzymes which are converted to active two-chain enzymes by limited proteolysis, thus demonstrating a third step in a cascade reaction leading to extracellular proteolysis. Images Fig. 1.

Andreasen, P A; Nielsen, L S; Gr?ndahl-Hansen, J; Skriver, L; Zeuthen, J; Stephens, R W; Dan?, K

1984-01-01

330

Two progressive substrates of the M-intermediate can be identified in glucose-embedded, wild-type bacteriorhodopsin.  

PubMed Central

Glucose-embedded bacteriorhodopsin shows M-intermediates with different Amide I infrared bands when samples are illuminated at 240 or 260 K, in contrast with fully hydrated samples where a single M-intermediate is formed at all temperatures. In hydrated, but not in glucose-embedded specimens, the N intermediate is formed together with M at 260 K. Both Fourier transform infrared and electron diffraction data from glucose-embedded bacteriorhodopsin suggest that at 260 K a mixture is formed of the M-state that is trapped at 240 K, and a different M-intermediate (MN) that is also formed by mutant forms of bacteriorhodopsin that lack a carboxyl group at the 96 position, necessary for the M to N transition. The fact that an MN species is trapped in glucose-embedded, wild-type bacteriorhodopsin suggests that the glucose samples lack functionally important water molecules that are needed for the proton transfer aspartate 96 to the Schiff base (and, thus, to form the N-intermediate); thus, aspartate 96 is rendered ineffective as a proton donor.

Vonck, J; Han, B G; Burkard, F; Perkins, G A; Glaeser, R M

1994-01-01

331

Human CD25 ? CD4 ? T Suppressor Cell Clones Produce Transforming Growth Factor ? , but not Interleukin 10, and Are Distinct from Type 1 T Regulatory Cells  

Microsoft Academic Search

T regulatory (Tr) cells are essential for the induction of peripheral tolerance. Several types of Tr cells exist, including CD4 ? T cells which express CD25 constitutively and suppress immune responses via direct cell-to-cell interactions, and type 1 T regulatory (Tr1) cells, which function via secretion of interleukin (IL)-10 and transforming growth factor (TGF)- ? . The relationship between CD25

Megan K. Levings; Romina Sangregorio; Claudia Sartirana; Anna Lisa Moschin; Manuela Battaglia; Paul C. Orban

332

VPS9a, the common activator for two distinct types of Rab5 GTPases, is essential for the development of Arabidopsis thaliana.  

PubMed

Rab5, a subfamily of Rab GTPases, regulates a variety of endosomal functions as a molecular switch. Arabidopsis thaliana has two different types of Rab5-member GTPases: conventional type, ARA7 and RHA1, and a plant-specific type, ARA6. We found that only one guanine nucleotide exchange factor (GEF), named VPS9a, can activate all Rab5 members to GTP-bound forms in vitro in spite of their diverged structures. In the vps9a-1 mutant, whose GEF activity is completely lost, embryogenesis was arrested at the torpedo stage. Green fluorescent protein (GFP)-ARA7 and ARA6-GFP were diffused in cytosol like GDP-fixed mutants of Rab5 in vps9a-1, indicating that both types of GTPase are regulated by VPS9a. In the leaky vps9a-2 mutant, elongation of the primary root was severely affected. Overexpression of the GTP-fixed form of ARA7 suppressed the vps9a-2 mutation, but overexpression of ARA6 had no apparent effects. These results indicate that the two types of plant Rab5 members are functionally differentiated, even though they are regulated by the same activator, VPS9a. PMID:18055610

Goh, Tatsuaki; Uchida, Wakana; Arakawa, Satoko; Ito, Emi; Dainobu, Tomoko; Ebine, Kazuo; Takeuchi, Masaki; Sato, Ken; Ueda, Takashi; Nakano, Akihiko

2007-11-30

333

Distinctive Qualities of Expert Teachers  

ERIC Educational Resources Information Center

|This paper attempts to identify the distinctive qualities of successful veteran teachers, referred to as "expert teachers", which separates them not only from novice teachers but more importantly from experienced non-expert teachers. Based on earlier case studies, this paper maintains that the critical differences between expert and non-expert…

Tsui, Amy B. M.

2009-01-01

334

Distinctive qualities of expert teachers  

Microsoft Academic Search

This paper attempts to identify the distinctive qualities of successful veteran teachers, referred to as “expert teachers”, which separates them not only from novice teachers but more importantly from experienced non?expert teachers. Based on earlier case studies, this paper maintains that the critical differences between expert and non?expert teachers are manifested in three dimensions: their ability to integrate aspects of

Amy B. M. Tsui

2009-01-01

335

The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B cells.  

PubMed

Primary central nervous system lymphoma (PCNSL) is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood. In an attempt to clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL (26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations of BCL-6 5' noncoding regions, which are regarded as a marker of B-cell transition through the germinal center (GC). Expression of BCL-6 protein, which is restricted to GC B cells throughout physiologic B-cell maturation, was detected in 100% AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All but one PCNSL expressed hMSH2, which among mature B cells selectively stains GC B cells. These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6, LMP-1, and BCL-2. BCL-6(+)/LMP-1(-)/BCL-2(-) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology. Conversely, BCL-6(-)/LMP-1(+)/BCL-2(+) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features. These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas. PMID:9680371

Larocca, L M; Capello, D; Rinelli, A; Nori, S; Antinori, A; Gloghini, A; Cingolani, A; Migliazza, A; Saglio, G; Cammilleri-Broet, S; Raphael, M; Carbone, A; Gaidano, G

1998-08-01

336

Dominance of autoreactive T cell-mediated delayed-type hypersensitivity or antibody-mediated demyelination results in distinct forms of experimental autoimmune neuritis in the Lewis rat.  

PubMed

The role of anti-myelin antibodies in the pathogenesis of experimental autoimmune neuritis (EAN) induced in the Lewis rat by immunization with peripheral nerve myelin has been assessed. Passive transfer with lymph node cells (LNC) or purified serum immunoglobulin from rats with EAN was employed to directly measure the contribution of B cells and anti-myelin antibodies to demyelination and disease. Lewis rats with EAN transferred by LNC or purified serum immunoglobulin from EAN donors in conjunction with a low dose of P2-specific CD4+ T cells demonstrated profound histopathological and neurophysiological evidence of demyelination during disease. In contrast, the classical adoptive transfer model of EAN in the Lewis rat induced by the injection of P2-specific CD4+ T cells was characterized by histopathological and neurophysiological evidence of axonal dysfunction and degeneration with limited demyelination. These findings demonstrate that the synergistic action of T cells and anti-myelin antibodies mediating demyelination or purely T cell mediated axonal dysfunction and degeneration are distinct pathways by which a specific autoimmune response in the peripheral nervous system can cause neurological disease. PMID:11398840

Taylor, J M; Pollard, J D

2001-06-01

337

Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases  

PubMed Central

Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m2) compared to obese cases (BMI?30 Kg/m2). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m2) or 4,123 obese cases (BMI?30 kg/m2), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P?=?8.4×10?9, OR?=?1.13 [95% CI 1.09–1.18]), and this association was stronger than that in obese cases (P?=?0.04, OR?=?1.03 [95% CI 1.00–1.06]). A variant in HMG20A—previously identified in South Asians but not Europeans—was associated with type 2 diabetes in obese cases (P?=?1.3×10?8, OR?=?1.11 [95% CI 1.07–1.15]), although this association was not significantly stronger than that in lean cases (P?=?0.02, OR?=?1.09 [95% CI 1.02–1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P?=?0.0002). In the lean analysis, we observed a weighted per-risk allele OR?=?1.13 [95% CI 1.10–1.17], P?=?3.2×10?14. This was larger than the same model fitted in the obese analysis where the OR?=?1.06 [95% CI 1.05–1.08], P?=?2.2×10?16. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes.

Perry, John R. B.; Voight, Benjamin F.; Yengo, Loic; Amin, Najaf; Dupuis, Josee; Ganser, Martha; Grallert, Harald; Navarro, Pau; Li, Man; Qi, Lu; Steinthorsdottir, Valgerdur; Scott, Robert A.; Almgren, Peter; Arking, Dan E.; Aulchenko, Yurii; Balkau, Beverley; Benediktsson, Rafn; Bergman, Richard N.; Boerwinkle, Eric; Bonnycastle, Lori; Burtt, Noel P.; Campbell, Harry; Charpentier, Guillaume; Collins, Francis S.; Gieger, Christian; Green, Todd; Hadjadj, Samy; Hattersley, Andrew T.; Herder, Christian; Hofman, Albert; Johnson, Andrew D.; Kottgen, Anna; Kraft, Peter; Labrune, Yann; Langenberg, Claudia; Manning, Alisa K.; Mohlke, Karen L.; Morris, Andrew P.; Oostra, Ben; Pankow, James; Petersen, Ann-Kristin; Pramstaller, Peter P.; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, William; Roden, Michael; Rudan, Igor; Rybin, Denis; Scott, Laura J.; Sigurdsson, Gunnar; Sladek, Rob; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Vivequin, Sidonie; Weedon, Michael N.; Wright, Alan F.; Hu, Frank B.; Illig, Thomas; Kao, Linda; Meigs, James B.; Wilson, James F.; Stefansson, Kari; van Duijn, Cornelia; Altschuler, David; Morris, Andrew D.; Boehnke, Michael; McCarthy, Mark I.; Froguel, Philippe; Palmer, Colin N. A.; Wareham, Nicholas J.; Groop, Leif

2012-01-01

338

Angiocentric cutaneous T-cell lymphoma of childhood (hydroa-like lymphoma): A distinctive type of cutaneous T-cell lymphoma  

Microsoft Academic Search

Background: Angiocentric cutaneous T-cell lymphomas of childhood (ACTCLC) are an unusual type of T-cell lymphomas that present with a vesiculopapular eruption mimicking hydroa vacciniforme. Most patients have been children from Asia and Latin America. Objective: The purpose of this study was to describe four cases of ACTCLC; to discuss its clinical, histopathologic, and immunohistochemical features; to consider its possible relationship

Mario Magaña; Pastor Sangüeza; Javier Gil-Beristain; Sergio Sánchez-Sosa; Angeles Salgado; Guillermo Ramón; Omar P. Sangüeza

1998-01-01

339

FUNCTIONAL EVIDENCE FOR THE EXISTENCE OF A THIRD CELL TYPE IN THE RENAL GLOMERULUS: Phagocytosis of Filtration Residues by a Distinctive \\  

Microsoft Academic Search

Two types of cclls can bc recognized on the luminal side of the glomcrular base- ment membrane: the superficial endothelial cells which directly line the lumen and are comparable to endothclia lining the capillarics of other tissues, and thc deep cells, ordi- narily not in contact with the lumen, which arc distinguishcd by their long cytoplasmic arms cxtending for some

MARILYN G. FARQUHAR; GEORGE E. PALADE

1962-01-01

340

A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I Interferons*  

PubMed Central

Neutrophil-specific genes are abundant in PBMC microarrays from lupus patients due to presence of low density granulocytes (LDGs) in mononuclear cell fractions. The functionality and pathogenicity of these LDGs have not been characterized. We developed a technique to purify LDGs from lupus PBMCs and assessed their phenotype, function and potential role in disease pathogenesis. LDGs, their autologous lupus neutrophils and healthy control neutrophils were compared in their microbicidal and phagocytic capacities, generation of reactive oxygen species, activation status, inflammatory cytokine profile and type I IFN expression and signatures. The capacity of LDGs to kill endothelial cells and their antiangiogenic potential were also assessed. LDGs display an activated phenotype, secrete increased levels of type I IFNs, TNF-? and IFN-?, but show impaired phagocytic potential. LDGs induce significant endothelial cell cytotoxicity and synthesize sufficient levels of type I IFNs to disrupt the capacity of endothelial progenitor cells to differentiate into mature endothelial cells. Further, LDG depletion restores the functional capacity of endothelial progenitor cells. We conclude that lupus LDGs are proinflammatory and display pathogenic features, including the capacity to synthesize type I IFNs. They may play an important dual role in premature cardiovascular disease development in SLE by simultaneously mediating enhanced vascular damage while inhibiting vascular repair.

Denny, Michael F.; Yalavarthi, Srilakshmi; Zhao, Wenpu; Thacker, Seth G.; Anderson, Marc; Sandy, Ashley R.; McCune, W. Joseph; Kaplan, Mariana J.

2010-01-01

341

Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain  

Microsoft Academic Search

The cannabinoid receptor type 1 (CB1) displays unusual properties, including the dual capacity to inhibit or stimulate adenylate cyclase and a brain density considerably higher than the majority of G protein-coupled receptors. Together with overlapping expression patterns of dopamine and serotonin receptors this suggests a potential of CB1 to modulate the function of the dopamine and serotonin system. Indeed, pharmacological

H Hermann; G Marsicano; B Lutz

2002-01-01

342

Binding and Susceptibility to Postentry Restriction Factors in Monkey Cells Are Specified by Distinct Regions of the Human Immunodeficiency Virus Type 1 Capsid  

Microsoft Academic Search

In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIVmac is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1

Christopher M. Owens; Byeongwoon Song; Michel J. Perron; Peter C. Yang; Matthew Stremlau; Joseph Sodroski

2004-01-01

343

Human immunodeficiency virus type 1 subtypes have a distinct long terminal repeat that determines the replication rate in a host-cell-specific manner  

Microsoft Academic Search

The long terminal repeat (LTR) transcriptional promoters of different human immunodeficiency virus (HIV) type 1 subtypes were inserted into the LAI molecular clone of subtype B. The viral genotypes represent seven subtypes (A, B, C, D, E, F, and G) and one circulating recombinant form (AG). We performed replication studies with this isogenic set of viruses across six cellular environments.

Tim van Opijnen; Rienk E. Jeeninga; Maarten C. Boerlijst; Georgios P. Pollakis; Veera Zetterberg; Mika Salminen; Ben Berkhout

2004-01-01

344

Human Immunodeficiency Virus (HIV) Antibody Avidity Testing To Identify Recent Infection in Newly Diagnosed HIV Type 1 (HIV1)Seropositive Persons Infected with Diverse HIV1 Subtypes  

Microsoft Academic Search

A guanidine-based antibody avidity assay for the identification of recently acquired human immunodefi- ciency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <0.75 and <0.80 reproducibly identified seroconversion within the previous 125 (95% confi- dence

A. Chawla; G. Murphy; C. Donnelly; C. L. Booth; M. Johnson; J. V. Parry; A. Phillips; A. M. Geretti

2007-01-01

345

Identifying open-volume defects in doped and undoped perovskite-type LaCoO3, PbTiO3, and BaTiO3  

Microsoft Academic Search

Dopants, vacancies, and impurity-vacancy clusters have a substantial impact on the properties of perovskite-type metal oxides (general formula ABO3). In order to determine synthesis and processing conditions that optimize the desirable properties of these materials a careful study of these defects is required. It is essential to identify the defects and to map the defect densities. Positron annihilation spectroscopy has

Vinita J. Ghosh; Bent Nielsen; Thomas Friessnegg

2000-01-01

346

Clear Cell Carcinoma of the Ovary: A Distinct Histologic Type with Poor Prognosis and Resistance to Platinum-Based Chemotherapy in Stage III Disease  

Microsoft Academic Search

Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the

Barbara A. Goff; Ricardo Sainz de la Cuesta; Howard G. Muntz; Deborah Fleischhacker; Marit Ek; Laurel W. Rice; Najmosama Nikrui; Hisham K. Tamimi; Joanna M. Cain; Benjamin E. Greer; Arlan F. Fuller Jr.

1996-01-01

347

Recombinant Soluble, Multimeric HA and NA Exhibit Distinctive Types of Protection against Pandemic Swine-Origin 2009 A(H1N1) Influenza Virus Infection in Ferrets?  

PubMed Central

The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA3) and NA (sNA4) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-?g doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA3 dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log10 units), immunization with sNA4 markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.

Bosch, Berend Jan; Bodewes, Rogier; de Vries, Robert P.; Kreijtz, Joost H. C. M.; Bartelink, Willem; van Amerongen, Geert; Rimmelzwaan, Guus F.; de Haan, Cornelis A. M.; Osterhaus, Albert D. M. E.; Rottier, Peter J. M.

2010-01-01

348

Comparative genomics of the white-rot fungi, Phanerochaete carnosa and P. chrysosporium, to elucidate the genetic basis of the distinct wood types they colonize  

PubMed Central

Background Softwood is the predominant form of land plant biomass in the Northern hemisphere, and is among the most recalcitrant biomass resources to bioprocess technologies. The white rot fungus, Phanerochaete carnosa, has been isolated almost exclusively from softwoods, while most other known white-rot species, including Phanerochaete chrysosporium, were mainly isolated from hardwoods. Accordingly, it is anticipated that P. carnosa encodes a distinct set of enzymes and proteins that promote softwood decomposition. To elucidate the genetic basis of softwood bioconversion by a white-rot fungus, the present study reports the P. carnosa genome sequence and its comparative analysis with the previously reported P. chrysosporium genome. Results P. carnosa encodes a complete set of lignocellulose-active enzymes. Comparative genomic analysis revealed that P. carnosa is enriched with genes encoding manganese peroxidase, and that the most divergent glycoside hydrolase families were predicted to encode hemicellulases and glycoprotein degrading enzymes. Most remarkably, P. carnosa possesses one of the largest P450 contingents (266 P450s) among the sequenced and annotated wood-rotting basidiomycetes, nearly double that of P. chrysosporium. Along with metabolic pathway modeling, comparative growth studies on model compounds and chemical analyses of decomposed wood components showed greater tolerance of P. carnosa to various substrates including coniferous heartwood. Conclusions The P. carnosa genome is enriched with genes that encode P450 monooxygenases that can participate in extractives degradation, and manganese peroxidases involved in lignin degradation. The significant expansion of P450s in P. carnosa, along with differences in carbohydrate- and lignin-degrading enzymes, could be correlated to the utilization of heartwood and sapwood preparations from both coniferous and hardwood species.

2012-01-01

349

Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes.  

PubMed

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes. PMID:22930659

Ramachandran, Surya; Venugopal, Anila; Sathisha, K; Reshmi, G; Charles, Sona; Divya, G; Chandran, N S Pratap; Mullassari, Ajit; Pillai, M Radhakrishna; Kartha, C C

2012-09-01

350

Classification of extracellularly recorded neurons by their discharge patterns and their correlates with intracellularly identified neuronal types in the frontal cortex of behaving monkeys.  

PubMed

Neurons in the cerebral cortex are not homogeneous. However, neuronal types have been ignored in most previous work studying neuronal processes in behaving monkeys. We propose a new method to identify neuronal types in extracellular recording studies of behaving monkeys. We classified neurons as either bursting or non-bursting, and then classified the bursting neurons into three types: (i) neurons displaying a burst of many spikes (maximum number of spikes within a burst; NSB max > or = 8) at a high discharge rate (maximum interspike interval; ISI max < 5 ms); (ii) neurons displaying a burst of fewer spikes (NSB max < or = 5) at a high discharge rate (ISI max < 5 ms); and (iii) neurons displaying a burst of a few spikes (NSB max < or = 7) at relatively long ISIs (ISI max > 5 ms). We found that the discharge patterns of the four groups corresponded to those of regular spiking (RS), fast spiking (FS), fast rhythmic bursting (FRB) and intrinsic bursting (IB) neurons demonstrated in intracellular recording studies using in vitro slice preparations, respectively. In addition, we examined correlations with the task events for neurons recorded in the frontal eye field and neuronal interactions for pairs of neurons recorded simultaneously from a single electrode. We found that they were substantially different between RS and FS types. These results suggest that neurons in the frontal cortex of behaving monkeys can be classified into four types based on their discharge patterns, and that these four types contribute differentially to cortical operations. PMID:20345909

Katai, Satoshi; Kato, Keichiro; Unno, Shunpei; Kang, Youngnam; Saruwatari, Masanori; Ishikawa, Naoki; Inoue, Masato; Mikami, Akichika

2010-03-24

351

Distinct modulation of a gene expression of the type 1 and 2 IP 3 receptors by retinoic acid in brain areas  

Microsoft Academic Search

Inositol 1,4,5-trisphosphate (IP3) receptors belong to the intracellular calcium channels that release calcium from the intracellular stores after binding IP3. Three types of IP3 receptors occurred in a tissue specific manner and different promoters direct their gene expression. Thus, understanding of the transcriptional regulation is the first step towards comprehension of the function of these receptors. Since the retinoic acid

P. Stefanik; D. Macejova; B. Mravec; J. Brtko; O. Krizanova

2005-01-01

352

Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells  

Microsoft Academic Search

Dendritic cells (DCs) are key to the maintenance of peripheral tolerance to self-antigens and the orchestration of an immune reaction to foreign antigens. C-type lectins, expressed by DCs, recognize carbohydrate moieties on antigens that can be internalized for processing and presentation. Little is known about the exact glycan structures on self-antigens and pathogens that are specifically recognized by the different

Sandra J. van Vliet; Ellis van Liempt; Eirikur Saeland; Corlien A. Aarnoudse; Ben Appelmelk; Tatsuro Irimura; Teunis B. H. Geijtenbeek; Ola Blixt; Richard Alvarez; Die van I. M; Kooijk van Y

2005-01-01

353

Coronary Arterioles in Type 2 Diabetic (db/db) Mice Undergo a Distinct Pattern of Remodeling Associated with Decreased Vessel Stiffness  

PubMed Central

Background Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Methods and Results Passive structural properties of septal coronary arterioles isolated from 12- and 16-wk-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-wk-old db/db mice were structurally similar to age-matched controls. By 16-wks of age, coronary wall thickness was increased in db/db arterioles (p < 0.01), while luminal diameter was reduced (Control: 118±5?m; db/db: 102±4?m, p < 0.05), augmenting the wall-to-lumen ratio by 58% (Control: 5.9±0.6; db/db: 9.5±0.4, p < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in elastic modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental modulus were increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. Conclusions These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased coronary flow reserve. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM.

Katz, Paige S.; Trask, Aaron J.; Souza-Smith, Flavia M.; Hutchinson, Kirk R.; Galantowicz, Maarten L.; Lord, Kevin C.; Stewart, James A.; Cismowski, Mary J.; Varner, Kurt J.; Lucchesi, Pamela A.

2011-01-01

354

Distinct and Overlapping Patterns of Localization of Bone Morphogenetic Protein (BMP) Family Members and a BMP Type II Receptor During Fracture Healing in Rats  

Microsoft Academic Search

Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) are thought to play an important role in bone morphogenesis. The purpose of this study was to determine the locations of BMP-2\\/-4, osteogenic protein-1 (OP-1, also termed BMP-7), and BMP type II receptor (BMPR-II) during rat fracture healing by immunostaining, and thereby elucidate the possible roles of the BMPs and BMPR-II in

T Onishi; Y Ishidou; T Nagamine; K Yone; T Imamura; M Kato; T. K Sampath; P ten Dijke; T Sakou

1998-01-01

355

Evidence That HLA Class I and II Associations With Type 1 Diabetes, Autoantibodies to GAD and Autoantibodies to IA-2, Are Distinct  

PubMed Central

OBJECTIVE A major feature of type 1 diabetes is the appearance of islet autoantibodies before diagnosis. However, although the genetics of type 1 diabetes is advanced, the genetics of islet autoantibodies needs further investigation. The primary susceptibility loci in type 1 diabetes, the HLA class I and II genes, are believed to determine the specificity and magnitude of the autoimmune response to islet antigens. We investigated the association of glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen-2 autoantibodies (IA-2A) with the HLA region. RESEARCH DESIGN AND METHODS Associations of GADA and IA-2A with HLA-DRB1, HLA-DQB1, HLA-B, HLA-C, HLA-A, MICA, and 3,779 single nucleotide polymorphisms (SNPs) were analyzed in 2,531 childhood-onset case subjects (median time since diagnosis 5 years). All analyses were adjusted for age-at-diagnosis and duration of diabetes. RESULTS GADA and IA-2A were associated with an older age-at-diagnosis (P < 10?19). For GADA, the primary association was with HLA-DQB1 (P = 9.00 × 10?18), with evidence of a second independent effect in the HLA class I region with SNP, rs9266722 (P = 2.84 × 10?6). HLA-DRB1 had the strongest association with IA-2A (P = 1.94 × 10?41), with HLA-A*24 adding to the association, albeit negatively (P = 1.21 × 10?10). There was no evidence of association of either IA-2A or GADA with the highly type 1 diabetes predisposing genotype, HLA-DRB1*03/04. CONCLUSIONS Despite genetic association of type 1 diabetes and the islet autoantibodies localizing to the same HLA class II genes, HLA-DRB1 and HLA-DQB1, the effects of the class II alleles and genotypes involved are quite different. Therefore, the presence of autoantibodies is unlikely to be causal, and their role in pathogenesis remains to be established.

Howson, Joanna M.M.; Stevens, Helen; Smyth, Deborah J.; Walker, Neil M.; Chandler, Kyla A.; Bingley, Polly J.; Todd, John A.

2011-01-01

356

Genes encoding proteins with peritrophin A-type chitin-binding domains in Tribolium castaneum are grouped into three distinct families based on phylogeny, expression and function.  

PubMed

This study is focused on the characterization and expression of genes in the red flour beetle, Tribolium castaneum, encoding proteins that possess one or more six-cysteine-containing chitin-binding domains related to the peritrophin A domain (ChtBD2). An exhaustive bioinformatics search of the genome of T. castaneum queried with ChtBD2 sequences yielded 13 previously characterized chitin metabolic enzymes and 29 additional proteins with signal peptides as well as one to 14 ChtBD2s. Using phylogenetic analyses, these additional 29 proteins were classified into three large families. The first family includes 11 proteins closely related to the peritrophins, each containing one to 14 ChtBD2s. These are midgut-specific and are expressed only during feeding stages. We propose the name "Peritrophic Matrix Proteins" (PMP) for this family. The second family contains eight proteins encoded by seven genes (one gene codes for 2 splice variants), which are closely related to gasp/obstructor-like proteins that contain 3 ChtBD2s each. The third family has ten proteins that are of diverse sizes and sequences with only one ChtBD2 each. The genes of the second and third families are expressed in non-midgut tissues throughout all stages of development. We propose the names "Cuticular Proteins Analogous to Peritophins 3" (CPAP3) for the second family that has three ChtBD2s and "Cuticular Proteins Analogous to Peritophins 1 (CPAP1) for the third family that has 1 ChtBD2. Even though proteins of both CPAP1 and CPAP3 families have the "peritrophin A" domain, they are expressed only in cuticle-forming tissues. We determined the exon-intron organization of the genes, encoding these 29 proteins as well as the domain organization of the encoded proteins with ChtBD2s. All 29 proteins have predicted cleavable signal peptides and ChtBD2s, suggesting that they interact with chitin in extracellular locations. Comparison of ChtBD2s-containing proteins in different insect species belonging to different orders suggests that ChtBD2s are ancient protein domains whose affinity for chitin in extracellular matrices has been exploited many times for a range of biological functions. The differences in the expression profiles of PMPs and CPAPs indicate that even though they share the peritrophin A motif for chitin binding, these three families of proteins have quite distinct biological functions. PMID:20144715

Jasrapuria, Sinu; Arakane, Yasuyuki; Osman, Gamal; Kramer, Karl J; Beeman, Richard W; Muthukrishnan, Subbaratnam

2010-02-06

357

Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein  

PubMed Central

The dysregulation of cellular apoptosis pathways has emerged as a critical early event associated with the development of many types of human cancers. Numerous viral and cellular oncogenes, aside from their inherent transforming properties, are known to induce programmed cell death, consistent with the hypothesis that genetic defects are required to support tumor survival. Here, we report that nuclear expression of the CREB-binding protein (CBP)/p300-binding domain of the human T-cell lymphotropic virus type 1 (HTLV-1) transactivator, Tax, triggers an apoptotic death-inducing signal during short-term clonal analyses, as well as in transient cell death assays. Coexpression of the antiapoptotic factor Bcl-2 increased serum stimulation; incubation with the chemical caspase inhibitor z-Val-Ala-dl-Asp fluoromethylketone antagonized Tax-induced cell death. The CBP/p300-binding defective Tax mutants K88A and V89A exhibited markedly reduced cytotoxic effects compared to the wild-type Tax protein. Importantly, nuclear expression of the minimal CBP/p300-binding peptide of Tax induced apoptosis in the absence of Tax-dependent transcriptional activities, while its K88A counterpart did not cause cell death. Further, Tax-mediated apoptosis was effectively prevented by ectopic expression of the p300 coactivator. We also report that activation of the NF-?B transcription pathway by Tax, under growth arrest conditions, results in apoptosis that occurs independent of direct Tax coactivator effects. Our results allude to a novel pivotal role for the transcriptional coactivator p300 in determining cell fate and raise the possibility that dysregulated coactivator usage may pose an early barrier to transformation that must be selectively overcome as a prerequisite for the initiation of neoplasia.

Nicot, Christophe; Harrod, Robert

2000-01-01

358

Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.  

PubMed

Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2) were compared to those of type 1 and type 3 wild poliovirus (WPV) lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin) by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv) bias and strikingly lower Ts/Tv rate ratios at the 2(nd) codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd) codon position was also found in the large set of VP1 sequences of Nigerian circulating (c)VDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance. PMID:23840537

Hovi, Tapani; Savolainen-Kopra, Carita; Smura, Teemu; Blomqvist, Soile; Al-Hello, Haider; Roivainen, Merja

2013-06-28

359

Distinct Patterns of Inactivation of @15lN@@4B and @J6IN@@4A Characterize the Major Types of Hematological Malignancies1  

Microsoft Academic Search

Inactivation of the cyclin-dependent kinase inhibitors pJ6I@W@4d@ and pJ5INK4B are frequent alterations in neoplasia, often resulting from ho mozygous deletion or promoter region hypermethylation. We have ana lyzed both modes of inactivation of p15@'48and pJ6INK4A in the major types of adult and pediatric hematological malignancies. Hypermethyla tion 0fp151NK48, without alteration 0fpJ6INK4A, was an almost universal finding in adult acute myelogenous

James G. Herman; Curt I. Civin; Jean-Pierre J. Issa; Saul J. Sharkis; Stephen B. Baylin

360

Evolution of Type 2 Vaccine Derived Poliovirus Lineages. Evidence for Codon-Specific Positive Selection at Three Distinct Locations on Capsid Wall  

PubMed Central

Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003–2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2) were compared to those of type 1 and type 3 wild poliovirus (WPV) lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin) by 12.5–15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv) bias and strikingly lower Ts/Tv rate ratios at the 2nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (c)VDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

Hovi, Tapani; Savolainen-Kopra, Carita; Smura, Teemu; Blomqvist, Soile; Al-Hello, Haider; Roivainen, Merja

2013-01-01

361

Human Immunodeficiency Virus Type 1 Subtypes Have a Distinct Long Terminal Repeat That Determines the Replication Rate in a Host-Cell-Specific Manner  

PubMed Central

The long terminal repeat (LTR) transcriptional promoters of different human immunodeficiency virus (HIV) type 1 subtypes were inserted into the LAI molecular clone of subtype B. The viral genotypes represent seven subtypes (A, B, C, D, E, F, and G) and one circulating recombinant form (AG). We performed replication studies with this isogenic set of viruses across six cellular environments. This approach revealed strong cellular environment effects, but the method was not sensitive enough to detect small differences in the replication rate between the subtypes. By conducting pairwise competition experiments between the virus variants in six cellular environments, we could demonstrate significant differences in the replication rates of the subtypes and that LTR-determined viral fitness depends both on the host cell type and the activation state of the cell. In addition, we determined the degree of conservation of the transcription factor-binding sites (TFBS) in the different-subtype LTRs by analyzing sequences from the HIV sequence database. The sequence analyses revealed subtype-specific conservation of certain TFBS. The results indicate that one should consider the possibility of subtype-specific viral replication rates in vivo, which are strongly influenced by the host environment. We argue that the multidimensional host environment may have shaped the genetic structures of the subtype LTRs.

van Opijnen, Tim; Jeeninga, Rienk E.; Boerlijst, Maarten C.; Pollakis, Georgios P.; Zetterberg, Veera; Salminen, Mika; Berkhout, Ben

2004-01-01

362

Two distinct types of theca cells in the medaka gonad: germ cell-dependent maintenance of cyp19a1-expressing theca cells.  

PubMed

Aromatase is a steroidogenic enzyme catalyzing the production of estrogens and is important for the proper development and function of the reproductive system. The lineage of cyp19a1 (ovarian-type aromatase)-expressing cells in the developing gonad was analyzed using a transgenic medaka (Oryzias latipes) that recapitulates endogenous cyp19a1 expression with EGFP fluorescence. Our results show that cyp19a1-expressing cells arise in the ventral stromal cells of the developing female gonad, then expand anteriorly as the gonadal region extends anteriorly. These cells become located close to the developing follicles, and are distinguishable from the P450c17-I-expressing theca cells. In the adult ovary, the expression of P450c17-I and cyp19a1 are mutually exclusive in the outer theca-cell layer. Cyp19a1 expression in the granulosa cells is found only in the population of large follicles. These observations demonstrate two types of theca cells in the medaka ovary. We also show that the maintenance of cyp19a1-expressing cells depends on germ cells. PMID:19705448

Nakamura, Shuhei; Kurokawa, Hiromi; Asakawa, Shuichi; Shimizu, Nobuyoshi; Tanaka, Minoru

2009-10-01

363

Is mammary not otherwise specified-type sarcoma with CD10 expression a distinct entity? A rare case report with immunohistochemical and ultrastructural study  

PubMed Central

Abstract Mammary sarcoma is extremely rare and the diagnosis is established only after metaplastic carcinomas and malignant phyllodes tumours are excluded. A rare case of not otherwise specified-type sarcoma with CD10 expression in the left breast in a 45-year-old female was presented. It was a high-grade tumour composed of spindle cells histologically. The immunohistochemical results showed that CD10, vimentin and EGFR were positive diffusely and SMA presented focally, whereas epithelial markers and other myoepithelial or myogenic markers were all negative. The electron microscope investigation demonstrated fibroblast-like features. The exact entity of the tumour remains to be studied because it resembles undifferentiated sarcoma or sarcomatoid metaplastic carcinoma to some degree, as well as high-grade malignant phyllodes tumour in particular. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9019879588725702

2013-01-01

364

Why Halley-Types Resonate but Long-Period Comets Don't: A Dynamical Distinction between Short- and Long-Period Comets  

NASA Astrophysics Data System (ADS)

Several recent studies have noted that the orbital evolution of many comets is influenced by mean-motion resonances with Jupiter. However, the distribution and relative importance of these resonances and the orbital characteristics of the comets affected have not been addressed to date. Here I show analytically that cometary orbits with periods greater than a critical value, P_c, (which depends upon the orbital inclination) are prevented from undergoing librations about a mean-motion resonance. Conversely, numerical integrations indicate that resonances play an important role in the dynamics of comets with P < P_c. The inclination-averaged value of P_c approximately coincides with the traditional and arbitrary dividing line between Halley-type and long-period comets, which explains why many of the former are currently observed to be in resonance, whereas the latter are not. Thus, we now have a dynamical justification for separating comets into those of short and long period.

Chambers, J. E.

1997-01-01

365

The renal transcriptome of db/db mice identifies putative urinary biomarker proteins in patients with type 2 diabetes: a pilot study  

PubMed Central

We sought to identify novel urinary biomarkers of kidney function in type 2 diabetes. We screened the renal transcriptome of db/db and db/m mice for differentially expressed mRNA transcripts that encode secreted proteins with human orthologs. Whether elevated urine levels of the orthologous proteins correlated with diminished glomerular filtration rate was tested in a cross-sectional study of n = 56 patients with type 2 diabetes. We identified 36 putative biomarker genes in db/db kidneys: 31 upregulated and 5 downregulated. Urinary protein levels of six selected candidates (endothelin-1, lipocalin-2, transforming growth factor-?, growth and differentiation factor-15, interleukin-6, and macrophage chemoattractant protein-1) were elevated in type 2 diabetic patients with subnormal glomerular filtration rate (i.e., <90 ml·min?1·1.73 m?2), independent of microalbuminuria, age, sex, race, and use of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. In contrast, urinary levels of fibroblast growth factor were not increased. A composite variable of urine albumin and any of the six candidate markers was associated with subnormal estimated glomerular filtration rate more closely than albumin alone. In addition, urinary endothelin-1, growth and differentiation factor-15, and interleukin-6 were associated with a marker of proximal tubule damage, N-acetyl-?-d-glucosaminidase activity. These results suggest that gene expression profiling in diabetic mouse kidney can complement existing proteomic-based approaches for renal biomarker discovery in humans.

Tiktin, Margaret; Debanne, Sara M.; Rahman, Mahboob; Berger, Bruce; Hricik, Donald; Ismail-Beigi, Faramarz

2012-01-01

366

Early Progenitor Cell Marker Expression Distinguishes Type II From Type I Focal Cortical Dysplasias  

Microsoft Academic Search

Type I and type II focal cortical dysplasias (FCDs) exhibit distinct histopathologic features that suggest different pathogenic mechanisms. Type I FCDs are characterized by mild laminar disorganization and hypertrophic neurons, whereas type II FCDs exhibit dramatic laminar disorganization and cytomegalic cells (balloon cells). Both FCD types are associated with intractable epilepsy; therefore, identifying cellular or molecular differences between these lesion

Ksenia A. Orlova; Victoria Tsai; Marianna Baybis; Gregory G. Heuer; Sanjay Sisodiya; Maria Thom; Kevin Strauss; Eleonora Aronica; Phillip B. Storm; Peter B. Crino

2010-01-01

367

Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection  

PubMed Central

Summary Type I Interferons (IFN-I) promote antiviral CD8+T cell responses, but the contribution of different IFN-I sources and signaling pathways are ill-defined. While plasmacytoid dendritic cells (pDCs) produce IFN-I upon TLR stimulation, IFN-I are induced in most cells by helicases like MDA5. Using acute and chronic lymphocytic choriomeningitis virus (LCMV) infection models, we determined that pDCs transiently produce IFN-I that minimally impacts CD8+T cell responses and viral persistence. Rather, MDA5 is the key sensor that induces IFN-I required for CD8+T cell responses. In the absence of MDA5, CD8+T cell responses to acute infection rely on CD4+T cell help, and loss of both CD4+T cells and MDA5 results in CD8+T cell exhaustion and persistent infection. Chronic LCMV infection rapidly attenuates IFN-I responses, but early administration of exogenous IFN-I rescues CD8+T cells, promoting viral clearance. Thus, effective antiviral CD8+T cell responses depend on the timing and magnitude of IFN-I responses.

Wang, Yaming; Swiecki, Melissa; Cella, Marina; Alber, Gottfried; Schreiber, Robert D; Gilfillan, Susan; Colonna, Marco

2013-01-01

368

Fine mapping of the latency-related gene of herpes simplex virus type 1: alternative splicing produces distinct latency-related RNAs containing open reading frames  

SciTech Connect

The latency-related (LR) gene of herpes simplex virus type 1 (HSV-1) is transcriptionally active during HSV-1 latency, producing at least two LR-RNAs. The LR gene partially overlaps the immediate-early gene ICP0 and is transcribed in the opposite direction from ICP0, producing LR-RNAs that are complementary (antisense) to ICP0 mRNA. The LR gene is thought to be involved in HSV-1 latency. The authors report here the time mapping and partial sequence analysis of this HSV-1 LR gene. /sup 32/P-labeled genomic DNA restriction fragments and synthetic oligonucleotides were used as probes for in situ hybridizations and Northern (RNA) blot hybridizations of RNA from trigeminal ganglia of rabbits latently infected with HSV-1. The two most abundant LR-RNAs appeared to share their 5' and 3' ends and to be produced by alternative splicing. These LR-RNAs were approximately 2 and 1.3 to 1.5 kilobases in length and were designated LR-RNA 1 and LF-RNA 2, respectively. LR-RNA 1 appeared to have at least one intron removed, while LR-RNA 2 appeared to have at least two introns removed. The LR-RNAs contained two potential long open reading frames, suggesting the possibility that one or more of the LR-RNAs may be a functional mRNA.

Wechsler, S.L.; Nesburn, A.B.; Watson, R.; Slanina, S.M.; Ghiasi, H.

1988-11-01

369

Modulation of distinct isoforms of L-type calcium channels by G(q)-coupled receptors in Xenopus oocytes: antagonistic effects of G?? and protein kinase C.  

PubMed

L-type voltage dependent Ca(2+) channels (L-VDCCs; Ca(v)1.2) are crucial in cardiovascular physiology. In heart and smooth muscle, hormones and transmitters operating via G(q) enhance L-VDCC currents via essential protein kinase C (PKC) involvement. Heterologous reconstitution studies in Xenopus oocytes suggested that PKC and G(q)-coupled receptors increased L-VDCC currents only in cardiac long N-terminus (NT) isoforms of ?(1C), whereas known smooth muscle short-NT isoforms were inhibited by PKC and G(q) activators. We report a novel regulation of the long-NT ?(1C) isoform by G??. G?? inhibited whereas a G?? scavenger protein augmented the G(q)--but not phorbol ester-mediated enhancement of channel activity, suggesting that G?? acts upstream from PKC. In vitro binding experiments reveal binding of both G?? and PKC to ?(1C)-NT. However, PKC modulation was not altered by mutations of multiple potential phosphorylation sites in the NT, and was attenuated by a mutation of C-terminally located serine S1928. The insertion of exon 9a in intracellular loop 1 rendered the short-NT ?(1C) sensitive to PKC stimulation and to G?? scavenging. Our results suggest a complex antagonistic interplay between G(q)-activated PKC and G?? in regulation of L-VDCC, in which multiple cytosolic segments of ?(1C) are involved. PMID:22990911

Weiss, Sharon; Keren-Raifman, Tal; Oz, Shimrit; Ben Mocha, Adva; Haase, Hannelore; Dascal, Nathan

2012-09-18

370

The ligand-binding domains of the three RXR-USP nuclear receptor types support distinct tissue and ligand specific hormonal responses in transgenic Drosophila.  

PubMed

In insects, 20-hydroxyecdysone acts by binding on a heterodimer constituted by the ecdysone receptor (EcR) and Ultraspiracle (USP), the homolog to the vertebrate retinoid X receptor (RXR). Two types of USP have been characterized based on their structure and function, Mecopterida USP (Diptera/Lepidoptera USP), in particular the fruitfly Drosophila melanogaster USP (DmUSP) and non Mecopterida USP, exemplified by the beetle Tribolium castaneum USP (TcUSP) both showing structural differences from the vertebrate RXR. Here, by combining in vivo and organ culture observations in Drosophila transgenic animals, we show that ectopic expression of GAL4-DmUSP, GAL4-TcUSP or GAL4-HsRXR results in tissue- and ligand-dependent activities. In parallel, we show that neither juvenile hormone (JH) nor the related methyl farnesoate has an effect on GAL4-USP activation although JH induces the expression of a factor inhibiting the receptor transcriptional activity in the presence of EcR or RXR agonists. This study suggests that not only is USP important for hormonal regulation, via heterodimer formation, but that tissue-specific expression of cofactors may represent a higher level of control of this regulation. This in vivo approach should lead to a better understanding of the modes of action of USP and the identification of transcriptional cofactors essential for its function. PMID:19268446

Beck, Yannick; Delaporte, Claude; Moras, Dino; Richards, Geoff; Billas, Isabelle M L

2009-03-04

371

Pseudomonas aeruginosa Possesses Two Putative Type I Signal Peptidases, LepB and PA1303, Each with Distinct Roles in Physiology and Virulence  

PubMed Central

Type I signal peptidases (SPases) cleave signal peptides from proteins during translocation across biological membranes and hence play a vital role in cellular physiology. SPase activity is also of fundamental importance to the pathogenesis of infection for many bacteria, including Pseudomonas aeruginosa, which utilizes a variety of secreted virulence factors, such as proteases and toxins. P. aeruginosa possesses two noncontiguous SPase homologues, LepB (PA0768) and PA1303, which share 43% amino acid identity. Reverse transcription (RT)-PCR showed that both proteases were expressed, while a FRET-based assay using a peptide based on the signal sequence cleavage region of the secreted LasB elastase showed that recombinant LepB and PA1303 enzymes were both active. LepB is positioned within a genetic locus that resembles the locus containing the extensively characterized SPase of E. coli and is of similar size and topology. It was also shown to be essential for viability and to have high sequence identity with SPases from other pseudomonads (?78%). In contrast, PA1303, which is small for a Gram-negative SPase (20 kDa), was found to be dispensable. Mutation of PA1303 resulted in an altered protein secretion profile and increased N-butanoyl homoserine lactone production and influenced several quorum-sensing-controlled phenotypic traits, including swarming motility and the production of rhamnolipid and elastinolytic activity. The data indicate different cellular roles for these P. aeruginosa SPase paralogues; the role of PA1303 is integrated with the quorum-sensing cascade and includes the suppression of virulence factor secretion and virulence-associated phenotypes, while LepB is the primary SPase.

Rose, Ruth S.; Rangarajan, Minnie; Aduse-Opoku, Joseph; Hashim, Ahmed; Curtis, Michael A.

2012-01-01

372

Pseudomonas aeruginosa possesses two putative type I signal peptidases, LepB and PA1303, each with distinct roles in physiology and virulence.  

PubMed

Type I signal peptidases (SPases) cleave signal peptides from proteins during translocation across biological membranes and hence play a vital role in cellular physiology. SPase activity is also of fundamental importance to the pathogenesis of infection for many bacteria, including Pseudomonas aeruginosa, which utilizes a variety of secreted virulence factors, such as proteases and toxins. P. aeruginosa possesses two noncontiguous SPase homologues, LepB (PA0768) and PA1303, which share 43% amino acid identity. Reverse transcription (RT)-PCR showed that both proteases were expressed, while a FRET-based assay using a peptide based on the signal sequence cleavage region of the secreted LasB elastase showed that recombinant LepB and PA1303 enzymes were both active. LepB is positioned within a genetic locus that resembles the locus containing the extensively characterized SPase of E. coli and is of similar size and topology. It was also shown to be essential for viability and to have high sequence identity with SPases from other pseudomonads (? 78%). In contrast, PA1303, which is small for a Gram-negative SPase (20 kDa), was found to be dispensable. Mutation of PA1303 resulted in an altered protein secretion profile and increased N-butanoyl homoserine lactone production and influenced several quorum-sensing-controlled phenotypic traits, including swarming motility and the production of rhamnolipid and elastinolytic activity. The data indicate different cellular roles for these P. aeruginosa SPase paralogues; the role of PA1303 is integrated with the quorum-sensing cascade and includes the suppression of virulence factor secretion and virulence-associated phenotypes, while LepB is the primary SPase. PMID:22730125

Waite, Richard D; Rose, Ruth S; Rangarajan, Minnie; Aduse-Opoku, Joseph; Hashim, Ahmed; Curtis, Michael A

2012-06-22

373

Disease of distinction.  

PubMed

Gout is one of the rare diseases that defines its sufferers by class and culture. It is also one of the first chronic diseases to be clinically described. The Egyptians had identified gout as a distinct disorder by 2640 bce. This paper traces the history of gout from its earliest recorded period down to modern times, with a particular emphasis on the cultural, political, geopolitical, and social aspects. Included is a discussion of its role in the American Revolution. Today, gout is a well-understood clinically managed arthritic disease that excites little comment. This is an entirely modern perspective. For most of human history, gout was a disease of distinction that dominated much of medicine, playing the same role in Rome's third century bce aristocracy it would later play in the aristocracies of 17th and 18th century France and England, when each of these countries dominated the world. Because it was considered a disease of lifestyle until modern times, when genetics began to be understood, gout was associated with rich, high status Caucasian men and their excessive consumption of drink and rich foods. It was virtually unknown in Asia, until Western dietary practices became widespread there. From earliest history, gout has been linked with high IQ and sexual promiscuity, which made it grist for artists and writers, and their social commentary up to the time of Dickens; this is discussed, with examples. Because of its association with the rich, gout also developed a powerful moralistic aspect, particularly during the Christian era when the concept of sin was a cultural fundamental. The loose living and indulgence of the rich and the gout it produced made the disease a parable of Christian ethics. The Italian poet Francesco Petrarch (1304-1374) was one of the first to establish this nuance, and it influenced how gout was seen for centuries. Part of what gave gout its special character was that while it tortured, it rarely killed. Indeed, when death was a frequent visitor to families, it was thought a painful but welcomed prophylactic against diseases that did kill. Even in modern times, gout still favors the rich and powerful. American research conducted in the 1960s found that corporate executives, just like their English gentry, or Roman senatorial predecessors, had higher urate concentrations than their blue-collar employees. PMID:17113492

Schwartz, Stephan A

374

Teenage Drinking, Symbolic Capital and Distinction  

ERIC Educational Resources Information Center

|This article analyses alcohol-related lifestyles among Danish teenagers. Building on Bourdieu's reasoning on symbolic capital and distinction, we analyse three interrelated themes. First, we show that alcohol-related variables (drinking patterns, drinking debut, experience of intoxication, etc.) can be used to identify some very distinctive life…

Jarvinen, Margaretha; Gundelach, Peter

2007-01-01

375

Re-evaluation of the distinction between type I and type II cells: the necessary role of the mitochondria in both the extrinsic and intrinsic signaling pathways upon Fas receptor activation.  

PubMed

Cyclosporin A (CyA) and bongkrekic acid (BK) prevented Fas-induced apoptosis in two type I cell lines (H9 and SKW6.4) and two type II cell lines (Jurkat and CEM). CyA and BK inhibited the release of cytochrome c in all four cell lines. In type I cells and in CEM cells, CyA and BK did not prevent the translocation of Bax to the mitochondria. In these same cells, full-length Bid decreased in the mitochondria and cytosol. The cleavage product of Bid, tBid, appeared in the cytosol and to a lesser extent in the mitochondria. In Jurkat cells, Bid also decreased in the cytosol, but increased in the mitochondria. Similar to the other cells, tBid appeared in the mitochondria and cytosol. In the type I H9 and SKW6.4 cells and type II Jurkat cells, the caspase-8 inhibitor Z-Ile-Glu(OMe)-Thr-Asp(OMe)-CH2F (IETD) prevented the cell killing. In the type I cells, IETD prevented the translocation of Bax, the degradation of Bid and the accumulation of tBid. By contrast, IETD only marginally protected the type II CEM cells. In these cells in the presence of IETD, Bax translocated to the mitochondria, in the absence of any degradation of Bid or accumulation of tBid. In the type I H9 cells, IETD produced a depletion of ATP, an effect that did not occur in the type II CEM cells. It is concluded that in type I cells the extrinsic signaling pathway is mitochondrial dependent to the same extent as is the intrinsic pathway in type II cells. PMID:16741989

Tafani, Marco; Karpinich, Natalie O; Serroni, Ada; Russo, Matteo A; Farber, John L

2006-09-01

376

High-content RNAi screening identifies the Type 1 inositol triphosphate receptor as a modifier of TDP-43 localization and neurotoxicity.  

PubMed

Cytosolic aggregation of the nuclear RNA-binding protein (RBP) TDP-43 (43 kDa TAR DNA-binding domain protein) is a suspected direct or indirect cause of motor neuron deterioration in amyotrophic lateral sclerosis (ALS). In this study, we implemented a high-content, genome-wide RNAi screen to identify pathways controlling TDP-43 nucleocytoplasmic shuttling. We identified ?60 genes whose silencing increased the cytosolic localization of TDP-43, including nuclear pore complex components and regulators of G2/M cell cycle transition. In addition, we identified the type 1 inositol-1,4,5-trisphosphate (IP3) receptor (ITPR1), an IP3-gated, endoplasmic reticulum (ER)-resident Ca(2+) channel, as a strong modulator of TDP-43 nucleocytoplasmic shuttling. Knockdown or chemical inhibition of ITPR1 induced TDP-43 nuclear export in immortalized cells and primary neurons and strongly potentiated the recruitment of TDP-43 to Ubiquilin-positive autophagosomes, suggesting that diminished ITPR1 function leads to autophagosomal clearance of TDP-43. The functional significance of the TDP-43-ITPR1 genetic interaction was tested in Drosophila, where mutant alleles of ITPR1 were found to significantly extended lifespan and mobility of flies expressing TDP-43 under a motor neuron driver. These combined findings implicate IP3-gated Ca(2+) as a key regulator of TDP-43 nucleoplasmic shuttling and proteostasis and suggest pharmacologic inhibition of ITPR1 as a strategy to combat TDP-43-induced neurodegeneration in vivo. PMID:22872699

Kim, Sang Hwa; Zhan, Lihong; Hanson, Keith A; Tibbetts, Randal S

2012-08-07

377

High-throughput typing method to identify a non-outbreak-involved Legionella pneumophila strain colonizing the entire water supply system in the town of Rennes, France.  

PubMed

Two legionellosis outbreaks occurred in the city of Rennes, France, during the past decade, requiring in-depth monitoring of Legionella pneumophila in the water network and the cooling towers in the city. In order to characterize the resulting large collection of isolates, an automated low-cost typing method was developed. The multiplex capillary-based variable-number tandem repeat (VNTR) (multiple-locus VNTR analysis [MLVA]) assay requiring only one PCR amplification per isolate ensures a high level of discrimination and reduces hands-on and time requirements. In less than 2 days and using one 4-capillary apparatus, 217 environmental isolates collected between 2000 and 2009 and 5 clinical isolates obtained during outbreaks in 2000