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1

Nontoxigenic corynebacterium diphtheriae: an emerging pathogen in England and Wales?  

PubMed Central

Confirmed isolates of nontoxigenic Corynebacterium diphtheriae in England and Wales increased substantially from 1986 to 1994. Ribotyping of 121 isolates confirmed in 1995 showed that 90 were of a single strain isolated exclusively from the throat; none had previously been identified in toxigenic strains from U.K. or non-U.K. residents. The upward trend in nontoxigenic C. diphtheriae probably represented increased ascertainment, although dissemination of a particular strain or clone may have been a factor. PMID:11076724

Reacher, M.; Ramsay, M.; White, J.; De Zoysa, A.; Efstratiou, A.; Mann, G.; Mackay, A.; George, R. C.

2000-01-01

2

Nontoxigenic Vibrio parahaemolyticus Strains Causing Acute Gastroenteritis  

PubMed Central

We investigated the virulence properties of four Vibrio parahaemolyticus strains causing acute gastroenteritis following consumption of indigenous mussels in Italy. The isolated strains were cytotoxic and adhesive but, surprisingly, lacked tdh, trh, and type three secretion system 2 (T3SS2) genes. We emphasize that nontoxigenic V. parahaemolyticus can induce acute gastroenteritis, highlighting the need for more investigation of the pathogenicity of this microorganism. PMID:23052317

Leoni, Francesca; Serra, Roberto; Serracca, Laura; Decastelli, Lucia; Rocchegiani, Elena; Masini, Laura; Canonico, Cristina; Talevi, Giulia; Carraturo, Antonio

2012-01-01

3

Two Cases of Bacteriemia Caused by Nontoxigenic, Non-O1, Non-O139 Vibrio cholerae Isolates in Ho Chi Minh City, Vietnam  

PubMed Central

The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non-O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period. PMID:25122858

Lan, Nguyen Phu Huong; Nga, Tran Vu Thieu; Yen, Nguyen Thi Thu; Dung, Le Thi; Tuyen, Ha Thanh; Campbell, James I.; Whitehorn, Jamie; Thwaites, Guy; Chau, Nguyen Van Vinh

2014-01-01

4

Two Cases of Bacteriemia Caused by Nontoxigenic, Non-O1, Non-O139 Vibrio cholerae Isolates in Ho Chi Minh City, Vietnam.  

PubMed

The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non-O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period. PMID:25122858

Lan, Nguyen Phu Huong; Nga, Tran Vu Thieu; Yen, Nguyen Thi Thu; Dung, Le Thi; Tuyen, Ha Thanh; Campbell, James I; Whitehorn, Jamie; Thwaites, Guy; Chau, Nguyen Van Vinh; Baker, Stephen

2014-10-01

5

Amino acid-nutritional variants isolated from the Jensen sarcoma  

Microsoft Academic Search

Summary  Five separate primary variant cell populations were isolated from the Jensen sarcoma by culturing in media devoid of arginine,\\u000a leucine, lysine, phenylalanine, and tryptophan and compared to a variant of asparagine metabolism. The tryptophan variant,\\u000a however, may result from growth due to serum-adsorbed tryptophan. When challenged with media devoid of a second amino acid,\\u000a each variant responded differently. Transplantation of

M. K. Patterson; M. D. Maxwell; E. Conway

1971-01-01

6

Characterization of Colony Morphology Variants Isolated from Pseudomonas aeruginosa Biofilms  

PubMed Central

In this study, we report the isolation of small, rough, strongly cohesive colony morphology variants from aging Pseudomonas aeruginosa PAO1 biofilms. Similar to many of the P. aeruginosa colony morphology variants previously described in the literature, these variants autoaggregate in liquid culture and hyperadhere to solid surfaces. They also exhibit increased hydrophobicity and reduced motility compared to the wild-type parent strain. Despite the similarities in appearance of our colony morphology variant isolates on solid medium, the isolates showed a range of responses in various phenotypic assays. These variants form biofilms with significant three-dimensional structure and more biomass than the wild-type parent. To further explore the nature of the variants, their transcriptional profiles were evaluated. The variants generally showed increased expression of the psl and pel loci, which have been previously implicated in the adherence of P. aeruginosa to solid surfaces. When a mutation in the psl locus was introduced into a colony morphology variant, the colony morphology was only partially affected, but hyperadherence and autoaggregation were lost. Finally, similar colony morphology variants were found in isolates from cystic fibrosis patients. These variants displayed many of the same characteristics as the laboratory variants, suggesting a link between laboratory and cystic fibrosis biofilms. PMID:16085879

Kirisits, Mary Jo; Prost, Lynne; Starkey, Melissa; Parsek, Matthew R.

2005-01-01

7

Nontoxigenic tox-bearing Corynebacterium ulcerans infection among game animals, Germany.  

PubMed

Corynebacterium ulcerans may cause diphtheria in humans and caseous lymphadenitis in animals. We isolated nontoxigenic tox-bearing C. ulcerans from 13 game animals in Germany. Our results indicate a role for game animals as reservoirs for zoonotic C. ulcerans. PMID:24572455

Eisenberg, Tobias; Kutzer, Peter; Peters, Martin; Sing, Andreas; Contzen, Matthias; Rau, Jörg

2014-03-01

8

Toxigenic Corynebacterium ulcerans in human and non-toxigenic Corynebacterium diphtheriae in cat  

PubMed Central

Corynebacterium diphtheriae and Corynebacterium ulcerans are rarely isolated from clinical samples in Belgium. A case of toxigenic C. ulcerans in a woman is described, which confirms that this pathogen is still present. During investigation of the patient's cats, only a non-toxigenic toxin-bearing C. diphtheriae strain was detected.

Detemmerman, L; Rousseaux, D; Efstratiou, A; Schirvel, C; Emmerechts, K; Wybo, I; Soetens, O; Pierard, D

2013-01-01

9

Nontoxigenic tox-bearing Corynebacterium ulcerans Infection among Game Animals, Germany  

PubMed Central

Corynebacterium ulcerans may cause diphtheria in humans and caseous lymphadenitis in animals. We isolated nontoxigenic tox-bearing C. ulcerans from 13 game animals in Germany. Our results indicate a role for game animals as reservoirs for zoonotic C. ulcerans. PMID:24572455

Kutzer, Peter; Peters, Martin; Sing, Andreas; Contzen, Matthias; Rau, Jorg

2014-01-01

10

Isolating potentiated hsp104 variants using yeast proteinopathy models.  

PubMed

Many protein-misfolding disorders can be modeled in the budding yeast Saccharomyces cerevisiae. Proteins such as TDP-43 and FUS, implicated in amyotrophic lateral sclerosis, and ?-synuclein, implicated in Parkinson's disease, are toxic and form cytoplasmic aggregates in yeast. These features recapitulate protein pathologies observed in patients with these disorders. Thus, yeast are an ideal platform for isolating toxicity suppressors from libraries of protein variants. We are interested in applying protein disaggregases to eliminate misfolded toxic protein conformers. Specifically, we are engineering Hsp104, a hexameric AAA+ protein from yeast that is uniquely capable of solubilizing both disordered aggregates and amyloid and returning the proteins to their native conformations. While Hsp104 is highly conserved in eukaryotes and eubacteria, it has no known metazoan homologue. Hsp104 has only limited ability to eliminate disordered aggregates and amyloid fibers implicated in human disease. Thus, we aim to engineer Hsp104 variants to reverse the protein misfolding implicated in neurodegenerative disorders. We have developed methods to screen large libraries of Hsp104 variants for suppression of proteotoxicity in yeast. As yeast are prone to spontaneous nonspecific suppression of toxicity, a two-step screening process has been developed to eliminate false positives. Using these methods, we have identified a series of potentiated Hsp104 variants that potently suppress the toxicity and aggregation of TDP-43, FUS, and ?-synuclein. Here, we describe this optimized protocol, which could be adapted to screen libraries constructed using any protein backbone for suppression of toxicity of any protein that is toxic in yeast. PMID:25407485

Jackrel, Meredith E; Tariq, Amber; Yee, Keolamau; Weitzman, Rachel; Shorter, James

2014-01-01

11

Emergence and molecular characterisation of non-toxigenic tox gene-bearing Corynebacterium diphtheriae biovar mitis in the United Kingdom, 2003-2012.  

PubMed

Non-toxigenic Corynebacterium diphtheriae have become increasingly recognised as emerging pathogens across Europe causing severe invasive disease. A subset of non-toxigenic C. diphtheriae are ‘non-toxigenic tox gene-bearing’ (NTTB) strains; these strains are genotypically toxpositive, but do not express the protein. The circulation of NTTB strains was first observed during the 1990s upsurge of diphtheria in Eastern Europe but has not been reported in other European countries. Circulation of NTTB strains could be considered an increased risk for diphtheria and other related diseases, given their possible role as a tox gene reservoir with the theoretical risk of re-emerging toxin expression. Here we report the characterisation of 108 non-toxigenic C. diphtheriae biovar mitis isolates submitted to the World Health Organization (WHO) Global Reference Centre for Diphtheria at Public Health England, London, between 2003 and 2012, in order to determine the presence of NTTB strains. Using molecular methods, five NTTB isolates were identified; four human isolates (MLST type 212) and one isolate from a companion cat (MLST type 40). The emergence of these strains could indicate continuation of the circulation of potentially toxigenic strains and appropriate laboratory diagnostic methods should be used for detection. Given the complacency that currently exists in Europe awareness with regards to diphtheria diagnostics must be enhanced. PMID:24925458

Zakikhany, K; Neal, S; Efstratiou, A

2014-01-01

12

Isolation and morphological studies of a variant of Ceratodon purpureus  

Microsoft Academic Search

Summary Morphological variants from protonema ofCeratodon purpureus (Hedw.) were obtained using nitrosoguanidine (NTG). In one of the variants, reduced growth was accompagnied by hyperbranching and inhibition of caulogenesis. The deposition of branches in this strain can be studied by enzymatic analysis.

M. Larpent-Gourgaud; M. P. Aumaitre

1982-01-01

13

A Clinical and Epidemiological Review of Non-toxigenic Clostridium difficile  

PubMed Central

Clostridium difficile is a significant nosocomial threat to human health and is the most commonly identified cause of antibiotic associated diarrhea. The development of C. difficile colitis requires production of toxins A and/or B, but some strains do not express these proteins. These non-toxigenic C. difficile (NTCD) have garnered attention for their capacity to colonize humans and potentially reduce the risk for symptomatic colitis caused by toxigenic strains. Isolates of NTCD have been obtained from the environment as well as from animal and human sources. Studies in a hamster CDI model have demonstrated a protective effect of NTCD against toxigenic infection. The extent to which this protective effect of NTCD occurs in humans remains to be defined. Evidence for a therapeutic or preventive role for NTCD is limited but clinical prophylaxis studies are ongoing. NTCD potentially represents an exciting new tool in preventing CDI and its recurrences. PMID:23727391

Natarajan, Mukil; Walk, Seth T.; Young, Vincent B.; Aronoff, David M.

2013-01-01

14

Differential functional properties of calmodulin-dependent protein kinase IIgamma variants isolated from smooth muscle.  

PubMed Central

Six variants of calmodulin-dependent protein kinase IIgamma were isolated from a ferret-aorta smooth-muscle cDNA library. Variant G-2 is generated by a novel alternative polyadenylation, utilizing a site contained in an intron. The last 77 residues of the association domain are replaced with 99 residues of a unique sequence containing Src homology 3-domain-binding motifs, which alter catalytic activity. Variant C-2 has an eight-residue deletion in an ATP-binding motif and does not autophosphorylate Thr(286), but does phosphorylate exogenous substrate. Two variants, B and J, autodephosphorylate. Four variants differing only in the variable domain have differing catalytic activities, despite identical sequences in the catalytic domains. Thus structural features determined by variable and association domains are important for the catalytic activity of calmodulin-dependent protein kinase II. PMID:12603201

Gangopadhyay, Samudra S; Barber, Amy L; Gallant, Cynthia; Grabarek, Zenon; Smith, Janet L; Morgan, Kathleen G

2003-01-01

15

Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers  

PubMed Central

Clostridium difficile is a major nosocomial pathogen and the main causative agent of antibiotic-associated diarrhoea. The organism produces two potent toxins, A and B, which are its major virulence factors. These are chromosomally encoded on a region termed the pathogenicity locus (PaLoc), which also contains regulatory genes, and is absent in non-toxigenic strains. Here we show that the PaLoc can be transferred from the toxin-producing strain, 630?erm, to three non-toxigenic strains of different ribotypes. One of the transconjugants is shown by cytotoxicity assay to produce toxin B at a similar level to the donor strain, demonstrating that a toxigenic C. difficile strain is capable of converting a non-toxigenic strain to a toxin producer by horizontal gene transfer. This has implications for the treatment of C. difficile infections, as non-toxigenic strains are being tested as treatments in clinical trials. PMID:24131955

Brouwer, Michael S.M.; Roberts, Adam P.; Hussain, Haitham; Williams, Rachel J.; Allan, Elaine; Mullany, Peter

2013-01-01

16

Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain  

Microsoft Academic Search

Two patients with relapsingClostridium difficilediarrhoea following metronidazole and vancomycin therapy were colonised with a non-toxigenic avirulentClostridium difficilestrain given orally in three doses. Both patients appeared to respond without sideeffects. Oral bacteriotherapy with a defined nontoxigenic strain ofClostridium difficilewould appear to represent an acceptable, alternative and novel way to treat hospitalised patients who relapse withClostridium difficilediarrhoea after specific antibiotic therapy.

D. Seal; S. P. Borriello; F. Barclay; A. Welch; M. Piper; M. Bonnycastle

1987-01-01

17

Isolation and characterization of brewer's yeast variants with improved fermentation performance under high-gravity conditions.  

PubMed

To save energy, space, and time, today's breweries make use of high-gravity brewing in which concentrated medium (wort) is fermented, resulting in a product with higher ethanol content. After fermentation, the product is diluted to obtain beer with the desired alcohol content. While economically desirable, the use of wort with an even higher sugar concentration is limited by the inability of brewer's yeast (Saccharomyces pastorianus) to efficiently ferment such concentrated medium. Here, we describe a successful strategy to obtain yeast variants with significantly improved fermentation capacity under high-gravity conditions. We isolated better-performing variants of the industrial lager strain CMBS33 by subjecting a pool of UV-induced variants to consecutive rounds of fermentation in very-high-gravity wort (>22 degrees Plato). Two variants (GT336 and GT344) showing faster fermentation rates and/or more-complete attenuation as well as improved viability under high ethanol conditions were identified. The variants displayed the same advantages in a pilot-scale stirred fermenter under high-gravity conditions at 11 degrees C. Microarray analysis identified several genes whose altered expression may be responsible for the superior performance of the variants. The role of some of these candidate genes was confirmed by genetic transformation. Our study shows that proper selection conditions allow the isolation of variants of commercial brewer's yeast with superior fermentation characteristics. Moreover, it is the first study to identify genes that affect fermentation performance under high-gravity conditions. The results are of interest to the beer and bioethanol industries, where the use of more-concentrated medium is economically advantageous. PMID:17158628

Blieck, Lies; Toye, Geert; Dumortier, Françoise; Verstrepen, Kevin J; Delvaux, Freddy R; Thevelein, Johan M; Van Dijck, Patrick

2007-02-01

18

Isolation and Characterization of Brewer's Yeast Variants with Improved Fermentation Performance under High-Gravity Conditions?  

PubMed Central

To save energy, space, and time, today's breweries make use of high-gravity brewing in which concentrated medium (wort) is fermented, resulting in a product with higher ethanol content. After fermentation, the product is diluted to obtain beer with the desired alcohol content. While economically desirable, the use of wort with an even higher sugar concentration is limited by the inability of brewer's yeast (Saccharomyces pastorianus) to efficiently ferment such concentrated medium. Here, we describe a successful strategy to obtain yeast variants with significantly improved fermentation capacity under high-gravity conditions. We isolated better-performing variants of the industrial lager strain CMBS33 by subjecting a pool of UV-induced variants to consecutive rounds of fermentation in very-high-gravity wort (>22° Plato). Two variants (GT336 and GT344) showing faster fermentation rates and/or more-complete attenuation as well as improved viability under high ethanol conditions were identified. The variants displayed the same advantages in a pilot-scale stirred fermenter under high-gravity conditions at 11°C. Microarray analysis identified several genes whose altered expression may be responsible for the superior performance of the variants. The role of some of these candidate genes was confirmed by genetic transformation. Our study shows that proper selection conditions allow the isolation of variants of commercial brewer's yeast with superior fermentation characteristics. Moreover, it is the first study to identify genes that affect fermentation performance under high-gravity conditions. The results are of interest to the beer and bioethanol industries, where the use of more-concentrated medium is economically advantageous. PMID:17158628

Blieck, Lies; Toye, Geert; Dumortier, Françoise; Verstrepen, Kevin J.; Delvaux, Freddy R.; Thevelein, Johan M.; Van Dijck, Patrick

2007-01-01

19

A rare functional cardioprotective APOC3 variant has risen in frequency in distinct population isolates.  

PubMed

Isolated populations can empower the identification of rare variation associated with complex traits through next generation association studies, but the generalizability of such findings remains unknown. Here we genotype 1,267 individuals from a Greek population isolate on the Illumina HumanExome Beadchip, in search of functional coding variants associated with lipids traits. We find genome-wide significant evidence for association between R19X, a functional variant in APOC3, with increased high-density lipoprotein and decreased triglycerides levels. Approximately 3.8% of individuals are heterozygous for this cardioprotective variant, which was previously thought to be private to the Amish founder population. R19X is rare (<0.05% frequency) in outbred European populations. The increased frequency of R19X enables discovery of this lipid traits signal at genome-wide significance in a small sample size. This work exemplifies the value of isolated populations in successfully detecting transferable rare variant associations of high medical relevance. PMID:24343240

Tachmazidou, Ioanna; Dedoussis, George; Southam, Lorraine; Farmaki, Aliki-Eleni; Ritchie, Graham R S; Xifara, Dionysia K; Matchan, Angela; Hatzikotoulas, Konstantinos; Rayner, Nigel W; Chen, Yuan; Pollin, Toni I; O'Connell, Jeffrey R; Yerges-Armstrong, Laura M; Kiagiadaki, Chrysoula; Panoutsopoulou, Kalliope; Schwartzentruber, Jeremy; Moutsianas, Loukas; Tsafantakis, Emmanouil; Tyler-Smith, Chris; McVean, Gil; Xue, Yali; Zeggini, Eleftheria

2013-01-01

20

A Severe Hellenic CMV Tomato Isolate: Symptom Variability in Tobacco, Characterization and Discrimination of Variants  

Microsoft Academic Search

A severe strain of Cucumber mosaic virus (CMV) originating from an infected tomato plant (Gastouni-Olympia, Greece) was isolated in tobacco (Nicotiana tabacum cv. Xanthi nc), after three serial local lesion passages in Chenopodium quinoa and designated CMV-G. CMV-G induces yellow mosaic (YM) symptoms in tobacco. When CMV-G was passed mechanically through C. quinoa, phenotypic variants inducing YM or green mild

A. P. Sclavounos; A. E. Voloudakis; Ch. Arabatzis; P. E. Kyriakopoulou

2006-01-01

21

Isolation of UV-sensitive variants of CHO-K1 by nylon cloth replica plating  

Microsoft Academic Search

Techniques are described which permit the identification and isolation of UV-sensitive variants from mutagenized populations of Chinese hamster ovary (CHO) cells. Identification is based on the observation that within two days after receiving a dose of approximately 240 ergs\\/mm2 of UV irradiation most of the cells in a colony of CHO detach from the surface of a plastic tissue culture

T. D. Stamato; Charles A. Waldren

1977-01-01

22

Emergence of Clostridium botulinum type B-like nontoxigenic organisms in a patient with type B infant botulism.  

PubMed Central

We encountered a patient with infant botulism caused by a single clone of Clostridium botulinum type B. In the early convalescent phase, a C. botulinum type B-like nontoxigenic organism emerged in the feces instead. Growth inhibition of toxigenic strains by nontoxigenic strains was examined. PMID:9230406

Yamakawa, K; Karasawa, T; Kakinuma, H; Maruyama, H; Takahashi, H; Nakamura, S

1997-01-01

23

High Risk Population Isolate Reveals Low Frequency Variants Predisposing to Intracranial Aneurysms  

PubMed Central

3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases. PMID:24497844

Kurki, Mitja I.; Gaal, Emilia Ilona; Kettunen, Johannes; Lappalainen, Tuuli; Menelaou, Androniki; Anttila, Verneri; van 't Hof, Femke N. G.; von und zu Fraunberg, Mikael; Helisalmi, Seppo; Hiltunen, Mikko; Lehto, Hanna; Laakso, Aki; Kivisaari, Riku; Koivisto, Timo; Ronkainen, Antti; Rinne, Jaakko; Kiemeney, Lambertus A. L.; Vermeulen, Sita H.; Kaunisto, Mari A.; Eriksson, Johan G.; Aromaa, Arpo; Perola, Markus; Lehtimaki, Terho; Raitakari, Olli T.; Salomaa, Veikko; Gunel, Murat; Dermitzakis, Emmanouil T.; Ruigrok, Ynte M.; Rinkel, Gabriel J. E.; Niemela, Mika; Hernesniemi, Juha; Ripatti, Samuli; de Bakker, Paul I. W.; Palotie, Aarno; Jaaskelainen, Juha E.

2014-01-01

24

High risk population isolate reveals low frequency variants predisposing to intracranial aneurysms.  

PubMed

3% of the population develops saccular intracranial aneurysms (sIAs), a complex trait, with a sporadic and a familial form. Subarachnoid hemorrhage from sIA (sIA-SAH) is a devastating form of stroke. Certain rare genetic variants are enriched in the Finns, a population isolate with a small founder population and bottleneck events. As the sIA-SAH incidence in Finland is >2× increased, such variants may associate with sIA in the Finnish population. We tested 9.4 million variants for association in 760 Finnish sIA patients (enriched for familial sIA), and in 2,513 matched controls with case-control status and with the number of sIAs. The most promising loci (p<5E-6) were replicated in 858 Finnish sIA patients and 4,048 controls. The frequencies and effect sizes of the replicated variants were compared to a continental European population using 717 Dutch cases and 3,004 controls. We discovered four new high-risk loci with low frequency lead variants. Three were associated with the case-control status: 2q23.3 (MAF 2.1%, OR 1.89, p 1.42×10-9); 5q31.3 (MAF 2.7%, OR 1.66, p 3.17×10-8); 6q24.2 (MAF 2.6%, OR 1.87, p 1.87×10-11) and one with the number of sIAs: 7p22.1 (MAF 3.3%, RR 1.59, p 6.08×-9). Two of the associations (5q31.3, 6q24.2) replicated in the Dutch sample. The 7p22.1 locus was strongly differentiated; the lead variant was more frequent in Finland (4.6%) than in the Netherlands (0.3%). Additionally, we replicated a previously inconclusive locus on 2q33.1 in all samples tested (OR 1.27, p 1.87×10-12). The five loci explain 2.1% of the sIA heritability in Finland, and may relate to, but not explain, the increased incidence of sIA-SAH in Finland. This study illustrates the utility of population isolates, familial enrichment, dense genotype imputation and alternate phenotyping in search for variants associated with complex diseases. PMID:24497844

Kurki, Mitja I; Gaál, Emília Ilona; Kettunen, Johannes; Lappalainen, Tuuli; Menelaou, Androniki; Anttila, Verneri; van 't Hof, Femke N G; von Und Zu Fraunberg, Mikael; Helisalmi, Seppo; Hiltunen, Mikko; Lehto, Hanna; Laakso, Aki; Kivisaari, Riku; Koivisto, Timo; Ronkainen, Antti; Rinne, Jaakko; Kiemeney, Lambertus A L; Vermeulen, Sita H; Kaunisto, Mari A; Eriksson, Johan G; Aromaa, Arpo; Perola, Markus; Lehtimäki, Terho; Raitakari, Olli T; Salomaa, Veikko; Gunel, Murat; Dermitzakis, Emmanouil T; Ruigrok, Ynte M; Rinkel, Gabriel J E; Niemelä, Mika; Hernesniemi, Juha; Ripatti, Samuli; de Bakker, Paul I W; Palotie, Aarno; Jääskeläinen, Juha E

2014-01-01

25

Isolation of Chlamydia pneumoniae Clonal Variants by a Focus-Forming Assay  

PubMed Central

Chlamydia pneumoniae is an obligate intracellular prokaryotic human pathogen that causes community-acquired respiratory infection and has been associated with atherosclerosis and cardiovascular disease. Unexpected results from genomic sequencing indicate that significant intrastrain polymorphism exists for some C. pneumoniae isolates. These polymorphisms could reflect genotypes with differing disease-causing characteristics. A definitive means to test this hypothesis is to obtain genetically homogeneous clonal populations of the pathogen and test them in models of infection and disease. To date, methods for cloning C. pneumoniae have not been reported. In this study, we describe the isolation of clonal variants with genetic differences in the tyrP locus from a polymorphic respiratory isolate, using a novel focus-forming assay. These results now allow investigations on the biology and pathogenesis of C. pneumoniae clonal genovars that could lead to new insights into the pathogenesis of this important human pathogen. PMID:12228314

Gieffers, Jens; Belland, Robert J.; Whitmire, William; Ouellette, Scot; Crane, Deborah; Maass, Matthias; Byrne, Gerald I.; Caldwell, Harlan D.

2002-01-01

26

Isolation of UV-sensitive variants of CHO-K1 by nylon cloth replica plating.  

PubMed

Techinques are described which permit the identification and isolation of UV-sensitive variants from mutagenized populations of Chinese hamster ovary (CHO) cells. Identification is based on the observation that within two days after receiving a dose of approximately 240 ergs/mm2 of UV irradiation most of the cells in a colony of CHO detach from the surface of a plastic tissue culture dish. At a lower dose of UV, which does not kill or detach a significant number of parental cells, UV-sensitive colonies are killed and become detached. Thus a clear plaque is produced in a lawn of unirradiated parental cells, marking the site occupied by a sensitive colony. Live cells from such sensitive colonies have been recovered from a nylon cloth replica prepared prior to irradiation and characterized. One UV-sensitive variant (CHO-UV-1) is indistinguishable from parental cells in X-ray resistance, chromosome number, generation time, and duration of the phases of the cell cycle. For UV irradiation the hit number (-n), shoulder width (Dq), and mean lethal dose (Do) for the variant are 2.8, 21 ergs/mm2, and 21 ergs/mm2, respectively, as compared to 2.6, 36 ergs/mm2, and 45 ergs/mm2 for CHO-K1 cells. These values have not changed for a period of eight months in culture. PMID:341370

Stamato, T D; Waldren, C A

1977-07-01

27

Immunogenic capacity of tum--variants isolated from a rat rhabdomyosarcoma.  

PubMed

An increasing number of reports highlight the fact that tumour cells are able to give rise in vitro to immunogenic variants, which are defined in vivo as being non tumorigenic, tum-. We have observed the emergence of immunogenic variants, derived from a primary nickel-induced rat rhabdomyosarcoma established in culture (RMS 9-4/0), resistant to treatment with the chloronitrosourea, chlorozotocin (CZT) (R-lines). They were separated from the whole population of cells by a cloning procedure. Furthermore, we demonstrate that the cloning procedure by itself allows the isolation of tum- variant designated as C-lines. In both cases, the tum- phenotype was observed after s.c. injection of cells into syngeneic rats with a broad range of R9 or C8 cells (10(4) to 10(7). This characteristic was inherited in a stable manner. Athymic mice developed tumours of rat rhabdomyosarcoma origin when grafted with 10(5) cells. Immunization of rats with one R variant (R9) tum- protected the rats grafted with the parental RMS 9-4/0 cells against metastatic invasion of the lungs, but not against local tumour growth, and rats grafted with a CZT-resistant tum+ cell variant S4T (in vivo-derived) against its hepatic and pulmonary metastases, while the local tumour progressed as usual. Immunization of rats with one C variant (C8) tum- cells did not protect them against either metastases or local growth of the implanted tumours. Both R and C lines cells became progressively resistant to NK- and macrophage-induced cytotoxicity. Splenic lymphocyte transfer from immune rats into nude mice, i.e., the Winn test, showed a complete degree of protection against C8 or R9 tumour growth. We conclude that two different antigenicities were revealed, one common to R9 and C8 cells in relation with their selection procedure by repeated cloning. Another antigenicity appeared in the R9 line, selected by CZT-resistance. The anti R9 cell immunization against CZT-resistant tum+ S4T could argue in favour of CZT action in the acquisition of R9 cell antigenicity. More likely, an amplification of antigens rather than induction of a new antigen could explain the protection of anti R9 immunized rats against parental tumour metastases. PMID:2956985

Pauwels-Vergely, C; Poupon, M F

1987-07-01

28

More than one variant of Listeria monocytogenes isolated from each of two human cases of invasive listeriosis.  

PubMed

Two variants of Listeria monocytogenes were isolated from blood cultures from each of two patients with listeriosis. Each variant displayed a two-band difference in DNA profile from the other by pulsed-field gel electrophoresis. Although this difference in profile is insufficient to distinguish clearly between the variants, the possibility of co-infection with different strains of L. monocytogenes needs to be considered. We suggest that more than one colony should be selected for molecular typing to aid interpretation during investigation of the sources and routes of Listeria infection. PMID:17109771

Tham, W; Valladares, G Lopez; Helmersson, S; Osterlund, A; Danielsson-Tham, M-L

2007-07-01

29

Verotoxins in Bovine and Meat Verotoxin-Producing Escherichia coli Isolates: Type, Number of Variants, and Relationship to Cytotoxicity?  

PubMed Central

In this study, we determined vt subtypes and evaluated verotoxicity in basal as well as induced conditions of verotoxin-producing Escherichia coli (VTEC) strains isolated from cattle and meat products. Most (87%) of the 186 isolates carried a vt2 gene. Moreover, the vt2 subtype, which is associated with serious disease, was present in 42% of our VTEC collection. The other vt subtypes detected were vt1, vt1d, vt2vha, vt2vhb, vt2O118, vt2d (mucus activatable), and vt2g. A total of 41 (22%) of the isolates possessed more than one vt subtype in its genome, and among them the most frequent combination was vt1/vt2, but we also observed multiple combinations among vt2 subtypes. Differences in verotoxicity titers were found among a selection of 54 isolates. Among isolates with a single vt2 variant, those carrying the vt2 subtype had high titers under both uninduced and induced conditions. However, the highest increase in cytotoxicity under mitomycin C treatment was detected among the strains carrying vt2vha or vt2hb variants. Notably, the isolates carrying the vt1 subtype showed a lesser increase than that of most of the vt2-positive VTEC strains. Furthermore, the presence of more than one vt gene variant in the same isolate was not reflected in higher titers, and generally the titers were lower than those for strains with only one gene variant. The main observation was that both basal and induced cytotoxic effects seemed to be associated with the type and number of vt variants more than with the serotype or origin of the isolate. PMID:21037301

Kruger, Alejandra; Lucchesi, Paula M. A.; Parma, Alberto E.

2011-01-01

30

Region of Difference 4 in Alpine Mycobacterium caprae Isolates Indicates Three Variants  

PubMed Central

The lack of complete genome sequence information for Mycobacterium caprae complicates a robust differentiation of M. caprae and Mycobacterium bovis. In this study, the presence or absence of M. caprae-specific single nucleotide polymorphisms in lepA and gyrB genes was assessed. The region of difference 4 (RD4) was analyzed for the identification and characterization of M. caprae. Molecular characteristics were evaluated in 12 recent M. caprae isolates from livestock and wildlife collected over a 3-year period in Bavaria, Germany. Conventional PCR strategies, sequence analysis of PCR fragments, and data from a next-generation sequencing approach together with variable-number tandem-repeat genotyping were utilized. Single nucleotide polymorphisms in the lepA and gyrB genes indicating the presence of M. caprae were detected in all the isolates. At least three different RD4 variants were found for Alpine M. caprae isolates. The results demonstrate that the RD4 region is rather heterogeneous in M. caprae genomes. As assumed by others, the presence of RD4 is critical for PCR-based differentiation of M. caprae from M. bovis, but in addition, the observed variability of RD4 allows the identification of M. caprae genotypes and may be indicative of a geographical-type appearance. PMID:23408688

Prodinger, Wolfgang M.; Blum, Helmut; Krebs, Stefan; Gellert, Susanne; Muller, Matthias; Neuendorf, Erdmute; Sedlmaier, Florian; Buttner, Mathias

2013-01-01

31

Identification and characterization of porcine kobuvirus variant isolated from suckling piglet in Gansu province, China.  

PubMed

Kobuviruses comprise three species, the Aichivirus A, Aichivirus B, and Aichivirus C (porcine kobuvirus). Porcine kobuvirus is endemic to pig farms and is not restricted geographically but, rather, is distributed worldwide. The complete genomic sequences of four porcine kobuvirus strains isolated during a diarrhea outbreak in piglets in the Gansu province of China were determined. Two of these strains exhibited variations relative to the traditional strains. The potential 3C/3D cleavage sites of the variant strains were Q/C, which differed from the Q/S in the traditional porcine kobuvirus genome. A 90-nucleotide deletion in the 2B protein and a single nucleotide insertion in the 3'UTR were found in the variant strains. The VP1 regions of all four porcine kobuviruses in our study were highly variable (81%-86%). Ten common amino acid mutations were found specifically at certain positions within the VP1 region. Significant recombination sites were identified using SimPlot scans of whole genome sequences. Porcine kobuviruses were also detected in pig serum, indicating that the virus can escape the gastrointestinal tract and travel to the circulatory system. These findings suggest that mutations and recombination events may have contributed to the high level of genetic diversity of porcine kobuviruses and serve as a driving force in its evolution. PMID:24145960

Fan, Shengtao; Sun, Heting; Ying, Ying; Gao, Xiaolong; Wang, Zheng; Yu, Yicong; Li, Yuanguo; Wang, Tiecheng; Yu, Zhijun; Yang, Songtao; Zhao, Yongkun; Qin, Chuan; Gao, Yuwei; Xia, Xianzhu

2013-10-01

32

Novel Allelic Variants of Mycobacteria Isolated in Brazil as Determined by PCR-Restriction Enzyme Analysis of hsp65  

Microsoft Academic Search

Human isolates of Mycobacterium collected in 16 different states of Brazil were submitted to PCR-restriction analysis (PRA) of a 439-bp fragment of the hsp65 gene with HaeIII and BstEII. Fourteen allelic variants not described in clinical isolates so far were observed among 36 (10%) of 356 Brazilian strains, including a new pattern for Mycobacterium scrofulaceum, M. intracellulare, and M. flavescens,

A. da Silva Rocha; A. M. Werneck Barreto; C. E. Dias Campos; M. Villas-Boas da Silva; L. Fonseca; M. H. Saad; W. M. Degrave; P. N. Suffys

2002-01-01

33

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants.  

PubMed

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10(-26)). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10(-36)). We demonstrate significant power gains in detecting medical trait associations. PMID:25373335

Panoutsopoulou, Kalliope; Hatzikotoulas, Konstantinos; Xifara, Dionysia Kiara; Colonna, Vincenza; Farmaki, Aliki-Eleni; Ritchie, Graham R S; Southam, Lorraine; Gilly, Arthur; Tachmazidou, Ioanna; Fatumo, Segun; Matchan, Angela; Rayner, Nigel W; Ntalla, Ioanna; Mezzavilla, Massimo; Chen, Yuan; Kiagiadaki, Chrysoula; Zengini, Eleni; Mamakou, Vasiliki; Athanasiadis, Antonis; Giannakopoulou, Margarita; Kariakli, Vassiliki-Eirini; Nsubuga, Rebecca N; Karabarinde, Alex; Sandhu, Manjinder; McVean, Gil; Tyler-Smith, Chris; Tsafantakis, Emmanouil; Karaleftheri, Maria; Xue, Yali; Dedoussis, George; Zeggini, Eleftheria

2014-01-01

34

Isolation and characterization of a Salmonella enterica serotype Typhi variant and its clinical and public health implications.  

PubMed

We report the isolation and characterization of a member of the family Enterobacteriaceae isolated from the gallbladder pus of a food handler. Conventional biochemical tests suggested Salmonella enterica serotype Typhi, but the isolate agglutinated with poly(O), 2O, 9O, and Vi Salmonella antisera but not with poly(H) or any individual H Salmonella antisera. 16S rRNA gene sequencing showed that there were two base differences between the isolate and Salmonella enterica serotype Montevideo, four base differences between the isolate and serotype Typhi, five base differences between the isolate and Salmonella enterica serotype Typhimurium, and six base differences between the isolate and Salmonella enterica serotype Dublin, indicating that the isolate was a strain of S. enterica. Electron microscopy confirmed that the isolate was aflagellated. The flagellin gene sequence of the isolate was 100% identical to that of the H1-d flagellin gene of serotype Typhi. Sequencing of the rfbE gene, which encoded the CDP-tyvelose epimerase of the isolate, showed that there was a point mutation at position +694 (G-->T), leading to an amino acid substitution (Gly-->Cys). This may have resulted in a protein of reduced catalytic activity and hence the presence of both 2O and 9O antigens. We therefore concluded that the isolate was a variant of serotype Typhi. Besides antibiotic therapy and cholecystectomy, removal of all stones in the biliary tree was performed for eradication of the carrier state. PMID:11230457

Woo, P C; Fung, A M; Wong, S S; Tsoi, H W; Yuen, K Y

2001-03-01

35

New approach to the management of Clostridium difficile infection: colonisation with non-toxigenic C. difficile during daily ampicillin or ceftriaxone administration  

Microsoft Academic Search

Non-toxigenic strains of Clostridium difficile are highly effective in preventing toxigenic C. difficile infection in hamsters when given following a single dose of an antimicrobial agent. The goal of this study was to determine the ability of non-toxigenic C. difficile to colonise hamsters during administration of an antibiotic to which the organisms are resistant — ceftriaxone — and an antibiotic

Michelle M. Merrigan; Susan P. Sambol; Stuart Johnson; Dale N. Gerding

2009-01-01

36

Isolation of a Variant Strain of Pleurotus eryngii and the Development of Specific DNA Markers to Identify the Variant Strain  

PubMed Central

A degenerated strain of Pleurotus eryngii KNR2312 was isolated from a commercial farm. Random amplified polymorphic DNA analysis performed on the genomic DNA of the normal and degenerated strains of this species revealed differences in the DNA banding pattern. A unique DNA fragment (1.7 kbp), which appeared only in the degenerated strain, was isolated and sequenced. Comparing this sequence with the KNR2312 genomic sequence showed that the sequence of the degenerated strain comprised three DNA regions that originated from nine distinct scaffolds of the genomic sequence, suggesting that chromosome-level changes had occurred in the degenerated strain. Using the unique sequence, three sets of PCR primers were designed that targeted the full length, the 5' half, and the 3' half of the DNA. The primer sets P2-1 and P2-2 yielded 1.76 and 0.97 kbp PCR products, respectively, only in the case of the degenerated strain, whereas P2-3 generated a 0.8 kbp product in both the normal and the degenerated strains because its target region was intact in the normal strain as well. In the case of the P2-1 and P2-2 sets, the priming regions of the forward and reverse primers were located at distinct genomic scaffolds in the normal strain. These two primer sets specifically detected the degenerate strain of KNR2312 isolated from various mushrooms including 10 different strains of P. eryngii, four strains of P. ostreatus, and 11 other wild mushrooms. PMID:24808734

Lee, Hyun-Jun; Kim, Sang-Woo; Ryu, Jae-San; Lee, Chang-Yun

2014-01-01

37

Characterization of novel alleles of toxin co-regulated pilus A gene (tcpA) from environmental isolates of Vibrio cholerae.  

PubMed

Vibrio cholerae is causative agent of life threatening diarrheal disease, cholera. The toxin co-regulated pilus (TCP) is a critical colonization factor of V. cholerae and it also serves as receptor for CTX?. In this study, we describe nucleotide sequence of four novel alleles of tcpA gene from toxigenic and non-toxigenic V. cholerae isolated from environmental sources. The phylogenetic analysis of tcpA revealed that it is related to tcpA of newly emerged O1 strain and unrelated to tcpA of wild type (classical and El Tor strains). All strains showed variant tcpA and also harbored intact Vibrio Pathogenicity Island (VPI). The expression of all variant alleles was demonstrated by RT-PCR. PMID:20967447

Kumar, Praveen; Thulaseedharan, Anuja; Chowdhury, Gautam; Ramamurthy, Thandavarayan; Thomas, Sabu

2011-03-01

38

Isolation of colonial variants of Bacteroides gingivalis W50 with a reduced virulence  

Microsoft Academic Search

Summary. The spontaneous appearance of unusual colony forms was observed during prolonged growth of Bacteroides gingivalis W50 in a chemostat. Two variants were selected for further study which could be distinguished from the parent strain by the rate and intensity of pigmentation of their colonies. For example, after anaerobic incubation for 14 days, variant WSO\\/BRl produced brown colonies whereas those

A. S. Mckee; A. S. Mcdermid; R. Wait; A. Baskerville; P. D. Marsh

1988-01-01

39

Isolation and characterization of invasive and noninvasive variants of a rat bladder tumor cell line.  

PubMed

We isolated, in vitro, spontaneous variants of the rat bladder tumor NBT-II cell line with a distinctive morphology. Of five sublines obtained, three (NBT-L1, L2a and L2b) exhibited an elongated shape and moderate to high invasive activity in vitro. The other two sublines (NBT-T1 and T2) formed tight colonies and exhibited very low or negligible invasive activity. The contents of mRNAs coding for E-cadherin and cadherin-associated molecules (alpha-catenin and beta-catenin) were not correlated with the invasive activity of the cells. However, the expression level of the E-cadherin protein, but not those of catenins, was lower in invasive cells (NBT-L1, L2a and L2b) than in noninvasive cells (NBT-T1 and T2). Analysis of mRNAs coding for several growth factors and their receptors showed that the transforming growth factor alpha mRNA content in invasive cells was higher than that in noninvasive cells, and that the content of epidermal growth factor receptor mRNA was low in NBT-T2. Although NBT-II is known to acquire a fibroblastic appearance and cell motility in response to several growth factors, the conditioned media of the invasive sublines hardly affected the morphology or motility of noninvasive cells. These results indicate that the decreased E-cadherin expression is closely associated with the transition from the noninvasive to the invasive phenotype of the bladder tumor cells, and that a post-transcriptional process is important in the control of E-cadherin expression in the cells. These sublines may be useful as models for studies on the progression of bladder tumors. PMID:9369930

Nishi, N; Inui, M; Kishi, Y; Miyanaka, H; Wada, F

1997-09-01

40

Emergence of an Invasive Clone of Nontoxigenic Corynebacterium diphtheriae in the Urban Poor Population of Vancouver, Canada  

Microsoft Academic Search

Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae

M. G. Romney; D. L. Roscoe; K. Bernard; S. Lai; A. Efstratiou; A. M. Clarke

2006-01-01

41

Isolation of a variant human adenovirus identified based on phylogenetic analysis during an outbreak of acute keratoconjunctivitis in Chennai  

PubMed Central

Background & objectives: Though several viruses are responsible for conjunctivitis, but human adenovirus (HAdV) is by far the most common cause. Epidemic conjunctivitis causes morbidity and early detection of aetiological agent is essential in preventing spread of disease as some of serotypes of adenoviruses cause a severe form of conjunctivitis. This study was undertaken to identify the causative agent of conjunctivitis outbreak in Chennai in 2010. Methods: Conjunctival samples collected from 17 patients with conjunctivitis were subjected to virological investigations. Culture and PCR for detection of adenovirus and enterovirus were carried out. PCR positive products were further subjected for DNA sequencing. The nucleotide sequences of the hexons of isolates were analyzed by comparison with all 51 human adenovirus strains. Phylogenetic tree was constructed using DAMBE software. Results: Among 17 patients, seven were positive for adenovirus by PCR on the direct specimen, none was positive for enterovirus. Eleven of 30 conjunctival swabs showed cytopathic effect in HEp-2 cell line and were confirmed as HAdV by PCR. The DNA sequence data of the 11 isolates had equal percentage of homology with HAdV 6 and 2 on blast analysis. On phylogenetic analysis with GeneBank data of 51 adenovirus strains, 11 isolates from patients during the outbreak of conjunctivitis formed a separate clade indicating a new variant strain. Interpretation & conclusions: Based on phylogenetic analysis it was concluded that the recent conjunctivitis outbreak that occurred in Chennai was caused by a variant adenovirus strain. PMID:22960893

Janani, M.K.; Malathi, J.; Madhavan, H.N.

2012-01-01

42

Pullulan-hyperproducing color variant strain of Aureobasidium pullulans FB-1 newly isolated from phylloplane of Ficus sp.  

PubMed

The studies were carried out for the isolation of efficient pullulan producing strains of Aureobasidium pullulans. Five strains were isolated from phylloplane of different plants. Amongst these, three were producing black pigment melanin, while the remaining two produced pink pigment. These two color variant isolates of A. pullulans were designated as FB-1 and FG-1, and obtained from phylloplane of Ficus benjamina and Ficus glometa, respectively. The parameters employed for the identification of the isolates included morphology, nutritional assimilation patterns and exopolysaccharide (EPS) production. Isolates were compared with standard cultures for EPS production. A. pullulans FB-1 was the best producer of pullulan giving up to 1.9, 1.4 and 1.7 times more pullulan than the control of A. pullulans NCIM 976, NCIM 1048 and NCIM 1049, respectively. The IR spectra of the isolates and standard strains revealed that the polysaccharide was pullulan, but not aubasidan. The study also supported the fact that A. pullulans is a ubiquitous organism and phylloplane being the important niche of the organism. PMID:17869506

Singh, R S; Saini, G K

2008-06-01

43

Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants  

Microsoft Academic Search

The colonization of respiratory tract by Staphylococcus aureus is a frequent feature of cystic fibrosis (CF), especially in pediatric patients. The formation of small colony variants (SCVs), which produce reduced amounts of ?-toxin, is one of the proposed ways of staphylococcal accommodation in an intracellular niche. The aim of the present study was to compare some properties of S. aureus

Beata Sadowska; Agnieszka Bonar; Christof von Eiff; Richard A. Proctor; Magdalena Chmiela; Wies Rudnicka; Barbara Ró?alska

2002-01-01

44

Isolation of a variant Porphyromonas sp. from polymicrobial infections in central bearded dragons (Pogona vitticeps).  

PubMed

Isolates of gram-negative anaerobic bacteria from reptiles have only occasionally been identified to the genus and species level in the veterinary medical literature. In particular, reports identifying Porphyromonas spp. from infections in reptiles are scarce. The present report describes unique Porphyromonas isolates obtained from necrosuppurative infections in central bearded dragons (Pogona vitticeps). The isolates grew in the presence of oxygen, were strongly hemolytic, and did not produce detectable black, iron porphyrin pigment. Biochemical identification kit numeric biocodes gave high but unreliable probabilities (>99.9%) for identification as Porphyromonas gingivalis. Partial 16S ribosomal RNA gene sequences of the isolates were identical to each other and shared 91% identity with those of Porphyromonas gulae. The isolates may represent a new reptile-associated Porphyromonas species. PMID:21217036

Bemis, David A; Greenacre, Cheryl B; Bryant, Mary Jean; Jones, Rebekah D; Kania, Stephen A

2011-01-01

45

Isolation of Salmonella enterica Serovar Kentucky Strain ST 198 and Its H2S-Negative Variant from a Patient: Implications for Diagnosis.  

PubMed

H2S-producing multiresistant Salmonella enterica serovar Kentucky strain sequence type (ST) 198 and its non-H2S-producing variant were isolated from a patient. Whole-genome comparison showed a base addition in the gene encoding molybdenum cofactor biosynthesis protein C, which could affect H2S production in the variant. Lack of H2S production has implications for diagnosis of salmonella. PMID:25143568

Albert, M John; Al Obaid, Khaled; Alfouzan, Wadha; Sheikh, Abdul Rashid; Udo, Edet; Izumiya, Hidemasa; Bulach, Dieter M; Seemann, Torsten

2014-11-01

46

Mitochondrial DNA variant in COX1 subunit significantly alters energy metabolism of geographically divergent wild isolates in Caenorhabditis elegans.  

PubMed

Mitochondrial DNA (mtDNA) sequence variation can influence the penetrance of complex diseases and climatic adaptation. While studies in geographically defined human populations suggest that mtDNA mutations become fixed when they have conferred metabolic capabilities optimally suited for a specific environment, it has been challenging to definitively assign adaptive functions to specific mtDNA sequence variants in mammals. We investigated whether mtDNA genome variation functionally influences Caenorhabditis elegans wild isolates of distinct mtDNA lineages and geographic origins. We found that, relative to N2 (England) wild-type nematodes, CB4856 wild isolates from a warmer native climate (Hawaii) had a unique p.A12S amino acid substitution in the mtDNA-encoded COX1 core catalytic subunit of mitochondrial complex IV (CIV). Relative to N2, CB4856 worms grown at 20°C had significantly increased CIV enzyme activity, mitochondrial matrix oxidant burden, and sensitivity to oxidative stress but had significantly reduced lifespan and mitochondrial membrane potential. Interestingly, mitochondrial membrane potential was significantly increased in CB4856 grown at its native temperature of 25°C. A transmitochondrial cybrid worm strain, chpIR (M, CB4856>N2), was bred as homoplasmic for the CB4856 mtDNA genome in the N2 nuclear background. The cybrid strain also displayed significantly increased CIV activity, demonstrating that this difference results from the mtDNA-encoded p.A12S variant. However, chpIR (M, CB4856>N2) worms had significantly reduced median and maximal lifespan relative to CB4856, which may relate to their nuclear-mtDNA genome mismatch. Overall, these data suggest that C. elegans wild isolates of varying geographic origins may adapt to environmental challenges through mtDNA variation to modulate critical aspects of mitochondrial energy metabolism. PMID:24534730

Dingley, Stephen D; Polyak, Erzsebet; Ostrovsky, Julian; Srinivasan, Satish; Lee, Icksoo; Rosenfeld, Amy B; Tsukikawa, Mai; Xiao, Rui; Selak, Mary A; Coon, Joshua J; Hebert, Alexander S; Grimsrud, Paul A; Kwon, Young Joon; Pagliarini, David J; Gai, Xiaowu; Schurr, Theodore G; Hüttemann, Maik; Nakamaru-Ogiso, Eiko; Falk, Marni J

2014-05-29

47

Temporal Expression and Localization Patterns of Variant Surface Antigens in Clinical Plasmodium falciparum Isolates during Erythrocyte Schizogony  

PubMed Central

Avoidance of antibody-mediated immune recognition allows parasites to establish chronic infections and enhances opportunities for transmission. The human malaria parasite Plasmodium falciparum possesses a number of multi-copy gene families, including var, rif, stevor and pfmc-2tm, which encode variant antigens believed to be expressed on the surfaces of infected erythrocytes. However, most studies of these antigens are based on in vitro analyses of culture-adapted isolates, most commonly the laboratory strain 3D7, and thus may not be representative of the unique challenges encountered by P. falciparum in the human host. To investigate the expression of the var, rif-A, rif-B, stevor and pfmc-2tm family genes under conditions that mimic more closely the natural course of infection, ex vivo clinical P. falciparum isolates were analyzed using a novel quantitative real-time PCR approach. Expression patterns in the clinical isolates at various time points during the first intraerythrocytic developmental cycle in vitro were compared to those of strain 3D7. In the clinical isolates, in contrast to strain 3D7, there was a peak of expression of the multi-copy gene families rif-A, stevor and pfmc-2tm at the young ring stage, in addition to the already known expression peak in trophozoites. Furthermore, most of the variant surface antigen families were overexpressed in the clinical isolates relative to 3D7, with the exception of the pfmc-2tm family, expression of which was higher in 3D7 parasites. Immunofluorescence analyses performed in parallel revealed two stage-dependent localization patterns of RIFIN, STEVOR and PfMC-2TM. Proteins were exported into the infected erythrocyte at the young trophozoite stage, whereas they remained inside the parasite membrane during schizont stage and were subsequently observed in different compartments in the merozoite. These results reveal a complex pattern of expression of P. falciparum multi-copy gene families during clinical progression and are suggestive of diverse functional roles of the respective proteins. PMID:23166704

Bachmann, Anna; Petter, Michaela; Tilly, Ann-Kathrin; Biller, Laura; Uliczka, Karin A.; Duffy, Michael F.; Tannich, Egbert; Bruchhaus, Iris

2012-01-01

48

Temporal expression and localization patterns of variant surface antigens in clinical Plasmodium falciparum isolates during erythrocyte schizogony.  

PubMed

Avoidance of antibody-mediated immune recognition allows parasites to establish chronic infections and enhances opportunities for transmission. The human malaria parasite Plasmodium falciparum possesses a number of multi-copy gene families, including var, rif, stevor and pfmc-2tm, which encode variant antigens believed to be expressed on the surfaces of infected erythrocytes. However, most studies of these antigens are based on in vitro analyses of culture-adapted isolates, most commonly the laboratory strain 3D7, and thus may not be representative of the unique challenges encountered by P. falciparum in the human host. To investigate the expression of the var, rif-A, rif-B, stevor and pfmc-2tm family genes under conditions that mimic more closely the natural course of infection, ex vivo clinical P. falciparum isolates were analyzed using a novel quantitative real-time PCR approach. Expression patterns in the clinical isolates at various time points during the first intraerythrocytic developmental cycle in vitro were compared to those of strain 3D7. In the clinical isolates, in contrast to strain 3D7, there was a peak of expression of the multi-copy gene families rif-A, stevor and pfmc-2tm at the young ring stage, in addition to the already known expression peak in trophozoites. Furthermore, most of the variant surface antigen families were overexpressed in the clinical isolates relative to 3D7, with the exception of the pfmc-2tm family, expression of which was higher in 3D7 parasites. Immunofluorescence analyses performed in parallel revealed two stage-dependent localization patterns of RIFIN, STEVOR and PfMC-2TM. Proteins were exported into the infected erythrocyte at the young trophozoite stage, whereas they remained inside the parasite membrane during schizont stage and were subsequently observed in different compartments in the merozoite. These results reveal a complex pattern of expression of P. falciparum multi-copy gene families during clinical progression and are suggestive of diverse functional roles of the respective proteins. PMID:23166704

Bachmann, Anna; Petter, Michaela; Tilly, Ann-Kathrin; Biller, Laura; Uliczka, Karin A; Duffy, Michael F; Tannich, Egbert; Bruchhaus, Iris

2012-01-01

49

CCR5, GPR15, and CXCR6 are major coreceptors of human immunodeficiency virus type 2 variants isolated from individuals with and without plasma viremia.  

PubMed

Human immunodeficiency virus type 2 (HIV-2) is generally considered capable of using a broad range of coreceptors. Since HIV-2 variants from individuals with nonprogressive infection were not studied previously, the possibility that broad coreceptor usage is a property of variants associated with progressive infection could not be excluded. To test this, we determined the coreceptor usage of 43 HIV-2 variants isolated from six long-term-infected individuals with undetectable plasma viremia. Using GHOST indicator cells, we showed for the first time that the only coreceptors efficiently used by low-pathogenic HIV-2 variants are CCR5, GPR15 (BOB), and CXCR6 (BONZO). Surprisingly, control HIV-2 variants (n = 45) isolated from seven viremic individuals also mainly used these three coreceptors, whereas use of CCR1, CCR2b, or CCR3 was rare. Nearly a quarter of all HIV-2 variants tested could infect the parental GHOST cells, which could be partially explained by CXCR4 usage. Use of CXCR4 was observed only for HIV-2 variants from viremic individuals. Thirty-eight variants from aviremic and viremic HIV-2-infected individuals were additionally tested in U87 cells. All except one were capable of infecting the parental U87 cells, often with high efficiency. When virus production in parental cells was regarded as background in the coreceptor-transduced cell lines, the results in U87 cells were largely in agreement with the findings in GHOST cells. HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells. Broad coreceptor usage, therefore, does not appear to be associated with pathogenicity of HIV-2. PMID:15650194

Blaak, H; Boers, P H M; Gruters, R A; Schuitemaker, H; van der Ende, M E; Osterhaus, A D M E

2005-02-01

50

Isolation and characterization of human immunodeficiency virus type 1 variants infectious to brain-derived cells: detection of common point mutations in the V3 region of the env gene of the variants.  

PubMed Central

T-cell-line-tropic human immunodeficiency virus type 1 cannot infect CD4-positive, brain-derived cells. We isolated several new variants that readily infected brain-derived cells. Mutation of proline to serine, to alanine, or to threonine in the well-conserved GPGR sequence in the V3 region of the envelope glycoprotein was found in all these variants. This indicates the importance of amino acid sequences at the tip of the V3 region for brain cell tropism of human immunodeficiency virus type 1. PMID:7980782

Shimizu, N S; Shimizu, N G; Takeuchi, Y; Hoshino, H

1994-01-01

51

Characterization of herpes simplex virus clinical isolate Y3369 as a glycoprotein G variant and its bearing on virus typing  

PubMed Central

Background Herpes simplex viruses exist as two major serotypes, type 1 (HSV-1) and type 2 (HSV-2). Determination of type, either HSV-1 or HSV-2, is important in accurate diagnosis and clinical control of transmission. Several tests are available for typing HSV, including a monoclonal antibody specific for glycoprotein G and several PCR assays. Findings A clinical isolate was identified as herpes simplex virus, but tested negative for both HSV-1 and HSV-2 antigens using type-specific monoclonal antibody assays. The isolate was determined to be HSV-1 by PCR analysis. A mutation which likely caused the monoclonal antibody non-reactivity was found in glycoprotein G. Phylogenetic analysis revealed two groups of HSV, one with the mutation and one without. Three population studies examining mutations in HSV-1 glycoprotein G were analyzed by chi-squared test. To this point, the epitope which the monoclonal antibody recognizes was only found in HSV-1 isolates from human European populations (p < 0.0001). Conclusions These findings suggest that the PCR-based methods for HSV typing may be more useful than the standard monoclonal antibody test in areas of the world where the variant in glycoprotein G is more prevalent. PMID:21658271

2011-01-01

52

Microsatellite analysis of Japanese sea cucumber, Stichopus (Apostichopus) japonicus, supports reproductive isolation in color variants.  

PubMed

The genetic relationship among the three color variants (Red, Green, and Black) of the Japanese sea cucumber, S. japonicus, was investigated using 11 microsatellite markers. Genetic differentiation testing among the three sympatric color types showed the strong heterogeneity of Red (p<0.001), while no significant difference was observed between Green and Black (p=0.301 to 0.961). UPGMA trees constructed from 10 sample lots from 5 localities showed two distinct clusters, one from the Red types and the other from the Green and Black types. In addition, the sympatric Green and Black formed one subcluster with strong bootstrap support at each locality. These results indicate the separate species status of Red and the other color types, and also support the population identity of sympatric Green and Black. PMID:17043749

Kanno, Manami; Suyama, Yoshihisa; Li, Qi; Kijima, Akihiro

2006-01-01

53

Urease-positive thermophilic Campylobacter (Campylobacter laridis variant) isolated from an appendix and from human feces.  

PubMed Central

Urease-positive thermophilic campylobacters were isolated for the first time from the feces of two adults with diarrheal disease and from the appendix of a child with appendicitis. They were identified as Campylobacter laridis by a hybridization dot blot assay. Urease testing should be included in the tests used for the identification of campylobacters at the species level, even for those strains which are not of gastric origin. PMID:3384898

Mégraud, F; Chevrier, D; Desplaces, N; Sedallian, A; Guesdon, J L

1988-01-01

54

Antigenic variants of rabies virus in isolates from eastern, central and northern Canada.  

PubMed Central

Street rabies virus isolated from 51 specimens from Ontario, Quebec, Manitoba and the Northwest Territories have been typed by a panel of 36 antinucleocapsid monoclonal antibodies. Three main groups were found. The first group comprised those terrestrial mammals originating in Ontario, Quebec and the Northwest Territories. The second group was found in terrestrial mammals from Manitoba. The third heterogenous group was made up of bats from Ontario. PMID:3893660

Webster, W A; Casey, G A; Charlton, K M; Wiktor, T J

1985-01-01

55

Effect of Light Intensity on the Relative Dominance of Toxigenic and Nontoxigenic Strains of Microcystis aeruginosa ?  

PubMed Central

In aquatic ecosystems, the factors that regulate the dominance of toxin-producing cyanobacteria over non-toxin-producing strains of the same species are largely unknown. One possible hypothesis is that limiting resources lead to the dominance of the latter because of the metabolic costs associated with toxin production. In this study, we tested the effect of light intensity on the performance of a microcystin-producing strain of Microcystis aeruginosa (UTCC 300) when grown in mixed cultures with non-microcystin-producing strains with similar intrinsic growth rates (UTCC 632 and UTCC 633). The endpoints measured included culture growth rates, microcystin concentrations and composition, and mcyD gene copy numbers determined using quantitative PCR (Q-PCR). In contrast to the predicted results, under conditions of low light intensity (20 ?mol·m?2·s?1), the toxigenic strain became dominant in both of the mixed cultures based on gene copy numbers and microcystin concentrations. When grown under conditions of high light intensity (80 ?mol·m?2·s?1), the toxigenic strain still appeared to dominate over nontoxigenic strain UTCC 632 but less so over strain UTCC 633. Microcystins may not be so costly to produce that toxigenic cyanobacteria are at a disadvantage in competition for limiting resources. PMID:21841026

LeBlanc Renaud, Susan; Pick, Frances R.; Fortin, Nathalie

2011-01-01

56

Expression Analysis of a Highly Adherent and Cytotoxic Small Colony Variant of Pseudomonas aeruginosa Isolated from a Lung of a Patient with Cystic Fibrosis  

Microsoft Academic Search

The heterogeneous environment of the lung of the cystic fibrosis (CF) patient gives rise to Pseudomonas aeruginosa small colony variants (SCVs) with increased antibiotic resistance, autoaggregative growth behavior, and an enhanced ability to form biofilms. In this study, oligonucleotide DNA microarrays were used to perform a genome-wide expression study of autoaggregative and highly adherent P. aeruginosa SCV 20265 isolated from

Franz von Gotz; Susanne Haussler; Doris Jordan; Senthil Selvan Saravanamuthu; Dirk Wehmhoner; A. Strussmann; J. Lauber; I. Attree; J. Buer; B. Tummler; I. Steinmetz

2004-01-01

57

Distribution of Gifsy-3 and of Variants of ST64B and Gifsy-1 Prophages amongst Salmonella enterica Serovar Typhimurium Isolates: Evidence that Combinations of Prophages Promote Clonality  

PubMed Central

Salmonella isolates harbour a range of resident prophages which can influence their virulence and ability to compete and survive in their environment. Phage gene profiling of a range of phage types of Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) indicates a significant level of correlation of phage gene profile with phage type as well as correlation with genotypes determined by a combination of multi-locus variable-number tandem repeat (VNTR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Variation in phage gene profiles appears to be partly linked to differences in composition of variants of known prophages. We therefore conducted a study of the distribution of variants of ST64B and Gifsy-1 prophages and coincidently the presence of Gifsy-3 prophage in a range of S. Typhimurium phage types and genotypes. We have discovered two variants of the DT104 variant of ST64B and at least two new variants of Gifsy-1 as well as variants of related phage genes. While there is definite correlation between phage type and the prophage profile based on ST64B and Gifsy-1 variants we find stronger correlation between the VNTR/CRISPR genotype and prophage profile. Further differentiation of some genotypes is obtained by addition of the distribution of Gifsy-3 and a sequence variant of the substituted SB26 gene from the DT104 variant of ST64B. To explain the correlation between genotype and prophage profile we propose that suites of resident prophages promote clonality possibly through superinfection exclusion systems. PMID:24475087

Hiley, Lester; Fang, Ning-Xia; Micalizzi, Gino R.; Bates, John

2014-01-01

58

Isolation of two physiologically induced variant strains of Bacillus stearothermophilus NRS 2004/3a and characterization of their S-layer lattices.  

PubMed Central

During growth of Bacillus stearothermophilus NRS 2004/3a in continuous culture on complex medium, the chemical properties of the S-layer glycoprotein and the characteristic oblique lattice were maintained only if glucose was used as the sole carbon source. With increased aeration, amino acids were also metabolized, accompanied by liberation of ammonium and by changes in the S-layer protein. Depending on the stage of fermentation at which oxygen limitation was relieved, two different variants, one with a more delicate oblique S-layer lattice (variant 3a/V1) and one with a square S-layer lattice (variant 3a/V2), were isolated. During the switch from the wild-type strain to a variant or from variant 3a/V2 to variant 3a/V1, monolayers of two types of S-layer lattices could be demonstrated on the surfaces of single cells. S-layer proteins from variants had different molecular sizes and a significantly lower carbohydrate content than S-layer proteins from the wild-type strain did. Although the S-layer lattices from the wild-type and variant strains showed quite different protein mass distributions in two- and three-dimensional reconstructions, neither the amino acid composition nor the pore size, as determined by permeability studies, was significantly changed. Peptide mapping and N-terminal sequencing results strongly indicated that the three S-layer proteins are encoded by different genes and are not derived from a universal precursor form. Images PMID:8300538

Sára, M; Pum, D; Küpcü, S; Messner, P; Sleytr, U B

1994-01-01

59

Isolation of highly fusogenic variants of simian virus 5 from persistently infected cells that produce and respond to interferon.  

PubMed Central

A series of experiments were undertaken to examine how interferon and neutralizing antibodies influence the ability of simian virus 5 (SV5) (strain W3) to establish and maintain persistent infections in murine cells. In contrast to the rapid decline in SV5 protein synthesis observed in murine BALB/c fibroblasts (BF cells), which produce and respond to interferon, between 24 and 48 h postinfection there was no inhibition of virus protein synthesis in MSFI- cells, skin fibroblasts derived from alpha/beta-interferon receptor knockout BALB/c mice. Furthermore, the addition of anti-interferon antibodies to the culture medium of infected BF cells significantly reduced the observed decline in virus protein synthesis. Following infection of untreated BF cells, the majority replicated virus but survived the infection and eventually cleared the virus after 8 to 15 days. However, not all the cells were cured, and the cultures became persistently infected. Upon passage of persistently infected cultures, the virus fluxed between active and repressed states as a consequence of interferon production. This resulted in a balance being reached in which only 5 to 20% of the cells were infected at any one time. After 30 passages of the persistently infected cells, highly fusogenic virus variants arose (one of which was isolated and termed W3-f). W3-f remained as sensitive to interferon as the parental W3 isolate but, in the absence of interferon, spread much more rapidly than the parental W3 strain through BF cell monolayers. Sequence analysis revealed no deduced amino acid differences between the F proteins of W3 and W3-f. BF cell cultures persistently infected with W3-f were rapidly cleared of virus by the addition of virus-neutralizing antibodies to the culture medium. In contrast, neutralizing antibodies had little effect on the numbers of cells persistently infected with W3 over several passages. These results suggest that the ability of paramyxoviruses to cause cell-cell fusion may be selected for in vivo as a consequence of their adaptation to the interferon response rather than their need to escape from neutralizing antibodies. The significance of these observations with regard to persistent parainfluenza virus infections in vivo is further discussed. PMID:9371592

Young, D F; Didcock, L; Randall, R E

1997-01-01

60

Isolation and characterization of Chinese hamster ovary cell variants defective in adhesion to fibronectin-coated collagen  

PubMed Central

Variant clones of Chinese hamster ovary (CHO) cells were selected for reduced adhesion to serum-coated tissue culture plates. These clones also displayed reduced adhesion to substrata composed of collagen layers coated with bovine serum or with fibronectin (cold-insoluble globulin). Wild-type (WT) and adhesion variant (ADv) cells grew at comparable rates in suspension culture, but the adhesion variants could not be grown in monolayer culture because of their inability to attach to the substratum. The adhesion deficit in these cells was not corrected by raising the concentration of divalent cations or of serum to levels 10-fold greater than those normally utilized in cell culture. However, both WT and ADv clones could adhere, spread, and attain a normal CHO morphology on substrata coated with concanavalin A or poly-L- lysine. In addition, the adhesion variants could attach to substrata coated with "footpad" material (substratum-attached material) derived from monolayers of human diploid fibroblasts or WT CHO cells. These observations suggest that the variant clones may have a cell surface defect that prevents them from utilizing exogeneous fibronectin as an adhesion-promoting ligand; however the variants seem to have normal cytoskeletal and metabolic capacities that allow them to attach and spread on substrata coated with alternative ligands. These variants should be extremely useful in studying the molecular basis of cell adhesion. PMID:7193214

1980-01-01

61

The Kiss2 receptor (Kiss2r) gene in Southern Bluefin Tuna, Thunnus maccoyii and in Yellowtail Kingfish, Seriola lalandi - functional analysis and isolation of transcript variants.  

PubMed

The kisspeptin system plays an essential role in reproductive function in vertebrates, particularly in the onset of puberty. We investigated the kisspeptin system in two Perciform teleosts, the Southern Bluefin Tuna (SBT; Thunnus maccoyii), and the Yellowtail Kingfish (YTK; Seriola lalandi), by characterising their kisspeptin 2 receptor (Kiss2r) genes. In addition to the full length Kiss2r cDNA sequences, we have isolated from SBT and YTK a transcript variant that retained an intron. We have further obtained three ytkKiss2r transcript variants that contained deletions. In vitro functional analysis of the full length SBT and YTK Kiss2r showed higher response to Kiss2-10 than to Kiss1-10, with stronger transduction via PKC than PKA. The full length ytkKiss2r and two deletion variants were differentially expressed in the brain of male, but not in female, juvenile YTK treated with increasing doses of Kiss2-10 peptide. In the gonads, the expression level of the ytkKiss2r transcripts did not vary significantly either in the male or female fish. This is the first time that transcript variants of the Kiss2r gene that contain deletions and show responsiveness to treatments with kisspeptin have been reported in any teleost. PMID:22824208

Nocillado, J N; Biran, J; Lee, Y Y; Levavi-Sivan, B; Mechaly, A S; Zohar, Y; Elizur, A

2012-10-15

62

A rapid and simple method for the isolation of mutant variants regulating tissue-specific expression of the TnI gene through drug selection  

SciTech Connect

TnINEO fusion gene was constructed by fusing 3.4-kbp of quail TnI genomic DNA sequences spanning the promoter to exon 5 and a neo gene in frame. A myoblast cell line was established after transfection of pTnINEO. Since this cell line was passaged several times, a high frequency of neomycin (G418) sensitivity conversion was detected. Two drug-resistant variants were analyzed through genomic Southern blot and S1 nuclease protection assay. One variant has a mutation(s) in the regulatory element that activated the dormant TnI promoter-enhancer in myoblast, and the other has shown the geonomic rearrangement. This result presented the possibility of isolating factor(s) that activate the muscle-specific TnI promoter simply by screening drug-resistant cells having appropriate mutations. 12 refs., 4 fig.

Lee, Youngwon; Kim, Myoung Hee [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea, Republic of); Emerson, C.P. Jr. [Fox Chase Cancer Center, Philadelphia, PA (United States)

1995-12-01

63

In vitro Isolation and Identification of Human Immunodeficiency Virus (HIV) Variants with Reduced Sensitivity to C-2 Symmetrical Inhibitors of HIV Type 1 Protease  

NASA Astrophysics Data System (ADS)

Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi(CHOH)]_2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val -> Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.

Otto, M. J.; Garber, S.; Winslow, D. L.; Reid, C. D.; Aldrich, P.; Jadhav, P. K.; Patterson, C. E.; Hodge, C. N.; Cheng, Y.-S. E.

1993-08-01

64

Characterization of Vibrio cholerae O1 El Tor biotype variant clinical isolates from Bangladesh and Haiti, including a molecular genetic analysis of virulence genes.  

PubMed

Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease cholera, is divided into two biotypes: classical and El Tor. Both biotypes produce the major virulence factors toxin-coregulated pilus (TCP) and cholera toxin (CT). Although possessing genotypic and phenotypic differences, El Tor biotype strains displaying classical biotype traits have been reported and subsequently were dubbed El Tor variants. Of particular interest are reports of El Tor variants that produce various levels of CT, including levels typical of classical biotype strains. Here, we report the characterization of 10 clinical isolates from the International Centre for Diarrhoeal Disease Research, Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We observed that all 11 strains produced increased CT (2- to 10-fold) compared to that of wild-type El Tor strains under in vitro inducing conditions, but they possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant MQ1795, which produced the highest level of CT and very high levels of TcpA and ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type strains in the infant mouse cholera model. Additional genotypic and phenotypic tests were conducted to characterize the variants, including an assessment of biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some El Tor variants revealed two copies of classical ctxB, one per chromosome, contrary to previous reports that located ctxAB only on the large chromosome of El Tor biotype strains. PMID:21880975

Son, Mike S; Megli, Christina J; Kovacikova, Gabriela; Qadri, Firdausi; Taylor, Ronald K

2011-11-01

65

Four DNA-A variants among Pakistani isolates of cotton leaf curl virus and their affinities to DNA-A of geminivirus isolates from okra  

Microsoft Academic Search

Complete DNA-A sequences of nine Pakistani geminivirus isolates from leaf curl-affected cotton (CLCuV-PK) or from okra, and the partial sequences of several additional isolates were determined. Sequences of isolates from cotton were of four types. Isolates from leaf curl-affected okra had virtually the same sequences as those from cotton. Isolates from yellow vein mosaic-affected okra were of two types (OYVMV

Xueping Zhou; Yule Liu; David J. Robinson; Bryan D. Harrison

66

Identification of Two Novel Mycobacterium avium Allelic Variants in Pig and Human Isolates from Brazil by PCR-Restriction Enzyme Analysis  

PubMed Central

Mycobacterium avium complex (MAC) is composed of environmental mycobacteria found widely in soil, water, and aerosols that can cause disease in animals and humans, especially disseminated infections in AIDS patients. MAC consists of two closely related species, M. avium and M. intracellulare, and may also include other, less-defined groups. The precise differentiation of MAC species is a fundamental step in epidemiological studies and for the evaluation of possible reservoirs for MAC infection in humans and animals. In this study, which included 111 pig and 26 clinical MAC isolates, two novel allelic M. avium PCR-restriction enzyme analysis (PRA) variants were identified, differing from the M. avium PRA prototype in the HaeIII digestion pattern. Mutations in HaeIII sites were confirmed by DNA sequencing. Identification of these isolates as M. avium was confirmed by PCR with DT1-DT6 and IS1245 primers, nucleic acid hybridization with the AccuProbe system, 16S ribosomal DNA sequencing, and biochemical tests. The characterization of M. avium PRA variants can be useful in the elucidation of factors involved in mycobacterial virulence and routes of infection and also has diagnostic significance, since they can be misidentified as M. simiae II and M. kansasii I if the PRA method is used in the clinical laboratory for identification of mycobacteria. PMID:10405407

Leao, Sylvia Cardoso; Briones, Marcelo R. S.; Sircili, Marcelo Palma; Balian, Simone Carvalho; Mores, Nelson; Ferreira-Neto, Jose Soares

1999-01-01

67

Genome Sequences of Simian Hemorrhagic Fever Virus Variant NIH LVR42-0/M6941 Isolates (Arteriviridae: Arterivirus).  

PubMed

Simian hemorrhagic fever virus (SHFV) variant NIH LVR42-0/M6941 is the only remaining SHFV in culture, and only a single genome sequence record exists in GenBank/RefSeq. We compared the genomic sequence of NIH LVR42-0/M6941 acquired from the ATCC in 2011 to NIH LVR42-0/M6941 genomes sequenced directly from nonhuman primates experimentally infected in 1989. PMID:25301647

Lauck, Michael; Palacios, Gustavo; Wiley, Michael R; L, Yànhuá; F?ng, Y?ng; Lackemeyer, Matthew G; Caì, Yíngyún; Bailey, Adam L; Postnikova, Elena; Radoshitzky, Sheli R; Johnson, Reed F; Alkhovsky, Sergey V; Deriabin, Petr G; Friedrich, Thomas C; Goldberg, Tony L; Jahrling, Peter B; O'Connor, David H; Kuhn, Jens H

2014-01-01

68

Genome Sequences of Simian Hemorrhagic Fever Virus Variant NIH LVR42-0/M6941 Isolates (Arteriviridae: Arterivirus)  

PubMed Central

Simian hemorrhagic fever virus (SHFV) variant NIH LVR42-0/M6941 is the only remaining SHFV in culture, and only a single genome sequence record exists in GenBank/RefSeq. We compared the genomic sequence of NIH LVR42-0/M6941 acquired from the ATCC in 2011 to NIH LVR42-0/M6941 genomes sequenced directly from nonhuman primates experimentally infected in 1989. PMID:25301647

Lauck, Michael; Palacios, Gustavo; Wiley, Michael R.; L?, Yànhuá; F?ng, Y?ng; Lackemeyer, Matthew G.; Caì, Yíngyún; Bailey, Adam L.; Postnikova, Elena; Radoshitzky, Sheli R.; Johnson, Reed F.; Alkhovsky, Sergey V.; Deriabin, Petr G.; Friedrich, Thomas C.; Goldberg, Tony L.; Jahrling, Peter B.; O’Connor, David H.

2014-01-01

69

Isolated Cerebellar Variant of Adrenoleukodystrophy with a de novo Adenosine Triphosphate-Binding Cassette D1 (ABCD1) Gene Mutation  

PubMed Central

X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic expression, but clinical presentation as an isolated lesion of the cerebellar white matter and dentate nuclei has not been reported. We report an unusual presentation of X-ALD only with an isolated lesion of the cerebellar white matter and dentate nuclei. The proband, a 37-year-old man presented with bladder incontinence, slurred speech, dysmetria in all limbs, difficulties in balancing, and gait ataxia. Brain magnetic resonance imaging showed an isolated signal change of white matter around the dentate nucleus in cerebellum. With high level of very long chain fatty acid, gene study showed a de novo mutation in exon 1 at nucleotide position c.277_296dup20 (p.Ala100Cysfs*10) of the adenosine triphosphate-binding cassette D1 gene. It is advised to consider X-ALD as a differential diagnosis in patients with isolated cerebellar degeneration symptoms. PMID:24954351

Kang, Joon Won; Lee, Sang Mi; Koo, Kyo Yeon; Lee, Young-Mock; Nam, Hyo Suk; Quan, Zhejiu

2014-01-01

70

Non-toxigenic Clostridium sordellii: clinical and microbiological features of a case of cholangitis-associated bacteremia  

PubMed Central

Toxigenic C. sordellii strains are increasingly recognized to cause highly lethal infections in humans that are typified by a toxic shock syndrome (TSS). Two glucosylating toxins, lethal toxin (TcsL) and hemorrhagic toxin (TcsH) are believed to be important in the pathogenesis of TSS. While non-toxigenic strains of C. sordellii demonstrate reduced cytotoxicity in vitro and lower virulence in animal models of infection, there are few data regarding their behavior in humans. Here we report a non-TSS C. sordellii infection in the context of a polymicrobial bacterial cholangitis. The C. sordellii strain associated with this infection did not carry either the TcsL-encoding tcsL gene or the tcsH gene for TcsH. In addition, the strain was neither cytotoxic in vitro nor lethal in a murine sepsis model. These results provide additional correlative evidence that TcsL and TcsH increase the risk of mortality during C. sordellii infections. PMID:21726656

Walk, Seth T.; Jain, Ruchika; Trivedi, Itishree; Grossman, Sylvia; Newton, Duane W.; Thelen, Tennille; Hao, Yibai; Songer, J. Glenn; Carter, Glen P.; Lyras, Dena; Young, Vincent B.; Aronoff, David M.

2011-01-01

71

Multi-drug resistant Vibrio cholerae O1 variant El Tor isolated in northern Vietnam between 2007 and 2010  

PubMed Central

Since 2007, there has been a re-emergence of cholera outbreaks in northern Vietnam. To understand the molecular epidemiological relatedness and determine the antibiotic susceptibility profiles of responsible V. cholerae O1 outbreak strains, a representative collection of 100 V. cholerae O1 strains was characterized. V. cholerae O1 strains isolated from diarrhoeal patients in northern Vietnam between 2007 and 2010 were investigated for antibiotic susceptibility and characterized by using phenotypic and genotypic tests, including PFGE analysis. Ten clinical V. cholerae O1 isolates from Bangladesh and Zimbabwe were included for comparison. The results revealed that all isolates were resistant to co-trimoxazole and nalidixic acid, 29?% were resistant to tetracycline and 1?% were resistant to azithromycin. All strains were susceptible to ampicillin–sulbactam, doxycycline, chloramphenicol and ciprofloxacin and 95?% were susceptible to azithromycin. MIC values did show reduced susceptibility to fluoroquinolones and 63?% of the strains were intermediately resistant to tetracycline. The isolates expressed phenotypic traits of both serogroup O1 Ogawa and El Tor and harboured an rstR El Tor and ctxB classical biotype. Among the outbreak isolates, only a single PFGE pattern was observed throughout the study period. This study shows that multi-drug resistant V. cholerae altered El Tor producing classical CT strains are now predominant in northern Vietnam. PMID:22016560

Alam, Munirul; Trung, Nguyen Vu; Van Kinh, Nguyen; Nguyen, Hong Ha; Pham, Van Ca; Ansaruzzaman, Mohammad; Rashed, Shah Manzur; Bhuiyan, Nurul A.; Dao, Tuyet Trinh; Endtz, Hubert P.; Wertheim, Heiman F. L.

2012-01-01

72

Genome Sequence of the Small-Colony Variant Pseudomonas aeruginosa MH27, Isolated from a Chronic Urethral Catheter Infection  

PubMed Central

Pseudomonas aeruginosa is a notable nosocomial pathogen causing severe chronic infections. Here we present the draft genome sequence of P. aeruginosa MH27, isolated from a patient with a chronic hospital-acquired catheter-associated urinary tract infection. The 7.1-Mb genome sequence organized in 24 scaffolds contributes to the understanding of biofilm formation and antibiotic resistance. PMID:24459261

Tielen, Petra; Wibberg, Daniel; Blom, Jochen; Rosin, Nathalie; Meyer, Ann-Kathrin; Bunk, Boyke; Schobert, Max; Tupker, Reinhilde; Schatschneider, Sarah; Ruckert, Christian; Albersmeier, Andreas; Goesmann, Alexander; Vorholter, Frank-Jorg; Puhler, Alfred

2014-01-01

73

Nontoxigenic protein A vaccine for methicillin-resistant Staphylococcus aureus infections in mice  

PubMed Central

The current epidemic of hospital- and community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections has caused significant human morbidity, but a protective vaccine is not yet available. Prior infection with S. aureus is not associated with protective immunity. This phenomenon involves staphylococcal protein A (SpA), an S. aureus surface molecule that binds to Fc? of immunoglobulin (Ig) and to the Fab portion of VH3-type B cell receptors, thereby interfering with opsonophagocytic clearance of the pathogen and ablating adaptive immune responses. We show that mutation of each of the five Ig-binding domains of SpA with amino acid substitutions abolished the ability of the resulting variant SpAKKAA to bind Fc? or Fab VH3 and promote B cell apoptosis. Immunization of mice with SpAKKAA raised antibodies that blocked the virulence of staphylococci, promoted opsonophagocytic clearance, and protected mice against challenge with highly virulent MRSA strains. Furthermore, SpAKKAA immunization enabled MRSA-challenged mice to mount antibody responses to many different staphylococcal antigens. PMID:20713595

Kim, Hwan Keun; Cheng, Alice G.; Kim, Hye-Young; Missiakas, Dominique M.

2010-01-01

74

Familial Isolated Hyperparathyroidism as a Variant of Multiple Endocrine Neoplasia Type 1 in a Large Danish Pedigree  

Microsoft Academic Search

We report here our genetic findings of a family in which 14 mem- bers were affected with isolated primary hyperparathyroidism. Hy- perparathyroidism is the main feature of multiple endocrine neopla- sia type 1 (MEN1), making the recently cloned MEN1 gene a prime candidate gene in this family. Significantly positive lod scores were achieved with D11S4946 (3.36) and D11S4940 (3.53), and

MUSTAPHA KASSEM; TORBEN A. KRUSE; FUNG KI WONG; CATHARINA LARSSON; BIN TEAN TEH

2010-01-01

75

Isolation of a Chinese hamster fibroblast variant defective in dihydroxyacetonephosphate acyltransferase activity and plasmalogen biosynthesis: use of a novel two-step selection protocol.  

PubMed Central

We have developed a two-step selection protocol to generate a population of Chinese hamster ovary (CHO) cell variants that are plasmalogen-deficient, but contain intact, functional peroxisomes (plasmalogen-/peroxisome+). This involved sequential exposures of a mutagenized cell population to photodynamic damage by using two different pyrene-labelled sensors, 9-(1'-pyrene)nonanol and 12-(1'-pyrene)dodecanoic acid. By this procedure we generated several isolates, all except one of which displayed a severe decrease in plasmalogen biosynthesis. Further characterization of one of the plasmalogen-deficient isolates, NRel-4, showed that it contained intact, functional peroxisomes. Whole-cell homogenates from NRel-4 displayed severely decreased dihydroxyacetone phosphate acyltransferase, which catalyses the first step in plasmalogen biosynthesis. NRel-4 and another, recently described, plasmalogen-deficient cell line, NZel-1 [Nagan, Hajra, Das, Moser, Moser, Lazarow, Purdue and Zoeller (1997) Proc. Natl. Acad. Sci. U.S. A. 94, 4475-4480] were hypersensitive to singlet oxygen, supporting the notion of plasmalogens as radical oxygen scavengers. Wild-type-like resistance could be conferred on NRel-4 upon restoration of plasmalogen content by supplementation with a bypass compound, sn-1-hexadecylglycerol. NRel-4 and other plasmalogen-/peroxisome+ strains will allow us to examine further the role of ether lipids in cellular functions without complications associated with peroxisome deficiency, and might serve as an animal cell model for certain forms of the human genetic disorder rhizomelic chondrodysplasia punctata. PMID:9576878

Nagan, N; Hajra, A K; Larkins, L K; Lazarow, P; Purdue, P E; Rizzo, W B; Zoeller, R A

1998-01-01

76

Stone Lakes Virus (Family Togaviridae, Genus Alphavirus), a Variant of Fort Morgan Virus Isolated From Swallow Bugs (Hemiptera: Cimicidae) West of the Continental Divide  

PubMed Central

Multiple isolates of an alphaviruses within the western equine encephalomyelitis-serocomplex that were related closely to Ft. Morgan and its variant Buggy Creek virus were made from swallow bugs, Oeciacus vicarius Horvath (Hemiptera: Cimicidae), collected from cliff swallow (Petrochelidon pyrrhonota) nests at the Stone Lakes National Wildlife Refuge, Sacramento County, CA, during the summers of 2005 and 2006. This virus (hereafter Stone Lakes virus, family Togaviridae, genus Alphavirus, STLV) was the first record of this viral group west of the Continental Divide. STLV replicated well in Vero and other vertebrate cell cultures but failed to replicate in C6/36 cells or infect Culex tarsalis Coquillett mosquitoes. STLV failed to produce elevated viremias in adult chickens or house sparrows and was weakly immunogenic. In addition, STLV was not isolated from cliff swallow nestlings nor was antibody detected in adults collected at mist nets. We suggest that STL and related swallow bug viruses may be primarily infections of cimicids that are maintained and amplified either by vertical or nonviremic transmission and that cliff swallows may primarily be important as a bloodmeal source for the bugs rather than as an amplification host for the viruses. PMID:19769055

Brault, Aaron C.; Armijos, M. Veronica; Wheeler, Sarah; Wright, Stan; Fang, Ying; Langevin, Stanley; Reisen, William K.

2009-01-01

77

Stone Lakes virus (family Togaviridae, genus Alphavirus), a variant of Fort Morgan virus isolated from swallow bugs (Hemiptera: Cimicidae) west of the Continental Divide.  

PubMed

Multiple isolates of an alphaviruses within the western equine encephalomyelitis-serocomplex that were related closely to Ft. Morgan and its variant Buggy Creek virus were made from swallow bugs, Oeciacus vicarius Horvath (Hemiptera: Cimicidae), collected from cliff swallow (Petrochelidon pyrrhonota) nests at the Stone Lakes National Wildlife Refuge, Sacramento County, CA, during the summers of 2005 and 2006. This virus (hereafter Stone Lakes virus, family Togaviridae, genus Alphavirus, STLV) was the first record of this viral group west of the Continental Divide. STLV replicated well in Vero and other vertebrate cell cultures but failed to replicate in C6/36 cells or infect Culex tarsalis Coquillett mosquitoes. STLV failed to produce elevated viremias in adult chickens or house sparrows and was weakly immunogenic. In addition, STLV was not isolated from cliff swallow nestlings nor was antibody detected in adults collected at mist nets. We suggest that STL and related swallow bug viruses may be primarily infections of cimicids that are maintained and amplified either by vertical or nonviremic transmission and that cliff swallows may primarily be important as a bloodmeal source for the bugs rather than as an amplification host for the viruses. PMID:19769055

Brault, Aaron C; Armijos, M Veronica; Wheeler, Sarah; Wright, Stan; Fang, Ying; Langevin, Stanley; Reisen, William K

2009-09-01

78

Draft Genome Sequences of Two Genetic Variant Strains of Edwardsiella piscicida, JF1305 and RSB1309, Isolated from Olive Flounder (Paralichythys olivaceus) and Red Sea Bream (Pagrus major) Cultured in Japan, Respectively  

PubMed Central

Edwardsiella piscicida is a new species discovered within the group of organisms traditionally classified as Edwardsiella tarda. We present draft genome sequences of two variant strains of E. piscicida, JF1305 and RSB1309. Differences in protein-coding sequence between these isolates are associated with virulence, disease, and defense, suggesting differences in pathogenicity. PMID:24926054

Oguro, Kazuki; Tamura, Kazuki; Yamane, Jin; Shimizu, Masato; Yamamoto, Takeshi; Ikawa, Takuya; Ohnishi, Kouhei; Oshima, Syun-ichirou

2014-01-01

79

Competition of a sporidesmin-producing Pithomyces strain with a non-toxigenic Pithomyces strain.  

PubMed

Sporidesmin, a mycotoxin produced by some strains of Pithomyces chartarum, is responsible for the hepatogenous photosensitisation disease facial eczema, which causes severe losses in agricultural revenue in New Zealand. A sporidesmin-producing strain of P. chartarum, isolated in New Zealand, was grown in co-culture with a South African strain that does not produce the mycotoxin. Competition occurred between the two strains when grown both on agar plates and on dried ryegrass, with a significant decrease in the total amount of sporidesmin produced. Biological control of toxigenic P. chartarum can thus occur under laboratory conditions, raising the possibility of similar control in the field situation. PMID:16031836

Collin, R G; Towers, N R

1995-08-01

80

Characterization of a genetic and antigenic variant of avian paramyxovirus 6 isolated from a migratory wild bird, the red-necked stint (Calidris ruficollis).  

PubMed

A hemagglutinating virus (8KS0813) was isolated from a red-necked stint. Hemagglutination inhibition and neutralization tests indicated that 8KS0813 was antigenically related to a prototype strain, APMV-6/duck/Hong Kong/18/199/77, but with an 8- and 16-fold difference, respectively, in their titers. The full genome sequence of 8KS0813 showed 98.6 % nucleotide sequence identity to that of APMV-6/duck/Italy/4524-2/07, which has been reported to belong to an APMV-6 subgroup, and showed less similarity to that of the prototype strain (70.6 % similarity). The growth of 8KS0813 and the prototype strain in four different cell cultures was greatly enhanced by adding trypsin. Interestingly, this virus induced syncytia only in Vero cells. 8KS0813 was identified as APMV-6/red-necked stint/Japan/8KS0813/08, but it is antigenically and genetically distinguishable from the prototype strain, suggesting that variant APMV-6 is circulating in migratory birds. PMID:25000900

Bui, Vuong Nghia; Mizutani, Tetsuya; Nguyen, Tung Hoang; Trinh, Dai Quang; Awad, Sanaa S A; Minoungou, Germaine L; Yamamoto, Yu; Nakamura, Kikuyasu; Saito, Keisuke; Watanabe, Yukiko; Runstadler, Jonathan; Huettmann, Falk; Ogawa, Haruko; Imai, Kunitoshi

2014-11-01

81

Variant surface glycoprotein of Trypanosoma brucei brucei AnTat 1.1: influence of the isolation conditions upon the disulfide linked dimer/monomer ratio.  

PubMed

1. Using the variant surface glycoprotein (VSG) isolation procedure described by Baltz et al. ([1976] Ann. Immunol. (Inst. Pasteur) 127 C, 761-774) which involves suspension of the trypanosomes in a pH 5.5 buffer, the Antwerpen trypanozoon antigenic type (AnTat) 1.1 VSG is mainly obtained as a disulfide linked dimeric form with a trace amount of a monomeric form. 2. The use of a parasite suspension buffer at pH 7.0 results in a slight decrease of the VSG dimer/monomer ratio. 3. pH 5.5 and 7.0 supernatants of centrifuged parasite suspensions were submitted to kinetic incubations at different temperatures and pH, and we found conditions involving transformation of the AnTat 1.1 VSG dimer into the AnTat 1.1 VSG monomer (shifting the pH 5.5 supernatant to pH 7.0 and incubation at room temperature). 4. This transformation of the AnTat 1.1 VSG dimer into the AnTat 1.1 VSG monomer is activated by the addition of 1 mM reduced glutathione, and is inhibited by the addition of 1 mM oxidized glutathione or 0.1 mM N-ethylmaleimide or cadmium acetate. PMID:2328568

Boutignon, F; Huet-Duvillier, G; Mendonca-Previato, L; Gomes, V; Hublart, M; Degand, P

1990-01-01

82

Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013.  

PubMed

Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n=168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs. PMID:24449767

Sleeman, K; Mishin, V P; Guo, Z; Garten, R J; Balish, A; Fry, A M; Villanueva, J; Stevens, J; Gubareva, L V

2014-01-01

83

Antiviral Susceptibility of Variant Influenza A(H3N2)v Viruses Isolated in the United States from 2011 to 2013  

PubMed Central

Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n = 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs. PMID:24449767

Sleeman, K.; Mishin, V. P.; Guo, Z.; Garten, R. J.; Balish, A.; Fry, A. M.; Villanueva, J.; Stevens, J.

2014-01-01

84

Identification of the Long Polar Fimbriae gene variants in Locus of Enterocyte Effacement-negative Shiga toxin-producing Escherichia coli strains isolated from humans and cattle in Argentina  

PubMed Central

The Long Polar Fimbriae (Lpf) is one of few adhesive factors of Shiga toxin-producing Escherichia coli (STEC) and it is associated with colonization of the intestine. Studies have demonstrated the presence of lpf genes in several pathogenic E. coli strains and classification of variants based on polymorphisms in the lpfA1 and lpfA2 genes has been adopted. Using a collection of Argentinean Locus of Enterocyte Effacement (LEE)-negative STEC strains, we determined that the different lpfA types were present in a wide variety of serotypes and no apparent association was observed between the types of lpfA1 or lpfA2 genes and the severity of human disease. The lpfA2-1 was the most prevalent variant identified, which was present in 95.8% of the isolates, and the lpfA1-3 and lpfA2-2, proposed as specific biomarkers of E. coli O157:H7, were not found in any of the serotypes studied. The prevalence of lpf genes in a large number of strains is useful to understand the genetic diversity of LEE-negative STEC and to define the association of some of these isolates carrying specific lpf-variants with disease. PMID:20497228

Galli, Lucia; Torres, Alfredo G.; Rivas, Marta

2010-01-01

85

A Molecular Surveillance Reveals the Prevalence of Vibrio cholerae O139 Isolates in China from 1993 to 2012  

PubMed Central

Vibrio cholerae serogroup O139 was first identified in 1992 in India and Bangladesh, in association with major epidemics of cholera in both countries; cases were noted shortly thereafter in China. We characterized 211 V. cholerae O139 isolates that were isolated at multiple sites in China between 1993 and 2012 from patients (n = 92) and the environment (n = 119). Among clinical isolates, 88 (95.7%) of 92 were toxigenic, compared with 47 (39.5%) of 119 environmental isolates. Toxigenic isolates carried the El Tor CTX prophage and toxin-coregulated pilus A gene (tcpA), as well as the Vibrio seventh pandemic island I (VSP-I) and VSP-II. Among a subset of 42 toxigenic isolates screened by multilocus sequence typing (MLST), all were in the same sequence type as a clinical isolate (MO45) from the original Indian outbreak. Nontoxigenic isolates, in contrast, generally lacked VSP-I and -II, and fell within13 additional sequence types in two clonal complexes distinct from the toxigenic isolates. In further pulsed-field gel electrophoresis (PFGE) (with NotI digestion) studies, toxigenic isolates formed 60 pulsotypes clustered in one group, while the nontoxigenic isolates formed 43 pulsotypes which clustered into 3 different groups. Our data suggest that toxigenic O139 isolates from widely divergent geographic locations, while showing some diversity, have maintained a relatively tight clonal structure across a 20-year time span. Nontoxigenic isolates, in contrast, exhibited greater diversity, with multiple clonal lineages, than did their toxigenic counterparts. PMID:24452176

Zhang, Ping; Zhou, Haijian; Diao, Baowei; Li, Fengjuan; Du, Pengcheng; Li, Jie; Morris, J. Glenn

2014-01-01

86

PCR for Detection of cdt-III and the Relative Frequencies of Cytolethal Distending Toxin Variant-Producing Escherichia coli Isolates from Humans and Cattle  

Microsoft Academic Search

A PCR assay that uses primers whose sequences were obtained from the published sequence of the cdt-III gene was developed to determine the frequencies of the cdt-I, cdt-II, and cdt-III genes in Escherichia coli isolates from humans and animals. E. coli isolates producing cytolethal distending toxin (CDT) were infrequently detected. The cdt-I gene was preferentially detected in strains with the

Clifford G. Clark; Shelley T. Johnson; Russell H. Easy; Jennifer L. Campbell; Frank G. Rodgers

2002-01-01

87

Nontoxigenic Clostridium difficile protects hamsters against challenge with historic and epidemic strains of toxigenic BI/NAP1/027 C. difficile.  

PubMed

Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 10(6) CFU of spores of NTCD strain M3 or T7, and were challenged on day 5 with 100 CFU of spores of BI1 or BI6. To conserve animals, results for control hamsters challenged with BI1 or BI6 from the present study and controls from previous identical experiments were combined for statistical comparisons. NTCD strains M3 and T7 achieved 100% colonization and were 100% protective against challenge with BI1 (P ? 0.001). M3 colonized 9/10 hamsters and protected against BI6 challenge in the colonized hamsters (P = 0.0003). T7 colonized 10/10 hamsters, but following BI6 challenge, cocolonization occurred in 5 hamsters, 4 of which died, for protection of 6/10 animals (P = 0.02). NTCD colonization provides protection against challenge with toxigenic BI group strains. M3 is more effective than T7 in preventing C. difficile infection caused by the BI6 epidemic strain. Prevention of C. difficile infection caused by the epidemic BI6 strain may be more challenging than that of infections caused by historic BI1 and non-BI C. difficile strains. PMID:23939887

Nagaro, Kristin J; Phillips, S Tyler; Cheknis, Adam K; Sambol, Susan P; Zukowski, Walter E; Johnson, Stuart; Gerding, Dale N

2013-11-01

88

Presence of New mecA and mph(C) Variants Conferring Antibiotic Resistance in Staphylococcus spp. Isolated from the Skin of Horses before and after Clinic Admission  

Microsoft Academic Search

Because of the frequency of multiple antibiotic resistance, Staphylococcus species often represent a challenge in incisional infections of horses undergoing colic surgery. To investigate the evolution of antibiotic resistance patterns before and after preventative peri- and postoperative penicillin treatment, staphylococci were isolated from skin and wound samples at different times during hospitalization. Most staphylococci were normal skin commensals and belonged

Christina Schnellmann; Vinzenz Gerber; Alexandra Rossano; Valentine Jaquier; Yann Panchaud; Marcus G. Doherr; Andreas Thomann; Reto Straub; Vincent Perreten

2006-01-01

89

Presence of New mecA and mph(C) Variants Conferring Antibiotic Resistance in Staphylococcus spp. Isolated from the Skin of Horses before and after Clinic Admission  

Microsoft Academic Search

Because of the frequency of multiple antibiotic resistance, Staphylococcus species often represent a challenge in incisional infections of horses undergoing colic surgery. To investigate the evolution of antibiotic resistance patterns before and after preventative peri- and postoperative penicillin treatment, staphylococci were isolated from skin and wound samples at different times during hospitalization. Most staphylococci were normal skin commensals and belonged

Christina Schnellmann; Vinzenz Gerber; Alexandra Rossano; Valentine Jaquier; Yann Panchaud; Marcus G. Doherr; Andreas Thomann; Reto Straub; Vincent Perreten

90

OXA-15, an Extended-Spectrum Variant of OXA-2 bLactamase, Isolated from aPseudomonas aeruginosaStrain  

Microsoft Academic Search

Pseudomonas aeruginosa AH, isolated in Ankara, Turkey, was highly resistant to ceftazidime (MIC, 128 mg\\/ml) and produced a b-lactamase that gave a doublet of bands at pIs 8.7 and 8.9. b-Lactamase production was transferable toP. aeruginosaPU21 by conjugation and was determined by a ca. 450-kb plasmid, pMLH54. The transconjugant andEscherichia colitransformed with the cloned gene showed increased resistance to ceftazi-

FRANCK DANEL; LUCINDA M. C. HALL; DENIZ GUR; ANDDAVID M. LIVERMORE

1997-01-01

91

Selection during Cefepime Treatment of a New Cephalosporinase Variant with Extended-Spectrum Resistance to Cefepime in an Enterobacter aerogenes Clinical Isolate  

Microsoft Academic Search

Enterobacter aerogenes resistant to cefepime (MIC, 32 g\\/ml) was isolated from a patient treated with cefepime for an infection caused by a strain of E. aerogenes overproducing its AmpC -lactamase (MIC of cefepime, 0.5 g\\/ml). The AmpC -lactamase of the resistant strain had an L-293-P amino acid substitution and a high kcat\\/Km ratio for cefepime. Both of these modifications were

G. Barnaud; Y. Benzerara; J. Gravisse; L. Raskine; M. J. Sanson-Le Pors; R. Labia; G. Arlet

2004-01-01

92

Production of Cytolethal Distending Toxins by Pathogenic Escherichia coli Strains Isolated from Human and Animal Sources: Establishment of the Existence of a New cdt Variant (Type IV)  

Microsoft Academic Search

Three types of cytolethal distending toxin (CDT), namely, CDT-I, CDT-II, and CDT-III, have been described in Escherichia coli. Using primers designed for the detection of sequences common to the cdtB genes, we analyzed by PCR a set of 21 CDT-producing E. coli strains of intestinal and extraintestinal origins isolated from human and different animal species in several European countries and

Istvan Toth; Frederique Herault; Lothar Beutin; Eric Oswald

93

Characterization of Tn5801.Sag, a Variant of Staphylococcus aureus Tn916 Family Transposon Tn5801 That Is Widespread in Clinical Isolates of Streptococcus agalactiae  

PubMed Central

Tn5801, originally detected in Staphylococcus aureus Mu50, is a Tn916 family element in which a unique int gene (int5801) replaces the int and xis genes in Tn916 (int916 and xis916). Among 62 tet(M)-positive tetracycline-resistant Streptococcus agalactiae isolates, 43 harbored Tn916, whereas 19 harbored a Tn5801-like element (Tn5801.Sag, ?20.6 kb). Tn5801.Sag was characterized (PCR mapping, partial sequencing, and chromosomal integration) and compared to other Tn5801-like elements. Similar to Tn5801 from S. aureus Mu50, tested in parallel, Tn5801.Sag was unable to undergo circularization and conjugal transfer. PMID:23817370

Mingoia, Marina; Morici, Eleonora; Tili, Emily; Giovanetti, Eleonora; Montanari, Maria Pia

2013-01-01

94

Mdm2 Splice Variants.  

National Technical Information Service (NTIS)

The invention provides polypeptide and polynucleotide splice variants of the mouse Mdm2 gene, including Mdm2-b, which is homologous to the human Hdm2-b variant, as well as host cells, vectors and transgenic mice comprising the variants, and methods for th...

S. N. Jones, H. Steinman

2004-01-01

95

Reversion of CTL escape–variant immunodeficiency viruses in vivo  

Microsoft Academic Search

Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to

Thomas C Friedrich; Elizabeth J Dodds; Levi J Yant; Lara Vojnov; Richard Rudersdorf; Candice Cullen; David T Evans; Ronald C Desrosiers; Bianca R Mothé; John Sidney; Alessandro Sette; Kevin Kunstman; Steven Wolinsky; Michael Piatak; Jeffrey Lifson; Austin L Hughes; Nancy Wilson; David H O'Connor; David I Watkins

2004-01-01

96

Hemoglobin variants in Cyprus.  

PubMed

Cyprus, located at the eastern end of the Mediterranean region, has been a place of eastern and western civilizations, and the presence of various hemoglobin (Hb) variants can be considered a testimony to past colonizations of the island. In this study, we report the structural Hb variants identified in the Cypriot population (Greek Cypriots, Maronites, Armenians, and Latinos) during the thalassemia screening of 248,000 subjects carried out at the Thalassaemia Centre, Nicosia, Cyprus, over a period of 26 years. A sample population of 65,668 people was used to determine the frequency and localization of several of the variants identified in Cyprus. The localization of some of the variants in regions where the presence of foreign people was most prevalent provides important clues to the origin of the variants. Twelve structural variants have been identified by DNA sequencing, nine concerning the beta-globin gene and three concerning the alpha-globin gene. The most common beta-globin variants identified were Hb S (0.2%), Hb D-Punjab (0.02%), and Hb Lepore-Washington-Boston (Hb Lepore-WB) (0.03%); the most common alpha-globin variant was Hb Setif (0.1%). The presence of some of these variants is likely to be directly linked to the history of Cyprus, as archeological monuments have been found throughout the island which signify the presence for many years of the Greeks, Syrians, Persians, Arabs, Byzantines, Franks, Venetians, and Turks. PMID:19373583

Kyrri, Andreani R; Felekis, Xenia; Kalogerou, Eleni; Wild, Barbara J; Kythreotis, Loukas; Phylactides, Marios; Kleanthous, Marina

2009-01-01

97

In Vitro Activities of Cephalosporins and Quinolones against Escherichia coli Strains Isolated from Diarrheic Dairy Calves  

PubMed Central

The in vitro activities of several cephalosporins and quinolones against 195 strains of Escherichia coli isolated from dairy calves affected by neonatal diarrhea were determined. One hundred thirty-seven of these strains produced one or more potential virulence factors (F5, F41, F17, cytotoxic necrotizing factor, verotoxin, and the eae gene), but the remaining 58 strains did not produce any of these factors. From 11 to 18% of the E. coli strains were resistant to cephalothin, nalidixic acid, enoxacin, and enrofloxacin. However, cefuroxime, cefotaxime, and cefquinome were highly effective against the E. coli isolates tested. Some significant differences (P < 0.05) in resistance to quinolones between the strains producing potential virulence factors and nonfimbriated, nontoxigenic, eae-negative strains were found. Thus, eae-positive, necrotoxigenic, and verotoxigenic (except for nalidixic acid) E. coli strains were significantly more sensitive to nalidixic acid, enoxacin, and enrofloxacin than nonfimbriated, nontoxigenic, eae-negative strains. Moreover, eae-positive strains were significantly more sensitive to enoxacin and enrofloxacin than F5-positive strains. Thus, the results of this study suggest that the bovine E. coli strains that produce some potential virulence factors are more sensitive to quinolones than those that do not express these factors. PMID:10049259

Orden, José Antonio; Ruiz-Santa-Quiteria, José Antonio; García, Silvia; Cid, Dolores; de la Fuente, Ricardo

1999-01-01

98

Human papillomavirus genome variants  

PubMed Central

Amongst the human papillomaviruses (HPVs), the genus Alphapapillomavirus contains HPV types that are uniquely pathogenic. They can be classified into species and types based on genetic distances between viral genomes. Current circulating infectious HPVs constitute a set of viral genomes that have evolved with the rapid expansion of the human population. Viral variants were initially identified through restriction enzyme polymorphisms and more recently through sequence determination of viral fragments. Using partial sequence information, the history of variants, and the association of HPV variants with disease will be discussed with the main focus on the recent utilization of full genome sequence information for variant analyses. The use of multiple sequence alignments of complete viral genomes and phylogenetic analyses have begun to define variant lineages and sublineages using empirically defined differences of 1.0–10.0% and 0.5–1.0%, respectively. These studies provide the basis to define the genetics of HPV pathogenesis. PMID:23998342

Burk, Robert D.; Harari, Ariana; Chen, Zigui

2014-01-01

99

The [PSI+] Prion Exists as a Dynamic Cloud of Variants  

PubMed Central

[PSI+] is an amyloid-based prion of Sup35p, a subunit of the translation termination factor. Prion “strains” or “variants” are amyloids with different conformations of a single protein sequence, conferring different phenotypes, but each relatively faithfully propagated. Wild Saccharomyces cerevisiae isolates have SUP35 alleles that fall into three groups, called reference, ?19, and E9, with limited transmissibility of [PSI+] between cells expressing these different polymorphs. Here we show that prion transmission pattern between different Sup35 polymorphs is prion variant-dependent. Passage of one prion variant from one Sup35 polymorph to another need not change the prion variant. Surprisingly, simple mitotic growth of a [PSI+] strain results in a spectrum of variant transmission properties among the progeny clones. Even cells that have grown for >150 generations continue to vary in transmission properties, suggesting that simple variant segregation is insufficient to explain the results. Rather, there appears to be continuous generation of a cloud of prion variants, with one or another becoming stochastically dominant, only to be succeeded by a different mixture. We find that among the rare wild isolates containing [PSI+], all indistinguishably “weak” [PSI+], are several different variants based on their transmission efficiencies to other Sup35 alleles. Most show some limitation of transmission, indicating that the evolved wild Sup35 alleles are effective in limiting the spread of [PSI+]. Notably, a “strong [PSI+]” can have any of several different transmission efficiency patterns, showing that “strong” versus “weak” is insufficient to indicate prion variant uniformity. PMID:23382698

Bateman, David A.; Wickner, Reed B.

2013-01-01

100

Bladder exstrophy variants.  

PubMed

In the literature it is possible to find many case reports of bladder exstrophy variants, although a thorough classification with all possible associated malformations is not yet available. On the basis of a rare case observed at their Department, the authors studied the embryology of these conditions and their associated malformations. The purpose of this study is to review the literature currently available and suggest a classification for bladder exstrophy variants. Despite the rarity of these variants, surgeons need to know all possible associated malformations in order to have the most complete and correct clinical picture of their patients. PMID:17431375

Corroppolo, M; Zampieri, N; Pietrobelli, A; Giacomello, L; Camoglio, F S

2007-03-01

101

Mucopolysaccharidosis: A New Variant?  

ERIC Educational Resources Information Center

Described is a possibly new variant of mucopolysaccharidosis characterized by progressive mental and motor deficiency, bone abnormalities, a generalized skin lesion, and abnormal mucopolysaccharides in the urine as seen in a 20-year-old female. (DB)

Primrose, D. A.

1972-01-01

102

Variant Creutzfeldt Jakob Disease  

Microsoft Academic Search

The young and stable median age of those who die of variant Creutzfeldt-Jakob disease has been attributed to age-dependent infection rates. This analysis shows that an influence of age on risk for death after infection better explains age patterns, suggesting that biologic factors peaking in the third decade of life may hasten disease. T he epidemic of variant Creutzfeldt-Jakob disease

M. J. Painter

2000-01-01

103

Maisonneuve-hyperplantarflexion variant ankle fracture.  

PubMed

Maisonneuve fractures are rare ankle injuries, accounting for up to 7% of all ankle fractures. They consist of a proximal third fibula fracture, syndesmotic disruption, and medial ankle injury (either a deltoid ligament disruption or a medial malleolus fracture), and are often successfully managed with nonoperative treatment of the proximal fibula fracture and open reduction and internal fixation (ORIF) of the medial ankle injury and syndesmotic disruption. The hyperplantarflexion variant ankle fracture comprises approximately 7% of all ankle fractures and features dual posterior tibial lip fractures featuring a posterolateral fragment and a posteromedial fragment. Good functional results have been reported in the literature after ORIF of both the posterolateral and posteromedial fragments of this variant fracture that is not described by the Lauge-Hansen classification. In this report, the authors present the unique case of an isolated ankle fracture demonstrating characteristics of both a Maisonneuve fracture and a hyperplantarflexion variant ankle fracture. They also highlight the diagnostic imaging characteristics, including magnetic resonance imaging (MRI) and preoperative radiograph findings, surgical treatment, and postoperative clinical outcome for this patient with a Maisonneuve-hyperplantarflexion variant ankle fracture. To the authors' knowledge, this unique fracture pattern has not been reported previously in the literature. The authors conclude that although good results were seen postoperatively in this case, the importance of ORIF of both the posteromedial and posterolateral fragments of variant fractures cannot be overstated. They also found MRI to be a particularly helpful adjunct in formulating the correct diagnosis and treatment plan. PMID:25361368

Hinds, Richard M; Tran, Wesley H; Lorich, Dean G

2014-11-01

104

Occurrence of genetic variants of Listeria monocytogenes strains.  

PubMed

Isolates of Listeria monocytogenes saved from outbreaks of listeriosis, cases of sporadic listeriosis, and similar events do not always belong to a solitary genetic variant. Variants of the same strain may have evolved from a unique clone, and plasmid loss or gain and phage-mediated genetic changes are suggested as the main mechanism. Some of these reports are summarized in this short communication. PMID:23988078

Tham, Wilhem; Lopez-Valladares, Gloria; Helmersson, Seved; Wennström, Stefan; Österlund, Anders; Danielsson-Tham, Marie-Louise

2013-09-01

105

VARIANT project - further progress  

Microsoft Academic Search

VARIANT is a joint international space experiment which will be performed onboard the Ukrainian remote sensing satellite SICH-1M, that will be launched in 2003 at the polar circular orbit with the altitude 670s30 km. The scientific payload includes three instruments for registration of space current density: split Langmuir probe, Rogovski coil and Faraday cup. The equipment also includes sensors for

V. Korepanov; O. Negoda; H. Alleyne; M. Balikhin; A. Fedorov; J. Juchniewicz; S. Klimov; V. Krasnoselskikh; F. Lefeuvre; G. Lizunov

2002-01-01

106

Morphological Variants of Proteus hauseri  

Microsoft Academic Search

SUMMARY Cultures of Proteus hauseri may consist of one or more of five colonial variants. Population pressure experiments started with one variant eventually yielded all other variants. Y variants form raised non-swarming colonies on a MacConkey-type agar at 37O, but swarm in concentric step-like rings at room temperature on this medium; they swarm in step-like concentric rings on nutrient agar

J. N. COETZEE; T. G. SACKS

1960-01-01

107

Comparability of Essay Question Variants  

ERIC Educational Resources Information Center

Writing task variants can increase test security in high-stakes essay assessments by substantially increasing the pool of available writing stimuli and by making the specific writing task less predictable. A given prompt (parent) may be used as the basis for one or more different variants. Six variant types based on argument essay prompts from a…

Bridgeman, Brent; Trapani, Catherine; Bivens-Tatum, Jennifer

2011-01-01

108

Persistence of newly detected human papillomavirus type 31 infection, stratified by variant lineage.  

PubMed

Variants of human papillomavirus (HPV) type 31 have been shown to be related both to risk of cervical lesions and racial composition of a population. It is largely undetermined whether variants differ in their likelihood of persistence. Study subjects were women who participated in the ASCUS-LSIL Triage Study and who had a newly detected HPV31 infection during a two-year follow-up with six-month intervals. HPV31 isolates were characterized by sequencing and assigned to one of three variant lineages. Loss of the newly detected HPV31 infection was detected in 76 (47.5%) of the 160 women (32/67 with A variants, 16/27 with B variants and 28/66 with C variants). The adjusted hazard ratio associating loss of the infection was 1.2 (95% CI, 0.7-2.1) for women with A variants and 2.1 (95% CI, 1.2-3.5) for women with B variants when compared with those with C variants. Infections with A and C variants were detected in 50 and 41 Caucasian women and in 15 and 23 African-American women, respectively. The likelihood of clearance of the infection was significantly lower in African-American women with C variants than in African-American women with A variants (p = 0.05). There was no difference in the likelihood of clearance between A and C variants among Caucasian women. Our data indicated that infections with B variants were more likely to resolve than those with C variants. The difference in clearance of A vs. C variants in African-Americans, but not in Caucasians, suggests a possibility of the race-related influence in retaining the variant-specific infection. PMID:22729840

Xi, Long Fu; Schiffman, Mark; Koutsky, Laura A; He, Zhonghu; Winer, Rachel L; Hulbert, Ayaka; Lee, Shu-Kuang; Ke, Yang; Kiviat, Nancy B

2013-02-01

109

Molecular characterization of a Chinese isolate of potato virus A (PVA) and evidence of a genome recombination event between PVA variants at the 3'-proximal end of the genome.  

PubMed

Potato plants that exhibited mosaic symptoms were collected in Xiangxi, Hunan province, China. Multiplex RT-PCR screening for common viruses revealed the presence of potato virus A (PVA) in these samples. ELISA with virus-specific antibodies confirmed infection by PVA in the plants. Rod-shaped virions of ~750 nm in length and ~13 nm in width were observed by transmission electron microscopy. One virus isolate (designated PVA-Hunan) was subjected to molecular characterization. The viral genome consisted of 9,567 nucleotides, excluding the poly(A) tail, and encoded a polyprotein of 3,059 amino acids. A second characteristic potyvirus open reading frame (ORF), pretty interesting Potyviridae ORF (pipo), was located at nucleotides 2,834-3,139. The isolate shared 84 % to 98 % and 93 % to 99 % sequence identity with other PVA isolates at the nucleotide and amino acid level, respectively. Phylogenetic analysis demonstrated that, within the PVA group, PVA-Hunan clustered most closely with the Finnish isolate Her, then with isolates 143, U, Ali, M and B11. The isolate TamMV stood alone at a separate branch. However, scanning of complete genome sequences using SimPlot revealed 99 %-sequence identity between PVA-Hunan and TamMV in the 3'-proximal end of the genome (~nt 9,160 to the 3'end) and a 50 %-94 % (average ~83 %) identity upstream of nt 9,160. In contrast, 98 % identity between PVA-Hunan and isolates M and B11 was detected for nucleotides 1 to ~9,160, but only ~94 % for the 3'-proximal region, suggesting a genome recombination event (RE) at nt 9,133. The recombination breakpoint also was identified by the Recombination Detection Program (RDP). The RE was further confirmed by analysis of the CP gene, where the apparent RE was located. PMID:24722969

He, Changzheng; Zhang, Wei; Hu, Xinxi; Singh, Mathuresh; Xiong, Xingyao; Nie, Xianzhou

2014-09-01

110

Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant  

PubMed Central

Native type I heat-labile toxins (LTs) produced by enterotoxigenic Escherichia coli (ETEC) strains exert strong adjuvant effects on both antibody and T cell responses to soluble and particulate antigens following co-administration via mucosal routes. However, inherent enterotoxicity and neurotoxicity (following intra-nasal delivery) had reduced the interest in the use of these toxins as mucosal adjuvants. LTs can also behave as powerful and safe adjuvants following delivery via parenteral routes, particularly for activation of cytotoxic lymphocytes. In the present study, we evaluated the adjuvant effects of a new natural LT polymorphic form (LT2), after delivery via intradermal (i.d.) and subcutaneous (s.c.) routes, with regard to both antibody and T cell responses. A recombinant HIV-1 p24 protein was employed as a model antigen for determination of antigen-specific immune responses while the reference LT (LT1), produced by the ETEC H10407 strain, and a non-toxigenic LT form (LTK63) were employed as previously characterized LT types. LT-treated mice submitted to a four dose-base immunization regimen elicited similar p24-specific serum IgG responses and CD4+ T cell activation. Nonetheless, mice immunized with LT1 or LT2 induced higher numbers of antigen-specific CD8+ T cells and in vivo cytotoxic responses compared to mice immunized with the non-toxic LT derivative. These effects were correlated with stronger activation of local dendritic cell populations. In addition, mice immunized with LT1 and LT2, but not with LTK63, via s.c. or i.d. routes developed local inflammatory reactions. Altogether, the present results confirmed that the two most prevalent natural polymorphic LT variants (LT1 or LT2) display similar and strong adjuvant effects for subunit vaccines administered via i.d. or s.c. routes. PMID:24432018

Braga, Catarina J. M.; Rodrigues, Juliana F.; Medina-Armenteros, Yordanka; Farinha-Arcieri, Luís E.; Ventura, Armando M.; Boscardin, Silvia B.; Sbrogio-Almeida, Maria E.; Ferreira, Luís C. S.

2014-01-01

111

In vivo evaluation of pathogenicity and transmissibility of influenza A(H1N1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient.  

PubMed

The influenza A(H1N1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. Reports have identified an increased prevalence of the hemagglutinin receptor binding domain D222G mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. Virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the D222, but isolates collected later in his course from a bronchoalveolar lavage contained primarily the G222 mutation and was mixed with a minor population of D222. These clinical isolates were compared to a G222 plaque purified virus in the ferret model. The G222 predominant clinical isolate was the most pathogenic in ferrets and developed the most diversity at the 222 amino acid position during infection, suggesting that increased diversity and not a specific polymorphism at HA 222 may be important in predicting pathogenic potential. PMID:22575875

Memoli, Matthew J; Bristol, Tyler; Proudfoot, Kathleen E; Davis, A Sally; Dunham, Eleca J; Taubenberger, Jeffery K

2012-06-20

112

Japanese encephalitis virus antigenic variants with characteristic differences in neutralization resistance and mouse virulence  

Microsoft Academic Search

Two different plaque variants of Japanese encephalitis virus were selected from a wild-type Taiwanese isolate using Vero cells. One variant was found to exhibit small plaque morphology with retarded virus replication kinetics in Vero cells, and was demonstrated to be resistant to monoclonal antibody (mAb) E3.3 neutralization. The other variant showed large plaque morphology, was sensitive to mAb E3.3 neutralization,

Suh-Chin Wu; Wei-Cheng Lian; Li-Ching Hsu; Ming-Yi Liau

1997-01-01

113

Variants of Aspergillus alutaceus var. alutaceus (formerly Aspergillus ochraceus) with altered ochratoxin a production  

SciTech Connect

The present studies, using Asperigillus alutaceus var. alutaceus Berkeley et Curtis (formerly A. ochraceus Wilhelm) NRRL 3174 along with three other wild-type strains, were undertaken in an attempt to understand the effects of irradiation and other treatments on mycotoxin production in grain. Bedford barley was inoculated with spores of NRRL 3174, gamma irradiated, and incubated at 28C and 25% moisture. After 10 days of incubation, two colony types, ocher (parental) and yellow (variant), were isolated from the grain. Further culturing of the yellow variant resulted in the spontaneous appearance of a white variant that exhibited greatly enhanced fluorescence under UV light. In subsequent work, we have also isolated variants producing a soluble red pigment. In addition, in model experiments involving irradiation (1 kGy) of pure cultures, induction frequencies ranging between 2 and 4% (survival basis) were observed for the yellow and red variants. Inoculation of these variants into wheat and incubation for 14 days at 28C and 32% moisture resulted in ochratoxin A production in the relative amounts of 0.09:1:4.6:9.3 for the red, ocher (parental), yellow, and white variants, respectively. Additional characteristics of these isolates are described. Confirmation that the white high-ochratoxin-A-producing variants were derived from the parental strain was demonstrated by obtaining revertant sectors in monoclonal cultures of the variants.

Chelack, W.S.; Borsa, J.; Szekely, J.G. (Whiteshell Labs., Pinawa, Manitoba (Canada)); Marquardt, R.R.; Frohlich, A.A. (Univ. of Manitoba, Winnipeg (Canada))

1991-09-01

114

A phylogenetic reconstruction of the epidemiological history of canine rabies virus variants in Colombia  

Microsoft Academic Search

Historically, canine rabies in Colombia has been caused by two geographically distinct canine variants of rabies virus (RV) which between 1992 and 2002 accounted for ?95% of Colombian rabies cases. Genetic variant 1 (GV1) has been isolated up until 1997 in the Central Region and the Department of Arauca, and is now considered extinct through a successful vaccination program. Genetic

Gareth J Hughes; Andrés Páez; Jorge Bóshell; Charles E Rupprecht

2004-01-01

115

Genetic Analysis of Prototrophic Natural Variants of Candida Albicans  

PubMed Central

To facilitate genetic analysis of Candida albicans natural variants, we have isolated a dominant mycophenolic acid-resistant mutant. Mycophenolic acid-resistant auxotrophs were used to analyze prototrophic natural variants by spheroplast fusion. The fusion products were shown to be heterozygous for many of the parental chromosomes by molecular and genetic criteria. Using this approach, we have found that one type of morphologic variation is due to a recessive change and identified three dominant 5-fluorocytosine-resistant mutants. Rare fusion products express recessive parental markers. These exceptional progeny should be useful for linkage analysis and strain construction. PMID:2575557

Goshorn, A. K.; Scherer, S.

1989-01-01

116

Heteromorphic variants of chromosome 9  

PubMed Central

Background Heterochromatic variants of pericentromere of chromosome 9 are reported and discussed since decades concerning their detailed structure and clinical meaning. However, detailed studies are scarce. Thus, here we provide the largest ever done molecular cytogenetic research based on >300 chromosome 9 heteromorphism carriers. Results In this study, 334 carriers of heterochromatic variants of chromosome 9 were included, being 192 patients from Western Europe and the remainder from Easter-European origin. A 3-color-fluorescence in situ hybridization (FISH) probe-set directed against for 9p12 to 9q13~21.1 (9het-mix) and 8 different locus-specific probes were applied for their characterization. The 9het-mix enables the characterization of 21 of the yet known 24 chromosome 9 heteromorphic patterns. In this study, 17 different variants were detected including five yet unreported; the most frequent were pericentric inversions (49.4%) followed by 9qh-variants (23.9%), variants of 9ph (11.4%), cenh (8.2%), and dicentric- (3.8%) and duplication-variants (3.3%). For reasons of simplicity, a new short nomenclature for the yet reported 24 heteromorphic patterns of chromosome 9 is suggested. Six breakpoints involved in four of the 24 variants could be narrowed down using locus-specific probes. Conclusions Based on this largest study ever done in carriers of chromosome 9 heteromorphisms, three of the 24 detailed variants were more frequently observed in Western than in Eastern Europe. Besides, there is no clear evidence that infertility is linked to any of the 24 chromosome 9 heteromorphic variants. PMID:23547710

2013-01-01

117

Variant view: visualizing sequence variants in their gene context.  

PubMed

Scientists use DNA sequence differences between an individual's genome and a standard reference genome to study the genetic basis of disease. Such differences are called sequence variants, and determining their impact in the cell is difficult because it requires reasoning about both the type and location of the variant across several levels of biological context. In this design study, we worked with four analysts to design a visualization tool supporting variant impact assessment for three different tasks. We contribute data and task abstractions for the problem of variant impact assessment, and the carefully justified design and implementation of the Variant View tool. Variant View features an information-dense visual encoding that provides maximal information at the overview level, in contrast to the extensive navigation required by currently-prevalent genome browsers. We provide initial evidence that the tool simplified and accelerated workflows for these three tasks through three case studies. Finally, we reflect on the lessons learned in creating and refining data and task abstractions that allow for concise overviews of sprawling information spaces that can reduce or remove the need for the memory-intensive use of navigation. PMID:24051821

Ferstay, Joel A; Nielsen, Cydney B; Munzner, Tamara

2013-12-01

118

Characteristics of a Pathogenic Molecular Clone of an End-Stage Serum-Derived Variant of Simian Immunodeficiency Virus (SIVF359)  

Microsoft Academic Search

End-stage simian immunodeficiency virus (SIV) isolates are suggested to be the most fit of the evolved virulent variants that precipitate the progression to AIDS. To determine if there were common characteristics of end-stage variants which emerge from accelerated cases of AIDS, a molecular clone was derived directly from serum following in vivo selection of a highly virulent SIV isolate obtained

LENNART HOLTERMAN; ROB DUBBES; JAMES MULLINS; GERALD LEARN; HENK NIPHUIS; WIM KOORNSTRA; GERRIT KOOPMAN; EVA-MARIA KUHN; ALISON WADE-EVANS; BRIGITTE ROSENWIRTH; JOOST HAAIJMAN; JONATHAN HEENEY

2001-01-01

119

Characterization of purified CuZn SOD variants from adult rat liver  

SciTech Connect

Rat liver CuZn SOD was purified by chloroform-ethanol extraction, ion exchange and molecular seive gel filtration. On electrofocussing six variants of SOD with isoelectric points of 5.16, 4.88, 4.76, 4.65, 4.57 and 4.50 were isolated. Variant PI 4.88 was the major component, variants PI 4.57 and PI 4.50 were minor components. This pattern was also obtained from SOD isolated by acetone-powder method or ultrafiltration dialysis method and even from liver homogenates incubated at 37/sup 0/C for 4 hrs. All SOD variants had m.w. of 32 kDa and were inhibitable by cyanide and Tris-HcL buffer. All variants contained 1 mole each of Cu and Zn/mole SOD except for variant PI 4.88 which contained 3 moles of Cu and Zn/mole SOD. Specific activity of SOD was measured by xanthine-xanthine oxidase cytochrome c method. At pH 7.8 in phosphate buffer the variant PI 4.88 showed highest activity (11,927 units per mgm) and PI 4.57 variant the lowest (1170 units). At pH 10.0 in carbonate buffer all variants had enhanced activities, however PI 4.50 variant showed least increase enhancement. Thus, CuZn SOD in normal rat liver consists of six variants of varying behaviors. It is possible that changes in their relative contents may thus affect the outcome of oxidant injury.

Yano, S.; Kikkawa, Y.; Desai, U.; Mettler, N.

1986-03-01

120

Chemical Composition of Variants of Aerobic Actinomycetes  

PubMed Central

It has been shown previously that aerobic actinomycetes can be separated into four main groups on the basis of their cell wall composition. Six representatives of aerobic actinomycetes (Nocardia asteroides and Micropolyspora brevicatena, cell wall type IV; N. madurae, Microbispora rosea, cell wall type III; Actinoplanes sp., cell wall type II; Streptomyces griseus, cell wall type I) were subjected to selecting agents which permitted the isolation of stable variants morphologically different from the parent strain. Whole cell analyses of 134 substrains from the six parents revealed no significant change in the isomeric form of diaminopimelic acid or in sugar constituents. Analyses of cell wall preparations from 52 of these did not reveal any change in the diagnostic constituents of their murein or polysaccharides. PMID:16349745

Suput, Jelena; Lechevalier, Mary P.; Lechevalier, H. A.

1967-01-01

121

Rare variants and cardiovascular disease.  

PubMed

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the Western world. Large genome-wide association studies (GWASs) of coronary artery disease, myocardial infarction, stroke and dilated cardiomyopathy have identified a number of common genetic variants with modest effects on disease risk. Similarly, studies of important modifiable risk factors of CVD have identified a large number of predominantly common variant associations, for example, with blood pressure and blood lipid levels. In each case, despite the often large numbers of loci identified, only a small proportion of the phenotypic variance is explained. It has been hypothesised that rare variants with large effects may account for some of the missing variance but large-scale studies of rare variation are in their infancy for cardiovascular traits and have yet to produce fruitful results. Studies of monogenic CVDs, inherited disorders believed to be entirely driven by individual rare mutations, have highlighted genes that play a key role in disease aetiology. In this review, we discuss how findings from studies of rare variants in monogenic disease and GWAS of predominantly common variants are converging to provide further insight into biological disease mechanisms. PMID:24771349

Wain, Louise V

2014-09-01

122

Gene variants influence insulin production  

Cancer.gov

A new analytical tool has found three previously unknown gene variants relevant to diabetes, and researchers say it also may be useful in unraveling other complex diseases like obesity and cancer. In research published online December 23 in Nature Genetics, scientists say the relatively rare genetic variants influence insulin production,a finding that could offer new clues about the genetic factors behind diabetes. The study included participants from the University of North Carolina School of Medicine (home to the Lineberger Comprehensive Cancer Center), the University of Michigan (home to the University of Michigan Comprehensive Cancer Center), and the University of Eastern Finland.

123

Histone variants in metazoan development  

PubMed Central

Embryonic development is regulated by both genetic and epigenetic mechanisms, with nearly all DNA-templated processes influenced by chromatin architecture. Sequence variations in histone proteins, core components of chromatin, provide a means to generate diversity in the chromatin structure, resulting in distinct and profound biological outcomes in the developing embryo. Emerging literature suggests that epigenetic contributions from histone variants play key roles in a number of developmental processes such as the initiation and maintenance of pericentric heterochromatin, X-inactivation, and germ cell differentiation. Here, we review the role of histone variants in the embryo with particular emphasis on early mammalian development. PMID:21074717

Banaszynski, Laura A.; Allis, C. David; Lewis, Peter W.

2010-01-01

124

Space-variant optical systems  

NASA Astrophysics Data System (ADS)

Analytical and experimental investigations of 2-D space-variant optical processing techniques were conducted. Coherent processing investigations have included (1) an experimental study of the characteristics of photoresist phase masks for multiplex holography, (2) the development of facility for generating high quality computer-generated holograms by use of a laser plotter, and (3) analytical investigation of an idea for using 1-D techniques to perform 2-D space variant operations. In the incoherent processing area experiments have proceeded to test the tristimulus-based technique for performing complex operations using hue, saturation, and intensity parameters to represent complex numbers.

Walkup, J. F.; Krile, T. F.

1981-11-01

125

Molecular epidemiology of hepatitis B virus variants in nonhuman primates.  

PubMed

We characterized hepatitis B virus (HBV) isolates from sera of 21 hepatitis B virus surface antigen-positive apes, members of the families Pongidae and Hylobatidae (19 gibbon spp., 1 chimpanzee, and 1 gorilla). Sera originate from German, French, Thai, and Vietnamese primate-keeping institutions. To estimate the phylogenetic relationships, we sequenced two genomic regions, one located within the pre-S1/pre-S2 region and one including parts of the polymerase and the X protein open reading frames. By comparison with published human and ape HBV isolates, the sequences could be classified into six genomic groups. Four of these represented new genomic groups of gibbon HBV variants. The gorilla HBV isolate was distantly related to the chimpanzee isolate described previously. To confirm these findings, the complete HBV genome from representatives of each genomic group was sequenced. The HBV isolates from gibbons living in different regions of Thailand and Vietnam could be classified into four different phylogenetically distinct genomic groups. The same genomic groups were found in animals from European zoos. Therefore, the HBV infections of these apes might have been introduced into European primate-keeping facilities by direct import of already infected animals from different regions in Thailand. Taken together, our data suggest that HBV infections are indigenous in the different apes. One event involving transmission between human and nonhuman primates in the Old World of a common ancestor of human HBV genotypes A to E and the ape HBV variants might have occurred. PMID:10799618

Grethe, S; Heckel, J O; Rietschel, W; Hufert, F T

2000-06-01

126

Comparison of Different DNA Fingerprinting Techniques for Molecular Typing of Bartonella henselae Isolates  

PubMed Central

Seventeen isolates of Bartonella henselae from the region of Freiburg, Germany, obtained from blood cultures of domestic cats, were examined for their genetic heterogeneity. On the basis of different DNA fingerprinting methods, including pulsed-field gel electrophoresis (PFGE), enterobacterial repetitive intergenic consensus (ERIC)-PCR, repetitive extragenic palindromic (REP) PCR, and arbitrarily primed (AP)-PCR, three different variants were identified among the isolates (variants I to III). Variant I included 6 strains, variant II included 10 strains, and variant III included only one strain. By all methods used, the isolates could be clearly distinguished from the type strain, Houston-1, which was designated variant IV. A previously published type-specific amplification of 16S rDNA differentiated two types of the B. henselae isolates (16S rRNA types 1 and 2). The majority of the isolates (16 of 17), including all variants I and II, were 16S rRNA type 2. Only one isolate (variant III) and the Houston-1 strain (variant IV) comprised the 16S rRNA type 1. Comparison of the 16S rDNA sequences from one representative strain from each of the three variants (I to III) confirmed the results obtained by 16S rRNA type-specific PCR. The sequences from variant I and variant II were identical, whereas the sequence of variant III differed in three positions. All methods applied in this study allowed subtyping of the isolates. PFGE and ERIC-PCR provided the highest discriminatory potential for subtyping B. henselae strains, whereas AP-PCR with the M13 primer showed a very clear differentiation between the four variants. Our results suggest that the genetic heterogeneity of B. henselae strains is high. The methods applied were found useful for typing B. henselae isolates, providing tools for epidemiological and clinical follow-up studies. PMID:9738053

Sander, Anna; Ruess, Michael; Bereswill, Stefan; Schuppler, Markus; Steinbrueckner, Bernhard

1998-01-01

127

Isolation of a Variant of Subtilosin A with Hemolytic Activity?  

PubMed Central

Bacillus subtilis produces an anionic bacteriocin called subtilosin A that possesses antibacterial activity against certain gram-positive bacteria. In this study, we uncovered a hemolytic mutant of B. subtilis that produces an altered form of subtilosin A. The mutant bacteriocin, named subtilosin A1, has a replacement of threonine at position 6 with isoleucine. In addition to the hemolytic activity, subtilosin A1 was found to exhibit enhanced antimicrobial activity against specific bacterial strains. The B. subtilis albB mutant that does not produce a putative immunity peptide was more sensitive to both subtilosin A and subtilosin A1. A spontaneous suppressor mutation of albB that restored resistance to subtilosin A and subtilosin A1 was obtained. The sbr (subtilosin resistance) mutation conferring the resistance is not linked to the sboA-alb locus. The sbr mutation does not increase the resistance of B. subtilis to other cell envelope-targeted antimicrobial agents, indicating that the mutation specifically confers the resistance to subtilosins. The findings suggest possible bioengineering approaches for obtaining anionic bacteriocins with enhanced and/or altered bactericidal activity. Furthermore, future identification of the subtilosin-resistant mutation could provide insights into the mechanism of subtilosin A activity. PMID:19633086

Huang, Tai; Geng, Hao; Miyyapuram, Venugopal R.; Sit, Clarissa S.; Vederas, John C.; Nakano, Michiko M.

2009-01-01

128

Isolation of a variant of subtilosin A with hemolytic activity.  

PubMed

Bacillus subtilis produces an anionic bacteriocin called subtilosin A that possesses antibacterial activity against certain gram-positive bacteria. In this study, we uncovered a hemolytic mutant of B. subtilis that produces an altered form of subtilosin A. The mutant bacteriocin, named subtilosin A1, has a replacement of threonine at position 6 with isoleucine. In addition to the hemolytic activity, subtilosin A1 was found to exhibit enhanced antimicrobial activity against specific bacterial strains. The B. subtilis albB mutant that does not produce a putative immunity peptide was more sensitive to both subtilosin A and subtilosin A1. A spontaneous suppressor mutation of albB that restored resistance to subtilosin A and subtilosin A1 was obtained. The sbr (subtilosin resistance) mutation conferring the resistance is not linked to the sboA-alb locus. The sbr mutation does not increase the resistance of B. subtilis to other cell envelope-targeted antimicrobial agents, indicating that the mutation specifically confers the resistance to subtilosins. The findings suggest possible bioengineering approaches for obtaining anionic bacteriocins with enhanced and/or altered bactericidal activity. Furthermore, future identification of the subtilosin-resistant mutation could provide insights into the mechanism of subtilosin A activity. PMID:19633086

Huang, Tai; Geng, Hao; Miyyapuram, Venugopal R; Sit, Clarissa S; Vederas, John C; Nakano, Michiko M

2009-09-01

129

Swine Influenza/Variant Influenza Viruses  

MedlinePLUS

... this? Submit What's this? Submit Button Information on Swine Influenza/Variant Influenza Viruses Language: English Español ... pigs and variant influenza virus infections in humans. Swine Flu in Swine (pigs) Swine Flu in Swine ( ...

130

Are isolated wetlands isolated?  

USGS Publications Warehouse

While federal regulations during the past 10 years have treated isolated wetlands as unconnected to aquatic resources protected by the Clean Water Act, they provide critical ecosystem services to society that extend well beyond their wetland boundaries. The authors offer well-documented examples from the scientific literature on some of the ecosystem services provided by isolated wetlands to society and other ecosystems.

Smith, Loren M.; Euliss, Ned H.; Haukos, David A.

2011-01-01

131

Prevalence of ATM Sequence Variants in Northern Plains American Indian Cancer Patients  

PubMed Central

Purpose: To identify sequence variants of the ataxia telangiectasia mutated (ATM) gene and establish their prevalence rate among American Indian (AI) as compared with non-AI cancer patients. Materials and Methods: DNA was isolated from blood samples collected from 100 AI and 100 non-AI cancer patients undergoing radiation therapy, and a blinded assessment of the ATM sequence was conducted. Quantitative PCR assessment of copy number for each exon was also performed. The main outcome measure was the prevalence of ATM variants in the two patient populations. Results: No statistically significant differences for total prevalence of ATM variants among AI and non-AI patients were found. Of the 25 variants identified, 5 variants had a prevalence of >2%, of which 4 occurred at a rate of >5% in one or both groups. The prevalence of these four variants could meaningfully be compared between the two groups. The only statistically significant difference among the groups was the c.4138C?>?T variant which is predicted not to affect protein function, seen in 8% of AI versus 0% of non-AI patients (P?=?0.007). No exonic copy number changes were found in these patients. Conclusion: This study is the first to determine the prevalence of ATM variants in AIs. PMID:24416720

Petereit, Daniel G.; Hahn, L. Jennifer; Kanekar, Shalini; Boylan, Amy; Bentzen, S?ren M.; Ritter, Mark; Moser, Amy R.

2013-01-01

132

Cognition and Anatomy in Three Variants of Primary Progressive Aphasia  

PubMed Central

We performed a comprehensive cognitive, neuroimaging, and genetic study of 31 patients with primary progressive aphasia (PPA), a decline in language functions that remains isolated for at least 2 years. Detailed speech and language evaluation was used to identify three different clinical variants: nonfluent progressive aphasia (NFPA; n = 11), semantic dementia (SD; n = 10), and a third variant termed logopenic progressive aphasia (LPA; n = 10). Voxel-based morphometry (VBM) on MRIs showed that, when all 31 PPA patients were analyzed together, the left perisylvian region and the anterior temporal lobes were atrophied. However, when each clinical variant was considered separately, distinctive patterns emerged: (1) NFPA, characterized by apraxia of speech and deficits in processing complex syntax, was associated with left inferior frontal and insular atrophy; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension and naming, showed atrophy in the left posterior temporal cortex and inferior parietal lobule. Apolipoprotein E ?4 haplotype frequency was 20% in NFPA, 0% in SD, and 67% in LPA. Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes. PMID:14991811

Gorno-Tempini, Maria Luisa; Dronkers, Nina F.; Rankin, Katherine P.; Ogar, Jennifer M.; Phengrasamy, La; Rosen, Howard J.; Johnson, Julene K.; Weiner, Michael W.; Miller, Bruce L.

2008-01-01

133

Fecal Influenza in Mammals: Selection of Novel Variants  

PubMed Central

In aquatic birds, influenza A viruses mainly replicate in the intestinal tract without significantly affecting the health of the host, but in mammals, they replicate in the respiratory tract and often cause disease. Occasionally, influenza viruses have been detected in stool samples of hospitalized patients and in rectal swabs of naturally or experimentally infected mammals. In this study, we compared the biological and molecular differences among four wild-type avian H1N1 influenza viruses and their corresponding fecal and lung isolates in DBA/2J and BALB/cJ mice. All fecal and lung isolates were more pathogenic than the original wild-type viruses, when inoculated into mice of both strains. The increased virulence was associated with the acquisition of genetic mutations. Most of the novel genotypes emerged as PB2E627K, HAF128V, HAF454L, or HAH300P variations, and double mutations frequently occurred in the same isolate. However, influenza virus strain- and host-specific differences were also observed in terms of selected variants. The avian H1N1 virus of shorebird origin appeared to be unique in its ability to rapidly adapt to BALB/cJ mice via the fecal route, compared to the adaptability of the H1N1 virus of mallard origin. Furthermore, a bimodal distribution in fecal shedding was observed in mice infected with the fecal isolates, while a normal distribution was observed after infection with the lung isolates or wild-type virus. Fecal isolates contained HA mutations that increased the activation pH of the HA protein. We conclude that influenza virus variants that emerge in fecal isolates in mammals might influence viral transmission, adaptation to mammals, and viral ecology or evolution. PMID:23966381

Kocer, Zeynep A.; Obenauer, John; Zaraket, Hassan; Zhang, Jinghui; Rehg, Jerold E.; Russell, Charles J.

2013-01-01

134

Evaluation of Perceived Threat Differences Posed by Filovirus Variants  

PubMed Central

In the United States, filoviruses (ebolaviruses and marburgviruses) are listed as National Institute of Allergy and Infectious Diseases (NIAID) Category A Priority Pathogens, Select Agents, and Centers for Disease Control and Prevention (CDC) Category A Bioterrorism Agents. In recent months, U.S. biodefense professionals and policy experts have initiated discussions on how to optimize filovirus research in regard to medical countermeasure (ie, diagnostics, antiviral, and vaccine) development. Standardized procedures and reagents could accelerate the independent verification of research results across government agencies and establish baselines for the development of animal models acceptable to regulatory entities, such as the Food and Drug Administration (FDA), while being fiscally responsible. At the root of standardization lies the question of which filovirus strains, variants, or isolates ought to be the prototypes for product development, evaluation, and validation. Here we discuss a rationale for their selection. We conclude that, based on currently available data, filovirus biodefense research ought to focus on the classical taxonomic filovirus prototypes: Marburg virus Musoke in the case of marburgviruses and Ebola virus Mayinga in the case of Zaire ebolaviruses. Arguments have been made in various committees in favor of other variants, such as Marburg virus Angola, Ci67 or Popp, or Ebola virus Kikwit, but these rationales seem to be largely based on anecdotal or unpublished and unverified data, or they may reflect a lack of awareness of important facts about the variants' isolation history and genomic properties. PMID:22070137

Kuhn, Jens H.; Dodd, Lori E.; Wahl-Jensen, Victoria; Radoshitzky, Sheli R.; Bavari, Sina

2011-01-01

135

Variant forms of autoimmune hepatitis  

Microsoft Academic Search

Variant forms of autoimmune hepatitis have features that are intermixed with another disorder (overlap syndrome) or findings\\u000a that are inconsistent with or insufficient for a confident diagnosis of classic disease (outlier syndrome). Diagnostic criteria\\u000a have not been codified, but application of a modified scoring system provides a template that can be combined with clinical\\u000a findings to ensure uniform evaluation and

Albert J. Czaja

1999-01-01

136

Unusual variants of malignant melanoma  

Microsoft Academic Search

A potential diagnostic pitfall in the histologic assessment of melanoma is the inability to recognize unusual melanoma variants. Of these, the more treacherous examples include the desmoplastic melanoma, the nevoid melanoma, the so-called ‘minimal-deviation melanoma,’ melanoma with prominent pigment synthesis or ‘animal-type melanoma,’ and the malignant blue nevus. Also problematic are the unusual phenotypic profiles seen in vertical growth phase

Cynthia M Magro; A Neil Crowson; Martin C Mihm

2006-01-01

137

Variant-specific prion interactions  

PubMed Central

Prions are protein conformations that “self-seed” the misfolding of their non-prion iso-forms into prion, often amyloid, conformations. The most famous prion is the mammalian PrP protein that in its prion form causes transmissible spongiform encephalopathy. Curiously there can be distinct conformational differences even between prions of the same protein propagated in the same host species. These are called prion strains or variants. For example, different PrP variants are faithfully transmitted during self-seeding and are associated with distinct disease characteristics. Variant-specific PrP prion differences include the length of the incubation period before the disease appears and the deposition of prion aggregates in distinct regions of the brain.1 Other more common neurodegenerative diseases (e.g., Alzheimer disease, Parkinson disease, type 2 diabetes and ALS) are likewise caused by the misfolding of a normal protein into a self-seeding aggregate.2-4 One of the most important unanswered questions is how the first prion-like seed arises de novo, resulting in the pathological cascade. PMID:24475372

Sharma, Jaya; Liebman, Susan W

2013-01-01

138

Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone?  

PubMed Central

Summary Background New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype. Aim To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England. Methods Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains. Findings By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 × 10?6, Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006. Conclusions Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms. PMID:24433924

Miller, R.R.; Price, J.R.; Batty, E.M.; Didelot, X.; Wyllie, D.; Golubchik, T.; Crook, D.W.; Paul, J.; Peto, T.E.A.; Wilson, D.J.; Cule, M.; Ip, C.L.C.; Day, N.P.J.; Moore, C.E.; Bowden, R.; Llewelyn, M.J.

2014-01-01

139

PBHoney: identifying genomic variants via long-read discordance and interrupted mapping  

PubMed Central

Background As resequencing projects become more prevalent across a larger number of species, accurate variant identification will further elucidate the nature of genetic diversity and become increasingly relevant in genomic studies. However, the identification of larger genomic variants via DNA sequencing is limited by both the incomplete information provided by sequencing reads and the nature of the genome itself. Long-read sequencing technologies provide high-resolution access to structural variants often inaccessible to shorter reads. Results We present PBHoney, software that considers both intra-read discordance and soft-clipped tails of long reads (>10,000 bp) to identify structural variants. As a proof of concept, we identify four structural variants and two genomic features in a strain of Escherichia coli with PBHoney and validate them via de novo assembly. PBHoney is available for download at http://sourceforge.net/projects/pb-jelly/. Conclusions Implementing two variant-identification approaches that exploit the high mappability of long reads, PBHoney is demonstrated as being effective at detecting larger structural variants using whole-genome Pacific Biosciences RS II Continuous Long Reads. Furthermore, PBHoney is able to discover two genomic features: the existence of Rac-Phage in isolate; evidence of E. coli’s circular genome. PMID:24915764

2014-01-01

140

Space-variant optical systems  

NASA Astrophysics Data System (ADS)

Analytical and experimental investigations of 2-D space-variant optical processing techniques have been conducted. Coherent processing investigations have included (1) a continuing experimental study of the characteristics of UV-exposed photoresist phase masks for multiplex holography, and (2) both analytical and experimental studies of a technique for using wavelength-encoded tandem 1-D processors for performing 2-D processing. In the area of incoherent processing, we have completed an investigation of a tristimulus-based technique for performing complex operations using hue, saturation, and intensity parameters to represent complex numbers.

Walkup, J. F.; Krile, T. F.

1982-11-01

141

Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode  

PubMed Central

Toxigenic Corynebacterium diphtheriae strains cause diphtheria in humans. The toxigenic C. diphtheriae isolate NCTC13129 produces three distinct heterotrimeric pili that contain SpaA, SpaD, and SpaH, making up the shaft structure. The SpaA pili are known to mediate bacterial adherence to pharyngeal epithelial cells. However, to date little is known about the expression of different pili in various clinical isolates and their importance in bacterial pathogenesis. Here, we characterized a large collection of C. diphtheriae clinical isolates for their pilin gene pool by PCR and for the expression of the respective pilins by immunoblotting with antibodies against Spa pilins. Consistent with the role of a virulence factor, the SpaA-type pili were found to be prevalent among the isolates, and most significantly, corynebacterial adherence to pharyngeal epithelial cells was strictly correlated with isolates that were positive for the SpaA pili. By comparison, the isolates were heterogeneous for the presence of SpaD- and SpaH-type pili. Importantly, using Caenorhabditis elegans as a model host for infection, we show here that strain NCTC13129 rapidly killed the nematodes, the phenotype similar to isolates that were positive for toxin and all pilus types. In contrast, isogenic mutants of NCTC13129 lacking SpaA-type pili or devoid of toxin and SpaA pili exhibited delayed killing of nematodes with similar kinetics. Consistently, nontoxigenic or toxigenic isolates that lack one, two, or all three pilus types were also attenuated in virulence. This work signifies the important role of pili in corynebacterial pathogenesis and provides a simple host model to identify additional virulence factors. PMID:23772071

Broadway, Melissa M.; Rogers, Elizabeth A.; Chang, Chungyu; Huang, I-Hsiu; Dwivedi, Prabhat; Yildirim, Suleyman; Schmitt, Michael P.; Das, Asis

2013-01-01

142

Modeling and Selection of Software Service Variants.  

E-print Network

??Providers and consumers have to deal with variants, meaning alternative instances of a service?s design, implementation, deployment, or operation, when developing or delivering software services.… (more)

Wittern, John Erik

2014-01-01

143

[PSI+] Prion Variant Establishment in Yeast  

PubMed Central

Summary Differences in the clinical pathology of mammalian prion diseases reflect distinct heritable conformations of aggregated PrP proteins, called prion strains. Here, using the yeast [PSI+] prion, we examine the de novo establishment of prion strains (called variants in yeast). The [PSI+] prion protein, Sup35, is efficiently induced to take on numerous prion variant conformations following transient overexpression of Sup35 in the presence of another prion, e.g. [PIN+]. One hypothesis is that the first [PSI+] prion seed to arise in a cell causes propagation of only that seed’s variant, but that different variants could be initiated in different cells. However, we now show that even within a single cell, Sup35 retains the potential to fold into more than one variant type. When individual cells segregating different [PSI+] variants were followed in pedigrees, establishment of a single variant phenotype generally occurred in daughters, granddaughters or great granddaughters—but in 5% of the pedigrees cells continued to segregate multiple variants indefinitely. The data is consistent with the idea that many newly formed prions go through a maturation phase before they reach a single specific variant conformation. These findings may be relevant to mammalian PrP prion strain establishment and adaptation. PMID:22998111

Sharma, Jaya; Liebman, Susan W.

2012-01-01

144

First Report of Brain Abscess Caused by a Satelliting Phenotypic Variant of Helcococcus kunzii  

PubMed Central

Helcococcus kunzii was isolated from a brain abscess in a diabetic patient with cholesteatoma and demonstrated satellitism around Staphylococcus aureus in culture. This is the first reported case of severe central nervous system infection due to H. kunzii and the first description of a satelliting phenotypic variant of this organism. PMID:24172152

Sridhar, Siddharth; Chan, Jasper F. W.

2014-01-01

145

Genetic Tracking of the Raccoon Variant of Rabies Virus in Eastern North America  

Microsoft Academic Search

To gain insight into the incursion of the raccoon variant of rabies into the raccoon population in three Canadian provinces, a collection of 192 isolates of the raccoon rabies virus (RRV) strain was acquired from across its North American range and was genetically characterized. A 516-nucleotide segment of the non-coding region between the G and L protein open reading frames,

Annamaria G. Szanto; Susan A. Nadin-Davis; Richard C. Rosatte; Bradley N. White

2011-01-01

146

First Case of Human Rabies in Chile Caused by an Insectivorous Bat Virus Variant  

PubMed Central

The first human rabies case in Chile since 1972 occurred in March 1996 in a patient without history of known exposure. Antigenic and genetic characterization of the rabies isolate indicated that its reservoir was the insectivorous bat Tadarida brasiliensis. This is the first human rabies case caused by an insectivorous bat rabies virus variant reported in Latin America. PMID:11749754

Favi, Myriam; Yung, Veronica; Chala, Evelyn; Lopez, Luis R.

2002-01-01

147

Prevalence of the archetypal regulatory region and sequence polymorphisms in nonpassaged BK virus variants.  

PubMed Central

Since the first isolation and characterization of BK virus (BKV), a number of BKV variants which differ in genomic structure or antigenic determinants have been described. The regulatory region, in particular, the enhancer elements, show the most divergent sequences among different isolates. The structural organization of a putative ancestral prototype or archetype, from which all of the variants are probably derived, has been proposed. By sequencing the regulatory regions of 13 different isolates from the urine of bone marrow transplant recipients, we determined the structures and sequences of BKV variants diffused in the human population. The enhancer region was amplified by polymerase chain reaction to avoid passage in culture, and the product was directly sequenced. The structure most frequently observed is in agreement with the postulated archetype, containing a single enhancer element with no repeats. By sequence analysis we identified four hot spots of nucleotide variation. These variations are consistent with the existence of two consensus sequences. One sequence motif, observed in about 85% of the isolates, is referred to as the archetypal BKV, while a second motif, observed in the remaining 15% of the variants, is highly reminiscent of the AS strain. PMID:1651425

Negrini, M; Sabbioni, S; Arthur, R R; Castagnoli, A; Barbanti-Brodano, G

1991-01-01

148

Small Colony Variant of Methicillin-Resistant Staphylococcus pseudintermedius ST71 Presenting as a Sticky Phenotype  

PubMed Central

We first observed the phenomenon of small colony variants (SCVs) in a Staphylococcus pseudintermedius sequence type 71 (ST71) strain, isolated from a non-pet owner. Although we found that small-sized colonies share main features with Staphylococcus aureus SCVs, they nevertheless show a novel, particular, and sticky phenotype, whose expression was extremely stable, even after subcultivation. PMID:24452163

Carretto, Edoardo; Polilli, Ennio; Marrollo, Roberta; Santarone, Stella; Fazii, Paolo; D'Antonio, Domenico; Rossano, Alexandra; Perreten, Vincent

2014-01-01

149

Outbreak of cholera caused by Vibrio cholerae O1 El Tor variant strain in Bihar, India.  

PubMed

An outbreak of cholera struck Bihar, an Indian state, in August 2008 following a massive flood. Here we report the phenotypic and genotypic characteristics of Vibrio cholerae strains isolated from patients with diarrhea. Rectal swabs were obtained from patients with diarrhea who were admitted to medical camps or the hospital, and the strains were biochemically and serologically characterized. V. cholerae was isolated from 21 (65.6%) of 32 rectal swabs. Serological studies revealed that all the 21 isolates belonged to V. cholerae O1 Ogawa. Mismatch amplification mutation assay (MAMA)-PCR showed that the isolates belonged to El Tor variant group, and pulsed-field gel electrophoresis (PFGE) proved that these isolates were of a different lineage than the conventional El Tor variant strains. These isolates were resistant to several drugs, including ampicillin, streptomycin, tetracycline, nalidixic acid, and furazolidone. The uniqueness of the current report arises from the fact that records of cholera in Bihar are availiable for the early 1960s but not for the next 4 decades. Moreover, the present study is the first to report a cholera outbreak in Bihar that was caused by an El Tor variant strain. PMID:24858614

Koley, Hemanta; Ray, Nivedita; Chowdhury, Goutam; Barman, Soumik; Mitra, Soma; Ramamurthy, T; Mukhopadhyay, Asish K; Sarkar, B L; Katyal, Rakesh; Das, Pradeep; Panda, Samiran; Ghosh, Subrata

2014-01-01

150

Pseudomonas aeruginosa induces pigment production and enhances virulence in a white phenotypic variant of Staphylococcus aureus  

PubMed Central

Staphyloxanthin is a virulence factor which protects Staphylococcus aureus in stress conditions. We isolated two pigment variants of S. aureus and one strain of Pseudomonas aeruginosa from a single wound infection. S. aureus variants displayed white and yellow colony phenotypes. The sequence of the operons for staphyloxanthin synthesis indicated that coding and promoter regions were identical between the two pigment variants. Quorum sensing controls pigment synthesis in some bacteria. It is also shown that P. aeruginosa quorum-sensing molecules affect S. aureus transcription. We explored whether the co-infecting P. aeruginosa can affect pigment production in the white S. aureus variant. In co-culture experiments between the white variants and a selected number of Gram-positive and Gram-negative bacteria, only P. aeruginosa induced pigment production in the white variant. Gene expression analysis of the white variant did not indicate upregulation of the crtM and other genes known to be involved in pigment production (sigB, sarA, farnesyl pyrophosphate synthase gene [FPP-synthase], hfq). In contrast, transcription of the catalase gene was significantly upregulated after co-culture. P. aeruginosa-induced pigment synthesis and catalase upregulation correlated with increased resistance to polymyxin B, hydrogen peroxide, and the intracellular environment of macrophages. Our data indicate the presence of silent but functional staphyloxanthin synthesis machinery in a white phenotypic variant of S. aureus which is activated by a co-infecting P. aeruginosa via inter-species communication. Another S. aureus virulence factor, catalase is also induced by this co-infecting bacterium. The resulting phenotypic changes are directly correlated with resistance of the white variant to stressful conditions. PMID:24232573

Antonic, Vlado; Stojadinovic, Alexander; Zhang, Binxue; Izadjoo, Mina J; Alavi, Mohammad

2013-01-01

151

The KRAS-Variant and miRNA Expression in RTOG Endometrial Cancer Clinical Trials 9708 and 9905  

PubMed Central

Objective To explore the association of a functional germline variant in the 3?-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. Methods/Materials The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. Results The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p?=?0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p?=?0.24), respectively, favoring the variant. Conclusions The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology. PMID:24732316

Uduman, Mohamed; Winter, Kathryn; Boeke, Marta; Greven, Kathryn M.; King, Stephanie; Burke, Thomas W.; Underhill, Kelly; Kim, Harold; Boulware, Raleigh J.; Yu, Herbert; Parkash, Vinita; Lu, Lingeng; Gaffney, David; Dicker, Adam P.; Weidhaas, Joanne

2014-01-01

152

Mitochondrial DNA Variants in Obesity  

PubMed Central

Heritability estimates for body mass index (BMI) variation are high. For mothers and their offspring higher BMI correlations have been described than for fathers. Variation(s) in the exclusively maternally inherited mitochondrial DNA (mtDNA) might contribute to this parental effect. Thirty-two to 40 mtDNA single nucleotide polymorphisms (SNPs) were available from genome-wide association study SNP arrays (Affymetrix 6.0). For discovery, we analyzed association in a case-control (CC) sample of 1,158 extremely obese children and adolescents and 435 lean adult controls. For independent confirmation, 7,014 population-based adults were analyzed as CC sample of n?=?1,697 obese cases (BMI?30 kg/m2) and n?=?2,373 normal weight and lean controls (BMI<25 kg/m2). SNPs were analyzed as single SNPs and haplogroups determined by HaploGrep. Fisher's two-sided exact test was used for association testing. Moreover, the D-loop was re-sequenced (Sanger) in 192 extremely obese children and adolescents and 192 lean adult controls. Association testing of detected variants was performed using Fisher's two-sided exact test. For discovery, nominal association with obesity was found for the frequent allele G of m.8994G/A (rs28358887, p?=?0.002) located in ATP6. Haplogroup W was nominally overrepresented in the controls (p?=?0.039). These findings could not be confirmed independently. For two of the 252 identified D-loop variants nominal association was detected (m.16292C/T, p?=?0.007, m.16189T/C, p?=?0.048). Only eight controls carried the m.16292T allele, five of whom belonged to haplogroup W that was initially enriched among these controls. m.16189T/C might create an uninterrupted poly-C tract located near a regulatory element involved in replication of mtDNA. Though follow-up of some D-loop variants still is conceivable, our hypothesis of a contribution of variation in the exclusively maternally inherited mtDNA to the observed larger correlations for BMI between mothers and their offspring could not be substantiated by the findings of the present study. PMID:24788344

Knoll, Nadja; Jarick, Ivonne; Volckmar, Anna-Lena; Klingenspor, Martin; Illig, Thomas; Grallert, Harald; Gieger, Christian; Wichmann, Heinz-Erich; Peters, Annette; Wiegand, Susanna; Biebermann, Heike; Fischer-Posovszky, Pamela; Wabitsch, Martin; Volzke, Henry; Nauck, Matthias; Teumer, Alexander; Rosskopf, Dieter; Rimmbach, Christian; Schreiber, Stefan; Jacobs, Gunnar; Lieb, Wolfgang; Franke, Andre; Hebebrand, Johannes; Hinney, Anke

2014-01-01

153

The odontogenic keratocyst: orthokeratinized variant.  

PubMed

The histopathologic and clinical features of sixty cases of orthokeratinized odontogenic cysts were compared with those of odontogenic keratocysts (typically parakeratinized). According to the results of this study, the orthokeratinized odontogenic cyst appears to be a distinct clinicopathologic entity. This cyst is histologically characterized by a thin, uniform, epithelial lining with orthokeratinization and a subjacent granular cell layer. The basal cells are usually cuboidal or flattened. Clinically, the orthokeratinized cyst is a single cyst, shows a predilection for males, and is most often found in the second to the fifth decade, it appears most commonly as a dentigerous cyst in the posterior mandible. The orthokeratinized cyst shows little clinical aggressiveness. Follow-up of twenty-four patients revealed only one recurrence; of nineteen patients evaluated, none had features of the basal cell nevus-bifid rib syndrome. It is suggested that this cyst be called odontogenic keratocyst, orthokeratinized variant. PMID:6166916

Wright, J M

1981-06-01

154

Primary pleural liposarcoma, pleomorphic variant  

PubMed Central

Primary pleural liposarcoma (PPL) is a rare tumor derived from primitive mesenchymal tissue. We report a case of a 49-year-old female patient complaining of thoracic pain and dyspnea for 3 months. The chest X-ray showed a left basal opacity of lobulated contours and the thoracic computer tomography (CT) scan revealed a left pleural collection/mass, of 18 HU density and passive pulmonary atelectasis. The patient was taken to surgery and the cytologic examination of the gelatinous mass found in the procedure confirmed the diagnosis of a pleomorphic variant of pleural liposarcoma. We emphasise in the importance of careful inspection of the origin of the tumor in the diagnostic images to allow accurate diagnosis. PMID:25276389

Navarrete, Constanza; Lopez Arias, Maria Alejandra; Pelaez, Mauricio

2014-01-01

155

Primary pleural liposarcoma, pleomorphic variant.  

PubMed

Primary pleural liposarcoma (PPL) is a rare tumor derived from primitive mesenchymal tissue. We report a case of a 49-year-old female patient complaining of thoracic pain and dyspnea for 3 months. The chest X-ray showed a left basal opacity of lobulated contours and the thoracic computer tomography (CT) scan revealed a left pleural collection/mass, of 18 HU density and passive pulmonary atelectasis. The patient was taken to surgery and the cytologic examination of the gelatinous mass found in the procedure confirmed the diagnosis of a pleomorphic variant of pleural liposarcoma. We emphasise in the importance of careful inspection of the origin of the tumor in the diagnostic images to allow accurate diagnosis. PMID:25276389

Carrillo B, Jorge Alberto; Navarrete, Constanza; López Arias, María Alejandra; Peláez, Mauricio

2014-09-01

156

New Gene Variants for Prostate Cancer Identified  

MedlinePLUS

... page, please enable JavaScript. New Gene Variants for Prostate Cancer Identified 23 new variants associated with increased risk ... 2014 Related MedlinePlus Pages Genes and Gene Therapy Prostate Cancer MONDAY, Sept. 15, 2014 (HealthDay News) -- An international ...

157

Characterization of variant forms of organophosphorus hydrolase  

E-print Network

to the enzyme's activity and stability by identifying regions of the enzyme necessary for each. PCR mutagenesis was used to create 67 variant forms of the gene that encodes OPH. Eight variant genes were then sequenced to locate the mutations in the enzymes...

Rowe, Claire E.

2013-02-22

158

Variants in GATA4 Are a Rare Cause of Familial and Sporadic Congenital Diaphragmatic Hernia  

PubMed Central

Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm, occurring as either an isolated defect or in association with other anomalies. Genetic factors including aneuploidies and copy number variants are important in the pathogenesis of many cases of CDH, but few single genes have been definitively implicated in human CDH. In this study, we used whole exome sequencing (WES) to identify a paternally inherited novel missense GATA4 variant (c. 754C>T, p. R252W) in a familial case of CDH with incomplete penetrance. Phenotypic characterization of the family included magnetic resonance imaging (MRI) of the chest and abdomen demonstrating asymptomatic defects in the diaphragm in the two “unaffected” missense variant carriers. Screening 96 additional CDH patients identified a de novo heterozygous GATA4 variant (c.848G>A; p.R283H) in a non-isolated CDH patient. In summary, GATA4 is implicated in both familial and sporadic CDH, and our data suggests that WES may be a powerful tool to discover rare variants for CDH. PMID:23138528

Yu, Lan; Wynn, Julia; Cheung, Yee Him; Shen, Yufeng; Mychaliska, George B.; Crombleholme, Timothy M.; Azarow, Kenneth S.; Lim, Foong Yen; Chung, Dai H.; Potoka, Douglas; Warner, Brad W.; Bucher, Brian; Stolar, Charles; Aspelund, Gudrun; Arkovitz, Marc S.; Chung, Wendy K.

2012-01-01

159

Role of the Goat K222-PrPC Polymorphic Variant in Prion Infection Resistance  

PubMed Central

ABSTRACT The prion protein-encoding gene (prnp) strongly influences the susceptibility of small ruminants to transmissible spongiform encephalopathies (TSEs). Hence, selective breeding programs have been implemented to increase sheep resistance to scrapie. For goats, epidemiological and experimental studies have provided some association between certain polymorphisms of the cellular prion protein (PrPC) and resistance to TSEs. Among them, the Q/K polymorphism at PrPC codon 222 (Q/K222) yielded the most promising results. In this work, we investigated the individual effects of the K222-PrPC variant on the resistance/susceptibility of goats to TSEs. For that purpose, we generated two transgenic mouse lines, expressing either the Q222 (wild type) or K222 variant of goat PrPC. Both mouse lines were challenged intracerebrally with a panel of TSE isolates. Transgenic mice expressing the wild-type (Q222) allele were fully susceptible to infection with all tested isolates, whereas transgenic mice expressing similar levels of the K222 allele were resistant to all goat scrapie and cattle BSE isolates but not to goat BSE isolates. Finally, heterozygous K/Q222 mice displayed a reduced susceptibility to the tested panel of scrapie isolates. These results demonstrate a highly protective effect of the K222 variant against a broad panel of different prion isolates and further reinforce the argument supporting the use of this variant in breeding programs to control TSEs in goat herds. IMPORTANCE The objective of this study was to determine the role of the K222 variant of the prion protein (PrP) in the susceptibility/resistance of goats to transmissible spongiform encephalopathies (TSEs). Results showed that transgenic mice expressing the goat K222-PrP polymorphic variant are resistant to scrapie and bovine spongiform encephalopathy (BSE) agents. This protective effect was also observed in heterozygous Q/K222 animals. Therefore, the single amino acid exchange from Q to K at codon 222 of the cellular prion protein provides resistance against TSEs. All the results presented here support the view that the K222 polymorphic variant is a good candidate for selective breeding programs to control and eradicate scrapie in goat herds. PMID:24352451

Aguilar-Calvo, Patricia; Espinosa, Juan Carlos; Pintado, Belen; Gutierrez-Adan, Alfonso; Alamillo, Elia; Miranda, Alberto; Prieto, Irene; Bossers, Alex; Andreoletti, Olivier

2014-01-01

160

Phenotypic and Enzymatic Comparative Analysis of the KPC Variants, KPC-2 and Its Recently Discovered Variant KPC-15  

PubMed Central

Sixteen different variants (KPC-2 to KPC-17) in the KPC family have been reported, and most current studies are focusing on KPC-2 and KPC-3. The KPC-15 variant, which isolated from Klebsiella pneumoniae in a Chinese hospital, was a recently discovered KPC enzyme. To compare the characteristics of KPC-15 and KPC-2, the variants were determined by susceptibility testing, PCR amplification and sequencing, and study of kinetic parameters. The strain harboring the KPC-15 showed resistance to 18 conventional antimicrobial agents, especially to cabapenem antibiotics, and the strain involving the KPC-2 also indicated resistance to cabapenem antibiotics, but both strains were susceptible to polymyxin B and colistin. The conjugation experiments showed that the changes of MIC values to the antibiotics were due to the transferred plasmids. The differences of amino acids were characterised at sites of 119 leucine and 146 lysine with KPC-15 and KPC-2. The minimum evolution tree indicated the KPC alleles evolution, and showed that the KPC-15 appeared to be homogenous with KPC-4 closely. Steady-state kinetic parameters showed the catalytic efficiency of KPC-15 was higher than that of KPC-2 for all tested antibiotics in this study. The catalytic efficiency of KPC-15 caused resistance to ?-lactam antibiotics was higher than that of KPC-2. Meanwhile, an evolutionary transformation changed KPC from an efficient carbapenemase to its variants (KPC-15) with better ceftazidimase catalytic efficiency, and the old antibiotics polymyxin B and colistin might play a role in the therapy for multi-resistant strains. PMID:25360633

Yang, Yijun

2014-01-01

161

Disease variants in genomes of 44 centenarians.  

PubMed

To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30× coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as "pathogenic" or "likely pathogenic" based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE ?4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer's disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions. In genome sequences of 44 Ashkenazi centenarians, we identified many coding variants that were annotated as "pathogenic" or "likely pathogenic" based on the ClinVar database. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions. PMID:25333069

Freudenberg-Hua, Yun; Freudenberg, Jan; Vacic, Vladimir; Abhyankar, Avinash; Emde, Anne-Katrin; Ben-Avraham, Danny; Barzilai, Nir; Oschwald, Dayna; Christen, Erika; Koppel, Jeremy; Greenwald, Blaine; Darnell, Robert B; Germer, Soren; Atzmon, Gil; Davies, Peter

2014-09-01

162

Disease variants in genomes of 44 centenarians  

PubMed Central

To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30× coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as “pathogenic” or “likely pathogenic” based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE ?4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer's disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions. In genome sequences of 44 Ashkenazi centenarians, we identified many coding variants that were annotated as “pathogenic” or “likely pathogenic” based on the ClinVar database. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions. PMID:25333069

Freudenberg-Hua, Yun; Freudenberg, Jan; Vacic, Vladimir; Abhyankar, Avinash; Emde, Anne-Katrin; Ben-Avraham, Danny; Barzilai, Nir; Oschwald, Dayna; Christen, Erika; Koppel, Jeremy; Greenwald, Blaine; Darnell, Robert B; Germer, Soren; Atzmon, Gil; Davies, Peter

2014-01-01

163

In search of low-frequency and rare variants affecting complex traits.  

PubMed

The allelic architecture of complex traits is likely to be underpinned by a combination of multiple common frequency and rare variants. Targeted genotyping arrays and next-generation sequencing technologies at the whole-genome sequencing (WGS) and whole-exome scales (WES) are increasingly employed to access sequence variation across the full minor allele frequency (MAF) spectrum. Different study design strategies that make use of diverse technologies, imputation and sample selection approaches are an active target of development and evaluation efforts. Initial insights into the contribution of rare variants in common diseases and medically relevant quantitative traits point to low-frequency and rare alleles acting either independently or in aggregate and in several cases alongside common variants. Studies conducted in population isolates have been successful in detecting rare variant associations with complex phenotypes. Statistical methodologies that enable the joint analysis of rare variants across regions of the genome continue to evolve with current efforts focusing on incorporating information such as functional annotation, and on the meta-analysis of these burden tests. In addition, population stratification, defining genome-wide statistical significance thresholds and the design of appropriate replication experiments constitute important considerations for the powerful analysis and interpretation of rare variant association studies. Progress in addressing these emerging challenges and the accrual of sufficiently large data sets are poised to help the field of complex trait genetics enter a promising era of discovery. PMID:23922232

Panoutsopoulou, Kalliope; Tachmazidou, Ioanna; Zeggini, Eleftheria

2013-10-15

164

In search of low-frequency and rare variants affecting complex traits  

PubMed Central

The allelic architecture of complex traits is likely to be underpinned by a combination of multiple common frequency and rare variants. Targeted genotyping arrays and next-generation sequencing technologies at the whole-genome sequencing (WGS) and whole-exome scales (WES) are increasingly employed to access sequence variation across the full minor allele frequency (MAF) spectrum. Different study design strategies that make use of diverse technologies, imputation and sample selection approaches are an active target of development and evaluation efforts. Initial insights into the contribution of rare variants in common diseases and medically relevant quantitative traits point to low-frequency and rare alleles acting either independently or in aggregate and in several cases alongside common variants. Studies conducted in population isolates have been successful in detecting rare variant associations with complex phenotypes. Statistical methodologies that enable the joint analysis of rare variants across regions of the genome continue to evolve with current efforts focusing on incorporating information such as functional annotation, and on the meta-analysis of these burden tests. In addition, population stratification, defining genome-wide statistical significance thresholds and the design of appropriate replication experiments constitute important considerations for the powerful analysis and interpretation of rare variant association studies. Progress in addressing these emerging challenges and the accrual of sufficiently large data sets are poised to help the field of complex trait genetics enter a promising era of discovery. PMID:23922232

Panoutsopoulou, Kalliope; Tachmazidou, Ioanna; Zeggini, Eleftheria

2013-01-01

165

Studies on color type variants from mutagenized protoplasts of Porphyra haitanensis Chang et Zheng & P. Yezoensis ueda (rhodophycease)  

NASA Astrophysics Data System (ADS)

Isolated protoplasts from thalli of Porphyra haitanensis and Porphyra yezoensis were treated with colchicine or irradiated by ultraviolet (UV). Several types of color variants were observed among the protoplast offspring. After treatment with colchicine: (1) 0.04 0.09% of red type variants in P. haitanensis were obtained; (2) The rate of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were 0.31 1.11% in P. yezoensis. After irradiation with UV: (1) 3.5 10.5% of red type variants in P. yezoensis were obtained: (2) 0.5 2.0% of red type variants and the variegated chimeral thalli composed of red type and wild type of sectors were obtained in P. haitanensis. Colchicine and UV’s mutangenic effects on P. yezoensis protoplasts were stronger than those on P. haitanensis protoplasts. The most efficient concentration of colchicine was 0.05%. The optimal length of UV-radiation was 1/2 min (radiation distance 5 cm). The red type variants induced by colchicine treatment grew faster than the wild type thalli. The clones of vegetative propagation from protoplasts of red type variants were still red type thalli. The red type variants will be good materials for genetic studies and improvement of Porphyra strains.

Yan, Xinghong

1993-09-01

166

Ghrelin gene variants and eating disorders.  

PubMed

Genetic factors have been implicated in playing a significant role in susceptibility to eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). Genetic variants of ghrelin, an endogenous acylated peptide that stimulates growth hormone secretion, enhances appetite, and increases body weight, have been investigated in association with eating disorders, as changes in the ghrelin/growth hormone secretagogue receptor (GHSR)/ghrelin O-acyltransferase (GOAT) system have been implicated in its pathology. Although most candidate-gene association studies have not been able to identify ghrelin gene variants as being significantly associated with either AN or BN, some ghrelin variants may be associated with BN in Japanese. Furthermore, a significant association of a GHSR gene variant with BN and that of a GOAT gene variant with AN have been found. However, there have been relatively few studies, tested variants are restricted, and sample sizes are often modest. Therefore, further studies are needed to elucidate the role of ghrelin-related gene variants in the predisposition and pathology of eating disorders. PMID:23601422

Ando, Tetsuya

2013-01-01

167

Synthesis of spatially variant lattices.  

PubMed

It is often desired to functionally grade and/or spatially vary a periodic structure like a photonic crystal or metamaterial, yet no general method for doing this has been offered in the literature. A straightforward procedure is described here that allows many properties of the lattice to be spatially varied at the same time while producing a final lattice that is still smooth and continuous. Properties include unit cell orientation, lattice spacing, fill fraction, and more. This adds many degrees of freedom to a design such as spatially varying the orientation to exploit directional phenomena. The method is not a coordinate transformation technique so it can more easily produce complicated and arbitrary spatial variance. To demonstrate, the algorithm is used to synthesize a spatially variant self-collimating photonic crystal to flow a Gaussian beam around a 90° bend. The performance of the structure was confirmed through simulation and it showed virtually no scattering around the bend that would have arisen if the lattice had defects or discontinuities. PMID:22772224

Rumpf, Raymond C; Pazos, Javier

2012-07-01

168

Variants of cerebral arteries - anterior circulation  

PubMed Central

Summary Advances in imaging techniques allow for in vivo identification of abnormalities and normal variants of cerebral arteries. These arterial variations can be asymptomatic and uncomplicated although, some of them increase the risk of aneurysm formation, acute intracranial hemorrhage, play a vital role in neurosurgical planning or can be misidentified as serious pathology and medical errors. The goal of this publication is to discuss arterial anomalies of anterior cerebral circulation, their prevalence and demonstrate radiological images of some of those variants. In this article we will discuss variants of internal carotid artery, anterior cerebral artery, anterior communicating artery, middle cerebral artery, persistent stapedial artery and fenestration. PMID:24115959

Makowicz, Grzegorz; Poniatowska, Renata; Lusawa, Malgorzata

2013-01-01

169

Rapid detection of New Delhi metallo-?-lactamase gene and variants coding for carbapenemases with different activities by use of a PCR-based in vitro protein expression method.  

PubMed

New Delhi metallo-?-lactamase (NDM)-producing bacteria are considered potential global health threats. It is necessary to monitor NDM-1 and its variants in clinical isolates in order to understand the NDM-1 epidemic and the impact of its variants on ?-lactam resistance. To reduce the lengthy time needed for cloning and expression of NDM-1 variants, a novel PCR-based in vitro protein expression (PCR-P) method was used to detect blaNDM-1 and its variants coding for carbapenemases with different activities (functional variants). The PCR-P method combined a long-fragment real-time quantitative PCR (LF-qPCR) with in vitro cell-free expression to convert the blaNDM-1 amplicons into NDM for carbapenemase assay. The method could screen for blaNDM-1 within 3 h with a detection limit of 5 copies and identify functional variants within 1 day. Using the PCR-P to analyze 5 recent blaNDM-1 variants, 2 functional variants, blaNDM-4 and blaNDM-5, were revealed. In the initial testing of 23 clinical isolates, the PCR-P assay correctly found 8 isolates containing blaNDM-1. This novel method provides the first integrated approach for rapidly detecting the full-length blaNDM-1 and revealing its functional variants in clinical isolates. PMID:24671780

Huang, Li; Hu, Xiumei; Zhou, Man; Yang, Yinmei; Qiao, Jinjuan; Wang, Dianbing; Yu, Junping; Cui, Zongqiang; Zhang, Zhiping; Zhang, Xian-En; Wei, Hongping

2014-06-01

170

Guillain-Barré Syndrome and Variants  

PubMed Central

Synopsis Guillain-Barré syndrome (GBS) is characterized by rapidly evolving ascending weakness, mild sensory loss and hypo- or areflexia, progressing to a nadir over up to four weeks. Cerebrospinal fluid evaluation demonstrates albuminocytologic dissociation in 90% of cases. Acute inflammatory demyelinating polyneuropathy (AIDP) was the first to be recognized over a century ago and is the most common form of GBS. In AIDP, the immune attack is directed at peripheral nerve myelin with secondary by-stander axon loss. Axonal motor and sensorimotor variants have been described in the last 3 decades and are mediated by molecular mimicry targeting peripheral nerve motor axons. Besides the Miller-Fisher syndrome (MFS) and descending weakness, other rare phenotypic variants have been recently described with pure sensory variant, restricted autonomic manifestations and the pharyngeal-cervical-brachial pattern. It is important to recognize GBS and its variants due to the availability of equally effective therapies in the form of plasmapheresis and intravenous immunoglobulins. PMID:23642721

Barohn, Richard J.

2014-01-01

171

Immunological characterization of metallothioneins in mouse LMTK cells and in a variant resistant to cadmium  

SciTech Connect

A cadmium-resistant variant isolated from mouse fibroblast LMTK cells can grow in the presence of 40 ..mu..M Cd/sup 2 +/. This variant retained its properties in the absence of selecting agent. Induction of metallothionein was measured in cell extracts by radioimmunoassay. The maximum amount of metallothioneins in the cells was reached after 36 hours. The cadmium resistant variant produced two times more metallothionein than the wild-type when exposed to 10-20 ..mu..MCd/sup 2 +/. By Ouchterlony double diffusion, the metallothioneins from cultured cells formed a line of partial identity with the mouse liver serotype and a line of complete identity with one of the two mouse kidney serotypes. These observations raise the possibility of a tissue-specific expression of metallothionein genes.

Maiti; I.; Mbikay, M.; Marengo, C.; Thirion, J.-P.

1982-07-01

172

Immunological characterization of metallothioneins in mouse LMTK cells and in a variant resistant to cadmium.  

PubMed

A cadmium-resistant variant isolated from mouse fibroblast LMTK cells can grow in the presence of 40 muM Cd2+. This variant retained its properties in the absence of selecting agent. Induction of metallothionein was measured in cell extracts by radioimmunoassay. The maximum amount of metallothioneins in the cells was reached after 36 hours. The cadmium resistant variant produced two times more metallothionein than the wild-type when exposed to 10-20 muM Cd2+. By Ouchterlony double diffusion, the metallothioneins from cultured cells formed a line of partial identity with the mouse liver serotype and a line of complete identity with one of the two mouse kidney serotypes. These observations raise the possibility of a tissue-specific expression of metallothionein genes. PMID:6809772

Maiti, I; Mbikay, M; Marengo, C; Thirion, J P

1982-07-01

173

Filovirus RefSeq entries: evaluation and selection of filovirus type variants, type sequences, and names.  

PubMed

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information's (NCBI's) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()/<isolation host-suffix>///variant designation>-<isolate designation>], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences. PMID:25256396

Kuhn, Jens H; Andersen, Kristian G; Bào, Y?míng; Bavari, Sina; Becker, Stephan; Bennett, Richard S; Bergman, Nicholas H; Blinkova, Olga; Bradfute, Steven; Brister, J Rodney; Bukreyev, Alexander; Chandran, Kartik; Chepurnov, Alexander A; Davey, Robert A; Dietzgen, Ralf G; Doggett, Norman A; Dolnik, Olga; Dye, John M; Enterlein, Sven; Fenimore, Paul W; Formenty, Pierre; Freiberg, Alexander N; Garry, Robert F; Garza, Nicole L; Gire, Stephen K; Gonzalez, Jean-Paul; Griffiths, Anthony; Happi, Christian T; Hensley, Lisa E; Herbert, Andrew S; Hevey, Michael C; Hoenen, Thomas; Honko, Anna N; Ignatyev, Georgy M; Jahrling, Peter B; Johnson, Joshua C; Johnson, Karl M; Kindrachuk, Jason; Klenk, Hans-Dieter; Kobinger, Gary; Kochel, Tadeusz J; Lackemeyer, Matthew G; Lackner, Daniel F; Leroy, Eric M; Lever, Mark S; Mühlberger, Elke; Netesov, Sergey V; Olinger, Gene G; Omilabu, Sunday A; Palacios, Gustavo; Panchal, Rekha G; Park, Daniel J; Patterson, Jean L; Paweska, Janusz T; Peters, Clarence J; Pettitt, James; Pitt, Louise; Radoshitzky, Sheli R; Ryabchikova, Elena I; Saphire, Erica Ollmann; Sabeti, Pardis C; Sealfon, Rachel; Shestopalov, Aleksandr M; Smither, Sophie J; Sullivan, Nancy J; Swanepoel, Robert; Takada, Ayato; Towner, Jonathan S; van der Groen, Guido; Volchkov, Viktor E; Volchkova, Valentina A; Wahl-Jensen, Victoria; Warren, Travis K; Warfield, Kelly L; Weidmann, Manfred; Nichol, Stuart T

2014-09-01

174

Filovirus RefSeq Entries: Evaluation and Selection of Filovirus Type Variants, Type Sequences, and Names  

PubMed Central

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information’s (NCBI’s) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()/<isolation host-suffix>///variant designation>-<isolate designation>], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences. PMID:25256396

Kuhn, Jens H.; Andersen, Kristian G.; Bao, Yiming; Bavari, Sina; Becker, Stephan; Bennett, Richard S.; Bergman, Nicholas H.; Blinkova, Olga; Bradfute, Steven; Brister, J. Rodney; Bukreyev, Alexander; Chandran, Kartik; Chepurnov, Alexander A.; Davey, Robert A.; Dietzgen, Ralf G.; Doggett, Norman A.; Dolnik, Olga; Dye, John M.; Enterlein, Sven; Fenimore, Paul W.; Formenty, Pierre; Freiberg, Alexander N.; Garry, Robert F.; Garza, Nicole L.; Gire, Stephen K.; Gonzalez, Jean-Paul; Griffiths, Anthony; Happi, Christian T.; Hensley, Lisa E.; Herbert, Andrew S.; Hevey, Michael C.; Hoenen, Thomas; Honko, Anna N.; Ignatyev, Georgy M.; Jahrling, Peter B.; Johnson, Joshua C.; Johnson, Karl M.; Kindrachuk, Jason; Klenk, Hans-Dieter; Kobinger, Gary; Kochel, Tadeusz J.; Lackemeyer, Matthew G.; Lackner, Daniel F.; Leroy, Eric M.; Lever, Mark S.; Muhlberger, Elke; Netesov, Sergey V.; Olinger, Gene G.; Omilabu, Sunday A.; Palacios, Gustavo; Panchal, Rekha G.; Park, Daniel J.; Patterson, Jean L.; Paweska, Janusz T.; Peters, Clarence J.; Pettitt, James; Pitt, Louise; Radoshitzky, Sheli R.; Ryabchikova, Elena I.; Saphire, Erica Ollmann; Sabeti, Pardis C.; Sealfon, Rachel; Shestopalov, Aleksandr M.; Smither, Sophie J.; Sullivan, Nancy J.; Swanepoel, Robert; Takada, Ayato; Towner, Jonathan S.; van der Groen, Guido; Volchkov, Viktor E.; Volchkova, Valentina A.; Wahl-Jensen, Victoria; Warren, Travis K.; Warfield, Kelly L.; Weidmann, Manfred; Nichol, Stuart T.

2014-01-01

175

Alkalophilic Bacillus firmus RAB generates variants which can grow at lower Na/sup +/ concentrations than the parental strain  

SciTech Connect

Obligately alkalophilic Bacillus firmus RAB cannot grow well on media containing less than 5 mM Na/sup +/. However, variant strains can be isolated on plates containing 2 to 3 mM Na/sup +/. These variants are observed only rarely in cultures that are plated before being subjected to repeated transfers in liquid medium. Cultures which have been transferred several times produce variants at an apparent frequency of 2 x 10/sup -4/. Most of these variants are unstable, generating parental types at the high frequency of 10%; however, stable variants can be isolated. These strains grow better than the parental strain at very high pH values in the presence of 5 mM Na/sup +/ and have enhanced activity of the Na/sup +/ -H/sup +/ antiporter that has been implicated in pH homeostasis. By contrast, Na/sup +/-coupled solute uptake is indistinguishable from that of the parental strain, and no obvious changes in the respiratory chain components are apparent in reduced versus oxidized difference spectra. The membranes of the variants show a marked enhancement, on sodium dodecyl sulfate-polyacrylamide gradient electrophoresis, in one polypeptide band with a molecular weight in the range of 90,000. The findings are discussed from the point of view of genetic mechanisms that might confer adaptability to even more extreme environments than usual and in view of earlier models relating the Na/sup +/-translocating activities of the alkalophiles.

Krulwich, T.A.; Guffanti, A.A.; Fong, M.Y.; Falk, L.; Hicks, D.B.

1986-03-01

176

Alternative Technical Summary Report: Electrometallurgical Treatment Variant  

SciTech Connect

Immobilization is the fixation of the surplus fissile materials in an acceptable matrix such as glass or ceramics to create an environmentally benign form for disposal in a repository. In addition to the traditional characteristics required of an immobilization form to achieve isolation of the fissile material from the biosphere over geologic times, the immobilization form for the Fissile Materials Disposition Program (FMDP) must also possess the property that it is inherently as unattractive and inaccessible as the fissile material from commercial spent fuel. This latter requirement is similar to the wording of the ''spent fuel standard'' invoked in the National Academy of Sciences (NAS) study on plutonium disposition. High-level wastes (HLW) or separated cesium ({sup 137}Cs), can be added with the fissile material into the waste form to create a radiation field that increases the proliferation resistance and decreases reuse by the host nation in the following ways: (1) Plutonium will be diluted with elements that must be removed by extensive chemical processing to return it to weapons-usable purity; (2) The immobilized plutonium canisters will contain approximately 2 tonnes (2000 kg; 2.2 tons) of mass, thereby forcing the use of heavy equipment to move the canisters; (3) A gamma radiation barrier will be added to the immobilized plutonium canisters; the present concept is to add a radiation barrier that is greater than 1 Gy (100 rad) per hour at 1 m (3 ft) 30 years after fabrication; (4) These canisters will then be sealed in casks and emplaced into drifts in a federal repository where they will be monitored for 100 years before the repository is sealed. This immobilization process is shown conceptually in Figure 1. In the electrometallurgical treatment (ET) variant, plutonium-rich residues are shipped to existing Argonne National Laboratory-West (ANL-W) facilities where the plutonium is converted to plutonium chloride, dissolved in a molten salt solution, sorbed on zeolites, and then immobilized in a glass-bonded zeolite (GBZ) waste form. The immobilization operations will be performed in facilities and equipment that are being prepared to treat Department of Energy (DOE)-owned spent fuels in the ANL-W hot cells. Costs are also estimated for a secondary case for simultaneous plutonium disposition and spent fuel treatment. The fission products from these fuels may contribute some radiation to the immobilization forms, but the {sup 137}Cs from the Hanford capsules will provide most of the radiation field to create a radiation barrier.

Gray, L.W.

1995-11-30

177

Phenotypic and functional characterization of mouse attenuated and virulent variants of foot-and-mouth disease virus type O1 Campos.  

PubMed

A series of genetically related variants arising from a parental wild-type isolate of O1 Campos and its tissue culture adapted variant were differentiated by various cell culture markers (temperature sensitivity, plaque size, viral yield) and lethality in mice. These isolates were additionally characterized functionally and biochemically by examining poly(C) length, RNA synthesis, protein synthesis, and cell receptor binding. In primary bovine kidney cells, the virulent isolates had greater levels of protein synthesis, whereas in baby hamster kidney cells, the attenuated variant outproduced the wild-type parent. The tissue culture adapted variant had substantially greater ability to attach to cells than the parental wild type. The parental wild-type and the tissue culture-adapted variant were similarly neutralized by various sera against whole virus, but the parental wild type was less effectively neutralized by sera prepared from either full or truncated (variable region) bacterially expressed VP1 polypeptides. The capsid region of the genomes of both these variants was sequenced and a nucleotide substitution resulting in a change in amino acid 56 in VP3 was found. The nucleotide sequence change for the remaining two variants was that of the parental wild-type virus. PMID:8384748

Jensen, M J; Moore, D M

1993-04-01

178

LUMPY: a probabilistic framework for structural variant discovery  

PubMed Central

Comprehensive discovery of structural variation (SV) from whole genome sequencing data requires multiple detection signals including read-pair, split-read, read-depth and prior knowledge. Owing to technical challenges, extant SV discovery algorithms either use one signal in isolation, or at best use two sequentially. We present LUMPY, a novel SV discovery framework that naturally integrates multiple SV signals jointly across multiple samples. We show that LUMPY yields improved sensitivity, especially when SV signal is reduced owing to either low coverage data or low intra-sample variant allele frequency. We also report a set of 4,564 validated breakpoints from the NA12878 human genome. https://github.com/arq5x/lumpy-sv. PMID:24970577

2014-01-01

179

Early learning of discrete call variants in red crossbills: implications for reliable signaling  

Microsoft Academic Search

The identification of appropriate companions and mates is essential to both speciation and the maintenance of species through\\u000a prezygotic isolation. In many birds, social assortment is mediated by vocalizations learned through imitation. When imitative\\u000a vocal learning occurs throughout life, emergent shared signals reflect current social associations. However, when vocal and\\u000a genetic variation arises among populations, shared learned signal variants have

Kendra B. Sewall

2011-01-01

180

Essential Oil Composition of a Citronella-like Variant of Lemongrass  

Microsoft Academic Search

A natural variant of lemongrass (Cymbopogon flexuosus), with a citronella-like odor which was isolated from cycle-4 population of a recurrent selection program in lemongrass, was studied for its essential oil composition by GC and GC\\/MS. The main components of the oil were geraniol (13.1%), citronellyl acetate (11.2%) and geranyl acetate (25.9%), while neral (3.7%) and geranial (5.8%) were minor constituents.

R. N. Kulkarni; G. R. Mallavarapu; K. Baskaran; S. Ramesh; Sushil Kumar

1997-01-01

181

R factor variants with enhanced sex factor activity in Pseudomonas aeruginosa  

Microsoft Academic Search

The R factor R68 readily promotes chromosome transfer in Pseudomonas aeruginosa strain PAT, but shows little such sex factor activity in strain PAO. A variant of this plasmid, R68.45, has been isolated which produces recombinants in PAO plate matings at frequencies of 10-3–10-5 per donor cell for markers in the 0–60 min region of the chromosome. Little or no chromosome

Dieter Haas; Bruce W. Holloway

1976-01-01

182

1952] Rollins,Cruciferae of the Nashville Basin, Tenn. 185 considerable variation. There is some indication that variants  

E-print Network

and these isolated species of Lesquerella needs consider- ably more field study. However, I find it tempting to offer has not played a part in producing some of the variant populations of Lesquerella in the Nashville naturally. Following is a synoptic treatment of Lesquerella for the State of Tennessee: KEY TO THE SPECIES

183

Determination of a novel integron-located variant (blaOXA -320 ) of Class D ?-lactamase in Proteus mirabilis.  

PubMed

Proteus mirabilis (P. mirabilis) is one of Gram-negative pathogens encountered in clinical specimens. A clinical isolate (TRP41) of P. mirabilis was isolated from a Turkish patient in Turkey. The isolate was identified using the API 32GN system and 16S rRNA gene sequencing and it was found resistant to ampicillin/sulbactam, piperacillin, tetracycline, and trimethoprim/sulfamethoxazole. This isolate was harboring a Class 1 integron gene cassette and its DNA sequence analysis revealed a novel blaOXA variant exhibiting one amino acid substitution (Asn266Ile) from blaOXA-1 . This new variant of OXA was located on Class 1 integron together with aadA1 gene encoding aminoglycoside-modifying enzymes. According to sequence records, the new variant was named as blaOXA-320 . Cassette array and size of integron were found as blaOXA-320 -aadA1 and 2086?bp, respectively. The blaOXA-320 gene is not transferable according to conjugation experiment. In this study, we report the first identification of blaOXA-320 -aadA1 gene cassette, a novel variant of Class D ?-lactamase, in P. mirabilis from Turkey. PMID:24027220

Cicek, Aysegul Copur; Duzgun, Azer Ozad; Saral, Aysegul; Sandalli, Cemal

2014-10-01

184

Transient midventricular ballooning syndrome: a new variant.  

PubMed

We describe a new variant of transient left ventricular (LV) ballooning in North American Caucasian patients in which only the midventricle is affected. The patients described in this case series initially presented with emotional or physical stress and had similarities to transient apical ballooning syndrome; however, this variant is unique in that the transient ballooning involves the midventricle with hypercontractility of the apical and basal segments. The presentation, clinical features, and transient nature of the reported cases in this series are similar to transient LV apical ballooning and suggest a shared pathophysiologic etiology. Sparing of the apical segment with involvement of midventricle only supports etiologies not related to an epicardial coronary artery distribution. Although the pathophysiologic mechanism of the transient ventricular ballooning syndromes and other cases of catecholamine-associated transient ventricular dysfunction are not well understood, the emergence of this new variant raises further questions in the understanding of the "brain-heart" relationship. PMID:16875987

Hurst, R Todd; Askew, J Wells; Reuss, Christina S; Lee, Richard W; Sweeney, John P; Fortuin, F David; Oh, Jae K; Tajik, A Jamil

2006-08-01

185

A novel variant of avian infectious bronchitis virus resulting from recombination among three different strains.  

PubMed

An antigenic variant of avian infectious bronchitis virus (IBV), a coronavirus, was isolated and characterized. This strain, CU-T2, possesses a number of unusual features, which have not been previously observed in IBV. The S1 glycoprotein of CU-T2 carries virus-neutralizing and serotype-specific epitopes of two IBV serotypes, Arkansas (Ark) and Massachusetts (Mass). Sequence analysis revealed that the virus, originally an Ark serotype, has acquired the Mass-specific epitope by mutation(s). This provides evidence that point mutations may lead to generation of IBV antigenic variants in the field. It was further observed that two independent recombination events involving three different IBV strains had occurred in the S2 glycoprotein gene and N protein gene of CU-T2, indicating that genomic RNA recombination in IBV may occur in multiple genes in nature. It was especially significant that a sequence of Holland 52 (a vaccine strain) had replaced half of the N gene of CU-T2. This proves that recombination among vaccine strains is contributing to the generation of IBV variants in the field. Based on these observations it is predicted that every IBV field isolate could have unique genetic nature. Therefore, several recently reported diagnostic and serotyping methods of IBV which are based on dot-blot hybridization, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR), may not reveal the true antigenic and/or genetic nature of IBV isolates, and may in fact yield misleading information. PMID:7710354

Jia, W; Karaca, K; Parrish, C R; Naqi, S A

1995-01-01

186

Genetic tracking of the raccoon variant of rabies virus in eastern North America.  

PubMed

To gain insight into the incursion of the raccoon variant of rabies into the raccoon population in three Canadian provinces, a collection of 192 isolates of the raccoon rabies virus (RRV) strain was acquired from across its North American range and was genetically characterized. A 516-nucleotide segment of the non-coding region between the G and L protein open reading frames, corresponding to the most variable region of the rabies virus genome, was sequenced. This analysis identified 119 different sequences, and phylogenetic analysis of the dataset supports the documented history of RRV spread. Three distinct geographically restricted RRV lineages were identified. Lineage 1 was found in Florida, Alabama and Georgia and appears to form the ancestral lineage of the raccoon variant of rabies. Lineage 2, represented by just two isolates, was found only in Florida, while the third lineage appears broadly distributed throughout the rest of the eastern United States and eastern Canada. In New York State, two distinct spatially segregated variants were identified; the one occupying the western and northern portions of the state was responsible for an incursion of raccoon rabies into the Canadian province of Ontario. Isolates from New Brunswick and Quebec form distinct, separate clusters, consistent with their independent origins from neighboring areas of the United States. The data are consistent with localized northward incursion into these three separate areas with no evidence of east-west viral movement between the three Canadian provinces. PMID:21624778

Szanto, Annamaria G; Nadin-Davis, Susan A; Rosatte, Richard C; White, Bradley N

2011-06-01

187

Histone variants: dynamic punctuation in transcription  

PubMed Central

Eukaryotic gene regulation involves a balance between packaging of the genome into nucleosomes and enabling access to regulatory proteins and RNA polymerase. Nucleosomes are integral components of gene regulation that restrict access to both regulatory sequences and the underlying template. Whereas canonical histones package the newly replicated genome, they can be replaced with histone variants that alter nucleosome structure, stability, dynamics, and, ultimately, DNA accessibility. Here we consider how histone variants and their interacting partners are involved in transcriptional regulation through the creation of unique chromatin states. PMID:24696452

Weber, Christopher M.; Henikoff, Steven

2014-01-01

188

Heat sensitivity in a bentgrass variant. Failure to accumulate a chloroplast heat shock protein isoform implicated in heat tolerance.  

PubMed

Two variants of creeping bentgrass (Agrostis stolonifera cv palustris), developed using tissue culture, have been used to determine the roles of chloroplast-localized small heat shock proteins (CP-sHSPs) in heat tolerance. Results from previous research indicate that the heat-tolerant variant expressed two additional CP-sHSP isoforms not expressed in the heat-sensitive variant, that accumulation of the additional CP-sHSP isoforms was genetically linked to thermotolerance, and that the presence of the additional isoforms in the heat-tolerant variant provided greater protection to photosystem II during heat stress. To determine the basis of the differential expression, we isolated the genes encoding the CP-sHSPs from both variants and characterized their structure and expression. Two genes, ApHsp26.2 and ApHsp26.7a, were isolated from the heat-tolerant variant, and three genes, ApHsp26.2m, ApHsp26.8, and ApHsp26.7b, were isolated from the heat-sensitive variant. The sequence of ApHsp26.2m from the heat-sensitive variant was identical to ApHsp26.2, except for a point mutation that generated a premature stop codon. Therefore, the protein product of ApHsp26.2m did not accumulate in the heat-sensitive line. Mass spectrometry analysis confirmed that ApHsp26.2 encoded for the CP-sHSP isoforms unique to the heat-tolerant variant. An identical mutation was detected in one of the three parental lines used to develop the creeping bentgrass variants. This suggests that ApHsp26.2m was inherited from this parent and did not arise from a mutation that occurred during tissue culture. The presence of two isoforms encoded by the same gene might be due to differential processing of the N-terminal amino acids during or after import into the chloroplast. PMID:12970497

Wang, Dongfang; Luthe, Dawn S

2003-09-01

189

Genetic Analysis of Isolates of Botrytis cinerea Sensitive and Resistant to Benzimidazole and Dicarboximide Fungicides.  

PubMed

ABSTRACT A total of 56 isolates of B. cinerea collected from ornamental crops from commercial greenhouses were examined by random amplified polymorphic DNA (RAPD) fingerprint analyses. Isolates were examined as two independent sets of 35 and 36 isolates, with 15 isolates common to both sets. The isolates had four phenotypes: 17 were sensitive to two commonly used fungicides, thiophanate-methyl (a benzimidazole) and vinclozolin (a dicarboximide) (S(T)S(V)); 18 were resistant to both fungicides (R(T)R(V)); 16 were resistant to thiophanate-methyl but sensitive to vinclozolin (R(T)S(V)); and 5 were sensitive to thiophanate-methyl but resistant to vinclozolin (S(T)R(V)). Relationships among the isolates were determined by cluster analyses of mean character differences using the unweighted pair group method using arithmetic average and cladograms were constructed. Isolates were clustered primarily by fungicide-sensitivity phenotype. In one set of greenhouse isolates, 6 of 10 S(T)S(V) isolates clustered together with a bootstrap confidence value of 91%. In the other fingerprint set of greenhouse isolates, 9 of 11 S(T)S(V) isolates clustered together and had a bootstrap confidence value of 98%. Isolates resistant to thiophanate-methyl, vinclozolin, or both fungicides usually were not clustered with other isolates or were clustered with isolates of the same phenotype. To further elucidate these relationships, variant isolates resistant to one or both fungicides were produced on fungicide-amended agar medium from 14 S(T)S(V) greenhouse isolates. These 14 S(T)S(V) parent isolates, 57 resistant variant isolates, and 11 resistant greenhouse isolates were analyzed as three independent RAPD fingerprint sets. Variants selected from eight S(T)S(V) parent isolates were resistant to both thiophanate-methyl and vinclozolin even though parent isolates were exposed to only one of the fungicides. Isolates resistant only to vinclozolin (S(T)R(V)) had fingerprint patterns similar to and clustered with those of parent isolates, while fingerprint patterns of isolates resistant to thiophanate-methyl (i.e., R(T)R(V) or R(T)S(V)), regardless of sensitivity to vinclozolin, clustered differently from both those of S(T)S(V) parent isolates and those of S(T)R(V) isolates derived from the same parent. R(T)R(V) and R(T)S(V) variant isolates derived from the same fungicide-sensitive parents only clustered with other variants having the same phenotype. PMID:18944506

Yourman, L F; Jeffers, S N; Dean, R A

2000-08-01

190

Comparison of Different DNA Fingerprinting Techniques for Molecular Typing of Bartonella henselae Isolates  

Microsoft Academic Search

Seventeen isolates of Bartonella henselae from the region of Freiburg, Germany, obtained from blood cultures of domestic cats, were examined for their genetic heterogeneity. On the basis of different DNA fingerprinting methods, including pulsed-field gel electrophoresis (PFGE), enterobacterial repetitive intergenic consensus (ERIC)-PCR, repetitive extragenic palindromic (REP) PCR, and arbitrarily primed (AP)-PCR, three different variants were identified among the isolates (variants

ANNA SANDER; MICHAEL RUESS; STEFAN BERESWILL; MARKUS SCHUPPLER; BERNHARD STEINBRUECKNER

1998-01-01

191

Guidelines for investigating causality of sequence variants in human disease  

PubMed Central

The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. PMID:24759409

MacArthur, D. G.; Manolio, T. A.; Dimmock, D. P.; Rehm, H. L.; Shendure, J.; Abecasis, G. R.; Adams, D. R.; Altman, R. B.; Antonarakis, S. E.; Ashley, E. A.; Barrett, J. C.; Biesecker, L. G.; Conrad, D. F.; Cooper, G. M.; Cox, N. J.; Daly, M. J.; Gerstein, M. B.; Goldstein, D. B.; Hirschhorn, J. N.; Leal, S. M.; Pennacchio, L. A.; Stamatoyannopoulos, J. A.; Sunyaev, S. R.; Valle, D.; Voight, B. F.; Winckler, W.; Gunter, C.

2014-01-01

192

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants  

PubMed Central

Background Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n=13 viruses), five clinically-matched nontransmitting mothers (n=16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses). Results There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants. Conclusion Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies. PMID:23305422

2013-01-01

193

Efficacy of commercial canarypox vaccine for protecting Hawai'i 'Amakihi from field isolates of Avipoxvirus  

USGS Publications Warehouse

At least three variants of avian pox virus are present in Hawai‘i - Fowlpox from domestic poultry and a group of genetically distinct viruses that cluster within two clades (Pox Variant 1 and Pox Variant 2) that are most similar to Canarypox based on DNA sequence of the virus 4b core protein gene. We tested whether Hawai‘i ‘Amakihi can be protected from wild virus isolates with an attenuated live Canarypox vaccine that is closely related to isolates that cluster within clade 1 (Pox Variant 1) based on sequence of the attenuated Canarypox virus 4b core protein. Thirty-one (31) Hawai`i ‘Amakihi (Hemignathus virens) with no prior physical evidence of pox infection were collected on Mauna Kea from xeric, high elevation habitats with low pox prevalence and randomly divided into two groups. One group of 16 was vaccinated with Poximmune C® while the other group received a sham vaccination with virus diluent. Four of 15 (27%) vaccinated birds developed potentially life-threatening disseminated lesions or lesions of unusually long duration, while one bird never developed a vaccine-associated lesion or "take". After vaccine-associated lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox, a Hawai`i `Amakihi isolate of a Canarypox-like virus from clade 1 (Pox Variant 1) or a Hawai`i `Amakihi isolate of a Canarypox-like virus from clade 2 (Pox Variant 2). Similarly, three random groups of five unvaccinated ‘Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated ‘Amakihi challenged with Fowlpox had transient infections with no clinical signs of infection. Mortality in vaccinated ‘Amakihi that were challenged with Pox Variant 1 and Pox Variant 2 ranged from 0% (0/5) for Pox Variant 1 to 60% (3/5) for Pox Variant 2. Mortality in unvaccinated ‘Amakihi ranged from 40% (2/5) for Pox Variant 1 to 100% (5/5) for Pox Variant 2. While the vaccine provided some protection against Pox Variant 1, serious side effects and low efficacy against Pox Variant 2 make it risky to use in captive or wild honeycreepers.

Atkinson, Carter T.; Wiegand, Kimberly C.; Triglia, Dennis; Jarvi, Susan I.

2010-01-01

194

Realistic Simulation of Seasonal Variant Maples  

Microsoft Academic Search

This paper presents a biologically-motivated system of seasonal variant scene generation for maples, which have an obvious leaf color transformation. Given climate data and knowledge of the environmental influence to maples, our system is able to simulate this seasonal leaf color transformation process. Our system consists of three steps: environment configuration, climate influence simulation, and leaf texture acquisition. The first

Ning Zhou; Weiming Dong; Xing Mei

2006-01-01

195

A unique ALCAPA variant in a neonate.  

PubMed

Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly present in approximately one in 300,000 live births. Here, we present a unique ALCAPA variant identified in a neonate. The left anterior descending artery originated posterolaterally on the main pulmonary artery, and the circumflex originated separately from the distal right pulmonary artery. PMID:23480565

Smith, Deane E; Adams, Robert; Argilla, Michael; Phoon, Colin K L; Chun, Anne J L; Bendel, Marci; Mosca, Ralph S

2013-05-01

196

Regional Phonological Variants in Louisiana Speech.  

ERIC Educational Resources Information Center

Based on tape recorded conversations of 28 informants in 18 Louisiana communities, this study investigated regional phonological variants in Louisiana speech. On the basis of settlement history and previous dialect studies, four regions are defined: northern Louisiana, the Florida Parishes, French Louisiana, and New Orleans. The informants are all…

Rubrecht, August Weston

197

Cellobiohydrolase I gene and improved variants  

DOEpatents

The disclosure provides a method for preparing an active exoglucanase in a heterologous host of eukaryotic origin. The method includes mutagenesis to reduce glycosylation of the exoglucanase when expressed in a heterologous host. It is further disclosed a method to produce variant cellobiohydrolase that is stable at high temperature through mutagenesis.

Adney, William S. (Golden, CO); Decker, Stephen R. (Berthoud, CO); Mc Carter, Suzanne (San Carlos, CA); Baker, John O. (Golden, CO); Nieves, Raphael (Lakewood, CO); Himmel, Michael E. (Littleton, CO); Vinzant, Todd B. (Golden, CO)

2008-05-20

198

Identification of rare variants in Alzheimer's disease  

PubMed Central

Much progress has been made in recent years in identifying genes involved in the risk of developing Alzheimer’s disease (AD), the most common form of dementia. Yet despite the identification of over 20 disease associated loci, mainly through genome wide association studies (GWAS), a large proportion of the genetic component of the disorder remains unexplained. Recent evidence from the AD field, as with other complex diseases, suggests a large proportion of this “missing heritability” may be due to rare variants of moderate to large effect size, but the methodologies to detect such variants are still in their infancy. The latest studies in the field have been focused on the identification of coding variation associated with AD risk, through whole-exome or whole-genome sequencing. Such variants are expected to have larger effect sizes than GWAS loci, and are easier to functionally characterize, and develop cellular and animal models for. This review explores the issues involved in detecting rare variant associations in the context of AD, highlighting some successful approaches utilized to date. PMID:25389433

Lord, Jenny; Lu, Alexander J.; Cruchaga, Carlos

2014-01-01

199

Clinical Implications of HIV-1 Minority Variants  

PubMed Central

Technologic advances in human immunodeficiency virus type 1 (HIV-1) sequencing have revolutionized the study of antiretroviral drug resistance and are increasingly moving from the laboratory to clinical practice. These techniques are able to detect HIV-1 drug resistance mutations present at low frequencies not detectable by current HIV-1 genotyping assays. For a number of commonly used antiretroviral medications, such as nonnucleoside reverse transcriptase inhibitors, the detection of these drug-resistant minority variants significantly increases the risk of treatment failure. The level of evidence, however, is insufficient to determine the impact of HIV-1 minority variants for several other classes of antiretroviral medications. Clinicians should be aware of the novel technologies that are moving into routine clinical use and the clinical implications of HIV-1 minority variants. Additional studies are needed to determine the optimal platform for clinical application of these new technologies and to provide guidance to clinicians on the type and frequency of clinically important HIV-1 minority variants. PMID:23446628

Li, Jonathan Z.; Kuritzkes, Daniel R.

2013-01-01

200

INVESTIGATION Common Variants of Drosophila melanogaster  

E-print Network

INVESTIGATION Common Variants of Drosophila melanogaster Cyp6d2 Cause Camptothecin Sensitivity affect an organism's response to chemotherapeutic drugs. In this study, we focused on camptothecin that result in extreme sensitivity to camptothecin but not top- otecan or irinotecan. We confirmed

McVey, Mitch

201

DISCRETE VARIANTS OF EVENING GROSBEAK FLIGHT CALLS  

Microsoft Academic Search

We describe four discrete variants of the frequency-modulated flight calls of Evening Grosbeaks (Coccothraustes vespertinus) in the United States and southwestern Canada. Each call type is aurally and spectrographically distinct, and individual birds appear to produce only one call type. The observed geograph- ic distributions of these call types are roughly concor- dant with described subspecies ranges. The long-term geographic

Kendra Sewall; Rodd Kelsey; Thomas P. Hahn

2004-01-01

202

Discovery of variants unmasked by hemizygous deletions  

PubMed Central

Array-based genome-wide segmental aneuploidy screening detects both de novo and inherited copy number variations (CNVs). In sporadic patients de novo CNVs are interpreted as potentially pathogenic. However, a deletion, transmitted from a healthy parent, may be pathogenic if it overlaps with a mutated second allele inherited from the other healthy parent. To detect such events, we performed multiplex enrichment and next-generation sequencing of the entire coding sequence of all genes within unique hemizygous deletion regions in 20 patients (1.53?Mb capture footprint). Out of the detected 703 non-synonymous single-nucleotide variants (SNVs), 8 represented variants being unmasked by a hemizygous deletion. Although evaluation of inheritance patterns, Grantham matrix scores, evolutionary conservation and bioinformatic predictions did not consistently indicate pathogenicity of these variants, no definitive conclusions can be drawn without functional validation. However, in one patient with severe mental retardation, lack of speech, microcephaly, cheilognathopalatoschisis and bilateral hearing loss, we discovered a second smaller deletion, inherited from the other healthy parent, resulting in loss of both alleles of the highly conserved heat shock factor binding protein 1 (HSBP1) gene. Conceivably, inherited deletions may unmask rare pathogenic variants that may exert a phenotypic impact through a recessive mode of gene action. PMID:22258528

Hochstenbach, Ron; Poot, Martin; Nijman, Isaac J; Renkens, Ivo; Duran, Karen J; van'T Slot, Ruben; van Binsbergen, Ellen; van der Zwaag, Bert; Vogel, Maartje J; Terhal, Paulien A; Ploos van Amstel, Hans Kristian; Kloosterman, Wigard P; Cuppen, Edwin

2012-01-01

203

Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR.  

PubMed

Naturally occurring genetic variants of human papillomavirus type 16 (HPV16) are common and have previously been classified into 4 major lineages; European-Asian (EAS), including the sublineages European (EUR) and Asian (As), African 1 (AFR1), African 2 (AFR2), and North-American/Asian-American (NA/AA). We aimed to improve the classification of HPV16 variant lineages by using a large resource of HPV16-positive cervical samples collected from geographically diverse populations in studies on HPV and/or cervical cancer undertaken by the International Agency for Research on Cancer. In total, we sequenced the entire E6 genes and long control regions (LCRs) of 953 HPV16 isolates from 27 different countries worldwide. Phylogenetic analyses confirmed previously described variant lineages and subclassifications. We characterized two new sublineages within each of the lineages AFR1 and AFR2 that are robustly classified using E6 and/or the LCR. We could differentiate previously identified AA1, AA2, and NA sublineages, although they could not be distinguished by E6 alone, requiring the LCR for correct phylogenetic classification. We thus provide a classification system for HPV16 genomes based on 13 and 32 phylogenetically distinguishing positions in E6 and the LCR, respectively, that distinguish nine HPV16 variant sublineages (EUR, As, AFR1a, AFR1b, AFR2a, AFR2b, NA, AA1, and AA2). Ninety-seven percent of all 953 samples fitted this classification perfectly. Other positions were frequently polymorphic within one or more lineages but did not define phylogenetic subgroups. Such a standardized classification of HPV16 variants is important for future epidemiological and biological studies of the carcinogenic potential of HPV16 variant lineages. PMID:22491459

Cornet, Iris; Gheit, Tarik; Franceschi, Silvia; Vignat, Jerome; Burk, Robert D; Sylla, Bakary S; Tommasino, Massimo; Clifford, Gary M

2012-06-01

204

Multiple Lupus Associated ITGAM Variants Alter Mac-1 Function on Neutrophils  

PubMed Central

Objective Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678, rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the ?2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1. Methods Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor ?-stimulated endothelial cells was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Results Mac-1–mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the ?-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fc? receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. Conclusion The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE. PMID:23918739

Zhou, Yebin; Wu, Jianming; Kucik, Dennis F.; White, Nathan B.; Redden, David T.; Szalai, Alexander J.; Bullard, Daniel C.; Edberg, Jeffrey C.

2014-01-01

205

The Distribution and Common Amino Acid Polymorphisms of Human Papillomavirus (HPV)-31 Variants in 2700 Women from Northern China  

PubMed Central

To investigate the distribution of Human papillomavirus (HPV)-31 A, B and C variants as well as the common amino acid polymorphisms in Chinese women, all 14 HPV-31 positive cervical exfoliated cell specimens identified from a descriptive study including ?2700 women from Northern China were analyzed. HPV-31 positive specimens were identified by Mass Spectrometry and the fragments of partial Long Control Region, E6 and E7 were amplified and directly sequenced or cloned into vector and then sequenced to confirm the variant information. HPV-31 prevalence in Northern Chinese female population was 0.52%. Six different sequences represented all 14 isolates, and these isolates were subsequently classified into variant lineage A (9), B (0) and C (5) by phylogenetic analysis. Five common amino acid polymorphism sites (2 in E6 and 3 in E7) and a novel non-synonymous mutation were detected in the current study. Our investigation suggested that HPV-31 was much less detected in Chinese women population than that in western countries. A and C variants were commonly detected while B variants were rarely detected in this population. PMID:24901850

Xi, Longfu; Li, Jingjing; Liu, Fangfang; Liu, Ying; Pan, Yaqi; Ning, Tao; Guo, Chuanhai; Xu, Ruiping; Zhang, Lixin; Cai, Hong; Ke, Yang

2014-01-01

206

Social isolation.  

PubMed

Social species, by definition, form organizations that extend beyond the individual. These structures evolved hand in hand with behavioral, neural, hormonal, cellular, and genetic mechanisms to support them because the consequent social behaviors helped these organisms survive, reproduce, and care for offspring sufficiently long that they too reproduced. Social isolation represents a lens through which to investigate these behavioral, neural, hormonal, cellular, and genetic mechanisms. Evidence from human and nonhuman animal studies indicates that isolation heightens sensitivity to social threats (predator evasion) and motivates the renewal of social connections. The effects of perceived isolation in humans share much in common with the effects of experimental manipulations of isolation in nonhuman social species: increased tonic sympathetic tonus and HPA activation; and decreased inflammatory control, immunity, sleep salubrity, and expression of genes regulating glucocorticoid responses. Together, these effects contribute to higher rates of morbidity and mortality in older adults. PMID:21651565

Cacioppo, John T; Hawkley, Louise C; Norman, Greg J; Berntson, Gary G

2011-08-01

207

Social isolation  

PubMed Central

Social species, by definition, form organizations that extend beyond the individual. These structures evolved hand in hand with behavioral, neural, hormonal, cellular, and genetic mechanisms to support them because the consequent social behaviors helped these organisms survive, reproduce, and care for offspring sufficiently long that they too reproduced. Social isolation represents a lens through which to investigate these behavioral, neural, hormonal, cellular, and genetic mechanisms. Evidence from human and nonhuman animal studies indicates that isolation heightens sensitivity to social threats (predator evasion) and motivates the renewal of social connections. The effects of perceived isolation in humans share much in common with the effects of experimental manipulations of isolation in nonhuman social species: increased tonic sympathetic tonus and HPA activation, and decreased inflammatory control, immunity, sleep salubrity, and expression of genes regulating glucocorticoid responses. Together, these effects contribute to higher rates of morbidity and mortality in older adults. PMID:21651565

Cacioppo, John T.; Hawkley, Louise C.; Norman, Greg J.; Berntson, Gary G.

2011-01-01

208

Dynamic bayesian testing of sets of variants in complex diseases.  

PubMed

Rare genetic variants have recently been studied for genome-wide associations with human complex diseases. Existing rare variant methods are based on the hypothesis-testing framework that predefined variant sets need to be tested separately. The power of those methods is contingent upon accurate selection of variants for testing, and frequently, common variants are left out for separate testing. In this article, we present a novel Bayesian method for simultaneous testing of all genome-wide variants across the whole frequency range. The method allows for much more flexible grouping of variants and dynamically combines them for joint testing. The method accounts for correlation among variant sets, such that only direct associations with the disease are reported, whereas indirect associations due to linkage disequilibrium are not. Consequently, the method can obtain much improved power and flexibility and simultaneously pinpoint multiple disease variants with high resolution. Additional covariates of categorical, discrete, and continuous values can also be added. We compared our method with seven existing categories of approaches for rare variant mapping. We demonstrate that our method achieves similar power to the best methods available to date when testing very rare variants in small SNP sets. When moderately rare or common variants are included, or when testing a large collection of variants, however, our method significantly outperforms all existing methods evaluated in this study. We further demonstrate the power and the usage of our method in a whole-genome resequencing study of type 1 diabetes. PMID:25217050

Zhang, Yu; Ghosh, Soumitra; Hakonarson, Hakon

2014-11-01

209

Inactivation of a novel gene produces a phenotypic variant cell and affects the symbiotic behavior of Xenorhabdus nematophilus.  

PubMed

Xenorhabdus nematophilus is an insect pathogen that lives in a symbiotic association with a specific entomopathogenic nematode. During prolonged culturing, variant cells arise that are deficient in numerous properties. To understand the genetic mechanism underlying variant cell formation, a transposon mutagenesis approach was taken. Three phenotypically similar variant strains of X. nematophilus, each of which contained a single transposon insertion, were isolated. The insertions occurred at different locations in the chromosome. The variant strain, ANV2, was further characterized. It was deficient in several properties, including the ability to produce antibiotics and the stationary-phase-induced outer membrane protein, OpnB. Unlike wild-type cells, ANV2 produced lecithinase. The emergence of ANV2 from the nematode host was delayed relative to the emergence of the parental strain. The transposon in ANV2 had inserted in a gene designated var1, which encodes a novel protein composed of 121 amino acid residues. Complementation analysis confirmed that the pleiotropic phenotype of the ANV2 strain was produced by inactivation of var1. Other variant strains were not complemented by var1. These results indicate that inactivation of a single gene was sufficient to promote variant cell formation in X. nematophilus and that disruption of genetic loci other than var1 can result in the same pleiotropic phenotype. PMID:10742251

Volgyi, A; Fodor, A; Forst, S

2000-04-01

210

Monoclonal antibodies distinguish phase variants of Coxiella burnetii.  

PubMed Central

Monoclonal antibodies (MAbs) directed against phase I and II variants of Coxiella burnetii were produced by fusing myeloma SP2/O-AG 14 cells with spleen cells from mice immunized with the chloroform-methanol extraction residue of phase I whole cells. Two hybridoma clones which distinguished the phase variants by microimmunofluorescence assay were isolated and characterized. The MAbs showing specificity for phase I cells (MAbI-1, immunoglobulin G, subclass 3 kappa) reacted with the hot phenol-water extract of phase I C. burnetii in immunodiffusion and enzyme-linked immunosorbent assays. MAbI-1 reacted with high-molecular-weight components from phase I phenol-water extract and whole cell in an immunoblot assay. Specificity of MAbI-1 for a carbohydrate epitope in the phenol-water extract was demonstrated by periodic acid inactivation of binding by a competitive enzyme-linked immunosorbent assay. Phase I antigenic sites were apparently well represented on the surface of cells as demonstrated by complete fluorescence and microagglutination. The MAb showing specificity for phase II cells (MAbII-1, immunoglobulin G, subclass 2b kappa) reacted with whole cells in the microimmunofluorescence assay, microagglutination test, complement fixation test, and the enzyme-linked immunosorbent assay. MAbII-1 reacted specifically with a 29,500-dalton surface protein as demonstrated by immunoprecipitation of 125I-surface-labeled cells. Although MAbII-1 reacted with detergent-solubilized protein, it did not react with sodium-dodecyl sulfate-denatured protein by immunoblot assay. This protein was not exposed on the surface of phase I cells, but chloroform-methanol extraction of phase I cells exposed the phase II epitope. Images PMID:6418662

Williams, J C; Johnston, M R; Peacock, M G; Thomas, L A; Stewart, S; Portis, J L

1984-01-01

211

A coagulase-negative variant of Staphylococcus aureus from bovine mastitis milk.  

PubMed

Bacteriological analysis of milk samples from quarters of a dairy cow suffering from subclinical mastitis yielded two isolates of Staphylococcus aureus which gave a negative reaction in the standard coagulase test. Both isolates were also clumping factor and thermonuclease negative, and gave a negative reaction in the Staphaurex® test. The isolates were identified by using commercial biochemical systems, and by PCR analysis of different staphylococcal cell surface protein and exoprotein genes. Further molecular identification of the isolates, which included sequencing of the 16S rRNA gene and RT-PCR of coagulase (coa), clumping-factor (clfA) and thermonuclease (nuc) genes, was consistent with the diagnosis phenotypically 'coagulase-negative variant of Staph. aureus'. The fact that coagulase-negative Staph. aureus variants can occur in the context of intramammary infections in cattle may result in the incorrect diagnosis 'coagulase-negative staphylococci (CNS)' in routine mastitis diagnostic, at least in rare cases. To fully ensure correct species diagnosis, sequencing of the 16S rRNA gene and amplification of specific genes such as coa is necessary in these cases. PMID:21118611

Akineden, Omer; Hassan, Abdulwahed Ahmed; Schneider, Elisabeth; Usleber, Ewald

2011-02-01

212

MARS Attacks! Preliminary Cryptanalysis of ReducedRound MARS Variants  

E-print Network

MARS Attacks! Preliminary Cryptanalysis of Reduced­Round MARS Variants John Kelsey and Bruce,schneier}@counterpane.com Abstract. In this paper, we discuss ways to attack various reduced­ round variants of MARS. We consider cryptanalysis of two reduced­ round variants of MARS: MARS with the full mixing layers but fewer core rounds

Schneier, Bruce

213

MARS Attacks! Preliminary Cryptanalysis of Reduced-Round MARS Variants  

E-print Network

MARS Attacks! Preliminary Cryptanalysis of Reduced-Round MARS Variants John Kelsey and Bruce,schneier}@counterpane.com Abstract. In this paper, we discuss ways to attack various reduced- round variants of MARS. We consider cryptanalysis of two reduced- round variants of MARS: MARS with the full mixing layers but fewer core rounds

Schneier, Bruce

214

Processing of No-Release Variants in Connected Speech  

ERIC Educational Resources Information Center

The cross modal repetition priming paradigm was used to investigate how potential lexically ambiguous no-release variants are processed. In particular we focus on segmental regularities that affect the variant's frequency of occurrence (voicing of the critical segment) and phonological context in which the variant occurs (status of the following…

LoCasto, Paul C.; Connine, Cynthia M.

2011-01-01

215

Emergence of Influenza A Virus Variants after Prolonged Shedding from Pheasants?  

PubMed Central

We previously demonstrated the susceptibility of pheasants to infection with influenza A viruses of 15 hemagglutinin (HA) subtypes: 13/23 viruses tested were isolated for ?14 days, all in the presence of serum-neutralizing antibodies; one virus (H10) was shed for 45 days postinfection. Here we confirmed that 20% of pheasants shed low-pathogenic influenza viruses for prolonged periods. We aimed to determine why the antibody response did not clear the virus in the usual 3 to 10 days, because pheasants serve as a long-term source of influenza viruses in poultry markets. We found evidence of virus replication and histological changes in the large intestine, bursa of Fabricius, and cecal tonsil. The virus isolated 41 days postinfection was antigenically distinct from the parental H10 virus, with corresponding changes in the HA and neuraminidase. Ten amino acid differences were found between the parental H10 and the pheasant H10 virus; four were in potential antigenic sites of the HA molecule. Prolonged shedding of virus by pheasants results from a complex interplay between the diversity of virus variants and the host response. It is often argued that vaccination pressure is a mechanism that contributes to the generation of antigenic-drift variants in poultry. This study provided evidence that drift variants can occur naturally in pheasants after prolonged shedding of virus, thus strengthening our argument for the removal of pheasants from live-bird retail markets. PMID:17267493

Humberd, Jennifer; Boyd, Kelli; Webster, Robert G.

2007-01-01

216

A Practical, Typed Variant Object Model  

E-print Network

object a { 2 } 1 let a = fun msg -> 2 match msg with 3 . . . #12;Variant-Based Encoding (Scala) (OCaml) 1 object a { 2 val v = 5 3 } 1 let v = ref 5 in 2 let a = fun msg -> 3 match msg with 4 . . . Fields+v } 5 def foo(x:Unit ){} 6 } 1 let v = ref 5 in 2 let a = fun msg -> 3 match msg with 4 | `mth (self ,x

Smith, Scott F.

217

Mapping common regulatory variants to human haplotypes  

Microsoft Academic Search

Inter-individual variation in gene expression has proven to be in part governed by genetic determinants, which may be trans -o rcis-acting. The underlying cause of cis-acting regulatory variation has been identified in only a handful of the hundreds of genes shown to display differential allelic expression. In this report, we describe a systematic effort to map common cis-acting variants in

Tomi Pastinen; Bing Ge; Scott Gurd; Tiffany Gaudin; Carole Dore; Mathieu Lemire; Pierre Lepage; Eef Harmsen; Thomas J. Hudson

2005-01-01

218

Optimal brain surgeon variants for feature selection  

Microsoft Academic Search

This paper presents three pruning algorithms based on optimal brain surgeon (OBS) and unit-optimal brain surgeon (unit-OBS). The first variant performs a backward selection by successively removing single weights from the input variables to the hidden units in a fully connected multilayer perceptron (MLP) for variable selection. The second one removes a subset of non-significant weights in one step. The

Mohammed Attik; Laurent Bougrain; Fkdtric Alexandre

2004-01-01

219

Sex steroids and variants of gender identity.  

PubMed

This article summarizes for the practicing endocrinologist the current literature on the psychobiology of the development of gender identity and its variants in individuals with disorders of sex development (DSD) or with non-DSD transgenderism. Gender reassignment remains the treatment of choice for strong and persistent gender dysphoria in both categories, but more research is needed on the short-term and long-term effects of puberty-suppressing medications and cross-sex hormones on brain and behavior. PMID:24011879

Meyer-Bahlburg, Heino F L

2013-09-01

220

Expression of CD44 variants in osteosarcoma  

Microsoft Academic Search

The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells,\\u000a epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44\\u000a has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated\\u000a 44 tumour specimens

M. Kuryu; T. Ozaki; K. Nishida; M. Shibahara; A. Kawai; H. Inoue

1999-01-01

221

Keratoameloblastoma, a very rare variant of ameloblastoma.  

PubMed

The keratoameloblastoma is a rare histologic variant of ameloblastoma. Fewer than 15 cases of keratoameloblastoma have been documented in the literature. We report a new case of keratoameloblastoma in a 21-year-old female patient with a unilocular radiolucent lesion between the roots of the right mandibular incisors. We describe the clinical, radiographic, and histopathologic features of this lesion along with a review on the characteristics of previous cases. We also discuss about classification and management of this lesion. PMID:24220437

Ketabi, Mohammad Ali; Dehghani, Nima; Sadeghi, Hasan Mirmohammad; Shams, Mohammad Ghasem; Mohajerani, Hasan; Azarsina, Mohadese; Azizi, Arshia

2013-11-01

222

Characterization of the two intra-individual sequence variants in the 18S rRNA gene in the plant parasitic nematode, Rotylenchulus reniformis.  

PubMed

The 18S rRNA gene is fundamental to cellular and organismal protein synthesis and because of its stable persistence through generations it is also used in phylogenetic analysis among taxa. Sequence variation in this gene within a single species is rare, but it has been observed in few metazoan organisms. More frequently it has mostly been reported in the non-transcribed spacer region. Here, we have identified two sequence variants within the near full coding region of 18S rRNA gene from a single reniform nematode (RN) Rotylenchulus reniformis labeled as reniform nematode variant 1 (RN_VAR1) and variant 2 (RN_VAR2). All sequences from three of the four isolates had both RN variants in their sequences; however, isolate 13B had only RN variant 2 sequence. Specific variable base sites (96 or 5.5%) were found within the 18S rRNA gene that can clearly distinguish the two 18S rDNA variants of RN, in 11 (25.0%) and 33 (75.0%) of the 44 RN clones, for RN_VAR1 and RN_VAR2, respectively. Neighbor-joining trees show that the RN_VAR1 is very similar to the previously existing R. reniformis sequence in GenBank, while the RN_VAR2 sequence is more divergent. This is the first report of the identification of two major variants of the 18S rRNA gene in the same single RN, and documents the specific base variation between the two variants, and hypothesizes on simultaneous co-existence of these two variants for this gene. PMID:23593343

Nyaku, Seloame T; Sripathi, Venkateswara R; Kantety, Ramesh V; Gu, Yong Q; Lawrence, Kathy; Sharma, Govind C

2013-01-01

223

[Non-pharmacological therapies for language deficits in the agrammatic and logopenic variants of primary progressive aphasia: a literature review].  

PubMed

Primary progressive aphasia is a neurodegenerative condition characterised by a progressive and isolated disorder of expressive language, associated with atrophy of the left posterior frontoinsular region (nonfluent/agrammatic variant) or with atrophy of the left temporoparietal junction area (logopenic variant). This literature review reports studies about language therapies for these two variants of primary progressive aphasia. More precisely, the review presents the behavioral interventions and the augmentative/alternative communication tools reported in the literature to improve language performances or to compensate for language difficulties. Most of these studies reported that interventions are efficient. However, inconsistent results are found regarding maintenance of improvement and generalization to untreated language abilities. Other studies are still required to establish the clinical relevance of interventions for language and communication disorders in primary progressive aphasia. In these studies, the use of more ecological interventions focusing on the specific needs of people living with this disease should be specifically addressed. PMID:23508325

Routhier, Sonia; Gravel-Laflamme, Karine; Macoir, Joël

2013-03-01

224

Alphavirus mutator variants present host-specific defects and attenuation in mammalian and insect models.  

PubMed

Arboviruses cycle through both vertebrates and invertebrates, which requires them to adapt to disparate hosts while maintaining genetic integrity during genome replication. To study the genetic mechanisms and determinants of these processes, we use chikungunya virus (CHIKV), a re-emerging human pathogen transmitted by the Aedes mosquito. We previously isolated a high fidelity (or antimutator) polymerase variant, C483Y, which had decreased fitness in both mammalian and mosquito hosts, suggesting this residue may be a key molecular determinant. To further investigate effects of position 483 on RNA-dependent RNA-polymerase (RdRp) fidelity, we substituted every amino acid at this position. We isolated novel mutators with decreased replication fidelity and higher mutation frequencies, allowing us to examine the fitness of error-prone arbovirus variants. Although CHIKV mutators displayed no major replication defects in mammalian cell culture, they had reduced specific infectivity and were attenuated in vivo. Unexpectedly, mutator phenotypes were suppressed in mosquito cells and the variants exhibited significant defects in RNA synthesis. Consequently, these replication defects resulted in strong selection for reversion during infection of mosquitoes. Since residue 483 is conserved among alphaviruses, we examined the analogous mutations in Sindbis virus (SINV), which also reduced polymerase fidelity and generated replication defects in mosquito cells. However, replication defects were mosquito cell-specific and were not observed in Drosophila S2 cells, allowing us to evaluate the potential attenuation of mutators in insect models where pressure for reversion was absent. Indeed, the SINV mutator variant was attenuated in fruit flies. These findings confirm that residue 483 is a determinant regulating alphavirus polymerase fidelity and demonstrate proof of principle that arboviruses can be attenuated in mammalian and insect hosts by reducing fidelity. PMID:24453971

Rozen-Gagnon, Kathryn; Stapleford, Kenneth A; Mongelli, Vanesa; Blanc, Hervé; Failloux, Anna-Bella; Saleh, Maria-Carla; Vignuzzi, Marco

2014-01-01

225

Suggestive linkage of ADHD to chromosome 18q22 in a young genetically isolated Dutch population  

Microsoft Academic Search

Attention deficit\\/hyperactivity disorder (ADHD) is a common, highly heritable, neuropsychiatric disorder among children. Linkage studies in isolated populations have proved powerful to detect variants for complex diseases, such as ADHD. We performed a genome-wide linkage scan for ADHD in nine patients from a genetically isolated population in the Netherlands, who were linked to each other within 10 generations through multiple

Najaf Amin; Yuri S Aulchenko; Marieke C Dekker; Robert F Ferdinand; Alwin van Spreeken; Alfons H Temmink; Frank C Verhulst; Ben A Oostra; Cornelia M van Duijn; CM van Duijn

2009-01-01

226

A three-dimensional interactive atlas of cerebral arterial variants.  

PubMed

The knowledge of cerebrovascular variants is essential in education, training, diagnosis and treatment. The current way of presentation of vasculature and, particularly, vascular variants is insufficient. Our purpose is to construct a three-dimensional (3D) interactive atlas of cerebral arterial variants along with exploration tools allowing the investigator just with a few clicks to better and faster understand the variants and their spatial relationships. A 3D model of the cerebral arterial system created earlier, fully labeled with names and diameters, is used as a reference. As the vast material about vascular variability is incomplete and not fully documented, our approach synthesizes variants in 3D based on existing knowledge. The variants are created from literature using a dedicated vascular editor and embedded into the reference model. Sixty 3D variants and branching patterns are created including the internal carotid, middle cerebral, anterior cerebral, posterior cerebral, vertebral and basilar arteries, and circle of Willis. Their prevalence rates are given. The atlas is developed to explore the variants individually or embedded into the reference vasculature. Real-time interactive manipulation of variants and reference vasculature (rotate/zoom/pan/view) is provided. This atlas facilitates the investigator to easily get familiarized with the variants and rapidly explore them. It aids in presentation of vascular variants and understanding their spatial relationships either individually or embedded into the surrounding reference cerebrovasculature. It is useful for medical students, educators to prepare teaching materials, and clinicians for scan interpretation. It is easily extensible with additional variant instances, new variants, branching patterns, and supporting textual materials. PMID:19957055

Nowinski, Wieslaw L; Thirunavuukarasuu, A; Volkau, Ihar; Marchenko, Yevgen; Aminah, Bivi; Puspitasari, Fiftarina; Runge, Val M

2009-12-01

227

Whole-Exome Sequencing Reveals a Rapid Change in the Frequency of Rare Functional Variants in a Founding Population of Humans  

PubMed Central

Whole-exome or gene targeted resequencing in hundreds to thousands of individuals has shown that the majority of genetic variants are at low frequency in human populations. Rare variants are enriched for functional mutations and are expected to explain an important fraction of the genetic etiology of human disease, therefore having a potential medical interest. In this work, we analyze the whole-exome sequences of French-Canadian individuals, a founder population with a unique demographic history that includes an original population bottleneck less than 20 generations ago, followed by a demographic explosion, and the whole exomes of French individuals sampled from France. We show that in less than 20 generations of genetic isolation from the French population, the genetic pool of French-Canadians shows reduced levels of diversity, higher homozygosity, and an excess of rare variants with low variant sharing with Europeans. Furthermore, the French-Canadian population contains a larger proportion of putatively damaging functional variants, which could partially explain the increased incidence of genetic disease in the province. Our results highlight the impact of population demography on genetic fitness and the contribution of rare variants to the human genetic variation landscape, emphasizing the need for deep cataloguing of genetic variants by resequencing worldwide human populations in order to truly assess disease risk. PMID:24086152

Hussin, Julie; Idaghdour, Youssef; Bruat, Vanessa; de Maillard, Thibault; Grenier, Jean-Cristophe; Gbeha, Elias; Hamdan, Fadi F.; Girard, Simon; Spinella, Jean-Francois; Lariviere, Mathieu; Saillour, Virginie; Healy, Jasmine; Fernandez, Isabel; Sinnett, Daniel; Michaud, Jacques L.; Rouleau, Guy A.; Haddad, Elie; Le Deist, Francoise; Awadalla, Philip

2013-01-01

228

[Syndrom Corrao--cough variant asthma].  

PubMed

Asthma is one of the most common aetiologies of chronic cough. In a subgroup of asthmatics, cough may be the predominant or sole symptom. This condition is referred to as cough variant asthma (CVA). The diagnosis of CVA often presents a challenge since physical examination and spirometric tests may be normal. Up to 50% of patients with CVA have associated eosinophilic bronchitis, with the degree of eosinophilia being similar to that of other asthmatics. Demonstration of bronchial hyperresponsiveness by methacholine inhalation challenge, elevated level of exhaled nitric oxide and sputum eosinophilia support the presence of CVA, but the diagnosis is confirmed only upon resolution of the cough with specific antiinflammatory treatment. PMID:17642148

Zietkowski, Ziemowit; Tomasiak, Maria Magdalena; Skiepko, Roman; Bodzenta-Lukaszyk, Anna

2006-01-01

229

Rare Variant of Lycanthropy and Ecstasy  

PubMed Central

Background: Lycanthropy is an unusual belief or delusion in which the patient thinks that he/she has been transformed into an animal. In rare cases, the patient believes that another person has been transformed into an animal. Case Report: We report a patient with an uncommon variant of lycanthropy is introduced. The symptoms appeared after consumption of ecstasy. This shows the occurrences of uncommon and rare psychosis after ecstasy drug use especially in patients susceptible to schizophrenia. Ecstasy drug can induce paranoid psychosis similar to schizophrenia. In the presented case, ecstasy seemed to have a role in patient's underlying susceptibility to schizophrenia. PMID:24494083

Nasirian, Mansoureh; Banazadeh, Nabi; Kheradmand, Ali

2009-01-01

230

Lymphoblastic crisis of chronic myelogenous leukemia. Hand mirror variant.  

PubMed

We present, to our knowledge, the first extensively studied case of lymphoid L2 blast crisis of chronic myelogenous leukemia with a hand mirror cell (HMC) variant. Special stains revealed the leukemic cells to be terminal deoxynucleotidyl transferase positive by immunofluorescence and cytochemically positive for alpha-naphthyl acetate esterase and acid phosphatase (diffuse granular). Immunophenotyping identified the major leukemic cell population as B-cells that expressed CD10+, CD19+, and HLA-DR+. It was not possible to separate the HMC and the non-HMC leukemic population by gating various cell populations, dual staining, cytochemistry, or by terminal deoxynucleotidyl transferase. Gene rearrangements were observed in both Ig heavy-chain alleles and one T-cell antigen receptor gamma-subunit allele. The rearrangements occupied all of the cells, indicating that the HMC and non-HMC were of a common clonal origin. The patient had a mosaic karyotype, with 90% of the cells having t(9;22), t(8;14), and t(9;15) translocations, an additional chromosome 8, and deleted chromosomes 9 and 15. Antibodies to simian sarcoma-associated virus and baboon endogenous virus were isolated in the patient's peripheral blood plasma. PMID:2363626

Kowal-Vern, A; Birdsong, B A; Dizikes, G; Radvany, R; Desai, S N; Schumacher, H

1990-07-01

231

Detecting Novel Genetic Variants Associated with Isoniazid-Resistant Mycobacterium tuberculosis  

PubMed Central

Background Isoniazid (INH) is a highly effective antibiotic central for the treatment of Mycobacterium tuberculosis (MTB). INH-resistant MTB clinical isolates are frequently mutated in the katG gene and the inhA promoter region, but 10 to 37% of INH-resistant clinical isolates have no detectable alterations in currently known gene targets associated with INH-resistance. We aimed to identify novel genes associated with INH-resistance in these latter isolates. Methodology/Principal Findings INH-resistant clinical isolates of MTB were pre-screened for mutations in the katG, inhA, kasA and ndh genes and the regulatory regions of inhA and ahpC. Twelve INH-resistant isolates with no mutations, and 17 INH-susceptible MTB isolates were subjected to whole genome sequencing. Phylogenetically related variants and synonymous mutations were excluded and further analysis revealed mutations in 60 genes and 4 intergenic regions associated with INH-resistance. Sanger sequencing verification of 45 genes confirmed that mutations in 40 genes were observed only in INH-resistant isolates and not in INH-susceptible isolates. The ratios of non-synonymous to synonymous mutations (dN/dS ratio) for the INH-resistance associated mutations identified in this study were 1.234 for INH-resistant and 0.654 for INH-susceptible isolates, strongly suggesting that these mutations are indeed associated with INH-resistance. Conclusion The discovery of novel targets associated with INH-resistance described in this study may potentially be important for the development of improved molecular detection strategies. PMID:25025225

Chan, Maurice K. L.; Ong, Danny C. T.; Tongyoo, Pumipat; Wong, Sin-Yew; Lee, Ann S. G.

2014-01-01

232

Cloning of interleukin-4 delta2 splice variant (IL4d2) in chimpanzee and cynomolgus macaque: phylogenetic analysis of d2 splice variant appearance, and implications for the study of IL4-driven immune processes  

Microsoft Academic Search

The human interleukin-4 (IL-4) gene produces an exon 2-lacking alternative splice variant, termed IL-4ƈ, and described as a naturally occurring antagonist of IL-4-driven activity. We report the isolation of an IL-4ƈ cDNA from chimpanzee (Pan troglodytes) bone marrow samples and cynomolgus macaque (Macaca fascicularis) activated peripheral lymph node cells. The complete IL-4 cDNA sequence from chimpanzee is also provided for

Isabelle Gautherot; Nicolas Burdin; Delphine Seguin; Luc Aujame; Régis Sodoyer

2002-01-01

233

Variantes 2 IFT6299 H2014 UdeM Miklos Csuros VARIANTES G ENOMIQUES II  

E-print Network

= y2) ou h´et´erozygotes (y1 = y2) . . . #12;G´enotypes : Hardy-Weinberg Variantes 2 IFT6299 H2014 UdeM Mikl´os Csur¨os vi ´equilibre Hardy-Weinberg : population infinie g´en´erations discr`etes panmixie

Csürös, Miklós

234

Complex Assembly Variant Design in Agile Manufacturing. Part II: Assembly Variant Design Methodology  

E-print Network

the AVM and then the constraint groups are identified by manipulating the AMGs. Then the assem- bly methods are focused on the redesign of single components. The research is motivated by this serious lack down to the requirements of constituent components. Based on the operation of assembly variants model

Nagi, Rakesh

235

Differential expression of U5snRNA gene variants in maize (Zea mays) protoplasts  

Microsoft Academic Search

The small nuclear ribonucleoprotein particles U1, U2, U4\\/U6 and U5 participate in the removal of introns from pre-messenger RNAs in the nucleus. Three genes encoding U5snRNAs, the RNA moiety of U5snRNPs, have been isolated from maize. As in other plant UsnRNA gene families the three maize U5snRNA genes exhibit sequence variation. Two of the gene variants (MzU5.1 and MzU5.2) are

David Leader; Sheila Connelly; Witold Filipowicz; Robbie Waugh; John W. S. Brown

1993-01-01

236

Genetic variants improve breast cancer risk prediction on mammograms.  

PubMed

Several recent genome-wide association studies have identified genetic variants associated with breast cancer. However, how much these genetic variants may help advance breast cancer risk prediction based on other clinical features, like mammographic findings, is unknown. We conducted a retrospective case-control study, collecting mammographic findings and high-frequency/low-penetrance genetic variants from an existing personalized medicine data repository. A Bayesian network was developed using Tree Augmented Naive Bayes (TAN) by training on the mammographic findings, with and without the 22 genetic variants collected. We analyzed the predictive performance using the area under the ROC curve, and found that the genetic variants significantly improved breast cancer risk prediction on mammograms. We also identified the interaction effect between the genetic variants and collected mammographic findings in an attempt to link genotype to mammographic phenotype to better understand disease patterns, mechanisms, and/or natural history. PMID:24551380

Liu, Jie; Page, David; Nassif, Houssam; Shavlik, Jude; Peissig, Peggy; McCarty, Catherine; Onitilo, Adedayo A; Burnside, Elizabeth

2013-01-01

237

Genetic variants associated with disordered eating  

PubMed Central

Objective While the genetic contribution to the development of anorexia nervosa (AN) has long been recognized, there has been little progress relative to other psychiatric disorders in identifying specific susceptibility genes. Here we have carried out a GWAS on an unselected community sample of female twins surveyed for eating disorders. Method We conducted genome wide association analyses in 2564 female twins for four different phenotypes derived from self-report data relating to lifetime presence of 15 types of disordered eating: anorexia nervosa spectrum, bulimia nervosa spectrum, purging via substances, and a binary measure of no disordered eating behaviors versus 3 or more. To complement the variant level results we also conducted gene-based association tests using VEGAS. Results While no variants reached genome-wide significance at the level of p<10?8, six regions were suggestive (p<5×10?7). The current results implicate the following genes: CLEC5A; LOC136242, TSHZ1 and SYTL5 for the anorexia nervosa spectrum phenotype, NT5C1B for the bulimia nervosa spectrum phenotype, and ATP8A2 for the disordered eating behaviors phenotype. Discussion As with other medical and psychiatric phenotypes, much larger samples and meta-analyses will ultimately be needed to identify genes and pathways contributing to predisposition to eating disorders. PMID:23568457

Wade, Tracey D; Gordon, Scott; Medland, Sarah; Bulik, Cynthia M.; Heath, Andrew C; Montgomery, Grant W; Martin, Nicholas G

2013-01-01

238

Novel Variants of Clade 2.3.4 Highly Pathogenic Avian Influenza A(H5N1) Viruses, China  

PubMed Central

We characterized 7 highly pathogenic avian influenza A(H5N1) viruses isolated from poultry in China during 2009–2012 and found that they belong to clade 2.3.4 but do not fit within the 3 defined subclades. Antigenic drift in subtype H5N1 variants may reduce the efficacy of vaccines designed to control these viruses in poultry. PMID:24274396

Gu, Min; Zhao, Guo; Zhao, Kunkun; Zhong, Lei; Huang, Junqing; Wan, Hongquan; Wang, Xiaoquan; Liu, Wenbo; Liu, Huimou; Peng, Daxin

2013-01-01

239

A unified phylogeny-based nomenclature for histone variants  

PubMed Central

Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and complicate database searches. We propose here a unified nomenclature for variants of all five classes of histones that uses consistent but flexible naming conventions to produce names that are informative and readily searchable. The nomenclature builds on historical usage and incorporates phylogenetic relationships, which are strong predictors of structure and function. A key feature is the consistent use of punctuation to represent phylogenetic divergence, making explicit the relationships among variant subtypes that have previously been implicit or unclear. We recommend that by default new histone variants be named with organism-specific paralog-number suffixes that lack phylogenetic implication, while letter suffixes be reserved for structurally distinct clades of variants. For clarity and searchability, we encourage the use of descriptors that are separate from the phylogeny-based variant name to indicate developmental and other properties of variants that may be independent of structure. PMID:22650316

2012-01-01

240

Isolating prompt photons with narrow cones  

NASA Astrophysics Data System (ADS)

We discuss the isolation of prompt photons in hadronic collisions by means of narrow isolation cones and the QCD computation of the corresponding cross sections. We reconsider the occurence of large perturbative terms with logarithmic dependence on the cone size and their impact on the fragmentation scale dependence. We cure the apparent perturbative violation of unitarity for small cone sizes, which had been noticed earlier in next-to-leading-order (NLO) calculations, by resumming the leading logarithmic dependence on the cone size. We discuss possible implications regarding the implementation of some hollow cone variants of the cone criterion, which simulate the experimental difficulty to impose isolation inside the region filled by the electromagnetic shower that develops in the calorimeter.

Catani, S.; Fontannaz, M.; Guillet, J. Ph.; Pilon, E.

2013-09-01

241

RcsB Contributes to the Distinct Stress Fitness among Escherichia coli O157:H7 Curli Variants of the 1993 Hamburger-Associated Outbreak Strains  

PubMed Central

Curli are adhesive fimbriae of Enterobactericaeae and are involved in surface attachment, cell aggregation, and biofilm formation. We reported previously that curli-producing (C+) variants of E. coli O157:H7 (EcO157) were much more acid sensitive than their corresponding curli-deficient (C?) variants; however, this difference was not linked to the curli fimbriae per se. Here, we investigated the underlying molecular basis of this phenotypic divergence. We identified large deletions in the rcsB gene of C+ variants isolated from the 1993 U.S. hamburger-associated outbreak strains. rcsB encodes the response regulator of the RcsCDB two-component signal transduction system, which regulates curli biogenesis negatively but acid resistance positively. Further comparison of stress fitness revealed that C+ variants were also significantly more sensitive to heat shock but were resistant to osmotic stress and oxidative damage, similar to C? variants. Transcriptomics analysis uncovered a large number of differentially expressed genes between the curli variants, characterized by enhanced expression in C+ variants of genes related to biofilm formation, virulence, catabolic activity, and nutrient uptake but marked decreases in transcription of genes related to various types of stress resistance. Supplying C+ variants with a functional rcsB restored resistance to heat shock and acid challenge in cells but blocked curli production, confirming that inactivation of RcsB in C+ variants was the basis of fitness segregation within the EcO157 population. This study provides an example of how genome instability of EcO157 promotes intrapopulation diversification, generating subpopulations carrying an array of distinct phenotypes that may confer the pathogen with survival advantages in diverse environments. PMID:22923406

Parker, Craig T.; Louie, Jacqueline W.; Huynh, Steven; Fagerquist, Clifton K.; Mandrell, Robert E.

2012-01-01

242

Phenotypic variation of Staphylococcus epidermidis isolated from a patient with native valve endocarditis.  

PubMed Central

Two colonial variants of Staphylococcus epidermidis were isolated from the valvular tissue of a patient with native valve endocarditis. In addition to differing in colonial morphology, the two variants differed in hemolysis on blood-containing media, in adherence capacity, and in the expression of certain enzymes. Under suitable conditions, both variants were themselves capable of phenotypic variation, although they differed in the rate at which variants were generated. The variants yielded identical profiles on restriction endonuclease analysis of plasmid DNA and pulsed-field gel electrophoresis of whole-cell DNA. This report suggests a possible role for phenotypic variation in coagulase-negative staphylococcal virulence. Congo red agar would be an excellent medium for studying the contribution of variation to the virulence of these organisms. Images PMID:1401003

Deighton, M; Pearson, S; Capstick, J; Spelman, D; Borland, R

1992-01-01

243

Natural Variants of C. elegans Demonstrate Defects in Both Sperm Function and Oogenesis at Elevated Temperatures  

PubMed Central

The temperature sensitivity of the germ line is conserved from nematodes to mammals. Previous studies in C. briggsae and Drosophila showed that isolates originating from temperate latitudes lose fertility at a lower temperature than strains originating from tropical latitudes. In order to investigate these relationships in C. elegans, analysis of the fertility of 22 different wild-type isolates of C. elegans isolated from equatorial, tropical and temperate regions was undertaken. It was found that there are significant temperature, genotype and temperature × genotype effects on fertility but region of isolation showed no significant effect on differences in fertility. For most isolates 100% of the population maintained fertility from 20°C to 26°C, but there was a precipitous drop in the percentage of fertile hermaphrodites at 27°C. In contrast, all isolates show a progressive decrease in brood size as temperature increases from 20°C to 26°C, followed by a brood size near zero at 27°C. Temperature shift experiments were performed to better understand the causes of high temperature loss of fertility. Males up-shifted to high temperature maintained fertility, while males raised at high temperature lost fertility. Down-shifting males raised at high temperature generally did not restore fertility. This result differs from that observed in Drosophila and suggested that in C. elegans spermatogenesis or sperm function is irreversibly impaired in males that develop at high temperature. Mating and down-shifting experiments with hermaphrodites were performed to investigate the relative contributions of spermatogenic and oogenic defects to high temperature loss of fertility. It was found that the hermaphrodites of all isolates demonstrated loss in both spermatogenic and oogenic germ lines that differed in their relative contribution by isolate. These studies uncovered unexpectedly high variation in both the loss of fertility and problems with oocyte function in natural variants of C. elegans at high temperature. PMID:25380048

Petrella, Lisa N.

2014-01-01

244

Ribavirin-Resistant Variants of Foot-and-Mouth Disease Virus: the Effect of Restricted Quasispecies Diversity on Viral Virulence  

PubMed Central

ABSTRACT Mutagenic nucleoside analogues can be used to isolate RNA virus high-fidelity RNA-dependent RNA polymerase (RdRp) variants, the majority of which are attenuated in vivo. However, attenuated foot-and-mouth disease virus (FMDV) high-fidelity RdRp variants have not been isolated, and the correlations between RdRp fidelity and virulence remain unclear. Here, the mutagen ribavirin was used to select a ribavirin-resistant population of FMDV, and 4 amino acid substitutions (D5N, A38V, M194I, and M296V) were identified in the RdRp-coding region of the population. Through single or combined mutagenesis using a reverse genetics system, we generated direct experimental evidence that the rescued D5N, A38V, and DAMM mutants but not the M194I and M296V mutants are high-fidelity RdRp variants. Mutagen resistance assays revealed that the higher replication fidelity was associated with higher-level resistance to ribavirin. In addition, significantly attenuated fitness and virulence phenotypes were observed for the D5N, A38V, and DAMM mutants. Based on a systematic quantitative analysis of fidelity and virulence, we concluded that higher replication fidelity is associated with a more attenuated virus. These data suggest that the resulting restricted quasispecies diversity compromises the adaptability and virulence of an RNA virus population. The modulation of replication fidelity to attenuate virulence may represent a general strategy for the rational design of new types of live, attenuated vaccine strains. IMPORTANCE The ribavirin-isolated poliovirus (PV) RdRp G64S variant, the polymerases of which were of high replication fidelity, was attenuated in vivo. It has been proposed (M. Vignuzzi, E. Wendt, and R. Andino, Nat. Med. 14:154–161, http://dx.doi.org/10.1038/nm1726) that modulation of replication fidelity is a promising approach for engineering attenuated virus vaccines. The subsequently mutagen-isolated RdRp variants also expressed the high-fidelity polymerase, but not all of them were attenuated. Few studies have shown the exact correlation between fidelity and virulence. The present study investigates the effect of restricted quasispecies diversity on viral virulence via several attenuated FMDV high-fidelity RdRp variants. Our findings may aid in the rational design of a new type of vaccine strain. PMID:24453363

Zeng, Jianxiong; Wang, Haiwei; Xie, Xiaochun; Li, Chen; Zhou, Guohui; Yang, Decheng

2014-01-01

245

Possible new variant of Nijmegen breakage syndrome  

SciTech Connect

We report on a child with microcephaly, small facial and body size, and immune deficiency. The phenotype is consistent with Nijmegen breakage syndrome (NBS), with additional clinical manifestations and laboratory findings not reported heretofore. Most investigations, including the results of radiation-resistant DNA synthesis, concurred with the diagnosis of NBS. Cytogenetic analysis documented abnormalities in virtually all cells examined. Along with the high frequency of breaks and rearrangements of chromosomes 7 and 14, we found breakage and monosomies involving numerous other chromosomes. Because of some variation in the clinical presentation and some unusual cytogenetic findings, we suggest that our patient may represent a new variant of Nijmegen breakage syndrome. 34 refs., 3 figs., 7 tabs.

Der Kaloustian, V.M.; Booth, A.; Elliott, A.M. [Montreal Children`s Hospital and McGill Univ., Montreal (Canada)] [and others] [Montreal Children`s Hospital and McGill Univ., Montreal (Canada); and others

1996-10-02

246

Hyperlexia: a variant of aphasia or dyslexia.  

PubMed

We report five patients with hyperlexia who presented for evaluation in the Learning Disabilities Clinic at the Medical College of Georgia over a two year period. Analysis of the data from the neurologic and neuropsychologic evaluations indicates that the primary and essential cognitive deficit in these children is a disorder in speech and language involving a severe deficit in their ability to comprehend language whether it be spoken or written, as opposed to a dyslexia syndrome involving only recognition and/or comprehension of written language. This finding is in contrast to the Nosology of Disorders of Higher Cerebral Function proposed by the Child Neurology Society which views hyperlexia as a variant of the language disorder subtype of dyslexia. PMID:2468342

Cohen, M; Campbell, R; Gelardo, M

1987-01-01

247

Gene variant raises risk for colorectal cancer  

Cancer.gov

A common genetic variant that affects one in three people significantly increases the risk of colorectal cancer from the consumption of red meat and processed meat, according to a study presented by researchers from the Keck School of Medicine of USC (home of the USC Norris Comprehensive Cancer Center) at the annual American Society of Human Genetics meeting. In addition to identifying a gene that raises risk for colorectal cancer from eating red or processed meat, the study — the first to identify the interactions of genes and diet on a genome-wide scale — also revealed another specific genetic variation that appears to modify whether eating more fruits, vegetables and fiber actually lowers your colorectal cancer risk.

248

A rare variant angioarchitecture of upper abdomen.  

PubMed

Vascular anomalies are frequently encountered in abdomen. But they are usually asymptomatic and diagnosed accidently during angiography or surgery leading into severe complications. Thus knowledge of angioarchitecture in abdomen, whether normal or variant, is considered prerequisite for successful, uncomplicated surgeries and interventional radiology. This case report describes one of such varying branching pattern of celiac trunk and superior mesenteric artery. During routine abdominal dissection, gastroduodenal artery was seen arising from celiac trunk along with its usual three branches. Common hepatic artery continued as left hepatic artery after giving rise the right gastric artery and a tortuous replaced right hepatic artery arose from superior mesenteric artery. An unusually long cystic artery arose from left hepatic artery and gave rise to 2-3 small anastomotic branches towards hepatic flexor of colon, in addition to its normal gallbladder supply. Awareness of such variations would certainly be helpful in upper abdominal surgeries. PMID:24693485

Singh, Badal; Anand, Mamta; Gupta, Smrity

2014-03-01

249

Time-variant statics corrections during interpretation  

SciTech Connect

Even though statics processing is well advanced and is routinely applied, interpreters are still required to evaluate seismic data that has either no statics corrections or poor statics corrections. It is a critical interpretation skill to recognize uncorrected statics and to correct for their effects. Poor decisions and dry holes are often the result of failure to do this. Since multifold seismic data has become the norm, statics are no longer time invariant. The method of flattening stacked data on a shallow reflector that worked so well for single fold data will show anomalous structure and isochron variation caused by the time-variant effects of uncorrected statics. Uncorrected statics can be identified by anomalous undulations in a shallow reflector, by the time-variant effects with increasing reflection time, and by the variations in optimal stacking velocities, all of which have been documented in the literature. Knowledge of these properties from stacked data observations can lead to robust estimates of the surface position delay profile necessary for all statics corrections. Although prestack analysis and correction provide the best solutions, full spatial and temporal corrections can be calculated easily and applied to the interpretation of stacked data on most work stations to enable quicker, less expensive decision making. Prestack reprocessing is only one action that may result from a quality poststack analysis. Stacked data time picks can be fully corrected with a statics term and a velocity term. Partial corrections, applied only to the center trace of a static-causing body can be made without knowledge of the exact surface position delay model. The ratio of central trace delays of two reflectors is approximately equal to the ratio of effective spread lengths used to stack the two reflectors. This method is applied to a real data example published last year in Geophysics where the anomalous isochron thinning is accurately predicted.

Musgrove, F.W. (Mobil North Sea Limited, London (United Kingdom))

1994-03-01

250

Genetic variants associated with protein C levels  

PubMed Central

Summary Background Normal protein C (PC) plasma levels range widely in the general population. Factors influencing normal PC levels are thought to influence the risk of venous thrombosis. Little is known about the underlying genetic variants. Objectives We performed a genome scan of normal PC levels to identify genes that regulate normal PC levels. Patients/Methods We performed a variance components linkage analysis for normal PC levels in 275 individuals from a single, large family. We then sequenced candidate genes under the identified linkage peak in eight family members: four with high and four with low, but normal PC levels. For variants showing a difference in carriers between those with high and low PC levels, we re-evaluated linkage in the 275 family members conditional on the measured genotype effect. Genotype-specific mean PC levels were determined using likelihood analysis. Findings were replicated in the Leiden Thrombophilia Study (LETS). Results We identified a quantitative trait locus at chromosome 5q14.1 affecting normal PC plasma level variability. Next-generation sequencing of 113 candidate genes under the linkage peak revealed four SNPs in BHMT2, ACOT12, SSBP2 and XRCC4, which significantly increased PC levels in our thrombophilic family, but not in LETS. Conclusions We identified four genes at chromosome 5q14.1 that might influence normal PC levels. BHMT2 seems the most likely candidate to regulate PC levels via homocysteine, a competitive inhibitor to thrombin. Failure to replicate our findings in LETS might be due to differences between the studies in genetic background and linkage disequilibrium patterns. PMID:23387557

Vossen, C.Y.; Koeleman, B.P.; Hasstedt, S.J.; Nijman, I.J.; Renkens, I.J.; Callas, P.W.; Rosendaal, F.R.; Bovill, E.G.

2013-01-01

251

VIRUS NOMENCLATURE BELOW THE SPECIES LEVEL: A STANDARDIZED NOMENCLATURE FOR LABORATORY ANIMAL-ADAPTED STRAINS AND VARIANTS OF VIRUSES ASSIGNED TO THE FAMILY FILOVIRIDAE  

PubMed Central

The International Committee on Taxonomy of Viruses (ICTV) organizes the classification of viruses into taxa, but is not responsible for the nomenclature for taxa members. International experts groups, such as the ICTV Study Groups, recommend the classification and naming of viruses and their strains, variants, and isolates. The ICTV Filoviridae Study Group has recently introduced an updated classification and nomenclature for filoviruses. Subsequently, and together with numerous other filovirus experts, a consistent nomenclature for their natural genetic variants and isolates was developed that aims at simplifying the retrieval of sequence data from electronic databases. This is a first important step toward a viral genome annotation standard as sought by the US National Center for Biotechnology Information (NCBI). Here, this work is extended to include filoviruses obtained in the laboratory by artificial selection through passage in laboratory hosts. The previously developed template for natural filovirus genetic variant naming ( <isolation host-suffix>///variant designation>-<isolate designation>) is retained, but it is proposed to adapt the type of information added to each field for laboratory animal-adapted variants. For instance, the full-length designation of an Ebola virus Mayinga variant adapted at the State Research Center for Virology and Biotechnology “Vector” to cause disease in guinea pigs after seven passages would be akin to “Ebola virus VECTOR/C.porcellus-lab/COD/1976/Mayinga-GPA-P7”. As was proposed for the names of natural filovirus variants, we suggest using the full-length designation in databases, as well as in the method section of publications. Shortened designations (such as “EBOV VECTOR/C.por/COD/76/May-GPA-P7”) and abbreviations (such as “EBOV/May-GPA-P7”) could be used in the remainder of the text depending on how critical it is to convey information contained in the full-length name. “EBOV” would suffice if only one EBOV strain/variant/isolate is addressed. PMID:23358612

Kuhn, Jens H.; Bao, Yiming; Bavari, Sina; Becker, Stephan; Bradfute, Steven; Brister, J. Rodney; Bukreyev, Alexander A.; Cai, Yingyun; Chandran, Kartik; Davey, Robert A.; Dolnik, Olga; Dye, John M.; Enterlein, Sven; Gonzalez, Jean-Paul; Formenty, Pierre; Freiberg, Alexander N.; Hensley, Lisa E.; Honko, Anna N.; Ignatyev, Georgy M.; Jahrling, Peter B.; Johnson, Karl M.; Klenk, Hans-Dieter; Kobinger, Gary; Lackemeyer, Matthew G.; Leroy, Eric M.; Lever, Mark S.; Lofts, Loreen L.; Muhlberger, Elke; Netesov, Sergey V.; Olinger, Gene G.; Palacios, Gustavo; Patterson, Jean L.; Paweska, Janusz T.; Pitt, Louise; Radoshitzky, Sheli R.; Ryabchikova, Elena I.; Saphire, Erica Ollmann; Shestopalov, Aleksandr M.; Smither, Sophie J.; Sullivan, Nancy J.; Swanepoel, Robert; Takada, Ayato; Towner, Jonathan S.; van der Groen, Guido; Volchkov, Viktor E.; Wahl-Jensen, Victoria; Warren, Travis K.; Warfield, Kelly L.; Weidmann, Manfred; Nichol, Stuart T.

2013-01-01

252

Nine-Year Longitudinal Study of Antibodies to Variant Antigens on the Surface of Plasmodium falciparum-Infected Erythrocytes  

PubMed Central

PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This response was often, but not always, specific for the antigenic variants expressed by the parasite isolate causing disease. Our study provides evidence that Palciparum falciparum malaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes. Furthermore, our data suggest that the antigenic repertoires of variant antigens expressed by different parasite isolates show considerable overlapping, at least under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission. Finally, we demonstrate the existence of persistent differences among individuals in the capacity to mount antibody responses to variant surface antigens. PMID:10417178

Giha, Haider A.; Staalsoe, Trine; Dodoo, Daniel; Elhassan, Ibrahim M.; Roper, Cally; Satti, Gwiria M. H.; Arnot, David E.; Theander, Thor G.; Hviid, Lars

1999-01-01

253

Spontaneous Variants of the [RNQ+] Prion in Yeast Demonstrate the Extensive Conformational Diversity Possible with Prion Proteins  

PubMed Central

Prion strains (or variants) are structurally distinct amyloid conformations arising from a single polypeptide sequence. The existence of prion strains has been well documented in mammalian prion diseases. In many cases, prion strains manifest as variation in disease progression and pathology, and in some cases, these prion strains also show distinct biochemical properties. Yet, the underlying basis of prion propagation and the extent of conformational possibilities available to amyloidogenic proteins remain largely undefined. Prion proteins in yeast that are also capable of maintaining multiple self-propagating structures have provided much insight into prion biology. Here, we explore the vast structural diversity of the yeast prion [RNQ+] in Saccharomyces cerevisiae. We screened for the formation of [RNQ+] in vivo, allowing us to calculate the rate of spontaneous formation as ~2.96x10-6, and successfully isolate several different [RNQ+] variants. Through a comprehensive set of biochemical and biological analyses, we show that these prion variants are indeed novel. No individual property or set of properties, including aggregate stability and size, was sufficient to explain the physical basis and range of prion variants and their resulting cellular phenotypes. Furthermore, all of the [RNQ+] variants that we isolated were able to facilitate the de novo formation of the yeast prion [PSI+], an epigenetic determinant of translation termination. This supports the hypothesis that [RNQ+] acts as a functional amyloid in regulating the formation of [PSI+] to produce phenotypic diversity within a yeast population and promote adaptation. Collectively, this work shows the broad spectrum of available amyloid conformations, and thereby expands the foundation for studying the complex factors that interact to regulate the propagation of distinct aggregate structures. PMID:24205387

Huang, Vincent J.; Stein, Kevin C.; True, Heather L.

2013-01-01

254

Metallo--Lactamase Detection: Comparative Evaluation of Double-Disk Synergy versus Combined Disk Tests for IMP, GIM, SIM, SPM, or VIM-Producing Isolates  

Microsoft Academic Search

The emergence of metallo--lactamase (MBL)-producing isolates is a challenge to routine microbiology laboratories, since there are no standardized methods for detecting such isolates. The aim of this study was to evaluate the accuracy of different phenotypic methods to detect MBL production among Pseudomonas spp., Acinetobacter spp., and enterobacterial isolates, including GIM, IMP, SIM, SPM, and VIM variants. A total of

Renata C. Picao; Soraya S. Andrade; Adriana Gianinni Nicoletti; Eloiza H. Campana; Gabriela C. Moraes; Rodrigo E. Mendes; Ana C. Gales

255

Naturally Occurring Variants of Human ?9 Nicotinic Receptor Differentially Affect Bronchial Cell Proliferation and Transformation  

PubMed Central

Isolation of polyadenilated mRNA from human immortalized bronchial epithelial cell line BEP2D revealed the presence of multiple isoforms of RNA coded by the CHRNA9 gene for ?9 nicotinic acetylcholine receptor (nAChR). BEP2D cells were homozygous for the rs10009228 polymorphism encoding for N442S amino acid substitution, and also contained mRNA coding for several truncated isoforms of ?9 protein. To elucidate the biologic significance of the naturally occurring variants of ?9 nAChR, we compared the biologic effects of overexpression of full-length ?9 N442 and S442 proteins, and the truncated ?9 variant occurring due to a loss of the exon 4 sequence that causes frame shift and early termination of the translation. These as well as control vector were overexpressed in the BEP2D cells that were used in the assays of proliferation rate, spontaneous vs. tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced cellular transformation, and tumorigenicity in cell culture and mice. Overexpression of the S442 variant significantly increased cellular proliferation, and spontaneous and NNK-induced transformation. The N442 variant significantly decreased cellular transformation, without affecting proliferation rate. Overexpression of the truncated ?9 significantly decreased proliferation and suppressed cellular transformation. These results suggested that ?9 nAChR plays important roles in regulation of bronchial cell growth by endogenous acetylcholine and exogenous nicotine, and susceptibility to NNK-induced carcinogenic transformation. The biologic activities of ?9 nAChR may be regulated at the splicing level, and genetic polymorphisms in CHRNA9 affecting protein levels, amino acid sequence and RNA splicing may influence the risk for lung cancer. PMID:22125646

Chikova, Anna; Grando, Sergei A.

2011-01-01

256

Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells  

PubMed Central

Epigenetic changes related to human disease cannot be fully addressed by studies of cells from cultures or from other mammals. We isolated human fat cells from subcutaneous abdominal fat tissue of female subjects and extracted histones from either purified nuclei or intact cells. Direct acid extraction of whole adipocytes was more efficient, yielding about 100 µg of protein with histone content of 60% –70% from 10 mL of fat cells. Differential proteolysis of the protein extracts by trypsin or ArgC-protease followed by nanoLC/MS/MS with alternating CID/ETD peptide sequencing identified 19 histone variants. Four variants were found at the protein level for the first time; particularly HIST2H4B was identified besides the only H4 isoform earlier known to be expressed in humans. Three of the found H2A potentially organize small nucleosomes in transcriptionally active chromatin, while two H2AFY variants inactivate X chromosome in female cells. HIST1H2BA and three of the identified H1 variants had earlier been described only as oocyte or testis specific histones. H2AFX and H2AFY revealed differential and variable N-terminal processing. Out of 78 histone modifications by acetylation/trimethylation, methylation, dimethylation, phosphorylation and ubiquitination, identified from six subjects, 68 were found for the first time. Only 23 of these modifications were detected in two or more subjects, while all the others were individual specific. The direct acid extraction of adipocytes allows for personal epigenetic analyses of human fat tissue, for profiling of histone modifications related to obesity, diabetes and metabolic syndrome, as well as for selection of individual medical treatments. PMID:21249133

Jufvas, Asa; Stralfors, Peter; Vener, Alexander V.

2011-01-01

257

Population structure of KPC-producing Klebsiella pneumoniae isolates from midwestern U.S. hospitals.  

PubMed

Genome sequencing of carbapenem-resistant Klebsiella pneumoniae isolates from regional U.S. hospitals was used to characterize strain diversity and the bla(KPC) genetic context. A phylogeny based on core single-nucleotide variants (SNVs) supports a division of sequence type 258 (ST258) into two distinct groups. The primary differences between the groups are in the capsular polysaccharide locus (cps) and their plasmid contents. A strict association between clade and KPC variant was found. The bla(KPC) gene was found on variants of two plasmid backbones. This study indicates that highly similar K. pneumoniae subpopulations coexist within the same hospitals over time. PMID:24913165

Wright, Meredith S; Perez, Federico; Brinkac, Lauren; Jacobs, Michael R; Kaye, Keith; Cober, Eric; van Duin, David; Marshall, Steven H; Hujer, Andrea M; Rudin, Susan D; Hujer, Kristine M; Bonomo, Robert A; Adams, Mark D

2014-08-01

258

Antimicrobial Susceptibilities and Serogroups of Clinical Strains of Clostridium difficile Isolated in France in 1991 and 1997  

PubMed Central

Glycopeptides (vancomycin and teicoplanin) and metronidazole are the drugs of choice for the treatment of Clostridium difficile infections, but trends in susceptibility patterns have not been assessed in the past few years. The objective was to study the MICs of glycopeptides and metronidazole for unrelated C. difficile strains isolated in 1991 (n = 100) and in 1997 (n = 98) by the agar macrodilution, the E-test, and the disk diffusion methods. Strain susceptibilities to erythromycin, clindamycin, tetracycline, rifampin, and chloramphenicol were also determined by the ATB ANA gallery (bioMérieux, La Balme-les-Grottes, France). The MICs at which 50% of isolates are inhibited (MIC50s) and MIC90s of glycopeptides and metronidazole remained stable between 1991 and 1997. All the strains were inhibited by concentrations that did not exceed 2 ?g/ml for vancomycin and 1 ?g/ml for teicoplanin. Comparison of MICs determined by the agar dilution method recommended by the National Committee for Clinical Laboratory Standards and the E test showed correlations (±2 dilutions) of 86.6, 95.9, and 99% for metronidazole, vancomycin, and teicoplanin, respectively. The E test always underestimated the MICs. Strains with decreased susceptibility to metronidazole (MICs, ?8 ?g/ml) were isolated from six patients (n = 4 in 1991 and n = 2 in 1997). These strains were also detected by the disk diffusion method (zone inhibition diameter, ?21 mm); they belonged to nontoxigenic serogroup D (n = 5) and toxigenic serogroup H (n = 1). Decreased susceptibility to erythromycin (MICs, ?1 ?g/ml), clindamycin (MICs, ?2 ?g/ml), tetracycline (MICs, ?8 ?g/ml), rifampin (MICs, ?4 ?g/ml), and chloramphenicol (MICs, ?16 ?g/ml) was observed in 64.2, 80.3, 23.7, 22.7, and 14.6% of strains, respectively. Strains isolated in 1997 were more susceptible than those isolated in 1991, and this trend was correlated to a major change in serogroup distribution. Periodic studies are needed in order to detect changes in serogroups and the emergence of strains with decreased susceptibility to therapeutic drugs. PMID:10543736

Barbut, Frederic; Decre, Dominique; Burghoffer, Beatrice; Lesage, Daniele; Delisle, Francoise; Lalande, Valerie; Delmee, Michel; Avesani, Veronique; Sano, Nassita; Coudert, Cyril; Petit, Jean-Claude

1999-01-01

259

Rare Variants in PLXNA4 and Parkinson’s Disease  

PubMed Central

Approximately 20% of individuals with Parkinson’s disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance. PMID:24244438

Schulte, Eva C.; Stahl, Immanuel; Czamara, Darina; Ellwanger, Daniel C.; Eck, Sebastian; Graf, Elisabeth; Mollenhauer, Brit; Zimprich, Alexander; Lichtner, Peter; Haubenberger, Dietrich; Pirker, Walter; Brücke, Thomas; Bereznai, Benjamin; Molnar, Maria J.; Peters, Annette; Gieger, Christian; Müller-Myhsok, Bertram; Trenkwalder, Claudia; Winkelmann, Juliane

2013-01-01

260

Hepatitis E Virus Variant in Farmed Mink, Denmark  

PubMed Central

Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety of species. PMID:24274600

Breum, Solvej ?.; Jensen, Trine H.; Larsen, Lars E.

2013-01-01

261

Hepatitis E virus variant in farmed mink, Denmark.  

PubMed

Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety of species. PMID:24274600

Krog, Jesper S; Breum, Solvej Ø; Jensen, Trine H; Larsen, Lars E

2013-12-01

262

The personal genome browser: visualizing functions of genetic variants  

PubMed Central

Advances in high-throughput sequencing technologies have brought us into the individual genome era. Projects such as the 1000 Genomes Project have led the individual genome sequencing to become more and more popular. How to visualize, analyse and annotate individual genomes with knowledge bases to support genome studies and personalized healthcare is still a big challenge. The Personal Genome Browser (PGB) is developed to provide comprehensive functional annotation and visualization for individual genomes based on the genetic–molecular–phenotypic model. Investigators can easily view individual genetic variants, such as single nucleotide variants (SNVs), INDELs and structural variations (SVs), as well as genomic features and phenotypes associated to the individual genetic variants. The PGB especially highlights potential functional variants using the PGB built-in method or SIFT/PolyPhen2 scores. Moreover, the functional risks of genes could be evaluated by scanning individual genetic variants on the whole genome, a chromosome, or a cytoband based on functional implications of the variants. Investigators can then navigate to high risk genes on the scanned individual genome. The PGB accepts Variant Call Format (VCF) and Genetic Variation Format (GVF) files as the input. The functional annotation of input individual genome variants can be visualized in real time by well-defined symbols and shapes. The PGB is available at http://www.pgbrowser.org/. PMID:24799434

Juan, Liran; Teng, Mingxiang; Zang, Tianyi; Hao, Yafeng; Wang, Zhenxing; Yan, Chengwu; Liu, Yongzhuang; Li, Jie; Zhang, Tianjiao; Wang, Yadong

2014-01-01

263

Hemimandibular Hypertrophy - Hybrid Variants: Report of Two Cases  

PubMed Central

Hemimandibular hypertrophy and its variants result from unilateral excessive growth of the mandible and involve both the body and ramus of mandible. This causes facial asymmetry and in turn accompanying psychological problems. In this report we discuss use of imaging in diagnosis of these lesions and investigate the different variants. PMID:24516768

Mohan, Ravi Prakash Sasankoti; Verma, Sankalp; Singh, Udita; Agarwal, Neha

2013-01-01

264

Congenital Nonspherocytic Hemolytic Anemia With an Unstable Hexokinase Variant  

Microsoft Academic Search

We report a family with a new hexokinase mal reaction kinetics, and normal dee- variant that gives rise to nonspherocytic trophoretic properties, but has reduced hemolytic anemia in one apparently activity and is apparently inactivated homozygous family member. The variant rapidly as the affected erythrocytes age. enzyme has a normal pH optimum, nor- B ECAUSE ERYTHROCYTE HEXOKINASE (HK) has a

P. G. Board; R. Trueworthy; J. E. Smith; Kateri Moore

1978-01-01

265

LMP1 Strain Variants: Biological and Molecular Properties  

PubMed Central

The ubiquitous herpesvirus Epstein-Barr virus (EBV) is linked to the development of several malignancies, including nasopharyngeal carcinoma. Latent membrane protein 1 (LMP1) is considered the EBV oncogene as it is necessary for EBV-induced transformation of B lymphocytes and is able to transform Rat-1 fibroblasts. LMP1 can activate a wide array of signaling pathways, including phosphatidylinositol 3-kinase (PI3K)-Akt and NF-?B. Six sequence variants of LMP1, termed Alaskan, China 1, China 2, Med+, Med?, and NC, have been identified, and individuals can be infected with multiple variants. The frequencies of detection of these variants differ for various EBV-associated malignancies from different geographic regions. In this study, the biological and signaling properties of the LMP1 variants have been characterized. All of the LMP1 variants transformed Rat-1 fibroblasts, induced increased motility of HFK cells, and induced increased homotypic adhesion of BJAB cells. While all the variants activated the PI3K-Akt signaling pathway to similar extents, the Alaskan, China 1, and Med+ variants had limited binding to the E3 ubiquitin ligase component homologue of Slimb and had slightly enhanced NF-?B signaling. These findings indicate that the signature amino acid changes of the LMP1 variants do not hinder or enhance their in vitro transforming potentials or affect their signaling properties. PMID:16775333

Mainou, Bernardo A.; Raab-Traub, Nancy

2006-01-01

266

Molecular and Genetic Characterization of Natural HIV-1 Tat Exon-1 Variants from North India and Their Functional Implications  

PubMed Central

Background Designing an ideal vaccine against HIV-1 has been difficult due to enormous genetic variability as a result of high replication rate and lack of proofreading activity of reverse transcriptase leading to emergence of genetic variants and recombinants. Tat transactivates HIV-1 LTR, resulting in a remarkable increase in viral gene expression, and plays a vital role in pathogenesis. The aim of this study was to characterize the genetic variations of Tat exon-1 from HIV-1 infected patients from North India. Methods Genomic DNA was isolated from PBMCs and Tat exon-1 was PCR amplified with specific primers followed by cloning, sequencing and sequence analyses using bioinformatic tools for predicting HIV-1 subtypes, recombination events, conservation of domains and phosphorylation sites, and LTR transactivation by luciferase assay. Results Phylogenetic analysis of Tat exon-1 variants (n?=?120) revealed sequence similarity with South African Tat C sequences and distinct geographical relationships were observed for B/C recombinants. Bootscan analysis of our variants showed 90% homology to Tat C and 10% to B/C recombinants with a precise breakpoint. Natural substitutions were observed with high allelic frequencies which may be beneficial for virus. High amino acid conservation was observed in Tat among Anti Retroviral Therapy (ART) recipients. Barring few changes, most of the functional domains, predicted motifs and phosphorylation sites were well conserved in most of Tat variants. dN/dS analysis revealed purifying selection, implying the importance of functional conservation of Tat exon-1. Our Indian Tat C variants and B/C recombinants showed differential LTR transactivation. Conclusions The possible role of Tat exon-1 variants in shaping the current HIV-1 epidemic in North India was highlighted. Natural substitutions across conserved functional domains were observed and provided evidence for the emergence of B/C recombinants within the ORF of Tat exon-1. These events are likely to have implications for viral pathogenesis and vaccine formulations. PMID:24465566

Ronsard, Larance; Lata, Sneh; Singh, Jyotsna; Ramachandran, Vishnampettai G.; Das, Shukla; Banerjea, Akhil C.

2014-01-01

267

Alternative Technical Summary Report: Electrometallurgical Treatment Variant  

Microsoft Academic Search

Immobilization is the fixation of the surplus fissile materials in an acceptable matrix such as glass or ceramics to create an environmentally benign form for disposal in a repository. In addition to the traditional characteristics required of an immobilization form to achieve isolation of the fissile material from the biosphere over geologic times, the immobilization form for the Fissile Materials

Gray

1995-01-01

268

Naturally occurring C-terminal splice variants of nuclear receptors.  

PubMed

Alternative mRNA splicing in the region encoding the C-terminus of nuclear receptors results in receptor variants lacking the entire ligand-binding domain (LBD), or a part of it, and instead contain a sequence of splice variant-specific C-terminal amino acids. A total of thirteen such splice variants have been shown to occur in vertebrates, and at least nine occur in humans. None of these receptor variants appear to be able to bind endogenous ligands and to induce transcription on promoters containing the response element for the respective canonical receptor variant. Interestingly, ten of these C-terminal splice variants have been shown to display dominant-negative activity on the transactivational properties of their canonical equivalent. Research on most of these splice variants has been limited, and the dominant-negative effect of these receptor variants has only been demonstrated in reporter assays in vitro, using transiently transfected receptors and reporter constructs. Therefore, the in vivo function and relevance of most C-terminal splice variants remains unclear. By reviewing the literature on the human glucocorticoid receptor beta-isoform (hGRbeta), we show that the dominant-negative effect of hGRbeta is well established using more physiologically relevant readouts. The hGR beta-isoform may alter gene transcription independent from the canonical receptor and increased hGRbeta levels correlate with glucocorticoid resistance and the occurrence of several immune-related diseases. Thus, available data suggests that C-terminal splice variants of nuclear receptors act as dominant-negative inhibitors of receptor-mediated signaling in vivo, and that aberrant expression of these isoforms may be involved in the pathogenesis of a variety of diseases. PMID:19636396

van der Vaart, Michiel; Schaaf, Marcel J M

2009-01-01

269

High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of ?(v)?(3) integrin.  

PubMed

Altered expression of ?v?3 integrin is associated with tumor progression and metastasis in several types of cancer, including metastatic osteosarcoma. In this study, we demonstrate that in vivo passaging of lung metastasis in nude mice can generate an aggressive variant of human osteosarcoma cells. Experimental metastases were established by injecting 143B human osteosarcoma cells, expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm, in the tail vein of nude mice. Lung metastases were harvested under fluorescence microscopy from nude mice to establish cell lines which were then injected via the tail vein of additional nude mice. This procedure was repeated for four passages in order to isolate highly metastatic variant sublines. When the parental and metastatic variants were transplanted orthotopically into the tibia of nude mice, the 143B-LM4 variant had the highest metastatic rate, approximately 18-fold higher than the parent (p<0.01). ?v?3 integrin expression was increased approximately 5.6-fold in 143B-LM4 compared to parental cells (p<0.05). Thus, serial passage of lung metastases created a highly metastatic variant of human osteosarcoma cells which had increased expression of ?v?3 integrin, suggesting that ?v?3 integrin plays an essential role in osteosarcoma metastasis. With this highly metastatic variant overexpressing ?v?3 integrin, it will now be possible to further investigate the mechanism by which ?v?3 integrin facilitates metastasis. PMID:24023288

Tome, Yasunori; Kimura, Hiroaki; Maehara, Hiroki; Sugimoto, Naotoshi; Bouvet, Michael; Tsuchiya, Hiroyuki; Kanaya, Fuminori; Hoffman, Robert M

2013-09-01

270

Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.  

PubMed

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121*], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited. PMID:24507774

Peloso, Gina M; Auer, Paul L; Bis, Joshua C; Voorman, Arend; Morrison, Alanna C; Stitziel, Nathan O; Brody, Jennifer A; Khetarpal, Sumeet A; Crosby, Jacy R; Fornage, Myriam; Isaacs, Aaron; Jakobsdottir, Johanna; Feitosa, Mary F; Davies, Gail; Huffman, Jennifer E; Manichaikul, Ani; Davis, Brian; Lohman, Kurt; Joon, Aron Y; Smith, Albert V; Grove, Megan L; Zanoni, Paolo; Redon, Valeska; Demissie, Serkalem; Lawson, Kim; Peters, Ulrike; Carlson, Christopher; Jackson, Rebecca D; Ryckman, Kelli K; Mackey, Rachel H; Robinson, Jennifer G; Siscovick, David S; Schreiner, Pamela J; Mychaleckyj, Josyf C; Pankow, James S; Hofman, Albert; Uitterlinden, Andre G; Harris, Tamara B; Taylor, Kent D; Stafford, Jeanette M; Reynolds, Lindsay M; Marioni, Riccardo E; Dehghan, Abbas; Franco, Oscar H; Patel, Aniruddh P; Lu, Yingchang; Hindy, George; Gottesman, Omri; Bottinger, Erwin P; Melander, Olle; Orho-Melander, Marju; Loos, Ruth J F; Duga, Stefano; Merlini, Piera Angelica; Farrall, Martin; Goel, Anuj; Asselta, Rosanna; Girelli, Domenico; Martinelli, Nicola; Shah, Svati H; Kraus, William E; Li, Mingyao; Rader, Daniel J; Reilly, Muredach P; McPherson, Ruth; Watkins, Hugh; Ardissino, Diego; Zhang, Qunyuan; Wang, Judy; Tsai, Michael Y; Taylor, Herman A; Correa, Adolfo; Griswold, Michael E; Lange, Leslie A; Starr, John M; Rudan, Igor; Eiriksdottir, Gudny; Launer, Lenore J; Ordovas, Jose M; Levy, Daniel; Chen, Y-D Ida; Reiner, Alexander P; Hayward, Caroline; Polasek, Ozren; Deary, Ian J; Borecki, Ingrid B; Liu, Yongmei; Gudnason, Vilmundur; Wilson, James G; van Duijn, Cornelia M; Kooperberg, Charles; Rich, Stephen S; Psaty, Bruce M; Rotter, Jerome I; O'Donnell, Christopher J; Rice, Kenneth; Boerwinkle, Eric; Kathiresan, Sekar; Cupples, L Adrienne

2014-02-01

271

Association of Low-Frequency and Rare Coding-Sequence Variants with Blood Lipids and Coronary Heart Disease in 56,000 Whites and Blacks  

PubMed Central

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the “Exome Array” to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121?], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited. PMID:24507774

Peloso, Gina M.; Auer, Paul L.; Bis, Joshua C.; Voorman, Arend; Morrison, Alanna C.; Stitziel, Nathan O.; Brody, Jennifer A.; Khetarpal, Sumeet A.; Crosby, Jacy R.; Fornage, Myriam; Isaacs, Aaron; Jakobsdottir, Johanna; Feitosa, Mary F.; Davies, Gail; Huffman, Jennifer E.; Manichaikul, Ani; Davis, Brian; Lohman, Kurt; Joon, Aron Y.; Smith, Albert V.; Grove, Megan L.; Zanoni, Paolo; Redon, Valeska; Demissie, Serkalem; Lawson, Kim; Peters, Ulrike; Carlson, Christopher; Jackson, Rebecca D.; Ryckman, Kelli K.; Mackey, Rachel H.; Robinson, Jennifer G.; Siscovick, David S.; Schreiner, Pamela J.; Mychaleckyj, Josyf C.; Pankow, James S.; Hofman, Albert; Uitterlinden, Andre G.; Harris, Tamara B.; Taylor, Kent D.; Stafford, Jeanette M.; Reynolds, Lindsay M.; Marioni, Riccardo E.; Dehghan, Abbas; Franco, Oscar H.; Patel, Aniruddh P.; Lu, Yingchang; Hindy, George; Gottesman, Omri; Bottinger, Erwin P.; Melander, Olle; Orho-Melander, Marju; Loos, Ruth J.F.; Duga, Stefano; Merlini, Piera Angelica; Farrall, Martin; Goel, Anuj; Asselta, Rosanna; Girelli, Domenico; Martinelli, Nicola; Shah, Svati H.; Kraus, William E.; Li, Mingyao; Rader, Daniel J.; Reilly, Muredach P.; McPherson, Ruth; Watkins, Hugh; Ardissino, Diego; Zhang, Qunyuan; Wang, Judy; Tsai, Michael Y.; Taylor, Herman A.; Correa, Adolfo; Griswold, Michael E.; Lange, Leslie A.; Starr, John M.; Rudan, Igor; Eiriksdottir, Gudny; Launer, Lenore J.; Ordovas, Jose M.; Levy, Daniel; Chen, Y.-D. Ida; Reiner, Alexander P.; Hayward, Caroline; Polasek, Ozren; Deary, Ian J.; Borecki, Ingrid B.; Liu, Yongmei; Gudnason, Vilmundur; Wilson, James G.; van Duijn, Cornelia M.; Kooperberg, Charles; Rich, Stephen S.; Psaty, Bruce M.; Rotter, Jerome I.; O'Donnell, Christopher J.; Rice, Kenneth; Boerwinkle, Eric; Kathiresan, Sekar; Cupples, L. Adrienne

2014-01-01

272

A changing gastric environment leads to adaptation of lipopolysaccharide variants in Helicobacter pylori populations during colonization.  

PubMed

The human gastric pathogen Helicobacter pylori colonizes the stomachs of half of the human population, and causes development of peptic ulcer disease and gastric adenocarcinoma. H. pylori-associated chronic atrophic gastritis (ChAG) with loss of the acid-producing parietal cells, is correlated with an increased risk for development of gastric adenocarcinoma. The majority of H. pylori isolates produce lipopolysaccharides (LPS) decorated with human-related Lewis epitopes, which have been shown to phase-vary in response to different environmental conditions. We have characterized the adaptations of H. pylori LPS and Lewis antigen expression to varying gastric conditions; in H. pylori isolates from mice with low or high gastric pH, respectively; in 482 clinical isolates from healthy individuals and from individuals with ChAG obtained at two time points with a four-year interval between endoscopies; and finally in isolates grown at different pH in vitro. Here we show that the gastric environment can contribute to a switch in Lewis phenotype in the two experimental mouse models. The clinical isolates from different human individuals showed that intra-individual isolates varied in Lewis antigen expression although the LPS diversity was relatively stable within each individual over time. Moreover, the isolates demonstrated considerable diversity in the levels of glycosylation and in the sizes of fucosylated O-antigen chains both within and between individuals. Thus our data suggest that different LPS variants exist in the colonizing H. pylori population, which can adapt to changes in the gastric environment and provide a means to regulate the inflammatory response of the host during disease progression. PMID:19517017

Skoglund, Anna; Bäckhed, Helene Kling; Nilsson, Christina; Björkholm, Britta; Normark, Staffan; Engstrand, Lars

2009-01-01

273

Genetic characterization of an isolate of HIV type 1 AG recombinant form circulating in Siberia, Russia.  

PubMed

Before 2008, HIV-1 subtype A was the predominant genetic variant in the Novosibirsk oblast of Russia as well as in most parts of this country. However, a rapid spread of the recombinant HIV-1 02_AG form has been reported in Novosibirsk since 2009. We have analyzed the genome of the 10.RU.6637 isolate, a HIV-1 02_AG recombinant form, which represents a monophyletic cluster of the HIV-1 variants widespread in this region. Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan. However, recombination analysis of 10.RU.6637 has demonstrated that this isolate is a recombinant form between HIV-1 subtype A and CRF02_AG, differing in its genetic structure from both the CRF02_AG reference sequences and the Central Asian variants of HIV-1 02_AG. PMID:22903393

Baryshev, P B; Bogachev, V V; Gashnikova, N M

2012-12-01

274

Release of ?-casomorphin-7/5 during simulated gastrointestinal digestion of milk ?-casein variants from Indian crossbred cattle (Karan Fries).  

PubMed

Crossbred Karan Fries (KF) cows, among the best yielders of milk in India are carriers of A1 and A2 alleles. These genetic variants have been established as the source of ?-casomorphins (BCMs) bioactive peptides that are implicated with various physiological and health issues. Therefore, the present study was aimed to investigate the release of BCM-7/5 from ?-casein variants of KF by simulated gastrointestinal digestion (SGID) performed with proteolytic enzymes, in vitro. ?-Casein variants (A1A1, A1A2 and A2A2) were isolated from milk samples of genotyped Karan Fries animals and subjected to hydrolysis by SGID using proteolytic enzymes (pepsin, trypsin, chymotrypsin and pancreatin), in vitro. Detection of BCMs were carried out in two peptide fractions (A and B) of RP-HPLC collected at retention time (RT) 24 and 28min respectively corresponding to standard BCM-5 and BCM-7 by MS-MS and competitive ELISA. One of the RP-HPLC fractions (B) showed the presence of 14 amino acid peptide (VYPFPGPIHNSLPQ) having encrypted internal BCMs sequence while no such peptide or precursor was observed in fraction A by MS-MS analysis. Further hydrolysis of fraction B of A1A1 and A1A2 variants of ?-casein with elastase and leucine aminopeptidase revealed the release of BCM-7 by competitive ELISA. The yield of BCM-7 (0.20±0.02mg/g ?-casein) from A1A1 variant was observed to be almost 3.2 times more than A1A2 variant of ?-casein. However, release of BCM-7/5 could not be detected from A2A2 variant of ?-casein. The biological activity of released peptides on rat ileum by isolated organ bath from A1A1 (IC50=0.534-0.595?M) and A1A2 (IC50=0.410-0.420?M) hydrolysates further confirmed the presence of opioid peptide BCM-7. PMID:25172685

Ul Haq, Mohammad Raies; Kapila, Rajeev; Kapila, Suman

2015-02-01

275

HIV-1 isolation from infected peripheral blood mononuclear cells.  

PubMed

Human immunodeficiency virus 1 (HIV-1) isolation from peripheral blood mononuclear cells (PBMCs) allows retrieval of replication-competent viral variants. In order to impose the smallest possible selective pressure on the viral isolates, isolation must be carried out in primary cultures of cells and not in tumor derived cell lines. The procedure involves culture of PBMCs from an infected patient with phytohemagglutinin (PHA)-stimulated PBMC from seronegative donors, which provide susceptible target cells for HIV replication. HIV can be isolated from the bulk population of PBMCs or after cloning of the cells to obtain viral biological clones. Viral production is determined with p24 antigen (Ag) detection assays or with reverse transcriptase (RT) activity assay. Once isolated, HIV-1 can be propagated by infecting PHA-stimulated PBMCs from healthy donors. Aliquots from culture with a high production of virus are stored for later use. PMID:24158823

Dispinseri, Stefania; Saba, Elisa; Vicenzi, Elisa; Kootstra, Neeltje A; Schuitemaker, Hanneke; Scarlatti, Gabriella

2014-01-01

276

Conformational characterization of the charge variants of a human IgG1 monoclonal antibody using H/D exchange mass spectrometry  

PubMed Central

MAb1, a human IgG1 monoclonal antibody produced in a NS0 cell line, exhibits charge heterogeneity because of the presence of variants formed by processes such as N-terminal glutamate cyclization, C-terminal lysine truncation, deamidation, aspartate isomerization and sialylation in the carbohydrate moiety. Four major charge variants of MAb1 were isolated and the conformations of these charge variants were studied using hydrogen/deuterium exchange mass spectrometry, including the H/D exchange time course (HX-MS) and the stability of unpurified proteins from rates of H/D exchange (SUPREX) techniques. HX-MS was used to evaluate the conformation and solution dynamics of MAb1 charge variants by measuring their deuterium buildup over time at the peptide level. The SUPREX technique evaluated the unfolding profile and relative stability of the charge variants by measuring the exchange properties of globally protected amide protons in the presence of a chemical denaturant. The H/D exchange profiles from both techniques were compared among the four charge variants of MAb1. The two techniques together offered extensive understanding about the local and subglobal/global unfolding of the charge variants of MAb1. Our results demonstrated that all four charge variants of MAb1 were not significantly different in conformation, solution dynamics and chemical denaturant-induced unfolding profile and stability, which aids in understanding the biofunctions of the molecules. The analytical strategy used for conformational characterization may also be applicable to comparability studies done for antibody therapeutics. PMID:23222183

Tang, Liangjie; Sundaram, Shanmuuga; Zhang, Jingming; Carlson, Ping; Matathia, Alice; Parekh, Babita; Zhou, Qinwei; Hsieh, Ming-Ching

2013-01-01

277

NECTAR: a database of codon-centric missense variant annotations  

PubMed Central

NECTAR (Non-synonymous Enriched Coding muTation ARchive; http://nectarmutation.org) is a database and web application to annotate disease-related and functionally important amino acids in human proteins. A number of tools are available to facilitate the interpretation of DNA variants identified in diagnostic or research sequencing. These typically identify previous reports of DNA variation at a given genomic location, predict its effects on transcript and protein sequence and may predict downstream functional consequences. Previous reports and functional annotations are typically linked by the genomic location of the variant observed. NECTAR collates disease-causing variants and functionally important amino acid residues from a number of sources. Importantly, rather than simply linking annotations by a shared genomic location, NECTAR annotates variants of interest with details of previously reported variation affecting the same codon. This provides a much richer data set for the interpretation of a novel DNA variant. NECTAR also identifies functionally equivalent amino acid residues in evolutionarily related proteins (paralogues) and, where appropriate, transfers annotations between them. As well as accessing these data through a web interface, users can upload batches of variants in variant call format (VCF) for annotation on-the-fly. The database is freely available to download from the ftp site: ftp://ftp.nectarmutation.org. PMID:24297257

Gong, Sungsam; Ware, James S.; Walsh, Roddy; Cook, Stuart A.

2014-01-01

278

Testing Genetic Association With Rare Variants in Admixed Populations  

PubMed Central

Recent studies suggest that rare variants play an important role in the etiology of many traits. Although a number of methods have been developed for genetic association analysis of rare variants, they all assume a relatively homogeneous population under study. Such an assumption may not be valid for samples collected from admixed populations such as African Americans and Hispanic Americans as there is a great extent of local variation in ancestry in these populations. To ensure valid and more powerful rare variant association tests performed in admixed populations, we have developed a local ancestry-based weighted dosage test, which is able to take into account local ancestry of rare alleles, uncertainties in rare variant imputation when imputed data are included, and the direction of effect that rare variants exert on phenotypic outcome. We used simulated sequence data to show that our proposed test has controlled type I error rates, whereas naïve application of existing rare variants tests and tests that adjust for global ancestry lead to inflated type I error rates. We showed that our test has higher power than tests without proper adjustment of ancestry. We also applied the proposed method to a candidate gene study on low-density lipoprotein cholesterol. Our results suggest that it is important to appropriately control for potential population stratification induced by local ancestry difference in the analysis of rare variants in admixed populations. PMID:23032398

Mao, Xianyun; Li, Yun; Liu, Yichuan; Lange, Leslie; Li, Mingyao

2012-01-01

279

CRY2 Genetic Variants Associate with Dysthymia  

PubMed Central

People with mood disorders often have disruptions in their circadian rhythms. Recent molecular genetics has linked circadian clock genes to mood disorders. Our objective was to study two core circadian clock genes, CRY1 and CRY2 as well as TTC1 that interacts with CRY2, in relation to depressive and anxiety disorders. Of these three genes, 48 single-nucleotide polymorphisms (SNPs) whose selection was based on the linkage disequilibrium and potential functionality were genotyped in 5910 individuals from a nationwide population-based sample. The diagnoses of major depressive disorder, dysthymia and anxiety disorders were assessed with a structured interview (M-CIDI). In addition, the participants filled in self-report questionnaires on depressive and anxiety symptoms. Logistic and linear regression models were used to analyze the associations of the SNPs with the phenotypes. Four CRY2 genetic variants (rs10838524, rs7121611, rs7945565, rs1401419) associated significantly with dysthymia (false discovery rate q<0.05). This finding together with earlier CRY2 associations with winter depression and with bipolar type 1 disorder supports the view that CRY2 gene has a role in mood disorders. PMID:23951166

Kovanen, Leena; Kaunisto, Mari; Donner, Kati; Saarikoski, Sirkku T.; Partonen, Timo

2013-01-01

280

Identification of copy number variants in horses.  

PubMed

Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds. PMID:22383489

Doan, Ryan; Cohen, Noah; Harrington, Jessica; Veazey, Kylee; Veazy, Kylee; Juras, Rytis; Cothran, Gus; McCue, Molly E; Skow, Loren; Dindot, Scott V

2012-05-01

281

Study on Variant Anatomy of Sciatic Nerve  

PubMed Central

Introduction: Sciatic Nerve (SN) is the nerve of the posterior compartment of thigh formed in the pelvis from the ventral rami of the L4 to S3 spinal nerves. It leaves the pelvis via the greater sciatic foramen below piriformis and divides into Common Peroneal Nerve (CPN) and Tibial Nerve (TN) at the level of the upper angle of the popliteal fossa. Higher division of the sciatic nerve is the most common variation where the TN and CPN may leave the pelvis through different routes. Such variation may lead to compression of the nerve and lead to Non-discogenic sciatica. Materials and Methods: Fifty lower limbs were used for the study from Department of Anatomy, J.J.M.M.C Davangere, Karnataka, India. Observation and Results: In our study on 25 cadavers (50 lower limbs), we have observed 4 (8 %) lower limbs high division of sciatic nerve was noted. High division of sciatic nerve in the back of thigh was noted in one specimen (2%), while high division within the pelvis was noted in 3 specimens (6%), while in 46 (92%) it occurred outside the pelvis. Conclusion: Knowledge regarding such variation and differences in the course of SN is important for the surgeons to plan for various surgical interventions pertaining to the gluteal region. The variant anatomy of SN may cause piriformis syndrome and failure of SN block. Hence present study is undertaken to know the level of division, exit, course, relationship to piriformis and variations in the branching pattern of SN.

V, Sangeetha

2014-01-01

282

The association of Duffy binding protein region II polymorphisms and its antigenicity in Plasmodium vivax isolates from Thailand.  

PubMed

Plasmodium vivax Duffy binding protein II (DBPII) plays an important role in reticulocyte invasion and is a potential vaccine candidate against vivax malaria. However, polymorphisms in DBPII are a challenge for the successful design of a broadly protective vaccine. In this study, the genetic diversity of DBPII among Thai isolates was analyzed from Plasmodium vivax-infected blood samples and polymorphism characters were defined with the MEGA4 program. Sequence analysis identified 12 variant residues that are common among Thai DBPII haplotypes with variant residues L333F, L424I, W437R and I503K having the highest frequency. Variant residue D384K occurs in combination with either E385K or K386N/Q. Additionally, variant residue L424I occurs in conjunction with W437R in most Thai DBPII alleles and these variants frequently occur in combination with the I503K variant. The polymorphic patterns of Thai isolates were defined into 9 haplotypes (Thai DBL-1, -2, -3, etc.…). Thai DBL-2, -5, -6 haplotypes are the most common DBPII variants in Thai residents. To study the association of these Thai DBPII polymorphisms with antigenic character, the functional inhibition of anti-DBPII monoclonal antibodies against a panel of Thai DBL variants was characterized by an in vitro erythrocyte binding inhibition assay. The functional inhibition of anti-DBPII monoclonal antibodies 3C9, 2D10 and 2C6 against Thai variants was significantly different, suggesting that polymorphisms of Thai DBPII variants alter the antigenic character of the target epitopes. In contrast, anti-DBPII monoclonal antibody 2H2 inhibited all Thai DBPII variants equally well. Our results suggest that the immune efficacy of a DBPII vaccine will depend on the specificity of the anti-DBPII antibodies induced and that it is preferable to optimize responses to conserved epitopes for broadly neutralizing protection against P. vivax. PMID:25108177

Chootong, Patchanee; McHenry, Amy M; Ntumngia, Francis B; Sattabongkot, Jetsumon; Adams, John H

2014-12-01

283

Variant selection and transformation texture in zirconium alloy Excel  

NASA Astrophysics Data System (ADS)

The crystallographic texture and variant selection during phase transformations in zirconium alloy Excel (Zr-3.5% Sn-0.8% Mo-0.8% Nb) was investigated. It was shown that upon water-quenching from ?Zr + ?Zr or fully ?Zr regions, variant selection occurs during ?Zr ? ??Zr martensitic transformation. Also during air-cooling from the ?Zr + ?Zr region, only a partial memory effect and some transformation texture with variant selection was observed which is contrary to previous reports on zirconium alloys heat treated in the ?Zr + ?Zr region.

Sattari, M.; Holt, R. A.; Daymond, M. R.

2014-10-01

284

Isolated sleep paralysis  

MedlinePLUS

Sleep paralysis - isolated; Parasomnia - Isolated sleep paralysis ... Episodes of isolated sleep paralysis last from a few seconds to 1 or 2 minutes in which the person is unable to move or speak. ...

285

Additive effects of certain transforming agents from some variants of pneumococcus.  

PubMed

It has proved possible to transform an extreme rough variant of pneumococcus back to the rough state by the action of the desoxyribonucleate fractions of either rough or Type III smooth pneumococci. In a second step, the rough pneumococci produced by this transformation were further changed to the Type III smooth state by means of the desoxyribonucleate fraction of Type III smooth organisms. With use of the Type III desoxyribonucleate, the two steps could be accomplished successively, but not simultaneously, during the growth of a single inoculum of the extreme rough form. These findings have been interpreted as indicating that the desoxyribonucleic acid fraction of Type III smooth pneumococci contains two transforming principles of differing specificity, while the same fraction of rough pneumococci contains but one of these principles. Two distinct spontaneous variants of Type III smooth pneumococci have been isolated which seem to differ from normal Type III smooth pneumococci in synthesizing smaller amounts of the specific polysaccharide. Tests have indicated that these variant Type III races differ from the normal in possessing altered Type III transforming principles. Each of the new transforming agents when influencing rough bacteria, is strictly specific in its action, inducing as it does the formation of the corresponding variant Type III pneumococci. Interaction between the two new transforming principles and rough pneumococci can lead to the production of normal Type III organisms, although neither principle alone can do it. This is interpreted as indicating that the two mutated Type III transforming principles are qualitatively different from each other. Another kind of two-step transformation was accomplished by converting rough pneumococci first into the variant Type III pneumococci which produced very little specific polysaccharide, and then by transforming these latter into normal Type III organisms. After the two-step transformation of the extreme rough pneumococcus, both transforming principles used to effect this can be recognized in the Type III smooth pneumococci finally recovered. By contrast, in the two-step transformation of the rough pneumococcus by way of an intermediate smooth form, only the second transforming principle can be obtained from the resulting fully smooth organisms. The meaning of these facts is discussed. PMID:18113913

TAYLOR, H E

1949-04-01

286

Hierarchical Generalized Linear Models for Multiple Groups of Rare and Common Variants: Jointly Estimating Group and Individual-Variant Effects  

PubMed Central

Complex diseases and traits are likely influenced by many common and rare genetic variants and environmental factors. Detecting disease susceptibility variants is a challenging task, especially when their frequencies are low and/or their effects are small or moderate. We propose here a comprehensive hierarchical generalized linear model framework for simultaneously analyzing multiple groups of rare and common variants and relevant covariates. The proposed hierarchical generalized linear models introduce a group effect and a genetic score (i.e., a linear combination of main-effect predictors for genetic variants) for each group of variants, and jointly they estimate the group effects and the weights of the genetic scores. This framework includes various previous methods as special cases, and it can effectively deal with both risk and protective variants in a group and can simultaneously estimate the cumulative contribution of multiple variants and their relative importance. Our computational strategy is based on extending the standard procedure for fitting generalized linear models in the statistical software R to the proposed hierarchical models, leading to the development of stable and flexible tools. The methods are illustrated with sequence data in gene ANGPTL4 from the Dallas Heart Study. The performance of the proposed procedures is further assessed via simulation studies. The methods are implemented in a freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/). PMID:22144906

Yi, Nengjun; Liu, Nianjun; Zhi, Degui; Li, Jun

2011-01-01

287

Cys-27 Variant of Human ?-Opioid Receptor Modulates Maturation and Cell Surface Delivery of Phe-27 Variant via Heteromerization*  

PubMed Central

The important role of G protein-coupled receptor homo/heteromerization in receptor folding, maturation, trafficking, and cell surface expression has become increasingly evident. Here we investigated whether the human ?-opioid receptor (h?OR) Cys-27 variant that shows inherent compromised maturation has an effect on the behavior of the more common Phe-27 variant in the early secretory pathway. We demonstrate that h?OR-Cys-27 acts in a dominant negative manner and impairs cell surface delivery of the co-expressed h?OR-Phe-27 and impairs conversion of precursors to the mature form. This was demonstrated by metabolic labeling, Western blotting, flow cytometry, and confocal microscopy in HEK293 and human SH-SY5Y neuroblastoma cells using differentially epitope-tagged variants. The h?OR-Phe-27 precursors that were redirected to the endoplasmic reticulum-associated degradation were, however, rescued by a pharmacological chaperone, the opioid antagonist naltrexone. Co-immunoprecipitation of metabolically labeled variants revealed that both endoplasmic reticulum-localized precursors and mature receptors exist as homo/heteromers. The existence of homo/heteromers was confirmed in living cells by bioluminescence resonance energy transfer measurements, showing that the variants have a similar propensity to form homo/heteromers. By forming both homomers and heteromers, the h?OR-Cys-27 variant may thus regulate the levels of receptors at the cell surface, possibly leading to altered responsiveness to opioid ligands in individuals carrying the Cys-27 variant. PMID:22184124

Leskela, Tarja T.; Lackman, Jarkko J.; Vierimaa, Miia M.; Kobayashi, Hiroyuki; Bouvier, Michel; Petaja-Repo, Ulla E.

2012-01-01

288

Spectrum of Pneumococcal Serotype 11A Variants Results from Incomplete Loss of Capsule O-Acetylation  

PubMed Central

Streptococcus pneumoniae is a significant bacterial pathogen that expresses >90 capsule serotypes. Conventional serotyping methods assume that each serotype is a genetically and antigenically distinct entity; however, recent investigations have revealed pneumococcal isolates that cannot be unambiguously serotyped because they share the properties of more than one serotype. Here, we employed a novel serotyping method and NMR spectroscopy to examine clinical isolates sharing properties of serotypes 11A and 11E. These ambiguous clinical isolates were provisionally named 11A variant (11Av) isolates. Serotype 11A pneumococci characteristically express capsule ?-galactose-6-O-acetylation (?Gal6OAc) mediated by the capsule synthesis gene wcjE, while 11E strains contain loss-of-function mutations in wcjE and completely lack the expression of ?Gal6OAc. Although 11Av isolates also contained mutated wcjE alleles, 11Av clinical isolates were composed of antigenically homogeneous bacteria expressing reduced amounts of 11A-specific capsule antigen. NMR data confirmed reduced but detectable amounts of ?Gal6OAc on 11Av capsule polysaccharide. Furthermore, the transformation of strains with wcjE alleles from 11Av strains was sufficient to restore partial ?Gal6OAc in an 11E background. We conclude that, instead of being distinct entities, serotypes 11A and 11E represent two extremes of an antigenic spectrum resulting from variable capsule O-acetylation secondary to heterologous wcjE mutations. These findings challenge whether all clinically relevant pneumococci can be definitively categorized into distinct serotypes. PMID:24352997

Calix, Juan J.; Brady, Allison M.; Du, Victor Y.; Saad, Jamil S.

2014-01-01

289

Meta-analysis of gene-level associations for rare variants based on single-variant statistics.  

PubMed

Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are performed at the gene level rather than at the variant level poses unprecedented challenges in the meta-analysis. First, different studies may adopt different gene-level tests, so the results are not compatible. Second, gene-level tests require multivariate statistics (i.e., components of the test statistic and their covariance matrix), which are difficult to obtain. To overcome these challenges, we propose to perform gene-level tests for rare variants by combining the results of single-variant analysis (i.e., p values of association tests and effect estimates) from participating studies. This simple strategy is possible because of an insight that multivariate statistics can be recovered from single-variant statistics, together with the correlation matrix of the single-variant test statistics, which can be estimated from one of the participating studies or from a publicly available database. We show both theoretically and numerically that the proposed meta-analysis approach provides accurate control of the type I error and is as powerful as joint analysis of individual participant data. This approach accommodates any disease phenotype and any study design and produces all commonly used gene-level tests. An application to the GWAS summary results of the Genetic Investigation of ANthropometric Traits (GIANT) consortium reveals rare and low-frequency variants associated with human height. The relevant software is freely available. PMID:23891470

Hu, Yi-Juan; Berndt, Sonja I; Gustafsson, Stefan; Ganna, Andrea; Hirschhorn, Joel; North, Kari E; Ingelsson, Erik; Lin, Dan-Yu

2013-08-01

290

Isolation of useful variants in alloplasmic crop brassicas in the cytoplasmic background of Erucastrum gallicum  

Microsoft Academic Search

Alloplasmic Brassica juncea was synthesized by repeatedly backcrossing amphidiploid of Erucastrum gallicum B. juncea with\\u000a pollen of B. juncea. The E. gallicum cytoplasm was also transferred to B. napus and B. carinata through alloplasmic (E. gallicum)\\u000a B. juncea. RFLP analyses of organelle DNA confirmed the presence of E. gallicum cytoplasm in all the alloplasmics. The cytoplasm\\u000a of E. gallicum, though

Gadde U. Rao; Akshay K. Pradhan; Kundaranahalli R. Shivanna

1998-01-01

291

A novel cloning strategy for isolating, genotyping and phenotyping genetic variants of geminiviruses  

Microsoft Academic Search

BACKGROUND: Viruses of the genus Begomovirus (Geminiviridae) are emerging economically important plant viruses with a circular, single-stranded DNA genome. Previous studies have shown that geminiviruses and RNA viruses exhibit similar mutation frequencies, although geminiviruses are replicated by host DNA polymerases and RNA viruses by their own virus-encoded error-prone RNA-dependent RNA-polymerase. However, the phenotypic effects of naturally occurring mutations have never

Cica Urbino; Gael Thébaud; Martine Granier; Stéphane Blanc; Michel Peterschmitt

2008-01-01

292

Leapfrog variants of iterative methods for linear algebra equations  

NASA Technical Reports Server (NTRS)

Two iterative methods are considered, Richardson's method and a general second order method. For both methods, a variant of the method is derived for which only even numbered iterates are computed. The variant is called a leapfrog method. Comparisons between the conventional form of the methods and the leapfrog form are made under the assumption that the number of unknowns is large. In the case of Richardson's method, it is possible to express the final iterate in terms of only the initial approximation, a variant of the iteration called the grand-leap method. In the case of the grand-leap variant, a set of parameters is required. An algorithm is presented to compute these parameters that is related to algorithms to compute the weights and abscissas for Gaussian quadrature. General algorithms to implement the leapfrog and grand-leap methods are presented. Algorithms for the important special case of the Chebyshev method are also given.

Saylor, Paul E.

1988-01-01

293

Salmonella enterica serovar Typhi variants in long-term carriers.  

PubMed

Long-term typhoid carriers can simultaneously excrete Salmonella enterica serovar Typhi variants with considerable genetic differences, a situation that complicates the interpretation of the subtyping data used in outbreak investigations and disease surveillance. PMID:23241373

Chiou, Chien-Shun; Wei, Hsiao-Lun; Mu, Jung-Jung; Liao, Ying-Shu; Liang, Shiu-Yun; Liao, Chun-Hsing; Tsao, Chi-Sen; Wang, Shu-Chuan

2013-02-01

294

Coreceptor specificity of temporal variants of simian immunodeficiency virus Mne.  

PubMed

The simian immunodeficiency virus (SIV) Mne envelope undergoes genetic changes that alter tropism, syncytium-inducing capacity, and antigenic properties of the emerging variant virus population during the course of an infection. Here we investigated whether the mutations in envelope of SIVMne also influence coreceptor usage. The data demonstrate that the infecting macrophage-tropic SIVMne clone as well as the envelope variants that are selected during the course of disease progression all recognize both CCR5 and Bob (GPR15) but not Bonzo (STRL33), CXCR4, or CCR3. Although it remains to be determined if there are other coreceptors specific for dualtropic or T-cell-tropic variants of SIVMne that emerge during late stages of infection, these data suggest that such SIV variants that evolve in pathogenic infections do not lose the ability to recognize CCR5 or Bob/GPR15. PMID:9882375

Kimata, J T; Gosink, J J; KewalRamani, V N; Rudensey, L M; Littman, D R; Overbaugh, J

1999-02-01

295

Common Gene Variants Account for Most Genetic Risk for Autism  

MedlinePLUS

... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study Most of the genetic risk for autism comes from versions of genes that are common ...

296

Variant of Usher Syndrome Gene Preserves Vision and Balance  

MedlinePLUS

... preserves vision and balance Variant of Usher Syndrome Gene Preserves Vision and Balance Usher syndrome, an inherited, ... mutant copy of any one of several different genes. But surprisingly, some mutations of the same genes ...

297

ANTIGENIC VARIANTS OF EASTERN EQUINE ENCEPHALITIS VIRUS  

PubMed Central

A study by hemagglutination-inhibition test showed that 19 strains of eastern equine encephalitis virus grouped themselves in two main types, which have been designated North American and South American. The former consists of ten strains from the eastern half of the United States, from Massachusetts to Florida; Jamaica, the Dominican Republic, and, subject to confirmation, Thailand. The South American type comprises nine strains from Panama, Trinidad, British Guiana, Brazil, and Argentina. The strains were isolated from different natural hosts over a period of 30 years. PMID:14151098

Casals, Jordi

1964-01-01

298

Two Novel Toxin Variants Revealed by Whole-Genome Sequencing of 175 Clostridium botulinum Type E Strains.  

PubMed

We sequenced 175 Clostridium botulinum type E strains isolated from food, clinical, and environmental sources from northern Canada and analyzed their botulinum neurotoxin (bont) coding sequences (CDSs). In addition to bont/E1 and bont/E3 variant types, neurotoxin sequence analysis identified two novel BoNT type E variants termed E10 and E11. Strains producing type E10 were found along the eastern coastlines of Hudson Bay and the shores of Ungava Bay, while strains producing type E11 were only found in the Koksoak River region of Nunavik. Strains producing BoNT/E3 were widespread throughout northern Canada, with the exception of the coast of eastern Hudson Bay. PMID:25107978

Weedmark, K A; Lambert, D L; Mabon, P; Hayden, K L; Urfano, C J; Leclair, D; Van Domselaar, G; Austin, J W; Corbett, C R

2014-10-15

299

Protein variants in Hiroshima and Nagasaki: tales of two cities.  

PubMed

The results of 1,465,423 allele product determinations based on blood samples from Hiroshima and Nagasaki, involving 30 different proteins representing 32 different gene products, are analyzed in a variety of ways, with the following conclusions: (1) Sibships and their parents are included in the sample. Our analysis reveals that statistical procedures designed to reduce the sample to equivalent independent genomes do not in population comparisons compensate for the familial cluster effect of rare variants. Accordingly, the data set was reduced to one representative of each sibship (937,427 allele products). (2) Both chi 2-type contrasts and a genetic distance measure (delta) reveal that rare variants (P less than .01) are collectively as effective as polymorphisms in establishing genetic differences between the two cities. (3) We suggest that rare variants that individually exhibit significant intercity differences are probably the legacy of tribal private polymorphisms that occurred during prehistoric times. (4) Despite the great differences in the known histories of the two cities, both the overall frequency of rare variants and the number of different rare variants are essentially identical in the two cities. (5) The well-known differences in locus variability are confirmed, now after adjustment for sample size differences for the various locus products; in this large series we failed to detect variants at only three of 29 loci for which sample size exceeded 23,000. (6) The number of alleles identified per locus correlates positively with subunit molecular weight. (7) Loci supporting genetic polymorphisms are characterized by more rare variants than are loci at which polymorphisms were not encountered. (8) Loci whose products do not appear to be essential for health support more variants than do loci the absence of whose product is detrimental to health. (9) There is a striking excess of rare variants over the expectation under the neutral mutation/drift/equilibrium theory. We suggest that this finding is primarily due to the relatively recent (in genetic time) agglomeration of previously separated tribal populations; efforts to test for agreement with the expectations of this theory by using data from modern cosmopolitan populations are exercises in futility. (10) All of these findings should characterize DNA variants in exons as more data become available, since the finding are the protein expression of such variants. PMID:3195587

Neel, J V; Satoh, C; Smouse, P; Asakawa, J; Takahashi, N; Goriki, K; Fujita, M; Kageoka, T; Hazama, R

1988-12-01

300

Variant maple syrup urine disease (MSUD)—The entire spectrum  

Microsoft Academic Search

Summary  \\u000a Background: In the rare inborn autosomal recessive disorder maple syrup urine disease (MSUD) the accumulation of the branched-chain\\u000a amino acids (BCAAs) and their metabolic products results in acute and chronic brain dysfunction. About 20% of the patients\\u000a suffer from non-classic variant forms of MSUD of different clinical severity. Aim: Up to now variant cases have mostly been published as

E. Simon; N. Flaschker; P. Schadewaldt; U. Langenbeck; U. Wendel

2006-01-01

301

Variants at the 9p21 locus and melanoma risk  

PubMed Central

Background The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS). Methods In the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region. Results All the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3’ UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A–allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54). Conclusions Our data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes. PMID:23816148

2013-01-01

302

Recognizing target variants and articulations in synthetic aperture radar images  

Microsoft Academic Search

The focus of this paper is recognizing articulated vehicles and actual vehicle configuration variants in real synthetic aperture radar (SAR) images. Using SAR scattering-center locations and magnitudes as features, the invariance of these features is shown with articulation (e.g., rotation of a tank turret), with configuration variants, and with a small change in depression angle. This scatterer-location and magnitude quasiinvariance

Bir Bhanu; Grinnell Jones

2000-01-01

303

Avian tuberculosis which occurred in an imported pigeon and pathogenicity of the isolates.  

PubMed

A tubercular lesion (15 mm in diameter) was found on the skin of the caudal part of the cloaca in a 2-year-old male carrier-pigeon. Mycobacterium avium serovar 2 was isolated from the tubercular lesion on the skin and in the feces. The smooth and dome (SmD) variant (4.9 x 10(6) CFU) and rough and granular (RG) variant (3.7 x 10(7) CFU) of the isolates were injected into chickens intravenously. The chickens inoculated with the RG variant died on the 39th day and the one with the SmD variant died on the 77th day after inoculation. Enlargement of the liver and spleen was observed in all the inoculated chickens. Many white tubercular lesions were observed in the liver, spleen and lung of the chicken inoculated with the SmD variant, while no macroscopical change was observed in the bird inoculated with the RG variant. Inoculated organisms were recovered from the liver, spleen, kidneys, lungs and pancreas of each inoculated chicken. PMID:7948399

Morita, Y; Arai, M; Nomura, O; Maruyama, S; Katsube, Y

1994-06-01

304

Integrated Analysis of Germline and Somatic Variants in Ovarian Cancer  

PubMed Central

We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyze germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2, and PALB2. Additionally, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B, and MLL3). Evidence for loss of heterozygosity was found in 100% and 76% of cases with germline BRCA1 and BRCA2 truncations respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 237 candidate functional germline truncation and missense variants, including 2 pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK, and MLL pathways. PMID:24448499

Kanchi, Krishna L.; Johnson, Kimberly J.; Lu, Charles; McLellan, Michael D.; Leiserson, Mark D.M.; Wendl, Michael C.; Zhang, Qunyuan; Koboldt, Daniel C.; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F.; Wyczalkowski, Matthew A.; Larson, David E.; Schmidt, Heather K.; Miller, Christopher A.; Fulton, Robert S.; Spellman, Paul T.; Mardis, Elaine R.; Druley, Todd E.; Graubert, Timothy A.; Goodfellow, Paul J.; Raphael, Benjamin J.; Wilson, Richard K.; Ding, Li

2014-01-01

305

Exploring the role of exposure frequency in recognizing pronunciation variants  

PubMed Central

Words can be pronounced in multiple ways in casual speech. Corpus analyses of the frequency with which these pronunciation variants occur (e.g., Patterson & Connine, 2001) show that typically, one pronunciation variant tends to predominate; this raises the question of whether variant recognition is aligned with exposure frequency. We explored this issue in words containing one of four phonological contexts, each of which favors one of four surface realizations of word-medial /t/: [t], [?], [?], or a deleted variant. The frequencies of the four realizations in all four contexts were estimated for a set of words in a production experiment. Recognition of all pronunciation variants was then measured in a lexical decision experiment. Overall, the data suggest that listeners are sensitive to variant frequency: Word classification rates closely paralleled production frequency. The exceptions to this were [t] realizations (i.e., canonical pronunciations of the words), a finding which confirms other results in the literature and indicates that factors other than exposure frequency affect word recognition. PMID:21822340

Pitt, Mark A.; Dilley, Laura; Tat, Michael

2010-01-01

306

Homolog-specific PCR primer design for profiling splice variants  

PubMed Central

To study functional diversity of proteins encoded from a single gene, it is important to distinguish the expression levels among the alternatively spliced variants. A variant-specific primer pair is required to amplify each alternatively spliced variant individually. For this purpose, we developed a new feature, homolog-specific primer design (HSPD), in our high-throughput primer and probe design software tool, PRIMEGENS-v2. The algorithm uses a de novo approach to design primers without any prior information of splice variants or close homologs for an input query sequence. It not only designs primer pairs but also finds potential isoforms and homologs of the input sequence. Efficiency of this algorithm was tested for several gene families in soybean. A total of 187 primer pairs were tested under five different abiotic stress conditions with three replications at three time points. Results indicate a high success rate of primer design. Some primer pairs designed were able to amplify all splice variants of a gene. Furthermore, by utilizing combinations within the same multiplex pool, we were able to uniquely amplify a specific variant or duplicate gene. Our method can also be used to design PCR primers to specifically amplify homologs in the same gene family. PRIMEGENS-v2 is available at: http://primegens.org. PMID:21415011

Srivastava, Gyan Prakash; Hanumappa, Mamatha; Kushwaha, Garima; Nguyen, Henry T.; Xu, Dong

2011-01-01

307

Mutation update for GNE gene variants associated with GNE myopathy.  

PubMed

The GNE gene encodes the rate-limiting, bifunctional enzyme of sialic acid biosynthesis, uridine diphosphate-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). Biallelic GNE mutations underlie GNE myopathy, an adult-onset progressive myopathy. GNE myopathy-associated GNE mutations are predominantly missense, resulting in reduced, but not absent, GNE enzyme activities. The exact pathomechanism of GNE myopathy remains unknown, but likely involves aberrant (muscle) sialylation. Here, we summarize 154 reported and novel GNE variants associated with GNE myopathy, including 122 missense, 11 nonsense, 14 insertion/deletions, and seven intronic variants. All variants were deposited in the online GNE variation database (http://www.dmd.nl/nmdb2/home.php?select_db=GNE). We report the predicted effects on protein function of all variants well as the predicted effects on epimerase and/or kinase enzymatic activities of selected variants. By analyzing exome sequence databases, we identified three frequently occurring, unreported GNE missense variants/polymorphisms, important for future sequence interpretations. Based on allele frequencies, we estimate the world-wide prevalence of GNE myopathy to be ?4-21/1,000,000. This previously unrecognized high prevalence confirms suspicions that many patients may escape diagnosis. Awareness among physicians for GNE myopathy is essential for the identification of new patients, which is required for better understanding of the disorder's pathomechanism and for the success of ongoing treatment trials. PMID:24796702

Celeste, Frank V; Vilboux, Thierry; Ciccone, Carla; de Dios, John Karl; Malicdan, May Christine V; Leoyklang, Petcharat; McKew, John C; Gahl, William A; Carrillo-Carrasco, Nuria; Huizing, Marjan

2014-08-01

308

Active Narrow-Band Vibration Isolation of Large Engineering Structures  

NASA Technical Reports Server (NTRS)

We present a narrow-band tracking control method using a variant of the Least Mean Squares (LMS) algorithm to isolate slowly changing periodic disturbances from engineering structures. The advantage of the algorithm is that it has a simple architecture and is relatively easy to implement while it can isolate disturbances on the order of 40-50 dB over decades of frequency band. We also present the results of an experiment conducted on a flexible truss structure. The average disturbance rejection achieved is over 40 dB over the frequency band of 5 Hz to 50 Hz.

Rahman, Zahidul; Spanos, John

1994-01-01

309

Antigenic and genetic characterization of rabies virus isolates from Uruguay.  

PubMed

After 25 years without any reported cases of rabies in Uruguay, the northern region of the country experienced an epizootic of bovine paralytic rabies in October 2007. The outbreak affected bovines and equines, and the main source of infection was the bat Desmodus rotundus, the only hematophagous species in the country. From October 2007 to July 2008, 42 bovine, 3 equine and 120 chiropteran samples were submitted to the National Veterinary Diagnostic Laboratory for rabies testing. A total of 12 samples (7 bovine, 2 equine and 3 from D. rotundus) were positive by the fluorescent antibody test, and viruses were isolated by the mouse inoculation test. The objective of this study was to compare the antigenic and genetic characteristics of these isolates and three isolates from insectivorous bats from other regions. Antigenic typing using a panel of eight monoclonal antibodies identified all 12 viruses as variant 3 (AgV3), a variant associated with D. rotundus. Two isolates from insectivorous bats (Tadarida brasiliensis and Molossus sp.) were characterized as antigenic variant 4 (AgV4) while the third, from Myotis sp., could not be characterized using this panel as its reactivity pattern did not match that of any of the known antigenic variants. Partial N-gene sequences (nt 149-1420) of these isolates were aligned with homologous sequences derived from GenBank by the CLUSTAL/W method and used to build a neighbor-joining distance tree with the Kimura 2-parameter model. All 12 isolates were genetically grouped into the D. rotundus cluster as they shared 100% identity. In the phylogenetic analysis, the three isolates from insectivorous bats segregated into three clusters: one related to T. brasiliensis, one to Myotis sp. and the other to Lasiurus sp., although the isolate associated with the latter came from a Molossus sp. specimen. These results indicate that AgV3 was associated with the outbreak of bovine paralytic rabies in Uruguay. This is the first report of rabies virus having been detected in non-hematophagous bats in this country. PMID:23318595

Guarino, Helena; Castilho, Juliana Galera; Souto, Juanita; Oliveira, Rafael de Novaes; Carrieri, Maria Luiza; Kotait, Ivanete

2013-05-01

310

Fitness of Isogenic Colony Morphology Variants of Pseudomonas aeruginosa in Murine Airway Infection  

PubMed Central

Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called ‘dissociative behaviour’. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of–function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1% of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our discordant findings of mutant phenotypes in P. aeruginosa strains PAO1, PA14 and TBCF10839, we conclude that the current focus on few reference strains may miss modes of niche adaptation and dissociative behaviour that are relevant for the microevolution of complex traits in the wild. PMID:18301762

Rakhimova, Elza; Munder, Antje; Wiehlmann, Lutz; Bredenbruch, Florian; Tummler, Burkhard

2008-01-01

311

Engineering human interleukin-6 to obtain variants with strongly enhanced bioactivity.  

PubMed Central

Interleukin-6 (IL-6) triggers the formation of a high affinity receptor complex with the ligand binding subunit IL-6Ralpha and the signal transducing chain gp130. Since the intracytoplasmic region of the IL-6Ralpha does not contribute to signaling, soluble forms of the extracytoplasmic domain (sIL-6Ralpha), potentiate IL-6 bioactivity and induce a cytokine-responsive status in cells expressing gp130 only. This observation, together with the detection of high levels of circulating soluble human IL-6Ralpha (shIL-6Ralpha) in sera, suggests that the hIL-6-shIL-6Ralpha complex is an alternative form of the cytokine. Here we describe the generation of human IL-6 (hIL-6) variants with strongly enhanced shIL-6Ralpha binding activity and bioactivity. Homology modeling and site-directed mutagenesis of hIL-6 suggested that the binding interface for hIL-6Ralpha is constituted by the C-terminal portion of the D-helix and residues contained in the AB loop. Four libraries of hIL-6 mutants were generated by each time fully randomizing four different amino acids in the predicted AB loop. These libraries were displayed monovalently on filamentous phage surface and sorted separately for binding to immobilized shIL-6Ralpha. Mutants were selected which, when expressed as soluble proteins, showed a 10- to 40-fold improvement in shIL-6Ralpha binding; a further increase (up to 70-fold) was achieved by combining variants isolated from different libraries. Interestingly, high affinity hIL-6 variants show strongly enhanced bioactivity on cells expressing gp13O in the presence of shIL-6Ralpha at concentrations similar to those normally found in human sera. Images PMID:8654370

Toniatti, C; Cabibbo, A; Sporena, E; Salvati, A L; Cerretani, M; Serafini, S; Lahm, A; Cortese, R; Ciliberto, G

1996-01-01

312

Mapping Genetic Variants Underlying Differences in the Central Nitrogen Metabolism in Fermenter Yeasts  

PubMed Central

Different populations within a species represent a rich reservoir of allelic variants, corresponding to an evolutionary signature of withstood environmental constraints. Saccharomyces cerevisiae strains are widely utilised in the fermentation of different kinds of alcoholic beverages, such as, wine and sake, each of them derived from must with distinct nutrient composition. Importantly, adequate nitrogen levels in the medium are essential for the fermentation process, however, a comprehensive understanding of the genetic variants determining variation in nitrogen consumption is lacking. Here, we assessed the genetic factors underlying variation in nitrogen consumption in a segregating population derived from a cross between two main fermenter yeasts, a Wine/European and a Sake isolate. By linkage analysis we identified 18 main effect QTLs for ammonium and amino acids sources. Interestingly, majority of QTLs were involved in more than a single trait, grouped based on amino acid structure and indicating high levels of pleiotropy across nitrogen sources, in agreement with the observed patterns of phenotypic co-variation. Accordingly, we performed reciprocal hemizygosity analysis validating an effect for three genes, GLT1, ASI1 and AGP1. Furthermore, we detected a widespread pleiotropic effect on these genes, with AGP1 affecting seven amino acids and nine in the case of GLT1 and ASI1. Based on sequence and comparative analysis, candidate causative mutations within these genes were also predicted. Altogether, the identification of these variants demonstrate how Sake and Wine/European genetic backgrounds differentially consume nitrogen sources, in part explaining independently evolved preferences for nitrogen assimilation and representing a niche of genetic diversity for the implementation of practical approaches towards more efficient strains for nitrogen metabolism. PMID:24466135

Garcia, Veronica; Salinas, Francisco; Aguilera, Omayra; Liti, Gianni; Martinez, Claudio

2014-01-01

313

Identifying Mendelian disease genes with the Variant Effect Scoring Tool  

PubMed Central

Background Whole exome sequencing studies identify hundreds to thousands of rare protein coding variants of ambiguous significance for human health. Computational tools are needed to accelerate the identification of specific variants and genes that contribute to human disease. Results We have developed the Variant Effect Scoring Tool (VEST), a supervised machine learning-based classifier, to prioritize rare missense variants with likely involvement in human disease. The VEST classifier training set comprised ~ 45,000 disease mutations from the latest Human Gene Mutation Database release and another ~45,000 high frequency (allele frequency >1%) putatively neutral missense variants from the Exome Sequencing Project. VEST outperforms some of the most popular methods for prioritizing missense variants in carefully designed holdout benchmarking experiments (VEST ROC AUC = 0.91, PolyPhen2 ROC AUC = 0.86, SIFT4.0 ROC AUC = 0.84). VEST estimates variant score p-values against a null distribution of VEST scores for neutral variants not included in the VEST training set. These p-values can be aggregated at the gene level across multiple disease exomes to rank genes for probable disease involvement. We tested the ability of an aggregate VEST gene score to identify candidate Mendelian disease genes, based on whole-exome sequencing of a small number of disease cases. We used whole-exome data for two Mendelian disorders for which the causal gene is known. Considering only genes that contained variants in all cases, the VEST gene score ranked dihydroorotate dehydrogenase (DHODH) number 2 of 2253 genes in four cases of Miller syndrome, and myosin-3 (MYH3) number 2 of 2313 genes in three cases of Freeman Sheldon syndrome. Conclusions Our results demonstrate the potential power gain of aggregating bioinformatics variant scores into gene-level scores and the general utility of bioinformatics in assisting the search for disease genes in large-scale exome sequencing studies. VEST is available as a stand-alone software package at http://wiki.chasmsoftware.org and is hosted by the CRAVAT web server at http://www.cravat.us PMID:23819870

2013-01-01

314

Amino Acid Changes in Disease-Associated Variants Differ Radically from Variants Observed in the 1000 Genomes Project Dataset  

PubMed Central

The 1000 Genomes Project data provides a natural background dataset for amino acid germline mutations in humans. Since the direction of mutation is known, the amino acid exchange matrix generated from the observed nucleotide variants is asymmetric and the mutabilities of the different amino acids are very different. These differences predominantly reflect preferences for nucleotide mutations in the DNA (especially the high mutation rate of the CpG dinucleotide, which makes arginine mutability very much higher than other amino acids) rather than selection imposed by protein structure constraints, although there is evidence for the latter as well. The variants occur predominantly on the surface of proteins (82%), with a slight preference for sites which are more exposed and less well conserved than random. Mutations to functional residues occur about half as often as expected by chance. The disease-associated amino acid variant distributions in OMIM are radically different from those expected on the basis of the 1000 Genomes dataset. The disease-associated variants preferentially occur in more conserved sites, compared to 1000 Genomes mutations. Many of the amino acid exchange profiles appear to exhibit an anti-correlation, with common exchanges in one dataset being rare in the other. Disease-associated variants exhibit more extreme differences in amino acid size and hydrophobicity. More modelling of the mutational processes at the nucleotide level is needed, but these observations should contribute to an improved prediction of the effects of specific variants in humans. PMID:24348229

de Beer, Tjaart A. P.; Laskowski, Roman A.; Parks, Sarah L.; Sipos, Botond; Goldman, Nick; Thornton, Janet M.

2013-01-01

315

Soluble Variants of Human Recombinant Glutaminyl Cyclase  

PubMed Central

Recombinant human Glutaminyl Cyclase expressed in E. coli is produced as inclusion bodies. Lack of glycosylation is the main origin of its accumulation in insoluble aggregates. Mutation of single isolated hydrophobic amino acids into negative amino acids was not able to circumvent inclusion bodies formation. On the contrary, substitution with carboxyl-terminal residues of two or three aromatic residues belonging to extended hydrophobic patches on the protein surface provided soluble but still active forms of the protein. These mutants could be expressed in isotopically enriched forms for NMR studies and the maximal attainable concentration was sufficient for the acquisition of 1H-15N HSQC spectra that represent the starting point for future drug development projects targeting Alzheimer’s disease. PMID:23977104

Castaldo, Cristiana; Ciambellotti, Silvia; de Pablo-Latorre, Raquel; Lalli, Daniela; Porcari, Valentina; Turano, Paola

2013-01-01

316

First report of a variant bovine papillomavirus type 2 (BPV-2) in cattle in the Iberian Peninsula.  

PubMed

Infections caused by bovine papillomavirus (BPV) have been described worldwide. Some types, like BPV-1 and BPV-2, have been reported in association with skin warts and fibropapillomas in cattle and sarcoids in equids. In this study we have investigated the presence of BPV in cutaneous warts isolated from a steer in Spain. Cutaneous fibropapillomatosis was confirmed by histopathological analysis. Complete genome was amplified by multiple-primed rolling circle and the L1, E5 and E6 genes were sequenced. The isolate was classified as a variant of BPV-2 on the basis of the L1 gene sequences. Genetic variability of L1, E5 and E6 genes was compared with BPV-2 isolates from different hosts in several continents. Some mutations involved non-synonymous substitutions when compared to the prototype strain. One of these non-conservative mutations was located in the jelly roll ?-barrel of the EF loop of the capsid protein (encoded by L1). This study presents the first report of a variant of BPV-2 infection in the Iberian Peninsula and contributes to extend the knowledge of the spreading and circulation of BPV. PMID:25273965

Escudero, Clara; Vázquez, Rocío; Doménech, Ana; Gómez-Lucía, Esperanza; Benítez, Laura

2014-09-30

317

Insight into the complex genetic network of tetraploid Atlantic salmon (Salmo salar L.): description of multiple novel Pax-7 splice variants.  

PubMed

Paired box transcription factor 7 (Pax-7) cDNA was isolated from the skeletal muscle and brain of alevin and adult stages of Atlantic salmon, identifying 10 variants categorised as novel or established insertions (ins) or deletions (del). Two putative Pax-7 paralogs were identified (denoted Pax-7alpha and Pax-7beta) on the basis of the length and sequences of intron 3 (218 and 248 bp) and versions of ins1 and ins2. Pax-7beta contained a threonine variant of ins1 (GQY[T]GPEYVYCGT), and a shortened variant of ins2 (GEAS). Pattern identification revealed the threonine variant of ins1 includes a potential phosphorylation site (casein kinase II). Thus, the tetraploid Atlantic salmon genome appears to contain at least two putative copies and multiple splice variants of Pax-7. In situ hybridisation localised Pax-7 to mononuclear cells in the fast muscle of adult Atlantic salmon, while quantitative real-time PCR showed Pax-7alpha to be more highly expressed in brain than in skeletal muscle. PMID:16567062

Gotensparre, Susan M; Andersson, Eva; Wargelius, Anna; Hansen, Tom; Johnston, Ian A

2006-05-24

318

DECIPHER: web-based, community resource for clinical interpretation of rare variants in developmental disorders  

PubMed Central

Patients with developmental disorders often harbour sub-microscopic deletions or duplications that lead to a disruption of normal gene expression or perturbation in the copy number of dosage-sensitive genes. Clinical interpretation for such patients in isolation is hindered by the rarity and novelty of such disorders. The DECIPHER project (https://decipher.sanger.ac.uk) was established in 2004 as an accessible online repository of genomic and associated phenotypic data with the primary goal of aiding the clinical interpretation of rare copy-number variants (CNVs). DECIPHER integrates information from a variety of bioinformatics resources and uses visualization tools to identify potential disease genes within a CNV. A two-tier access system permits clinicians and clinical scientists to maintain confidential linked anonymous records of phenotypes and CNVs for their patients that, with informed consent, can subsequently be shared with the wider clinical genetics and research communities. Advances in next-generation sequencing technologies are making it practical and affordable to sequence the whole exome/genome of patients who display features suggestive of a genetic disorder. This approach enables the identification of smaller intragenic mutations including single-nucleotide variants that are not accessible even with high-resolution genomic array analysis. This article briefly summarizes the current status and achievements of the DECIPHER project and looks ahead to the opportunities and challenges of jointly analysing structural and sequence variation in the human genome. PMID:22962312

Swaminathan, Ganesh J.; Bragin, Eugene; Chatzimichali, Eleni A.; Corpas, Manuel; Bevan, A. Paul; Wright, Caroline F.; Carter, Nigel P.; Hurles, Matthew E.; Firth, Helen V.

2012-01-01

319

Homonuclear 1H NMR and circular dichroism study of the HIV-1 Tat Eli variant  

PubMed Central

Background The HIV-1 Tat protein is a promising target to develop AIDS therapies, particularly vaccines, due to its extracellular role that protects HIV-1-infected cells from the immune system. Tat exists in two different lengths, 86 or 87 residues and 99 or 101 residues, with the long form being predominant in clinical isolates. We report here a structural study of the 99 residue Tat Eli variant using 2D liquid-state NMR, molecular modeling and circular dichroism. Results Tat Eli was obtained from solid-phase peptide synthesis and the purified protein was proven biologically active in a trans-activation assay. Circular dichroism spectra at different temperatures up to 70°C showed that Tat Eli is not a random coil at 20°C. Homonuclear 1H NMR spectra allowed us to identify 1639 NMR distance constraints out of which 264 were interresidual. Molecular modeling satisfying at least 1474 NMR constraints revealed the same folding for different model structures. The Tat Eli model has a core region composed of a part of the N-terminus including the highly conserved Trp 11. The extra residues in the Tat Eli C-terminus protrude from a groove between the basic region and the cysteine-rich region and are well exposed to the solvent. Conclusion We show that active Tat variants share a similar folding pattern whatever their size, but mutations induce local structural changes. PMID:18808674

Watkins, Jennifer D; Campbell, Grant R; Halimi, Hubert; Loret, Erwann P

2008-01-01

320

New V. cholerae atypical El Tor variant emerged during the 2006 epidemic outbreak in Angola  

PubMed Central

Background V. cholerae is the etiological agent of cholera, a major public health concern in most developing countries. Virulence of V. cholerae relies on the powerful cholera toxin, encoded by the CTX prophage. The emergence of new pathogenic variants in the recent years has been mostly associated with new CTX prophage rearrangements. Results In this retrospective study, we show that the epidemic V. cholerae O1 El Tor strain responsible for the 2006 outbreak in Angola is clonally and genetically different from El Tor strains circulating in the 1990s in the same area. Strains from 2006 carry ICEVchAng3 of the SXT/R391 family. This ICE is associated with a narrower multidrug resistance profile compared to the one conferred by plasmid p3iANG to strains of the 1990s. The CTX prophage carried by 2006 El Tor strains is characterized by rstRET and ctxBCla alleles organized in a RS1-RS2-Core array on chromosome I. Interestingly, the newly emerging atypical strain belongs to a clade previously known to comprise only clinical isolates from the Indian subcontinent that also contain the same ICE of the SXT/R391 family. Conclusions Our findings remark the appearance of a novel V. cholerae epidemic variant in Africa with a new CTX? arrangement previously described only in the Indian Subcontinent. PMID:21668969

2011-01-01

321

Gene activation and re-expression of a Trypanosoma brucei variant surface glycoprotein.  

PubMed Central

The expression of the Trypanosoma brucei variant surface glycoprotein AnTat 1.1 proceeds by a mechanism that transfers a duplicated gene copy into a new genomic environment, the so-called expression site, where it will be expressed. We have isolated a genomic fragment containing the region spanning the expression site-transposon junction, and the 5' half of the coding sequence. Comparing this DNA segment with its template copy (basic copy) allowed us to identify the exact breaking point and indicated a base sequence which could be involved in initiating the transposition event. Sequencing data also indicated that the co-transposed segment 5' to the coding sequence is 430 bp in length. The extreme 5' end of the mRNA is derived from a region in the expression site not immediately adjacent to the transposed DNA segment. This particular sequence exists in multiple copies in the genome and is common to the mRNA of all variant surface glycoproteins so far analysed. Images Fig. 1. Fig. 5. PMID:6313354

Michiels, F; Matthyssens, G; Kronenberger, P; Pays, E; Dero, B; Van Assel, S; Darville, M; Carvador, A; Steinert, M; Hamers, R

1983-01-01

322

The hutterite variant of Treacher Collins syndrome: a 28-year-old story solved.  

PubMed

Treacher Collins syndrome (TCS), the best known form of mandibulofacial dysostosis (MFD) comprises a recognizable pattern of anomalies. In 1985, Lowry et al. reported on two Hutterite sisters born to apparently unaffected parents with TCS, raising the possibility of an autosomal recessive (AR) variant of TCS, subsequently given a unique Mendelian Inheritance of Man (MIM) number (248390). Recently, biallelic mutations in POLR1C were found in TCS patients, confirming AR TCS as a distinct entity. The Hutterites, an endogamous Anabaptist group, like other genetically isolated populations, provide a powerful resource for mapping AR disorders. We elected to study the molecular basis of TCS in the Hutterite population including the original kindred described in 1985, and another unrelated Hutterite patient. Prior to starting this study, a TCOF1 mutation had apparently been excluded in the original family at two outside institutions. We hypothesized that an AR variant of TCS was present in the three Hutterite patients, but homozygosity mapping did not show convincing evidence of shared regions between the affected individuals. TCOF1 analysis was undertaken and mutations were found in the three affected patients and an unaffected parent. These data show that the initial Hutterite family reported with AR TCS in fact has classic TCS due to a TCOF1 mutation, despite recent data confirming the existence of AR TCS in other populations. These results have significant counseling implications for the affected families in the Hutterite population and in the population at large. © 2013 Wiley Periodicals, Inc. PMID:24108658

Caluseriu, Oana; Lowry, Brian R; McLeod, Ross; Lamont, Ryan; Parboosingh, Jillian S; Bernier, Francois P; Innes, A Micheil

2013-11-01

323

Diverse Functional Properties of Wilson Disease ATP7B Variants  

PubMed Central

BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

Huster, Dominik; Kuhne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mossner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

2012-01-01

324

Functionally Significant, Rare Transcription Factor Variants in Tetralogy of Fallot  

PubMed Central

Objective Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF). Methods and Results We sequenced the coding, 5?UTR, and 3?UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1) in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network. Significance This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3–13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease. PMID:25093829

Topf, Ana; Griffin, Helen R.; Glen, Elise; Soemedi, Rachel; Brown, Danielle L.; Hall, Darroch; Rahman, Thahira J.; Eloranta, Jyrki J.; Jungst, Christoph; Stuart, A. Graham; O'Sullivan, John; Keavney, Bernard D.; Goodship, Judith A.

2014-01-01

325

Likelihood ratio tests in rare variant detection for continuous phenotypes.  

PubMed

It is believed that rare variants play an important role in human phenotypes; however, the detection of rare variants is extremely challenging due to their very low minor allele frequency. In this paper, the likelihood ratio test (LRT) and restricted likelihood ratio test (ReLRT) are proposed to test the association of rare variants based on the linear mixed effects model, where a group of rare variants are treated as random effects. Like the sequence kernel association test (SKAT), a state-of-the-art method for rare variant detection, LRT and ReLRT can effectively overcome the problem of directionality of effect inherent in the burden test in practice. By taking full advantage of the spectral decomposition, exact finite sample null distributions for LRT and ReLRT are obtained by simulation. We perform extensive numerical studies to evaluate the performance of LRT and ReLRT, and compare to the burden test, SKAT and SKAT-O. The simulations have shown that LRT and ReLRT can correctly control the type I error, and the controls are robust to the weights chosen and the number of rare variants under study. LRT and ReLRT behave similarly to the burden test when all the causal rare variants share the same direction of effect, and outperform SKAT across various situations. When both positive and negative effects exist, LRT and ReLRT suffer from few power reductions compared to the other two competing methods; under this case, an additional finding from our simulations is that SKAT-O is no longer the optimal test, and its power is even lower than that of SKAT. The exome sequencing SNP data from Genetic Analysis Workshop 17 were employed to illustrate the proposed methods, and interesting results are described. PMID:25117149

Zeng, Ping; Zhao, Yang; Liu, Jin; Liu, Liya; Zhang, Liwei; Wang, Ting; Huang, Shuiping; Chen, Feng

2014-09-01

326

The identification of mitochondrial DNA variants in glioblastoma multiforme  

PubMed Central

Background Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation. PMID:24383468

2014-01-01

327

An Escherichia coli Expression Assay and Screen for Human Immunodeficiency Virus Protease Variants with Decreased Susceptibility to Indinavir  

PubMed Central

We have developed a recombinant Escherichia coli screening system for the rapid detection and identification of amino acid substitutions in the human immunodeficiency virus (HIV) protease associated with decreased susceptibility to the protease inhibitor indinavir (MK-639; Merck & Co.). The assay depends upon the correct processing of a segment of the HIV-1 HXB2 gag-pol polyprotein followed by detection of HIV reverse transcriptase activity by a highly sensitive, colorimetric enzyme-linked immunosorbent assay. The highly sensitive system detects the contributions of single substitutions such as I84V, L90M, and L63P. The combination of single substitutions further decreases the sensitivity to indinavir. We constructed a library of HIV protease variant genes containing dispersed mutations and, using the E. coli recombinant system, screened for mutants with decreased indinavir sensitivity. The discovered HIV protease variants contain amino acid substitutions commonly associated with indinavir resistance in clinical isolates, including the substitutions L90M, L63P, I64V, V82A, L24I, and I54T. One substitution, W6R, is also frequently found by the screen and has not been reported elsewhere. Of a total of 12,000 isolates that were screened, 12 protease variants with decreased sensitivity to indinavir were found. The L63P substitution, which is also associated with indinavir resistance, increases the stability of the isolated protease relative to that of the native HXB2 protease. The rapidity, sensitivity, and accuracy of this screen also make it useful for screening for novel inhibitors. We have found the approach described here to be useful for the detection of amino acid substitutions in HIV protease that have been associated with drug resistance as well as for the screening of novel compounds for inhibitory activity. PMID:9835523

Melnick, Laurence; Yang, Shiow-Shong; Rossi, Rick; Zepp, Charlie; Heefner, Donald

1998-01-01

328

Reconsidering association testing methods using single-variant test statistics as alternatives to pooling tests for sequence data with rare variants.  

PubMed

Association tests that pool minor alleles into a measure of burden at a locus have been proposed for case-control studies using sequence data containing rare variants. However, such pooling tests are not robust to the inclusion of neutral and protective variants, which can mask the association signal from risk variants. Early studies proposing pooling tests dismissed methods for locus-wide inference using nonnegative single-variant test statistics based on unrealistic comparisons. However, such methods are robust to the inclusion of neutral and protective variants and therefore may be more useful than previously appreciated. In fact, some recently proposed methods derived within different frameworks are equivalent to performing inference on weighted sums of squared single-variant score statistics. In this study, we compared two existing methods for locus-wide inference using nonnegative single-variant test statistics to two widely cited pooling tests under more realistic conditions. We established analytic results for a simple model with one rare risk and one rare neutral variant, which demonstrated that pooling tests were less powerful than even Bonferroni-corrected single-variant tests in most realistic situations. We also performed simulations using variants with realistic minor allele frequency and linkage disequilibrium spectra, disease models with multiple rare risk variants and extensive neutral variation, and varying rates of missing genotypes. In all scenarios considered, existing methods using nonnegative single-variant test statistics had power comparable to or greater than two widely cited pooling tests. Moreover, in disease models with only rare risk variants, an existing method based on the maximum single-variant Cochran-Armitage trend chi-square statistic in the locus had power comparable to or greater than another existing method closely related to some recently proposed methods. We conclude that efficient locus-wide inference using single-variant test statistics should be reconsidered as a useful framework for devising powerful association tests in sequence data with rare variants. PMID:22363423

Kinnamon, Daniel D; Hershberger, Ray E; Martin, Eden R

2012-01-01

329

Expression of growth hormone-releasing hormone (GHRH) and splice variants of GHRH receptors in human experimental prostate cancers  

Microsoft Academic Search

The expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors in LNCaP, MDA-PCa-2b and PC-3 human prostate cancers grown in nude mice was investigated by RT-PCR. The expression of mRNA for GHRH was detected in LNCaP and PC-3, but not in MDA-PCa-2b prostatic carcinoma. RT-PCR analyses of mRNA isolated from LNCaP, MDA-PCa-2b and PC-3 cancers, revealed the

Artur Plonowski; Andrew V Schally; Rebeca Busto; Magdalena Krupa; Jozsef L Varga; Gabor Halmos

2002-01-01

330

Pulmonary medium vessel vasculitis in an 11 year old boy: Hughes Stovin syndrome as a variant of polyarteritis nodosa?  

PubMed Central

We present the case of an 11-year-old boy presenting with haemoptysis, dyspnoea and weight loss as a manifestation of isolated pulmonary vasculitis, leading to pulmonary hypertension. He also appeared to have a longstanding dural venous sinus thrombosis. This rare presentation, especially in childhood, might represent a case of the seldomly reported Hughes-Stovin syndrome. The patient achieved remission after therapy with cyclophosphamide pulses and high-dose steroids. Based on the presented case and review of the literature, we propose that this syndrome might be a variant of polyarteritis nodosa. This report highlights diagnostic issues and describes a successful treatment regimen. PMID:21816089

2011-01-01

331

An intron 9 containing splice variant of PAX2  

PubMed Central

Background PAX2 is a transcription factor with an important role in embryogenic development. However, PAX2 expression was frequently identified in neoplasia responsible for the growth and survival of cancer cells. Due to alternative splicing of exon 6, exon 10 and exon 12 four isoforms of PAX2 are described so far. Methods The expression of an intron 9 containing PAX2 splice variant was analyzed in neoplastic B cell and solid tumor cell lines as well as in primary tumor samples by quantitative RT-PCR. PAX2 proteins were detected by Western Blot in a subset of cell lines. Results All 14 lymphoma cell lines expressed an undescribed PAX2 splice variant containing the entire intron 9 sequence and the exon 10 sequence. This splice variant could also be detected in 35 solid tumor cell lines, in leukemia and lymphoma as well as in colon carcinoma and melanoma patient samples and in blood samples of healthy donors. Expression of this new splice variant on protein level was verified by Western Blot analysis. Conclusion We discovered a previously undescribed intron 9 and exon 10 containing splice variant of PAX2 in B-cell neoplasia and in solid tumors on mRNA and protein level. PMID:19467152

Busse, Antonia; Rietz, Anika; Schwartz, Stefan; Thiel, Eckhard; Keilholz, Ulrich

2009-01-01

332

Expression and Secretion of Defined Cutinase Variants by Aspergillus awamori  

PubMed Central

Several cutinase variants derived by molecular modelling and site-directed mutagenesis of a cutinase gene from Fusarium solani pisi are poorly secreted by Saccharomyces cerevisiae. The majority of these variants are successfully produced by the filamentous fungus Aspergillus awamori. However, the L51S and T179Y mutations caused reductions in the levels of extracellular production of two cutinase variants by A. awamori. Metabolic labelling studies were performed to analyze the bottleneck in enzyme production by the fungus in detail. These studies showed that because of the single L51S substitution, rapid extracellular degradation of cutinase occurred. The T179Y substitution did not result in enhanced sensitivity towards extracellular proteases. Presumably, the delay in the extracellular accumulation of this cutinase variant is caused by the enhanced hydrophobicity of the molecule. Overexpression of the A. awamori gene encoding the chaperone BiP in the cutinase-producing A. awamori strains had no significant effect on the secretion efficiency of the cutinases. A cutinase variant with the amino acid changes G28A, A85F, V184I, A185L, and L189F that was known to aggregate in the endoplasmic reticulum of S. cerevisiae, resulting in low extracellular protein levels, was successfully produced by A. awamori. An initial bottleneck in secretion occurred before or during translocation into the endoplasmic reticulum but was rapidly overcome by the fungus. PMID:9687432

van Gemeren, I. A.; Beijersbergen, A.; van den Hondel, C. A. M. J. J.; Verrips, C. T.

1998-01-01

333

Factor IX variants improve gene therapy efficacy for hemophilia B.  

PubMed

Intramuscular injection of adeno-associated viral (AAV) vector to skeletal muscle of humans with hemophilia B is safe, but higher doses are required to achieve therapeutic factor IX (F.IX) levels. The efficacy of this approach is hampered by the retention of F.IX in muscle extracellular spaces and by the limiting capacity of muscle to synthesize fully active F.IX at high expression rates. To overcome these limitations, we constructed AAV vectors encoding F.IX variants for muscle- or liver-directed expression in hemophilia B mice. Circulating F.IX levels following intramuscular injection of AAV-F.IX-K5A/V10K, a variant with low-affinity to extracellular matrix, were 2-5 fold higher compared with wild-type (WT) F.IX, while the protein-specific activities remained similar. Expression of F.IX-R338A generated a protein with 2- or 6-fold higher specific activity than F.IX-WT following vector delivery to skeletal muscle or liver, respectively. F.IX-WT and variant forms provide effective hemostasis in vivo upon challenge by tail-clipping assay. Importantly, intramuscular injection of AAV-F.IX variants did not trigger antibody formation to F.IX in mice tolerant to F.IX-WT. These studies demonstrate that F.IX variants provide a promising strategy to improve the efficacy for a variety of gene-based therapies for hemophilia B. PMID:15550487

Schuettrumpf, Joerg; Herzog, Roland W; Schlachterman, Alexander; Kaufhold, Antje; Stafford, Darrel W; Arruda, Valder R

2005-03-15

334

MOLECULAR CHARACTERIZATION OF RABIES VIRUS ISOLATES FROM MEXICO: IMPLICATIONS FOR TRANSMISSION DYNAMICS AND HUMAN RISK  

Microsoft Academic Search

Twenty-eight samples from humans and domestic and wild animals collected in Mexico between 1990 and 1995 were characterized by using anti-nucleoprotein monoclonal antibodies and limited sequence analysis of the nucleoprotein gene. The variants of rabies viruses identified in these samples were compared with other isolates from Mexico and the rest of the Americas to establish epidemiologic links between cases and

CECILIA C. DE MATTOS; CARLOS A. DE MATTOS; ELIZABETH LOZA-RUBIO; ALVARO AGUILAR-SETIEN; LILLIAN A. ORCIARI; JEAN S. SMITH

1999-01-01

335

Is Phonological Context Always Used to Recognize Variant Forms in Spoken Word Recognition? The Role of Variant Frequency and Context Distribution  

Microsoft Academic Search

Several mechanisms have been proposed to account for how listeners accommodate regular phonological variation in connected speech. Using a corpus analysis and 5 cross-modal priming experiments, the authors investigate phonological variant recognition for the American English word-final flap. The corpus analysis showed that the flap variant occurs relatively frequently compared with the citation form [t] variant and is only probabilistically

Larissa J. Ranbom; Cynthia M. Connine; Elana M. Yudman

2009-01-01

336

7-O-Malonyl Macrolactin A, a New Macrolactin Antibiotic from Bacillus subtilis Active against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococci, and a Small-Colony Variant of Burkholderia cepacia  

Microsoft Academic Search

We report here the discovery, isolation, and chemical and preliminary biological characterization of a new antibiotic compound, 7-O-malonyl macrolactin A (MMA), produced by a Bacillus subtilis soil isolate. MMA is a bacteriostatic antibiotic that inhibits a number of multidrug-resistant gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and a small-colony variant of Burkholderia cepacia. MMA-treated staphylococci and enterococci were

Magally Romero-Tabarez; Rolf Jansen; Marita Sylla; Heinrich Lunsdorf; Dwi A. Santosa; Kenneth N. Timmis; Gabriella Molinari

2006-01-01

337

Iowa Variant of Familial Alzheimer's Disease  

PubMed Central

Mutations within the amyloid-? (A?) sequence, especially those clustered at residues 21-23, which are linked to early onset familial Alzheimer’s disease (AD), are primarily associated with cerebral amyloid angiopathy (CAA). The basis for this predominant vascular amyloid burden and the differential clinical phenotypes of cerebral hemorrhage/stroke in some patients and dementia in others remain unknown. The A?D23N Iowa mutation is associated with progressive AD-like dementia, often without clinically manifested intracerebral hemorrhage. Neuropathologically, the disease is characterized by predominant preamyloid deposits, severe CAA, and abundant neurofibrillary tangles in the presence of remarkably few mature plaques. Biochemical analyses using a combination of immunoprecipitation, mass spectrometry, amino acid sequence, and Western blot analysis performed after sequential tissue extractions to separately isolate soluble components, preamyloid, and fibrillar amyloid species indicated that the Iowa deposits are complex mixtures of mutated and nonmutated A? molecules. These molecules exhibited various degrees of solubility, were highly heterogeneous at both the N- and C-termini, and showed partial aspartate isomerization at positions 1, 7, and 23. This collection of A? species—the Iowa brain A? peptidome—contained clear imprints of amyloid clearance mechanisms yet highlighted the unique neuropathological features shared by a non-A? cerebral amyloidosis, familial Danish dementia, in which neurofibrillary tangles coexist with extensive pre-amyloid deposition in the virtual absence of fibrillar lesions. These data therefore challenge the importance of neuritic plaques as the sole contributors for the development of dementia. PMID:20228223

Tomidokoro, Yasushi; Rostagno, Agueda; Neubert, Thomas A.; Lu, Yun; Rebeck, G. William; Frangione, Blas; Greenberg, Steven M.; Ghiso, Jorge

2010-01-01

338

Characterization of Pratylenchus penetrans from Ten Geographically Isolated Populations Based on Their Reaction on Potato.  

PubMed

Single female cuhures of Pratylenchus penetrans were established from soil and root samples collected from 10 geographically isolated locations in North America. The resultant isolates were used to evaluate nematode egression from and multiplication on roots of potato clones to distinguish intraspecific differences among isolates. The 10 nematode isolates were statistically separated into four groups based on percentage of nematodes that egressed from the P. penetrans-resistant potato done L 118-2. The Cornell (CR), Wisconsin (WI), Long Island (LI), and Adirondack (AD) isolates, selected as representative isolates of each of the four groups, exhibited 53%, 39%, 25%, and 10% egression from L118-2, respectively. Reproduction of these four isolates was measured on three potato cultivars (Russet Burbank, Butte, and Hudson) and two breeding lines (NY85 and L118-2). The LI and AD isolates reproduced well on all five potato clones. The CR isolate reproduced well on Russet Burbank and NY85 but significantly less on Butte, Hudson, and L118-2. Reproduction of the WI isolate was less than the LI and AD isolates but more than the CR isolate on all potato clones tested except Russet Burbank. Reproduction of the WI isolate on Russet Burbank was less than the other three isolates. Based on these results, four distinct intraspecific variants of P. penetrans are proposed: Cornell, Wisconsin, Long Island, and Adirondack. PMID:19277170

France, R A; Brodie, B B

1996-12-01

339

Alternative Splicing of the Cardiac Sodium Channel Creates Multiple Variants of Mutant T1620K Channels  

PubMed Central

Alternative splicing creates several Nav1.5 transcripts in the mammalian myocardium and in various other tissues including brain, dorsal root ganglia, breast cancer cells as well as neuronal stem cell lines. In total nine Nav1.5 splice variants have been discovered. Four of them, namely Nav1.5a, Nav1.5c, Nav1.5d, and Nav1.5e, generate functional channels in heterologous expression systems. The significance of alternatively spliced transcripts for cardiac excitation, in particular their role in SCN5A channelopathies, is less well understood. In the present study, we systematically investigated electrophysiological properties of mutant T1620K channels in the background of all known functional Nav1.5 splice variants in HEK293 cells. This mutation has been previously associated with two distinct cardiac excitation disorders: with long QT syndrome type 3 (LQT3) and isolated cardiac conduction disease (CCD). When investigating the effect of the T1620K mutation, we noticed similar channel defects in the background of hNav1.5, hNav1.5a, and hNav1.5c. In contrast, the hNav1.5d background produced differential effects: In the mutant channel, some gain-of-function features did not emerge, whereas loss-of-function became more pronounced. In case of hNav1.5e, the neonatal variant of hNav1.5, both the splice variant itself as well as the corresponding mutant channel showed electrophysiological properties that were distinct from the wild-type and mutant reference channels, hNav1.5 and T1620K, respectively. In conclusion, our data show that alternative splicing is a mechanism capable of generating a variety of functionally distinct wild-type and mutant hNav1.5 channels. Thus, the cellular splicing machinery is a potential player affecting genotype-phenotype correlations in SCN5A channelopathies. PMID:21552533

Walzik, Stefan; Schroeter, Annett; Benndorf, Klaus; Zimmer, Thomas

2011-01-01

340

Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV1 envelope glycoprotein variants from patients with AIDS  

Microsoft Academic Search

BACKGROUND: CCR5-restricted (R5) human immunodeficiency virus type 1 (HIV-1) variants cause CD4+ T-cell loss in the majority of individuals who progress to AIDS, but mechanisms underlying the pathogenicity of R5 strains are poorly understood. To better understand envelope glycoprotein (Env) determinants contributing to pathogenicity of R5 viruses, we characterized 37 full-length R5 Envs from cross-sectional and longitudinal R5 viruses isolated

Jasminka Sterjovski; Melissa J Churchill; Anne Ellett; Lachlan R Gray; Michael J Roche; Rebecca L Dunfee; Damian FJ Purcell; Nitin Saksena; Bin Wang; Secondo Sonza; Steven L Wesselingh; Ingrid Karlsson; Eva-Maria Fenyo; Dana Gabuzda; Anthony L Cunningham; Paul R Gorry

2007-01-01

341

Coexpression of MDR-associated markers, including P-170, MRP and LRP and cytoskeletal proteins, in three resistant variants of the human ovarian carcinoma cell line, OAW42  

Microsoft Academic Search

Variants of the human ovarian carcinoma cell line, OAW42, exhibiting low-level intrinsic resistance (OAW42-SR) and drug-induced higher-level resistance (OAW42-A1 & OAW42-A), were studied along with a sensitive clonal population (OAW42-S) which was isolated from OAW42-SR. Expression of the MDR-associated protein P-170, the more recently discovered LRP (lung resistance-related protein) and MRP (multidrug resistance-associated protein), topoisomerase Hoc and ?, GST? and

E. Moran; I. Cleary; A. M. Larkin; R. Nic Amhlaoibh; A. Masterson; R. J. Scheper; M. A. Izquierdo; F. O'Sullivan; M. Clynes

1997-01-01

342

Two genetic variants of the crustacean hyperglycemic hormone (CHH) from the Australian crayfish, Cherax destructor: detection of chiral isoforms due to posttranslational modification  

Microsoft Academic Search

From sinus glands of the Australian crayfish Cherax destructor, two genetic variants of the crustacean hyperglycemic hormone (CHH) were isolated by HPLC and fully characterized by mass spectrometry and Edman sequencing. Both CHH A (8350.38Da) and CHH B (8370.34Da) consist of 72 amino acid residues, with pyroGlu as N-terminus and an amidated (Val-NH2) C-terminus. They differ in 14 residues (81%

Patrick Bulau; Iris Meisen; Barbara Reichwein-Roderburg; Jasna Peter-Katalini?; Rainer Keller

2003-01-01

343

Mycosis fungoides: an updated review of clinicopathologic variants.  

PubMed

: Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. Although it was first described in 1833, our understanding of this disease has continued to evolve. From a diagnostic perspective, the diagnosis of MF can be challenging particularly in the early stages of the disease, because of overlap between the histological features of early MF lesions and many other inflammatory dermatoses. Furthermore, there has been an emergence of numerous clinicopathologic and immunohistochemical variants of MF reported in the literature. Although the prognostic significance of some of the rare variants is still not fully understood, certain variants, such as folliculotropic and bullous MF, have demonstrated less indolent clinical courses compared with classic MF and necessitate aggressive therapeutic measures. Thus, it is important for dermatologists and dermatopathologists to be knowledgeable of the widely varied clinical, histological, and immunohistochemical presentations of MF to arrive at a prompt and accurate diagnosis and initiate appropriate treatment. PMID:25415138

Ahn, Christine S; ALSayyah, Ahmed; Sangüeza, Omar P

2014-12-01

344

Dandy-Walker variant in Coffin-Siris syndrome.  

PubMed

We describe a five-month-old male infant with Coffin-Siris syndrome, the so-called Dandy-Walker variant (hypoplasia of the cerebellar vermis with cystic dilatation of the fourth ventricle, but without enlargement of the posterior fossa), and partial agenesis of the corpus callosum. Dandy-Walker malformation and mega cisterna magna, but not Dandy-Walker variant, have been reported in Coffin-Siris syndrome. The presence of Dandy-Walker variant in the infant we described confirms that the full continuum of the Dandy-Walker complex can occur in Coffin-Siris syndrome. The yet unidentified gene(s) for the syndrome may be related to the development of the hindbrain. PMID:11298377

Imai, T; Hattori, H; Miyazaki, M; Higuchi, Y; Adachi, S; Nakahata, T

2001-04-22

345

Time-variant 1D photonic crystals using flowing microdroplets.  

PubMed

In this paper we propose a time-variant photonic crystal, which can be formed by a stream of wave-length-scale microdroplets flowing through a microfluidic channel. The functionality stems from the photonic bandgap generated from the 1D periodic perturbation of refractive index. The periodicity, volume fraction and composition of both the dispersed and the continuous phases can be conveniently tuned in real time by hydrodynamic or pneumatic methods. By simulation, it is found that the time-variant nature of the proposed structure can induce an abnormal energy evolution, which is distinct from any existing photonic crystal structures. As a basic component for optofluidic systems, the droplet-based photonic crystal may find potential applications in light modulation and light confinement, and could be an ideal model for pursuing physical insights into time-variant optofluidic systems. PMID:23187195

Chen, Zefeng; Yong, Zehui; Leung, Chi Wah; Zhang, Xuming; Chen, Yihang; Chan, Helen L W; Wang, Yu

2012-10-22

346

Engineering unnatural variants of plantazolicin through codon reprogramming  

PubMed Central

Plantazolicin (PZN) is a polyheterocyclic natural product derived from a ribosomal peptide that harbors remarkable antibiotic selectivity for the causative agent of anthrax, Bacillus anthracis. To simultaneously establish the structure-activity relationship of PZN and the substrate tolerance of the biosynthetic pathway, an Escherichia coli expression strain was engineered to heterologously produce PZN analogs. Variant PZN precursor genes were produced by site-directed mutagenesis and later screened by mass spectrometry to assess posttranslational modification and export by E. coli. From a screen of 72 precursor peptides, 29 PZN variants were detected. This analog collection provided insight into the selectivity of the posttranslational modifying enzymes and established the boundaries of the natural biosynthetic pathway. Unlike other studied thiazole/oxazole-modified microcins, the biosynthetic machinery appeared to be finely tuned towards the production of PZN, such that the cognate enzymes did not process even other naturally occurring sequences from similar biosynthetic clusters. The modifying enzymes were exquisitely selective, installing heterocycles only at pre-defined positions within the precursor peptides while leaving neighboring residues unmodified. Nearly all substitutions at positions normally harboring heterocycles prevented maturation of a PZN variant, though some exceptions were successfully produced lacking a heterocycle at the penultimate residue. No variants containing additional heterocycles were detected, although several peptide sequences yielded multiple PZN variants as a result of varying oxidation states of select residues. Eleven PZN variants were produced in sufficient quantity to facilitate purification and assessment of their antibacterial activity, providing insight into the structure-activity relationship of PZN. PMID:23823732

Deane, Caitlin D.; Melby, Joel O.; Molohon, Katie J.; Susarrey, Aziz R.; Mitchell, Douglas A.

2013-01-01

347

Classification of BRCA1 missense variants of unknown clinical significance  

PubMed Central

Background: BRCA1 is a tumour suppressor with pleiotropic actions. Germline mutations in BRCA1 are responsible for a large proportion of breast–ovarian cancer families. Several missense variants have been identified throughout the gene but because of lack of information about their impact on the function of BRCA1, predictive testing is not always informative. Classification of missense variants into deleterious/high risk or neutral/low clinical significance is essential to identify individuals at risk. Objective: To investigate a panel of missense variants. Methods and results: The panel was investigated in a comprehensive framework that included (1) a functional assay based on transcription activation; (2) segregation analysis and a method of using incomplete pedigree data to calculate the odds of causality; (3) a method based on interspecific sequence variation. It was shown that the transcriptional activation assay could be used as a test to characterise mutations in the carboxy-terminus region of BRCA1 encompassing residues 1396–1863. Thirteen missense variants (H1402Y, L1407P, H1421Y, S1512I, M1628T, M1628V, T1685I, G1706A, T1720A, A1752P, G1788V, V1809F, and W1837R) were specifically investigated. Conclusions: While individual classification schemes for BRCA1 alleles still present limitations, a combination of several methods provides a more powerful way of identifying variants that are causally linked to a high risk of breast and ovarian cancer. The framework presented here brings these variants nearer to clinical applicability. PMID:15689452

Phelan, C; Dapic, V; Tice, B; Favis, R; Kwan, E; Barany, F; Manoukian, S; Radice, P; van der Luijt, R B; van Nesselrooij, B P M; Chenevix-Trench, G; kConFab; Caldes, T; de La Hoya, M; Lindquist, S; Tavtigian, S; Goldgar, D; Borg, A; Narod, S; Monteiro, A

2005-01-01

348

FHL2 expression and variants in hypertrophic cardiomyopathy.  

PubMed

Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated ?-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM. PMID:25358972

Friedrich, Felix W; Reischmann, Silke; Schwalm, Aileen; Unger, Andreas; Ramanujam, Deepak; Münch, Julia; Müller, Oliver J; Hengstenberg, Christian; Galve, Enrique; Charron, Philippe; Linke, Wolfgang A; Engelhardt, Stefan; Patten, Monica; Richard, Pascale; van der Velden, Jolanda; Eschenhagen, Thomas; Isnard, Richard; Carrier, Lucie

2014-11-01

349

A novel splice variant of the transcription factor Nrf1 interacts with the TNFalpha promoter and stimulates transcription.  

PubMed Central

Common signaling chains of various receptor families, despite some similarities, are able to provoke quite different cellular responses. This suggests that they are linked to different cascades and transcription factors, dependent on the context of the ligand binding moiety and the cell type. The ITAM (immunoreceptor tyrosine-based activation motif) containing gamma chain of the FcepsilonRI, FcgammaRI, FcgammaRIII and the T-cell receptor is one of these shared signaling molecules. Here, we show that in the context of the FcgammaRIII, the gamma chain activates the transcription factor Nrf1 or a closely related protein that specifically interacts with the extended kappa3 site in the TNFalpha promoter. A novel splice variant of Nrf1 with a 411 bp deletion of the serine-rich region, resulting in an overall structure reminiscent of the BTB and CNC homology (Bach) proteins, was isolated from the corresponding DC18 cells. In a gel shift analysis, this bacterially expressed splice variant binds to the TNFalpha promoter site after in vitro phosphorylation by casein kinase II (CKII). In addition, cotransfection studies demonstrate that this splice variant mediates induced transcription at the TNFalpha promoter after stimulation/activation in a heterologous system. PMID:9580677

Prieschl, E E; Novotny, V; Csonga, R; Jaksche, D; Elbe-Burger, A; Thumb, W; Auer, M; Stingl, G; Baumruker, T

1998-01-01

350

CYP2C9 Allelic Variants and Frequencies in a Pediatric Sickle Cell Disease Cohort: Implications for NSAIDs Pharmacotherapy.  

PubMed

Nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism-PCR assays and the Tag-It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate-specific effects of variant alleles common in populations with genetic susceptibility to SCD. PMID:24889181

Jaja, Cheedy; Patel, Niren; Scott, Stuart A; Gibson, Robert; Kutlar, Abdullah

2014-10-01

351

Functional gene variants of CYP3A4.  

PubMed

Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more drugs in clinical use than any other foreign compound-metabolizing enzyme in humans. Recently, increasing evidence has been found showing that variants in the CYP3A4 gene have functional significance and--in rare cases--lead to loss of activity, implying tremendous consequences for patients. This review article highlights the functional consequences of all CYP3A4 variants recognized by the Human Cytochrome P450 (CYP) Allele Nomenclature Database. PMID:24926778

Werk, A N; Cascorbi, I

2014-09-01

352

Crystallographic variant selection in {alpha}-{beta} brass  

SciTech Connect

The transformation texture of {alpha}/{beta} brass with a diffusional Widmanstaetten {alpha} growth morphology has been investigated. Electron micrographs and electron backscattered diffraction was used to determine that the orientation relationship between the {beta} phase and the {alpha} associated with nucleation at {beta} grain boundaries was 44.3 deg <1 1 6>. Crystallographic variant selection was observed across those prior {beta}/{beta} grain boundaries, but this has little effect on the transformation texture due to the crystal symmetry. The effect of the crystallographic variant selection on texture is further weakened by nucleation of diffusional transformed {alpha} in the grain interior.

Stanford, N. [Manchester Materials Science Centre, University of Manchester, Grosvenor Street, Manchester M1 7HS (United Kingdom); Bate, P.S. [Manchester Materials Science Centre, University of Manchester, Grosvenor Street, Manchester M1 7HS (United Kingdom)]. E-mail: pete.bate@man.ac.uk

2005-02-01

353

Coding variants in TREM2 increase risk for Alzheimer's disease.  

PubMed

The triggering receptor expressed on myeloid 2 (TREM2) is an immune phagocytic receptor expressed on brain microglia known to trigger phagocytosis and regulate the inflammatory response. Homozygous mutations in TREM2 cause Nasu-Hakola disease, a rare recessive form of dementia. A heterozygous TREM2 variant, p.R47H, was recently shown to increase Alzheimer''s disease (AD) risk. We hypothesized that if TREM2 is truly an AD risk gene, there would be additional rare variants in TREM2 that substantially affect AD risk. To test this hypothesis, we performed pooled sequencing of TREM2 coding regions in 2082 AD cases and 1648 cognitively normal elderly controls of European American descent. We identified 16 non-synonymous variants, six of which were not identified in previous AD studies. Two variants, p.R47H [P = 9.17 × 10(-4), odds ratio (OR) = 2.63 (1.44-4.81)] and p.R62H [P = 2.36 × 10(-4), OR = 2.36 (1.47-3.80)] were significantly associated with disease risk in single-variant analyses. Gene-based tests demonstrate variants in TREM2 are genome-wide significantly associated with AD [PSKAT-O = 5.37 × 10(-7); OR = 2.55 (1.80-3.67)]. The association of TREM2 variants with AD is still highly significant after excluding p.R47H [PSKAT-O = 7.72 × 10(-5); OR = 2.47 (1.62-3.87)], indicating that additional TREM2 variants affect AD risk. Genotyping in available family members of probands suggested that p.R47H (P = 4.65 × 10(-2)) and p.R62H (P = 6.87 × 10(-3)) were more frequently seen in AD cases versus controls within these families. Gel electrophoresis analysis confirms that at least three TREM2 transcripts are expressed in human brains, including one encoding a soluble form of TREM2. PMID:24899047

Jin, Sheng Chih; Benitez, Bruno A; Karch, Celeste M; Cooper, Breanna; Skorupa, Tara; Carrell, David; Norton, Joanne B; Hsu, Simon; Harari, Oscar; Cai, Yefei; Bertelsen, Sarah; Goate, Alison M; Cruchaga, Carlos

2014-11-01

354

Six variant readings in the first folio of Shakespeare  

E-print Network

gloriously, if somewhat disconcerting ly, when the machine is in actual use. Moreover it has—or at least all the more recently manufactured models have, like the one here —a certain amount of real chrome trim. A collation machine can hardly be said... that went into the making of our book. And I think you will in the end agree that what might be described as their cumulative candle-power is tolerably illuminating. Variant 1. The first of my six variants I take from that grue some tragedy, Titus...

Hinman, Charlton

1961-01-01

355

Biotinidase K m -variants: detection and detailed biochemical investigations  

Microsoft Academic Search

Summary  We describe a simple method for the detection of biotinidaseK\\u000a m-variants and detailed biochemical investigations in 5 such patient. They were detected among 103 patients with plasma biotinidase\\u000a activity which ranged from undetectable to 30% of the mean normal value. Two different types of biotinidaseK\\u000a m-variants were found. (1) In 3 infants biotinidase had a single 105–430-fold elevatedK\\u000a m for

T. Suormala; V. T. Ramaekers; S. Schweitzer; B. Fowler; M. C. Laub; C. Schwermer; J. Bachmann; E. R. Baumgartner

1995-01-01

356

Nonparaxial and paraxial focusing of azimuthal-variant vector beams.  

PubMed

Based on the vectorial Rayleigh-Sommerfeld formulas under the weak nonparaxial approximation, we investigate the propagation behavior of a lowest-order Laguerre-Gaussian beam with azimuthal-variant states of polarization. We present the analytical expressions for the radial, azimuthal, and longitudinal components of the electric field with an arbitrary integer topological charge m focused by a nonaperturing thin lens. We illustrate the three-dimensional optical intensities, energy flux distributions, beam waists, and focal shifts of the focused azimuthal-variant vector beams under the nonparaxial and paraxial approximations. PMID:23038320

Gu, Bing; Cui, Yiping

2012-07-30

357

Calculation of VVER reactor computational benchmark pin cell variants  

SciTech Connect

In the framework of the joint US/Russian project to update, verify, and validate reactor design/safety computer codes associated with mixed-oxide (MOX) usage in VVER reactors, a computational benchmark was constructed. The calculational results of pin cell variants from the benchmark are given in this paper. The pin cells contain low-enriched uranium (LEU), weapons-grade (W-G) MOX fuel, and reactor MOX fuel. The calculations call for a wide range of temperatures and soluble boron concentrations. Several of the variants include burnup analyses.

Kalashnikov, A.G. [IPPE (Russian Federation); Kalugin, M.A.; Lazarenko, A.P. [Kurchatov RRC (Russian Federation); Gehin, J.C. [Oak Ridge National Lab., TN (United States)

1998-12-31

358

Effects of Variant Rates and Noise on Epidemic Spreading  

NASA Astrophysics Data System (ADS)

We introduce variant rates, for both infection and recovery and noise into the susceptible-infected-removed (SIR) model for epidemic spreading. The changing rates are taken mainly due to the changing profiles of an epidemic during its evolution. However, the noise parameter which is taken from a given distribution, i.e. Gaussian can describe the fluctuations of the infection and recovery rates. The numerical simulations show that the SIR model with variant rates and noise and can improve the fitting with real SARS data in the near-stationary stage.

Li, Wei; Gao, Zong-Mao; Gu, Jiao

2011-05-01

359

Base isolation case study  

E-print Network

The primary objective of this thesis is the introduction of the current code, ASCE 7-05 into the base isolation design and the analysis of base isolation response due to seismic forces. An eight story irregular structure ...

Ching, Kenneth A. (Kenneth Apostol)

2008-01-01

360

Integrated optical isolators  

E-print Network

Introduction: Optical isolators are important components in lasers. Their main function is to eliminate noise caused by back-reflections into these lasers. The need for integrated isolators comes from the continuing growth ...

Zaman, Tauhid R

2005-01-01

361

Analog signal isolation techniques  

SciTech Connect

This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

Beadle, E.R.

1992-01-01

362

Analog signal isolation techniques  

SciTech Connect

This paper discusses several techniques for isolating analog signals in an accelerator environment. The techniques presented here encompass isolation amplifiers, voltage-to-frequency converters (VIFCs), transformers, optocouplers, discrete fiber optics, and commercial fiber optic links. Included within the presentation of each method are the design issues that must be considered when selecting the isolation method for a specific application.

Beadle, E.R.

1992-12-31

363

Enterobacter cloacae with a novel variant of ACT AmpC beta-lactamase originating from glaucous gull (Larus hyperboreus) in Svalbard.  

PubMed

We aimed at Escherichia coli and Enterobacter cloacae isolates resistant to cephalosporins and fluoroquinolones and Salmonella isolates in wild birds in Arctic Svalbard, Norway. Cloacal swabs of little auks (Alle alle, n=215) and samples of faeces of glaucous gulls (Larus hyperboreus, n=15) were examined. Inducible production of AmpC enzyme was detected in E. cloacae KW218 isolate. Sequence analysis of the 1146 bp PCR product of the ampC gene from this isolate revealed 99% sequence homology with the blaACT-14 and blaACT-5 AmpC beta-lactamase genes. Four, respectively six of the identified single nucleotide polymorphisms generated amino acid substitutions in the amino acid chain. As the ampC sequence polymorphism in the investigated E. cloacae strain was identified as unique, we revealed a novel variant of the ampC beta-lactamase gene blaACT-23. PMID:24629772

Literak, Ivan; Manga, Ivan; Wojczulanis-Jakubas, Katarzyna; Chroma, Magdalena; Jamborova, Ivana; Dobiasova, Hana; Sedlakova, Miroslava Htoutou; Cizek, Alois

2014-07-16

364

Malakal virus from Africa and Kimberley virus from Australia are geographic variants of a widely distributed ephemerovirus.  

PubMed

Kimberley virus (KIMV) is an arthropod-borne rhabdovirus that was isolated in 1973 and on several subsequent occasions from healthy cattle, mosquitoes (Culex annulirostris) and biting midges (Culicoides brevitarsis) in Australia. Malakal virus (MALV) is an antigenically related rhabdovirus isolated in 1963 from mosquitoes (Mansonia uniformis) in Sudan. We report here the complete genome sequences of KIMV (15442 nt) and MALV (15444 nt). The genomes have a similar organisation (3'-l-N-P-M-G-G(NS)-?1-?2-?-?-L-t-5') to that of bovine ephemeral fever virus (BEFV). High levels of amino acid identity in each gene, similar gene expression profiles, clustering in phylogenetic analyses of the N, P, G and L proteins, and strong cross-neutralisation indicate that KIMV and MALV are geographic variants of the same ephemerovirus that, like BEFV, occurs in Africa, Asia and Australia. PMID:22925335

Blasdell, Kim R; Voysey, Rhonda; Bulach, Dieter M; Trinidad, Lee; Tesh, Robert B; Boyle, David B; Walker, Peter J

2012-11-10

365

New molecular variants of epsilon and beta IncP-1 plasmids are present in estuarine waters.  

PubMed

In this work the presence of broad-host-plasmids in an estuary in Portugal has been investigated. Pseudomonas putida KT2442 was used as model recipient bacteria in biparental matings with tetracycline and mercury to select for resistance phenotypes. As a result, 7 transconjugants were shown to carry broad-host-plasmids from the IncP-1 group, as seen by PCR amplification of the trfA gene. Sequence analysis confirmed the isolation of 4 plasmids from ?-1 subgroup and 3 assigned to the recently described ? subgroup. To our knowledge this is the first report concerning the detection and isolation of IncP-1? and ? plasmids in estuarine waters. Moreover it is shown that, even though the retrieved plasmids are phylogenetically close to previously characterized plasmids, such as pB10 and pKJK5, respectively, they constitute new molecular variants. PMID:22107909

Oliveira, C S; Lázaro, B; Azevedo, J S N; Henriques, I; Almeida, A; Correia, A

2012-05-01

366

Identification of antigenically important domains in the glycoproteins of Sindbis virus by analysis of antibody escape variants.  

PubMed Central

To study important epitopes on glycoprotein E2 of Sindbis virus, eight variants selected to be singly or multiply resistant to six neutralizing monoclonal antibodies reactive against E2, as well as four revertants which had regained sensitivity to neutralization, were sequenced throughout the E2 region. To study antigenic determinants in glycoprotein E1, four variants selected for resistance to a neutralizing monoclonal antibody reactive with E1 were sequenced throughout the E2 and E1 regions. All of the salient changes in E2 occurred within a relatively small region between amino acids 181 and 216, a domain that encompasses a glycosylation site at residue 196 and that is rich in charged amino acids. Almost all variants had a change in charge, suggesting that the charged nature of this domain is important for interaction with antibodies. Variants independently isolated for resistance to the same antibody were usually altered in the same amino acid, and reversion to sensitivity occurred at the sites of the original mutations, but did not always restore the parental amino acid. The characteristics of this region suggest that this domain is found on the surface of E2 and constitutes a prominent antigenic domain that interacts directly with neutralizing antibodies. Previous studies have shown that this domain is also important for penetration of cells and for virulence of the virus. Resistance to the single E1-specific neutralizing monoclonal antibody resulted from changes of Gly-132 of E1 to either Arg or Glu. Analogous to the findings with E2, these changes result in a change in charge and are found near a glycosylation site at residue 139. This domain of E1 may therefore be found near the 181 to 216 domain of E2 on the surface of the E1-E2 heterodimer; together, they could form a domain important in virus penetration and neutralization. Images PMID:1714515

Strauss, E G; Stec, D S; Schmaljohn, A L; Strauss, J H

1991-01-01

367

Y chromosome variants in cattle Bos taurus and Bos indicus  

E-print Network

Y chromosome variants in cattle Bos taurus and Bos indicus C.R.E. HALNAN Janine I. WATSON Karyotype Summary It is shown that comparison of the size of the Y chromosome between individuals may be made as reliably by computation of measurement relative to the X chromosome as by proportionation relative

Paris-Sud XI, Université de

368

[Molecular variants of histone H5 of linnet (Acanthis flammea)].  

PubMed

Five electrophoretic variants of H5 histone were detected in the population of linnet (Acanthis flammea). Using the method of incomplete succinilation the number of lysine residues, electrophoretic positive charge and molecular length were determined for some variants of H5 histone and for their fragments, obtained after treatment with n-bromosuccinimide and chymotrypsin. The difference in structure of H5 variants was found to be connected with the region, confined by the phenylalanine residue and the C-end of the molecule. The minimal difference in molecular length of fragments carrying the variable region was found to be 6 amino acids, two of them are basic. A series of "regular" fragments was detected after mild treatment with trypsin. The number of these fragments increased in parallel with the increase of histone length. In accordance with the scheme proposed, the difference in structure of linnet H5 variants is caused by insertion of the regular region consisting of tandem repeats (from 3 to 7 times) of the elementary hexapeptide. PMID:7121462

Gorel', F L; Berdnikov, V A; Rozov, S M

1982-01-01

369

Tafazzin splice variants and mutations in Barth syndrome.  

PubMed

Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28. The human tafazzin gene produces four major mRNA splice variants; two of which have been shown to be functional (TAZ lacking exon 5 and full-length) in complementation studies with yeast and Drosophila. This study characterizes the multiple alternative splice variants of TAZ mRNA and their proportions in blood samples from a cohort of individuals with Barth syndrome (BTHS). Because it has been reported that collection and processing methods can affect the expression of various genes, we tested and chose a stabilizing medium for collecting, shipping and processing of the blood samples of these individuals. In both healthy controls and in BTHS individuals, we found a greater variety of alternatively spliced forms than previously described, with a sizeable proportion of minor splice variants besides the four dominant isoforms. Individuals with certain exonic and intronic splice mutations produce additional mutant mRNAs that could be translated into two or more proteins with different amino acid substitutions in a single individual. A fraction of the minor splice variants is predicted to be non-productive. PMID:24342716

Kirwin, Susan M; Manolakos, Athena; Barnett, Sarah Swain; Gonzalez, Iris L

2014-01-01

370

Middle Interhemispheric Variant of Holoprosencephaly Associated with Diffuse Polymicrogyria  

Microsoft Academic Search

Summary: An 11-month-old boy was discovered to have a cleft palate, club foot, hypospadias, and myoclonic seizures. No in utero exposure to teratogens was identified. Brain MR imaging revealed a middle interhemispheric fusion variant of holoprosencephaly, diffuse polymicrogyria, and a hypoplastic brain stem; this was a distinctly unusual asso- ciation of findings. We hypothesize that an unknown ge- netic factor

Jun-ichi Takanashi; A. James Barkovich; Nancy J. Clegg; Mauricio R. Delgado

2003-01-01

371

Resolution variant visual cryptography for street view of Google Maps  

Microsoft Academic Search

Resolution variant visual cryptography takes the idea of using a single share of visual cryptography (VC) to recover a secret from an image at multiple resolutions. That means, viewing the image on a one-to-one basis and superimposing the share will recover the secret. However, if the image is zoomed, using that same share we can recover other secrets at different

Jonathan Weir; WeiQi Yan

2010-01-01

372

A sibship with a mild variant of Zellweger syndrome  

Microsoft Academic Search

Summary A mild variant of Zellweger (cerebro-hepato-renal) syndrome was diagnosed in male and female siblings aged 7 and 2 years. They had mild facial dysmorphia, moderate psychomotor retardation, tapetoretinal degeneration, sensorineural deafness and hepatomegaly. Ultrastructural examination of a liver biopsy in the younger patient revealed the absence of recognizable peroxisomes. In both patients plasma levels of pipecolic acid, phytanic acid,

P. G. Barth; R. B. H. Schutgens; R. J. A. Wanders; H. S. A. Heymans; A. E. Moser; H. W. Moser; E. M. Bleeker-Wagemakers; K. Jansonius-Schultheiss; M. Derix; G. F. Nelck

1987-01-01

373

Genetic variant near cytosolic phospholipase A 2 associated with schizophrenia  

Microsoft Academic Search

Two studies were undertaken to determine a possible genetic basis for alterations in phospholipid metabolism in schizophrenia. Initial results demonstrated an association in 65 schizophrenics compared with a matched normal control population. A follow-up haplotype relative risk study of 44 triads (mother, father, affected offspring), confirmed the results seen in the association study. Results suggest that a genetic variant near

Craig J. Hudson; James L. Kennedy; Andrew Gotowiec; Anna Lin; Nicole King; Katherine Gojtan; Fabio Macciardi; Karl Skorecki; Herbert Y. Meltzer; Jerry J. Warsh; David F. Horrobin

1996-01-01

374

Allosteric Site Variants of Haemophilus influenzae ?-Carbonic Anhdyrase†, ‡  

PubMed Central

Haemophilus influenzae ?-carbonic anhydrase (HICA) is hypothesized to be an allosteric protein that is regulated by the binding of bicarbonate ion to a non-catalytic (inhibitory) site that controls the ligation of Asp44 to the catalytically essential zinc ion. We report here the X-ray crystallographic structures of two variants (W39F and Y181F) involved in the binding of bicarbonate ion in the non-catalytic site and an active site variant (D44N) that is incapable of forming a strong zinc ligand. The alteration of Trp39 to Phe increases the apparent Ki for bicarbonate inhibition by 4.8-fold. While the structures of W39F and Y181F are very similar to the wild-type enzyme, the X-ray crystal structure of the D44N variant reveals that it has adopted an active site conformation nearly identical to that of non-allosteric ?-carbonic anhydrases. We propose that the structure of the D44N variant is likely to be representative of the active conformation of the enzyme. These results lend additional support to the hypothesis that HICA is an allosteric enzyme that can adopt active and inactive conformations, the latter of which is stabilized by bicarbonate ion binding to a non-catalytic site. PMID:19459702

Rowlett, Roger S.; Tu, Chingkuang; Lee, Joseph; Herman, Ariel G.; Chapnick, Douglas A.; Shah, Shalini H.; Gareiss, Peter C.

2009-01-01

375

A Variant of Young's Double Slit Experiment for Educational Purposes  

ERIC Educational Resources Information Center

We describe a variant of the classical Young's double slit experiment that can be easily realized in any classroom, in order to evidence the wave nature of light. The proposed apparatus and its simplified theory are described and pictures of fringes, readily obtained using only cheap and off-the-shelf optical components, are reproduced. The…

Henault, Francois; Spang, Alain

2011-01-01

376

Discovery of recurrent structural variants in nasopharyngeal carcinoma  

PubMed Central

We present the discovery of genes recurrently involved in structural variation in nasopharyngeal carcinoma (NPC) and the identification of a novel type of somatic structural variant. We identified the variants with high complexity mate-pair libraries and a novel computational algorithm specifically designed for tumor-normal comparisons, SMASH. SMASH combines signals from split reads and mate-pair discordance to detect somatic structural variants. We demonstrate a >90% validation rate and a breakpoint reconstruction accuracy of 3 bp by Sanger sequencing. Our approach identified three in-frame gene fusions (YAP1-MAML2, PTPLB-RSRC1, and SP3-PTK2) that had strong levels of expression in corresponding NPC tissues. We found two cases of a novel type of structural variant, which we call “coupled inversion,” one of which produced the YAP1-MAML2 fusion. To investigate whether the identified fusion genes are recurrent, we performed fluorescent in situ hybridization (FISH) to screen 196 independent NPC cases. We observed recurrent rearrangements of MAML2 (three cases), PTK2 (six cases), and SP3 (two cases), corresponding to a combined rate of structural variation recurrence of 6% among tested NPC tissues. PMID:24214394

Valouev, Anton; Weng, Ziming; Sweeney, Robert T.; Varma, Sushama; Le, Quynh-Thu; Kong, Christina; Sidow, Arend; West, Robert B.

2014-01-01

377

Investigating the role of FUS exonic variants in Essential Tremor  

PubMed Central

Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence. PMID:23601511

Labbe, Catherine; Soto-Ortolaza, Alexandra I; Rayaprolu, Sruti; Harriott, Andrea M.; Strongosky, Audrey J; Uitti, Ryan J; Van Gerpen, Jay A; Wszolek, Zbigniew K; Ross, Owen A

2013-01-01

378

Power Spectra for Cold Dark Matter and Its Variants  

Microsoft Academic Search

The bulk of recent cosmological research has focused on the adiabatic cold dark matter model and its simple extensions. Here we present an accurate fitting formula that describes the matter transfer functions of all common variants, including mixed dark matter models. The result is a function of wavenumber, time, and six cosmological parameters: the massive neutrino density, number of neutrino

Daniel J. Eisenstein; Wayne Hu

1999-01-01

379

Innate Immune Activity Conditions the Effect of Regulatory Variants upon  

E-print Network

, Katharine Plant, Robert Andrews, Chris McGee, Julian C. Knight* Introduction: Many genetic variantsQTLs). To investigate the effect of innate immune stimuli on eQTLs, we exposed primary CD14+ human monocytes from 432 pathophysiologically relevant immune stimuli. By considering the cellular and environmental context relevant to disease

Napp, Nils

380

Terminological variants for document selection and question/answer matching  

E-print Network

system, term extraction, terminological variant, named entity, information retrieval Contact Author takes advantage of a question analysis module and a recognition of numeric and named entities takes advantage of a question analysis module and a recognition of numeric and named entities

Illouz, Gabriel

381

Biomechanical modeling of English /r/ variants Ian Stavness  

E-print Network

Biomechanical modeling of English /r/ variants Ian Stavness Department of Bioengineering, Stanford an investigation of the well-known con- text-dependent variation in English /r/ using a biomechanical tongue- jaw a previously unknown mechanism in tongue biomechanics for /r/ produc- tion: Torque in the sagittal plane about

British Columbia, University of

382

Common variants at 30 loci contribute to polygenic dyslipidemia  

E-print Network

,7,38 Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P o 10Ã?15

Abecasis, Goncalo

383

Common and Rare ABCA1 Variants Affecting Plasma HDL Cholesterol  

Microsoft Academic Search

Mutations in ABCA1, a member of the ATP-binding cassette family, have been shown to underlie Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA), which are genetic disorders that are characterized by depressed concentrations of plasma high density lipoprotein (HDL) cholesterol. An important question is whether common variants within the coding sequence of ABCA1 can affect plasma HDL cholesterol in the general

Jian Wang; John R. Burnett; Kue Young; Bernard Zinman; Anthony J. G. Hanley; Philip W. Connelly; Stewart B. Harris; Robert A. Hegele

2009-01-01

384

Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis  

PubMed Central

Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis. PMID:25374727

Sharma, Brij; Raina, Sujeet; Sharma, Rajesh

2014-01-01

385

Coreceptor Specificity of Temporal Variants of Simian Immunodeficiency Virus Mne  

Microsoft Academic Search

The simian immunodeficiency virus (SIV) Mne envelope undergoes genetic changes that alter tropism, syncytium-inducing capacity, and antigenic properties of the emerging variant virus population during the course of an infection. Here we investigated whether the mutations in envelope of SIVMne also influence coreceptor usage. The data demonstrate that the infecting macrophage-tropic SIVMne clone as well as the envelope vari- ants

JASON T. KIMATA; JOHN J. GOSINK; VINEET N. KEWALRAMANI; LYLE M. RUDENSEY; DAN R. LITTMAN; JULIE OVERBAUGH

1999-01-01

386

The CNN problem and other k-server variants  

Microsoft Academic Search

We study several interesting variants of the k-server problem. In the CNN problem, one server services requests in the Euclidean plane. The difference from the k-server problem is that the server does not have to move to a request, but it has only to move to a point that lies in the same horizontal or vertical line with the request.

Elias Koutsoupias; David Scot Taylor

2004-01-01

387

The CNN Problem and Other k-Server Variants  

Microsoft Academic Search

We study several interesting variants of the k-server problem. In the cnn problem, one server services requests in the Euclidean plane. The dierence from the k- server problem is that the server does not have to move to a request, but it has only to move to a point that lies in the same horizontal or vertical line with the

Elias Koutsoupias; David Scot Taylor

2000-01-01

388

A PYY Q62P variant linked to human obesity  

SciTech Connect

Members of the pancreatic polypeptide family and the irreceptors have been implicated in the control of food intake in rodents and humans. To investigate whether nucleotide changes in these candidate genes result in abnormal weight in humans, we sequenced the coding exons and splice sites of seven family members (NPY, PYY, PPY, NPY1R, NPY2R, NPY4R, and NPY5R) in a large cohort of extremely obese (n=379) and lean (n=378) individuals. In total we found eleven rare non-synonymous variants, four of which exhibited familial segregation, NPY1R L53P and PPY P63L with leanness and NPY2R D42G and PYY Q62P with obesity. Functional analysis of the obese variants revealed NPY2R D42G to have reduced cell surface expression, while previous cell culture based studies indicated variant PYY Q62P to have altered receptor binding selectivity and we show that it fails to reduce food intake through mouse peptide injection experiments. These results support that rare non-synonymous variants within these genes can alter susceptibility to human body mass index extremes.

Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska,Anna; Collier, John Michael; Hebert, Sybil; Doelle, Heather; Dent,Robert; Pennacchio, Len A.; McPherson, Ruth

2005-06-27

389

GFP variants for multispectral imaging of living cells. Jim Haseloff  

E-print Network

1 GFP variants for multispectral imaging of living cells. Jim Haseloff MRC Laboratory of Molecular expression in transformed cells, and the Ã?-glucuronidase (GUS) gene (Jefferson et al. 1987) has been used extensively in transgenic plants. Transformed tissues or patterns of gene expression can be identified

Franks, Robert

390

Rare variants of cutaneous leishmaniasis presenting as eczematous lesions  

PubMed Central

Cutaneous Leishmaniasis may present with clinical presentation such as zosteriform, sporotrichoid and erysipeloid. The eczema variant has rarely been reported. We report a 27- year- old patient with atypical cutaneous leishmaniasis resembling eczema on the hand of a man in Yazd province in the central of Iran.

Ayatollahi, Jamshid; Fattahi Bafghi, Ali; Shahcheraghi, Seyed Hossein

2014-01-01

391

Oncogenic potential diverge among human papillomavirus type 16 natural variants  

SciTech Connect

We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

Sichero, Laura, E-mail: lsichero@gmail.com [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil) [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Simao Sobrinho, Joao [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil) [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Lina Villa, Luisa [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil) [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Department of Radiology, School of Medicine, University of Sao Paulo (Brazil)

2012-10-10

392

A rare anatomic variant of the superior glenohumeral ligament  

Microsoft Academic Search

The attachment of the superior glenohumeral ligament (SGHL) to the upper pole of the glenoid is variable and 3 types have been described. We report an anatomic variant of SGHL attachment to the upper pole of the glenoid that has not heretofore been reported in the literature. In this case, the SGHL overrode the biceps origin, continued to the superior

Rabindra L. Pradhan; Eiji Itoi; Wataru Watanabe; Shin Yamada; Hiroyuki Nagasawa; Togo Shimizu; Ikuko Wakabayashi; Kozo Sato

2001-01-01

393

Host Genetic Variants in the Pathogenesis of Hepatitis C  

PubMed Central

Direct-acting antiviral drugs (DAAs) are currently replacing antiviral therapy for Hepatitis C infection. Treatment related side effects are even worse and the emergence of resistant viruses must be avoided because of the direct-antiviral action. Altogether it remains a challenge to take treatment decisions in a clinical setting with cost restrictions. Genetic host factors are hereby essential to implement an individualized treatment concept. In recent years results on different genetic variants have been published with a strong association with therapy response, fibrosis and treatment-related side effects. Polymorphisms of the IL28B gene were identified as accurate predictors for therapy response and spontaneous clearance of HCV infection and are already used for diagnostic decisions. For RBV-induced side effects, such as hemolytic anemia, associations to genetic variants of inosine triphosphatase (ITPA) were described and different SLC28 transporters for RBV-uptake have been successfully analyzed. Fibrosis progression has been associated with variants of Vitamin D receptor (VDR) and ABCB11 (bile salt export pump). Cirrhotic patients especially have a high treatment risk and low therapy response, so that personalized antiviral treatment is mandatory. This review focuses on different host genetic variants in the pathogenesis of Hepatitis C at the beginning of a new area of treatment. PMID:23342360

Rau, Monika; Baur, Katharina; Geier, Andreas

2012-01-01

394

Tailoring a stabilized variant of hydroxynitrile lyase from Arabidopsis thaliana.  

PubMed

The R-selective hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) cannot be applied for stereoselective cyanohydrin syntheses in aqueous media because of its limited stability at pH<5, which is required in order to suppress the uncatalyzed racemic cyanohydrin formation. To stabilize AtHNL we designed a surface-modified variant incorporating 11 changes in the amino acids on the protein surface. Comparative characterization of the variant and the wild-type enzyme showed a broadened pH optimum towards the acidic range, along with enhancement of activity by up to twofold and significantly increased pH- and thermostabilities. The effect can most probably be explained by a shift of the isoelectic point from pH 5.1 to 4.8. Application of the variant for the synthesis of (R)-cyanohydrins in an aqueous/organic two-phase system at pH 4.5 demonstrated the high stereoselectivity and robustness of the variant relative to the wild-type enzyme, which is immediately inactivated under these conditions. PMID:22378361

Okrob, Daniel; Metzner, Julia; Wiechert, Wolfgang; Gruber, Karl; Pohl, Martina

2012-04-16

395

Mathematical induction: variants and subtleties October 29, 2010  

E-print Network

Mathematical induction: variants and subtleties October 29, 2010 Mathematical induction is one method and its modifications (e.g. "strong induction"), and also that you know why induction doesn is that induction is a machine for automatically proving anything, and my intention is to convince you that there

Sarkar, Amites

396

Independence results for variants of sharply bounded induction  

E-print Network

Independence results for variants of sharply bounded induction Leszek Aleksander Kolodziejczyk February 19, 2011 Abstract The theory T0 2 , axiomatized by the induction scheme for sharply bounded is reminiscent of those known from the study of open induction. We make the connection to open induction explicit

Kolodziejczyk, Leszek

397

Outbreak of acute hemorrhagic conjunctivitis due to coxsackie A24 variant--Taiwan.  

PubMed

Outbreaks of acute hemorrhagic conjunctivitis caused by enterovirus 70 and several serotypes of adenovirus have occurred in Taiwan since 1971. In 1980-1981, there was a pandemic of acute hemorrhagic conjunctivitis in southeast Asia caused by coxsackie A24 variant (CA24v); however, this virus did not affect Taiwan. In October 1985, CA24v was isolated for the first time from patients with acute hemorrhagic conjunctivitis in southern Taiwan. The following summer, a large epidemic of acute hemorrhagic conjunctivitis due to CA24v occurred. An epidemiologic investigation of patients seen at one ophthalmology clinic in Taipei City revealed that school-age children were the most likely group to introduce illness into households (p less than 0.001) and that males were more often household index cases than were females (p less than 0.01). Multiple case households tended to be more crowded (3.0 vs. 2.5 persons per bathroom; p less than 0.05) and had illness introduced by younger family members (median age of index case = 10 vs. 17 years; p less than 0.01). It is unknown whether this outbreak is an isolated occurrence or represents another resurgence of CA24v in the area. PMID:2833097

Chou, M Y; Malison, M D

1988-04-01

398

Antigenic typing of Brazilian rabies virus samples isolated from animals and humans, 1989-2000.  

PubMed

Animal and human rabies samples isolated between 1989 and 2000 were typified by means of a monoclonal antibody panel against the viral nucleoprotein. The panel had been previously established to study the molecular epidemiology of rabies virus in the Americas. Samples were isolated in the Diagnostic Laboratory of the Pasteur Institute and in other rabies diagnostic centers in Brazil. In addition to the fixed virus samples CVS-31/96-IP, preserved in mouse brain, and PV-BHK/97, preserved in cell culture, a total of 330 rabies virus samples were isolated from dogs, cats, cattle, horses, bats, sheep, goat, swine, foxes, marmosets, coati and humans. Six antigenic variants that were compatible with the pre-established monoclonal antibodies panel were defined: numbers 2 (dog), 3 (Desmodus rotundus), 4 (Tadarida brasiliensis), 5 (vampire bat from Venezuela), 6 (Lasiurus cinereus) and Lab (reacted to all used antibodies). Six unknown profiles, not compatible with the panel, were also found. Samples isolated from insectivore bats showed the greatest variability and the most commonly isolated variant was variant-3 (Desmodus rotundus). These findings may be related to the existence of multiple independent transmission cycles, involving different bat species. PMID:12048546

Favoretto, Silvana Regina; Carrieri, Maria Luiza; Cunha, Elenice Maria S; Aguiar, Elizabeth A C; Silva, Luzia Helena Q; Sodre, Miriam M; Souza, Maria Conceição A M; Kotait, Ivanete

2002-01-01

399

Prion variants and species barriers among Saccharomyces Ure2 proteins.  

PubMed

As hamster scrapie cannot infect mice, due to sequence differences in their PrP proteins, we find "species barriers" to transmission of the [URE3] prion in Saccharomyces cerevisiae among Ure2 proteins of S. cerevisiae, paradoxus, bayanus, cariocanus, and mikatae on the basis of differences among their Ure2p prion domain sequences. The rapid variation of the N-terminal Ure2p prion domains results in protection against the detrimental effects of infection by a prion, just as the PrP residue 129 Met/Val polymorphism may have arisen to protect humans from the effects of cannibalism. Just as spread of bovine spongiform encephalopathy prion variant is less impaired by species barriers than is sheep scrapie, we find that some [URE3] prion variants are infectious to another yeast species while other variants (with the identical amino acid sequence) are not. The species barrier is thus prion variant dependent as in mammals. [URE3] prion variant characteristics are maintained even on passage through the Ure2p of another species. Ure2p of Saccharomyces castelli has an N-terminal Q/N-rich "prion domain" but does not form prions (in S. cerevisiae) and is not infected with [URE3] from Ure2p of other Saccharomyces. This implies that conservation of its prion domain is not for the purpose of forming prions. Indeed the Ure2p prion domain has been shown to be important, though not essential, for the nitrogen catabolism regulatory role of the protein. PMID:19124570

Edskes, Herman K; McCann, Lindsay M; Hebert, Andrea M; Wickner, Reed B

2009-03-01

400

Identifying Candidate Hirschsprung Disease-Associated RET Variants  

PubMed Central

Patients with sporadic Hirschsprung disease (HSCR) show increased allele sharing at markers in the 5? region of the RET locus, indicating the presence of a common ancestral RET mutation. In a previous study, we found a haplotype of six SNPs that was transmitted to 55.6% of our patients, whereas it was present in only 16.2% of the controls we used. Among the patients with that haplotype, 90.8% had it on both chromosomes, which led to a much higher risk of developing HSCR than when the haplotype occurred heterozygously. To more precisely define the HSCR-associated region and to identify candidate disease-associated variant(s), we sequenced the shared common haplotype region from 10 kb upstream of the RET gene through intron 1 and exon 2 (in total, 33 kb) in a patient homozygous for the common risk haplotype and in a control individual homozygous for the most common nonrisk haplotype. A comparison of these sequences revealed 86 sequence differences. Of these 86 variations, 8 proved to be in regions highly conserved among different vertebrates and within putative transcription factor binding sites. We therefore considered these as candidate disease-associated variants. Subsequent genotyping of these eight variants revealed a strong disease association for six of the eight markers. These six markers also showed the largest distortions in allele transmission. Interspecies comparison showed that only one of the six variations was located in a region also conserved in a nonmammalian species, making it the most likely candidate HSCR-associated variant. PMID:15759212

Burzynski, Grzegorz M.; Nolte, Ilja M.; Bronda, Agnes; Bos, Krista K.; Osinga, Jan; Plaza Menacho, Ivan; Twigt, Bas; Maas, Saskia; Brooks, Alice S.; Verheij, Joke B. G. M.; Buys, Charles H. C. M.; Hofstra, Robert M. W.

2005-01-01