The PpaA/AerR regulators of photosynthesis gene expression from anoxygenic phototrophic proteobacteria contain heme-binding SCHIC domains.

PubMed

Moskvin, Oleg V; Gilles-Gonzalez, Marie-Alda; Gomelsky, Mark

2010-10-01

The SCHIC domain of the B12-binding domain family present in the Rhodobacter sphaeroides AppA protein binds heme and senses oxygen. Here we show that the predicted SCHIC domain PpaA/AerR regulators also bind heme and respond to oxygen in vitro, despite their low sequence identity with AppA.

Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

PubMed Central

MacFabe, Derrick F.

2012-01-01

Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental agents that can trigger ASDs or ASD-related behaviors and deserve further exploration in basic science, agriculture, and clinical medicine. PMID:23990817

Episodic and working memory function in Primary Progressive Aphasia: A meta-analysis.

PubMed

Eikelboom, Willem S; Janssen, Nikki; Jiskoot, Lize C; van den Berg, Esther; Roelofs, Ardi; Kessels, Roy P C

2018-06-18

The distinction between Primary Progressive Aphasia (PPA) variants remains challenging for clinicians, especially for the non-fluent (nfv-PPA) and the logopenic variants (lv-PPA). Previous research suggests that memory tests might aid this differentiation. This meta-analysis compares memory function among PPA variants. Effects sizes were extracted from 41 studies (N = 849). Random-effects models were used to compare performance on episodic and working memory tests among PPA patients and healthy controls, and between the PPA variants. Memory deficits were frequently observed in PPA compared to controls, with large effect sizes for lv-PPA (Hedges' g = -2.04 [-2.58 to -1.49]), nfv-PPA (Hedges' g = -1.34 [-1.69 to -1.00]), and the semantic variant (sv-PPA; Hedges' g = -1.23 [-1.50 to -0.97]). Sv-PPA showed primarily verbal memory deficits, whereas lv-PPA showed worse performance than nfv-PPA on both verbal and non-verbal memory tests. Memory deficits were more pronounced in lv-PPA compared to nfv-PPA. This suggests that memory tests may be helpful to distinguish between these PPA variants. Copyright © 2018. Published by Elsevier Ltd.

Deep-Layer Microvasculature Dropout by Optical Coherence Tomography Angiography and Microstructure of Parapapillary Atrophy.

PubMed

Suh, Min Hee; Zangwill, Linda M; Manalastas, Patricia Isabel C; Belghith, Akram; Yarmohammadi, Adeleh; Akagi, Tadamichi; Diniz-Filho, Alberto; Saunders, Luke; Weinreb, Robert N

2018-04-01

To investigate the association between the microstructure of β-zone parapapillary atrophy (βPPA) and parapapillary deep-layer microvasculature dropout assessed by optical coherence tomography angiography (OCT-A). Thirty-seven eyes with βPPA devoid of the Bruch's membrane (BM) (γPPA) ranging between completely absent and discontinuous BM were matched by severity of the visual field (VF) damage with 37 eyes with fully intact BM (βPPA+BM) based on the spectral-domain (SD) OCT imaging. Parapapillary deep-layer microvasculature dropout was defined as a dropout of the microvasculature within choroid or scleral flange in the βPPA on the OCT-A. The widths of βPPA, γPPA, and βPPA+BM were measured on six radial SD-OCT images. Prevalence of the dropout was compared between eyes with and without γPPA. Logistic regression was performed for evaluating association of the dropout with the width of βPPA, γPPA, and βPPA+BM, and the γPPA presence. Eyes with γPPA had significantly higher prevalence of the dropout than did those without γPPA (75.7% versus 40.8%; P = 0.004). In logistic regression, presence and longer width of the γPPA, worse VF mean deviation, and presence of focal lamina cribrosa defects were significantly associated with the dropout (P < 0.05), whereas width of the βPPA and βPPA+BM, axial length, and choroidal thickness were not (P > 0.10). Parapapillary deep-layer microvasculature dropout was associated with the presence and larger width of γPPA, but not with the βPPA+BM width. Presence and width of the exposed scleral flange, rather than the retinal pigmented epithelium atrophy, may be associated with deep-layer microvasculature dropout.

Deep-Layer Microvasculature Dropout by Optical Coherence Tomography Angiography and Microstructure of Parapapillary Atrophy

PubMed Central

Suh, Min Hee; Zangwill, Linda M.; Manalastas, Patricia Isabel C.; Belghith, Akram; Yarmohammadi, Adeleh; Akagi, Tadamichi; Diniz-Filho, Alberto; Saunders, Luke; Weinreb, Robert N.

2018-01-01

Purpose To investigate the association between the microstructure of β-zone parapapillary atrophy (βPPA) and parapapillary deep-layer microvasculature dropout assessed by optical coherence tomography angiography (OCT-A). Methods Thirty-seven eyes with βPPA devoid of the Bruch's membrane (BM) (γPPA) ranging between completely absent and discontinuous BM were matched by severity of the visual field (VF) damage with 37 eyes with fully intact BM (βPPA+BM) based on the spectral-domain (SD) OCT imaging. Parapapillary deep-layer microvasculature dropout was defined as a dropout of the microvasculature within choroid or scleral flange in the βPPA on the OCT-A. The widths of βPPA, γPPA, and βPPA+BM were measured on six radial SD-OCT images. Prevalence of the dropout was compared between eyes with and without γPPA. Logistic regression was performed for evaluating association of the dropout with the width of βPPA, γPPA, and βPPA+BM, and the γPPA presence. Results Eyes with γPPA had significantly higher prevalence of the dropout than did those without γPPA (75.7% versus 40.8%; P = 0.004). In logistic regression, presence and longer width of the γPPA, worse VF mean deviation, and presence of focal lamina cribrosa defects were significantly associated with the dropout (P < 0.05), whereas width of the βPPA and βPPA+BM, axial length, and choroidal thickness were not (P > 0.10). Conclusions Parapapillary deep-layer microvasculature dropout was associated with the presence and larger width of γPPA, but not with the βPPA+BM width. Presence and width of the exposed scleral flange, rather than the retinal pigmented epithelium atrophy, may be associated with deep-layer microvasculature dropout. PMID:29677362

Non-Verbal Episodic Memory Deficits in Primary Progressive Aphasias are Highly Predictive of Underlying Amyloid Pathology.

PubMed

Ramanan, Siddharth; Flanagan, Emma; Leyton, Cristian E; Villemagne, Victor L; Rowe, Christopher C; Hodges, John R; Hornberger, Michael

2016-01-01

Diagnostic distinction of primary progressive aphasias (PPA) remains challenging, in particular for the logopenic (lvPPA) and nonfluent/agrammatic (naPPA) variants. Recent findings highlight that episodic memory deficits appear to discriminate these PPA variants from each other, as only lvPPA perform poorly on these tasks while having underlying amyloid pathology similar to that seen in amnestic dementias like Alzheimer's disease (AD). Most memory tests are, however, language based and thus potentially confounded by the prevalent language deficits in PPA. The current study investigated this issue across PPA variants by contrasting verbal and non-verbal episodic memory measures while controlling for their performance on a language subtest of a general cognitive screen. A total of 203 participants were included (25 lvPPA; 29 naPPA; 59 AD; 90 controls) and underwent extensive verbal and non-verbal episodic memory testing, with a subset of patients (n = 45) with confirmed amyloid profiles as assessed by Pittsburgh Compound B and PET. The most powerful discriminator between naPPA and lvPPA patients was a non-verbal recall measure (Rey Complex Figure delayed recall), with 81% of PPA patients classified correctly at presentation. Importantly, AD and lvPPA patients performed comparably on this measure, further highlighting the importance of underlying amyloid pathology in episodic memory profiles. The findings demonstrate that non-verbal recall emerges as the best discriminator of lvPPA and naPPA when controlling for language deficits in high load amyloid PPA cases.

Walking the interactome for candidate prioritization in exome sequencing studies of Mendelian diseases

DOE PAGES

Smedley, Damian; Kohler, Sebastian; Czeschik, Johanna Christina; ...

2014-07-30

Here, whole-exome sequencing (WES) has opened up previously unheard of possibilities for identifying novel disease genes in Mendelian disorders, only about half of which have been elucidated to date. However, interpretation of WES data remains challenging. As a result, we analyze protein–protein association (PPA) networks to identify candidate genes in the vicinity of genes previously implicated in a disease. The analysis, using a random-walk with restart (RWR) method, is adapted to the setting of WES by developing a composite variant-gene relevance score based on the rarity, location and predicted pathogenicity of variants and the RWR evaluation of genes harboring themore » variants. Benchmarking using known disease variants from 88 disease-gene families reveals that the correct gene is ranked among the top 10 candidates in ≥50% of cases, a figure which we confirmed using a prospective study of disease genes identified in 2012 and PPA data produced before that date. In conclusion, we implement our method in a freely available Web server, ExomeWalker, that displays a ranked list of candidates together with information on PPAs, frequency and predicted pathogenicity of the variants to allow quick and effective searches for candidates that are likely to reward closer investigation.« less

Walking the interactome for candidate prioritization in exome sequencing studies of Mendelian diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smedley, Damian; Kohler, Sebastian; Czeschik, Johanna Christina

Here, whole-exome sequencing (WES) has opened up previously unheard of possibilities for identifying novel disease genes in Mendelian disorders, only about half of which have been elucidated to date. However, interpretation of WES data remains challenging. As a result, we analyze protein–protein association (PPA) networks to identify candidate genes in the vicinity of genes previously implicated in a disease. The analysis, using a random-walk with restart (RWR) method, is adapted to the setting of WES by developing a composite variant-gene relevance score based on the rarity, location and predicted pathogenicity of variants and the RWR evaluation of genes harboring themore » variants. Benchmarking using known disease variants from 88 disease-gene families reveals that the correct gene is ranked among the top 10 candidates in ≥50% of cases, a figure which we confirmed using a prospective study of disease genes identified in 2012 and PPA data produced before that date. In conclusion, we implement our method in a freely available Web server, ExomeWalker, that displays a ranked list of candidates together with information on PPAs, frequency and predicted pathogenicity of the variants to allow quick and effective searches for candidates that are likely to reward closer investigation.« less

Slowed articulation rate is a sensitive diagnostic marker for identifying non-fluent primary progressive aphasia

PubMed Central

Cordella, Claire; Dickerson, Bradford C.; Quimby, Megan; Yunusova, Yana; Green, Jordan R.

2016-01-01

Background Primary progressive aphasia (PPA) is a neurodegenerative aphasic syndrome with three distinct clinical variants: non-fluent (nfvPPA), logopenic (lvPPA), and semantic (svPPA). Speech (non-) fluency is a key diagnostic marker used to aid identification of the clinical variants, and researchers have been actively developing diagnostic tools to assess speech fluency. Current approaches reveal coarse differences in fluency between subgroups, but often fail to clearly differentiate nfvPPA from the variably fluent lvPPA. More robust subtype differentiation may be possible with finer-grained measures of fluency. Aims We sought to identify the quantitative measures of speech rate—including articulation rate and pausing measures—that best differentiated PPA subtypes, specifically the non-fluent group (nfvPPA) from the more fluent groups (lvPPA, svPPA). The diagnostic accuracy of the quantitative speech rate variables was compared to that of a speech fluency impairment rating made by clinicians. Methods and Procedures Automatic estimates of pause and speech segment durations and rate measures were derived from connected speech samples of participants with PPA (N=38; 11 nfvPPA, 14 lvPPA, 13 svPPA) and healthy age-matched controls (N=8). Clinician ratings of fluency impairment were made using a previously validated clinician rating scale developed specifically for use in PPA. Receiver operating characteristic (ROC) analyses enabled a quantification of diagnostic accuracy. Outcomes and Results Among the quantitative measures, articulation rate was the most effective for differentiating between nfvPPA and the more fluent lvPPA and svPPA groups. The diagnostic accuracy of both speech and articulation rate measures was markedly better than that of the clinician rating scale, and articulation rate was the best classifier overall. Area under the curve (AUC) values for articulation rate were good to excellent for identifying nfvPPA from both svPPA (AUC=.96) and lvPPA (AUC=.86). Cross-validation of accuracy results for articulation rate showed good generalizability outside the training dataset. Conclusions Results provide empirical support for (1) the efficacy of quantitative assessments of speech fluency and (2) a distinct non-fluent PPA subtype characterized, at least in part, by an underlying disturbance in speech motor control. The trend toward improved classifier performance for quantitative rate measures demonstrates the potential for a more accurate and reliable approach to subtyping in the fluency domain, and suggests that articulation rate may be a useful input variable as part of a multi-dimensional clinical subtyping approach. PMID:28757671

Memory and emotion processing performance contributes to the diagnosis of non-semantic primary progressive aphasia syndromes.

PubMed

Piguet, Olivier; Leyton, Cristian E; Gleeson, Liam D; Hoon, Chris; Hodges, John R

2015-01-01

The two non-semantic variants of primary progressive aphasia (PPA), nonfluent/agrammatic PPA (nfv-PPA) and logopenic variant PPA (lv-PPA), share language features despite their different underlying pathology, and may be difficult to distinguish for non-language experts. To improve diagnostic accuracy of nfv-PPA and lv-PPA using tasks measuring non-language cognition and emotion processing. Thirty-eight dementia patients meeting diagnostic criteria for PPA (nfv-PPA 20, lv-PPA 18) and 21 matched healthy Controls underwent a comprehensive assessment of cognition and emotion processing, as well as a high-resolution structural MRI and a PiB-PET scan, a putative biomarker of Alzheimer's disease. Task performances were compared between the groups and those found to differ significantly were entered into a logistic regression analysis. Analyses revealed a double dissociation between nfv-PPA and lv-PPA. nfv-PPA exhibited significant emotion processing disturbance compared to lv-PPA and Controls. In contrast, only the lv-PPA group was significantly impaired on tasks of episodic memory. Logistic regression analyses showed that 87% of patients were correctly classified using emotion processing and episodic memory composite scores, together with a measure of visuospatial ability. Non-language presenting features can help differentiate between the two non-semantic PPA syndromes, with a double dissociation observed on tasks of episodic memory and emotion processing. Based on performance on these tasks, we propose a decision tree as a complementary method to differentiate between the two non-semantic variants. These findings have important clinical implications, with identification of patients who may potentially benefit existing therapeutic interventions currently available for Alzheimer's disease.

Pax2/Pax8-defined subdomains and the occurrence of apoptosis in the posterior placodal area of mice.

PubMed

Washausen, Stefan; Knabe, Wolfgang

2017-08-01

The present work aims to improve our understanding of the causes and functions of apoptosis during the morphogenesis of epibranchial placodes in mice. Schematic maps helped to compare the spatiotemporal sequence of apoptotic events with the protein expression patterns of general (Six1) and specific placodal markers (Pax2, Pax8). Our findings challenge the view that, in mammals, all three epibranchial placodes spring from the original posterior placodal area (PPA) of presomite or early somite embryos. Instead, close-meshed analysis of the Pax2/Pax8 expression patterns demonstrates the stepwise emergence of two subdomains which both belong to the gradually expanding PPA, and which largely give rise to the otic placode and epibranchial placode 1 (anterior subdomain), or to the caudal epibranchial placodes (posterior subdomain). Our observations reinforce previous doubts raised on the PPA progeny of early somite Xenopus embryos (Schlosser and Ahrens, Dev Biol 271:439-466, 2004). They also demonstrate that partly different Pax2/Pax8 codes accompany epibranchial placode development in Xenopus laevis and mice. In mice, interplacodal apoptosis assists in the establishment of the two PPA subdomains and, subsequently, of individualized placodes by predominantly eliminating Six1 + placodal precursor cells. Onset of interplacodal and intraplacodal large-scale apoptosis is almost always preceded and/or paralleled by Pax2/Pax8 expression minima in the very same region. Future work will demand the use of knock-out mice and whole embryo culture to experimentally test, whether the combined action of differentially expressed Pax2 and Pax8 genes exerts antiapoptotic effects in the mammalian PPA.

Microstructure of β-zone parapapillary atrophy and rate of retinal nerve fiber layer thinning in primary open-angle glaucoma.

PubMed

Kim, Yong Woo; Lee, Eun Ji; Kim, Tae-Woo; Kim, Mijin; Kim, Hyunjoong

2014-07-01

To investigate whether the rate of retinal nerve fiber layer (RNFL) thinning differs according to the microstructure of β-zone parapapillary atrophy (PPA) as evaluated by spectral-domain (SD) optical coherence tomography (OCT) in primary open-angle glaucoma (POAG). Prospective, observational, comparative study. A total of 195 eyes with POAG that had been evaluated by serial SD-OCT RNFL thickness measurements for ≥ 2 years. On the basis of the extent of Bruch's membrane (BM) within the β-zone PPA (area without retinal pigment epithelium [RPE]), as shown in the infrared fundus images, PPA was divided into PPA+BM (PPA with intact BM) and PPA-BM (PPA devoid of BM). Eyes were categorized into group A (having PPA+BM only, n=64), group B (having both PPA+BM and PPA-BM, n=58), group C (having PPA-BM only, n=32), and group D (without β-zone PPA, n=41). The rate of progressive OCT RNFL thinning was determined by linear regression and compared between groups. Factors influencing the rate of RNFL thinning were evaluated, including age, sex, follow-up duration, history of filtering surgery, baseline RNFL thickness, baseline intraocular pressure (IOP), mean IOP and IOP fluctuation during follow-up, PPA types, baseline PPA width, PPA width increase, axial length (AXL), central corneal thickness, and visual field mean deviation (MD). Rate of thinning of OCT RNFL thicknesses over time. Patients in groups B and C were significantly younger and more myopic, and had a greater AXL, than those in groups A and D (all P<0.001). The rate of global RNFL thinning was significantly faster in group A (-1.66 ± 2.94 μm/year) than in the other groups (group B, -0.87 ± 1.28 μm/year; group C, 0.20 ± 1.86 μm/year; group D, -0.28 ± 1.74 μm/year; P = 0.001). Multivariate regression showed a significant association of shorter follow-up period (P = 0.016), greater baseline global RNFL thickness (P = 0.035), type of β-zone PPA (group A, P = 0.023), and greater baseline PPA+BM width (P = 0.034) with a faster rate of RNFL thinning. The rate of RNFL thinning differed according to the microstructure of β-zone PPA. It was faster for eyes with β-zone PPA with intact BM than for eyes without β-zone PPA or with β-zone PPA devoid of BM. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Production of phenylpyruvic acid from L-phenylalanine using an L-amino acid deaminase from Proteus mirabilis: comparison of enzymatic and whole-cell biotransformation approaches.

PubMed

Hou, Ying; Hossain, Gazi Sakir; Li, Jianghua; Shin, Hyun-Dong; Liu, Long; Du, Guocheng

2015-10-01

Phenylpyruvic acid (PPA) is an important organic acid that has a wide range of applications. In this study, the membrane-bound L-amino acid deaminase (L-AAD) gene from Proteus mirabilis KCTC 2566 was expressed in Escherichia coli BL21(DE3) and then the L-AAD was purified. After that, we used the purified enzyme and the recombinant E. coli whole-cell biocatalyst to produce PPA via a one-step biotransformation from L-phenylalanine. L-AAD was solubilized from the membrane and purified 52-fold with an overall yield of 13 %, which corresponded to a specific activity of 0.94 ± 0.01 μmol PPA min(-1)·mg(-1). Then, the biotransformation conditions for the pure enzyme and the whole-cell biocatalyst were optimized. The maximal production was 2.6 ± 0.1 g·L(-1) (specific activity of 1.02 ± 0.02 μmol PPA min(-1)·mg(-1) protein, 86.7 ± 5 % mass conversion rate, and 1.04 g·L(-1)·h(-1) productivity) and 3.3 ± 0.2 g L(-1) (specific activity of 0.013 ± 0.003 μmol PPA min(-1)·mg(-1) protein, 82.5 ± 4 % mass conversion rate, and 0.55 g·L(-1)·h(-1) productivity) for the pure enzyme and whole-cell biocatalyst, respectively. Comparative studies of the enzymatic and whole-cell biotransformation were performed in terms of specific activity, production, conversion, productivity, stability, need of external cofactors, and recycling. We have developed two eco-friendly and efficient approaches for PPA production. The strategy described herein may aid the biotransformational synthesis of other α-keto acids from their corresponding amino acids.

Functional imaging correlates of impaired distractor suppression following sleep deprivation.

PubMed

Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

2012-05-15

Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. Copyright © 2012 Elsevier Inc. All rights reserved.

Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia.

PubMed

Multani, Namita; Galantucci, Sebastiano; Wilson, Stephen M; Shany-Ur, Tal; Poorzand, Pardis; Growdon, Matthew E; Jang, Jung Yun; Kramer, Joel H; Miller, Bruce L; Rankin, Katherine P; Gorno-Tempini, Maria Luisa; Tartaglia, Maria Carmela

2017-01-01

Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.

Logopenic and Nonfluent Variants of Primary Progressive Aphasia Are Differentiated by Acoustic Measures of Speech Production

PubMed Central

Ballard, Kirrie J.; Savage, Sharon; Leyton, Cristian E.; Vogel, Adam P.; Hornberger, Michael; Hodges, John R.

2014-01-01

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r 2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA. PMID:24587083

Grammatical comprehension deficits in non-fluent/agrammatic primary progressive aphasia.

PubMed

Charles, Dorothy; Olm, Christopher; Powers, John; Ash, Sharon; Irwin, David J; McMillan, Corey T; Rascovsky, Katya; Grossman, Murray

2014-03-01

Grammatical comprehension difficulty is an essential supporting feature of the non-fluent/agrammatic variant of primary progressive aphasia (naPPA), but well-controlled clinical measures of grammatical comprehension are unavailable. To develop a measure of grammatical comprehension and examine this comparatively in PPA variants and behavioural-variant frontotemporal degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in white matter tracts. Case-control study. Academic medical centre. 39 patients with variants of PPA (naPPA=12, lvPPA=15 and svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls. Grammatical comprehension accuracy. Patients with naPPA had selective difficulty understanding cleft sentence structures, while all PPA variants and patients with bvFTD were impaired with sentences containing a centre-embedded subordinate clause. Patients with bvFTD were also impaired understanding sentences involving short-term memory. Linear regressions related grammatical comprehension difficulty in naPPA to left anterior-superior temporal atrophy and reduced FA in corpus callosum and inferior frontal-occipital fasciculus. Difficulty with centre-embedded sentences in other PPA variants was related to other brain regions. These findings emphasise a distinct grammatical comprehension deficit in naPPA and associate this with interruption of a frontal-temporal neural network.

Grammatical Impairments in PPA

PubMed Central

Thompson, Cynthia K.; Mack, Jennifer E.

2015-01-01

Background Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. Aims We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. Main Contribution PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Conclusions Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real-time processes underlying grammatical impairments in PPA, as well as the structural and functional neural correlates of grammatical impairments across linguistic domains. Few studies have examined the effects of treatment for grammatical impairments in PPA; research in this area is needed to better understand how (or if) grammatical processing ability can be improved, the potential for spared neural tissue to be recruited to support this, and whether the neural connections within areas of dysfunctional tissue required for grammatical processing can be enhanced using cortical stimulation. PMID:25642014

Grammatical Impairments in PPA.

PubMed

Thompson, Cynthia K; Mack, Jennifer E

2014-09-01

Grammatical impairments are commonly observed in the agrammatic subtype of primary progressive aphasia (PPA-G), whereas grammatical processing is relatively preserved in logopenic (PPA-L) and semantic (PPA-S) subtypes. We review research on grammatical deficits in PPA and associated neural mechanisms, with discussion focused on production and comprehension of four aspects of morphosyntactic structure: grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures. We also address assessment of grammatical deficits in PPA, with emphasis on behavioral tests of grammatical processing. Finally, we address research examining the effects of treatment for progressive grammatical impairments. PPA-G is associated with grammatical deficits that are evident across linguistic domains in both production and comprehension. PPA-G is associated with damage to regions including the left inferior frontal gyrus (IFG) and dorsal white matter tracts, which have been linked to impaired comprehension and production of complex sentences. Detailing grammatical deficits in PPA is important for estimating the trajectory of language decline and associated neuropathology. We, therefore, highlight several new assessment tools for examining different aspects of morphosyntactic processing in PPA. Individuals with PPA-G present with agrammatic deficit patterns distinct from those associated with PPA-L and PPA-S, but similar to those seen in agrammatism resulting from stroke, and patterns of cortical atrophy and white matter changes associated with PPA-G have been identified. Methods for clinical evaluation of agrammatism, focusing on comprehension and production of grammatical morphology, functional categories, verbs and verb argument structure, and complex syntactic structures are recommended and tools for this are emerging in the literature. Further research is needed to investigate the real-time processes underlying grammatical impairments in PPA, as well as the structural and functional neural correlates of grammatical impairments across linguistic domains. Few studies have examined the effects of treatment for grammatical impairments in PPA; research in this area is needed to better understand how (or if) grammatical processing ability can be improved, the potential for spared neural tissue to be recruited to support this, and whether the neural connections within areas of dysfunctional tissue required for grammatical processing can be enhanced using cortical stimulation.

Primary progressive aphasia: classification of variants in 100 consecutive Brazilian cases

PubMed Central

Senaha, Mirna Lie Hosogi; Caramelli, Paulo; Brucki, Sonia M.D.; Smid, Jerusa; Takada, Leonel T.; Porto, Claudia S.; César, Karolina G.; Matioli, Maria Niures P.; Soares, Roger T.; Mansur, Letícia L.; Nitrini, Ricardo

2013-01-01

Primary progressive aphasia (PPA) is a neurodegenerative clinical syndrome characterized primarily by progressive language impairment. Recently, consensus diagnostic criteria were published for the diagnosis and classification of variants of PPA. The currently recognized variants are nonfluent/agrammatic (PPA-G), logopenic (PPA-L) and semantic (PPA-S). OBJECTIVE To analyze the demographic data and the clinical classification of 100 PPA cases. METHODS Data from 100 PPA patients who were consecutively evaluated between 1999 and 2012 were analyzed. The patients underwent neurological, cognitive and language evaluation. The cases were classified according to the proposed variants, using predominantly the guidelines proposed in the consensus diagnostic criteria from 2011. RESULTS The sample consisted of 57 women and 43 men, aged at onset 67.2±8.1 years (range of between 53 and 83 years). Thirty-five patients presented PPA-S, 29 PPA-G and 16 PPA-L. It was not possible to classify 20% of the cases into any one of the proposed variants. CONCLUSION It was possible to classify 80% of the sample into one of the three PPA variants proposed. Perhaps the consensus classification requires some adjustments to accommodate cases that do not fit into any of the variants and to avoid overlap where cases fit more than one variant. Nonetheless, the established current guidelines are a useful tool to address the classification and diagnosis of PPA and are also of great value in standardizing terminologies to improve consistency across studies from different research centers. PMID:29213827

Anatomic, Clinical, and Neuropsychological Correlates of Spelling Errors in Primary Progressive Aphasia

ERIC Educational Resources Information Center

Shim, HyungSub; Hurley, Robert S.; Rogalski, Emily; Mesulam, M.-Marsel

2012-01-01

This study evaluates spelling errors in the three subtypes of primary progressive aphasia (PPA): agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S). Forty-one PPA patients and 36 age-matched healthy controls were administered a test of spelling. The total number of errors and types of errors in spelling to dictation of regular words,…

Extra cellular pH influences uptake and photodynamic action of pyropheophorbide-a entrapped in folate receptor targeted organically modified silica nanoparticle.

PubMed

Singh, Surya Prakash; Sharma, Mrinalini; Patel, Harishankar; Gupta, Pradeep Kumar

2014-06-01

Photodynamic efficacy of pyropheophorbide-a (PPa) is limited due to poor aqueous solubility. In the present study, organically modified silica nanoparticles (ORMOSIL) entrapping PPa and its folate receptor targeted conjugate (FR-Np-PPa) were prepared and the effect of pH on uptake and photodynamic action of plain and FR-Np-PPa in squamous cell carcinoma (Nt-8e) cells and adenocarcinoma of breast (MCF-7) cells were studied. Nanoformulations of PPa were characterized by absorption and fluorescence spectroscopy. Dynamic light scattering was used for size measurements. The uptake of the two nanoformulations by cells incubated in media of pH 6.5 and 7.4 was studied by confocal fluorescence microscopy and spectrofluoremetrically. Phototoxicity of PPa was studied by MTT assay. In MCF-7 and Nt-8e cells, while the uptake of PPa was observed to increase with a decrease in pH of the incubation media for folate receptor targeted Np, uptake of Np-PPa was not influenced by a change in the pH of the media. Inhibition in the uptake of PPa in presence of free folic acid for cells incubated in a medium of pH 6.5 with targeted nanoparticles was higher compared to physiological pH. Consistent with uptake studies in both the cell lines phototoxicity of PPa delivered through FR-Np-PPa was higher in medium of pH 6.5 as compared to physiological pH and phototoxicity induced by NP-PPa was independent of the pH of medium. Acidic pH enhances the photodynamic efficacy of FR-targeted nanoformulated PPa. Copyright © 2014 Elsevier B.V. All rights reserved.

Cerebral microbleeds and CSF Alzheimer biomarkers in primary progressive aphasias.

PubMed

Mendes, Aline; Bertrand, Anne; Lamari, Foudil; Colliot, Olivier; Routier, Alexandre; Godefroy, Olivier; Etcharry-Bouyx, Frédérique; Moreaud, Olivier; Pasquier, Florence; Couratier, Philippe; Bennys, Karim; Vercelletto, Martine; Martinaud, Olivier; Laurent, Bernard; Pariente, Jérémie; Puel, Michèle; Epelbaum, Stéphane; Belliard, Serge; Kaaouana, Takoua; Fillon, Ludovic; Chupin, Marie; Dubois, Bruno; Teichmann, Marc

2018-03-20

To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown. We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities. CSF Alzheimer disease biomarker analyses available in 63 of the 82 patients provided the stratification of PPA into subgroups with patients who had or did not have probable underlying Alzheimer pathology. The prevalence of CMBs was higher in patients with PPA (28%) than in controls (16%). They were more prevalent in logopenic PPA (50%) than in semantic PPA (18%) and nonfluent/agrammatic PPA (17%). The localization of CMBs was mainly lobar (81%) with no difference between the PPA variants. CMBs were more frequent in PPA patients with positive than with negative CSF Alzheimer disease biomarkers (67% vs 20%). Patients with and without lobar CMBs had similar volumes of white matter hyperintensities. Language and general cognitive impairment in PPA was unrelated to CMB rates. CMB prevalence in PPA is higher than in healthy controls. CMBs were most prevalent in the logopenic variant, were related to underlying Alzheimer pathology, and did not affect the language/cognitive impairment. Our findings also suggest that CMB detection with MRI contributes to PPA variant diagnosis, especially of logopenic PPA, and provides an estimator of the underlying neuropathology. © 2018 American Academy of Neurology.

Effects of phenylpropanolamine (PPA) on in vitro human erythrocyte membranes and molecular models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suwalsky, Mario, E-mail: msuwalsk@udec.cl; Zambrano, Pablo; Mennickent, Sigrid

Research highlights: {yields} PPA is a common ingredient in cough-cold medication and appetite suppressants. {yields} Reports on its effects on human erythrocytes are very scarce. {yields} We found that PPA induced in vitro morphological changes to human erythrocytes. {yields} PPA interacted with isolated unsealed human erythrocyte membranes. {yields} PPA interacted with class of lipid present in the erythrocyte membrane outer monolayer. -- Abstract: Norephedrine, also called phenylpropanolamine (PPA), is a synthetic form of the ephedrine alkaloid. After reports of the occurrence of intracranial hemorrhage and other adverse effects, including several deaths, PPA is no longer sold in USA and Canada.more » Despite the extensive information about PPA toxicity, reports on its effects on cell membranes are scarce. With the aim to better understand the molecular mechanisms of the interaction of PPA with cell membranes, ranges of concentrations were incubated with intact human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), and molecular models of cell membranes. The latter consisted in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), phospholipid classes present in the outer and inner monolayers of most plasmatic cell membranes, respectively. The capacity of PPA to perturb the bilayer structures of DMPC and DMPE was assessed by X-ray diffraction, DMPC large unilamellar vesicles (LUV) and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). This study presents evidence that PPA affects human red cell membranes as follows: (a) in SEM studies on human erythrocytes it was observed that 0.5 mM PPA induced shape changes; (b) in IUM PPA induced a sharp decrease in the fluorescence anisotropy in the lipid bilayer acyl chains in a concentration range lower than 100 {mu}M; (c) X-ray diffraction studies showed that PPA in the 0.1-0.5 mM range induced increasing structural perturbation to DMPC, but no effects on DMPE multibilayers were detected.« less

The eyes reveal uncertainty about object distinctions in semantic variant primary progressive aphasia.

PubMed

Faria, Andreia V; Race, David; Kim, Kevin; Hillis, Argye E

2018-06-01

At least three distinct variants of primary progressive aphasia (PPA) have been described, but they are difficult to distinguish early in the course, when individuals experience primarily anomia. People with svPPA are often the hardest to care for, because they have impaired comprehension of words and objects and often have negative changes in comportment. We sought to identify an early marker of semantic variant primary progressive aphasia (svPPA) and to enhance the understanding of the semantic deficit in svPPA. We hypothesized that the pattern of eye tracking in a word picture matching task can differentiate svPPA from other variants and can predict which participants with unclassifiable PPA will progress to svPPA. We tested 19 individuals with PPA on a word picture matching task with eye tracking. We found that individuals with svPPA were less accurate than other variants when the foils were semantic coordinates (horse-cow) or schematically related (horse-saddle), but not when they were thematically related (saw-horse) or unrelated. Moreover, even in the condition in which they were highly accurate (unrelated foils) they looked much more often to the foils and for longer, than other variants or controls. Unclassifiable PPA participants who eventually developed svPPA showed the same pattern. This abnormal pattern was associated with atrophy in bilateral temporal poles. Copyright © 2018. Published by Elsevier Ltd.

Quantitative template for subtyping primary progressive aphasia.

PubMed

Mesulam, Marsel; Wieneke, Christina; Rogalski, Emily; Cobia, Derin; Thompson, Cynthia; Weintraub, Sandra

2009-12-01

The syndrome of primary progressive aphasia (PPA) is diagnosed when a gradual failure of word usage or comprehension emerges as the principal feature of a neurodegenerative disease. To provide a quantitative algorithm for classifying PPA into agrammatic (PPA-G), semantic (PPA-S), and logopenic (PPA-L) variants, each of which is known to have a different probability of association with Alzheimer disease vs frontotemporal lobar degeneration. Prospective study. University medical center. Sixteen consecutively enrolled patients with PPA who underwent neuropsychological testing and magnetic resonance imaging recruited nationally in the United States as part of a longitudinal study. A 2-dimensional template that reflects performance on tests of syntax (Northwestern Anagram Test) and lexical semantics (Peabody Picture Vocabulary Test-Fourth Edition) classified all 16 patients in concordance with a clinical diagnosis that had been made before the administration of quantitative tests. All 3 PPA subtypes had distinctly asymmetrical atrophy of the left perisylvian language network. Each subtype also had distinctive peak atrophy sites: PPA-G in the inferior frontal gyrus (Broca area), PPA-S in the anterior temporal lobe, and PPA-L in Brodmann area 37. Once an accurate root diagnosis of PPA is made, subtyping can be quantitatively guided using a 2-dimensional template based on orthogonal tasks of grammatical competence and word comprehension. Although the choice of tasks and the precise cutoff levels may need to be adjusted to fit linguistic and educational backgrounds, these 16 patients demonstrate the feasibility of using a simple algorithm for clinicoanatomical classification in PPA. Prospective studies will show whether this subtyping can improve clinical prediction of the underlying neuropathologic condition.

White matter disease correlates with lexical retrieval deficits in primary progressive aphasia.

PubMed

Powers, John P; McMillan, Corey T; Brun, Caroline C; Yushkevich, Paul A; Zhang, Hui; Gee, James C; Grossman, Murray

2013-01-01

To relate fractional anisotropy (FA) changes associated with the semantic and logopenic variants of primary progressive aphasia (PPA) to measures of lexical retrieval. We collected neuropsychological testing, volumetric magnetic resonance imaging, and diffusion-weighted imaging on semantic variant PPA (svPPA) (n = 11) and logopenic variant PPA (lvPPA) (n = 13) patients diagnosed using published criteria. We also acquired neuroimaging data on a group of demographically comparable healthy seniors (n = 34). FA was calculated and analyzed using a white matter (WM) tract-specific analysis approach. This approach utilizes anatomically guided data reduction to increase sensitivity and localizes results within canonically defined tracts. We used non-parametric, cluster-based statistical analysis to relate language performance to FA and determine regions of reduced FA in patients. We found widespread FA reductions in WM for both variants of PPA. FA was related to both confrontation naming and category naming fluency performance in left uncinate fasciculus and corpus callosum in svPPA and left superior and inferior longitudinal fasciculi in lvPPA. SvPPA and lvPPA are associated with distinct disruptions of a large-scale network implicated in lexical retrieval, and the WM disease in each phenotype may contribute to language impairments including lexical retrieval.

Predicting primary progressive aphasias with support vector machine approaches in structural MRI data.

PubMed

Bisenius, Sandrine; Mueller, Karsten; Diehl-Schmid, Janine; Fassbender, Klaus; Grimmer, Timo; Jessen, Frank; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Ludolph, Albert; Schneider, Anja; Anderl-Straub, Sarah; Stuke, Katharina; Danek, Adrian; Otto, Markus; Schroeter, Matthias L

2017-01-01

Primary progressive aphasia (PPA) encompasses the three subtypes nonfluent/agrammatic variant PPA, semantic variant PPA, and the logopenic variant PPA, which are characterized by distinct patterns of language difficulties and regional brain atrophy. To validate the potential of structural magnetic resonance imaging data for early individual diagnosis, we used support vector machine classification on grey matter density maps obtained by voxel-based morphometry analysis to discriminate PPA subtypes (44 patients: 16 nonfluent/agrammatic variant PPA, 17 semantic variant PPA, 11 logopenic variant PPA) from 20 healthy controls (matched for sample size, age, and gender) in the cohort of the multi-center study of the German consortium for frontotemporal lobar degeneration. Here, we compared a whole-brain with a meta-analysis-based disease-specific regions-of-interest approach for support vector machine classification. We also used support vector machine classification to discriminate the three PPA subtypes from each other. Whole brain support vector machine classification enabled a very high accuracy between 91 and 97% for identifying specific PPA subtypes vs. healthy controls, and 78/95% for the discrimination between semantic variant vs. nonfluent/agrammatic or logopenic PPA variants. Only for the discrimination between nonfluent/agrammatic and logopenic PPA variants accuracy was low with 55%. Interestingly, the regions that contributed the most to the support vector machine classification of patients corresponded largely to the regions that were atrophic in these patients as revealed by group comparisons. Although the whole brain approach took also into account regions that were not covered in the regions-of-interest approach, both approaches showed similar accuracies due to the disease-specificity of the selected networks. Conclusion, support vector machine classification of multi-center structural magnetic resonance imaging data enables prediction of PPA subtypes with a very high accuracy paving the road for its application in clinical settings.

Differentiating primary progressive aphasias in a brief sample of connected speech

PubMed Central

Evans, Emily; O'Shea, Jessica; Powers, John; Boller, Ashley; Weinberg, Danielle; Haley, Jenna; McMillan, Corey; Irwin, David J.; Rascovsky, Katya; Grossman, Murray

2013-01-01

Objective: A brief speech expression protocol that can be administered and scored without special training would aid in the differential diagnosis of the 3 principal forms of primary progressive aphasia (PPA): nonfluent/agrammatic PPA, logopenic variant PPA, and semantic variant PPA. Methods: We used a picture-description task to elicit a short speech sample, and we evaluated impairments in speech-sound production, speech rate, lexical retrieval, and grammaticality. We compared the results with those obtained by a longer, previously validated protocol and further validated performance with multimodal imaging to assess the neuroanatomical basis of the deficits. Results: We found different patterns of impaired grammar in each PPA variant, and additional language production features were impaired in each: nonfluent/agrammatic PPA was characterized by speech-sound errors; logopenic variant PPA by dysfluencies (false starts and hesitations); and semantic variant PPA by poor retrieval of nouns. Strong correlations were found between this brief speech sample and a lengthier narrative speech sample. A composite measure of grammaticality and other measures of speech production were correlated with distinct regions of gray matter atrophy and reduced white matter fractional anisotropy in each PPA variant. Conclusions: These findings provide evidence that large-scale networks are required for fluent, grammatical expression; that these networks can be selectively disrupted in PPA syndromes; and that quantitative analysis of a brief speech sample can reveal the corresponding distinct speech characteristics. PMID:23794681

Macromolecular Systems with MSA-Capped CdTe and CdTe/ZnS Core/Shell Quantum Dots as Superselective and Ultrasensitive Optical Sensors for Picric Acid Explosive.

PubMed

Dutta, Priyanka; Saikia, Dilip; Adhikary, Nirab Chandra; Sarma, Neelotpal Sen

2015-11-11

This work reports the development of highly fluorescent materials for the selective and efficient detection of picric acid explosive in the nanomolar range by fluorescence quenching phenomenon. Poly(vinyl alcohol) grafted polyaniline (PPA) and its nanocomposites with 2-mercaptosuccinic acid (MSA)-capped CdTe quantum dots (PPA-Q) and with MSA-capped CdTe/ZnS core/shell quantum dots (PPA-CSQ) are synthesized in a single step free radical polymerization reaction. The thermal stability and photo stability of the polymer increases in the order of PPA < PPA-Q < PPA-CSQ. The polymers show remarkably high selectivity and efficient sensitivity toward picric acid, and the quenching efficiency for PPA-CSQ reaches up to 99%. The detection limits of PPA, PPA-Q, and PPA-CSQ for picric acid are found to be 23, 1.6, and 0.65 nM, respectively, which are remarkably low. The mechanism operating in the quenching phenomenon is proposed to be a combination of a strong inner filter effect and ground state electrostatic interaction between the polymers and picric acid. A portable and cost-effective electronic device for the visual detection of picric acid by the sensory system is successfully fabricated. The device is further employed for quantitative detection of picric acid in real water samples.

QUANTITATIVE TEMPLATE FOR SUBTYPING PRIMARY PROGRESSIVE APHASIA

PubMed Central

Mesulam, Marsel; Wieneke, Christina; Rogalski, Emily; Cobia, Derin; Thompson, Cynthia; Weintraub, Sandra

2009-01-01

Objective To provide a quantitative algorithm for classifying primary progressive aphasia (PPA) into agrammatic (PPA-G), semantic (PPA-S) and logopenic (PPA-L) variants, each of which is known to have a different probability of association with Alzheimer’s disease (AD) versus frontotemporal lobar degeneration (FTLD). Design Prospectively and consecutively enrolled 16 PPA patients tested with neuropsychological instruments and magnetic resonance imaging (MRI). Setting University medical center. Participants PPA patients recruited nationally in the USA as part of a longitudinal study. Results A two-dimensional template, reflecting performance on tests of syntax (Northwestern Anagram Test) and lexical semantics (Peabody Picture Vocabulary Test), classified all 16 patients in concordance with a clinical diagnosis that had been made prior to the administration of the quantitative tests. All three subtypes had distinctly asymmetrical atrophy of the left perisylvian language network. Each subtype also had distinctive peak atrophy sites. Only PPA-G had peak atrophy in the IFG (Broca’s area), only PPA-S had peak atrophy in the anterior temporal lobe, and only PPA-L had peak atrophy in area 37. Conclusions Once an accurate root diagnosis of PPA is made, subtyping can be quantitatively guided using a two-dimensional template based on orthogonal tasks of grammatical competence and word comprehension. Although the choice of tasks and precise cut-off levels may evolve in time, this set of 16 patients demonstrates the feasibility of using a simple algorithm for clinico-anatomical classification in PPA. Prospective studies will show whether this suptyping can improve the clinical prediction of underlying neuropathology. PMID:20008661

Group Communication Treatment for Individuals with PPA and Their Partners.

PubMed

Mooney, Aimee; Beale, Naomi; Fried-Oken, Melanie

2018-07-01

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by insidious language deterioration. This young-onset disorder leaves adults with reduced communication skills for participation in social activities. There is limited evidence regarding group treatment for individuals with PPA, though the principles of chronic aphasia groups can be applied to this clinical population. We developed a PPA group treatment model incorporating compensatory strategies from augmentative and alternative communication (AAC), communication partner training from aphasia rehabilitation, and systematic instruction from dementia management. Six modules were designed and delivered to people with PPA and their communication partners in a university clinic setting over a 6-week period. Treatment was provided by graduate clinicians with supervision from a certified speech-language pathologist and faculty member. Primary treatment goals were to provide education about PPA symptoms and progression; to increase practice and use of multimodal communication by people with PPA; and to establish an environment where people with PPA and their partners could connect for training and support. We present pre/post comparisons and satisfaction data provided by five individuals with PPA and their partners in the group. Results suggest that group training is an effective service delivery model. Participants reported gains in both knowledge about PPA and in using many different modalities to communicate. The new compensatory strategies learned provide tools for maintenance and improvement of language use. Participants saw increased confidence and participation in daily activities, and highlighted the value of the PPA group for individuals with this relatively rare condition and their family members. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Accelerated Thermal Depolymerization of Cyclic Polyphthalaldehyde with a Polymeric Thermoacid Generator.

PubMed

Lopez Hernandez, Hector; Lee, Olivia P; Possanza, Catherine; Kaitz, Joshua A; Park, Chan Woo; Plantz, Christopher L; Moore, Jeffrey S; White, Scott R

2018-04-30

Thermally triggerable polymer films that degrade at modest temperatures (≈85 °C) are created from a blend of cyclic polyphthalaldehyde (cPPA) and a polymeric thermoacid generator, poly(vinyl tert-butyl carbonate sulfone) (PVtBCS). PVtBCS depolymerizes when heated, generating acid which initiates the depolymerization of cPPA into volatile byproducts. The mass loss onset for 2 wt% PVtBCS/cPPA is 22 °C lower than the onset for neat cPPA alone in dynamic thermogravimetric analysis experiments. Increased concentrations of PVtBCS increase the rate of depolymerization of cPPA. Raman spectroscopy reveals that the monomer, o-phthalaldehyde, is the main depolymerization product of the acid-catalyzed depolymerization of cPPA. The PVtBCS/cPPA blend is a promising material for the design and manufacture of transient electronic packaging and polymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neuropathologic Associations of Learning and Memory in Primary Progressive Aphasia.

PubMed

Kielb, Stephanie; Cook, Amanda; Wieneke, Christina; Rademaker, Alfred; Bigio, Eileen H; Mesulam, Marek-Marsel; Rogalski, Emily; Weintraub, Sandra

2016-07-01

The dementia syndrome of primary progressive aphasia (PPA) can be caused by 1 of several neuropathologic entities, including forms of frontotemporal lobar degeneration (FTLD) or Alzheimer disease (AD). Although episodic memory is initially spared in this syndrome, the subtle learning and memory features of PPA and their neuropathologic associations have not been characterized. To detect subtle memory differences on the basis of autopsy-confirmed neuropathologic diagnoses in PPA. Retrospective analysis was conducted at the Northwestern Cognitive Neurology and Alzheimer's Disease Center in August 2015 using clinical and postmortem autopsy data that had been collected between August 1983 and June 2012. Thirteen patients who had the primary clinical diagnosis of PPA and an autopsy-confirmed diagnosis of either AD (PPA-AD) or a tau variant of FTLD (PPA-FTLD) and 6 patients who had the clinical diagnosis of amnestic dementia and autopsy-confirmed AD (AMN-AD) were included. Scores on the effortless learning, delayed retrieval, and retention conditions of the Three Words Three Shapes test, a specialized measure of verbal and nonverbal episodic memory. The PPA-FTLD (n = 6), PPA-AD (n = 7), and AMN-AD (n = 6) groups did not differ by demographic composition (all P > .05). The sample mean (SD) age was 64.1 (10.3) years at symptom onset and 67.9 (9.9) years at Three Words Three Shapes test administration. The PPA-FTLD group had normal (ie, near-ceiling) scores on all verbal and nonverbal test conditions. Both the PPA-AD and AMN-AD groups had deficits in verbal effortless learning (mean [SD] number of errors, 9.9 [4.6] and 14.2 [2.0], respectively) and verbal delayed retrieval (mean [SD] number of errors, 6.1 [5.9] and 12.0 [4.4], respectively). The AMN-AD group had additional deficits in nonverbal effortless learning (mean [SD] number of errors, 10.3 [4.0]) and verbal retention (mean [SD] number of errors, 8.33 [5.2]), which were not observed in the PPA-FTLD or PPA-AD groups (all P < .005). This study identified neuropathologic associations of learning and memory in autopsy-confirmed cases of PPA. Among patients with clinical PPA syndrome, AD neuropathology appeared to interfere with effortless learning and delayed retrieval of verbal information, whereas FTLD-tau pathology did not. The results provide directions for future research on the interactions between limbic and language networks.

Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia.

PubMed

Santos-Santos, Miguel A; Rabinovici, Gil D; Iaccarino, Leonardo; Ayakta, Nagehan; Tammewar, Gautam; Lobach, Iryna; Henry, Maya L; Hubbard, Isabel; Mandelli, Maria Luisa; Spinelli, Edoardo; Miller, Zachary A; Pressman, Peter S; O'Neil, James P; Ghosh, Pia; Lazaris, Andreas; Meyer, Marita; Watson, Christa; Yoon, Soo Jin; Rosen, Howard J; Grinberg, Lea; Seeley, William W; Miller, Bruce L; Jagust, William J; Gorno-Tempini, Maria Luisa

2018-03-01

The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. Clinical, cognitive, neuroimaging, and pathology results. Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

Progranulin-Associated Primary Progressive Aphasia: A Distinct Phenotype?

ERIC Educational Resources Information Center

Rohrer, Jonathan D.; Crutch, Sebastian J.; Warrington, Elizabeth K.; Warren, Jason D.

2010-01-01

The neuropsychological features of the primary progressive aphasia (PPA) syndromes continue to be defined. Here we describe a detailed neuropsychological case study of a patient with a mutation in the progranulin ("GRN") gene who presented with progressive word-finding difficulty. Key neuropsychological features in this case included gravely…

Semantic Interference during Object Naming in Agrammatic and Logopenic Primary Progressive Aphasia (PPA)

ERIC Educational Resources Information Center

Thompson, Cynthia K.; Cho, Soojin; Price, Charis; Wieneke, Christina; Bonakdarpour, Borna; Rogalski, Emily; Weintraub, Sandra; Mesulam, M-Marsel

2012-01-01

This study examined the time course of object naming in 21 individuals with primary progressive aphasia (PPA) (8 agrammatic (PPA-G); 13 logopenic (PPA-L)) and healthy age-matched speakers (n=17) using a semantic interference paradigm with related and unrelated interfering stimuli presented at stimulus onset asynchronies (SOAs) of -1000, -500, -100…

Motor Speech Disorders Associated with Primary Progressive Aphasia

PubMed Central

Duffy, Joseph R.; Strand, Edythe A.; Josephs, Keith A.

2014-01-01

Background Primary progressive aphasia (PPA) and conditions that overlap with it can be accompanied by motor speech disorders. Recognition and understanding of motor speech disorders can contribute to a fuller clinical understanding of PPA and its management as well as its localization and underlying pathology. Aims To review the types of motor speech disorders that may occur with PPA, its primary variants, and its overlap syndromes (progressive supranuclear palsy syndrome, corticobasal syndrome, motor neuron disease), as well as with primary progressive apraxia of speech. Main Contribution The review should assist clinicians' and researchers' understanding of the relationship between motor speech disorders and PPA and its major variants. It also highlights the importance of recognizing neurodegenerative apraxia of speech as a condition that can occur with little or no evidence of aphasia. Conclusion Motor speech disorders can occur with PPA. Their recognition can contribute to clinical diagnosis and management of PPA and to understanding and predicting the localization and pathology associated with PPA variants and conditions that can overlap with them. PMID:25309017

Treatment of Paroxysmal Perceptual Alteration in Catatonic Schizophrenia by Switching to Aripiprazole from Risperidone: A Case Report.

PubMed

Yamashita, Satoko; Miyaoka, Tsuyoshi; Nagahama, Michiharu; Ieda, Masa; Tsuchie, Keiko; Wake, Rei; Horiguchi, Jun

2016-01-01

Paroxysmal perceptual alteration (PPA) is the occurrence of brief and recurrent episodes of perceptual changes. It is mainly caused by the treatment of schizophrenia patients with antipsychotics. However, diagnosis of PPA is not very prevalent among psychiatrists, partly due to underrecognition or misunderstanding that it is a worsening of psychiatric symptoms. If psychiatrists do not understand PPA, they cannot treat it appropriately, and the patient's quality of life is impaired. We present a case of PPA in catatonic schizophrenia that was successfully treated by switching to aripiprazole from risperidone. We suggest that the disappearance of PPA in our case was due to both discontinuing risperidone, which completely blocks D2 receptors, and replacing it with aripiprazole, which is characterized as a partial agonist of D2 receptors. Treatment of PPA will improve medication adherence and quality of life. It is important to recognize PPA as a possible side effect of treatment with antipsychotics.

Biotic and Abiotic Stimulation of Root Epidermal Cells Reveals Common and Specific Responses to Arbuscular Mycorrhizal Fungi1[W

PubMed Central

Genre, Andrea; Ortu, Giuseppe; Bertoldo, Chiara; Martino, Elena; Bonfante, Paola

2009-01-01

During arbuscular mycorrhizal (AM) colonization, a focal accumulation of organelles occurs in root epidermal cells, prior to fungal penetration, beneath adhering hyphopodia. This is followed by the appearance of the prepenetration apparatus (PPA), a transcellular column of cytoplasm connected to the nucleus and rich in cytoskeleton and secretory endomembranes. This apparatus appears to be responsible for the construction of an apoplastic compartment that confines the fungus within the cell lumen. To identify AM-specific elements within the PPA response, we challenged root cultures of Medicago truncatula, expressing a green fluorescent protein tag for the endoplasmic reticulum, with an AM symbiont, a necrotrophic pathogen, a hemibiotrophic pathogen, a noncompatible endomycorrhizal fungus, or abiotic physical stimuli. Parallel experiments were made on a M. truncatula nonsymbiotic mutant (doesn't make infections, dmi3-1). The results have highlighted a correlation between physical stimulation of the cell surface and nuclear repositioning. Cytoplasmic aggregation was only induced by contact with compatible fungi, whereas PPA appearance was specifically triggered by the AM fungus. The dmi3-1 mutant did not develop cytoplasmic aggregation or PPA and underwent cell death upon physical stimulation. The up-regulation of an expansin-like gene, already identified as an early marker of AM fungal contact, was triggered in wild-type roots by all the fungi tested. Such observations identify responses that are specific to mycorrhizal interactions and extend the role of the DMI3 protein, a calcium/calmodulin-dependent kinase, from symbiotic to pathogenic interactions. PMID:19151131

Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia

PubMed Central

Santos-Santos, Miguel A.; Rabinovici, Gil D.; Iaccarino, Leonardo; Ayakta, Nagehan; Tammewar, Gautam; Lobach, Iryna; Henry, Maya L.; Hubbard, Isabel; Mandelli, Maria Luisa; Spinelli, Edoardo; Miller, Zachary A.; Pressman, Peter S.; O’Neil, James P.; Ghosh, Pia; Lazaris, Andreas; Meyer, Marita; Watson, Christa; Yoon, Soo Jin; Rosen, Howard J.; Grinberg, Lea; Seeley, William W.; Miller, Bruce L.; Jagust, William J.; Gorno-Tempini, Maria Luisa

2018-01-01

IMPORTANCE The ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies. OBJECTIVE To determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA). DESIGN, SETTING, AND PARTICIPANTS This prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11–labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA. MAIN OUTCOMES AND MEASURES Clinical, cognitive, neuroimaging, and pathology results. RESULTS Twenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET–positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy. CONCLUSIONS AND RELEVANCE Primary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11–labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease. PMID:29309493

A deterministic, dynamic systems model of cow-calf production: The effects of the duration of postpartum anestrus on production parameters over a 10-year horizon.

PubMed

Shane, D D; Larson, R L; Sanderson, M W; Miesner, M; White, B J

2017-04-01

The duration of postpartum anestrus (dPPA) is important to consider for reproductive performance and efficiency in cow-calf operations. We developed a deterministic, dynamic systems model of cow-calf production over a 10-yr horizon to model the effects that dPPA had on measures of herd productivity, including the percentage of cows cycling before the end of the first 21 d of the breeding season (%C21), the percentage of cows pregnant at pregnancy diagnosis (%PPD), the distribution of pregnancy by 21-d breeding intervals, the kilograms of calf weaned (KW), the kilograms of calf weaned per cow exposed (KPC), and the replacement percentage. A 1,000-animal herd was modeled, with the beginning and ending dates for a 63-d natural service breeding season being the same for eligible replacement heifers (nulliparous cows) and cows (primiparous and multiparous cows). Herds were simulated to have a multiparous cow dPPA of 50, 60, 70, or 80 d, with the dPPA for primiparous cows being set to 50, 60, 70, 80, 90, 100, or 110 d. Only combinations where the primiparous dPPA was greater than or equal to the multiparous dPPA were included, resulting in 22 model herds being simulated in the analysis. All other model parameters were held constant between simulations. In model season 10, the %C21 was 96.2% when the multiparous cow and primiparous cow dPPA was 50 d and was 48.3% when the multiparous cow and primiparous cow dPPA was 80 d. The %PPD in model season 10 for these same herds was 95.1% and 86.0%, respectively. The percentage of the herd becoming pregnant in the first 21 d of the breeding season also differed between these herds (61.8% and 31.3%, respectively). The 10-yr total KW was more than 275,000 kg greater for the herd with a 50-d multiparous cow and primiparous cow dPPA when compared with the herd with the 80-d multiparous and primiparous cow dPPA and had a model season 10 KPC of 180.8 kg compared with 151.4 kg for the longer dPPA. The model results show that both the multiparous cow and primiparous cow dPPA affect herd productivity outcomes and that a dPPA less than 60 d results in improved production outcomes relative to longer dPPA. Veterinarians and producers should consider determining the dPPA to aid in making management decisions to improve reproductive performance of cow-calf herds.

[Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

PubMed

Watanabe, Ken

2009-01-01

The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation antipsychotics might be related to the differences in these agents regarding their affinity for the D2 receptor: RIS has a sustained and close binding affinity, which might be similar to those of conventional antipsychotics, OLZ shows a sustained and loose binding affinity, PRS exhibits a transient and close binding affinity, whereas QTP has a transient and loose binding affinity. APZ is a partial agonist of the D2 receptor; APZ acts as an agonist under the condition of intrinsic dopaminergic dysfunction, which might prevent the occurrence of PPA.

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents.

PubMed

McMillan, Lana J; Hepowit, Nathaniel L; Maupin-Furlow, Julie A

2016-01-15

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg(-1) for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg(2+). Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a "salt-loving" noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Functional Regulation of Sugar Assimilation by N-Glycan-specific Interaction of Pancreatic α-Amylase with Glycoproteins of Duodenal Brush Border Membrane*

PubMed Central

Asanuma-Date, Kimie; Hirano, Yuki; Le, Na; Sano, Kotone; Kawasaki, Nana; Hashii, Noritaka; Hiruta, Yoko; Nakayama, Ken-ichi; Umemura, Mariko; Ishikawa, Kazuhiko; Sakagami, Hiromi; Ogawa, Haruko

2012-01-01

Porcine pancreatic α-amylase (PPA) binds to N-linked glycans of glycoproteins (Matsushita, H., Takenaka, M., and Ogawa, H. (2002) J. Biol Chem., 277, 4680–4686). Immunostaining revealed that PPA is located at the brush-border membrane (BBM) of enterocytes in the duodenum and that the binding is inhibited by mannan but not galactan, indicating that PPA binds carbohydrate-specifically to BBM. The ligands for PPA in BBM were identified as glycoprotein N-glycans that are significantly involved in the assimilation of glucose, including sucrase-isomaltase (SI) and Na+/Glc cotransporter 1 (SGLT1). Binding of SI and SGLT1 in BBM to PPA was dose-dependent and inhibited by mannan. Using BBM vesicles, we found functional changes in PPA and its ligands in BBM due to the N-glycan-specific interaction. The starch-degrading activity of PPA and maltose-degrading activity of SI were enhanced to 240 and 175%, respectively, while Glc uptake by SGLT1 was markedly inhibited by PPA at high but physiologically possible concentrations, and the binding was attenuated by the addition of mannose-specific lectins, especially from Galanthus nivalis. Additionally, recombinant human pancreatic α-amylases expressed in yeast and purified by single-step affinity chromatography exhibited the same carbohydrate binding specificity as PPA in binding assays with sugar-biotinyl polymer probes. The results indicate that mammalian pancreatic α-amylases share a common carbohydrate binding activity and specifically bind to the intestinal BBM. Interaction with N-glycans in the BBM activated PPA and SI to produce much Glc on the one hand and to inhibit Glc absorption by enterocytes via SGLT1 in order to prevent a rapid increase in blood sugar on the other. PMID:22584580

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents

PubMed Central

McMillan, Lana J.; Hepowit, Nathaniel L.

2015-01-01

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg−1 for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg2+. Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a “salt-loving” noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. PMID:26546423

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muder, R.R.; Reddy, S.C.; Yu, V.L.

Using an objective scoring system, chest radiographs were reviewed in 23 cases of pneumonia due to the Pittsburgh pneumonia agent (PPA, Tatlockia micdadei, Legionella micdadei), including six cases of pneumonia with simultaneous isolation of PPA and L pneumophila (Legionnaires' disease). Infiltrates were typically segmental to lobar; nodular infiltrates were noted in three cases. Spread to additional lobes after presentation occurred in four of 17 PPA infections. Pneumonia caused by both PPA and L pneumophila was unusually severe, with involvement of all lobes occurring in four of six cases, compared with one of 17 cases of PPA infection (p>0.02). Radiographic severitymore » did not correlate with underlying disease, immune status, or outcome. The majority of patients receiving erythromycin demonstrated objective radiologic improvement. In a patients, population that included nonimmunosuppressed patient, nodule formation and rapid radiologic progression were not found to be characteristic of PPA pneumonia.« less

Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer.

PubMed

Jeong, Keunsoo; Park, Solji; Lee, Yong-Deok; Kang, Chi Soo; Kim, Hyun Jun; Park, Hyeonjong; Kwon, Ick Chan; Kim, Jungahn; Park, Chong Rae; Kim, Sehoon

2016-08-01

Current approaches in use of water-insoluble photosensitizers for photodynamic therapy (PDT) of cancer often demand a nano-delivery system. Here, we report a photosensitizer-loaded biocompatible nano-delivery formulation (PPaN-20) whose size was engineered to ca. 20nm to offer improved cell/tissue penetration and efficient generation of cytotoxic singlet oxygen. PPaN-20 was fabricated through the physical assembly of all biocompatible constituents: pyropheophorbide-a (PPa, water-insoluble photosensitizer), polycaprolactone (PCL, hydrophobic/biodegradable polymer), and Pluronic F-68 (clinically approved polymeric surfactant). Repeated microemulsification/evaporation method resulted in a fine colloidal dispersion of PPaN-20 in water, where the particulate PCL matrix containing well-dispersed PPa molecules inside was stabilized by the Pluronic corona. Compared to a control sample of large-sized nanoparticles (PPaN-200) prepared by a conventional solvent displacement method, PPaN-20 revealed optimal singlet oxygen generation and efficient cellular uptake by virtue of the suitably engineered size and constitution, leading to high in vitro phototoxicity against cancer cells. Upon administration to tumor-bearing mice by peritumoral route, PPaN-20 showed efficient tumor accumulation by the enhanced cell/tissue penetration evidenced by in vivo near-infrared fluorescence imaging. The in vivo PDT treatment with peritumorally administrated PPaN-20 showed significantly enhanced suppression of tumor growth compared to the control group, demonstrating great potential as a biocompatible photosensitizing agent for locoregional PDT treatment of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of a highly conserved sterile alpha motif domain gene (WEEP) results in pendulous branch growth in peach trees.

PubMed

Hollender, Courtney A; Pascal, Thierry; Tabb, Amy; Hadiarto, Toto; Srinivasan, Chinnathambi; Wang, Wanpeng; Liu, Zhongchi; Scorza, Ralph; Dardick, Chris

2018-05-15

Plant shoots typically grow upward in opposition to the pull of gravity. However, exceptions exist throughout the plant kingdom. Most conspicuous are trees with weeping or pendulous branches. While such trees have long been cultivated and appreciated for their ornamental value, the molecular basis behind the weeping habit is not known. Here, we characterized a weeping tree phenotype in Prunus persica (peach) and identified the underlying genetic mutation using a genomic sequencing approach. Weeping peach tree shoots exhibited a downward elliptical growth pattern and did not exhibit an upward bending in response to 90° reorientation. The causative allele was found to be an uncharacterized gene, Ppa013325 , having a 1.8-Kb deletion spanning the 5' end. This gene, dubbed WEEP , was predominantly expressed in phloem tissues and encodes a highly conserved 129-amino acid protein containing a sterile alpha motif (SAM) domain. Silencing WEEP in the related tree species Prunus domestica (plum) resulted in more outward, downward, and wandering shoot orientations compared to standard trees, supporting a role for WEEP in directing lateral shoot growth in trees. This previously unknown regulator of branch orientation, which may also be a regulator of gravity perception or response, provides insights into our understanding of how tree branches grow in opposition to gravity and could serve as a critical target for manipulating tree architecture for improved tree shape in agricultural and horticulture applications. Copyright © 2018 the Author(s). Published by PNAS.

Fourier power, subjective distance, and object categories all provide plausible models of BOLD responses in scene-selective visual areas

PubMed Central

Lescroart, Mark D.; Stansbury, Dustin E.; Gallant, Jack L.

2015-01-01

Perception of natural visual scenes activates several functional areas in the human brain, including the Parahippocampal Place Area (PPA), Retrosplenial Complex (RSC), and the Occipital Place Area (OPA). It is currently unclear what specific scene-related features are represented in these areas. Previous studies have suggested that PPA, RSC, and/or OPA might represent at least three qualitatively different classes of features: (1) 2D features related to Fourier power; (2) 3D spatial features such as the distance to objects in a scene; or (3) abstract features such as the categories of objects in a scene. To determine which of these hypotheses best describes the visual representation in scene-selective areas, we applied voxel-wise modeling (VM) to BOLD fMRI responses elicited by a set of 1386 images of natural scenes. VM provides an efficient method for testing competing hypotheses by comparing predictions of brain activity based on encoding models that instantiate each hypothesis. Here we evaluated three different encoding models that instantiate each of the three hypotheses listed above. We used linear regression to fit each encoding model to the fMRI data recorded from each voxel, and we evaluated each fit model by estimating the amount of variance it predicted in a withheld portion of the data set. We found that voxel-wise models based on Fourier power or the subjective distance to objects in each scene predicted much of the variance predicted by a model based on object categories. Furthermore, the response variance explained by these three models is largely shared, and the individual models explain little unique variance in responses. Based on an evaluation of previous studies and the data we present here, we conclude that there is currently no good basis to favor any one of the three alternative hypotheses about visual representation in scene-selective areas. We offer suggestions for further studies that may help resolve this issue. PMID:26594164

Concentrating Solar Power Projects - La Risca | Concentrating Solar Power |

Science.gov Websites

) project, with data organized by background, participants, and power plant configuration. Status Date : 350 Annual O&M Jobs: 31 PPA/Tariff Date: January 2010 PPA/Tariff Type: Real Decreto 661/2007 PPA

Hippocampal subfield surface deformity in non-semantic primary progressive aphasia.

PubMed

Christensen, Adam; Alpert, Kathryn; Rogalski, Emily; Cobia, Derin; Rao, Julia; Beg, Mirza Faisal; Weintraub, Sandra; Mesulam, M-Marsel; Wang, Lei

2015-03-01

Alzheimer neuropathology (AD) is found in almost half of patients with non-semantic primary progressive aphasia (PPA). This study examined hippocampal abnormalities in PPA to determine similarities to those described in amnestic AD. In 37 PPA patients and 32 healthy controls, we generated hippocampal subfield surface maps from structural MRIs and administered a face memory test. We analyzed group and hemisphere differences for surface shape measures and their relationship with test scores and ApoE genotype. The hippocampus in PPA showed inward deformity (CA1 and subiculum subfields) and outward deformity (CA2-4+DG subfield) and smaller left than right volumes. Memory performance was related to hippocampal shape abnormalities in PPA patients, but not controls, even in the absence of memory impairments. Hippocampal deformity in PPA is related to memory test scores. This may reflect a combination of intrinsic degenerative phenomena with transsynaptic or Wallerian effects of neocortical neuronal loss.

Adaptation to Early-Stage Nonfluent/Agrammatic Variant Primary Progressive Aphasia: A First-Person Account.

PubMed

Douglas, Joanne T

2014-06-01

Primary progressive aphasia (PPA) is a young-onset neurodegenerative disorder characterized by declining language ability. The nonfluent/agrammatic variant of PPA (PPA-G) has the core features of agrammatism in language production and effortful, halting speech. As with other frontotemporal spectrum disorders, there is currently no cure for PPA, nor is it possible to slow the course of progression. The primary goal of treatment is therefore palliative in nature. However, there is a paucity of published information about strategies to make meaningful improvements to the quality of life of people with PPA, particularly in the early stages of the disease where any benefit could most be appreciated by the affected person. This report describes a range of strategies and adaptations designed to improve the quality of life of a person with early-stage PPA-G, based on my experience under the care of a multidisciplinary medical team. © The Author(s) 2014.

Advanced Plasma Pyrolysis Assembly (PPA) Reactor and Process Development

NASA Technical Reports Server (NTRS)

Wheeler, Richard R., Jr.; Hadley, Neal M.; Dahl, Roger W.; Abney, Morgan B.; Greenwood, Zachary; Miller, Lee; Medlen, Amber

2012-01-01

Design and development of a second generation Plasma Pyrolysis Assembly (PPA) reactor is currently underway as part of NASA's Atmosphere Revitalization Resource Recovery effort. By recovering up to 75% of the hydrogen currently lost as methane in the Sabatier reactor effluent, the PPA helps to minimize life support resupply costs for extended duration missions. To date, second generation PPA development has demonstrated significant technology advancements over the first generation device by doubling the methane processing rate while, at the same time, more than halving the required power. One development area of particular interest to NASA system engineers is fouling of the PPA reactor with carbonaceous products. As a mitigation plan, NASA MSFC has explored the feasibility of using an oxidative plasma based upon metabolic CO2 to regenerate the reactor window and gas inlet ports. The results and implications of this testing are addressed along with the advanced PPA reactor development.

Cognitive deficits and reduced insight in primary progressive aphasia.

PubMed

Banks, Sarah Jane; Weintraub, Sandra

2008-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA.

Cognitive Deficits and Reduced Insight in Primary Progressive Aphasia

PubMed Central

Banks, Sarah Jane; Weintraub, Sandra

2009-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA. PMID:18836134

Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

PubMed

Teng, Christopher C; De Moraes, Carlos Gustavo V; Prata, Tiago S; Tello, Celso; Ritch, Robert; Liebmann, Jeffrey M

2010-05-01

Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. Retrospective, comparative study. Two hundred forty-five patients from the New York Glaucoma Progression Study. Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. The relationship between beta-zone PPA and the rate and risk of glaucoma progression. Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (<525 microm) had a weak but significant correlation with presence of beta-zone PPA (kappa = 0.13). Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance. Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Analytical results for a stochastic model of gene expression with arbitrary partitioning of proteins

NASA Astrophysics Data System (ADS)

Tschirhart, Hugo; Platini, Thierry

2018-05-01

In biophysics, the search for analytical solutions of stochastic models of cellular processes is often a challenging task. In recent work on models of gene expression, it was shown that a mapping based on partitioning of Poisson arrivals (PPA-mapping) can lead to exact solutions for previously unsolved problems. While the approach can be used in general when the model involves Poisson processes corresponding to creation or degradation, current applications of the method and new results derived using it have been limited to date. In this paper, we present the exact solution of a variation of the two-stage model of gene expression (with time dependent transition rates) describing the arbitrary partitioning of proteins. The methodology proposed makes full use of the PPA-mapping by transforming the original problem into a new process describing the evolution of three biological switches. Based on a succession of transformations, the method leads to a hierarchy of reduced models. We give an integral expression of the time dependent generating function as well as explicit results for the mean, variance, and correlation function. Finally, we discuss how results for time dependent parameters can be extended to the three-stage model and used to make inferences about models with parameter fluctuations induced by hidden stochastic variables.

Retropharyngeal and Parapharyngeal Abscesses Among Children and Adolescents in the United States: Epidemiology and Management Trends, 2003-2012.

PubMed

Woods, Charles R; Cash, Elizabeth D; Smith, Aaron M; Smith, Michael J; Myers, John A; Espinosa, Claudia M; Chandran, Swapna K

2016-09-01

The epidemiology and hospital course of children with retropharyngeal abscess (RPA) or parapharyngeal abscess (PPA) have not been fully described at the national level in the United States. Pediatric discharges for PPA and RPA were evaluated by using the Kids' Inpatient Database from 2003, 2006, 2009, and 2012. Cases were identified by using International Classification of Disease, Ninth Revision, Clinical Modification codes 478.22 and 478.24 for PPA and RPA, respectively. Nationally representative incidence data were calculated by using weighted case estimates and US census data. Demographic and cost analyses were conducted by using unweighted analyses. There were 2685 hospital discharges for PPA and 6233 hospital discharges for RPA during the 4 study years combined. The incidence of RPA increased from 2.98 per 100 000 population among children <20 years old in 2003 to 4.10 per 100 000 in 2012. The incidence of PPA peaked at 1.49 per 100 000 in 2006. Incidences were highest among children <5 years old and boys in all age groups for PPA and RPA. Winter-to-spring seasonality also was evident for both. PPA was managed surgically in 58.1% of the cases, and RPA was managed surgically in 46.7%. Surgery was performed most often on the day of admission or the following day, was more frequent at teaching hospitals, and was associated with higher hospital charges. The mean hospital length of stay was longer for children who had surgery versus those who did not (4.4 vs 3.1 days [for PPA] and 4.8 vs 3.2 days [for RPA], respectively; both P < .001). The median charges for RPA and PPA were similar. The proportions of children with RPA or PPA covered by Medicaid increased during the study period. PPA and RPA represent relatively common male-predominant childhood infections with similar epidemiologies. The incidence of hospital discharges with a diagnosis of RPA increased during the study period. Substantial proportions of children with PPA or RPA are now managed without surgery. Surgical drainage was associated with higher hospital charges and longer lengths of stay. © The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The mechanism of interactions between tea polyphenols and porcine pancreatic alpha‐amylase: Analysis by inhibition kinetics, fluorescence quenching, differential scanning calorimetry and isothermal titration calorimetry

PubMed Central

Sun, Lijun; Gidley, Michael J.

2017-01-01

Scope This study aims to use a combination of biochemical and biophysical methods to derive greater mechanistic understanding of the interactions between tea polyphenols and porcine pancreatic α‐amylase (PPA). Methods and results The interaction mechanism was studied through fluorescence quenching (FQ), differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC) and compared with inhibition kinetics. The results showed that a higher quenching effect of polyphenols corresponded to a stronger inhibitory activity against PPA. The red‐shift of maximum emission wavelength of PPA bound with some polyphenols indicated a potential structural unfolding of PPA. This was also suggested by the decreased thermostability of PPA with these polyphenols in DSC thermograms. Through thermodynamic binding analysis of ITC and inhibition kinetics, the equilibrium of competitive inhibition was shown to result from the binding of particularly galloylated polyphenols with specific sites on PPA. There were positive linear correlations between the reciprocal of competitive inhibition constant (1/K ic), quenching constant (K FQ) and binding constant (K itc). Conclusion The combination of inhibition kinetics, FQ, DSC and ITC can reasonably characterize the interactions between tea polyphenols and PPA. The galloyl moiety is an important group in catechins and theaflavins in terms of binding with and inhibiting the activity of PPA. PMID:28618113

Reduction of the pace polarization artefact for capture detection applications by a tri-phasic stimulation pulse.

PubMed

Sutton, R; Fröhlig, G; de Voogt, W G; Goethals, M; Hintringer, F; Kennergren, C; Scanu, P; Guilleman, D; Treese, N; Hartung, W M; Stammwitz, E; Muetstege, A

2004-11-01

This study investigated the ability to minimize pace polarization artefacts (PPA) by adjusting the post-stimulus pulse duration of a tri-phasic stimulation pulse. Adjustment of the stimulation pulse was enabled by downloading special study software into an already implanted pacemaker. Tests were performed in a total of 296 atrial leads and 311 ventricular leads. Both chronic and acute leads were included in the study. Statistically significant differences were found in the initial PPA (without any adjustment of the stimulus pulse) between atrial and ventricular leads. In addition, significant differences were observed among various lead models with respect to changes over time in the initial ventricular PPA. Successful PPA reduction was defined as a reduction of the PPA below 0.5 mV for atrial leads and below 1 mV for ventricular leads. Results show a success rate for ventricular and atrial PPA reduction of 97.8% and 98.7%, respectively. Threshold tests showed that after reduction of the PPA loss of ventricular capture can be reliably detected. However, atrial threshold tests showed many false positive evoked response detections. In addition, unexpectedly high evoked response amplitudes were observed in the atrium after reduction of the PPA. Results from additional measurements suggest that these high atrial evoked response amplitudes come from the influence of the input filter of the pacemaker.

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation.

PubMed

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA's phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans . We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation.

Relationship Between Physiological and Perceived Fall Risk in People With Multiple Sclerosis: Implications for Assessment and Management.

PubMed

Gunn, Hilary; Cameron, Michelle; Hoang, Phu; Lord, Stephen; Shaw, Steve; Freeman, Jennifer

2018-04-24

This study evaluated the relationship between physiological and perceived fall risk in people with multiple sclerosis (MS). Secondary analysis of data from prospective cohort studies undertaken in Australia, the United Kingdom, and the United States. Community. Ambulatory people with MS (N=416) (age 51.5±12.0 years; 73% female; 62% relapsing-remitting MS; 13.7±9.9 years disease duration). Not applicable. All participants completed measures of physiological (Physiological Profile Assessment [PPA]) and perceived (Falls Efficacy Scale-international [FESi]) fall risk and prospectively recorded falls for 3 months. 155 (37%) of the participants were recurrent fallers (≥2 falls). Mean PPA and FESi scores were high (PPA 2.14±1.87, FESi 34.27±11.18). The PPA and the FESi independently predicted faller classification in logistic regression, which indicated that the odds of being classified as a recurrent faller significantly increased with increasing scores (PPA odds ratio [OR] 1.30 [95% CI 1.17-1.46], FESi OR 1.05 [95% CI 1.03-1.07]). Classification and regression tree analysis divided the sample into four groups based on cutoff values for the PPA: (1) low physiological/low perceived risk (PPA <2.83, FESi <27.5), (2) low physiological/high perceived risk (PPA <2.83, FESi >27.5), (3) high physiological/low perceived risk (PPA >2.83, FESi <35.5), and (4) high physiological/high perceived risk (PPA <2.83, FESi >35.5). Over 50% of participants had a disparity between perceived and physiological fall risk; most were in group 2. It is possible that physiological risk factors not detected by the PPA may also be influential. This study highlights the importance of considering both physiological and perceived fall risk in MS and the need for further research to explore the complex interrelationships of perceptual and physiological risk factors in this population. This study also supports the importance of developing behavioral and physical interventions that can be tailored to the individual's needs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The neural correlates of auditory and visuospatial span in logopenic progressive aphasia and Alzheimer's disease.

PubMed

Foxe, David; Leyton, Cristian E; Hodges, John R; Burrell, James R; Irish, Muireann; Piguet, Olivier

2016-10-01

Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia and is predominantly associated with Alzheimer's disease (AD) pathology. The neuropsychological profiles of lv-PPA and typical clinical AD are, however, distinct. In particular, these two syndromes differ on attention span measures, where auditory attention span is more impaired in lv-PPA than in AD and visuospatial span appears more impaired in AD than in lv-PPA. The neural basis of these span profiles, however, remains unclear. Sixteen lv-PPA and 21 AD matched patients, and 15 education-matched healthy controls were recruited. All participants were assessed by a neurologist and completed a neuropsychological assessment that included the Wechsler Memory Scale-III Digit and Spatial Span tasks, and underwent a high-resolution structural brain MRI to conduct cortical thickness analyses. Patient groups were impaired on all span tasks compared to Controls. In addition, performance on Digit Span Forward (DSF) was significantly lower in the lv-PPA than the AD group, while Spatial Span Forward (SSF) was significantly lower in the AD than the lv-PPA group. No differences were found between patient groups on the Digit or Spatial Span Backward tasks. Neuroimaging analyses revealed that reduced DSF performance correlated to thinning of the left superior temporal gyrus in the lv-PPA group, whereas reduced SSF performance was related to bilateral precentral sulcus and parieto-occipital thinning in the AD group. Analyses of the backward span tasks revealed that reduced Spatial Span Backward (SSB) performance in the lv-PPA group related to cortical thinning of the left superior parietal lobule. This study demonstrates that while lv-PPA and AD commonly share the same underlying neuropathology, their span profiles are distinct and are mediated by divergent patterns of cortical degeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atrophy and structural covariance of the cholinergic basal forebrain in primary progressive aphasia.

PubMed

Teipel, Stefan; Raiser, Theresa; Riedl, Lina; Riederer, Isabelle; Schroeter, Matthias L; Bisenius, Sandrine; Schneider, Anja; Kornhuber, Johannes; Fliessbach, Klaus; Spottke, Annika; Grothe, Michel J; Prudlo, Johannes; Kassubek, Jan; Ludolph, Albert; Landwehrmeyer, Bernhard; Straub, Sarah; Otto, Markus; Danek, Adrian

2016-10-01

Primary progressive aphasia (PPA) is characterized by profound destruction of cortical language areas. Anatomical studies suggest an involvement of cholinergic basal forebrain (BF) in PPA syndromes, particularly in the area of the nucleus subputaminalis (NSP). Here we aimed to determine the pattern of atrophy and structural covariance as a proxy of structural connectivity of BF nuclei in PPA variants. We studied 62 prospectively recruited cases with the clinical diagnosis of PPA and 31 healthy older control participants from the cohort study of the German consortium for frontotemporal lobar degeneration (FTLD). We determined cortical and BF atrophy based on high-resolution magnetic resonance imaging (MRI) scans. Patterns of structural covariance of BF with cortical regions were determined using voxel-based partial least square analysis. We found significant atrophy of total BF and BF subregions in PPA patients compared with controls [F(1, 82) = 20.2, p < .001]. Atrophy was most pronounced in the NSP and the posterior BF, and most severe in the semantic variant and the nonfluent variant of PPA. Structural covariance analysis in healthy controls revealed associations of the BF nuclei, particularly the NSP, with left hemispheric predominant prefrontal, lateral temporal, and parietal cortical areas, including Broca's speech area (p < .001, permutation test). In contrast, the PPA patients showed preserved structural covariance of the BF nuclei mostly with right but not with left hemispheric cortical areas (p < .001, permutation test). Our findings agree with the neuroanatomically proposed involvement of the cholinergic BF, particularly the NSP, in PPA syndromes. We found a shift from a structural covariance of the BF with left hemispheric cortical areas in healthy aging towards right hemispheric cortical areas in PPA, possibly reflecting a consequence of the profound and early destruction of cortical language areas in PPA. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

When the Wedding March becomes sad: Semantic memory impairment for music in the semantic variant of primary progressive aphasia.

PubMed

Macoir, Joël; Berubé-Lalancette, Sarah; Wilson, Maximiliano A; Laforce, Robert; Hudon, Carol; Gravel, Pierre; Potvin, Olivier; Duchesne, Simon; Monetta, Laura

2016-12-01

Music can induce particular emotions and activate semantic knowledge. In the semantic variant of primary progressive aphasia (svPPA), semantic memory is impaired as a result of anterior temporal lobe (ATL) atrophy. Semantics is responsible for the encoding and retrieval of factual knowledge about music, including associative and emotional attributes. In the present study, we report the performance of two individuals with svPPA in three experiments. NG with bilateral ATL atrophy and ND with atrophy largely restricted to the left ATL. Experiment 1 assessed the recognition of musical excerpts and both patients were unimpaired. Experiment 2 studied the emotions conveyed by music and only NG showed impaired performance. Experiment 3 tested the association of semantic concepts to musical excerpts and both patients were impaired. These results suggest that the right ATL seems essential for the recognition of emotions conveyed by music and that the left ATL is involved in binding music to semantics. They are in line with the notion that the ATLs are devoted to the binding of different modality-specific properties and suggest that they are also differentially involved in the processing of factual and emotional knowledge associated with music.

Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

PubMed

Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C

2016-03-01

Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing. The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days. Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry. Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose. PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped. © 2015 The British Pharmacological Society.

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology

PubMed Central

Caso, Francesca; Mandelli, Maria Luisa; Henry, Maya; Gesierich, Benno; Bettcher, Brianne M.; Ogar, Jennifer; Filippi, Massimo; Comi, Giancarlo; Magnani, Giuseppe; Sidhu, Manu; Trojanowski, John Q.; Huang, Eric J.; Grinberg, Lea T.; Miller, Bruce L.; Dronkers, Nina; Seeley, William W.

2014-01-01

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes. Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD–transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data. Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand. Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP. PMID:24353332

Plateau-patella angle in evaluation of patellar height after total knee arthroplasty.

PubMed

Robin, Brett N; Ellington, Matthew D; Jupiter, Daniel C; Allen, Bryce C

2014-07-01

The plateau-patella angle (PPA) has been proposed as a new and simpler method to describe patellar height. This method has not been used or validated in knees following total knee arthroplasty (TKA). A modified PPA (mPPA) was developed for use in this population. The method was validated by determining the interobserver and intraobserver reliability of the technique in 50 consecutive patients compared to three well-described methods of describing patellar height after TKA. Three observers then evaluated the mPPA of 297 post-operative radiographs to describe a normal range after TKA for a given technique and implant. The interobserver reliability was the highest for the mPPA compared to the other methods. The mean mPPA for the entire cohort was 21.06, 20.49, and 19.94 for the three observers. The modified plateau-patella angle is a reliable way to evaluate patellar height in patients who have undergone total knee arthroplasty. Copyright © 2014 Elsevier Inc. All rights reserved.

Degenerative jargon aphasia: unusual progression of logopenic/phonological progressive aphasia?

PubMed

Caffarra, Paolo; Gardini, Simona; Cappa, Stefano; Dieci, Francesca; Concari, Letizia; Barocco, Federica; Ghetti, Caterina; Ruffini, Livia; Prati, Guido Dalla Rosa

2013-01-01

Primary progressive aphasia (PPA) corresponds to the gradual degeneration of language which can occur as nonfluent/agrammatic PPA, semantic variant PPA or logopenic variant PPA. We describe the clinical evolution of a patient with PPA presenting jargon aphasia as a late feature. At the onset of the disease (ten years ago) the patient showed anomia and executive deficits, followed later on by phonemic paraphasias and neologisms, deficits in verbal short-term memory, naming, verbal and semantic fluency. At recent follow-up the patient developed an unintelligible jargon with both semantic and neologistic errors, as well as with severe deficit of comprehension which precluded any further neuropsychological assessment. Compared to healthy controls, FDG-PET showed a hypometabolism in the left angular and middle temporal gyri, precuneus, caudate, posterior cingulate, middle frontal gyrus, and bilaterally in the superior temporal and inferior frontal gyri. The clinical and neuroimaging profile seems to support the hypothesis that the patient developed a late feature of logopenic variant PPA characterized by jargonaphasia and associated with superior temporal and parietal dysfunction.

Data-driven classification of patients with primary progressive aphasia.

PubMed

Hoffman, Paul; Sajjadi, Seyed Ahmad; Patterson, Karalyn; Nestor, Peter J

2017-11-01

Current diagnostic criteria classify primary progressive aphasia into three variants-semantic (sv), nonfluent (nfv) and logopenic (lv) PPA-though the adequacy of this scheme is debated. This study took a data-driven approach, applying k-means clustering to data from 43 PPA patients. The algorithm grouped patients based on similarities in language, semantic and non-linguistic cognitive scores. The optimum solution consisted of three groups. One group, almost exclusively those diagnosed as svPPA, displayed a selective semantic impairment. A second cluster, with impairments to speech production, repetition and syntactic processing, contained a majority of patients with nfvPPA but also some lvPPA patients. The final group exhibited more severe deficits to speech, repetition and syntax as well as semantic and other cognitive deficits. These results suggest that, amongst cases of non-semantic PPA, differentiation mainly reflects overall degree of language/cognitive impairment. The observed patterns were scarcely affected by inclusion/exclusion of non-linguistic cognitive scores. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Aphasic variant of Alzheimer disease

PubMed Central

Sridhar, Jaiashre; Rader, Benjamin; Martersteck, Adam; Chen, Kewei; Cobia, Derin; Thompson, Cynthia K.; Weintraub, Sandra; Bigio, Eileen H.; Mesulam, M.-Marsel

2016-01-01

Objective: To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. Methods: A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Results: Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. Conclusions: There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. PMID:27566743

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia.

PubMed

Rogalski, E; Cobia, D; Harrison, T M; Wieneke, C; Weintraub, S; Mesulam, M-M

2011-05-24

To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects.

Progression of language decline and cortical atrophy in subtypes of primary progressive aphasia

PubMed Central

Cobia, D.; Harrison, T.M.; Wieneke, C.; Weintraub, S.; Mesulam, M.-M.

2011-01-01

Objectives: To examine the longitudinal course of primary progressive aphasia (PPA) over a 2-year period and to offer quantitative ranges of expected change that could be used to guide the design and evaluation of therapeutic intervention trials. Methods: Regional changes of cortical thickness and whole-brain cortical volume loss as well as neuropsychological language performance were assessed at baseline and 2 years later in 13 rigorously characterized patients who fulfilled research criteria for logopenic, agrammatic, and semantic PPA subtypes (6 PPA-L, 3 PPA-G, and 4 PPA-S). Results: There was substantial progression of clinical deficits and cortical atrophy over 2 years. Neuropsychological language performance patterns lost the sharp distinctions that differentiated one PPA variant from another. Nonetheless, the subtype-specific differential impairment of word comprehension vs grammatical processing was largely maintained. Peak atrophy sites spread beyond the initial distinctive locations that characterized each of the 3 subtypes and displayed a more convergent distribution encompassing all 3 major components of the language network: the inferior frontal gyrus, the temporoparietal junction, and lateral temporal cortex. Despite the progression, overall peak atrophy remained lateralized to the left hemisphere. Conclusions: The results suggest that the unique features, which sharply differentiate the PPA variants at the early to middle stages, may lose their distinctiveness as the degeneration becomes more severe. Given the substantial atrophy over 2 years, PPA clinical trials may require fewer patients and shorter study durations than Alzheimer disease trials to detect significant therapeutic effects. PMID:21606451

Assessment of β-zone peripapillary atrophy by optical coherence tomography and scanning laser ophthalmoscopy imaging in glaucoma patients

PubMed Central

Seidensticker, Florian; Reznicek, Lukas; Mann, Thomas; Hübert, Irene; Kampik, Anselm; Ulbig, Michael; Hirneiss, Christoph; Neubauer, Aljoscha S; Kernt, Marcus

2014-01-01

Purpose To assess β-zone peripapillary atrophy (β-PPA) using spectral domain optical coherence tomography (SD-OCT), scanning laser ophthalmoscopy (SLO), and fundus auto-fluorescence (FAF) imaging in patients with primary open-angle glaucoma with advanced glaucomatous visual field defects. Methods A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma were included in this study. All study participants underwent a full ophthalmic examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic nerve head and the peripapillary region. Results Eighty-four glaucomatous eyes were included in our prospective study. Correlation analyses for horizontally and vertically obtained β-PPA for all three imaging modalities (color SLO, FAF, and SD-OCT) revealed highest correlations between FAF and color SLO (Pearson correlation coefficient: 0.904 [P<0.001] for horizontal β-PPA and 0.786 [P<0.001] for vertical β-PPA). Bland–Altman plotting revealed highest agreements between color SLO and FAF, with −2.1 pixels ±1.96 standard deviation (SD) for horizontal β-PPA, SD: 10.5 pixels and 2.4 pixels ±1.96 SD for vertical β-PPA. Conclusion β-PPA can be assessed using en-face SLO and cross-sectional SD-OCT imaging. Correlation analyses revealed highest correlations between color SLO and FAF imaging, while correlations between SLO and SD-OCT were weak. A more precise structural definition of β-PPA is needed. PMID:25061270

Characterization and Comparative Overview of Complete Sequences of the First Plasmids of Pandoraea across Clinical and Non-clinical Strains

PubMed Central

Yong, Delicia; Tee, Kok Keng; Yin, Wai-Fong; Chan, Kok-Gan

2016-01-01

To date, information on plasmid analysis in Pandoraea spp. is scarce. To address the gap of knowledge on this, the complete sequences of eight plasmids from Pandoraea spp. namely Pandoraea faecigallinarum DSM 23572T (pPF72-1, pPF72-2), Pandoraea oxalativorans DSM 23570T (pPO70-1, pPO70-2, pPO70-3, pPO70-4), Pandoraea vervacti NS15 (pPV15) and Pandoraea apista DSM 16535T (pPA35) were studied for the first time in this study. The information on plasmid sequences in Pandoraea spp. is useful as the sequences did not match any known plasmid sequence deposited in public databases. Replication genes were not identified in some plasmids, a situation that has led to the possibility of host interaction involvement. Some plasmids were also void of par genes and intriguingly, repA gene was also not discovered in these plasmids. This further leads to the hypothesis of host-plasmid interaction. Plasmid stabilization/stability protein-encoding genes were observed in some plasmids but were not established for participating in plasmid segregation. Toxin-antitoxin systems MazEF, VapBC, RelBE, YgiT-MqsR, HigBA, and ParDE were identified across the plasmids and their presence would improve plasmid maintenance. Conjugation genes were identified portraying the conjugation ability amongst Pandoraea plasmids. Additionally, we found a shared region amongst some of the plasmids that consists of conjugation genes. The identification of genes involved in replication, segregation, toxin-antitoxin systems and conjugation, would aid the design of drugs to prevent the survival or transmission of plasmids carrying pathogenic properties. Additionally, genes conferring virulence and antibiotic resistance were identified amongst the plasmids. The observed features in the plasmids shed light on the Pandoraea spp. as opportunistic pathogens. PMID:27790203

Generalization and Maintenance of Treatment Gains in Primary Progressive Aphasia (PPA): A Systematic Review

ERIC Educational Resources Information Center

Cadório, Inês; Lousada, Marisa; Martins, Paula; Figueiredo, Daniela

2017-01-01

Background: Cognitive-linguistic treatments and interventions targeting communication have been developed within the context of primary progressive aphasia (PPA), however knowledge about the scope of generalization and maintenance of therapy gains considering PPA subtypes remains scarce and awaits systematic investigation. Aims: To analyse the…

Oligomerization reactions of ribonucleotides - The reaction of the 5'-phosphorimidazolide of adenosine with diadenosine pyrophosphate on montmorillonite and other minerals

NASA Technical Reports Server (NTRS)

Ferris, James P.; Ertem, Gozen

1993-01-01

The overall regiospecificity of the 3',5'-phosphodiester bond formation is shown to be increased from 64 to 83 percent when a 9:1 ratio of ImpA to A5'ppA instead of ImpA alone is reacted in the presence of Na(+)-montmorillonite. The major factor in the regiospecificity increase is the formation of 3',5'-linked A5'ppA3'pA and A5'pp-A3'pA3'pA. The results obtained show that ImpA reacts more readily with A5'ppA than it does with another ImpA molecule and that A5'ppA plays a central role in directing the formation of 3',5'-phosphodiester bonds.

Examination of the abscission-associated transcriptomes for soybean, tomato, and Arabidopsis highlights the conserved biosynthesis of an extensible extracellular matrix and boundary layer

USDA-ARS?s Scientific Manuscript database

PAR1, photoassimilate-responsive-1, was originally identified in a subtraction library prepared from leaves of transgenic tobacco plants, ppa-1, that accumulate high concentrations of sucrose in source leaves. PAR1 genes are highly conserved in both dicots and monocots. All appear to have a signal...

Difunctional bacteriophage conjugated with photosensitizers for Candida albicans-targeting photodynamic inactivation

PubMed Central

Dong, Shuai; Shi, Hongxi; Zhang, Xintong; Chen, Xi; Cao, Donghui; Mao, Chuanbin; Gao, Xiang; Wang, Li

2018-01-01

Background Candida albicans is the most prevalent fungal pathogen of the human microbiota, causing infections ranging from superficial infections of the skin to life-threatening systemic infections. Due to the increasing occurrence of antibiotic-resistant C. albicans strains, new approaches to control this pathogen are needed. Photodynamic inactivation is an emerging alternative to treat infections based on the interactions between visible light and photosensitisers, in which pheophorbide a (PPA) is a chlorophyll-based photosensitizer that could induce cell death after light irradiation. Due to PPA’s phototoxicity and low efficiency, the main challenge is to implement photosensitizer cell targeting and attacking. Methods In this study, PPA was conjugated with JM-phage by EDC/NHS crosslinking. UV-Vis spectra was used to determine the optimum conjugation percentages of PPA and JM-phage complex for photodynamic inactivation. After photodynamic inactivation, the efficacy of PPA-JM-phage was assessed by performing in vitro experiments, such as MTS assay, scanning electron microscopy, measurement of dysfunctional mitochondria, ROS accumulation, S cell arrest and apoptotic pathway. Results A single-chain variable-fragment phage (JM) with high affinity to MP65 was screened from human single-fold single-chain variable-fragment libraries and designed as a binding target for C. albicans cells. Subsequently, PPa was integrated into JM phage to generate a combined nanoscale material, which was called PPA-JM-phage. After photodynamic inactivation, the growth of C. albicans was inhibited by PPA-JM-phage and apoptosis was observed. Scanning electron microscopy analysis revealed shrinking and rupturing of C. albicans. We also found that depolarization of mitochondrial membrane potential was decreased and intracellular reactive oxygen species levels were elevated significantly in C. albicans inhibited by PPA-JM-phage. Additionally, PPA-JM-phage also lead to S-phase arrest, and metacaspase activation resulting from mitochondrial dysfunction was also found to be involved in C. albicans apoptosis. Conclusion PPa-JM-phage may induce C. albicans apoptosis through a caspase-dependent pathway and the results herein shed light on the potential application of phtototherapeutic nanostructures in fungal inactivation. PMID:29692614

Cortical neuroanatomic correlates of symptom severity in primary progressive aphasia

PubMed Central

Sapolsky, D.; Bakkour, A.; Negreira, A.; Nalipinski, P.; Weintraub, S.; Mesulam, M.-M.; Caplan, D.; Dickerson, B.C.

2010-01-01

Objective: To test the validity and reliability of a new measure of clinical impairment in primary progressive aphasia (PPA), the Progressive Aphasia Severity Scale (PASS), and to investigate relationships with MRI-based cortical thickness biomarkers for localizing and quantifying the severity of anatomic abnormalities. Methods: Patients with PPA were rated using the PASS and underwent performance-based language testing and MRI scans that were processed for cortical thickness measures. Results: The level of impairment in PASS fluency, syntax/grammar, and word comprehension showed strong specific correlations with performance-based measures of these domains of language, and demonstrated high interrater reliability. Left inferior frontal thinning correlated with impairment in fluency and grammar/syntax, while left temporopolar thinning correlated with impairment in word comprehension. Discriminant function analysis demonstrated that a combination of left inferior frontal, left temporopolar, and left superior temporal sulcal thickness separated the 3 PPA subtypes from each other with 100% accuracy (87% accuracy in a leave-one-out analysis). Conclusions: The PASS, a novel measure of the severity of clinical impairment within domains of language typically affected in PPA, demonstrates reliable and valid clinical-behavioral properties. Furthermore, the presence of impairment in individual PASS domains demonstrates specific relationships with focal abnormalities in particular brain regions and the severity of impairment is strongly related to the severity of anatomic abnormality within the relevant brain region. These anatomic imaging biomarkers perform well in classifying PPA subtypes. These data provide robust support for the value of this novel clinical measure and the new imaging measure as markers for potential use in clinical research and trials in PPA. GLOSSARY AD = Alzheimer disease; BDAE = Boston Diagnostic Aphasia Examination; CDR = Clinical Dementia Rating; CSB = Cambridge Semantic Battery; ICC = intraclass correlation coefficient; NACC UDS = National Alzheimer's Coordinating Center Uniform Data Set; OC = older control participants; PASS = Progressive Aphasia Severity Scale; PPA = primary progressive aphasia; PPA-G = agrammatic primary progressive aphasia; PPA-L = logopenic primary progressive aphasia; PPA-S = semantic primary progressive aphasia; ROI = region of interest; WAB = Western Aphasia Battery. PMID:20660866

Neural Correlates of Verbal Episodic Memory and Lexical Retrieval in Logopenic Variant Primary Progressive Aphasia.

PubMed

Win, Khaing T; Pluta, John; Yushkevich, Paul; Irwin, David J; McMillan, Corey T; Rascovsky, Katya; Wolk, David; Grossman, Murray

2017-01-01

Objective: Logopenic variant primary progressive aphasia (lvPPA) is commonly associated with Alzheimer's disease (AD) pathology. But lvPPA patients display different cognitive and anatomical profile from the common clinical AD patients, whose verbal episodic memory is primarily affected. Reports of verbal episodic memory difficulty in lvPPA are inconsistent, and we hypothesized that their lexical retrieval impairment contributes to verbal episodic memory performance and is associated with left middle temporal gyrus atrophy. Methods: We evaluated patients with lvPPA ( n = 12) displaying prominent word-finding and repetition difficulties, and a demographically-matched cohort of clinical Alzheimer's disease (AD, n = 26), and healthy seniors ( n = 16). We assessed lexical retrieval with confrontation naming and verbal episodic memory with delayed free recall. Whole-brain regressions related naming and delayed free recall to gray matter atrophy. Medial temporal lobe (MTL) subfields were examined using high in-plane resolution imaging. Results: lvPPA patients had naming and delayed free recall impairments, but intact recognition memory. In lvPPA, delayed free recall was related to naming; both were associated with left middle temporal gyrus atrophy but not MTL atrophy. Despite cerebrospinal fluid evidence consistent with AD pathology, examination of MTL subfields revealed no atrophy in lvPPA. While AD patients displayed impaired delayed free recall, this deficit did not correlate with naming. Regression analyses related delayed free recall deficits in clinical AD patients to MTL subfield atrophy, and naming to left middle temporal gyrus atrophy. Conclusion: Unlike amnestic AD patients, MTL subfields were not affected in lvPPA patients. Verbal episodic memory deficit observed in lvPPA was unlikely to be due to a hippocampal-mediated mechanism but appeared to be due to poor lexical retrieval. Relative sparing of MTL volume and intact recognition memory are consistent with previous reports of hippocampal-sparing variant cases of AD pathology, where neurofibrillary tangles are disproportionately distributed in cortical areas with relative sparing of the hippocampus. This suggests that AD neuropathology in lvPPA may originate in neuronal networks outside of the MTL, which deviates from the typical Braak staging pattern of spreading pathology in clinical AD.

Aphasic variant of Alzheimer disease: Clinical, anatomic, and genetic features.

PubMed

Rogalski, Emily; Sridhar, Jaiashre; Rader, Benjamin; Martersteck, Adam; Chen, Kewei; Cobia, Derin; Thompson, Cynthia K; Weintraub, Sandra; Bigio, Eileen H; Mesulam, M-Marsel

2016-09-27

To identify features of primary progressive aphasia (PPA) associated with Alzheimer disease (AD) neuropathology. A related objective was to determine whether logopenic PPA is a clinical marker for AD. A total of 139 prospectively enrolled participants with a root diagnosis of PPA constituted the reference set. Those with autopsy or biomarker evidence of AD, and who had been evaluated at mild disease stages (Aphasia Quotient ≥85), were included (n = 19). All had quantitative language testing and APOE genotyping. Fifteen had MRI morphometry. Impaired word-finding was the universal presenting complaint in the aphasic AD group. PPA clinical subtype was logopenic (n = 13) and agrammatic (n = 6). Fluency, repetition, naming, and grammaticality ranged from preserved to severely impaired. All had relative preservation of word comprehension. Eight of the 15 aphasic participants with AD showed no appreciable cortical atrophy at the individual level on MRI. As a group, atrophy was asymmetrically concentrated in the left perisylvian cortex. APOE ε4 frequency was not elevated. There is a close, but not obligatory, association between logopenic PPA and AD. No language measure, with the possible exception of word comprehension, can confirm or exclude AD in PPA. Biomarkers are therefore essential for diagnosis. Asymmetry of cortical atrophy and normal APOE ε4 prevalence constitute deviations from typical AD. These and additional neuropathologic features suggest that AD has biological subtypes, one of which causes PPA. Better appreciation of this fact should promote the inclusion of individuals with PPA and positive AD biomarkers into relevant clinical trials. © 2016 American Academy of Neurology.

Behavioural and neuroanatomical correlates of auditory speech analysis in primary progressive aphasias.

PubMed

Hardy, Chris J D; Agustus, Jennifer L; Marshall, Charles R; Clark, Camilla N; Russell, Lucy L; Bond, Rebecca L; Brotherhood, Emilie V; Thomas, David L; Crutch, Sebastian J; Rohrer, Jonathan D; Warren, Jason D

2017-07-27

Non-verbal auditory impairment is increasingly recognised in the primary progressive aphasias (PPAs) but its relationship to speech processing and brain substrates has not been defined. Here we addressed these issues in patients representing the non-fluent variant (nfvPPA) and semantic variant (svPPA) syndromes of PPA. We studied 19 patients with PPA in relation to 19 healthy older individuals. We manipulated three key auditory parameters-temporal regularity, phonemic spectral structure and prosodic predictability (an index of fundamental information content, or entropy)-in sequences of spoken syllables. The ability of participants to process these parameters was assessed using two-alternative, forced-choice tasks and neuroanatomical associations of task performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. Relative to healthy controls, both the nfvPPA and svPPA groups had impaired processing of phonemic spectral structure and signal predictability while the nfvPPA group additionally had impaired processing of temporal regularity in speech signals. Task performance correlated with standard disease severity and neurolinguistic measures. Across the patient cohort, performance on the temporal regularity task was associated with grey matter in the left supplementary motor area and right caudate, performance on the phoneme processing task was associated with grey matter in the left supramarginal gyrus, and performance on the prosodic predictability task was associated with grey matter in the right putamen. Our findings suggest that PPA syndromes may be underpinned by more generic deficits of auditory signal analysis, with a distributed cortico-subcortical neuraoanatomical substrate extending beyond the canonical language network. This has implications for syndrome classification and biomarker development.

Phonologic errors as a clinical marker of the logopenic variant of PPA.

PubMed

Leyton, Cristian E; Ballard, Kirrie J; Piguet, Olivier; Hodges, John R

2014-05-06

To disentangle the clinical heterogeneity of nonsemantic variants of primary progressive aphasia (PPA) and to identify a coherent linguistic-anatomical marker for the logopenic variant of PPA (lv-PPA). Key speech and language features of 14 cases of lv-PPA and 18 cases of nonfluent/agrammatic variant of PPA were systematically evaluated and scored by an independent rater blinded to diagnosis. Every case underwent a structural MRI and a Pittsburgh compound B (PiB)-PET scan, a putative biomarker of Alzheimer disease. Key speech and language features that showed association with the PiB-PET status were entered into a hierarchical cluster analysis. The linguistic features and patterns of cortical thinning in each resultant cluster were analyzed. The cluster analysis revealed 3 coherent clinical groups, each of which was linked to a specific PiB-PET status. The first cluster was linked to high PiB retention and characterized by phonologic errors and cortical thinning focused on the left superior temporal gyrus. The second and third clusters were characterized by grammatical production errors and motor speech disorders, respectively, and were associated with low PiB brain retention. A fourth cluster, however, demonstrated nonspecific language deficits and unpredictable PiB-PET status. These findings suggest that despite the clinical and pathologic heterogeneity of nonsemantic variants, discrete clinical syndromes can be distinguished and linked to specific likelihood of PiB-PET status. Phonologic errors seem to be highly predictive of high amyloid burden in PPA and can provide a specific clinical marker for lv-PPA.

Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

ClinicalTrials.gov

2018-05-01

FTLD; Progressive Supranuclear Palsy (PSP); Frontotemporal Dementia (FTD); Corticobasal Degeneration (CBD); PPA Syndrome; Behavioral Variant Frontotemporal Dementia (bvFTD); Semantic Variant Primary Progressive Aphasia (svPPA); Nonfluent Variant Primary Progressive Aphasia (nfvPPA); FTD With Amyotrophic Lateral Sclerosis (FTD/ALS); Amyotrophic Lateral Sclerosis (ALS); Oligosymptomatic PSP (oPSP); Corticobasal Syndrome (CBS)

Fabrication of powdery polymer aerogel as the stationary phase for high-resolution gas chromatographic separation.

PubMed

Zheng, Juan; Lu, Cuiming; Huang, Junlong; Chen, Luyi; Ni, Chuyi; Xie, Xintong; Zhu, Fang; Wu, Dingcai; Ouyang, Gangfeng

2018-08-15

Novel powdery polymer aerogel (PPA) prepared via the (micro)emulsion polymerization and the following hyper crosslinking reaction was fabricated as stationary phase of capillary column for the first time. Due to its powdery morphology, unique 3D nano-network structure, high surface area and good thermostability, the PPA-coated capillary column demonstrated high-resolution chromatographic separation towards nonpolar and weakly polar organic compounds, including benzene series, n-alkanes, ketone mixtures and trichlorobenzenes. Moreover, the reproducibility, quantitative analysis ability and thermostability of PPA-coated capillary column were also evaluated. The relative standard deviations for three replicate determinations of selected analytes were 0.02-0.11%, 0.12-0.26% and 1.2-3.6% for run-to-run, day-to-day and column-to-column analyses, respectively. The PPA demonstrated good thermostability, and the PPA-coated capillary column was proved to be heat-resistant (270 °C). The results of this study show PPA is an excellent candidate to be employed as stationary phase for gas chromatography capillary. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of Polyphosphoric Acid on the Consistency and Composition of Formulated Bitumen: Standard Characterization and NMR Insights

PubMed Central

Varanda, Catarina; Ribeiro, Jorge

2016-01-01

Over the recent years, bitumen modification with polymers, acids, or mineral fillers has gained relevance to adjust its performance properties. This work reports the use of polyphosphoric acid (PPA) for the modification of formulated bitumen. With this objective, an in-depth literature review on PPA modification was firstly performed. Subsequently, five individual refinery components were selected for the preparation of bitumen blends, namely, asphaltic residue, vacuum residue, and three lube oils extracts. Seven binary/ternary bitumen blends were prepared and then treated with PPA. Afterwards, the five components and the unmodified and PPA-modified bitumen were characterized by standard methods (penetration, softening point, and penetration index), SARA analysis, elemental analysis, and 31P and 1H nuclear magnetic resonance (NMR) spectroscopy. The results evidenced higher asphaltenes and lower saturates/resins contents in PPA-modified bitumen. The NMR data suggest that the paraffinic chains became longer, the content of condensed aromatics increased, more substituted aromatic structures appeared, and α-hydrogen in aromatic structures diminished. These findings disclosed the improved consistency and oxidation stability of PPA-modified bitumen blends. PMID:27579214

A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

NASA Astrophysics Data System (ADS)

Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

2016-02-01

Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07785k

Detection of Bovine IgG Isotypes in a PPA-ELISA for Johne's Disease Diagnosis in Infected Herds

PubMed Central

Fernández, Bárbara; Gilardoni, Liliana Rosa; Jolly, Ana; Colavecchia, Silvia Beatriz; Paolicchi, Fernando Alberto; Mundo, Silvia Leonor

2012-01-01

Johne's Disease or Paratuberculosis is a chronic granulomatous enteritis disease affecting ruminants. Detection of subclinically infected animals is difficult, hampering the control of this disease. The aim of this work was to evaluate the performance of detection of IgG isotypes in a PPA-ELISA to improve the recognition of cattle naturally infected with Map in different stages. A total of 108 animals from Tuberculosis-free herds were grouped as follows: exposed (n = 30), subclinically infected (n = 26), clinically infected (n = 14), and healthy controls (n = 38). Receiver-operating characteristic (ROC) curves of isotypes/PPA-ELISAs were constructed and areas under the curves were compared to evaluate the performance of each test. Our study demonstrated that the conventional PPA-ELISA (detecting IgG) is the best to identify clinically infected animals with high sensitivity (92.9%) and specificity (100%). Meanwhile, IgG2/PPA-ELISA improved the number of subclinically infected cattle detected as compared with conventional IgG/PPA-ELISA (53.8 versus 23.1%). In addition, it had the maximum sensitivity (65.0%, taking into account all Map-infected cattle). In conclusion, the combination of IgG and IgG2/PPA-ELISAs may improve the identification of Map-infected cattle in different stages of disease. The usefulness of IgG2 detection in serological tests for Johne's Disease diagnosis should be further evaluated. PMID:22792511

Detection of Bovine IgG Isotypes in a PPA-ELISA for Johne's Disease Diagnosis in Infected Herds.

PubMed

Fernández, Bárbara; Gilardoni, Liliana Rosa; Jolly, Ana; Colavecchia, Silvia Beatriz; Paolicchi, Fernando Alberto; Mundo, Silvia Leonor

2012-01-01

Johne's Disease or Paratuberculosis is a chronic granulomatous enteritis disease affecting ruminants. Detection of subclinically infected animals is difficult, hampering the control of this disease. The aim of this work was to evaluate the performance of detection of IgG isotypes in a PPA-ELISA to improve the recognition of cattle naturally infected with Map in different stages. A total of 108 animals from Tuberculosis-free herds were grouped as follows: exposed (n = 30), subclinically infected (n = 26), clinically infected (n = 14), and healthy controls (n = 38). Receiver-operating characteristic (ROC) curves of isotypes/PPA-ELISAs were constructed and areas under the curves were compared to evaluate the performance of each test. Our study demonstrated that the conventional PPA-ELISA (detecting IgG) is the best to identify clinically infected animals with high sensitivity (92.9%) and specificity (100%). Meanwhile, IgG2/PPA-ELISA improved the number of subclinically infected cattle detected as compared with conventional IgG/PPA-ELISA (53.8 versus 23.1%). In addition, it had the maximum sensitivity (65.0%, taking into account all Map-infected cattle). In conclusion, the combination of IgG and IgG2/PPA-ELISAs may improve the identification of Map-infected cattle in different stages of disease. The usefulness of IgG2 detection in serological tests for Johne's Disease diagnosis should be further evaluated.

Peritraumatic panic attacks and health outcomes two years after psychological trauma: implications for intervention and research.

PubMed

Boscarino, Joseph A; Adams, Richard E

2009-05-15

Several studies have suggested that experiencing a peritraumatic panic attack (PPA) during a traumatic event predicts future mental health status. Some investigators have suggested that this finding has psychotherapeutic significance. We assessed the hypothesis that PPA was not related to longer-term health status after event exposure, once background confounders were controlled. In our study we assessed exposure to the World Trade Center disaster (WTCD) and other negative life events, demographic factors, social support, self-esteem, and panic attack onset in predicting health outcome among 1681 New York City residents 2 years after the attack. Initial bivariate results indicated that a PPA was related to a number of adverse outcomes 2 years after the WTCD, including posttraumatic stress disorder, depression, poor physical health, anxiety, binge drinking, and mental health treatment seeking. However, when multivariate (MV) models were estimated adjusting for potential confounders, most of these associations were either non-significant or substantially reduced. Contrary to previous predictions, these MV models revealed that recent negative life events and current self-esteem at follow-up were the best predictors of health outcomes, not PPA. Although post-trauma interventions may target individuals who experienced PPA after traumatic exposures, reducing the long-term health consequences following such exposures based on PPA alone may be problematic. Modifications of psychopathology constructs based on the reported correlation between PPA and post-trauma outcomes may be premature.

Phonological short-term memory in logopenic variant primary progressive aphasia and mild Alzheimer's disease.

PubMed

Meyer, Aaron M; Snider, Sarah F; Campbell, Rachael E; Friedman, Rhonda B

2015-10-01

It has been argued that individuals with logopenic variant primary progressive aphasia (lvPPA) have an impairment of the phonological loop, which is a component of the short-term memory (STM) system. In contrast, this type of impairment is not thought to be present in mild typical Alzheimer's disease (AD). Thus, one would predict that people with lvPPA would score significantly lower than a matched AD group on tasks that require phonological STM. In the current study, an lvPPA group was compared with a mild AD group that was matched on age, education, and general cognitive functioning. For a subset of the tasks that involved pseudowords, the AD and lvPPA groups were compared to a healthy control group that was matched on age and education. The lvPPA group was more impaired than the AD group on all of the tasks that required phonological STM, including the pseudoword tasks, but there were no significant differences between these groups on tasks that required visuospatial STM. Compared to the healthy controls, the lvPPA group performed significantly worse on the repetition and reading of pseudowords, while the AD group did not differ significantly from the controls on these tasks. These findings are consistent with the hypothesis that phonological STM is impaired in lvPPA. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arbuscular Mycorrhizal Fungi Elicit a Novel Intracellular Apparatus in Medicago truncatula Root Epidermal Cells before InfectionW⃞

PubMed Central

Genre, Andrea; Chabaud, Mireille; Timmers, Ton; Bonfante, Paola; Barker, David G.

2005-01-01

The penetration of arbuscular mycorrhizal (AM) fungi through the outermost root tissues of the host plant is a critical step in root colonization, ultimately leading to the establishment of this ecologically important endosymbiotic association. To evaluate the role played by the host plant during AM infection, we have studied in vivo cellular dynamics within Medicago truncatula root epidermal cells using green fluorescent protein labeling of both the plant cytoskeleton and the endoplasmic reticulum. Targeting roots with Gigaspora hyphae has revealed that, before infection, the epidermal cell assembles a transient intracellular structure with a novel cytoskeletal organization. Real-time monitoring suggests that this structure, designated the prepenetration apparatus (PPA), plays a central role in the elaboration of the apoplastic interface compartment through which the fungus grows when it penetrates the cell lumen. The importance of the PPA is underlined by the fact that M. truncatula dmi (for doesn't make infections) mutants fail to assemble this structure. Furthermore, PPA formation in the epidermis can be correlated with DMI-dependent transcriptional activation of the Medicago early nodulin gene ENOD11. These findings demonstrate how the host plant prepares and organizes AM infection of the root, and both the plant–fungal signaling mechanisms involved and the mechanistic parallels with Rhizobium infection in legume root hairs are discussed. PMID:16284314

75 FR 64123 - Hybrid Retirement Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-19

... has completed at least 3 years of service has a nonforfeitable right to 100 percent of the employee's... distributions made after August 17, 2006 (the date PPA '06 was enacted). Under section 701(e) of PPA '06, the 3.... Under section 701(e)(6) of PPA '06, as added by WRERA '08, the 3- year vesting rule under section 411(a...

Oligomerization of uridine phosphorimidazolides on montmorillonite: a model for the prebiotic synthesis of RNA on minerals

NASA Technical Reports Server (NTRS)

Ding, P. Z.; Kawamura, K.; Ferris, J. P.

1996-01-01

The 5'-phosphorimidazolide of uridine reacts on Na(+)-montmorillonite 22A in aqueous solution to give oligomers as long as 7 mers. The maximum chain length increases to 9 mers and the overall oligomer yield increases when 9:1 ImpU, A5' ppA mixtures react under the same conditions. The oligomer yield and maximum chain length decreases with the structure of the added pyrophosphate in the order A5' ppA > A5' ppU > U5' ppU. Structure analysis of individual oligomer fractions was performed by selective enzymatic hydrolyses followed by HPLC analysis of the products. The regioselectivity for 3',5'-bond formation is 80-90% in the 9:1 ImpU, A5' ppA reaction, a percentage comparable to that observed in the 9:1 ImpA, A5' ppA reaction. Oligomerization of ImpU is inhibited by addition of dA5' ppdA, and MeppA. No oligomers containing A5' ppU were products of the 9:1 ImpU,A5' ppA reaction, a finding consistent with the simple addition of the ImpU to the A5' ppA and not the rearrangement of an ImpU-A5' ppA adduct. Concentrations of lysine or arginine which were close to that of the ImpU did not inhibit oligomer formation. Treatment of Na(+)-montmorillonite with 1 M arginine yielded arginine-montmorillonite, an amino acid-mineral adduct which did not catalyze ImpU oligomerization. Neither the 4-9 mers formed in the 9:1 ImpU, A5' ppA reaction nor the 4-9 mers formed by the base hydrolysis of poly(U) served as templates for the formation of oligo(A)s.

Photometer Performance Assessment in TESS SPOC Pipeline

NASA Astrophysics Data System (ADS)

Li, Jie; Caldwell, Douglas A.; Jenkins, Jon Michael; Twicken, Joseph D.; Wohler, Bill; Chen, Xiaolan; Rose, Mark; TESS Science Processing Operations Center

2018-06-01

This poster describes the Photometer Performance Assessment (PPA) software component in the Transiting Exoplanet Survey Satellite (TESS) Science Processing Operations Center (SPOC) pipeline, which is developed based on the Kepler science pipeline. The PPA component performs two tasks: the first task is to assess the health and performance of the instrument based on the science data sets collected during each observation sector, identifying out of bounds conditions and generating alerts. The second is to combine the astrometric data collected for each CCD readout channel to construct a high fidelity record of the pointing history for each of the 4 cameras and an attitude solution for the TESS spacecraft for each 2-min data collection interval. PPA is implemented with multiple pipeline modules: PPA Metrics Determination (PMD), PMD Aggregator (PAG), and PPA Attitude Determination (PAD). The TESS Mission is funded by NASA's Science Mission Directorate. The SPOC is managed and operated by NASA Ames Research Center.

Toxicological studies on pipemidic acid. V. Effect on diarthrodial joints of experimental animals.

PubMed

Tatsumi, H; Senda, H; Yatera, S; Takemoto, Y; Yamayoshi, M; Ohnishi, K

1978-11-01

Pipemidic acid (PPA) orally given in a dose of 100 mg/kg/day or more was found to cause lame gait in immature beagle dogs of about 3 months old. Their diarthrodial joints were abnormal with increased synovial fluid and blister formation under the outer layer of the articular cartilage. However, such an abnormality was not found in dogs younger than 2 weeks or older than 12 months. The blisters were formed at the joint areas bearing the body weight at a time when PPA was considered to be present there. Nalidixic and piromidic acids, structural analogues of PPA, also caused abnormality similar to PPA. The severity of the arthropathy was slight with piromidic acid as compared with PPA and nalidixic acid. The gait abnormality was almost disappeared spontaneously even if medication was continued. The incidence of the arthropathy was not or rarely observed in any young rats, rabbits and monkeys.

Deletion polymorphisms in the angiotensin converting enzyme gene are associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease.

PubMed

Kanazawa, H; Okamoto, T; Hirata, K; Yoshikawa, J

2000-10-01

Angiotensin converting enzyme (ACE) plays an important role in the pathogenesis of pulmonary hypertension. In this study we determined whether the deletion (D)/insertion (I) polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with chronic obstructive pulmonary disease (COPD). ACE genotypes were determined in 19 patients with COPD. All patients underwent right heart catheterization followed by a constant-load exercise test while breathing room air or oxygen. Subgroups were created of seven patients with the II genotype, six with the ID genotype, and six with the DD genotype who were well-matched with respect to age, blood gas data at rest or after exercise, baseline lung function, results of incremental exercise testing, and hemodynamic data at rest. The mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (Rpv) at rest in the three subgrpoups did not differ significantly during breathing of either room air or oxygen. However, the Ppa after exercise challenge in patients with the DD genotype (55.7 +/- 4.9 mm Hg [mean +/- SD]) was significantly higher than in patients with the II genotype (42.6 +/- 7.1 mm Hg, p = 0.008). The Rpv after exercise in patients with the DD genotype was also significantly higher than in patients with the ID and II genotypes. During breathing of oxygen to diminish acute hypoxic pulmonary vasoconstriction, the Ppa in patients with the DD genotype (52.3 +/- 3.1 mm Hg) was higher than in patients with the ID genotype (40.5 +/- 5.9 mm Hg, p = 0.0049) or the II genotype (37.7 +/- 5.9 mm Hg, p = 0.0027). In addition, the Rpv in patients with the DD genotype was higher than in patients with the ID and II genotypes. These results suggest that D-I polymorphism in the ACE gene may be associated with pulmonary hypertension evoked by exercise challenge in patients with COPD. However, the number of patients in this study was very small for a genetic association study, and our results should be examined in larger studies.

29 CFR 4022.51 - Determination of section 4022(c) benefits in a PPA 2006 bankruptcy termination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Effective Date Note: § 4022.51 Determination of section 4022(c) benefits in a PPA 2006 bankruptcy... neither guaranteed by PBGC (taking into account section 4022(g) of ERISA) nor funded by the plan's assets (taking into account section 4044(e) of ERISA). (c) Determination of recovery ratio. In a PPA 2006...

Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA

PubMed Central

Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Lowe, Val J.; Jack, Clifford R.; Whitwell, Jennifer L.

2013-01-01

Objective: We assessed whether clinical and imaging features of subjects with apraxia of speech (AOS) more severe than aphasia (dominant AOS) are more similar to agrammatic primary progressive aphasia (agPPA) or to primary progressive AOS (PPAOS). Methods: Sixty-seven subjects (PPAOS = 18, dominant AOS = 10, agPPA = 9, age-matched controls = 30) who all had volumetric MRI, diffusion tensor imaging, F18-fluorodeoxyglucose and C11-labeled Pittsburgh compound B (PiB)-PET scanning, as well as neurologic and speech and language assessments, were included in this case-control study. AOS was classified as either type 1, predominated by sound distortions and distorted sound substitutions, or type 2, predominated by syllabically segmented prosodic speech patterns. Results: The dominant AOS subjects most often had AOS type 2, similar to PPAOS. In contrast, agPPA subjects most often had type 1 (p = 0.01). Both dominant AOS and PPAOS showed focal imaging abnormalities in premotor cortex, whereas agPPA showed widespread involvement affecting premotor, prefrontal, temporal and parietal lobes, caudate, and insula. Only the dominant AOS and PPAOS groups showed midbrain atrophy compared with controls. No differences were observed in PiB binding across all 3 groups, with the majority being PiB negative. Conclusion: These results suggest that dominant AOS is more similar to PPAOS than agPPA, with dominant AOS and PPAOS exhibiting a clinically distinguishable subtype of progressive AOS compared with agPPA. PMID:23803320

Apraxia of Speech and Phonological Errors in the Diagnosis of Nonfluent/Agrammatic and Logopenic Variants of Primary Progressive Aphasia

ERIC Educational Resources Information Center

Croot, Karen; Ballard, Kirrie; Leyton, Cristian E.; Hodges, John R.

2012-01-01

Purpose: The International Consensus Criteria for the diagnosis of primary progressive aphasia (PPA; Gorno-Tempini et al., 2011) propose apraxia of speech (AOS) as 1 of 2 core features of nonfluent/agrammatic PPA and propose phonological errors or absence of motor speech disorder as features of logopenic PPA. We investigated the sensitivity and…

[A study on europium sensitized chemiluminescence of pipemidic acid].

PubMed

Li, Xia; Qiang, Hong; Wang, Xiao-li; Chen, Shi-lü; Zhao, Hui-chun

2004-12-01

A flow injection chemiluminescence method for the determination of Pipemidic acid (PPA) was developed. It is based on luminescence produced with KMnO4-Na2S2O4 CL system sensitized by Eu3+-PPA. The familar excipients such as starch and dextrine do not cause interference. The several kinds of affect on chemiluminescence were studied. The linear range and detection limit for PPA are 7.00 x 10(-9)-9.00 x 10(-7) mol x L(-1) and 4.09 x 10(-9) mol x L(-1), respectively. This method have successfully been applied to the determination of PPA in tablet and urine. And the mechanism of chemiluminescence is proposed.

DISRUPTION OF LARGE-SCALE NEURAL NETWORKS IN NON-FLUENT/AGRAMMATIC VARIANT PRIMARY PROGRESSIVE APHASIA ASSOCIATED WITH FRONTOTEMPORAL DEGENERATION PATHOLOGY

PubMed Central

Grossman, Murray; Powers, John; Ash, Sherry; McMillan, Corey; Burkholder, Lisa; Irwin, David; Trojanowski, John Q.

2012-01-01

Non-fluent/agrammatic primary progressive aphasia (naPPA) is a progressive neurodegenerative condition most prominently associated with slowed, effortful speech. A clinical imaging marker of naPPA is disease centered in the left inferior frontal lobe. We used multimodal imaging to assess large-scale neural networks underlying effortful expression in 15 patients with sporadic naPPA due to frontotemporal lobar degeneration (FTLD) spectrum pathology. Effortful speech in these patients is related in part to impaired grammatical processing, and to phonologic speech errors. Gray matter (GM) imaging shows frontal and anterior-superior temporal atrophy, most prominently in the left hemisphere. Diffusion tensor imaging reveals reduced fractional anisotropy in several white matter (WM) tracts mediating projections between left frontal and other GM regions. Regression analyses suggest disruption of three large-scale GM-WM neural networks in naPPA that support fluent, grammatical expression. These findings emphasize the role of large-scale neural networks in language, and demonstrate associated language deficits in naPPA. PMID:23218686

Effect of dinucleoside pyrophosphates on the oligomerization of activated mononucleotides on Na(+)-montmorillonite: reaction of 5'-phosphoro-4-(dimethylamino)pyridinium [4-(CH3)2NpypA] with A5'ppA

NASA Technical Reports Server (NTRS)

Prabahar, K. J.; Ferris, J. P.

1997-01-01

The oligomerization of adenosine 5'-phosphoro-4-(dimethylamino)pyridinium (4-(CH3)2-NpypA) and diadenosine 5',5'-pyrophosphate (A5'ppA) (9:1) on Na(+)-montmorillonite was studied. The oligomers were isolated and analyzed by selective enzymatic hydrolyses and the oligomeric composition and the percent of 3',5'-phosphodiester linkages present in each fraction was determined. The longest oligomers formed (11-mers) are slightly shorter than those produced in the absence of A5'ppA (12-mers). Smaller amounts of A5'ppA are incorporated into the oligomers than in the ImpA/A5'ppA reaction. The regioselectivity of 3',5'-phosphodiester bond formation is comparable to that of the oligomerization of 4-(CH3)2NpypA alone. An explanation of these data is proposed and the possible effect of dinucleoside pyrophosphate on prebiotic RNA formation is discussed.

Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech.

PubMed

Poole, Matthew L; Brodtmann, Amy; Darby, David; Vogel, Adam P

2017-04-14

Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Speech and neuroimaging data described in studies of FTD and PPA were systematically reviewed. A meta-analysis was conducted for speech measures that were used consistently in multiple studies. The methods and nomenclature used to describe speech in these disorders varied between studies. Our meta-analysis identified 3 speech measures which differentiate variants or healthy control-group participants (e.g., nonfluent and logopenic variants of PPA from all other groups, behavioral-variant FTD from a control group). Deficits within the frontal-lobe speech networks are linked to motor speech profiles of the nonfluent variant of PPA and progressive apraxia of speech. Motor speech impairment is rarely reported in semantic and logopenic variants of PPA. Limited data are available on motor speech impairment in the behavioral variant of FTD. Our review identified several measures of speech which may assist with diagnosis and classification, and consolidated the brain-behavior associations relating to speech in FTD, PPA, and progressive apraxia of speech.

Theoretical study on the phenylpropanolamine drug interaction with the pristine, Si and Al doped [60] fullerenes

NASA Astrophysics Data System (ADS)

Moradi, Morteza; Nouraliei, Milad; Moradi, Reza

2017-03-01

Phenylpropanolamine (PPA) is a popular drug of abuse and its detection is of great importance for police and drug communities. Herein, we investigated the electronic sensitivity and reactivity of pristine, Al and Si doped C60 fullerenes to the PPA drug, using density functional theory calculations. Two adsorption mechanisms were predicted for PPA on the pristine C60 including cycloaddition and adsorption via -NH2 group. It was found that the pristine C60 has a good sensitivity to this drug but suffers from a weak interaction (adsorption energy -0.1 kcal/mol) because of structural deformation and aromaticity break. The PPA is adsorbed on the Al or Si doped C60 from its -OH or -NH2 groups. The Al-doping significantly improves the reactivity of C60 but decreases its electronic sensitivity. Unlike the Al-doping, the Si-doping increases both the reactivity and electronic sensitivity to the PPA drug. At the presence of PPA drug, the conductivity of the Si-doped C60 considerably increases due to the HOMO-LUMO gap reduction by about 30.3%. Different analyses were used to obtain the results including nucleus independent chemical shift (NICS), density of states (DOS), molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), etc.

Primary progressive aphasia: from syndrome to disease.

PubMed

Matías-Guiu, J A; García-Ramos, R

2013-01-01

Primary progressive aphasia (PPA) is a clinical syndrome characterised by a progressive decline in language and speech of neurodegenerative origin. Major breakthroughs made in recent years have lent us a better understanding of this syndrome, which may be the first manifestation of any of a number of neurodegenerative diseases. We reviewed the main aspects of PPA epidemiology, clinical manifestations, diagnosis, aetiology and treatment. Most cases manifest sporadically and the typical age of onset is between 50 and 70 years. Three clinically distinct variants have been described: nonfluent or agrammatic PPA, semantic PPA and logopenic PPA. Each of these variants tends to be associated with specific histopathological findings, but clinical diagnostic methods are imperfect predictors of underlying pathology. Anatomical and functional neuroimaging can provide useful biomarkers. Several treatments have been proposed, and while no clear benefits have been demonstrated, acetylcholinesterase inhibitors may be useful, especially in the logopenic variant. PPA is an emerging syndrome which may be more prevalent than we might expect. It was previously listed as part of the frontotemporal dementia spectrum, and it is also related to Alzheimer disease. Clinical diagnosis, complemented by a biomarker evaluation, may predict the underlying pathology, which in turn will improve treatment possibilities. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Nonlinear analysis of fetal heart rate dynamics in fetuses compromised by asymptomatic partial placental abruption.

PubMed

Choi, Won-Young; Hoh, Jeong-Kyu

2015-12-01

We analyzed fetal heart rate (FHR) parameters, dynamics, and outcomes in pregnancies with asymptomatic partial placental abruption (PPA) compared with those in normal pregnancies. We examined nonstress test (NST) data acquired from 2003 to 2012 at our institution. Normal pregnancies (N = 170) and PPA cases (N = 17) were matched for gestational age, fetal sex, and mean FHR. NSTs were performed at 33-42 weeks of gestation. FHR parameters obtained from the NST and perinatal outcomes were analyzed using linear methods. Nonlinear indices, including approximate entropy (ApEn), sample entropy (SampEn), short-term and long-term scaling exponents (α1 and α2), and correlation dimension (CD), were used to interpret FHR dynamics and system complexity. The area under a receiver operating characteristic curve (AUC) was used to evaluate the nonlinear indices. There were no significant differences in general characteristics and FHR parameters between the PPA and control groups. However, gestational age at delivery, birth weight, 5-min Apgar scores, ApEn, SampEn, and CD were significantly lower in the PPA group than in the control group (P < 0.05). The long-term scaling exponent (α2) and crossover index (α2/α1) of the PPA fetuses were significantly higher than those of the controls (P < 0.01). A multiple regression model showed better performance in predicting PPA (AUC, 0.92; sensitivity 82.35%; specificity, 94.12%). Nonlinear dynamic indices of FHR in asymptomatic PPA were qualitatively different from those in normal pregnancies, whereas the conventional FHR parameters were not significantly different. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anatomic, clinical, and neuropsychological correlates of spelling errors in primary progressive aphasia.

PubMed

Shim, Hyungsub; Hurley, Robert S; Rogalski, Emily; Mesulam, M-Marsel

2012-07-01

This study evaluates spelling errors in the three subtypes of primary progressive aphasia (PPA): agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S). Forty-one PPA patients and 36 age-matched healthy controls were administered a test of spelling. The total number of errors and types of errors in spelling to dictation of regular words, exception words and nonwords, were recorded. Error types were classified based on phonetic plausibility. In the first analysis, scores were evaluated by clinical diagnosis. Errors in spelling exception words and phonetically plausible errors were seen in PPA-S. Conversely, PPA-G was associated with errors in nonword spelling and phonetically implausible errors. In the next analysis, spelling scores were correlated to other neuropsychological language test scores. Significant correlations were found between exception word spelling and measures of naming and single word comprehension. Nonword spelling correlated with tests of grammar and repetition. Global language measures did not correlate significantly with spelling scores, however. Cortical thickness analysis based on MRI showed that atrophy in several language regions of interest were correlated with spelling errors. Atrophy in the left supramarginal gyrus and inferior frontal gyrus (IFG) pars orbitalis correlated with errors in nonword spelling, while thinning in the left temporal pole and fusiform gyrus correlated with errors in exception word spelling. Additionally, phonetically implausible errors in regular word spelling correlated with thinning in the left IFG pars triangularis and pars opercularis. Together, these findings suggest two independent systems for spelling to dictation, one phonetic (phoneme to grapheme conversion), and one lexical (whole word retrieval). Copyright © 2012 Elsevier Ltd. All rights reserved.

The Impact of Aphasia Camp Participation on Quality of Life: A Primary Progressive Aphasia Perspective.

PubMed

Kim, Esther S; Figeys, Mathieu; Hubbard, H Isabel; Wilson, Carlee

2018-07-01

Individuals with primary progressive aphasia (PPA) and their caregivers are at risk for decreased quality of life (QoL) due to their progressive condition. Aphasia camps are an intervention that can improve QoL, yet individuals with PPA are underrepresented at aphasia camps relative to those with poststroke aphasia. The purpose of this exploratory case study was to examine the effect of participation in aphasia camp on the QoL of a couple impacted by PPA. The Living with Aphasia: Framework for Outcome Measurement (A-FROM) was used to guide a semistructured interview with an individual with PPA and her spouse, both of whom had attended the Alberta Aphasia Camp for 4 years. Conventional content analysis with an inductive approach was used to analyze results. Concepts that emerged from the interview were organized into pre-camp, during, and post-camp categories. Aspects of camp that had an effect on post-camp QoL for this couple with PPA included expanding social connections and introduction to new activities. Personal characteristics exhibited by the couple had an impact on their experience of aphasia camp and how they incorporated their experiences into their everyday lives post-camp. Aphasia camps are a participation-based service approach that can benefit people with aphasia regardless of etiology. A consideration of personal factors of potential campers with PPA, and the provision of PPA-specific resources, is recommended for programs such as aphasia camps that incorporate participants with mixed etiologies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pre- and Neonatal Exposure to Lipopolysaccharide or the Enteric Metabolite, Propionic Acid, Alters Development and Behavior in Adolescent Rats in a Sexually Dimorphic Manner

PubMed Central

Foley, Kelly A.; Ossenkopp, Klaus-Peter; Kavaliers, Martin; MacFabe, Derrick F.

2014-01-01

Alterations in the composition of the gut microbiome and/or immune system function may have a role in the development of autism spectrum disorders (ASD). The current study examined the effects of prenatal and early life administration of lipopolysaccharide (LPS), a bacterial mimetic, and the short chain fatty acid, propionic acid (PPA), a metabolic fermentation product of enteric bacteria, on developmental milestones, locomotor activity, and anxiety-like behavior in adolescent male and female offspring. Pregnant Long-Evans rats were subcutaneously injected once a day with PPA (500 mg/kg) on gestation days G12–16, LPS (50 µg/kg) on G15–16, or vehicle control on G12–16 or G15–16. Male and female offspring were injected with PPA (500 mg/kg) or vehicle twice a day, every second day from postnatal days (P) 10–18. Physical milestones and reflexes were monitored in early life with prenatal PPA and LPS inducing delays in eye opening. Locomotor activity and anxiety were assessed in adolescence (P40–42) in the elevated plus maze (EPM) and open-field. Prenatal and postnatal treatments altered behavior in a sex-specific manner. Prenatal PPA decreased time spent in the centre of the open-field in males and females while prenatal and postnatal PPA increased anxiety behavior on the EPM in female rats. Prenatal LPS did not significantly influence those behaviors. Evidence for the double hit hypothesis was seen as females receiving a double hit of PPA (prenatal and postnatal) displayed increased repetitive behavior in the open-field. These results provide evidence for the hypothesis that by-products of enteric bacteria metabolism such as PPA may contribute to ASD, altering development and behavior in adolescent rats similar to that observed in ASD and other neurodevelopmental disorders. PMID:24466331

Simultaneous determination of cetirizine, phenyl propanolamine and nimesulide using third derivative spectrophotometry and high performance liquid chromatography in pharmaceutical preparations.

PubMed

Aly, Fatma Ahmed; El-Enany, Nahed; Elmansi, Heba; Nabil, Amany

2017-10-05

The combination between cetirizine (CET), phenylpropanolamine (PPA) and nimesulide (NMS) under trade name Nemeriv Cp tablet is prescribed for nasal congestion, cold, sneezing, and allergy. Among all published methods for the three drugs; there is no reported method concerning estimation of CTZ, PPA and NMS simultaneously and this motivates us to develop new and simple methods for their assay in pure form and tablet preparations. Two new methodologies were described for the simultaneous quantification of cetirizine (CTZ), PPA and NMS. Spectrophotometric procedures relies on measuring the amplitudes of the third derivative curves at 238 nm for CTZ, 218 nm for PPA and 305 nm for NMS. The calibration graphs were rectilinear over the ranges of 8-90 µg/mL for CTZ, 20-100 µg/mL for PPA and 20-200 µg/mL for NMS respectively. Regarding the HPLC method; monolithic column (100 mm × 4.6 mm i.d) was used for the separation. The used mobile phase composed of 0.1 M phosphate buffer and methanol in the ratio of 40:60, v/v at pH 7.0. The analysis was performed using UV detector at 215 nm. Calibration curves showed the linearity over concentration ranges of 5-40, 10-100 and 10-120 µg/mL for CTZ, PPA and NMS. Application of the proposed methods to the laboratory prepared tablets was carried out successfully. The results were compared with those obtained from previously published methods and they were satisfactory. Graphical abstract Graphical abstract represents the chemical structures, representative chromatogram for the HPLC separation of a PPA, b NMS and c CTZ and third derivative absorption spectra of a PPA, b NMS and c CTZ for the spectrophotometric method.

Genome-Wide Analysis of Germline Signaling Genes Regulating Longevity and Innate Immunity in the Nematode Pristionchus pacificus

PubMed Central

Sommer, Ralf J.

2012-01-01

Removal of the reproductive system of many animals including fish, flies, nematodes, mice and humans can increase lifespan through mechanisms largely unknown. The abrogation of the germline in Caenorhabditis elegans increases longevity by 60% due to a signal emitted from the somatic gonad. Apart from increased longevity, germline-less C. elegans is also resistant to other environmental stressors such as feeding on bacterial pathogens. However, the evolutionary conservation of this pathogen resistance, its genetic basis and an understanding of genes involved in producing this extraordinary survival phenotype are currently unknown. To study these evolutionary aspects we used the necromenic nematode Pristionchus pacificus, which is a genetic model system used in comparison to C. elegans. By ablation of germline precursor cells and subsequent feeding on the pathogen Serratia marcescens we discovered that P. pacificus shows remarkable resistance to bacterial pathogens and that this response is evolutionarily conserved across the Genus Pristionchus. To gain a mechanistic understanding of the increased resistance to bacterial pathogens and longevity in germline-ablated P. pacificus we used whole genome microarrays to profile the transcriptional response comparing germline ablated versus un-ablated animals when fed S. marcescens. We show that lipid metabolism, maintenance of the proteasome, insulin signaling and nuclear pore complexes are essential for germline deficient phenotypes with more than 3,300 genes being differentially expressed. In contrast, gene expression of germline-less P. pacificus on E. coli (longevity) and S. marcescens (immunity) is very similar with only 244 genes differentially expressed indicating that longevity is due to abundant gene expression also involved in immunity. By testing existing mutants of Ppa-DAF-16/FOXO and the nuclear hormone receptor Ppa-DAF-12 we show a conserved function of both genes in resistance to bacterial pathogens and longevity. This is the first study to show that the influence of the reproductive system on extending lifespan and innate immunity is conserved in evolution. PMID:22912581

Deep Retinal Layer Microvasculature Dropout detected by the Optical Coherence Tomography Angiography in Glaucoma

PubMed Central

Suh, Min Hee; Zangwill, Linda M.; Manalastas, Patricia Isabel C.; Belghith, Akram; Yarmohammadi, Adeleh; Medeiros, Felipe A.; Diniz-Filho, Alberto; Saunders, Luke J.; Weinreb, Robert N.

2016-01-01

Purpose To investigate factors associated with dropout of the deep retinal layer microvasculature within the β-zone parapapillary atrophy (βPPA) assessed by optical coherence tomography angiography (OCT-A) in glaucomatous eyes. Design Cross-sectional study. Participants Seventy-one eyes from 71 primary open angle glaucoma (POAG) patients with βPPA enrolled in the Diagnostic Innovations in Glaucoma Study. Methods βPPA deep layer microvasculature dropout was defined as a complete loss of the microvasculature located within deep retinal layer of the βPPA from OCT-A-derived optic nerve head vessel density maps by standardized qualitative assessment. Circumpapillary vessel density (cpVD) within the retinal nerve fiber layer (RNFL) was also calculated using OCT-A. Choroidal thickness and presence of the focal lamina cribrosa (LC) defect were determined using swept-source OCT. Main Outcome Measures Presence of the βPPA deep layer microvasculature dropout. Parameters including age, systolic and diastolic blood pressure, axial length, intraocular pressure, disc hemorrhage, cpVD, visual field (VF) mean deviation (MD), focal LC defect, βPPA area, and choroidal thickness were analyzed. Results βPPA deep layer microvasculature dropout was detected in 37 eyes (52.1%) of eyes with POAG. Eyes with dropouts had a higher prevalence of LC defect (70.3 vs. 32.4%), lower cpVD (52.7 vs. 58.8%), worse VF MD (-9.06 vs. -3.83dB), thinner total choroidal thickness (126.5 vs. 169.1/μm), longer axial length (24.7 vs. 24.0mm), larger βPPA (1.2 vs. 0.76mm2) and lower diastolic blood pressure (74.7 vs. 81.7mmHg) than those without dropouts (P< 0.05, respectively). In the multivariate logistic regression, higher prevalence of focal LC defect (odds ratio [OR], 6.27; P = 0.012), reduced cpVD (OR, 1.27; P = 0.002), worse VF MD (OR, 1.27; P = 0.001), thinner choroidal thickness (OR, 1.02; P = 0.014), and lower diastolic blood pressure (OR, 1.16; P = 0.003) were significantly associated with the dropout. Conclusions Certain systemic and ocular factors such as focal LC defect, more advanced disease status, reduced RNFL vessel density, thinner choroidal thickness, and lower diastolic blood pressure were factors associated with the βPPA deep layer microvasculature dropout in glaucomatous eyes. Longitudinal studies are required to elucidate the temporal relationship between βPPA deep layer dropout and these factors. PMID:27769587

Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro

PubMed Central

Lanter, Bernard B.

2015-01-01

In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. PMID:26216428

Status of the prototype Pulsed Photonuclear Assessment (PPA) inspection system

NASA Astrophysics Data System (ADS)

Jones, James L.; Blackburn, Brandon W.; Norman, Daren R.; Watson, Scott M.; Haskell, Kevin J.; Johnson, James T.; Hunt, Alan W.; Harmon, Frank; Moss, Calvin

2007-08-01

The Idaho National Laboratory, in collaboration with Idaho State University's Idaho Accelerator Center and the Los Alamos National Laboratory, continues to develop the Pulsed Photonuclear Assessment (PPA) technique for shielded nuclear material detection in large volume configurations, such as cargo containers. In recent years, the Department of Homeland Security has supported the development of a prototype PPA cargo inspection system. This PPA system integrates novel neutron and gamma-ray detectors for nuclear material detection along with a complementary and unique gray scale, density mapping component for significant shield material detection. This paper will present the developmental status of the prototype system, its detection performance using several INL Calibration Pallets, and planned enhancements to further increase its nuclear material detection capability.

What role does the anterior temporal lobe play in sentence-level processing? Neural correlates of syntactic processing in semantic PPA

PubMed Central

Wilson, Stephen M.; DeMarco, Andrew T.; Henry, Maya L.; Gesierich, Benno; Babiak, Miranda; Mandelli, Maria Luisa; Miller, Bruce L.; Gorno-Tempini, Maria Luisa

2014-01-01

Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA, also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the anterior temporal lobes is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA, in order to determine which regions normally involved in syntactic processing are damaged in semantic PPA, and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural and functional MRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, while anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the anterior temporal lobes, but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left anterior temporal lobe did show abnormal functionality in semantic PPA patients, however this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the anterior temporal lobe in sentence processing is less likely to relate to syntactic structure-building, and more likely to relate to higher level processes such as combinatorial semantic processing. PMID:24345172

Longitudinal effects of dysfunctional perfectionism and avoidant personality style on postpartum mental disorders: Pathways through antepartum depression and anxiety.

PubMed

Oddo-Sommerfeld, Silvia; Hain, Sarah; Louwen, Frank; Schermelleh-Engel, Karin

2016-02-01

There is first evidence that some personality characteristics raise the risk of postpartum depression (PPD). The present longitudinal study investigates whether dysfunctional perfectionism and avoidant personality style predict PPD, postpartum anxiety (PPA) and bonding impairment (BI) directly or indirectly through antepartum anxiety (APA) and antepartum depression (APD). Pregnant women were recruited in two obstetric departments in Germany. The assessment occurred at two measurement time points: In the third trimester of pregnancy (N=297) and twelve weeks postpartum (N=266). Six questionnaires were administered during pregnancy: perfectionism, personality styles, anxiety, and depression. Postpartum, data on PPA, PPD and BI were collected. We conducted two path analyses in order to examine direct and indirect effects of the two personality characteristics on postpartum disorders. Testing for direct effects of dysfunctional perfectionism and avoidant personality style on PPD, PPA, and BI did not yield significant results. Instead, significant indirect effects were found: PPD, PPA, and BI were influenced indirectly by dysfunctional perfectionism and avoidant personality style via APD and APA. This model explained high portions of the variance of PPD, PPA, and impaired bonding. Each of the two personality characteristics explained a unique part of the outcome measures. The influence on BI was mediated by PPD. APD affected PPD and PPA more strongly than APA. Path models with manifest (observed) variables may lead to measurement errors. Self-rating questionnaires may raise the problem of social desirability. Dysfunctional perfectionism and avoidant personality style are significant risk factors for PPD, PPA, and BI. Screenings of both variables, as well as of APA and APD, which mediated the effect of personality traits on postpartum syndromes, are necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

A language-based sum score for the course and therapeutic intervention in primary progressive aphasia.

PubMed

Semler, Elisa; Anderl-Straub, Sarah; Uttner, Ingo; Diehl-Schmid, Janine; Danek, Adrian; Einsiedler, Beate; Fassbender, Klaus; Fliessbach, Klaus; Huppertz, Hans-Jürgen; Jahn, Holger; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Lauer, Martin; Muche, Rainer; Prudlo, Johannes; Schneider, Anja; Schroeter, Matthias L; Ludolph, Albert C; Otto, Markus

2018-04-25

With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

Direct current stimulation over the anterior temporal areas boosts semantic processing in primary progressive aphasia.

PubMed

Teichmann, Marc; Lesoil, Constance; Godard, Juliette; Vernet, Marine; Bertrand, Anne; Levy, Richard; Dubois, Bruno; Lemoine, Laurie; Truong, Dennis Q; Bikson, Marom; Kas, Aurélie; Valero-Cabré, Antoni

2016-11-01

Noninvasive brain stimulation in primary progressive aphasia (PPA) is a promising approach. Yet, applied to single cases or insufficiently controlled small-cohort studies, it has not clarified its therapeutic value. We here address the effectiveness of transcranial direct current stimulation (tDCS) on the semantic PPA variant (sv-PPA), applying a rigorous study design to a large, homogeneous sv-PPA cohort. Using a double-blind, sham-controlled counterbalanced cross-over design, we applied three tDCS conditions targeting the temporal poles of 12 sv-PPA patients. Efficiency was assessed by a semantic matching task orthogonally manipulating "living"/"nonliving" categories and verbal/visual modalities. Conforming to predominantly left-lateralized damage in sv-PPA and accounts of interhemispheric inhibition, we applied left hemisphere anodal-excitatory and right hemisphere cathodal-inhibitory tDCS, compared to sham stimulation. Prestimulation data, compared to 15 healthy controls, showed that patients had semantic disorders predominating with living categories in the verbal modality. Stimulation selectively impacted these most impaired domains: Left-excitatory and right-inhibitory tDCS improved semantic accuracy in verbal modality, and right-inhibitory tDCS improved processing speed with living categories and accuracy and processing speed in the combined verbal × living condition. Our findings demonstrate the efficiency of tDCS in sv-PPA by generating highly specific intrasemantic effects. They provide "proof of concept" for future applications of tDCS in therapeutic multiday regimes, potentially driving sustained improvement of semantic processing. Our data also support the hotly debated existence of a left temporal-pole network for verbal semantics selectively modulated through both left-excitatory and right-inhibitory brain stimulation. Ann Neurol 2016;80:693-707. © 2016 American Neurological Association.

Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

PubMed

Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

2013-09-10

HAMLET is a complex of human α-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine α-lactalbumin (bLA) and β-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their α-helix and cross-β-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins.

Primary progressive aphasia and the evolving neurology of the language network

PubMed Central

Mesulam, M.-Marsel; Rogalski, Emily J.; Wieneke, Christina; Hurley, Robert S.; Geula, Changiz; Bigio, Eileen H.; Thompson, Cynthia K.; Weintraub, Sandra

2014-01-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke’s area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network. PMID:25179257

Control of impact loading during distracted running before and after gait retraining in runners.

PubMed

Cheung, Roy T H; An, Winko W; Au, Ivan P H; Zhang, Janet H; Chan, Zoe Y S; MacPhail, Aislinn J

2018-07-01

Gait retraining using visual biofeedback has been reported to reduce impact loading in runners. However, most of the previous studies did not adequately examine the level of motor learning after training, as the modified gait pattern was not tested in a dual-task condition. Hence, this study sought to compare the landing peak positive acceleration (PPA) and vertical loading rates during distracted running before and after gait retraining. Sixteen recreational runners underwent a two-week visual biofeedback gait retraining program for impact loading reduction, with feedback on the PPA measured at heel. In the evaluation of PPA and vertical loading rates before and after the retraining, the participants performed a cognitive and verbal counting task while running. Repeated measures ANOVA indicated a significant interaction between feedback and training on PPA (F = 4.642; P = 0.048) but not vertical loading rates (F > 1.953; P > 0.067). Pairwise comparisons indicated a significantly lower PPA and vertical loading rates after gait retraining (P < 0.007; Cohen's d > 0.68). Visual feedback after gait retraining reduced PPA and vertical loading rates during distracted running (P < 0.033; Cohen's d > 0.36). Gait retraining is effective in lowering impact loading even when the runners are distracted. In dual-task situation, visual biofeedback provided beneficial influence on kinetics control after gait retraining.

Interspecies differences and variability with time of protein precipitation activity of extractable tannins, crude protein, ash, and dry matter content of leaves from 13 species of Nepalese fodder trees.

PubMed

Wood, C D; Tiwari, B N; Plumb, V E; Powell, C J; Roberts, B T; Padmini Sirimane, V D; Rossiter, J T; Gill, M

1994-12-01

Dry matter, ash, crude protein, and protein precipitation activity (PPA) of 13 Nepalese tree fodder species were monitored in dried samples prepared monthly between November 1990 and May 1991, and additionally in November 1991, covering the season when they are particularly important as fodder. Monthly levels of dry matter, ash, and crude protein were fairly stable except when there was new leaf growth, although year to year differences in dry matter were found inBrassaiopsis hainla (Bh),Dendrocalamus strictus (Ds),Ficus roxburghii (Fr), andQuercus semecarpifolia (Qs). Tannin PPA fluctuated considerably inArtocarpus lakoocha (Al),Ficus glaberrima (Fg),F. nerrifolia (Fn), Fr,F. semicordata (Fs),Litsea polyantha (Lp), andPrunus cerasoides (Pc), and to a lesser extent in Bh,Castanopsis indica (Ci),C. tribuloides (Ct),Quercus lamellosa (Ql), and Qs. Similar fluctuations in PPA were observed in fresh leaf samples taken weekly. Ds did not have any detectable PPA. Trends in PPA fluctuation were generally similar for trees located at similar altitudes. Fr, Pc, Al, Fn, Ql, and Ci had falling PPAs before shedding leaves. Some of the fluctuations in Fr, Fs, Fg, Pc, and Lp were apparently due to changes in the extractability and quantity of condensed tannins. These fluctuations in PPA may affect the nutritive value of the fodders.

Mediation of oxidative stress in hypothalamic ghrelin-associated appetite control in rats treated with phenylpropanolamine.

PubMed

Yu, C-H; Chu, S-C; Chen, P-N; Hsieh, Y-S; Kuo, D-Y

2017-04-01

Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Primary progressive aphasia and the evolving neurology of the language network.

PubMed

Mesulam, M-Marsel; Rogalski, Emily J; Wieneke, Christina; Hurley, Robert S; Geula, Changiz; Bigio, Eileen H; Thompson, Cynthia K; Weintraub, Sandra

2014-10-01

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Nanobeads-based assays. The case of gluten detection

NASA Astrophysics Data System (ADS)

Venditti, Iole; Fratoddi, Ilaria; Vittoria Russo, Maria; Bellucci, Stefano; Crescenzo, Roberta; Iozzino, Luisa; Staiano, Maria; Aurilia, Vincenzo; Varriale, Antonio; Rossi, Mosè; D'Auria, Sabato

2008-11-01

In order to verify if the use of nanobeads of poly[phenylacetylene-(co-acrylic acid)] (PPA/AA) in the ELISA test would affect the immune-activity of the antibodies (Ab) and/or the activity of the enzymes used to label the Ab anti-rabbit IGg, in this work we immobilized the horse liver peroxidase labelled Ab anti-rabbit IGg onto PPA/AA nanobeads. The gluten test was chosen as the model to demonstrate the usefulness of these nanobeads in immunoassays. The synthesis of PPA/AA nanobeads was performed by a modified emulsion polymerization. Self-assembly of nanospheres with mean diameter equal to 200 nm was achieved by casting aqueous suspensions. The materials were characterized by traditional spectroscopic techniques, while the size and dispersion of the particles were analysed by scanning electron microscopy (SEM) measurements. The obtained results show that the immobilization process of the Abs onto PPA/AA did not affect either the immune-response of the Abs or the functional activity of the peroxidase suggesting the usefulness of PPA/AA for the design of advanced nanobeads-based assays for the simultaneous screening of several analytes in complex media.

Multi-functional electrospun antibacterial core-shell nanofibrous membranes for prolonged prevention of post-surgical tendon adhesion and inflammation.

PubMed

Shalumon, K T; Sheu, Chialin; Chen, Chih-Hao; Chen, Shih-Heng; Jose, Gils; Kuo, Chang-Yi; Chen, Jyh-Ping

2018-05-01

The possibility of endowing an electrospun anti-adhesive barrier membrane with multi-functionality, such as lubrication, prevention of fibroblast attachment and anti-infection and anti-inflammation properties, is highly desirable for the management of post-surgical tendon adhesion. To this end, we fabricated core-shell nanofibrous membranes (CSNMs) with embedded silver nanoparticles (Ag NPs) in the poly(ethylene glycol) (PEG)/poly(caprolactone) (PCL) shell and hyaluronic acid (HA)/ibuprofen in the core. HA imparted a lubrication effect for smooth tendon gliding and reduced fibroblast attachment, while Ag NPs and ibuprofen functioned as anti-infection and anti-inflammation agents, respectively. CSNMs with a PEG/PCL/Ag shell (PPA) and HA core containing 0% (H/PPA), 10% (HI10/PPA), 30% (HI30/PPA) and 50% (HI50/PPA) ibuprofen were fabricated through co-axial electrospinning and assessed through microscopic, spectroscopic, thermal, mechanical and drug release analyses. Considering nutrient passage through the barrier, the microporous CSNMs exerted the same barrier effect but drastically increased the mass transfer coefficients of bovine serum albumin compared with the commercial anti-adhesive membrane SurgiWrap®. Cell attachment/focal adhesion formation of fibroblasts revealed effective reduction of initial cell attachment on the CSNM surface with minimum cytotoxicity (except HI50/PPA). The anti-bacterial effect against both Gram-negative and Gram-positive bacteria was verified to be due to the Ag NPs in the membranes. In vivo studies using H/PPA and HI30/PPA CSNMs and SurgiWrap® in a rabbit flexor tendon rupture model demonstrated the improved efficacy of HI30/PPA CSNMs in reducing inflammation and tendon adhesion formation based on gross observation, histological analysis and functional assays. We conclude that HI30/PPA CSNMs can act as a multifunctional barrier membrane to prevent peritendinous adhesion after tendon surgery. A multi-functional anti-adhesion barrier membrane that could reduce fibroblasts attachment and penetration while simultaneously prevent post-surgical infection and inflammation is urgently needed. To this end, we prepared electrospun core-shell hyaluronic acid + ibuprofen/polyethylene glycol + polycaprolactone + Ag nanoparticles nanofibrous membranes by co-axial electrospinning as an ideal anti-adhesive membrane. The core-shell structure could meet the need of a desirable anti-adhesion barrier through release of ibuprofen and Ag nanoparticles to reduce infection and inflammation while hyaluronic acid can reduce fibroblasts adhesion. The superior performance of this multi-functional core-shell nanofibrous membrane in preventing peritendinous adhesion and post-surgical inflammation was demonstrated in a rabbit flexor tendon rupture model. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Photometer Performance Assessment in Kepler Science Data Processing

NASA Technical Reports Server (NTRS)

Li, Jie; Allen, Christopher; Bryson, Stephen T.; Caldwell, Douglas A.; Chandrasekaran, Hema; Clarke, Bruce D.; Gunter, Jay P.; Jenkins, Jon M.; Klaus, Todd C.; Quintana, Elisa V.;

Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes with glaucomatous optic neuropathy.

PubMed

De Moraes, Carlos Gustavo; Ketner, Scott; Teng, Christopher C; Ehrlich, Joshua R; Raza, Ali S; Liebmann, Jeffrey M; Ritch, Robert; Hood, Donald C

2011-08-01

We investigated changes in multifocal visual evoked potential (mfVEP) responses due to beta-zone parapapillary atrophy (ßPPA). Patients with glaucomatous optic neuropathy (GON) with or without standard achromatic perimetry (SAP) abnormalities were referred for mfVEP testing during a 2-year period. Eyes with good quality optic disc stereophotographs and reliable SAP results were included. The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed. Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical equivalent (SE) were analyzed in the multivariate model. Generalized estimated equations were used for comparisons between groups after adjusting for inter-eye associations. Of 394 eyes of 200 patients, 223 (57%) had ßPPA. The ßPPA eyes were older (59.6 ± 13.7 vs. 56.5 ± 13.7 year, P = 0.02), more myopic (-4.0 ± 3.5 vs. -1.3 ± 3.5 D, P < 0.01), and had poorer SAP scores (MD: -4.9 ± 5.2 vs. -2.6 ± 5.2 dB, P < 0.01; PSD: 4.3 ± 2.9 vs. 2.5 ± 3.0 dB, P < 0.01). By univariate analysis, mean latencies were longer in ßPPA eyes (6.1 ± 5.3 vs. 4.0 ± 5.5 ms, P < 0.01). After adjusting for differences in SE, age, and SAP MD, there was no significant difference between the two groups (P = 0.09). ßPPA eyes had lower amplitude log SNR (0.49 ± 0.16 vs. 0.56 ± 0.15, P < 0.01), which lost significance (P = 0.51) after adjusting for MD and PSD. Although eyes with ßPPA had significantly lower amplitudes and prolonged latencies than eyes without ßPPA, these differences were attributable to differences in SAP severity, age, and refractive error. Thus, ßPPA does not appear to be an independent factor affecting mfVEP responses in eyes with GON.

Beta-zone parapapillary atrophy and multifocal visual evoked potentials in eyes with glaucomatous optic neuropathy

PubMed Central

Ketner, Scott; Teng, Christopher C.; Ehrlich, Joshua R.; Raza, Ali S.; Liebmann, Jeffrey M.; Ritch, Robert; Hood, Donald C.

2015-01-01

We investigated changes in multifocal visual evoked potential (mfVEP) responses due to beta-zone parapapillary atrophy (βPPA). Patients with glaucomatous optic neuropathy (GON) with or without standard achromatic perimetry (SAP) abnormalities were referred for mfVEP testing during a 2-year period. Eyes with good quality optic disc stereophotographs and reliable SAP results were included. The mfVEP monocular mean latency delays (ms) and amplitudes (SNR) were analyzed. Age, SAP mean deviation (MD), pattern standard deviation (PSD), and spherical equivalent (SE) were analyzed in the multivariate model. Generalized estimated equations were used for comparisons between groups after adjusting for inter-eye associations. Of 394 eyes of 200 patients, 223 (57%) had βPPA. The βPPA eyes were older (59.6 ± 13.7 vs. 56.5 ± 13.7 year, P = 0.02), more myopic (−4.0 ± 3.5 vs. −1.3 ± 3.5 D, P < 0.01), and had poorer SAP scores (MD: −4.9 ± 5.2 vs. −2.6 ± 5.2 dB, P < 0.01; PSD: 4.3 ± 2.9 vs. 2.5 ± 3.0 dB, P < 0.01). By univariate analysis, mean latencies were longer in βPPA eyes (6.1 ± 5.3 vs. 4.0 ± 5.5 ms, P < 0.01). After adjusting for differences in SE, age, and SAP MD, there was no significant difference between the two groups (P = 0.09). βPPA eyes had lower amplitude log SNR (0.49 ± 0.16 vs. 0.56 ± 0.15, P < 0.01), which lost significance (P = 0.51) after adjusting for MD and PSD. Although eyes with βPPA had significantly lower amplitudes and prolonged latencies than eyes without βPPA, these differences were attributable to differences in SAP severity, age, and refractive error. Thus, βPPA does not appear to be an independent factor affecting mfVEP responses in eyes with GON. PMID:21735265

What role does the anterior temporal lobe play in sentence-level processing? Neural correlates of syntactic processing in semantic variant primary progressive aphasia.

PubMed

Wilson, Stephen M; DeMarco, Andrew T; Henry, Maya L; Gesierich, Benno; Babiak, Miranda; Mandelli, Maria Luisa; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2014-05-01

Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA; also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the ATLs is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA to determine which regions normally involved in syntactic processing are damaged in semantic PPA and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural MRI and fMRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that, in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, whereas anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the ATLs but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left ATL did show abnormal functionality in semantic PPA patients; however, this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the ATL in sentence processing is less likely to relate to syntactic structure-building and more likely to relate to higher-level processes such as combinatorial semantic processing.

Conjoint representation of texture ensemble and location in the parahippocampal place area.

PubMed

Park, Jeongho; Park, Soojin

2017-04-01

Texture provides crucial information about the category or identity of a scene. Nonetheless, not much is known about how the texture information in a scene is represented in the brain. Previous studies have shown that the parahippocampal place area (PPA), a scene-selective part of visual cortex, responds to simple patches of texture ensemble. However, in natural scenes textures exist in spatial context within a scene. Here we tested two hypotheses that make different predictions on how textures within a scene context are represented in the PPA. The Texture-Only hypothesis suggests that the PPA represents texture ensemble (i.e., the kind of texture) as is, irrespective of its location in the scene. On the other hand, the Texture and Location hypothesis suggests that the PPA represents texture and its location within a scene (e.g., ceiling or wall) conjointly. We tested these two hypotheses across two experiments, using different but complementary methods. In experiment 1 , by using multivoxel pattern analysis (MVPA) and representational similarity analysis, we found that the representational similarity of the PPA activation patterns was significantly explained by the Texture-Only hypothesis but not by the Texture and Location hypothesis. In experiment 2 , using a repetition suppression paradigm, we found no repetition suppression for scenes that had the same texture ensemble but differed in location (supporting the Texture and Location hypothesis). On the basis of these results, we propose a framework that reconciles contrasting results from MVPA and repetition suppression and draw conclusions about how texture is represented in the PPA. NEW & NOTEWORTHY This study investigates how the parahippocampal place area (PPA) represents texture information within a scene context. We claim that texture is represented in the PPA at multiple levels: the texture ensemble information at the across-voxel level and the conjoint information of texture and its location at the within-voxel level. The study proposes a working hypothesis that reconciles contrasting results from multivoxel pattern analysis and repetition suppression, suggesting that the methods are complementary to each other but not necessarily interchangeable. Copyright © 2017 the American Physiological Society.

Neural Codes for One's Own Position and Direction in a Real-World "Vista" Environment.

PubMed

Sulpizio, Valentina; Boccia, Maddalena; Guariglia, Cecilia; Galati, Gaspare

2018-01-01

Humans, like animals, rely on an accurate knowledge of one's spatial position and facing direction to keep orientated in the surrounding space. Although previous neuroimaging studies demonstrated that scene-selective regions (the parahippocampal place area or PPA, the occipital place area or OPA and the retrosplenial complex or RSC), and the hippocampus (HC) are implicated in coding position and facing direction within small-(room-sized) and large-scale navigational environments, little is known about how these regions represent these spatial quantities in a large open-field environment. Here, we used functional magnetic resonance imaging (fMRI) in humans to explore the neural codes of these navigationally-relevant information while participants viewed images which varied for position and facing direction within a familiar, real-world circular square. We observed neural adaptation for repeated directions in the HC, even if no navigational task was required. Further, we found that the amount of knowledge of the environment interacts with the PPA selectivity in encoding positions: individuals who needed more time to memorize positions in the square during a preliminary training task showed less neural attenuation in this scene-selective region. We also observed adaptation effects, which reflect the real distances between consecutive positions, in scene-selective regions but not in the HC. When examining the multi-voxel patterns of activity we observed that scene-responsive regions and the HC encoded both spatial information and that the RSC classification accuracy for positions was higher in individuals scoring higher to a self-reported questionnaire of spatial abilities. Our findings provide new insight into how the human brain represents a real, large-scale "vista" space, demonstrating the presence of neural codes for position and direction in both scene-selective and hippocampal regions, and revealing the existence, in the former regions, of a map-like spatial representation reflecting real-world distance between consecutive positions.

Prevalence of Mathematical and Visuospatial Learning Disabilities in Patients With Posterior Cortical Atrophy.

PubMed

Miller, Zachary A; Rosenberg, Lynne; Santos-Santos, Miguel A; Stephens, Melanie; Allen, Isabel E; Hubbard, H Isabel; Cantwell, Averill; Mandelli, Maria Luisa; Grinberg, Lea T; Seeley, William W; Miller, Bruce L; Rabinovici, Gil D; Gorno-Tempini, Maria Luisa

2018-06-01

Increased prevalence of language-based learning disabilities (LDs) has been previously reported in patients with primary progressive aphasia (PPA). This study hypothesized that patients with focal neurodegenerative syndromes outside the language network, such as posterior cortical atrophy (PCA), would have a higher rate of nonlanguage LDs, congruent with their mainly visuospatial presentation. To investigate the prevalence and type of LD (language and/or mathematical and visuospatial) in a large cohort of patients with PCA compared with patients with logopenic variant PPA (lvPPA) and amnestic Alzheimer disease (AD). This case-control study reviewed 279 medical records from a university-based clinic and research center for patients with neurodegenerative diseases for LD history, including patients with PCA (n = 95), patients with lvPPA (n = 84), and a matched cohort with amnestic AD (n = 100). No records were excluded. The study compared cognitive and neuroimaging features of patients with PCA with and without LDs. A review of the records of patients presenting from March 1, 1999, to August 31, 2014, revealed 95 PCA cases and 84 lvPPA cases. Then 100 patients with amnestic AD from this same period were chosen for comparison, matching against the groups for age, sex, and disease severity. Data analysis was performed from September 8, 2013, to November 6, 2017. Prevalence of total LD history and prevalence of language and mathematical or visuospatial LD history across all cohorts. A total of 179 atypical AD cases (95 with PCA and 84 with lvPPA) and 100 disease control cases (amnestic AD) were included in the study. The groups were not statistically different for mean (SD) age at first visit (PCA, 61.9 [7.0] years; lvPPA, 65.1 [8.7] years; amnestic AD, 64.0 [12.6] years; P = .08), mean (SD) age at first symptom (PCA, 57.5 [7.0] years; lvPPA, 61.1 [9.0] years; amnestic AD, 59.6 [13.7] years; P = .06), or sex (PCA, 66.3% female; lvPPA, 56.0% female; amnestic AD, 57.0% female; P = .30) but differed on non-right-hand preference (PCA, 18.3%; lvPPA, 20.2%; amnestic AD, 7.7%; P = .04), race/ethnicity (PCA, 88.3% white; lvPPA, 99.0% white; amnestic AD, 80.0% white; P < .001), and mean (SD) educational level (PCA, 15.7 [3.2] years; lvPPA, 16.2 [3.3] years; amnestic AD, 14.8 [3.5] years; P = .02). A total of 18 of the 95 patients with PCA (18.9%) reported a history of LD, which is greater than the 3 of 100 patients (3.0%) in the amnestic AD cohort (P < .001) and the 10.0% expected rate in the general population (P = .007). In the PCA cohort, 13 of 95 patients (13.7%) had a nonlanguage mathematical and/or visuospatial LD; this rate was greater than that in the amnestic AD (1 of 100 [1.0%]; P < .001) and lvPPA (2 of 84 [2.4%]; P = .006) cohorts and greater than the 6.0% expected general population rate of mathematical LD (P = .003). Compared with the patients with PCA without LDs, the group with LDs had greater preservation of global cognition and a more right-lateralized pattern of atrophy. Nonlanguage mathematical and visuospatial LDs were associated with focal, visuospatial predominant neurodegenerative clinical syndromes. This finding supports the hypothesis that neurodevelopmental differences in specific brain networks are associated with phenotypic manifestation of later-life neurodegenerative disease.

Principal polynomial analysis.

PubMed

Laparra, Valero; Jiménez, Sandra; Tuia, Devis; Camps-Valls, Gustau; Malo, Jesus

2014-11-01

This paper presents a new framework for manifold learning based on a sequence of principal polynomials that capture the possibly nonlinear nature of the data. The proposed Principal Polynomial Analysis (PPA) generalizes PCA by modeling the directions of maximal variance by means of curves, instead of straight lines. Contrarily to previous approaches, PPA reduces to performing simple univariate regressions, which makes it computationally feasible and robust. Moreover, PPA shows a number of interesting analytical properties. First, PPA is a volume-preserving map, which in turn guarantees the existence of the inverse. Second, such an inverse can be obtained in closed form. Invertibility is an important advantage over other learning methods, because it permits to understand the identified features in the input domain where the data has physical meaning. Moreover, it allows to evaluate the performance of dimensionality reduction in sensible (input-domain) units. Volume preservation also allows an easy computation of information theoretic quantities, such as the reduction in multi-information after the transform. Third, the analytical nature of PPA leads to a clear geometrical interpretation of the manifold: it allows the computation of Frenet-Serret frames (local features) and of generalized curvatures at any point of the space. And fourth, the analytical Jacobian allows the computation of the metric induced by the data, thus generalizing the Mahalanobis distance. These properties are demonstrated theoretically and illustrated experimentally. The performance of PPA is evaluated in dimensionality and redundancy reduction, in both synthetic and real datasets from the UCI repository.

JPRS Report, Science & Technology, USSR: Life Sciences

DTIC Science & Technology

1988-12-15

neering studies employed in studies on the effects of antisense RNA ( asRNA ) on the reproduction of type 5 adenovirus in cultured monkey Cos I cells...The asRNA was targeted against the EIA region of the adenoviral genome, which has a key role in the regulation of other adenoviral genes. A...recombinant vector designated ppS- NEO containing Moloney leukemia genome was employed in the synthesis of asRNA , as well as recom- binant plasmid ppA in

Propionibacterium acnes Recovered from Atherosclerotic Human Carotid Arteries Undergoes Biofilm Dispersion and Releases Lipolytic and Proteolytic Enzymes in Response to Norepinephrine Challenge In Vitro.

PubMed

Lanter, Bernard B; Davies, David G

2015-10-01

In the present study, human atherosclerotic carotid arteries were examined following endarterectomy for the presence of the Gram-positive bacterium Propionibacterium acnes and its potential association with biofilm structures within the arterial wall. The P. acnes 16S rRNA gene was detectable in 4 of 15 carotid artery samples, and viable P. acnes was one among 10 different bacterial species recoverable in culture. Fluorescence in situ hybridization analysis of 5 additional atherosclerotic carotid arteries demonstrated biofilm bacteria within all samples, with P. acnes detectable in 4 samples. We also demonstrated that laboratory-grown cultures of P. acnes biofilms were susceptible to induction of a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of iron-bound transferrin or with free iron. The production and release of lipolytic and proteolytic extracellular enzymes by P. acnes were shown to increase in iron-induced dispersed biofilms, and these dispersion-induced P. acnes VP1 biofilms showed increased expression of mRNAs for the triacylglycerol lipases PPA2105 and PPA1796 and the hyaluronate lyase PPA380 compared to that in untreated biofilms. These results demonstrate that P. acnes can infect the carotid arteries of humans with atherosclerosis as a component of multispecies biofilms and that dispersion is inducible for this organism, at least in vitro, with physiologically relevant levels of norepinephrine resulting in the production and release of degradative enzymes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Preformulation considerations for controlled release dosage forms. Part III. Candidate form selection using numerical weighting and scoring.

PubMed

Chrzanowski, Frank

2008-01-01

Two numerical methods, Decision Analysis (DA) and Potential Problem Analysis (PPA) are presented as alternative selection methods to the logical method presented in Part I. In DA properties are weighted and outcomes are scored. The weighted scores for each candidate are totaled and final selection is based on the totals. Higher scores indicate better candidates. In PPA potential problems are assigned a seriousness factor and test outcomes are used to define the probability of occurrence. The seriousness-probability products are totaled and forms with minimal scores are preferred. DA and PPA have never been compared to the logical-elimination method. Additional data were available for two forms of McN-5707 to provide complete preformulation data for five candidate forms. Weight and seriousness factors (independent variables) were obtained from a survey of experienced formulators. Scores and probabilities (dependent variables) were provided independently by Preformulation. The rankings of the five candidate forms, best to worst, were similar for all three methods. These results validate the applicability of DA and PPA for candidate form selection. DA and PPA are particularly applicable in cases where there are many candidate forms and where each form has some degree of unfavorable properties.

Longitudinal assessment of short-term memory deterioration in a logopenic variant primary progressive aphasia with post-mortem confirmed Alzheimer's Disease pathology.

PubMed

Tree, Jeremy; Kay, Janice

2015-09-01

In the field of dementia research, there are reports of neurodegenerative cases with a focal loss of language, termed primary progressive aphasia (PPA). Currently, this condition has been further sub-classified, with the most recent sub-type dubbed logopenic variant (PPA-LV). As yet, there remains somewhat limited evaluation of the characteristics of this condition, with no studies providing longitudinal assessment accompanied by post-mortem examination. Moreover, a key characteristic of the PPA-LV case is a deterioration of phonological short-term memory, but again little work has scrutinized the nature of this impairment over time. The current study seeks to redress these oversights and presents detailed longitudinal examination of language and memory function in a case of PPA-LV, with special focus on tests linked to components of phonological short-term memory function. Our findings are then considered with reference to a contemporary model of the neuropsychology of phonological short-term memory. Additionally, post-mortem examinations indicated Alzheimer's disease type pathology, providing further evidence that the PPA-LV presentation may reflect an atypical presentation of this condition. © 2014 The British Psychological Society.

Selective verbal recognition memory impairments are associated with atrophy of the language network in non-semantic variants of primary progressive aphasia.

PubMed

Nilakantan, Aneesha S; Voss, Joel L; Weintraub, Sandra; Mesulam, M-Marsel; Rogalski, Emily J

2017-06-01

Primary progressive aphasia (PPA) is clinically defined by an initial loss of language function and preservation of other cognitive abilities, including episodic memory. While PPA primarily affects the left-lateralized perisylvian language network, some clinical neuropsychological tests suggest concurrent initial memory loss. The goal of this study was to test recognition memory of objects and words in the visual and auditory modality to separate language-processing impairments from retentive memory in PPA. Individuals with non-semantic PPA had longer reaction times and higher false alarms for auditory word stimuli compared to visual object stimuli. Moreover, false alarms for auditory word recognition memory were related to cortical thickness within the left inferior frontal gyrus and left temporal pole, while false alarms for visual object recognition memory was related to cortical thickness within the right-temporal pole. This pattern of results suggests that specific vulnerability in processing verbal stimuli can hinder episodic memory in PPA, and provides evidence for differential contributions of the left and right temporal poles in word and object recognition memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Solar Resources for Universities | State, Local, and Tribal Governments |

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Federal Tax Incentives for Battery Storage Systems Non-Power Purchase Agreement (PPA) Options to Financing Financing for Solar Deployment on University Campuses Non-Power Purchase Agreement (PPA) Options to

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development Start Year: 2020 Do you have more information, corrections, or comments? Background Technology ): Alex Phocas-Cosmetatos Company: Nur Energie Start Production: 2020 PPA/Tariff Type: Feed-In Tariff PPA

Poly (p-phenyleneneacetylene) light-emitting diodes

DOEpatents

Shinar, Joseph; Swanson, Leland S.; Lu, Feng; Ding, Yiwei; Barton, Thomas J.; Vardeny, Zeev V.

1994-10-04

Acetylene containing poly(p-phenyleneacetylene) (PPA) - based light-emitting diodes (LEDs) are provided. The LEDs are fabricated by coating a hole-injecting electrode, preferably an indium tin oxide (ITO) coated glass substrate, with a PPA polymer, such as a 2,5-dibutoxy or a 2,5-dihexoxy derivative of PPA, dissolved in an organic solvent. This is then followed by evaporating a layer of material capable of injecting electrons, such as Al or Al/Ca, onto the polymer to form a base electrode. This composition is then annealed to form efficient EL diodes.

Poly (p-phenyleneacetylene) light-emitting diodes

DOEpatents

Shinar, J.; Swanson, L.S.; Lu, F.; Ding, Y.; Barton, T.J.; Vardeny, Z.V.

1994-10-04

Acetylene containing poly(p-phenyleneacetylene) (PPA) - based light-emitting diodes (LEDs) are provided. The LEDs are fabricated by coating a hole-injecting electrode, preferably an indium tin oxide (ITO) coated glass substrate, with a PPA polymer, such as a 2,5-dibutoxy or a 2,5-dihexoxy derivative of PPA, dissolved in an organic solvent. This is then followed by evaporating a layer of material capable of injecting electrons, such as Al or Al/Ca, onto the polymer to form a base electrode. This composition is then annealed to form efficient EL diodes. 8 figs.

Fabrication of poly(p-phenyleneacetylene) light-emitting diodes

DOEpatents

Shinar, J.; Swanson, L.S.; Lu, F.; Ding, Y.

1994-08-02

Acetylene-containing poly(p-phenyleneacetylene) (PPA)-based light-emitting diodes (LEDs) are provided. The LEDs are fabricated by coating a hole-injecting electrode, preferably an indium tin oxide (ITO) coated glass substrate, with a PPA polymer, such as a 2,5-dibutoxy or a 2,5-dihexoxy derivative of PPA, dissolved in an organic solvent. This is then followed by evaporating a layer of material capable of injecting electrons, such as Al or Al/Ca, onto the polymer to form a base electrode. This composition is then annealed to form efficient EL diodes. 8 figs.

Fabrication of poly(p-phenyleneacetylene) light-emitting diodes

DOEpatents

Shinar, Joseph; Swanson, Leland S.; Lu, Feng; Ding, Yiwei

1994-08-02

Acetylene containing poly(p-phenyleneacetylene) (PPA) - based light-emitting diodes (LEDs) are provided. The LEDs are fabricated by coating a hole-injecting electrode, preferably an indium tin oxide (ITO) coated glass substrate, with a PPA polymer, such as a 2,5-dibutoxy or a 2,5-dihexoxy derivative of PPA, dissolved in an organic solvent. This is then followed by evaporating a layer of material capable of injecting electrons, such as A1 or A1/Ca, onto the polymer to form a base electrode. This composition is then annealed to form efficient EL diodes.

Potentiation Following Ballistic and Nonballistic Complexes: The Effect of Strength Level.

PubMed

Suchomel, Timothy J; Sato, Kimitake; DeWeese, Brad H; Ebben, William P; Stone, Michael H

2016-07-01

Suchomel, TJ, Sato, K, DeWeese, BH, Ebben, WP, and Stone, MH. Potentiation following ballistic and nonballistic complexes: the effect of strength level. J Strength Cond Res 30(7): 1825-1833, 2016-The purpose of this study was to compare the temporal profile of strong and weak subjects during ballistic and nonballistic potentiation complexes. Eight strong (relative back squat = 2.1 ± 0.1 times body mass) and 8 weak (relative back squat = 1.6 ± 0.2 times body mass) males performed squat jumps immediately and every minute up to 10 minutes following potentiation complexes that included ballistic or nonballistic concentric-only half-squat (COHS) performed at 90% of their 1 repetition maximum COHS. Jump height (JH) and allometrically scaled peak power (PPa) were compared using a series of 2 × 12 repeated measures analyses of variance. No statistically significant strength level main effects for JH (p = 0.442) or PPa (p = 0.078) existed during the ballistic condition. In contrast, statistically significant main effects for time existed for both JH (p = 0.014) and PPa (p < 0.001); however, no statistically significant pairwise comparisons were present (p > 0.05). Statistically significant strength level main effects existed for PPa (p = 0.039) but not for JH (p = 0.137) during the nonballistic condition. Post hoc analysis revealed that the strong subjects produced statistically greater PPa than the weaker subjects (p = 0.039). Statistically significant time main effects existed for time existed for PPa (p = 0.015), but not for JH (p = 0.178). No statistically significant strength level × time interaction effects for JH (p = 0.319) or PPa (p = 0.203) were present for the ballistic or nonballistic conditions. Practical significance indicated by effect sizes and the relationships between maximum potentiation and relative strength suggest that stronger subjects potentiate earlier and to a greater extent than weaker subjects during ballistic and nonballistic potentiation complexes.

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development Start Year: 2017 Do you have more information, corrections, or comments? Background Technology PDF Break Ground: 2015 Start Production: 2017 PPA/Tariff Date: September 1, 2016 PPA/Tariff Type: Feed

Phenylacetic and Phenylpropionic Acids Do Not Affect Xylan Degradation by Ruminococcus albus

PubMed Central

Reveneau, Carine; Adams, Sarah E.; Cotta, M. A.; Morrison, M.

2003-01-01

Since the addition of either ruminal fluid or a combination of phenylacetic and phenylpropionic acids (PAA/PPA) has previously been shown to dramatically improve cellulose degradation and growth of Ruminococcus albus, it was of interest to determine the effects of these additives on xylan-grown cultures. Although cell-bound xylanase activity increased when either PAA/PPA or ruminal fluid was added to the growth medium, total xylanase did not change, and neither of these supplements affected the growth or xylan-degrading capacity of R. albus 8. Similarly, neither PAA/PPA nor ruminal fluid affected xylan degradation by multiple strains of R. albus when xylan prepared from oat spelts was used as a carbohydrate source. These results show that the xylanolytic potential of R. albus is not conditional on the availability of PAA/PPA or other components of ruminal fluid. PMID:14602663

The time course of neurolinguistic and neuropsychological symptoms in three cases of logopenic primary progressive aphasia.

PubMed

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Südmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-06-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease. However, the dynamics of changes in language and non-linguistic abilities are not well understood. Most studies on progression used cross-sectional designs, which provide only limited insight into the course of the disease. Here we report the results of a longitudinal study in three cases of logopenic PPA over a period of 18 months, with exemplary longitudinal data from one patient even over 46 months. A comprehensive battery of neurolinguistic and neuropsychological tests was applied four times at intervals of six months. Over this period, deterioration of verbal abilities such as picture naming, story retelling, and semantic word recall was found, and the individual decline was quantified and compared between the three patients. Furthermore, decrease in non-verbal skills such as divided attention and increasing apraxia was observed in all three patients. In addition, inter-subject variability in the progression with different focuses was observed, with one patient developing a non-fluent PPA variant. The longitudinal, multivariate investigation of logopenic PPA thus provides novel insights into the progressive deterioration of verbal as well as non-verbal abilities. These deficits may further interact and thus form a multi-causal basis for the patients' problems in every-day life which need to be considered when planning individually targeted intervention in PPA. Copyright © 2012 Elsevier Ltd. All rights reserved.

Identification of the Inorganic Pyrophosphate Metabolizing, ATP Substituting Pathway in Mammalian Spermatozoa

PubMed Central

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies. PMID:22485177

Pulmonary hypertension and computed tomography measurement of small pulmonary vessels in severe emphysema.

PubMed

Matsuoka, Shin; Washko, George R; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K; Hoffman, Eric; Fessler, Henry E; Criner, Gerard J; Marchetti, Nathaniel; Scharf, Steven M; Martinez, Fernando J; Reilly, John J; Hatabu, Hiroto

2010-02-01

Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm(2) (CSA(<5)) and 5 to 10 mm(2) (CSA(5-10)), and calculated the percentage of total CSA for the lung area (%CSA(<5) and %CSA(5-10), respectively). The correlations of %CSA(<5) and %CSA(5-10) with pulmonary arterial mean pressure (Ppa) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using Ppa as the dependent outcome was also performed. The %CSA(<5) had a significant negative correlation with Ppa (r = -0.512, P < 0.0001), whereas the correlation between %CSA(5-10) and Ppa did not reach statistical significance (r = -0.196, P = 0.083). Multiple linear regression analysis showed that %CSA(<5) and diffusing capacity of carbon monoxide (DL(CO)) % predicted were independent predictors of Ppa (r(2) = 0.541): %CSA (<5) (P < 0.0001), and DL(CO) % predicted (P = 0.022). The %CSA(<5) measured on CT images is significantly correlated to Ppa in severe emphysema and can estimate the degree of pulmonary hypertension.

Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa.

PubMed

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies.

Antagonism of LIN-17/Frizzled and LIN-18/Ryk in nematode vulva induction reveals evolutionary alterations in core developmental pathways.

PubMed

Wang, Xiaoyue; Sommer, Ralf J

2011-07-01

Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks.

Antagonism of LIN-17/Frizzled and LIN-18/Ryk in Nematode Vulva Induction Reveals Evolutionary Alterations in Core Developmental Pathways

PubMed Central

Wang, Xiaoyue; Sommer, Ralf J.

2011-01-01

Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks. PMID:21814488

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) project, with data organized by background, participants, and power plant configuration. Status Date Cost (approx): 1,042 € million PPA/Tariff Date: November 19, 2012 PPA/Tariff Rate: 1.62 Dirhams per

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Status: Operational Start Year: 2018 Do you have more information, corrections, or comments? Background Break Ground: May 2015 Start Production: January 10, 2018 PPA/Tariff Rate: 1.36 MAD per kWh PPA/Tariff

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Use of the Progressive Aphasia Severity Scale (PASS) in monitoring speech and language status in PPA

PubMed Central

Sapolsky, Daisy; Domoto-Reilly, Kimiko; Dickerson, Bradford C.

2014-01-01

Background Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome involving the gradual development of aphasia, slowly impairing the patient’s ability to communicate. Pharmaceutical treatments do not currently exist and intervention often focuses on speech-language behavioral therapies, although further investigation is warranted to determine how best to harness functional benefits. Efforts to develop pharmaceutical and behavioral treatments have been hindered by a lack of standardized methods to monitor disease progression and treatment efficacy. Aims Here we describe our current approach to monitoring progression of PPA, including the development and applications of a novel clinical instrument for this purpose, the Progressive Aphasia Severity Scale (PASS). We also outline some of the issues related to initial evaluation and longitudinal monitoring of PPA. Methods & Procedures In our clinical and research practice we perform initial and follow-up assessments of PPA patients using a multi-faceted approach. In addition to standardized assessment measures, we use the PASS to rate presence and severity of symptoms across distinct domains of speech, language, and functional and pragmatic aspects of communication. Ratings are made using the clinician’s best judgment, integrating information from patient test performance in the office as well as a companion’s description of routine daily functioning. Outcomes & Results Monitoring symptom characteristics and severity with the PASS can assist in developing behavioral therapies, planning treatment goals, and counseling patients and families on clinical status and prognosis. The PASS also has potential to advance the implementation of PPA clinical trials. Conclusions PPA patients display heterogeneous language profiles that change over time given the progressive nature of the disease. The monitoring of symptom progression is therefore crucial to ensure that proposed treatments are appropriate at any given stage, including speech-language therapy and potentially pharmaceutical treatments once these become available. Because of the discrepancy that can exist between a patient’s daily functioning and standardized test performance, we believe a comprehensive assessment and monitoring battery must include performance-based instruments, interviews with the patient and partner, questionnaires about functioning in daily life, and measures of clinician judgment. We hope that our clinician judgment-based rating scale described here will be a valuable addition to the PPA assessment and monitoring battery. PMID:25419031

Frontotemporal Dementia

PubMed Central

Olney, Nicholas T.; Spina, Salvatore; Miller, Bruce L.

2017-01-01

Frontotemporal Dementia (FTD) is a heterogeneous disorder with distinct clinical phenotypes associated with multiple neuropathologic entities. Presently, the term FTD encompasses clinical disorders that include changes in behavior, language, executive control and often motor symptoms. The core FTD spectrum disorders include: behavioral variant FTD (bvFTD), nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), and semantic variant PPA (svPPA). Related FTD disorders include frontotemporal dementia with motor neuron disease (FTD-MND), progressive supranuclear palsy syndrome (PSP-S) and corticobasal syndrome (CBS). In this chapter we will discuss the clinic presentation, diagnostic criteria, neuropathology, genetics and treatments of these disorders. PMID:28410663

Pyropheophorbide A and c(RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy.

PubMed

Zhou, Aiguo; Wei, Yanchun; Wu, Baoyan; Chen, Qun; Xing, Da

2012-06-04

Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-RGD was developed for targeted near-infrared photodynamic therapy. The properties of UCNP-Ppa-RGD, such as morphology, stability, optical spectroscopy and singlet oxygen generation efficiency, were investigated. The results show that covalently linked pyropheophorbide a molecule not only is stable but also retains its spectroscopic and functional properties. In vitro studies confirm a stronger targeting specificity of UCNP-Ppa-RGD to integrin α(v)β(3)-positive U87-MG cells compared with that in the corresponding negative group. The photosensitizer-attached nanostructure exhibited low dark toxicity and high phototoxicity against cancer cells upon 980 nm laser irradiation at an appropriate dosage. These results represent the first demonstration of a highly stable and efficient photosensitizer modified upconversion nanostructure for targeted near-infrared photodynamic therapy of cancer cells. The novel UCNP-Ppa-RGD nanoparticle may provide a powerful alternative for near-infrared photodynamic therapy with an improved tumor targeting specificity.

Progression of gyrate atrophy measured with ultra-wide-field imaging.

PubMed

Salcedo-Villanueva, Guillermo; Paciuc-Beja, Miguel; Villanueva-Mendoza, Cristina; Harasawa, Mariana; Smith, Jesse M; Velez-Montoya, Raul; Olson, Jeffrey L; Oliver, Scott C; Mandava, Naresh; Quiroz-Mercado, Hugo

2016-02-01

The study aims to determine the progression of gyrate atrophy by measuring the area growth of chorioretinal atrophic lesions using ultra-wide-field images (UWFI). A retrospective, observational, and comparative study was conducted and UWFI (200°) were obtained from two patients with gyrate atrophy at baseline and follow-up. Measurements of atrophy were obtained for three types of lesions: Solitary atrophic lesions (SAL), De novo solitary lesions (DNSL), and peripapillary atrophy (PPA). Comparison of baseline and follow-up was done using t tests. Two patients with gyrate atrophy were included. Patient 1 presented 16 SAL, 5 DNSL, and PPA measured for both eyes (BE). Overall area growth (OAG) for SAL (expressed in decimals) presented a mean of 3.41, σ 3.07. DNSL area for BE presented a mean of 1586.08 P (2), σ 1069.55. OAG for PPA presented a mean of 1.21, σ 0.17. Patient 2 presented 5 SAL, no DNSL, and PPA was measured for BE. OAG for SAL presented a mean of 1.58, σ 1.05 (range 1.02-3.47). OAG for PPA presented a mean of 1.05, σ 0.001. Gyrate atrophy progression can be determined by measuring the changes in area using UWFI.

Quantitative application of the primary progressive aphasia consensus criteria.

PubMed

Wicklund, Meredith R; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Whitwell, Jennifer L; Josephs, Keith A

2014-04-01

To determine how well the consensus criteria could classify subjects with primary progressive aphasia (PPA) using a quantitative speech and language battery that matches the test descriptions provided by the consensus criteria. A total of 105 participants with a neurodegenerative speech and language disorder were prospectively recruited and underwent neurologic, neuropsychological, and speech and language testing and MRI in this case-control study. Twenty-one participants with apraxia of speech without aphasia served as controls. Select tests from the speech and language battery were chosen for application of consensus criteria and cutoffs were employed to determine syndromic classification. Hierarchical cluster analysis was used to examine participants who could not be classified. Of the 84 participants, 58 (69%) could be classified as agrammatic (27%), semantic (7%), or logopenic (35%) variants of PPA. The remaining 31% of participants could not be classified. Of the unclassifiable participants, 2 clusters were identified. The speech and language profile of the first cluster resembled mild logopenic PPA and the second cluster semantic PPA. Gray matter patterns of loss of these 2 clusters of unclassified participants also resembled mild logopenic and semantic variants. Quantitative application of consensus PPA criteria yields the 3 syndromic variants but leaves a large proportion unclassified. Therefore, the current consensus criteria need to be modified in order to improve sensitivity.

75 FR 9418 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

... OMB Review; Comment Request Title: Evaluation of Adolescent Pregnancy Prevention Approaches-- Baseline... part of the Evaluation of Adolescent Pregnancy Prevention Approaches (PPA). PPA is being undertaken to expand available evidence on effective ways to reduce teen pregnancy. The evaluation will document and...

Preparation of enteric coated timed-release press-coated tablets and evaluation of their function by in vitro and in vivo tests for colon targeting.

PubMed

Fukui, E; Miyamura, N; Uemura, K; Kobayashi, M

2000-08-25

As a new oral drug delivery system for colon targeting, enteric coated timed-release press-coated tablets (ETP tablets) were developed by coating enteric polymer on timed-release press-coated tablets composed of an outer shell of hydroxypropylcellulose and core tablet containing diltiazem hydrochloride (DIL) as a model drug. The results of the in vitro dissolution tests in JP 1st fluid (pH 1.2) and JP 2nd fluid (pH 6.8) indicated that these tablets showed both acid resistance and timed-release. To clarify whether ETP tablets could have been of use in the gastrointestinal tract, ETP tablets with a layer of phenylpropanolamine hydrochloride (PPA) (a marker of gastric emptying) between the enteric coating layer and outer shell were prepared, and were administered to beagle dogs. The gastric emptying time and lag time after gastric emptying were evaluated by determining the times at which PPA and DIL first appeared in the plasma (TFA(PPA) and TFA(DIL), respectively). TFA(PPA) and TFA(DIL) were about 4 and 7 h, respectively. This value of TFA(PPA) indicated that ETP tablets displayed acid resistance in the stomach as well as in JP Ist fluid. Subtraction of TFA(PPA) from TFA(DIL) gave a value of about 3 h which agreed well with the lag time determined by in vitro dissolution test in JP 2nd fluid. Also, the results seemed to be in accordance with the time at which the tablets reached the colon after gastric emptying. Therefore, ETP tablets seemed to be an effective tool for oral site-specific delivery including targeting of the colon.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdelbaky, Mohammed S.M.; Amghouz, Zakariae; Department of Materials Science and Metallurgical Engineering, University of Oviedo, Campus Universitario, 33203 Gijón

Novel metal phosphonate [CuLi(PPA)] [H{sub 3}PPA=3-phosphonopropionic acid] was synthesized hydrothermally and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, scanning electron microscopy, infrared spectroscopy, and thermogravimetric analysis. It crystallizes in the space group C2/c, with cell parameters a=21.617(2) Å, b=4.9269(2) Å, c=14.342(1) Å, β=132.3(2)°, and Z=8. Its framework is built up from a main trimer, acting as a secondary building unit (SBU), which is formed by vertex-shared between two (LiO{sub 4}) and one (Cu(1)O{sub 4}) polyhedra. These units repeat along b-axis forming infinite inorganic chains, these chains are in turn cross-linked by corner sharing with (Cu(2)O{sub 4}) polyhedra to producemore » inorganic layers lying in the bc-plane. The neighboring layers are connected through the PPA ligand, leading to a 3D pillared-layered structure. The topological analysis reveals that the compound exhibits 3,4,10-c net. Finally, magnetic susceptibility measurement of this compound over the temperature range of 2–300 K reveals the occurrence of weak antiferromagnetic intrachain interactions. - Graphical abstract: Hydrothermal synthesis and structural characterization of a novel lithium-copper phosphonate, formulated as [CuLi(PPA)] (H{sub 3}PPA=3-phosphonopropionic acid), have been reported. This compound has a 3D pillared-layered structure with 3,4,10-c net topology. The magnetic susceptibility data over the temperature range of 2–300 K reveals the occurrence of weak antiferromagnetic interactions. - Highlights: • Novel metal phosphonate, [CuLi(PPA)] (1), has been synthesized and characterized. • Compound 1 has a 3D pillared-layered structure with 3,4,10-c net topology. • Magnetic susceptibility data reveals the occurrence of weak antiferromagnetic interactions.« less

Directed modification of L-LcLDH1, an L-lactate dehydrogenase from Lactobacillus casei, to improve its specific activity and catalytic efficiency towards phenylpyruvic acid.

PubMed

Li, Jian-Fang; Li, Xue-Qing; Liu, Yan; Yuan, Feng-Jiao; Zhang, Ting; Wu, Min-Chen; Zhang, Ji-Ru

2018-05-22

To improve the specific activity and catalytic efficiency of L-LcLDH1, an NADH-dependent allosteric L-lactate dehydrogenase from L. casei, towards phenylpyruvic acid (PPA), its directed modification was conducted based on the semi-rational design. The three variant genes, Lcldh1 Q88R , Lcldh1 I229A and Lcldh1 T235G , were constructed by whole-plasmid PCR as designed theoretically, and expressed in E. coli BL21(DE3), respectively. The purified mutant, L-LcLDH1 Q88R or L-LcLDH1 I229A , displayed the specific activity of 451.5 or 512.4 U/mg towards PPA, by which the asymmetric reduction of PPA afforded L-phenyllactic acid (PLA) with an enantiomeric excess (ee p ) more than 99%. Their catalytic efficiencies (k cat /K m ) without D-fructose-1,6-diphosphate (D-FDP) were 4.8- and 5.2-fold that of L-LcLDH1. Additionally, the k cat /K m values of L-LcLDH1 Q88R and L-LcLDH1 I229A with D-FDP were 168.4- and 8.5-fold higher than those of the same enzymes without D-FDP, respectively. The analysis of catalytic mechanisms by molecular docking (MD) simulation indicated that substituting I229 in L-LcLDH1 with Ala enlarges the space of substrate-binding pocket, and that the replacement of Q88 with Arg makes the inlet of pocket larger than that of L-LcLDH1. Copyright © 2018 Elsevier B.V. All rights reserved.

Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries.

PubMed

Hanson, Christy; Osberg, Mike; Brown, Jessie; Durham, George; Chin, Daniel P

2017-11-06

Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan. Across the 5 countries, 24% of patients with tuberculosis initiated care seeking in a facility with tuberculosis diagnostic capacity. Forty-two percent of patients sought care at level 0 facilities, where there was generally no tuberculosis diagnostic capacity; another 42% of patients sought care at level 1 facilities, of which 39% had diagnostic capacity. Sixty-six percent of patients initially sought care in private facilities, which had considerably less tuberculosis diagnostic capacity than public facilities; only 7% of notified cases were from the private sector. The GeneXpert system was available in 14%-41% of level 2 facilities in the 3 countries for which there were data. Tuberculosis treatment capacity tracked closely with the availability of diagnostic capacity. There were substantial subnational differences in care-seeking patterns and service availability. The PPA can be a valuable planning and programming tool to ensure that diagnostic and treatment services are available to patients where they seek care. Patient-centered care will require closing the diagnostic gap and engaging the private sector. Extensive subnational differences in patient pathways to care call for differentiated approaches to patient-centered care. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries

PubMed Central

Hanson, Christy; Osberg, Mike; Brown, Jessie; Durham, George; Chin, Daniel P

2017-01-01

Abstract Background Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. Methods This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan. Results Across the 5 countries, 24% of patients with tuberculosis initiated care seeking in a facility with tuberculosis diagnostic capacity. Forty-two percent of patients sought care at level 0 facilities, where there was generally no tuberculosis diagnostic capacity; another 42% of patients sought care at level 1 facilities, of which 39% had diagnostic capacity. Sixty-six percent of patients initially sought care in private facilities, which had considerably less tuberculosis diagnostic capacity than public facilities; only 7% of notified cases were from the private sector. The GeneXpert system was available in 14%–41% of level 2 facilities in the 3 countries for which there were data. Tuberculosis treatment capacity tracked closely with the availability of diagnostic capacity. There were substantial subnational differences in care-seeking patterns and service availability. Discussion The PPA can be a valuable planning and programming tool to ensure that diagnostic and treatment services are available to patients where they seek care. Patient-centered care will require closing the diagnostic gap and engaging the private sector. Extensive subnational differences in patient pathways to care call for differentiated approaches to patient-centered care. PMID:29117351

76 FR 17654 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-30

... OMB Review; Comment Request Title: Evaluation of Adolescent Pregnancy Prevention Approaches-- First... as part of the Evaluation of Adolescent Pregnancy Prevention Approaches (PPA). PPA is a random assignment evaluation designed to result in rigorous evidence on effective ways to reduce teen pregnancy. The...

Programmable Payload Release from Transient Polymer Microcapsules Triggered by a Specific Ion Coactivation Effect.

PubMed

Tang, Shijia; Tang, Liuyan; Lu, Xiaocun; Liu, Huiying; Moore, Jeffrey S

2018-01-10

Stimuli-responsive materials activated by a pair of molecular or ionic species are of interest in the design of chemical logic gates and signal amplification schemes. There are relatively few materials whose coactivated response has been well-characterized. Here, we demonstrate a specific ion coactivation (SICA) effect at the interfaces of transient polymer solids and liquid solutions. We found that depolymerization of the transient polymer, cyclic poly(phthalaldehyde) (cPPA), exhibited a SICA effect when the cPPA core-shell microcapsules were suspended in ion-containing acidic methanol solutions. Significant acceleration in cPPA depolymerization rate is triggered by the combination of acid and ion coactivators. Intriguingly, the SICA effect is related to the Hofmeister behavior. The SICA effect is primarily determined by anions, and cations exhibit a secondary effect that modulates the coactivation strength. Based on these observations, we developed cPPA programmable microcapsules whose payload release rates depend on the composition and concentration of the salt/acidic-methanol solutions.

Charge and energy transports via poly-phenylacetylene based dendrimers

NASA Astrophysics Data System (ADS)

Shin, Yongwoo; Li, Minghai; Lin, Xi

2010-03-01

Poly-Phenylacetylene (PPA) is widely used in photoconductivity, photoluminescence, and light harvesting applications. In this work, we investigate the charge and exciton transport energetics and mechanisms in the PPA-based dendrimers using our recently developed adapted Su-Schrieffer-Heeger (SSH) model Hamiltonians and ab initio Hartree-Fock (HF) calculations. We found both doping and photo-excitation lead to the formation of optical phonon dressed pi electron states, namely the self-localized polarons, in the energy gap. Independent from their origins, these polarons can be self-trapped at multiple lattice locations along the PPA chain, and migrate from one to the next with an activation barrier of ˜0.006 eV, slightly higher than the corresponding barrier found in trans-polyacetylene. The PPA-based dendrimers can be constructed via the meta-positions of phenyl rings. In this case, we found the dendrimer junctions form attractive potential wells for both polarons and excitons, and the width and height of these junction potential wells can be controlled by the geometry of the dendrimers.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

PubMed

Joubert, Sven; Vallet, Guillaume T; Montembeault, Maxime; Boukadi, Mariem; Wilson, Maximiliano A; Laforce, Robert Jr; Rouleau, Isabelle; Brambati, Simona M

2017-07-01

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Characterization and identification of novel antidiabetic and anti-obesity peptides from camel milk protein hydrolysates.

PubMed

Mudgil, Priti; Kamal, Hina; Yuen, Gan Chee; Maqsood, Sajid

2018-09-01

In-vitro inhibitory properties of peptides released from camel milk proteins against dipeptidyl peptidase-IV (DPP-IV), porcine pancreatic α-amylase (PPA), and porcine pancreatic lipase (PPL) were studied. Results revealed that upon hydrolysis by different enzymes, camel milk proteins displayed dramatic increase in inhibition of DPP-IV and PPL, but slight improvement in PPA inhibition was noticed. Peptide sequencing revealed a total of 20 and 3 peptides for A9 and B9 hydrolysates respectively, obtained the score of 0.8 or more on peptide ranker and were categorized as potential DPP-IV inhibitory peptides. KDLWDDFKGL in A9 and MPSKPPLL in B9 were identified as most potent PPA inhibitory peptide. For PPL inhibition only 7 and 2 peptides qualified as PPL inhibitory peptides from hydrolysates A9 and B9, respectively. The present study report for the first time PPA and PPL inhibitory and only second for DPP-IV inhibitory potential of protein hydrolysates from camel milk. Copyright © 2018 Elsevier Ltd. All rights reserved.

Correlative studies of structural and functional imaging in primary progressive aphasia.

PubMed

Panegyres, P K; McCarthy, M; Campbell, A; Lenzo, N; Fallon, M; Thompson, J

2008-01-01

To compare and contrast structural and functional imaging in primary progressive aphasia (PPA). A cohort of 8 patients diagnosed with PPA presenting with nonfluency were prospectively evaluated. All patients had structural imaging in the form of MRI and in 1 patient CAT scanning on account of a cardiac pacemaker. All patients had single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. SPECT and PET imaging had 100% correlation. Anatomical imaging was abnormal in only 6 of the 8 patients. Wernicke's area showed greater peak Z score reduction and extent of area affected than Broca's area (McNemar paired test: P = .008 for Z score reduction; P = .0003 for extent). PET scanning revealed significant involvement of the anterior cingulum. Functional imaging in PPA: (a) identified more patients correctly than anatomic imaging highlighting the importance of SPECT and PET in the diagnosis; and (b) demonstrated the heterogeneous involvement of disordered linguistic networks in PPA suggesting its syndromic nature.

Association between physiological falls risk and physical performance tests among community-dwelling older adults.

PubMed

Singh, Devinder K A; Pillai, Sharmila G K; Tan, Sin Thien; Tai, Chu Chiau; Shahar, Suzana

2015-01-01

Physical performance and balance declines with aging and may lead to increased risk of falls. Physical performance tests may be useful for initial fall-risk screening test among community-dwelling older adults. Physiological profile assessment (PPA), a composite falls risk assessment tool is reported to have 75% accuracy to screen for physiological falls risk. PPA correlates with Timed Up and Go (TUG) test. However, the association between many other commonly used physical performance tests and PPA is not known. The aim of the present study was to examine the association between physiological falls risk measured using PPA and a battery of physical performance tests. One hundred and forty older adults from a senior citizens club in Kuala Lumpur, Malaysia (94 females, 46 males), aged 60 years and above (65.77±4.61), participated in this cross-sectional study. Participants were screened for falls risk using PPA. A battery of physical performance tests that include ten-step test (TST), short physical performance battery (SPPB), functional reach test (FRT), static balance test (SBT), TUG, dominant hand-grip strength (DHGS), and gait speed test (GST) were also performed. Spearman's rank correlation and binomial logistic regression were performed to examine the significantly associated independent variables (physical performance tests) with falls risk (dependent variable). Approximately 13% older adults were at high risk of falls categorized using PPA. Significant differences (P<0.05) were demonstrated for age, TST, SPPB, FRT, SBT, TUG between high and low falls risk group. A significant (P<0.01) weak correlation was found between PPA and TST (r=0.25), TUG (r=0.27), SBT (r=0.23), SPPB (r=-0.33), and FRT (r=-0.23). Binary logistic regression results demonstrated that SBT measuring postural sways objectively using a balance board was the only significant predictor of physiological falls risk (P<0.05, odds ratio of 2.12). The reference values of physical performance tests in our study may be used as a guide for initial falls screening to categorize high and low physiological falls risk among community-dwelling older adults. A more comprehensive assessment of falls risk can be performed thereafter for more specific intervention of underlying impairments.

A study on the nature of interactions of mixed-mode ligands HEA and PPA HyperCel using phenylglyoxal modified lysozyme.

PubMed

Pezzini, J; Cabanne, C; Dupuy, J-W; Gantier, R; Santarelli, X

2014-06-01

Mixed mode chromatography, or multimodal chromatography, involves the exploitation of combinations of several interactions in a controlled manner, to facilitate the rapid capture of proteins. Mixed-mode ligands like HEA and PPA HyperCel™ facilitate different kinds of interactions (hydrophobic, ionic, etc.) under different conditions. In order to better characterize the nature of this multi-modal interaction, we sought to study a protein, lysozyme, which is normally not retained by these mixed mode resins under normal binding conditions. Lysozyme was modified specifically at Arginine residues by the action of phenylglyoxal, and was extensively studied in this work to better characterize the mixed-mode interactions of HEA HyperCel™ and PPA HyperCel™ chromatographic supports. We show here that the adsorption behaviour of lysozyme on HEA and PPA HyperCel™ mixed mode sorbents varies depending on the degree of charge modification at the surface of the protein. Experiments using conventional cation exchange and hydrophobic interaction chromatography confirm that both charge and hydrophobicity modification occurs at the surface of the protein after lysozyme reaction with phenylglyoxal. The results emanating from this work using HEA and PPA HyperCel sorbents strongly suggest that mixed mode chromatography can efficiently separate closely related proteins of only minor surface charge and/or hydrophobicity differences. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative application of the primary progressive aphasia consensus criteria

PubMed Central

Wicklund, Meredith R.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Whitwell, Jennifer L.

2014-01-01

Objective: To determine how well the consensus criteria could classify subjects with primary progressive aphasia (PPA) using a quantitative speech and language battery that matches the test descriptions provided by the consensus criteria. Methods: A total of 105 participants with a neurodegenerative speech and language disorder were prospectively recruited and underwent neurologic, neuropsychological, and speech and language testing and MRI in this case-control study. Twenty-one participants with apraxia of speech without aphasia served as controls. Select tests from the speech and language battery were chosen for application of consensus criteria and cutoffs were employed to determine syndromic classification. Hierarchical cluster analysis was used to examine participants who could not be classified. Results: Of the 84 participants, 58 (69%) could be classified as agrammatic (27%), semantic (7%), or logopenic (35%) variants of PPA. The remaining 31% of participants could not be classified. Of the unclassifiable participants, 2 clusters were identified. The speech and language profile of the first cluster resembled mild logopenic PPA and the second cluster semantic PPA. Gray matter patterns of loss of these 2 clusters of unclassified participants also resembled mild logopenic and semantic variants. Conclusions: Quantitative application of consensus PPA criteria yields the 3 syndromic variants but leaves a large proportion unclassified. Therefore, the current consensus criteria need to be modified in order to improve sensitivity. PMID:24598709

A form of 'parental presence/absence' (PPA) technique for the child patient with dental behaviour management problems.

PubMed

Kotsanos, N; Coolidge, T; Velonis, D; Arapostathis, K N

2009-06-01

This paper reports on the use of early introduction of a specific parental presence/absence (PPA) behavioural technique to manage the initially uncooperative child. Using a prospective design, 440 healthy children aged 3 to 10 years visited a paediatric dental practice within 33 months. Children exhibiting initially Frankl 'negative' and 'definitely negative' behaviour were empathically offered parental presence only if they were cooperative. Otherwise, the parent stepped out until behaviour improvement. t-tests and Chi-square tests were used to compare characteristics of initially cooperative and uncooperative children, as well as proportions of parents who were asked to leave the surgery. The technique's success was assessed by a one sample binomial test. 75 of the children presented as Frankl either 'negative' (30) or 'definitely negative' (45) at their first visit; 70 (93.3%, p<0.001) responded to the PPA technique by displaying positive behaviour as their first visit progressed. 38 responded without the need to ask the parent to exit the practice room, while the other 32 responded only after their parent exited. 52 children had additional appointments, and 8 required an application of PPA at a second appointment; all children cooperated in all subsequent appointments. Early and empathic application of the PPA technique appears very successful in managing initially uncooperative child patients, suggesting that a randomised controlled trial of the technique is warranted.

"What" precedes "which": developmental neural tuning in face- and place-related cortex.

PubMed

Scherf, K Suzanne; Luna, Beatriz; Avidan, Galia; Behrmann, Marlene

2011-09-01

Although category-specific activation for faces in the ventral visual pathway appears adult-like in adolescence, recognition abilities for individual faces are still immature. We investigated how the ability to represent "individual" faces and houses develops at the neural level. Category-selective regions of interest (ROIs) for faces in the fusiform gyrus (FG) and for places in the parahippocampal place area (PPA) were identified individually in children, adolescents, and adults. Then, using an functional magnetic resonance imaging adaptation paradigm, we measured category selectivity and individual-level adaptation for faces and houses in each ROI. Only adults exhibited both category selectivity and individual-level adaptation bilaterally for faces in the FG and for houses in the PPA. Adolescents showed category selectivity bilaterally for faces in the FG and houses in the PPA. Despite this profile of category selectivity, adolescents only exhibited individual-level adaptation for houses bilaterally in the PPA and for faces in the "left" FG. Children only showed category-selective responses for houses in the PPA, and they failed to exhibit category-selective responses for faces in the FG and individual-level adaptation effects anywhere in the brain. These results indicate that category-level neural tuning develops prior to individual-level neural tuning and that face-related cortex is disproportionately slower in this developmental transition than is place-related cortex.

“What” Precedes “Which”: Developmental Neural Tuning in Face- and Place-Related Cortex

PubMed Central

Luna, Beatriz; Avidan, Galia; Behrmann, Marlene

2011-01-01

Although category-specific activation for faces in the ventral visual pathway appears adult-like in adolescence, recognition abilities for individual faces are still immature. We investigated how the ability to represent “individual” faces and houses develops at the neural level. Category-selective regions of interest (ROIs) for faces in the fusiform gyrus (FG) and for places in the parahippocampal place area (PPA) were identified individually in children, adolescents, and adults. Then, using an functional magnetic resonance imaging adaptation paradigm, we measured category selectivity and individual-level adaptation for faces and houses in each ROI. Only adults exhibited both category selectivity and individual-level adaptation bilaterally for faces in the FG and for houses in the PPA. Adolescents showed category selectivity bilaterally for faces in the FG and houses in the PPA. Despite this profile of category selectivity, adolescents only exhibited individual-level adaptation for houses bilaterally in the PPA and for faces in the “left” FG. Children only showed category-selective responses for houses in the PPA, and they failed to exhibit category-selective responses for faces in the FG and individual-level adaptation effects anywhere in the brain. These results indicate that category-level neural tuning develops prior to individual-level neural tuning and that face-related cortex is disproportionately slower in this developmental transition than is place-related cortex. PMID:21257673

A deterministic, dynamic systems model of cow-calf production: The effects of breeding replacement heifers before mature cows over a 10-year horizon.

PubMed

Shane, D D; Larson, R L; Sanderson, M W; Miesner, M; White, B J

2017-10-01

Some cattle production experts believe that cow-calf producers should breed replacement heifers (nulliparous cows) before cows (primiparous and multiparous cows), sometimes referred to as providing a heifer lead time (tHL). Our objective was to model the effects different durations of tHL may have on measures of herd productivity, including the percent of the herd cycling before the end of the first 21 d of the breeding season (%C21), the percent of the herd pregnant at pregnancy diagnosis (%PPD), the distribution of pregnancy by 21-d breeding intervals, the kilograms of calf weaned per cow exposed (KPC), and the replacement percentage (%RH), using a deterministic, dynamic systems model of cow-calf production over a 10-yr horizon. We also wished to examine differences in the effect of tHL related to the primiparous duration of postpartum anestrus (dPPA). The study model examined 6 different dPPA for primiparous cows (60, 70, 80, 90, 100, or 110 d). The multiparous cow duration of postpartum anestrus was set to 60 d. The breeding season length for nulliparous cows was 63 d, as was the breeding season length for primiparous and multiparous cows. Nulliparous cows were modeled with a tHL of 0, 7, 14, 21, 28, 35, or 42 d. Results are reported for the final breeding season of the 10-yr horizon. Increasing tHL resulted in a greater %C21 for the herd and for primiparous cows. Length of tHL had minimal impact on the %PPD unless the dPPA was 80 d or greater. For a dPPA of 110 d, a 0 d tHL resulted in the herd having 88.1 %PPD. When tHL was 21 d, the %PPD increased to 93.0%. The KPC was 161.2 kg when the dPPA was 110 d and tHL was 0 d and improved to 183.2 kg when tHL was increased to 42 d. The %RH did not vary much unless the dPPA was 90 d or greater, but increasing tHL resulted in decreased %RH. Based on the model results, increasing tHL improves the production outcomes included in the analysis, but herds with dPPA of 90 d or greater had the greatest degree of improvement. For these herds, approximately two-thirds of the improvement in outcomes by increasing tHL from 0 d to 42 d was realized when tHL was 21 d. Costs are likely incurred when implementing tHL in a breeding management program, and an ideal tHL likely depends on the dPPA of the herd, the expected improvement in productivity, and the costs associated with increasing tHL. Determining the dPPA of a herd could help veterinarians and producers develop optimal herd management strategies.

Insights into the transposable mobilome of Paracoccus spp. (Alphaproteobacteria).

PubMed

Dziewit, Lukasz; Baj, Jadwiga; Szuplewska, Magdalena; Maj, Anna; Tabin, Mateusz; Czyzkowska, Anna; Skrzypczyk, Grazyna; Adamczuk, Marcin; Sitarek, Tomasz; Stawinski, Piotr; Tudek, Agnieszka; Wanasz, Katarzyna; Wardal, Ewa; Piechucka, Ewa; Bartosik, Dariusz

2012-01-01

Several trap plasmids (enabling positive selection of transposition events) were used to identify a pool of functional transposable elements (TEs) residing in bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25 strains representing 20 species of this genus led to the capture and characterization of (i) 37 insertion sequences (ISs) representing 9 IS families (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family) containing two predicted genetic modules, involved in the arginine deiminase pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g. Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to contain strong promoters able to drive transcription of genes placed downstream of the target site of transposition. Through the application of trap plasmid pCM132TC, containing a promoterless tetracycline resistance reporter gene, we identified five ways in which transposition can supply promoters to transcriptionally silent genes. Besides highlighting the diversity and specific features of several TEs, the analyses performed in this study have provided novel and interesting information on (i) the dynamics of the process of transposition (e.g. the unusually high frequency of transposition of TnPpa1) and (ii) structural changes in DNA mediated by transposition (e.g. the generation of large deletions in the recipient molecule upon transposition of ISPve1 of the IS21 family). We also demonstrated the great potential of TEs and transposition in the generation of diverse phenotypes as well as in the natural amplification and dissemination of genetic information (of adaptative value) by horizontal gene transfer, which is considered the driving force of bacterial evolution.

Insights into the Transposable Mobilome of Paracoccus spp. (Alphaproteobacteria)

PubMed Central

Dziewit, Lukasz; Baj, Jadwiga; Szuplewska, Magdalena; Maj, Anna; Tabin, Mateusz; Czyzkowska, Anna; Skrzypczyk, Grazyna; Adamczuk, Marcin; Sitarek, Tomasz; Stawinski, Piotr; Tudek, Agnieszka; Wanasz, Katarzyna; Wardal, Ewa; Piechucka, Ewa; Bartosik, Dariusz

2012-01-01

Several trap plasmids (enabling positive selection of transposition events) were used to identify a pool of functional transposable elements (TEs) residing in bacteria of the genus Paracoccus (Alphaproteobacteria). Complex analysis of 25 strains representing 20 species of this genus led to the capture and characterization of (i) 37 insertion sequences (ISs) representing 9 IS families (IS3, IS5, IS6, IS21, IS66, IS256, IS1182, IS1380 and IS1634), (ii) a composite transposon Tn6097 generated by two copies of the ISPfe2 (IS1634 family) containing two predicted genetic modules, involved in the arginine deiminase pathway and daunorubicin/doxorubicin resistance, (iii) 3 non-composite transposons of the Tn3 family, including Tn5393 carrying streptomycin resistance and (iv) a transposable genomic island TnPpa1 (45 kb). Some of the elements (e.g. Tn5393, Tn6097 and ISs of the IS903 group of the IS5 family) were shown to contain strong promoters able to drive transcription of genes placed downstream of the target site of transposition. Through the application of trap plasmid pCM132TC, containing a promoterless tetracycline resistance reporter gene, we identified five ways in which transposition can supply promoters to transcriptionally silent genes. Besides highlighting the diversity and specific features of several TEs, the analyses performed in this study have provided novel and interesting information on (i) the dynamics of the process of transposition (e.g. the unusually high frequency of transposition of TnPpa1) and (ii) structural changes in DNA mediated by transposition (e.g. the generation of large deletions in the recipient molecule upon transposition of ISPve1 of the IS21 family). We also demonstrated the great potential of TEs and transposition in the generation of diverse phenotypes as well as in the natural amplification and dissemination of genetic information (of adaptative value) by horizontal gene transfer, which is considered the driving force of bacterial evolution. PMID:22359677

Spousal Recollections of Early Signs of Primary Progressive Aphasia

ERIC Educational Resources Information Center

Pozzebon, Margaret; Douglas, Jacinta; Ames, David

2018-01-01

Background: Although primary progressive aphasia (PPA) is characterized by progressive loss of language and communication skills, knowledge about the earliest emerging signs announcing the onset of this condition is limited. Aims: To explore spousal recollections regarding the earliest signs of PPA and to compare the nature of the earliest…

Systematic Analysis and Comparison of Nucleotide-Binding Site Disease Resistance Genes in a Diploid Cotton Gossypium raimondii

PubMed Central

Wei, Hengling; Li, Wei; Sun, Xiwei; Zhu, Shuijin; Zhu, Jun

2013-01-01

Plant disease resistance genes are a key component of defending plants from a range of pathogens. The majority of these resistance genes belong to the super-family that harbors a Nucleotide-binding site (NBS). A number of studies have focused on NBS-encoding genes in disease resistant breeding programs for diverse plants. However, little information has been reported with an emphasis on systematic analysis and comparison of NBS-encoding genes in cotton. To fill this gap of knowledge, in this study, we identified and investigated the NBS-encoding resistance genes in cotton using the whole genome sequence information of Gossypium raimondii. Totally, 355 NBS-encoding resistance genes were identified. Analyses of the conserved motifs and structural diversity showed that the most two distinct features for these genes are the high proportion of non-regular NBS genes and the high diversity of N-termini domains. Analyses of the physical locations and duplications of NBS-encoding genes showed that gene duplication of disease resistance genes could play an important role in cotton by leading to an increase in the functional diversity of the cotton NBS-encoding genes. Analyses of phylogenetic comparisons indicated that, in cotton, the NBS-encoding genes with TIR domain not only have their own evolution pattern different from those of genes without TIR domain, but also have their own species-specific pattern that differs from those of TIR genes in other plants. Analyses of the correlation between disease resistance QTL and NBS-encoding resistance genes showed that there could be more than half of the disease resistance QTL associated to the NBS-encoding genes in cotton, which agrees with previous studies establishing that more than half of plant resistance genes are NBS-encoding genes. PMID:23936305

Genome-wide comparative analysis of NBS-encoding genes between Brassica species and Arabidopsis thaliana.

PubMed

Yu, Jingyin; Tehrim, Sadia; Zhang, Fengqi; Tong, Chaobo; Huang, Junyan; Cheng, Xiaohui; Dong, Caihua; Zhou, Yanqiu; Qin, Rui; Hua, Wei; Liu, Shengyi

2014-01-03

Plant disease resistance (R) genes with the nucleotide binding site (NBS) play an important role in offering resistance to pathogens. The availability of complete genome sequences of Brassica oleracea and Brassica rapa provides an important opportunity for researchers to identify and characterize NBS-encoding R genes in Brassica species and to compare with analogues in Arabidopsis thaliana based on a comparative genomics approach. However, little is known about the evolutionary fate of NBS-encoding genes in the Brassica lineage after split from A. thaliana. Here we present genome-wide analysis of NBS-encoding genes in B. oleracea, B. rapa and A. thaliana. Through the employment of HMM search and manual curation, we identified 157, 206 and 167 NBS-encoding genes in B. oleracea, B. rapa and A. thaliana genomes, respectively. Phylogenetic analysis among 3 species classified NBS-encoding genes into 6 subgroups. Tandem duplication and whole genome triplication (WGT) analyses revealed that after WGT of the Brassica ancestor, NBS-encoding homologous gene pairs on triplicated regions in Brassica ancestor were deleted or lost quickly, but NBS-encoding genes in Brassica species experienced species-specific gene amplification by tandem duplication after divergence of B. rapa and B. oleracea. Expression profiling of NBS-encoding orthologous gene pairs indicated the differential expression pattern of retained orthologous gene copies in B. oleracea and B. rapa. Furthermore, evolutionary analysis of CNL type NBS-encoding orthologous gene pairs among 3 species suggested that orthologous genes in B. rapa species have undergone stronger negative selection than those in B .oleracea species. But for TNL type, there are no significant differences in the orthologous gene pairs between the two species. This study is first identification and characterization of NBS-encoding genes in B. rapa and B. oleracea based on whole genome sequences. Through tandem duplication and whole genome triplication analysis in B. oleracea, B. rapa and A. thaliana genomes, our study provides insight into the evolutionary history of NBS-encoding genes after divergence of A. thaliana and the Brassica lineage. These results together with expression pattern analysis of NBS-encoding orthologous genes provide useful resource for functional characterization of these genes and genetic improvement of relevant crops.

Significant differentiation in the apolipoprotein(a)/lipoprotein(a) trait between chimpanzees from Western and Central Africa.

PubMed

Noureen, Asma; Ronke, Claudius; Khalifa, Mahmoud; Halbwax, Michel; Fischer, Anne; André, Claudine; Atencia, Rebeca; Garriga, Rosa; Mugisha, Lawrence; Ceglarek, Uta; Thiery, Joachim; Utermann, Gerd; Schmidt, Konrad

2017-09-01

Elevated Lipoprotein(a) (Lp(a)) plasma concentrations are a risk factor for cardiovascular disease in humans, largely controlled by the LPA gene encoding apolipoprotein(a) (apo(a)). Lp(a) is composed of low-density lipoprotein (LDL) and apo(a) and restricted to Catarrhini. A variable number of kringle IV (KIV) domains in LPA lead to a size polymorphism of apo(a) that is inversely correlated with Lp(a) concentrations. Smaller apo(a) isoforms and higher Lp(a) levels in central chimpanzees (Pan troglodytes troglodytes [PTT]) compared to humans from Europe had been reported. We studied apo(a) isoforms and Lp(a) concentrations in 75 western (Pan troglodytes verus [PTV]) and 112 central chimpanzees, and 12 bonobos (Pan paniscus [PPA]), all wild born and living in sanctuaries in Sierra Leone, Republic of the Congo, and DR Congo, respectively, and 116 humans from Gabon. Lp(a) levels were severalfold higher in western than in central chimpanzees (181.0 ± 6.7 mg/dl vs. 56.5 ± 4.3 mg/dl), whereas bonobos showed intermediate levels (134.8 ± 33.4 mg/dl). Apo(a) isoform sizes differed significantly between subspecies (means 20.9 ± 2.2, 22.9 ± 4.4, and 23.8 ± 3.8 KIV repeats in PTV, PTT, and PPA, respectively). However, far higher isoform-associated Lp(a) concentrations for all isoform sizes in western chimpanzees offered the main explanation for the higher overall Lp(a) levels in this subspecies. Human Lp(a) concentrations (mean 47.9 ± 2.8 mg/dl) were similar to those in central chimpanzees despite larger isoforms (mean 27.1 ± 4.9 KIV). Lp(a) and LDL, apoB-100, and total cholesterol levels only correlated in PTV. This remarkable differentiation between chimpanzees from different African habitats and the trait's similarity in humans and chimpanzees from Central Africa poses the question of a possible impact of an environmental factor that has shaped the genetic architecture of LPA. Overall, studies on the cholesterol-containing particles of Lp(a) and LDL in chimpanzees should consider differentiation between subspecies. © 2017 Wiley Periodicals, Inc.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

PubMed

Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

2009-03-11

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

Draft genome sequence of Actinotignum schaalii DSM 15541T: Genetic insights into the lifestyle, cell fitness and virulence.

PubMed

Yassin, Atteyet F; Langenberg, Stefan; Huntemann, Marcel; Clum, Alicia; Pillay, Manoj; Palaniappan, Krishnaveni; Varghese, Neha; Mikhailova, Natalia; Mukherjee, Supratim; Reddy, T B K; Daum, Chris; Shapiro, Nicole; Ivanova, Natalia; Woyke, Tanja; Kyrpides, Nikos C

2017-01-01

The permanent draft genome sequence of Actinotignum schaalii DSM 15541T is presented. The annotated genome includes 2,130,987 bp, with 1777 protein-coding and 58 rRNA-coding genes. Genome sequence analysis revealed absence of genes encoding for: components of the PTS systems, enzymes of the TCA cycle, glyoxylate shunt and gluconeogensis. Genomic data revealed that A. schaalii is able to oxidize carbohydrates via glycolysis, the nonoxidative pentose phosphate and the Entner-Doudoroff pathways. Besides, the genome harbors genes encoding for enzymes involved in the conversion of pyruvate to lactate, acetate and ethanol, which are found to be the end products of carbohydrate fermentation. The genome contained the gene encoding Type I fatty acid synthase required for de novo FAS biosynthesis. The plsY and plsX genes encoding the acyltransferases necessary for phosphatidic acid biosynthesis were absent from the genome. The genome harbors genes encoding enzymes responsible for isoprene biosynthesis via the mevalonate (MVA) pathway. Genes encoding enzymes that confer resistance to reactive oxygen species (ROS) were identified. In addition, A. schaalii harbors genes that protect the genome against viral infections. These include restriction-modification (RM) systems, type II toxin-antitoxin (TA), CRISPR-Cas and abortive infection system. A. schaalii genome also encodes several virulence factors that contribute to adhesion and internalization of this pathogen such as the tad genes encoding proteins required for pili assembly, the nanI gene encoding exo-alpha-sialidase, genes encoding heat shock proteins and genes encoding type VII secretion system. These features are consistent with anaerobic and pathogenic lifestyles. Finally, resistance to ciprofloxacin occurs by mutation in chromosomal genes that encode the subunits of DNA-gyrase (GyrA) and topisomerase IV (ParC) enzymes, while resistant to metronidazole was due to the frxA gene, which encodes NADPH-flavin oxidoreductase.

Parahippocampal and retrosplenial contributions to human spatial navigation

PubMed Central

Epstein, Russell A.

2010-01-01

Spatial navigation is a core cognitive ability in humans and animals. Neuroimaging studies have identified two functionally-defined brain regions that activate during navigational tasks and also during passive viewing of navigationally-relevant stimuli such as environmental scenes: the parahippocampal place area (PPA) and the retrosplenial complex (RSC). Recent findings indicate that the PPA and RSC play distinct and complementary roles in spatial navigation, with the PPA more concerned with representation of the local visual scene and RSC more concerned with situating the scene within the broader spatial environment. These findings are a first step towards understanding the separate components of the cortical network that mediates spatial navigation in humans. PMID:18760955

Health Risk Perceptions and Exercise in Older Adulthood: An Application of Protection Motivation Theory.

PubMed

Ruthig, Joelle C

2016-09-01

Protection Motivation Theory (PMT) was applied to explore the relationship between perceived risk of acute health crises and intent to exercise. Interviews of 351 community-living older adults assessed prior physical activity (PPA), all PMT components, and exercise intent. A multi-group structural equation model revealed gender differences in PMT predictors of exercise intent. PPA, age, self-efficacy, and response efficacy directly predicted men's intent. Women's PPA and age predicted PMT components of self-efficacy and response costs, which predicted intent. Findings have implications for devising interventions to enhance physical activity in later life by targeting different PMT components for older men and women. © The Author(s) 2014.

The Neural Basis of Syntactic Deficits in Primary Progressive Aphasia

ERIC Educational Resources Information Center

Wilson, Stephen M.; Galantucci, Sebastiano; Tartaglia, Maria Carmela; Gorno-Tempini, Maria Luisa

2012-01-01

Patients with primary progressive aphasia (PPA) vary considerably in terms of which brain regions are impacted, as well as in the extent to which syntactic processing is impaired. Here we review the literature on the neural basis of syntactic deficits in PPA. Structural and functional imaging studies have most consistently associated syntactic…

The Time Course of Neurolinguistic and Neuropsychological Symptoms in Three Cases of Logopenic Primary Progressive Aphasia

ERIC Educational Resources Information Center

Etcheverry, Louise; Seidel, Barbara; Grande, Marion; Schulte, Stephanie; Pieperhoff, Peter; Sudmeyer, Martin; Minnerop, Martina; Binkofski, Ferdinand; Huber, Walter; Grodzinsky, Yosef; Amunts, Katrin; Heim, Stefan

2012-01-01

Primary progressive aphasia (PPA) is a rare clinical dementia syndrome affecting predominantly language abilities. Word-finding difficulties and comprehension deficits despite relatively preserved cognitive functions are characteristic symptoms during the first two years, and distinguish PPA from other dementia types like Alzheimer's disease.…

Frontotemporal networks and behavioral symptoms in primary progressive aphasia.

PubMed

D'Anna, Lucio; Mesulam, Marsel M; Thiebaut de Schotten, Michel; Dell'Acqua, Flavio; Murphy, Declan; Wieneke, Christina; Martersteck, Adam; Cobia, Derin; Rogalski, Emily; Catani, Marco

2016-04-12

To determine if behavioral symptoms in patients with primary progressive aphasia (PPA) were associated with degeneration of a ventral frontotemporal network. We used diffusion tensor imaging tractography to quantify abnormalities of the uncinate fasciculus that connects the anterior temporal lobe and the ventrolateral frontal cortex. Two additional ventral tracts were studied: the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. We also measured cortical thickness of anterior temporal and orbitofrontal regions interconnected by these tracts. Thirty-three patients with PPA and 26 healthy controls were recruited. In keeping with the PPA diagnosis, behavioral symptoms were distinctly less prominent than the language deficits. Although all 3 tracts had structural pathology as determined by tractography, significant correlations with scores on the Frontal Behavioral Inventory were found only for the uncinate fasciculus. Cortical atrophy of the orbitofrontal and anterior temporal lobe cortex was also correlated with these scores. Our findings indicate that damage to a frontotemporal network mediated by the uncinate fasciculus may underlie the emergence of behavioral symptoms in patients with PPA. © 2016 American Academy of Neurology.

Frontotemporal networks and behavioral symptoms in primary progressive aphasia

PubMed Central

Mesulam, Marsel M.; Thiebaut de Schotten, Michel; Dell'Acqua, Flavio; Murphy, Declan; Wieneke, Christina; Martersteck, Adam; Cobia, Derin; Rogalski, Emily

2016-01-01

Objective: To determine if behavioral symptoms in patients with primary progressive aphasia (PPA) were associated with degeneration of a ventral frontotemporal network. Methods: We used diffusion tensor imaging tractography to quantify abnormalities of the uncinate fasciculus that connects the anterior temporal lobe and the ventrolateral frontal cortex. Two additional ventral tracts were studied: the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus. We also measured cortical thickness of anterior temporal and orbitofrontal regions interconnected by these tracts. Thirty-three patients with PPA and 26 healthy controls were recruited. Results: In keeping with the PPA diagnosis, behavioral symptoms were distinctly less prominent than the language deficits. Although all 3 tracts had structural pathology as determined by tractography, significant correlations with scores on the Frontal Behavioral Inventory were found only for the uncinate fasciculus. Cortical atrophy of the orbitofrontal and anterior temporal lobe cortex was also correlated with these scores. Conclusions: Our findings indicate that damage to a frontotemporal network mediated by the uncinate fasciculus may underlie the emergence of behavioral symptoms in patients with PPA. PMID:26992858

Primary Progressive Speech Abulia.

PubMed

Milano, Nicholas J; Heilman, Kenneth M

2015-01-01

Primary progressive aphasia (PPA) is a neurodegenerative disorder characterized by progressive language impairment. The three variants of PPA include the nonfluent/agrammatic, semantic, and logopenic types. The goal of this report is to describe two patients with a loss of speech initiation that was associated with bilateral medial frontal atrophy. Two patients with progressive speech deficits were evaluated and their examinations revealed a paucity of spontaneous speech; however their naming, repetition, reading, and writing were all normal. The patients had no evidence of agrammatism or apraxia of speech but did have impaired speech fluency. In addition to impaired production of propositional spontaneous speech, these patients had impaired production of automatic speech (e.g., reciting the Lord's Prayer) and singing. Structural brain imaging revealed bilateral medial frontal atrophy in both patients. These patients' language deficits are consistent with a PPA, but they are in the pattern of a dynamic aphasia. Whereas the signs-symptoms of dynamic aphasia have been previously described, to our knowledge these are the first cases associated with predominantly bilateral medial frontal atrophy that impaired both propositional and automatic speech. Thus, this profile may represent a new variant of PPA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reid, A.A.; Fleming, P.J.; Lake, C.R.

We modified a norepinephrine radioenzymatic method for determination of plasma phenylpropanolamine (PPA) concentrations. PPA is converted to N(methyl-/sup 3/H)ephedrine ((/sup 3/H)EPD) by the enzyme phenylethanolamine N-methyltransferase (PNMT) and S-(methyl-/sup 3/H)adenosyl-L-methionine ((/sup 3/H)AdoMet). The product, (/sup 3/H)EPD, is isolated from unreacted (/sup 3/H)AdoMet and labeled side products by an organic extraction and a TLC procedure. In addition, a preincubation organic extraction procedure is included to remove inhibitors of PNMT from plasma and to concentrate the sample for enhanced enzymatic conversion. In order to accurately quantitate PPA across the wide range of possible concentrations, the assay is conducted at two plasma volumes.more » PPA concentrations between 0.3 and 50 micrograms/liter can be detected with 1 ml of plasma, while concentrations between 4 and 1500 micrograms/liter can be detected with 0.1 ml of plasma. The intra-assay coefficients of variation (CVs) are 9.3 and 5.7% at 0.5 and 1500 micrograms/liter, respectively, while the mean interassay CV is 13.8%.« less

Efficient conversion of phenylpyruvic acid to phenyllactic acid by using whole cells of Bacillus coagulans SDM.

PubMed

Zheng, Zhaojuan; Ma, Cuiqing; Gao, Chao; Li, Fengsong; Qin, Jiayang; Zhang, Haiwei; Wang, Kai; Xu, Ping

2011-04-20

Phenyllactic acid (PLA), a novel antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi, can be produced by many microorganisms, especially lactic acid bacteria. However, the concentration and productivity of PLA have been low in previous studies. The enzymes responsible for conversion of phenylpyruvic acid (PPA) into PLA are equivocal. A novel thermophilic strain, Bacillus coagulans SDM, was isolated for production of PLA. When the solubility and dissolution rate of PPA were enhanced at a high temperature, whole cells of B. coagulans SDM could effectively convert PPA into PLA at a high concentration (37.3 g l(-1)) and high productivity (2.3 g l(-1) h(-1)) under optimal conditions. Enzyme activity staining and kinetic studies identified NAD-dependent lactate dehydrogenases as the key enzymes that reduced PPA to PLA. Taking advantage of the thermophilic character of B. coagulans SDM, a high yield and productivity of PLA were obtained. The enzymes involved in PLA production were identified and characterized, which makes possible the rational design and construction of microorganisms suitable for PLA production with metabolic engineering.

Nucleotide sequences of two genomic DNAs encoding peroxidase of Arabidopsis thaliana.

PubMed

Intapruk, C; Higashimura, N; Yamamoto, K; Okada, N; Shinmyo, A; Takano, M

1991-02-15

The peroxidase (EC 1.11.1.7)-encoding gene of Arabidopsis thaliana was screened from a genomic library using a cDNA encoding a neutral isozyme of horseradish, Armoracia rusticana, peroxidase (HRP) as a probe, and two positive clones were isolated. From the comparison with the sequences of the HRP-encoding genes, we concluded that two clones contained peroxidase-encoding genes, and they were named prxCa and prxEa. Both genes consisted of four exons and three introns; the introns had consensus nucleotides, GT and AG, at the 5' and 3' ends, respectively. The lengths of each putative exon of the prxEa gene were the same as those of the HRP-basic-isozyme-encoding gene, prxC3, and coded for 349 amino acids (aa) with a sequence homology of 89% to that encoded by prxC3. The prxCa gene was very close to the HRP-neutral-isozyme-encoding gene, prxC1b, and coded for 354 aa with 91% homology to that encoded by prxC1b. The aa sequence homology was 64% between the two peroxidases encoded by prxCa and prxEa.

Anatomy of Language Impairments in Primary Progressive Aphasia

PubMed Central

Rogalski, Emily; Cobia, Derin; Harrison, Theresa M.; Wieneke, Christina; Thompson, Cynthia K; Weintraub, Sandra; Mesulam, M.-Marsel

2011-01-01

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca’s area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions. PMID:21368046

Anatomy of language impairments in primary progressive aphasia.

PubMed

Rogalski, Emily; Cobia, Derin; Harrison, Theresa M; Wieneke, Christina; Thompson, Cynthia K; Weintraub, Sandra; Mesulam, M-Marsel

2011-03-02

Primary progressive aphasia (PPA) is a clinical dementia syndrome characterized by progressive decline in language function but relative sparing of other cognitive domains. There are three recognized PPA variants: agrammatic, semantic, and logopenic. Although each PPA subtype is characterized by the nature of the principal deficit, individual patients frequently display subtle impairments in additional language domains. The present study investigated the distribution of atrophy related to performance in specific language domains (i.e., grammatical processing, semantic processing, fluency, and sentence repetition) across PPA variants to better understand the anatomical substrates of language. Results showed regionally specific relationships, primarily in the left hemisphere, between atrophy and impairments in language performance. Most notable was the neuroanatomical distinction between fluency and grammatical processing. Poor fluency was associated with regions dorsal to the traditional boundaries of Broca's area in the inferior frontal sulcus and the posterior middle frontal gyrus, whereas grammatical processing was associated with more widespread atrophy, including the inferior frontal gyrus and supramarginal gyrus. Repetition performance was correlated with atrophy in the posterior superior temporal gyrus. The correlation of atrophy with semantic processing impairment was localized to the anterior temporal poles. Atrophy patterns were more closely correlated with domain-specific performance than with subtype. These results show that PPA reflects a selective disruption of the language network as a whole, with no rigid boundaries between subtypes. Further, these atrophy patterns reveal anatomical correlates of language that could not have been surmised in patients with aphasia resulting from cerebrovascular lesions.

Initial evaluation of 99m Tc-tricarbonyl-cyclopentadienyl fatty acids derivatives as SPECT tracers for myocardium.

PubMed

Liu, Jianping; Wang, Huan; Wang, Shuxia; Xue, Qianqian; Wang, Dawei; Wang, Hang; Zhang, Huabei

2017-05-15

Fatty acids are myocardial metabolic agent for detecting myocardial ischemia and infraction. However, no 99m Tc-labeled fatty acids had potential use in clinical practice. In this study, 99m Tc-CpTT-10-oxo-para-PPA (1d), 99m Tc-CpTT-11-oxo-para-PPA (2d), 99m Tc-CpTT-12-oxo-para-PPA (3d), 99m Tc-CpTT-11-oxo-ortho-PPA (4d), and 99m Tc-CpTT-11-oxo-meta-PPA (5d) were synthesized by a double ligand transfer reaction, and their biological behaviors were investigated. Compound 2d achieved good heart to blood ratio (3.39 at 5 min after intravenous), and 2d showed high-heart uptake of 6.20% ID/g at 5 minutes after injection. Compound 3d displayed a prolonged retention in the myocardium (1.43% ID/g at 60 min after injection). Radioactivity accumulation in the lungs, spleen, and blood was eliminated rapidly. In vivo, metabolite analysis presented that compound 6d may be metabolite of 2d through β-oxidation in tissue. Unfortunately, the biodistribution studies of 1d, 2d, 3d, 4d, and 5d showed fast heart clearance and poor heart to liver ratios, which suggested that the 5 99m Tc-labeled fatty acid analogues cannot be used for diagnosis. Copyright © 2017 John Wiley & Sons, Ltd.

[The phonological variant of primary progressive aphasia, a single case study].

PubMed

Diesfeldt, H F A

2011-04-01

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by an insidious onset and gradual progression of deficits that can involve any aspect of language, including word finding, object naming, fluency, syntax, phonology and word comprehension. The initial symptoms occur in the absence of major deficits in other cognitive domains, including episodic memory, visuospatial abilities and visuoconstruction. According to recent diagnostic guidelines, PPA is typically divided into three variants: nonfluent variant PPA (also termed progressive nonfluent aphasia), semantic variant PPA (also termed semantic dementia) and logopenic/phonological variant PPA (also termed logopenic progressive aphasia). The paper describes a 79-yr old man, who presented with normal motor speech and production rate, impaired single word retrieval and phonemic errors in spontaneous speech and confrontational naming. Confrontation naming was strongly affected by lexical frequency. He was impaired on repetition of sentences and phrases. Reading was intact for regularly spelled words but not for irregular words (surface dyslexia). Comprehension was spared at the single word level, but impaired for complex sentences. He performed within the normal range on the Dutch equivalent of the Pyramids and Palm Trees (PPT) Pictures Test, indicating that semantic processing was preserved. There was, however, a slight deficiency on the PPT Words Test, which appeals to semantic knowledge of verbal associations. His core deficit was interpreted as an inability to retrieve stored lexical-phonological information for spoken word production in spontaneous speech, confrontation naming, repetition and reading aloud.

Protective and restorative potency of Vitamin D on persistent biochemical autistic features induced in propionic acid-intoxicated rat pups.

PubMed

Alfawaz, Hanan A; Bhat, Ramesa Shafi; Al-Ayadhi, Laila; El-Ansary, Afaf K

2014-10-25

Reducing exposure to toxic environmental agents is a critical area of intervention. Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Propionic acid (PA) found in some foods and formed as a metabolic product of gut microbiota has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. The present study investigated the protective and/or therapeutic effects of vitamin D against brain intoxication induced by propionic acid (PPA) in rats. Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups of 7. The control group received only phosphate buffered saline; the oral buffered PPA-treated group received a neurotoxic dose of 250 mg/kg body weight/day for 3 days; and the Vitamin D-protected group received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks, after which the rats were injected with PPA 250 mg/Kg body weight/day for 3 days. The fourth group received PPA 250 mg/Kg body weight/day for 3 days followed by alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks (Vitamin D therapeutic effect). Vitamin D and calcium were measured in the plasma of the four studied groups. Serotonin, interferon gamma (IFN-γ), glutathione-s-transferase activity and DNA double helix breaks were assayed in the brain tissue of the rats for all groups. The obtained data showed that the PPA-treated group demonstrated higher plasma vitamin D levels compared to the control rats, together with multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), an increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA. Vitamin D showed a greater protective than therapeutic effect on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration of the impaired biochemically measured parameters representing neurochemical, inflammation, and detoxification processes.

Association between physiological falls risk and physical performance tests among community-dwelling older adults

PubMed Central

Singh, Devinder KA; Pillai, Sharmila GK; Tan, Sin Thien; Tai, Chu Chiau; Shahar, Suzana

2015-01-01

Background Physical performance and balance declines with aging and may lead to increased risk of falls. Physical performance tests may be useful for initial fall-risk screening test among community-dwelling older adults. Physiological profile assessment (PPA), a composite falls risk assessment tool is reported to have 75% accuracy to screen for physiological falls risk. PPA correlates with Timed Up and Go (TUG) test. However, the association between many other commonly used physical performance tests and PPA is not known. The aim of the present study was to examine the association between physiological falls risk measured using PPA and a battery of physical performance tests. Methods One hundred and forty older adults from a senior citizens club in Kuala Lumpur, Malaysia (94 females, 46 males), aged 60 years and above (65.77±4.61), participated in this cross-sectional study. Participants were screened for falls risk using PPA. A battery of physical performance tests that include ten-step test (TST), short physical performance battery (SPPB), functional reach test (FRT), static balance test (SBT), TUG, dominant hand-grip strength (DHGS), and gait speed test (GST) were also performed. Spearman’s rank correlation and binomial logistic regression were performed to examine the significantly associated independent variables (physical performance tests) with falls risk (dependent variable). Results Approximately 13% older adults were at high risk of falls categorized using PPA. Significant differences (P<0.05) were demonstrated for age, TST, SPPB, FRT, SBT, TUG between high and low falls risk group. A significant (P<0.01) weak correlation was found between PPA and TST (r=0.25), TUG (r=0.27), SBT (r=0.23), SPPB (r=−0.33), and FRT (r=−0.23). Binary logistic regression results demonstrated that SBT measuring postural sways objectively using a balance board was the only significant predictor of physiological falls risk (P<0.05, odds ratio of 2.12). Conclusion The reference values of physical performance tests in our study may be used as a guide for initial falls screening to categorize high and low physiological falls risk among community-dwelling older adults. A more comprehensive assessment of falls risk can be performed thereafter for more specific intervention of underlying impairments. PMID:26316727

Effect of Increased Blood Flow on Pulmonary Circulation Before and During High Altitude Acclimatization.

PubMed

Hilty, Matthias Peter; Müller, Andrea; Flück, Daniela; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Auinger, Katja; Lundby, Carsten; Maggiorini, Marco

2016-12-01

Matthias Peter Hilty, Andrea Mueller, Daniela Flück, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Katja Auinger, Carsten Lundby, and Marco Maggiorini. Effect of increased blood flow on the pulmonary circulation before and during high altitude acclimatization. High Alt Med Biol. 17:305-314, 2016.-Introduction and Methods: Acute exposure to high altitude increases pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR). The evolution of Ppa and PVR with continuous hypoxic exposure remains, however, elusive. To test the hypothesis that altitude exposure leads to a persistent elevation in Ppa and PVR throughout acclimatization in seven healthy male subjects, echocardiography was performed at sea level (SL; 488 m) weekly during a 4-week sojourn at 3454 m (HA1-HA4) and upon return (SL2). Pulmonary artery catheterization and bilateral thigh cuff release maneuver were performed at SL and HA3 to study the properties of pulmonary circulation after 3 weeks of acclimatization. Pulmonary artery catheter determined that systolic Ppa (mean ± SEM) was increased from 20 ± 1 at SL to 27 ± 2 mmHg at HA3 (p < 0.01). Echocardiography assessed that systolic Ppa remained equally increased throughout acclimatization (26 ± 2, 25 ± 2, 25 ± 2, and 24 ± 2 mmHg at HA1-HA4; p = 0.93) and returned to baseline upon return (17 ± 2, 18 ± 1 mmHg at SL, SL2; p = 0.3). The same was shown for PVR. Right heart function remained unaffected. Thigh cuff release maneuvers at SL and HA3 resulted in similar increase in cardiac output (2.5 ± 0.5 and 2.2 ± 0.4 L/min; p = 0.61) without affecting mean Ppa. Prolonged altitude exposure leads to a persistent increase in Ppa and PVR without affecting right heart function and is fully reversible within 1 week after return to SL. The thigh cuff release maneuver-induced increase in cardiac output suggests a preserved ability of pulmonary circulation to cope with sudden remarkable increase in pulmonary blood flow throughout acclimatization.

Degradation of Benzene by Pseudomonas veronii 1YdBTEX2 and 1YB2 Is Catalyzed by Enzymes Encoded in Distinct Catabolism Gene Clusters.

PubMed

de Lima-Morales, Daiana; Chaves-Moreno, Diego; Wos-Oxley, Melissa L; Jáuregui, Ruy; Vilchez-Vargas, Ramiro; Pieper, Dietmar H

2016-01-01

Pseudomonas veronii 1YdBTEX2, a benzene and toluene degrader, and Pseudomonas veronii 1YB2, a benzene degrader, have previously been shown to be key players in a benzene-contaminated site. These strains harbor unique catabolic pathways for the degradation of benzene comprising a gene cluster encoding an isopropylbenzene dioxygenase where genes encoding downstream enzymes were interrupted by stop codons. Extradiol dioxygenases were recruited from gene clusters comprising genes encoding a 2-hydroxymuconic semialdehyde dehydrogenase necessary for benzene degradation but typically absent from isopropylbenzene dioxygenase-encoding gene clusters. The benzene dihydrodiol dehydrogenase-encoding gene was not clustered with any other aromatic degradation genes, and the encoded protein was only distantly related to dehydrogenases of aromatic degradation pathways. The involvement of the different gene clusters in the degradation pathways was suggested by real-time quantitative reverse transcription PCR. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Rapid Identification of Five Classes of Carbapenem Resistance Genes Directly from Rectal Swabs by Use of the Xpert Carba-R Assay

PubMed Central

Cantón, Rafael; Carretto, Edoardo; Peterson, Lance R.; Sautter, Robert L.; Traczewski, Maria M.

2017-01-01

ABSTRACT Carbapenemase-producing organisms (CPO) have been identified by global health leaders as an urgent threat. Detection of patients with gastrointestinal carriage of CPO is necessary to interrupt their spread within health care facilities. In this multisite study, we assessed the performance of the Xpert Carba-R test, a rapid real-time quantitative PCR (qPCR) assay that detects five families of carbapenemase genes (blaIMP, blaKPC, blaNDM, blaOXA-48, and blaVIM) directly from rectal swab specimens. Using dual swabs, specimens from 755 patients were collected and tested prospectively. An additional 432 contrived specimens were prepared by seeding well-characterized carbapenem-susceptible and -nonsusceptible strains into a rectal swab matrix and inoculating them onto swabs prior to testing. Antimicrobial susceptibility testing, broth enriched culture, and DNA sequencing were performed by a central laboratory blind to the Xpert Carba-R results. The Xpert Carba-R assay demonstrated a positive percentage of agreement (PPA) between 60 and 100% for four targets (blaKPC, blaNDM, blaVIM, and blaOXA-48) and a negative percentage of agreement (NPA) ranging between 98.9 and 99.9% relative to the reference method (culture and sequencing of any carbapenem-nonsusceptible isolate). There were no prospective blaIMP-positive samples. Contrived specimens demonstrated a PPA between 95 and 100% and an NPA of 100% for all targets. Testing of rectal swabs directly using the Xpert Carba-R assay is effective for rapid detection and identification of CPO from hospitalized patients. PMID:28515213

Spectrophotometric determination of certain CNS stimulants in dosage forms and spiked human urine via derivatization with 2,4-Dinitrofluorobenzene

PubMed Central

2011-01-01

A new spectrophotometric method is developed for the determination of phenylpropanolamine HCl (PPA), ephedrine HCl (EPH) and pseudoephedrine HCl (PSE) in pharmaceutical preparations and spiked human urine. The method involved heat-catalyzed derivatization of the three drugs with 2,4-dinitrofluorobenzene (DNFB) producing a yellow colored product peaking at 370 nm for PPA and 380 nm for EPH and PSE, respectively. The absorbance concentration plots were rectilinear over the range of 2-20 for PPA and 1-14 μg/mL for both of EPH and PSE, respectively. The limit of detection (LOD) values were 0.20, 0.13 and 0.20 μg/mL for PPA, EPH and PSE, respectively and limit of quantitation (LOQ) values of 0.60 and 0.40 and 0.59 μg/mL for PPA, EPH and PSE, respectively. The analytical performance of the method was fully validated and the results were satisfactory. The proposed method was successfully applied to the determination of the three studied drugs in their commercial dosage forms including tablets, capsules and ampoules with good percentage recoveries. The proposed method was further applied for the determination of PSE in spiked human urine with a mean percentage recovery of 108.17 ± 1.60 for (n = 3). Statistical comparison of the results obtained with those of the comparison methods showed good agreement and proved that there was no significant difference in the accuracy and precision between the two methods. The mechanism of the reaction pathway was postulated. PMID:22032335

ODI - Portal, Pipeline, and Archive (ODI-PPA): a web-based astronomical compute archive, visualization, and analysis service

NASA Astrophysics Data System (ADS)

Gopu, Arvind; Hayashi, Soichi; Young, Michael D.; Harbeck, Daniel R.; Boroson, Todd; Liu, Wilson; Kotulla, Ralf; Shaw, Richard; Henschel, Robert; Rajagopal, Jayadev; Stobie, Elizabeth; Knezek, Patricia; Martin, R. Pierre; Archbold, Kevin

2014-07-01

The One Degree Imager-Portal, Pipeline, and Archive (ODI-PPA) is a web science gateway that provides astronomers a modern web interface that acts as a single point of access to their data, and rich computational and visualization capabilities. Its goal is to support scientists in handling complex data sets, and to enhance WIYN Observatory's scientific productivity beyond data acquisition on its 3.5m telescope. ODI-PPA is designed, with periodic user feedback, to be a compute archive that has built-in frameworks including: (1) Collections that allow an astronomer to create logical collations of data products intended for publication, further research, instructional purposes, or to execute data processing tasks (2) Image Explorer and Source Explorer, which together enable real-time interactive visual analysis of massive astronomical data products within an HTML5 capable web browser, and overlaid standard catalog and Source Extractor-generated source markers (3) Workflow framework which enables rapid integration of data processing pipelines on an associated compute cluster and users to request such pipelines to be executed on their data via custom user interfaces. ODI-PPA is made up of several light-weight services connected by a message bus; the web portal built using Twitter/Bootstrap, AngularJS and jQuery JavaScript libraries, and backend services written in PHP (using the Zend framework) and Python; it leverages supercomputing and storage resources at Indiana University. ODI-PPA is designed to be reconfigurable for use in other science domains with large and complex datasets, including an ongoing offshoot project for electron microscopy data.

Observing conversational laughter in frontotemporal dementia

PubMed Central

Pressman, Peter S; Simpson, Michaela; Gola, Kelly; Shdo, Suzanne M; Spinelli, Edoardo G; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Rankin, Katherine; Levenson, Robert W

2017-01-01

Background We performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant fronto-temporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer’s disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking. Methods Patients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant’s own vocalisation (‘self’ context) or during or shortly after the partner’s vocalisation (‘partner’ context). Results Individuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech compared with healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls. Conclusions Laughter in response to one’s own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis. PMID:28235777

Prominent microglial activation in cortical white matter is selectively associated with cortical atrophy in primary progressive aphasia.

PubMed

Ohm, D T; Kim, G; Gefen, T; Rademaker, A; Weintraub, S; Bigio, E H; Mesulam, M-M; Rogalski, E; Geula, C

2018-04-21

Primary progressive aphasia (PPA) is a clinical syndrome characterized by selective language impairments associated with focal cortical atrophy favouring the language dominant hemisphere. PPA is associated with Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and significant accumulation of activated microglia. Activated microglia can initiate an inflammatory cascade that may contribute to neurodegeneration, but their quantitative distribution in cortical white matter and their relationship with cortical atrophy remain unknown. We investigated white matter activated microglia and their association with grey matter atrophy in 10 PPA cases with either AD or FTLD-TDP pathology. Activated microglia were quantified with optical density measures of HLA-DR immunoreactivity in two regions with peak cortical atrophy, and one nonatrophied region within the language dominant hemisphere of each PPA case. Nonatrophied contralateral homologues of the language dominant regions were examined for hemispheric asymmetry. Qualitatively, greater densities of activated microglia were observed in cortical white matter when compared to grey matter. Quantitative analyses revealed significantly greater densities of activated microglia in the white matter of atrophied regions compared to nonatrophied regions in the language dominant hemisphere (P < 0.05). Atrophied regions of the language dominant hemisphere also showed significantly more activated microglia compared to contralateral homologues (P < 0.05). White matter activated microglia accumulate more in atrophied regions in the language dominant hemisphere of PPA. While microglial activation may constitute a response to neurodegenerative processes in white matter, the resultant inflammatory processes may also exacerbate disease progression and contribute to cortical atrophy. © 2018 British Neuropathological Society.

Nonpharmacological interventions for cognitive impairments following primary progressive aphasia: a systematic review of the literature

PubMed Central

Carthery-Goulart, Maria Teresa; da Silveira, Amanda da Costa; Machado, Thais Helena; Mansur, Leticia Lessa; Parente, Maria Alice de Mattos Pimenta; Senaha, Mirna Lie Hosogi; Brucki, Sonia Maria Dozzi; Nitrini, Ricardo

2013-01-01

This study provided a systematic review on nonpharmacological interventions applied to patients diagnosed with Primary Progressive Aphasia (PPA) and its variants: Semantic (SPPA), Nonfluent (NFPPA) and Logopenic (LPPA) to establish evidence-based recommendations for the clinical practice of cognitive rehabilitation for these patients. METHODS A PubMed and LILACS literature search with no time restriction was conducted with the keywords PPA (and its variants) AND rehabilitation OR training OR intervention OR therapy OR treatment OR effectiveness. To develop its evidence-based recommendations, a research committee identified questions to be addressed and determined the level of evidence for each study according to published criteria (Cicerone et al., 2000). Overall evidence for treatments was summarized and recommendations were derived. RESULTS Our search retrieved articles published from 1995 to 2013: 21 for SPPA, 8 for NFPPA, 3 for LPPA and 8 for PPA with no specification. Thirty-five studies were rated as Class III, consisting of studies with results obtained from one or more single-cases and that used appropriate single-subject methods with adequate quantification and analysis of results. The level of evidence of three functional interventions could not be established. One study was rated as Class II and consisted of a nonrandomized case-control investigation. CONCLUSION Positive results were reported in all reviewed studies. However, in order to be recommended, some investigation regarding the intervention efficacy was required. Results of the present review allows for recommendation of some nonpharmacological interventions for cognitive deficits following PPA as Practice Options. Suggestions for further studies on PPA interventions and future research are discussed. PMID:29213828

Quantifying accessible sites and reactivity on titania–silica (photo)catalysts: Refining TOF calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eaton, Todd R.; Campos, Michael P.; Gray, Kimberly A.

2014-01-01

It can be difficult to determine the number of active atoms accessible to the fluid phase in mixed oxide catalysts, as required for obtaining true turnover frequencies (TOF). Here, we utilize the selective titration of surface Ti atoms with phenylphosphonic acid (PPA) on TiO 2–SiO 2 materials to estimate the number of reactant-accessible sites. TiO 2–SiO 2 composites were synthesized over a range of Ti loadings from grafting of titanocene dichloride (Cp 2TiCl 2) or tetraethoxy orthotitanate (TEOT) on SiO 2 and sol–gel co-hydrolysis of Si and Ti alkoxides. The materials were characterized by DRUV–vis, XRD, BET, and XANES. Despitemore » the significant morphological and electronic differences, materials prepared by Cp 2TiCl 2 and TEOT yielded a near-constant TOF of 0.14 h -1 (±0.04) across Ti loadings, for benzyl alcohol photooxidation, when normalizing rates by sites titrated by PPA. The fraction of Ti atoms titrated by PPA was strongly dependent on synthesis method and surface density. PPA titration and benzyl alcohol photooxidation may be useful measures of surface accessibility in other supported oxides.« less

Efficient Conversion of Phenylpyruvic Acid to Phenyllactic Acid by Using Whole Cells of Bacillus coagulans SDM

PubMed Central

Zheng, Zhaojuan; Ma, Cuiqing; Gao, Chao; Li, Fengsong; Qin, Jiayang; Zhang, Haiwei; Wang, Kai; Xu, Ping

2011-01-01

Background Phenyllactic acid (PLA), a novel antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi, can be produced by many microorganisms, especially lactic acid bacteria. However, the concentration and productivity of PLA have been low in previous studies. The enzymes responsible for conversion of phenylpyruvic acid (PPA) into PLA are equivocal. Methodology/Principal Findings A novel thermophilic strain, Bacillus coagulans SDM, was isolated for production of PLA. When the solubility and dissolution rate of PPA were enhanced at a high temperature, whole cells of B. coagulans SDM could effectively convert PPA into PLA at a high concentration (37.3 g l−1) and high productivity (2.3 g l−1 h−1) under optimal conditions. Enzyme activity staining and kinetic studies identified NAD-dependent lactate dehydrogenases as the key enzymes that reduced PPA to PLA. Conclusions/Significance Taking advantage of the thermophilic character of B. coagulans SDM, a high yield and productivity of PLA were obtained. The enzymes involved in PLA production were identified and characterized, which makes possible the rational design and construction of microorganisms suitable for PLA production with metabolic engineering. PMID:21533054

Participating in a virtual reality balance exercise program can reduce risk and fear of falls.

PubMed

Singh, Devinder K A; Rajaratnam, Bala S; Palaniswamy, Vijayakumar; Pearson, Hannah; Raman, Vimal P; Bong, Pei Sien

2012-11-01

The objective of this study was to quantify the effectiveness of virtual reality balance games (VRBG) to decrease risk and fear of falls among women. Thirty six community dwelling women aged 56 and above were randomly divided into experimental (exercises using VRBG focus on improving balance) and control (conventional balance exercises) groups. Both groups attended a twice 6 weekly exercise session for an hour. Risk and fear of falls were measured with Physiological Profile Approach (PPA) and Activity Specific Balance Scale (ABC-6). Pre and post intervention differences between the groups were examined using two way repeated measures ANOVA. Both VRBG and conventional balance exercise groups had significant decrease in PPA (p<0.001) and ABC-6 (p<0.01) after the interventions. However, no significant effects were demonstrated between the groups in PPA (p=0.18) and ABC-6 (p=0.25) post intervention. Time and group interaction effect were not significant for PPA (p=0.18) and ABC-6 (p=0.45). Practising VRBG can increase balance confidence and decrease risk of falls among community dwelling women. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Methane Post-Processing for Oxygen Loop Closure

NASA Technical Reports Server (NTRS)

Greenwood, Zachary W.; Abney, Morgan B.; Miller, Lee

2016-01-01

State-of-the-art United States Atmospheric Revitalization carbon dioxide (CO2) reduction is based on the Sabatier reaction process, which recovers approximately 50% of the oxygen (O2) from crew metabolic CO2. Oxygen recovery from carbon dioxide is constrained by the limited availability of reactant hydrogen. Post-processing of methane to recover hydrogen with the Umpqua Research Company Plasma Pyrolysis Assembly (PPA) has the potential to further close the Atmospheric Revitalization oxygen loop. The PPA decomposes methane into hydrogen and hydrocarbons, predominantly acetylene, and a small amount of solid carbon. The hydrogen must then be purified before it can be recycled for additional oxygen recovery. Long duration testing and evaluation of a four crew-member sized PPA and a discussion of hydrogen recycling system architectures are presented.

Cyclooxygenase products contribute to endothelin-induced pulmonary hypertension and altered lung mechanics in sheep.

PubMed

Snapper, J R; Lu, W; Lefferts, P L; Thabes, J S

1997-01-01

Endothelins have potent biological effect in vivo which may, in part, be mediated by stimulation of cyclooxygenase metabolism of arachidonic acid. We administered endothelins (ETs) intravenously to chronically instrumented awake sheep with and without pretreatment with meclofenamate (n = 8). 30 micrograms doses of ET-1, ET-2, and ET-3 caused similar degrees of acute elevation of pulmonary artery pressure (PPA), reduction of the dynamic compliance of the lungs (Cdyn), and increases in lung lymph flow. Pretreatment with meclofenamate inhibited the rise in PPA and reduction in Cdyn, but had no effect on lung lymph flow. We conclude that the biological effects of the endothelins on PPA and Cdyn, but not lung fluid balance, are mediated in part by cyclooxygenase products of arachidonic acid metabolism.

IDH1 R132H Mutation Is Accompanied with Malignant Progression of Paired Primary-Recurrent Astrocytic Tumours.

PubMed

Mu, Luyan; Xu, Wanzhen; Li, Qingla; Ge, Haitao; Bao, Hongbo; Xia, Songsong; Ji, Jingjing; Jiang, Jie; Song, Yuwen; Gao, Qiang

2017-01-01

IDH1 R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH1 R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH1 R132H mutations were assessed by immunohistochemistry in 55 paired primary-recurrent astrocytomas tissues, including 5 paired primary pilocytic astrocytoma (pPA, WHO grade I), 35 paired primary low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired primary high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH1 exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH1 R132H mutation was 68.6% (24/35) in pLGA group, but no IDH1 mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with primary astrocytoma, there was no change of IDH1 status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups ( p<0.01 ), while the pHGA group has the shortest ones ( p<0.01 ). In pLGA group, the IDH1 R132H mutation subgroup has longer RFP than IDH1 wild type subgroup ( p<0.01 ), but the OS has no statistical difference between two subgroups ( p>0.6 ). Additionally, IDH1 R132H mutation independently predicted a long RFP in patients with pLGA (HR 1.073, 95% CI 0.151-0.775, p<0.01 ).

IDH1 R132H Mutation Is Accompanied with Malignant Progression of Paired Primary-Recurrent Astrocytic Tumours

PubMed Central

Mu, Luyan; Xu, Wanzhen; Li, Qingla; Ge, Haitao; Bao, Hongbo; Xia, Songsong; Ji, Jingjing; Jiang, Jie; Song, Yuwen; Gao, Qiang

2017-01-01

IDH1 R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH1 R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH1 R132H mutations were assessed by immunohistochemistry in 55 paired primary-recurrent astrocytomas tissues, including 5 paired primary pilocytic astrocytoma (pPA, WHO grade I), 35 paired primary low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired primary high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH1 exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH1 R132H mutation was 68.6% (24/35) in pLGA group, but no IDH1 mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with primary astrocytoma, there was no change of IDH1 status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups (p<0.01), while the pHGA group has the shortest ones (p<0.01). In pLGA group, the IDH1 R132H mutation subgroup has longer RFP than IDH1 wild type subgroup (p<0.01), but the OS has no statistical difference between two subgroups (p>0.6). Additionally, IDH1 R132H mutation independently predicted a long RFP in patients with pLGA (HR 1.073, 95% CI 0.151-0.775, p<0.01). PMID:28928859

Mollusk genes encoding lysine tRNA (UUU) contain introns.

PubMed

Matsuo, M; Abe, Y; Saruta, Y; Okada, N

1995-11-20

New intron-containing genes encoding tRNAs were discovered when genomic DNA isolated from various animal species was amplified by the polymerase chain reaction (PCR) with primers based on sequences of rabbit tRNA(Lys). From sequencing analysis of the products of PCR, we found that introns are present in several genes encoding tRNA(Lys) in mollusks, such as Loligo bleekeri (squid) and Octopus vulgaris (octopus). These introns were specific to genes encoding tRNA(Lys)(CUU) and were not present in genes encoding tRNA(Lys)(CUU). In addition, the sequences of the introns were different from one another. To confirm the results of our initial experiments, we isolated and sequenced genes encoding tRNA(Lys)(CUU) and tRNA(Lys)(UUU). The gene for tRNA(Lys)(UUU) from squid contained an intron, whose sequence was the same as that identified by PCR, and the gene formed a cluster with a corresponding pseudogene. Several DNA regions of 2.1 kb containing this cluster appeared to be tandemly arrayed in the squid genome. By contrast, the gene encoding tRNA(Lys)(CUU) did not contain an intron, as shown also by PCR. The tRNA(Lys)(UUU) that corresponded to the analyzed gene was isolated and characterized. The present study provides the first example of an intron-containing gene encoding a tRNA in mollusks and suggests the universality of introns in such genes in higher eukaryotes.

Human AZU-1 gene, variants thereof and expressed gene products

DOEpatents

Chen, Huei-Mei; Bissell, Mina

2004-06-22

A human AZU-1 gene, mutants, variants and fragments thereof. Protein products encoded by the AZU-1 gene and homologs encoded by the variants of AZU-1 gene acting as tumor suppressors or markers of malignancy progression and tumorigenicity reversion. Identification, isolation and characterization of AZU-1 and AZU-2 genes localized to a tumor suppressive locus at chromosome 10q26, highly expressed in nonmalignant and premalignant cells derived from a human breast tumor progression model. A recombinant full length protein sequences encoded by the AZU-1 gene and nucleotide sequences of AZU-1 and AZU-2 genes and variant and fragments thereof. Monoclonal or polyclonal antibodies specific to AZU-1, AZU-2 encoded protein and to AZU-1, or AZU-2 encoded protein homologs.

The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.

PubMed Central

Grohmann, L; Brennicke, A; Schuster, W

1992-01-01

The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed. Images PMID:1454526

On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups

PubMed Central

2011-01-01

Backgrounds The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. Objective To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA) in rats. Methods 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA), serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. Results The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA), serotonin (5HT) and dopamine (DA) as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6), tumor necrosis factor-α (TNF-α) as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC). Conclusions Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as there was a remarkable amelioration of most of the measured parameters (i.e. higher GABA, 5HT, DA, PE, PS and PC) and lower Il-6, TNF-α and caspase-3. PMID:21854591

Human-based percussion and self-similarity detection in electroacoustic music

NASA Astrophysics Data System (ADS)

Mills, John Anderson, III

Electroacoustic music is music that uses electronic technology for the compositional manipulation of sound, and is a unique genre of music for many reasons. Analyzing electroacoustic music requires special measures, some of which are integrated into the design of a preliminary percussion analysis tool set for electroacoustic music. This tool set is designed to incorporate the human processing of music and sound. Models of the human auditory periphery are used as a front end to the analysis algorithms. The audio properties of percussivity and self-similarity are chosen as the focus because these properties are computable and informative. A collection of human judgments about percussion was undertaken to acquire clearly specified, sound-event dimensions that humans use as a percussive cue. A total of 29 participants was asked to make judgments about the percussivity of 360 pairs of synthesized snare-drum sounds. The grouped results indicate that of the dimensions tested rise time is the strongest cue for percussivity. String resonance also has a strong effect, but because of the complex nature of string resonance, it is not a fundamental dimension of a sound event. Gross spectral filtering also has an effect on the judgment of percussivity but the effect is weaker than for rise time and string resonance. Gross spectral filtering also has less effect when the stronger cue of rise time is modified simultaneously. A percussivity-profile algorithm (PPA) is designed to identify those instants in pieces of music that humans also would identify as percussive. The PPA is implemented using a time-domain, channel-based approach and psychoacoustic models. The input parameters are tuned to maximize performance at matching participants' choices in the percussion-judgment collection. After the PPA is tuned, the PPA then is used to analyze pieces of electroacoustic music. Real electroacoustic music introduces new challenges for the PPA, though those same challenges might affect human judgment as well. A similarity matrix is combined with the PPA in order to find self-similarity in the percussive sounds of electroacoustic music. This percussive similarity matrix is then used to identify structural characteristics in two pieces of electroacoustic music.

Assessing the dysexecutive syndrome in dementia.

PubMed

Gansler, David A; Huey, Edward D; Pan, Jessica J; Wasserman, Eric; Grafman, Jordan H

2017-03-01

We compared performance on tests of dysexecutive behaviour (DB) and executive function (EF) in patients with behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and corticobasal syndrome (CBS). Patients diagnosed with bvFTD (n=124), PPA (n=34) and CBS (n=85) were recruited. EF was measured with the Delis-Kaplan Executive Function System (DKEFS: performance based), and DB was measured with the Frontal Systems Behavior Scale (FrSBe: caregiver-report based). Confirmatory factor analysis characterised the relationship between EF and DB, binary logistic regression evaluated the incremental diagnostic utility of the measures and neuroimaging data from 110 patients identified neural correlates. EF was lowest and DB was highest in bvFTD participants. EF and DB were distinct but related (r=-0.48). Measures correctly classified 89% of bvFTD from CBS patients and 93% of bvFTD from PPA patients-30% and 13% above base rates (59%, 80%), respectively. All modalities were useful in identifying CBS and PPA, whereas DB alone was useful for identifying bvFTD. EF was uniquely associated with caudal left dorsolateral prefrontal and lateral temporo-parietal cortices. DB was uniquely associated with the cingulate (R>L), right subcallosal and right anterior frontal cortex. EF and DB were associated with the rostral dorsolateral prefrontal cortex bilaterally. EF and DB measures displayed criterion and construct validity, had incremental utility at low DB levels (CBS and PPA) and were associated with overlapping and distinct neural correlates. EF and DB procedures can conjointly provide useful diagnostic and descriptive information in identifying and ruling out the dysexecutive syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Multiepitope HER2 targeting enhances photoimmunotherapy of HER2-overexpressing cancer cells with pyropheophorbide-a immunoconjugates.

PubMed

Savellano, Mark D; Pogue, Brian W; Hoopes, P Jack; Vitetta, Ellen S; Paulsen, Keith D

2005-07-15

Multi-targeting strategies improve the efficacy of antibody and immunotoxin therapies but have not yet been thoroughly explored for HER2-based cancer treatments. We investigated multi-epitope HER2 targeting to boost photosensitizer immunoconjugate uptake as a way of enhancing photoimmunotherapy. Photoimmunotherapy may allow targeted photodynamic destruction of malignancies and may also potentiate anticancer antibodies. However, one obstacle preventing its clinical use is the delivery of enough photosensitizer immunoconjugates to target cells. Anti-HER2 photosensitizer immunoconjugates were constructed from two monoclonal antibodies (mAb), HER50 and HER66, using a novel method originally developed to label photosensitizer immunoconjugates with the photosensitizer, benzoporphyrin derivative verteporfin. Photosensitizer immunoconjugates were labeled instead with a promising alternative photosensitizer, pyropheophorbide-a (PPa), which required only minor changes to the conjugation procedure. Uptake and phototoxicity experiments using human cancer cells were conducted with the photosensitizer immunoconjugates and, for comparison, with free PPa. SK-BR-3 and SK-OV-3 cells served as HER2-overexpressing target cells. MDA-MB-468 cells served as HER2-nonexpressing control cells. Photosensitizer immunoconjugates with PPa/mAb molar ratios up to approximately 10 specifically targeted and photodynamically killed HER2-overexpressing cells. On a per mole basis, photosensitizer immunoconjugates were less phototoxic than free PPa, but photosensitizer immunoconjugates were selective for target cells whereas free PPa was not. Multiepitope targeted photoimmunotherapy with a HER50 and HER66 photosensitizer immunoconjugate mixture was significantly more effective than single-epitope targeted photoimmunotherapy with a single anti-HER2 photosensitizer immunoconjugate, provided photosensitizer immunoconjugate binding was saturated. This study shows that multiepitope targeting enhances HER2-targeted photoimmunotherapy and maintains a high degree of specificity. Consequently, it seems that multitargeted photoimmunotherapy should also be useful against cancers that overexpress other receptors.

Observing conversational laughter in frontotemporal dementia.

PubMed

Pressman, Peter S; Simpson, Michaela; Gola, Kelly; Shdo, Suzanne M; Spinelli, Edoardo G; Miller, Bruce L; Gorno-Tempini, Maria Luisa; Rankin, Katherine; Levenson, Robert W

2017-05-01

We performed an observational study of laughter during seminaturalistic conversations between patients with dementia and familial caregivers. Patients were diagnosed with (1) behavioural variant frontotemporal dementia (bvFTD), (2) right temporal variant frontotemporal dementia (rtFTD), (3) semantic variant of primary progressive aphasia (svPPA), (4) non-fluent variant primary progressive aphasia (nfvPPA) or (5) early onset Alzheimer's disease (eoAD). We hypothesised that those with bvFTD would laugh less in response to their own speech than other dementia groups or controls, while those with rtFTD would laugh less regardless of who was speaking. Patients with bvFTD (n=39), svPPA (n=19), rtFTD (n=14), nfvPPA (n=16), eoAD (n=17) and healthy controls (n=156) were recorded (video and audio) while discussing a problem in their relationship with a healthy control companion. Using the audio track only, laughs were identified by trained coders and then further classed by an automated algorithm as occurring during or shortly after the participant's own vocalisation ('self' context) or during or shortly after the partner's vocalisation ('partner' context). Individuals with bvFTD, eoAD or rtFTD laughed less across both contexts of self and partner than the other groups. Those with bvFTD laughed less relative to their own speech comparedwith healthy controls. Those with nfvPPA laughed more in the partner context compared with healthy controls. Laughter in response to one's own vocalisations or those of a conversational partner may be a clinically useful measure in dementia diagnosis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Fall risk in Chinese community-dwelling older adults: A physiological profile assessment study.

PubMed

Siong, Kar-Ho; Kwan, Marcella Mun-San; Lord, Stephen R; Lam, Andrew Kwok-Cheung; Tsang, William Wai-Nam; Cheong, Allen Ming-Yan

2016-02-01

The short-form Physiological Profile Assessment (PPA) is increasingly used in clinical practice for assessing fall risk in older people. However, a normative database is only available for Caucasian populations. The purpose of the present study was to develop a normative database for Hong Kong Chinese older people and examine the fall risk profile of this population. A total of 622 participants aged 60-95 years were recruited. Participants underwent the PPA (containing tests of contrast sensitivity, proprioception, quadriceps strength, reaction time and sway), and composite fall risk scores were computed. Participants were then followed up for falls for 1 year. Quadriceps strength and lower limb proprioception scores were comparable with those reported for Caucasian populations. However, contrast sensitivity, simple reaction time and postural sway scores were relatively poor. The average composite fall risk score was 1.7 ± 1.5, showing a "moderate" fall risk when compared with the Caucasian norms. Despite the relatively poor physical performances and moderately high fall risk scores, the incidence of one plus falls in the 1-year follow-up period was just 16.4%, with just 2.6% reporting two plus falls. The area under the curve for composite fall risk scores in discriminating fallers from non-fallers was 0.53 (95% CI 0.45-0.60). Despite poorer performance in PPA tests, the incidence of prospective falls in a Hong Kong Chinese population was low. In consequence, the PPA could not discriminate well between fallers and non-fallers. The present study provided normality data for short-form PPA measures for older Chinese people as a reference for further studies. © 2015 Japan Geriatrics Society.

Pulmonary circulation and gas exchange at exercise in Sherpas at high altitude.

PubMed

Faoro, Vitalie; Huez, Sandrine; Vanderpool, Rebecca; Groepenhoff, Herman; de Bisschop, Claire; Martinot, Jean-Benot; Lamotte, Michel; Pavelescu, Adriana; Guénard, Hervé; Naeije, Robert

2014-04-01

Tibetans have been reported to present with a unique phenotypic adaptation to high altitude characterized by higher resting ventilation and arterial oxygen saturation, no excessive polycythemia, and lower pulmonary arterial pressures (Ppa) compared with other high-altitude populations. How this affects exercise capacity is not exactly known. We measured aerobic exercise capacity during an incremental cardiopulmonary exercise test, lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) at rest, and mean Ppa (mPpa) and cardiac output by echocardiography at rest and at exercise in 13 Sherpas and in 13 acclimatized lowlander controls at the altitude of 5,050 m in Nepal. In Sherpas vs. lowlanders, arterial oxygen saturation was 86 ± 1 vs. 83 ± 2% (mean ± SE; P = nonsignificant), mPpa at rest 19 ± 1 vs. 23 ± 1 mmHg (P < 0.05), DL(CO) corrected for hemoglobin 61 ± 4 vs. 37 ± 2 ml · min(-1) · mmHg(-1) (P < 0.001), DL(NO) 226 ± 18 vs. 153 ± 9 ml · min(-1) · mmHg(-1) (P < 0.001), maximum oxygen uptake 32 ± 3 vs. 28 ± 1 ml · kg(-1) · min(-1) (P = nonsignificant), and ventilatory equivalent for carbon dioxide at anaerobic threshold 40 ± 2 vs. 48 ± 2 (P < 0.001). Maximum oxygen uptake was correlated directly to DL(CO) and inversely to the slope of mPpa-cardiac index relationships in both Sherpas and acclimatized lowlanders. We conclude that Sherpas compared with acclimatized lowlanders have an unremarkable aerobic exercise capacity, but with less pronounced pulmonary hypertension, lower ventilatory responses, and higher lung diffusing capacity.

Generating Billion-Edge Scale-Free Networks in Seconds: Performance Study of a Novel GPU-based Preferential Attachment Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perumalla, Kalyan S.; Alam, Maksudul

A novel parallel algorithm is presented for generating random scale-free networks using the preferential-attachment model. The algorithm, named cuPPA, is custom-designed for single instruction multiple data (SIMD) style of parallel processing supported by modern processors such as graphical processing units (GPUs). To the best of our knowledge, our algorithm is the first to exploit GPUs, and also the fastest implementation available today, to generate scale free networks using the preferential attachment model. A detailed performance study is presented to understand the scalability and runtime characteristics of the cuPPA algorithm. In one of the best cases, when executed on an NVidiamore » GeForce 1080 GPU, cuPPA generates a scale free network of a billion edges in less than 2 seconds.« less

An Approach for Hydrogen Recycling in a Closed-loop Life Support Architecture to Increase Oxygen Recovery Beyond State-of-the-Art

NASA Technical Reports Server (NTRS)

Abney, Morgan B.; Miller, Lee; Greenwood, Zachary; Alvarez, Giraldo

2014-01-01

State-of-the-art atmosphere revitalization life support technology on the International Space Station is theoretically capable of recovering 50% of the oxygen from metabolic carbon dioxide via the Carbon Dioxide Reduction Assembly (CRA). When coupled with a Plasma Pyrolysis Assembly (PPA), oxygen recovery increases dramatically, thus drastically reducing the logistical challenges associated with oxygen resupply. The PPA decomposes methane to predominantly form hydrogen and acetylene. Because of the unstable nature of acetylene, a down-stream separation system is required to remove acetylene from the hydrogen stream before it is recycled to the CRA. A new closed-loop architecture that includes a PPA and downstream Hydrogen Purification Assembly (HyPA) is proposed and discussed. Additionally, initial results of separation material testing are reported.

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy.

PubMed

Zhang, Xin; Yan, Qi; Mulatihan, Di Naer; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-22

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Deconstructing Visual Scenes in Cortex: Gradients of Object and Spatial Layout Information

PubMed Central

Kravitz, Dwight J.; Baker, Chris I.

2013-01-01

Real-world visual scenes are complex cluttered, and heterogeneous stimuli engaging scene- and object-selective cortical regions including parahippocampal place area (PPA), retrosplenial complex (RSC), and lateral occipital complex (LOC). To understand the unique contribution of each region to distributed scene representations, we generated predictions based on a neuroanatomical framework adapted from monkey and tested them using minimal scenes in which we independently manipulated both spatial layout (open, closed, and gradient) and object content (furniture, e.g., bed, dresser). Commensurate with its strong connectivity with posterior parietal cortex, RSC evidenced strong spatial layout information but no object information, and its response was not even modulated by object presence. In contrast, LOC, which lies within the ventral visual pathway, contained strong object information but no background information. Finally, PPA, which is connected with both the dorsal and the ventral visual pathway, showed information about both objects and spatial backgrounds and was sensitive to the presence or absence of either. These results suggest that 1) LOC, PPA, and RSC have distinct representations, emphasizing different aspects of scenes, 2) the specific representations in each region are predictable from their patterns of connectivity, and 3) PPA combines both spatial layout and object information as predicted by connectivity. PMID:22473894

A novel system of galangin-potassium permanganate-polyphosphoric acid for the determination of tryptophan and its chemiluminescence mechanism.

PubMed

Li, Li; Guo, Ruibin; Zhang, Dongxia; Du, Xinzhen

2015-08-01

A novel galangin-potassium permanganate (KMnO4)-polyphosphoric acid (PPA) system was found to have an outstanding response to tryptophan (Trp). Trp determination using this KMnO4 -PPA system was enhanced significantly in the presence of galangin. A highly sensitive flow-injection chemiluminescence (CL) method to determine Trp was developed based on the CL reaction of galangin-KMnO4 -Trp in PPA media. The presence of galangin, a member of the flavonol class of flavonoid complexes, greatly increased the luminous intensity of Trp in KMnO4 -PPA systems. Under optimized conditions, Trp was determined in the 0.05-10 µg/mL range, with a detection limit (3σ) of 5.0 × 10(-3)  µg/mL. The relative standard deviation (RSD) was 1.0% for 11 replicate determinations of 1.0 µg/mL Trp. Two synthetic samples were determined selectively with recoveries of 98.4-100.1% in the presence of other amino acids. The possible mechanism is summarized as follows: excited states of Mn(II)(*) and Mn(III(*) types are the main means of generating chemical luminescent species, and Trp concentration and luminescence intensity have a linear relationship, which enables quantitative analysis. Copyright © 2014 John Wiley & Sons, Ltd.

A longitudinal study of behavior in frontotemporal dementia and primary progressive aphasia.

PubMed

Marczinski, Cecile A; Davidson, Wilda; Kertesz, Andrew

2004-12-01

To evaluate the construct validity of the Frontal Behavioral Inventory (FBI) and to describe the evolution of the behavioral abnormalities of the behavioral and aphasic presentations of frontotemporal dementia (FTD) by means of a 3-year longitudinal study. The FBI is a standardized behavioral questionnaire useful in the diagnosis and quantification of the personality and behavior disorder FTD. Patients who had three consecutive yearly assessments with the FBI were selected, 12 with the behavioral variant of FTD (FTD-bv) and 14 with Primary Progressive Aphasia (PPA). FBI scores rose as the disease progressed in both the FTD-bv and PPA groups over the 3 years of testing. Initial mean FBI scores of the FTD-bv group were above the cutoff for FTD as established for this diagnosis with previous standardization. By the third year, the mean FBI score of PPA patients was also above the established cutoff for FTD. The outcome of the study demonstrates that the FBI is sensitive to changes in behavior and personality in both variants of FTD. The FBI can be used to describe the evolution of symptoms and the course of the illness of Pick complex patients who present initially with FTD-bv or who present with PPA and subsequently develop the behavioral disorder.

The occipital place area represents the local elements of scenes

PubMed Central

Kamps, Frederik S.; Julian, Joshua B.; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D.

2016-01-01

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents in not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements – both in spatial boundary and scene content representation – while PPA and RSC represent global scene properties. PMID:26931815

Pharmaceutical micelles featured with singlet oxygen-responsive cargo release and mitochondrial targeting for enhanced photodynamic therapy

NASA Astrophysics Data System (ADS)

Zhang, Xin; Yan, Qi; Naer Mulatihan, Di; Zhu, Jundong; Fan, Aiping; Wang, Zheng; Zhao, Yanjun

2018-06-01

The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius of singlet oxygen as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria-targeting. An imidazole-bearing amphiphilic copolymer was employed as the micelle building block to encapsulate triphenylphosphonium-pyropheophorbide a (TPP-PPa) conjugate or PPa. Upon laser irradiation, the singlet oxygen produced by TPP-PPa/PPa oxidized the imidazole moiety to produce hydrophilic urea, leading to micelle disassembly and rapid cargo release. The co-localization analysis showed that the TPP moiety significantly enhanced the photosensitizer uptake by mitochondria, improved mitochondria depolarization upon irradiation, and hence boosted the cytotoxicity in 4T1 cells. The targeting strategy also dramatically reduced the intracellular ATP concentration as a consequence of mitochondria injury. The mitochondria damage was accompanied with the activation of the apoptosis signals (caspase 3 and caspase 9), whose level was directly correlated to the apoptosis extent. The current work provides a facile and robust means to enhance the efficacy of photodynamic therapy.

Template properties of oligocytidylates formed in the montmorillonite catalyzed condensation of ImpC. [Abstract only

NASA Technical Reports Server (NTRS)

Ferris, James P.; Ertem, Goezen

1994-01-01

In an attempt to investigate the prebiotic formation of phosphodiester bond in RNA, we have studied the self condensation of 5'-phosphorimidazolide of adenosine (ImpA), in aqueous solutions containing 0.2 M sodium chloride and 0.075 M magnesium chloride at pH 8 using clay minerals as catalyst. In the presence of certain montmorillonites, oligomers containing up to ten monomer units in their chain were formed, while in control experiments, where no catalyst was added, the major product was 5',5'-diadenosine diphosphate, A(sup 5')ppA. In reactions carried out with ImpA: A(sup 5')ppA mixtures at 9:1 mole ratio, oligomers of the type A(sup 5')p(pA)(sub n) and (A(sup 5')p)(sub n)A(sup 5')ppA(pA)(sub n) formed at the expense of (pA)(sub n) type oligomers. Addition of A(sup 5')ppA to the reaction mixture increased the regiospecifity of 3',5'-link formation from 67% to 79%. The condensation of the 5'-phosphorimidazolide of cytidine, ImpC, was also carried out in the presence and absence of A(sup 5')ppA under the same conditions and oligomers containing up to twelve monomer units were obtained.

Hemispheric Asymmetry of Visual Scene Processing in the Human Brain: Evidence from Repetition Priming and Intrinsic Activity

PubMed Central

Kahn, Itamar; Wig, Gagan S.; Schacter, Daniel L.

2012-01-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes. PMID:21968568

Hemispheric asymmetry of visual scene processing in the human brain: evidence from repetition priming and intrinsic activity.

PubMed

Stevens, W Dale; Kahn, Itamar; Wig, Gagan S; Schacter, Daniel L

2012-08-01

Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

The occipital place area represents the local elements of scenes.

PubMed

Kamps, Frederik S; Julian, Joshua B; Kubilius, Jonas; Kanwisher, Nancy; Dilks, Daniel D

2016-05-15

Neuroimaging studies have identified three scene-selective regions in human cortex: parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA). However, precisely what scene information each region represents is not clear, especially for the least studied, more posterior OPA. Here we hypothesized that OPA represents local elements of scenes within two independent, yet complementary scene descriptors: spatial boundary (i.e., the layout of external surfaces) and scene content (e.g., internal objects). If OPA processes the local elements of spatial boundary information, then it should respond to these local elements (e.g., walls) themselves, regardless of their spatial arrangement. Indeed, we found that OPA, but not PPA or RSC, responded similarly to images of intact rooms and these same rooms in which the surfaces were fractured and rearranged, disrupting the spatial boundary. Next, if OPA represents the local elements of scene content information, then it should respond more when more such local elements (e.g., furniture) are present. Indeed, we found that OPA, but not PPA or RSC, responded more to multiple than single pieces of furniture. Taken together, these findings reveal that OPA analyzes local scene elements - both in spatial boundary and scene content representation - while PPA and RSC represent global scene properties. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological falls risk assessment in older people with Alzheimer's disease.

PubMed

Lorbach, Edwina R; Webster, Kate E; Menz, Hylton B; Wittwer, Joanne E; Merory, John R

2007-01-01

Falls are common in people with Alzheimer's disease (AD). There is some evidence that deficits in vision, peripheral sensation, strength, reaction time and balance may be partly responsible for this increased risk. To determine the feasibility and test-retest reliability of a physiological test battery designed to assess falls risk [the Physiological Profile Assessment (PPA)] in people with AD, and to compare their PPA scores to age- and sex-matched controls. Twenty-one community-dwelling people with probable, mild to moderate AD aged 63-91 years, and 21 age- and sex-matched controls underwent the PPA tests and the Mini-Mental State Examination. All tests were then repeated in the AD group to determine test-retest reliability. Most of the PPA tests could be successfully administered to participants with AD. The AD group had a significantly higher overall falls risk score (t(40) = -2.41, p < 0.02), slower hand (t(40) = -4.86, p < 0.01) and foot reaction time (t(40) = -2.26, p < 0.05) and worse coordinated stability (t(40) = -2.40, p < 0.05) than the controls. Physiological falls risk assessment is feasible in older people with mild to moderate AD. Older people with AD demonstrate significant impairments in several physiological domains, particularly reaction time, compared to controls.

The organization of the fuc regulon specifying L-fucose dissimilation in Escherichia coli K12 as determined by gene cloning.

PubMed

Chen, Y M; Zhu, Y; Lin, E C

1987-12-01

In Escherichia coli the six known genes specifying the utilization of L-fucose as carbon and energy source cluster at 60.2 min and constitute a regulon. These genes include fucP (encoding L-fucose permease), fucI (encoding L-fucose isomerase), fucK (encoding L-fuculose kinase), fucA (encoding L-fuculose 1-phosphate aldolase), fucO (encoding L-1,2-propanediol oxidoreductase), and fucR (encoding the regulatory protein). In this study the fuc genes were cloned and their positions on the chromosome were established by restriction endonuclease and complementation analyses. Clockwise, the gene order is: fucO-fucA-fucP-fucI-fucK-fucR. The operons comprising the structural genes and the direction of transcription were determined by complementation analysis and Southern blot hybridization. The fucPIK and fucA operons are transcribed clockwise. The fucO operon is transcribed counterclockwise. The fucR gene product activates the three structural operons in trans.

Evolutionary Characteristics of Missing Proteins: Insights into the Evolution of Human Chromosomes Related to Missing-Protein-Encoding Genes.

PubMed

Xu, Aishi; Li, Guang; Yang, Dong; Wu, Songfeng; Ouyang, Hongsheng; Xu, Ping; He, Fuchu

2015-12-04

Although the "missing protein" is a temporary concept in C-HPP, the biological information for their "missing" could be an important clue in evolutionary studies. Here we classified missing-protein-encoding genes into two groups, the genes encoding PE2 proteins (with transcript evidence) and the genes encoding PE3/4 proteins (with no transcript evidence). These missing-protein-encoding genes distribute unevenly among different chromosomes, chromosomal regions, or gene clusters. In the view of evolutionary features, PE3/4 genes tend to be young, spreading at the nonhomology chromosomal regions and evolving at higher rates. Interestingly, there is a higher proportion of singletons in PE3/4 genes than the proportion of singletons in all genes (background) and OTCSGs (organ, tissue, cell type-specific genes). More importantly, most of the paralogous PE3/4 genes belong to the newly duplicated members of the paralogous gene groups, which mainly contribute to special biological functions, such as "smell perception". These functions are heavily restricted into specific type of cells, tissues, or specific developmental stages, acting as the new functional requirements that facilitated the emergence of the missing-protein-encoding genes during evolution. In addition, the criteria for the extremely special physical-chemical proteins were first set up based on the properties of PE2 proteins, and the evolutionary characteristics of those proteins were explored. Overall, the evolutionary analyses of missing-protein-encoding genes are expected to be highly instructive for proteomics and functional studies in the future.

[Genetic instability of probiotic characteristics in the Bifidobacterium longum subsp. longum B379M strain during cultivation and maintenance].

PubMed

Averina, O V; Nezametdinova, V Z; Alekseeva, M G; Danilenko, V N

2012-11-01

The stability of inheriting several genes in the Russian commercial strain Bifidobacterium longum subsp. longum B379M during cultivation and maintenance under laboratory conditions has been studied. The examined genes code for probiotic characteristics, such as utilization of several sugars (lacA2 gene, encoding beta-galactosidase; ara gene, encoding arabinosidase; and galA gene, encoding arabinogalactan endo-beta-galactosidase); synthesis of bacteriocins (lans gene, encoding lanthionine synthetase); and mobile gene tet(W), conferring resistance to the antibiotic tetracycline. The other gene families studied include the genes responsible for signal transduction and adaptation to stress conditions in the majority of bacteria (serine/threonine protein kinases and the toxin-antitoxin systems of MazEF and RelBE types) and transcription regulators (genes encoding WhiB family proteins). Genomic DNA was analyzed by PCR using specially selected primers. A loss of the genes galA and tet(W) has been shown. It is proposed to expand the requirements on probiotic strains, namely, to control retention of the key probiotic genes using molecular biological methods.

Isolated gene encoding an enzyme with UDP-glucose pyrophosphorylase and phosphoglucomutase activities from Cyclotella cryptica

DOEpatents

Jarvis, Eric E.; Roessler, Paul G.

1999-01-01

The present invention relates to a cloned gene which encodes an enzyme, the purified enzyme, and the applications and products resulting from the use of the gene and enzyme. The gene, isolated from Cyclotella cryptica, encodes a multifunctional enzyme that has both UDP-glucose pyrophosphorylase and phosphoglucomutase activities.

Human Genomic Signatures of Brain Oscillations During Memory Encoding.

PubMed

Berto, Stefano; Wang, Guang-Zhong; Germi, James; Lega, Bradley C; Konopka, Genevieve

2018-05-01

Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

Financing Solar PV at Government Sites with PPAs and Public Debt (Brochure)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

2011-11-01

Historically, state and local governmental agencies have employed one of two models to deploy solar photovoltaic (PV) projects: (1) self-ownership (financed through a variety of means) or (2) third-party ownership through a power purchase agreement (PPA). Morris County, New Jersey, administrators recently pioneered a way to combine many of the benefits of self-ownership and third-party PPAs through a bond-PPA hybrid, frequently referred to as the Morris Model. At the request of the Department of Energy's Solar Market Transformation group, NREL examined the hybrid model. This fact sheet describes how the hybrid model works, assesses the model's relative advantages and challengesmore » as compared to self-ownership and the third-party PPA model, provides a quick guide to project implementation, and assesses the replicability of the model in other jurisdictions across the United States.« less

Financing Solar PV at Government Sites with PPAs and Public Debt (Brochure)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

2011-12-01

Historically, state and local governmental agencies have employed one of two models to deploy solar photovoltaic (PV) projects: (1) self-ownership (financed through a variety of means) or (2) third-party ownership through a power purchase agreement (PPA). Morris County, New Jersey, administrators recently pioneered a way to combine many of the benefits of self-ownership and third-party PPAs through a bond-PPA hybrid, frequently referred to as the Morris Model. At the request of the Department of Energy?s Solar Market Transformation group, NREL examined the hybrid model. This fact sheet describes how the hybrid model works, assesses the model?s relative advantages and challengesmore » as compared to self-ownership and the third-party PPA model, provides a quick guide to project implementation, and assesses the replicability of the model in other jurisdictions across the United States.« less

Isolated gene encoding an enzyme with UDP-glucose pyrophosphorylase and phosphoglucomutase activities from Cyclotella cryptica

DOEpatents

Jarvis, E.E.; Roessler, P.G.

1999-07-27

The present invention relates to a cloned gene which encodes an enzyme, the purified enzyme, and the applications and products resulting from the use of the gene and enzyme. The gene, isolated from Cyclotella cryptica, encodes a multifunctional enzyme that has both UDP-glucose pyrophosphorylase and phosphoglucomutase activities. 8 figs.

Evolutionary analysis of hydrophobin gene family in two wood-degrading basidiomycetes, Phlebia brevispora and Heterobasidion annosum s.l.

PubMed Central

2013-01-01

Background Hydrophobins are small secreted cysteine-rich proteins that play diverse roles during different phases of fungal life cycle. In basidiomycetes, hydrophobin-encoding genes often form large multigene families with up to 40 members. The evolutionary forces driving hydrophobin gene expansion and diversification in basidiomycetes are poorly understood. The functional roles of individual genes within such gene families also remain unclear. The relationship between the hydrophobin gene number, the genome size and the lifestyle of respective fungal species has not yet been thoroughly investigated. Here, we present results of our survey of hydrophobin gene families in two species of wood-degrading basidiomycetes, Phlebia brevispora and Heterobasidion annosum s.l. We have also investigated the regulatory pattern of hydrophobin-encoding genes from H. annosum s.s. during saprotrophic growth on pine wood as well as on culture filtrate from Phlebiopsis gigantea using micro-arrays. These data are supplemented by results of the protein structure modeling for a representative set of hydrophobins. Results We have identified hydrophobin genes from the genomes of two wood-degrading species of basidiomycetes, Heterobasidion irregulare, representing one of the microspecies within the aggregate H. annosum s.l., and Phlebia brevispora. Although a high number of hydrophobin-encoding genes were observed in H. irregulare (16 copies), a remarkable expansion of these genes was recorded in P. brevispora (26 copies). A significant expansion of hydrophobin-encoding genes in other analyzed basidiomycetes was also documented (1–40 copies), whereas contraction through gene loss was observed among the analyzed ascomycetes (1–11 copies). Our phylogenetic analysis confirmed the important role of gene duplication events in the evolution of hydrophobins in basidiomycetes. Increased number of hydrophobin-encoding genes appears to have been linked to the species’ ecological strategy, with the non-pathogenic fungi having increased numbers of hydrophobins compared with their pathogenic counterparts. However, there was no significant relationship between the number of hydrophobin-encoding genes and genome size. Furthermore, our results revealed significant differences in the expression levels of the 16 H. annosum s.s. hydrophobin-encoding genes which suggest possible differences in their regulatory patterns. Conclusions A considerable expansion of the hydrophobin-encoding genes in basidiomycetes has been observed. The distribution and number of hydrophobin-encoding genes in the analyzed species may be connected to their ecological preferences. Results of our analysis also have shown that H. annosum s.l. hydrophobin-encoding genes may be under positive selection. Our gene expression analysis revealed differential expression of H. annosum s.s. hydrophobin genes under different growth conditions, indicating their possible functional diversification. PMID:24188142

Glutathione S-transferase-encoding gene as a potential probe for environmental bacterial isolates capable of degrading polycyclic aromatic hydrocarbons.

PubMed Central

Lloyd-Jones, G; Lau, P C

1997-01-01

Homologs of the glutathione S-transferase (GST)-encoding gene were identified in a collection of aromatic hydrocarbon-degrading Sphingomonas spp. isolated from New Zealand, Antarctica, and the United States by using PCR primers designed from the GST-encoding gene of Sphingomonas paucimobilis EPA505. Sequence analysis of PCR fragments generated from these isolates and of the GST gene amplified from DNA extracted from polycyclic aromatic hydrocarbon (PAH)-contaminated soil revealed a high degree of conservation, which may make the GST-encoding gene a potentially useful marker for PAH-degrading bacteria. PMID:9251217

Enterotoxin-encoding genes in Staphylococcus spp. from bulk goat milk.

PubMed

Lyra, Daniele G; Sousa, Francisca G C; Borges, Maria F; Givisiez, Patrícia E N; Queiroga, Rita C R E; Souza, Evandro L; Gebreyes, Wondwossen A; Oliveira, Celso J B

2013-02-01

Although Staphylococcus aureus has been implicated as the main Staphylococcus species causing human food poisoning, recent studies have shown that coagulase-negative Staphylococcus could also harbor enterotoxin-encoding genes. Such organisms are often present in goat milk and are the most important mastitis-causing agents. Therefore, this study aimed to investigate the occurrence of enterotoxin-encoding genes among coagulase-positive (CoPS) and coagulase-negative (CoNS) staphylococci isolated from raw goat milk produced in the semi-arid region of Paraiba, the most important region for goat milk production in Brazil. Enterotoxin-encoding genes were screened in 74 staphylococci isolates (30 CoPS and 44 CoNS) by polymerase chain reaction targeting the genes sea, seb, sec, sed, see, seg, seh, and sei. Enterotoxin-encoding genes were found in nine (12.2%) isolates, and four different genes (sea, sec, seg, and sei) were identified amongst the isolates. The most frequent genes were seg and sei, which were often found simultaneously in 44.5% of the isolates. The gene sec was the most frequent among the classical genes, and sea was found only in one isolate. All CoPS isolates (n=7) harboring enterotoxigenic genes were identified as S. aureus. The two coagulase-negative isolates were S. haemolyticus and S. hominis subsp. hominis and they harbored sei and sec genes, respectively. A higher frequency of enterotoxin-encoding genes was observed amongst CoPS (23.3%) than CoNS (4.5%) isolates (p<0.05), reinforcing the importance of S. aureus as a potential foodborne agent. However, the potential risk posed by CoNS in goat milk should not be ignored because it has a higher occurrence in goat milk and enterotoxin-encoding genes were detected in some isolates.

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

PubMed

Montembeault, M; Brambati, S M; Joubert, S; Boukadi, M; Chapleau, M; Laforce, R Jr; Wilson, M A; Macoir, J; Rouleau, I

2017-01-27

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Three copies of a single protein II-encoding sequence in the genome of Neisseria gonorrhoeae JS3: evidence for gene conversion and gene duplication.

PubMed

van der Ley, P

1988-11-01

Gonococci express a family of related outer membrane proteins designated protein II (P.II). These surface proteins are subject to both phase variation and antigenic variation. The P.II gene repertoire of Neisseria gonorrhoeae strain JS3 was found to consist of at least ten genes, eight of which were cloned. Sequence analysis and DNA hybridization studies revealed that one particular P.II-encoding sequence is present in three distinct, but almost identical, copies in the JS3 genome. These genes encode the P.II protein that was previously identified as P.IIc. Comparison of their sequences shows that the multiple copies of this P.IIc-encoding gene might have been generated by both gene conversion and gene duplication.

Non-Power Purchase Agreement (PPA) Options for Financing Solar Deployment at Universities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Financing solar using power purchase agreements (PPAs) has facilitated solar deployment of more than 100 megawatts (MW) at universities--as compared to 50 MW facilitated by financing models not using PPAs. This brochure, which overviews existing financing models and funding mechanisms available for solar procurement, focuses on non-PPA financing models. For more information on solar deployment at universities using PPAs, refer to Using Power Purchase Agreements for Solar Deployment at Universities.

User Driven Image Stacking for ODI Data and Beyond via a Highly Customizable Web Interface

NASA Astrophysics Data System (ADS)

Hayashi, S.; Gopu, A.; Young, M. D.; Kotulla, R.

2015-09-01

While some astronomical archives have begun serving standard calibrated data products, the process of producing stacked images remains a challenge left to the end-user. The benefits of astronomical image stacking are well established, and dither patterns are recommended for almost all observing targets. Some archives automatically produce stacks of limited scientific usefulness without any fine-grained user or operator configurability. In this paper, we present PPA Stack, a web based stacking framework within the ODI - Portal, Pipeline, and Archive system. PPA Stack offers a web user interface with built-in heuristics (based on pointing, filter, and other metadata information) to pre-sort images into a set of likely stacks while still allowing the user or operator complete control over the images and parameters for each of the stacks they wish to produce. The user interface, designed using AngularJS, provides multiple views of the input dataset and parameters, all of which are synchronized in real time. A backend consisting of a Python application optimized for ODI data, wrapped around the SWarp software, handles the execution of stacking workflow jobs on Indiana University's Big Red II supercomputer, and the subsequent ingestion of the combined images back into the PPA archive. PPA Stack is designed to enable seamless integration of other stacking applications in the future, so users can select the most appropriate option for their science.

Influence of Oxygenated Compounds on Reaction Products in a Microwave Plasma Methane Pyrolysis Assembly for Post-Processing of Sabatier Methane

NASA Technical Reports Server (NTRS)

Mansell, J. Matthew; Abney, Morgan B.; Miller, Lee A.

2011-01-01

The state-of-the-art Carbon Dioxide Reduction Assembly (CRA) was delivered to the International Space Station (ISS) in April 2010. The system is designed to accept carbon dioxide from the Carbon Dioxide Removal Assembly and hydrogen from the Oxygen Generation Assembly. The two gases are reacted in the CRA in a Sabatier reactor to produce water and methane. Venting of methane results in an oxygen resupply requirement of about 378 lbs per crew member per year. If the oxygen is supplied as water, the total weight for resupply is about 476 lb per crew member per year. For long-term missions beyond low Earth orbit, during which resupply capabilities will be further limited, recovery of hydrogen from methane is highly desirable. For this purpose, NASA is pursuing development of a Plasma Pyrolysis Assembly (PPA) capable of recovering hydrogen from methane. Under certain conditions, water vapor and carbon dioxide (nominally intended to be separated from the CRA outlet stream) may be present in the PPA feed stream. Thus, testing was conducted in 2010 to determine the effect of these "oxygenated" compounds on PPA performance, particularly the effect of inlet carbon dioxide and water variations on the PPA product stream. This paper discusses the test set-up, analysis, and results of this testing

TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease

PubMed Central

Mishra, Manjari; Hatanpaa, Kimmo J.; White, Charles L.; Johnson, Nancy; Rademaker, Alfred; Weitner, Bing Bing; Deng, Han-Xiang; Dubner, Steven D.; Weintraub, Sandra; Mesulam, Marsel

2010-01-01

The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain–behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinicoanatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies. PMID:20361198

Asymmetry of cortical decline in subtypes of primary progressive aphasia.

PubMed

Rogalski, Emily; Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M-Marsel

2014-09-23

The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. © 2014 American Academy of Neurology.

Asymmetry of cortical decline in subtypes of primary progressive aphasia

PubMed Central

Cobia, Derin; Martersteck, Adam; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Mesulam, M.-Marsel

2014-01-01

Objective: The aim of this study was to provide quantitative measures of changes in cortical atrophy over a 2-year period associated with 3 subtypes of primary progressive aphasia (PPA) using whole-brain vertex-wise and region-of-interest (ROI) neuroimaging methods. The purpose was to quantitate disease progression, establish an empirical basis for clinical expectations, and provide outcome measures for therapeutic trials. Methods: Changes in cortical thickness and volume loss as well as neuropsychological performance were assessed at baseline and 2-year follow-up in 26 patients who fulfilled criteria for logopenic (8 patients), agrammatic (10 patients), and semantic (8 patients) PPA subtypes. Whole-brain vertex-wise and ROI imaging analysis were conducted using the FreeSurfer longitudinal pipeline. Results: Clinical deficits and cortical atrophy patterns showed distinct patterns of change among the subtypes over 2 years. Results confirmed that progression for each of the 3 subtypes showed left greater than right hemisphere asymmetry. An ROI analysis also revealed that progression was greater within, rather than outside, the language network. Conclusions: Preferential neurodegeneration of the left hemisphere language network is a common denominator for all 3 PPA subtypes, even as the disease progresses. Using a focal cortical language network ROI as an outcome measure of disease progression appears to be more sensitive than whole-brain or ventricular volume measures of change and may be helpful for designing future clinical trials in PPA. PMID:25165386

Influence of Oxygenated Compounds on Reaction Products in a Microwave Plasma Methane Pyrolysis Assembly for Post-Processing of Sabatier Methane

NASA Technical Reports Server (NTRS)

Mansell, J. Matthew; Abney, Morgan B.

2012-01-01

The state-of-the-art Carbon Dioxide Reduction Assembly (CRA) was delivered to the International Space Station (ISS) in April 2010. The system is designed to accept carbon dioxide from the Carbon Dioxide Removal Assembly and hydrogen from the Oxygen Generation Assembly. The two gases are reacted in the CRA in a Sabatier reactor to produce water and methane. Venting of methane results in an oxygen resupply requirement of about 378 lbs per crew member per year. If the oxygen is supplied as water, the total weight for resupply is about 476 lb per crew member per year. For long-term missions beyond low Earth orbit, during which resupply capabilities will be further limited, recovery of hydrogen from methane is highly desirable. For this purpose, NASA is pursuing development of a Plasma Pyrolysis Assembly (PPA) capable of recovering hydrogen from methane. Under certain conditions, water vapor and carbon dioxide (nominally intended to be separated from the CRA outlet stream) may be present in the PPA feed stream. Thus, testing was conducted in 2010 to determine the effect of these oxygenated compounds on PPA performance, particularly the effect of inlet carbon dioxide and water variations on the PPA product stream. This paper discusses the test set-up, analysis, and results of this testing.

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.

PubMed

Bisenius, S; Neumann, J; Schroeter, M L

2016-04-01

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately. © 2016 EAN.

Predisposing factors and management of complications in acute tonsillitis.

PubMed

Gahleitner, Constanze; Hofauer, Benedikt; Stark, Thomas; Knopf, Andreas

2016-09-01

RPA and NF was diagnosed with a sensitivity/specificity of 100%/94% in patients with acute tonsillitis and without suspicion for disease complication after ENT examination, but an age >35 years and serum CRP >15.5mg/dl. Acute tonsillitis represents a frequent disease in the otorhinolaryngology. Some patients exhibit disease aggravations resulting in (descending) peritonsillar abscess (PTA, dPTA), para-/retropharyngeal abscess (PPA, RPA), or necrotising fasciitis (NF). The study analyses the underlying predisposing factors. The retrospective cohort study includes a total of 1636 patients comprising 852 outpatients with acute bacterial tonsillitis, 279 in-patients with acute bacterial tonsillitis, 452 patients with PTA, 31 patients with dPTA/PPA, 12 patients with RPA, and 10 patients with NF. Patients were analysed for disease-related data. While leucocytes do not distinguish the sub-groups, C-reactive protein demonstrated a significant increase resulting in the highest level for RPA and NF (p < 0.0001). PTA and RPA are usually caused by streptococcus, dPTA/PPA by anaerobic bacterias, and NF mixed infections (p < 0.0001). Patients with PTA were younger than dPTA/PPA (p = 0.002) or RPA/NF (p < 0.0001). Subsequently, the rate of internistic comorbidities was significantly increased in RPA/NF (p < 0.0001). ROC-analysis identified cut-offs for age <36 years and CRP <15.5mg/dl to distinguish acute bacterial tonsillitis from RPA.

Effects of transcranial direct current stimulation on language improvement and cortical activation in nonfluent variant primary progressive aphasia.

PubMed

Wang, Jie; Wu, Dongyu; Chen, Yan; Yuan, Ying; Zhang, Meikui

2013-08-09

We investigate the effects of transcranial direct current stimulation (tDCS) on language improvement and cortical activation in nonfluent variant primary progressive aphasia (nfvPPA). A 67-year-old woman diagnosed as nfvPPA received sham-tDCS for 5 days over the left posterior perisylvian region (PPR) in the morning and over left Broca's area in the afternoon in Phases A1 and A2, and tDCS for 5 days with an anodal electrode over the left PPR in the morning and over left Broca's area in the afternoon in Phases B1 and B2. Auditory word comprehension, picture naming, oral word reading and word repetition subtests of the Psycholinguistic Assessment in Chinese Aphasia (PACA) were administered before and after each phase. The EEG nonlinear index of approximate entropy (ApEn) was calculated before Phase A1, and after Phases B1 and B2. Our findings revealed that the patient improved greatly in the four subtests after A-tDCS and ApEn indices increased in stimulated areas and non-stimulated areas. We demonstrated that anodal tDCS over the left PPR and Broca's area can improve language performance of nfvPPA. tDCS may be used as an alternative therapeutic tool for PPA. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia

PubMed Central

McConathey, Eric M.; White, Nicole C.; Gervits, Felix; Ash, Sherry; Coslett, H. Branch; Grossman, Murray; Hamilton, Roy H.

2017-01-01

Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the present sham-controlled study, we examined whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants were recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants were naïve to stimulation condition). A battery of language tests was administered at baseline, immediately post-tDCS (real and sham), and 6 weeks and 12 weeks following stimulation. When we accounted for individuals’ baseline performance, our analyses demonstrated a stratification of tDCS effects. Individuals who performed worse at baseline showed tDCS-related improvements in global language performance, grammatical comprehension and semantic processing. Individuals who performed better at baseline showed a slight tDCS-related benefit on our speech repetition metric. Real tDCS may improve language performance in some individuals with PPA. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies. Clinicaltrials.gov ID: NCT02928848 PMID:28713256

Effect of intracellular photosensitized singlet oxygen production on the electrophysiological properties of cultured rat hippocampal neurons.

PubMed

Breitenbach, Thomas; Ogilby, Peter R; Lambert, John D C

2010-12-01

Whole-cell patch-clamp recordings from single cultured mammalian neurons have been used to provide insight into early membrane-dependent events that result upon the intracellular photosensitized production of singlet molecular oxygen, O(2)(a(1)Δ(g)). The singlet oxygen sensitizers used, pyropheophorbide a (PPa) and protoporphyrin IX (PpIX), locate mainly in cell membranes and mitochondria, respectively. Irradiation of these sensitizers altered both passive and dynamic electrophysiological properties of the neurons in a dose-dependent manner, though the response threshold was much lower with PPa than with PpIX. In particular, notable decreases were observed in the rising and falling rates of action potentials and, at higher light fluences, plateau potentials consistent with activation of Ca(2+) channels also developed. The data suggest that singlet oxygen production specifically influences Na(+), K(+) and Ca(2+) ionophores in the cell membrane. Upon terminating sensitizer irradiation, responses evoked by PPa stabilized immediately whereas those evoked by PpIX continued to develop. These data are consistent with a spatially-resolved sphere of intracellular singlet oxygen activity. While the response to PPa irradiation appears to be membrane specific, the response to PpIX irradiation appears to be systemic and possibly part of a cascade of apoptotic events. These results should contribute to a better understanding of membrane-dependent events pertinent to cell death mediated by singlet oxygen.

Prepenetration Apparatus Assembly Precedes and Predicts the Colonization Patterns of Arbuscular Mycorrhizal Fungi within the Root Cortex of Both Medicago truncatula and Daucus carota[W

PubMed Central

Genre, Andrea; Chabaud, Mireille; Faccio, Antonella; Barker, David G.; Bonfante, Paola

2008-01-01

Arbuscular mycorrhizas (AM) are widespread, ancient endosymbiotic associations that contribute significantly to soil nutrient uptake in plants. We have previously shown that initial fungal penetration of the host root is mediated via a specialized cytoplasmic assembly called the prepenetration apparatus (PPA), which directs AM hyphae through the epidermis (Genre et al., 2005). In vivo confocal microscopy studies performed on Medicago truncatula and Daucus carota, host plants with different patterns of AM colonization, now reveal that subsequent intracellular growth across the root outer cortex is also PPA dependent. On the other hand, inner root cortical colonization leading to arbuscule development involves more varied and complex PPA-related mechanisms. In particular, a striking alignment of polarized PPAs can be observed in adjacent inner cortical cells of D. carota, correlating with the intracellular root colonization strategy of this plant. Ultrastructural analysis of these PPA-containing cells reveals intense membrane trafficking coupled with nuclear enlargement and remodeling, typical features of arbusculated cells. Taken together, these findings imply that prepenetration responses are both conserved and modulated throughout the AM symbiosis as a function of the different stages of fungal accommodation and the host-specific pattern of root colonization. We propose a model for intracellular AM fungal accommodation integrating peri-arbuscular interface formation and the regulation of functional arbuscule development. PMID:18515499

Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romand, J.A.; Pinsky, M.R.; Firestone, L.

Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. The authors studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-minmore » exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial [beta]-adrenergic blockage (propanolol, 0.15 mg/kg iv) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa and calculated PVR, both of which decreased with 17 ppm NO. ALI decreased arterial Po[sub 2] and increased airway pressure, shunt, and dead space ventilation. Ppa and PVR were greater during ALI than during hyperoxia. NO inhalation had no measurable effect during ALI before or after [beta]-adrenergic blockage. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 [mu]g) induced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid-induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary circulation and specifically reduces HPV but not oleic acid-induced increases in pulmonary vasomotor tone. 28 refs., 3 figs., 2 tabs.« less

[Expression changes of major outer membrane protein antigens in Leptospira interrogans during infection and its mechanism].

PubMed

Zheng, Linli; Ge, Yumei; Hu, Weilin; Yan, Jie

2013-03-01

To determine expression changes of major outer membrane protein(OMP) antigens of Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai during infection of human macrophages and its mechanism. OmpR encoding genes and OmpR-related histidine kinase (HK) encoding gene of L.interrogans strain Lai and their functional domains were predicted using bioinformatics technique. mRNA level changes of the leptospiral major OMP-encoding genes before and after infection of human THP-1 macrophages were detected by real-time fluorescence quantitative RT-PCR. Effects of the OmpR-encoding genes and HK-encoding gene on the expression of leptospiral OMPs during infection were determined by HK-peptide antiserum block assay and closantel inhibitive assays. The bioinformatics analysis indicated that LB015 and LB333 were referred to OmpR-encoding genes of the spirochete, while LB014 might act as a OmpR-related HK-encoding gene. After the spirochete infecting THP-1 cells, mRNA levels of leptospiral lipL21, lipL32 and lipL41 genes were rapidly and persistently down-regulated (P <0.01), whereas mRNA levels of leptospiral groEL, mce, loa22 and ligB genes were rapidly but transiently up-regulated (P<0.01). The treatment with closantel and HK-peptide antiserum partly reversed the infection-based down-regulated mRNA levels of lipL21 and lipL48 genes (P <0.01). Moreover, closantel caused a decrease of the infection-based up-regulated mRNA levels of groEL, mce, loa22 and ligB genes (P <0.01). Expression levels of L.interrogans strain Lai major OMP antigens present notable changes during infection of human macrophages. There is a group of OmpR-and HK-encoding genes which may play a major role in down-regulation of expression levels of partial OMP antigens during infection.

Transcriptomic analysis of Arabidopsis developing stems: a close-up on cell wall genes

PubMed Central

Minic, Zoran; Jamet, Elisabeth; San-Clemente, Hélène; Pelletier, Sandra; Renou, Jean-Pierre; Rihouey, Christophe; Okinyo, Denis PO; Proux, Caroline; Lerouge, Patrice; Jouanin, Lise

2009-01-01

Background Different strategies (genetics, biochemistry, and proteomics) can be used to study proteins involved in cell biogenesis. The availability of the complete sequences of several plant genomes allowed the development of transcriptomic studies. Although the expression patterns of some Arabidopsis thaliana genes involved in cell wall biogenesis were identified at different physiological stages, detailed microarray analysis of plant cell wall genes has not been performed on any plant tissues. Using transcriptomic and bioinformatic tools, we studied the regulation of cell wall genes in Arabidopsis stems, i.e. genes encoding proteins involved in cell wall biogenesis and genes encoding secreted proteins. Results Transcriptomic analyses of stems were performed at three different developmental stages, i.e., young stems, intermediate stage, and mature stems. Many genes involved in the synthesis of cell wall components such as polysaccharides and monolignols were identified. A total of 345 genes encoding predicted secreted proteins with moderate or high level of transcripts were analyzed in details. The encoded proteins were distributed into 8 classes, based on the presence of predicted functional domains. Proteins acting on carbohydrates and proteins of unknown function constituted the two most abundant classes. Other proteins were proteases, oxido-reductases, proteins with interacting domains, proteins involved in signalling, and structural proteins. Particularly high levels of expression were established for genes encoding pectin methylesterases, germin-like proteins, arabinogalactan proteins, fasciclin-like arabinogalactan proteins, and structural proteins. Finally, the results of this transcriptomic analyses were compared with those obtained through a cell wall proteomic analysis from the same material. Only a small proportion of genes identified by previous proteomic analyses were identified by transcriptomics. Conversely, only a few proteins encoded by genes having moderate or high level of transcripts were identified by proteomics. Conclusion Analysis of the genes predicted to encode cell wall proteins revealed that about 345 genes had moderate or high levels of transcripts. Among them, we identified many new genes possibly involved in cell wall biogenesis. The discrepancies observed between results of this transcriptomic study and a previous proteomic study on the same material revealed post-transcriptional mechanisms of regulation of expression of genes encoding cell wall proteins. PMID:19149885

Trichoderma genes

DOEpatents

Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

2012-06-19

Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

The rice blast resistance gene Ptr encodes an atypical protein required for broad spectrum disease resistance

USDA-ARS?s Scientific Manuscript database

Plant resistance (R) genes typically encode proteins with nucleotide binding site-leucine rich repeat (NLR) domains. We identified a novel, broad-spectrum rice blast R gene, Ptr, encoding a non-NLR protein with four Armadillo repeats. Ptr was originally identified by fast neutron mutagenesis as a ...

Longitudinal white matter change in frontotemporal dementia subtypes and sporadic late onset Alzheimer's disease.

PubMed

Elahi, Fanny M; Marx, Gabe; Cobigo, Yann; Staffaroni, Adam M; Kornak, John; Tosun, Duygu; Boxer, Adam L; Kramer, Joel H; Miller, Bruce L; Rosen, Howard J

2017-01-01

Degradation of white matter microstructure has been demonstrated in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). In preparation for clinical trials, ongoing studies are investigating the utility of longitudinal brain imaging for quantification of disease progression. To date only one study has examined sample size calculations based on longitudinal changes in white matter integrity in FTLD. To quantify longitudinal changes in white matter microstructural integrity in the three canonical subtypes of frontotemporal dementia (FTD) and AD using diffusion tensor imaging (DTI). 60 patients with clinical diagnoses of FTD, including 27 with behavioral variant frontotemporal dementia (bvFTD), 14 with non-fluent variant primary progressive aphasia (nfvPPA), and 19 with semantic variant PPA (svPPA), as well as 19 patients with AD and 69 healthy controls were studied. We used a voxel-wise approach to calculate annual rate of change in fractional anisotropy (FA) and mean diffusivity (MD) in each group using two time points approximately one year apart. Mean rates of change in FA and MD in 48 atlas-based regions-of-interest, as well as global measures of cognitive function were used to calculate sample sizes for clinical trials (80% power, alpha of 5%). All FTD groups showed statistically significant baseline and longitudinal white matter degeneration, with predominant involvement of frontal tracts in the bvFTD group, frontal and temporal tracts in the PPA groups and posterior tracts in the AD group. Longitudinal change in MD yielded a larger number of regions with sample sizes below 100 participants per therapeutic arm in comparison with FA. SvPPA had the smallest sample size based on change in MD in the fornix (n = 41 participants per study arm to detect a 40% effect of drug), and nfvPPA and AD had their smallest sample sizes based on rate of change in MD within the left superior longitudinal fasciculus (n = 49 for nfvPPA, and n = 23 for AD). BvFTD generally showed the largest sample size estimates (minimum n = 140 based on MD in the corpus callosum). The corpus callosum appeared to be the best region for a potential study that would include all FTD subtypes. Change in global measure of functional status (CDR box score) yielded the smallest sample size for bvFTD (n = 71), but clinical measures were inferior to white matter change for the other groups. All three of the canonical subtypes of FTD are associated with significant change in white matter integrity over one year. These changes are consistent enough that drug effects in future clinical trials could be detected with relatively small numbers of participants. While there are some differences in regions of change across groups, the genu of the corpus callosum is a region that could be used to track progression in studies that include all subtypes.

Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells.

PubMed

Wang, Longqiong; Jing, Jinzhong; Yan, Hui; Tang, Jiayong; Jia, Gang; Liu, Guangmang; Chen, Xiaoling; Tian, Gang; Cai, Jingyi; Shang, Haiying; Zhao, Hua

2018-04-18

This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0 μmol Se/L) for 2 h, followed by LPS (100 ng/mL) stimulation for another 3 h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100 ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P < 0.05) mRNA profiles of 9 inflammation-related genes in cells, while short-time Se pretreatment modestly reversed (P < 0.05) the LPS-induced upregulation of 7 genes (COX-2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, and MCP-1) and further increased (P < 0.05) expression of IFN-β and TNF-α in stressed cells. Meanwhile, LPS decreased (P < 0.05) mRNA levels of 18 selenoprotein encoding genes and upregulated mRNA levels of TXNRD1 and TXNRD3 in cells. Se pretreatment recovered (P < 0.05) expression of 3 selenoprotein encoding genes (GPX1, SELENOH, and SELENOW) in a dose-dependent manner and increased (P < 0.05) expression of another 5 selenoprotein encoding genes (SELENOK, SELENOM, SELENOS, SELENOT, and TXNRD2) only at a high level (2.0 μmol Se/L). Taken together, LPS-induced immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.

Disruption of the psbA gene by the copy correction mechanism reveals that the expression of plastid-encoded genes is regulated by photosynthesis activity.

PubMed

Khan, Muhammad Sarwar; Hameed, Waqar; Nozoe, Mikio; Shiina, Takashi

2007-05-01

The functional analysis of genes encoded by the chloroplast genome of tobacco by reverse genetics is routine. Nevertheless, for a small number of genes their deletion generates heteroplasmic genotypes, complicating their analysis. There is thus the need for additional strategies to develop deletion mutants for these genes. We have developed a homologous copy correction-based strategy for deleting/mutating genes encoded on the chloroplast genome. This system was used to produce psbA knockouts. The resulting plants are homoplasmic and lack photosystem II (PSII) activity. Further, the deletion mutants exhibit a distinct phenotype; young leaves are green, whereas older leaves are bleached, irrespective of light conditions. This suggests that senescence is promoted by the absence of psbA. Analysis of the transcript levels indicates that NEP (nuclear-encoded plastid RNA polymerase)-dependent plastid genes are up regulated in the psbA deletion mutants, whereas the bleached leaves retain plastid-encoded plastid RNA polymerase activity. Hence, the expression of NEP-dependent plastid genes may be regulated by photosynthesis, either directly or indirectly.

Charge Transport between Coupling Colloidal Perovskite Quantum Dots Assisted by Functional Conjugated Ligands.

PubMed

Dai, Jinfei; Xi, Jun; Li, Lu; Zhao, JingFeng; Shi, Yifei; Zhang, Wenwen; Ran, Chenxin; Jiao, Bo; Hou, Xun; Duan, Xinhua; Wu, Zhaoxin

2018-05-14

Long alkyl-chain capping ligands are indispensable for preparing stable colloidal quantum dots. However, its insulating feature blocks efficient carrier transport among QDs, leading to inferior performance in light-emitting diodes (LEDs). The trade-off between conductivity and colloidal stability of QDs has now been overcome. Methylamine lead bromide (MAPbBr 3 ) QDs with a conjugated alkyl-amine, 3-phenyl-2-propen-1-amine (PPA), as ligands were prepared. Owing to electron cloud overlapping and the delocalization effect of conjugated molecules, the conductivity and carrier mobility of PPA-QDs films increased almost 22 times over that of OA-QD films without compromising colloidal stability and photoluminescence. PPA-QDs LEDs exhibit a maximum current efficiency of 9.08 cd A -1 , which is 8 times of that of OA-QDs LEDs (1.14 cd A -1 ). This work provides critical solution for the poor conductivity of QDs in applications of energy-related devices. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Increased Oxygen Recovery from Sabatier Systems Using Plasma Pyrolysis Technology and Metal Hydride Separation

NASA Technical Reports Server (NTRS)

Greenwood, Zachary W.; Abney, Morgan B.; Perry, Jay L.; Miller, Lee A.; Dahl, Roger W.; Hadley, Neal M.; Wambolt, Spencer R.; Wheeler, Richard R.

2015-01-01

State-of-the-art life support carbon dioxide (CO2) reduction technology is based on the Sabatier reaction where less than 50% of the oxygen required for the crew is recovered from metabolic CO2. The reaction produces water as the primary product and methane as a byproduct. Oxygen recovery is constrained by the limited availability of reactant hydrogen. This is further exacerbated when Sabatier methane (CH4) is vented as a waste product resulting in a continuous loss of reactant hydrogen. Post-processing methane with the Plasma Pyrolysis Assembly (PPA) to recover hydrogen has the potential to dramatically increase oxygen recovery and thus drastically reduce the logistical challenges associated with oxygen resupply. The PPA decomposes methane into predominantly hydrogen and acetylene. Due to the highly unstable nature of acetylene, a separation system is necessary to purify hydrogen before it is recycled back to the Sabatier reactor. Testing and evaluation of a full-scale Third Generation PPA is reported and investigations into metal hydride hydrogen separation technology is discussed.

Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study.

PubMed

Gervits, Felix; Ash, Sharon; Coslett, H Branch; Rascovsky, Katya; Grossman, Murray; Hamilton, Roy

2016-11-01

Primary progressive aphasia (PPA) is a neurodegenerative condition characterized by gradual deterioration of language function. We investigated whether two weeks of daily transcranial direct current stimulation (tDCS) treatment would improve language abilities in six people with a non-fluent form of PPA. tDCS was applied in an unblinded trial at an intensity of 1.5mA for 20min/day over 10days. At the time of stimulation, patients were engaged in narrating one of several children's wordless picture stories. A battery of neuropsychological assessments was administered four times: at baseline, immediately following the 2-week stimulation period, and then 6-weeks and 12-weeks following the end of stimulation. We observed improvement in linguistic performance in the domains of speech production and grammatical comprehension. Our encouraging results indicate that larger, sham-controlled studies of tDCS as a potential intervention for PPA are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Storm-time Convection Dynamics Viewed from Optical Auroras: from Streamer to Patchy Pulsating Aurora

NASA Astrophysics Data System (ADS)

Yang, B.; Donovan, E.; Liang, J.; Grono, E.

2016-12-01

In a series of statistical and event studies we have demonstrated that the motion of patches in regions of Patchy Pulsating Aurora (PPA) is very close to if not exactly convection. Thus, 2D maps of PPA motion provides us the opportunity to remote sense magnetospheric convection with relatively high space and time resolution, subject to uncertainties associated with mapping between the ionosphere and magnetosphere. In this study, we use THEMIS ASI aurora observations (streamers and patchy pulsating aurora) combined with SuperDARN convection measurements, Swarm ion drift velocity measurements, and RBSP electric field measurements to explore the convection dynamics in storm time. From 0500 UT to 0600 UT on March 19 2015, convection observations across 5 magnetic local time (MLT) inferred from the motion of PPA patches and SuperDARN measurements show that a westward SAPS (Subauroral Polarized Streams) enhancement occurs after an auroral streamer. This suggests that plasma sheet fast flows can affect the inner magnetospheric convection, and possibly trigger very fast flows in the inner magnetosphere.

Methane Post-Processing and Hydrogen Separation for Spacecraft Oxygen Loop Closure

NASA Technical Reports Server (NTRS)

Greenwood, Zachary W.; Abeny, Morgan B.; Wall, Terry; Miller, Lee A.; Wheeler, Richard R., Jr.

2017-01-01

State-of-the-art life support oxygen recovery technology on the International Space Station is based on the Sabatier reaction where only about half of the oxygen required for the crew is recovered from metabolic carbon dioxide (CO2). The Sabatier reaction produces water as the primary product and methane as a byproduct. Oxygen recovery is constrained by both the limited availability of reactant hydrogen from water electrolysis and Sabatier methane (CH4) being vented as a waste product resulting in a continuous loss of reactant hydrogen. Post-processing methane with the Plasma Pyrolysis Assembly (PPA) to recover this hydrogen has the potential to substantially increase oxygen recovery and thus dramatically reduce the logistical challenges associated with oxygen resupply. The PPA decomposes methane into predominantly hydrogen and acetylene. A purification system is necessary to purify hydrogen before it is recycled back to the Sabatier reactor. Testing and evaluation of acetylene removal systems and PPA system architectures are presented and discussed.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

PubMed

Harris, Jennifer M; Jones, Matthew; Gall, Claire; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Thompson, Jennifer C

2016-01-01

We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Enhanced biosynthesis of chiral phenyllactic acid from L-phenylalanine through a new whole-cell biocatalyst.

PubMed

Zheng, Zhaojuan; Xia, Meijuan; Fang, Xuchao; Jiang, Ting; Ouyang, Jia

2018-06-22

Phenyllactic acid (PLA) is a high-value compound, which was usually produced by lactic acid bacteria (LAB) as biocatalysts and glucose or phenylpyruvic acid (PPA) as starting materials for PLA synthesis in previous studies. However, the PLA produced using LAB is a racemic mixture. Besides, both glucose and PPA were unsatisfactory substrates, as the former could not produce high concentrations of PLA while the latter is not a renewable and green substrate. To overcome these drawbacks, in this study, a new biotransformation process was developed for chiral PLA production from L-phenylalanine via the intermediate PPA using recombinant Escherichia coli co-expressing L-amino acid deaminase, NAD-dependent L-lactate dehydrogenase or NAD-dependent D-lactate dehydrogenase, and formate dehydrogenase. After optimization, the recombinant E. coli produced L- and D-PLA at concentrations of 59.9 and 60.3 mM in 6 h, respectively. Hence, this process provides an effective and promising alternative method for chiral PLA production.

Characterization of Carbon Particulates in the Exit Flow of a Plasma Pyrolysis Assembly (PPA) Reactor

NASA Technical Reports Server (NTRS)

Green, Robert D.; Meyer, Marit E.; Agui, Juan H.; Berger, Gordon M.; Vijayakumar, R.; Abney, Morgan B.; Greenwood, Zachary

2015-01-01

The ISS presently recovers oxygen from crew respiration via a Carbon Dioxide Reduction Assembly (CRA) that utilizes the Sabatier chemical process to reduce captured carbon dioxide to methane (CH4) and water. In order to recover more of the hydrogen from the methane and increase oxygen recovery, NASA Marshall Space Flight Center (MSFC) is investigating a technology, plasma pyrolysis, to convert the methane to acetylene. The Plasma Pyrolysis Assembly (or PPA), achieves 90% or greater conversion efficiency, but a small amount of solid carbon particulates are generated as a side product and must be filtered before the acetylene is removed and the hydrogen-rich gas stream is recycled back to the CRA. In this work, we present the experimental results of an initial characterization of the carbon particulates in the PPA exit gas stream. We also present several potential options to remove these carbon particulates via carbon traps and filters to minimize resupply mass and required downtime for regeneration.

Clinical and MRI correlates of disease progression in a case of nonfluent/agrammatic variant of primary progressive aphasia due to progranulin (GRN) Cys157LysfsX97 mutation.

PubMed

Caso, Francesca; Agosta, Federica; Magnani, Giuseppe; Galantucci, Sebastiano; Spinelli, Edoardo G; Galimberti, Daniela; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

2014-07-15

Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN+). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN+ patient and this report offers new insights into the pathophysiology of the disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Two-photon absorption spectra of luminescent conducting polymers measured over wide spectral range

NASA Astrophysics Data System (ADS)

Meyer, Ron K.; Liess, Martin; Benner, Robert E.; Gellermann, Werner; Vardeny, Z. Valy; Ozaki, Masanori; Yoshino, Katsumi; Ding, Yi W.; Barton, Thomas J.

1997-12-01

We report the two-photon absorption (TPA) spectra of poly(2,5-dibutoxy-p-phenylene acetylene) (PPA-DBO), poly(2,5-dioctyloxy-p-phenylene vinylene) (PPV-DOO), and poly(3-hexylthiophene) in the spectral range extending from 576 nm to 846 nm. Using the Z-scan technique on the polymers in solution, we measured a strong two-photon allowed transition in all three materials which we attribute to the mAg essential state. In the case of PPA-DBO and PPV-DOO, TPA peaks were coincident with dispersion in the nonlinear refractive indices as detected by reduced aperture Z scan. In all three polymers this peak occurs at approximately 1.3 the bandgap energy. The excitonic nature of the excited electronic states in PPA-DBO is indicated by the lack of a TPA band at or near the 1Bu exciton position. Saturation was observed in the nonlinear index of refraction near spectral peaks, as well as an apparent reverse Kramers- Kronig effect.

Genome-Wide Identification and Mapping of NBS-Encoding Resistance Genes in Solanum tuberosum Group Phureja

PubMed Central

Lozano, Roberto; Ponce, Olga; Ramirez, Manuel; Mostajo, Nelly; Orjeda, Gisella

2012-01-01

The majority of disease resistance (R) genes identified to date in plants encode a nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domain containing protein. Additional domains such as coiled-coil (CC) and TOLL/interleukin-1 receptor (TIR) domains can also be present. In the recently sequenced Solanum tuberosum group phureja genome we used HMM models and manual curation to annotate 435 NBS-encoding R gene homologs and 142 NBS-derived genes that lack the NBS domain. Highly similar homologs for most previously documented Solanaceae R genes were identified. A surprising ∼41% (179) of the 435 NBS-encoding genes are pseudogenes primarily caused by premature stop codons or frameshift mutations. Alignment of 81.80% of the 577 homologs to S. tuberosum group phureja pseudomolecules revealed non-random distribution of the R-genes; 362 of 470 genes were found in high density clusters on 11 chromosomes. PMID:22493716

Apple S-RNase triggers inhibition of tRNA aminoacylation by interacting with a soluble inorganic pyrophosphatase in growing self-pollen tubes in vitro.

PubMed

Li, Wei; Meng, Dong; Gu, Zhaoyu; Yang, Qing; Yuan, Hui; Li, Yang; Chen, Qiuju; Yu, Jie; Liu, Chunsheng; Li, Tianzhong

2018-04-01

Apple exhibits S-RNase-based self-incompatibility (SI), in which S-RNase plays a central role in rejecting self-pollen. It has been proposed that the arrest of pollen growth in SI of Solanaceae plants is a consequence of the degradation of pollen rRNA by S-RNase; however, the underlying mechanism in Rosaceae is still unclear. Here, we used S 2 -RNase as a bait to screen an apple pollen cDNA library and characterized an apple soluble inorganic pyrophosphatase (MdPPa) that physically interacted with S-RNases. When treated with self S-RNases, apple pollen tubes showed a marked growth inhibition, as well as a decrease in endogenous soluble pyrophosphatase activity and elevated levels of inorganic pyrophosphate (PPi). In addition, S-RNase was found to bind to two variable regions of MdPPa, resulting in a noncompetitive inhibition of its activity. Silencing of MdPPa expression led to a reduction in pollen tube growth. Interestingly, tRNA aminoacylation was inhibited in self S-RNase-treated or MdPPa-silenced pollen tubes, resulting in the accumulation of uncharged tRNA. Furthermore, we provide evidence showing that this disturbance of tRNA aminoacylation is independent of RNase activity. We propose an alternative mechanism differing from RNA degradation to explain the cytotoxicity of the S-RNase apple SI process. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Diagnostic utility of FDG-PET in the differential diagnosis between different forms of primary progressive aphasia.

PubMed

Bouwman, Femke; Orini, Stefania; Gandolfo, Federica; Altomare, Daniele; Festari, Cristina; Agosta, Federica; Arbizu, Javier; Drzezga, Alexander; Nestor, Peter; Nobili, Flavio; Walker, Zuzana; Morbelli, Silvia; Boccardi, Marina

2018-05-09

A joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA). Seven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion. Critical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use. Quantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause.

Pharmacokinetic and pharmacodynamic effects of clonazepam in children with epilepsy treated with valproate: a preliminary study.

PubMed

Wang, Li; Wang, Xiao-Dong

2002-08-01

The authors report the use of the quantitative pharmaco-EEG (QPEEG) technique to study the pharmacokinetics (PK) and pharmacodynamics (PD) of clonazepam (CZP) in four epileptic children who suffered uncontrolled seizures despite long-term valproate (VPA) therapy. After a single dose of CZP (0.05 mg/kg, PO), blood samples were collected at 0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, 12.0, and 24.0 hours. CZP and VPA concentrations were measured by HPLC or GC assay, respectively. At each blood collection time point, EEG signals (60 s) were recorded for brain electrical activity mapping, and the power percentage average (PPA) of each frequency band was calculated. The relationship between drug concentrations and their corresponding PPA of each frequency band was analyzed. VPA steady-state drug concentrations (Css) were within the therapeutic range and not affected by CZP. The peak concentration (Cmax) of CZP and the time intervals from dosing to Cmax (Tmax) were 20.9 ng/mL to 113.8 ng/mL and 1 hour to 1.5 hours, respectively. There was no significant correlation between VPA concentrations and the PPA of any of the EEG frequency bands. CZP blood concentrations showed significant correlation with PPA in 3 of the 4 patients. Our results suggested CZP could affect fast wave activities in proportion to CZP blood concentrations. We propose that QPEEG is a promising technique to study the PK and PD of selected anti-epileptic drugs.

Loss of body fat and associated decrease in leptin in early lactation are related to shorter duration of postpartum anovulation in healthy US women.

PubMed

Domer, Mary Colleen; Beerman, Kathy A; Ahmadzadeh, Amin; Dasgupta, Nairanjana; Williams, Janet E; McGuire, Mark A; McGuire, Michelle K

2015-05-01

The mechanisms regulating postpartum anovulation (PPA) are not well understood, although poor nutritional status and "intense" breastfeeding behaviors are associated with longer durations. This study was designed primarily to investigate the hypothesis that higher body fat and leptin concentrations are related to shorter PPA in healthy, lactating US women. Nutrient intake, breastfeeding behaviors, prolactin, and insulin levels were also evaluated. Fasting serum was collected during the third trimester of pregnancy, at 2 and 4 weeks postpartum, and every 4 weeks until the occurrence of the first postpartum menses. Body composition and breastfeeding behaviors were assessed at the same times postpartum. Women (n = 13) were categorized based on initial percentage body fat and timing of first postpartum menses. There were no consistent relationships between body composition, leptin, or breastfeeding behaviors and duration of PPA. However, there was an interaction (P = .005) between ovulation group and time on adiposity; earlier ovulating women had less percentage body fat in early lactation than did later ovulating women. There was also an interaction (P = .1) between ovulation group and time postpartum on leptin, such that leptin concentrations tended to be greater in later than earlier ovulating groups beginning at 12 weeks postpartum. In summary, although baseline percentage body fat and leptin were not related to duration of PPA, fertility returned earlier in women who lost greater percentage body fat during the early postpartum period. © The Author(s) 2015.

The candidate histocompatibility locus of a Basal chordate encodes two highly polymorphic proteins.

PubMed

Nydam, Marie L; Netuschil, Nikolai; Sanders, Erin; Langenbacher, Adam; Lewis, Daniel D; Taketa, Daryl A; Marimuthu, Arumugapradeep; Gracey, Andrew Y; De Tomaso, Anthony W

2013-01-01

The basal chordate Botryllus schlosseri undergoes a natural transplantation reaction governed by a single, highly polymorphic locus called the fuhc. Our initial characterization of this locus suggested it encoded a single gene alternatively spliced into two transcripts: a 555 amino acid-secreted form containing the first half of the gene, and a full-length, 1008 amino acid transmembrane form, with polymorphisms throughout the ectodomain determining outcome. We have now found that the locus encodes two highly polymorphic genes which are separated by a 227 bp intergenic region: first, the secreted form as previously described, and a second gene encoding a 531 amino acid membrane-bound gene containing three extracellular immunoglobulin domains. While northern blotting revealed only these two mRNAs, both PCR and mRNA-seq detect a single capped and polyadenylated transcript that encodes processed forms of both genes linked by the intergenic region, as well as other transcripts in which exons of the two genes are spliced together. These results might suggest that the two genes are expressed as an operon, during which both genes are co-transcribed and then trans-spliced into two separate messages. This type of transcriptional regulation has been described in tunicates previously; however, the membrane-bound gene does not encode a typical Splice Leader (SL) sequence at the 5' terminus that usually accompanies trans-splicing. Thus, the presence of stable transcripts encoding both genes may suggest a novel mechanism of regulation, or conversely may be rare but stable transcripts in which the two mRNAs are linked due to a small amount of read-through by RNA polymerase. Both genes are highly polymorphic and co-expressed on tissues involved in histocompatibility. In addition, polymorphisms on both genes correlate with outcome, although we have found a case in which it appears that the secreted form may be major allorecognition determinant.

Development of a gene synthesis platform for the efficient large scale production of small genes encoding animal toxins.

PubMed

Sequeira, Ana Filipa; Brás, Joana L A; Guerreiro, Catarina I P D; Vincentelli, Renaud; Fontes, Carlos M G A

2016-12-01

Gene synthesis is becoming an important tool in many fields of recombinant DNA technology, including recombinant protein production. De novo gene synthesis is quickly replacing the classical cloning and mutagenesis procedures and allows generating nucleic acids for which no template is available. In addition, when coupled with efficient gene design algorithms that optimize codon usage, it leads to high levels of recombinant protein expression. Here, we describe the development of an optimized gene synthesis platform that was applied to the large scale production of small genes encoding venom peptides. This improved gene synthesis method uses a PCR-based protocol to assemble synthetic DNA from pools of overlapping oligonucleotides and was developed to synthesise multiples genes simultaneously. This technology incorporates an accurate, automated and cost effective ligation independent cloning step to directly integrate the synthetic genes into an effective Escherichia coli expression vector. The robustness of this technology to generate large libraries of dozens to thousands of synthetic nucleic acids was demonstrated through the parallel and simultaneous synthesis of 96 genes encoding animal toxins. An automated platform was developed for the large-scale synthesis of small genes encoding eukaryotic toxins. Large scale recombinant expression of synthetic genes encoding eukaryotic toxins will allow exploring the extraordinary potency and pharmacological diversity of animal venoms, an increasingly valuable but unexplored source of lead molecules for drug discovery.

Comprehensive search for accessory proteins encoded with archaeal and bacterial type III CRISPR-cas gene cassettes reveals 39 new cas gene families.

PubMed

Shah, Shiraz A; Alkhnbashi, Omer S; Behler, Juliane; Han, Wenyuan; She, Qunxin; Hess, Wolfgang R; Garrett, Roger A; Backofen, Rolf

2018-06-19

A study was undertaken to identify conserved proteins that are encoded adjacent to cas gene cassettes of Type III CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats - CRISPR associated) interference modules. Type III modules have been shown to target and degrade dsDNA, ssDNA and ssRNA and are frequently intertwined with cofunctional accessory genes, including genes encoding CRISPR-associated Rossman Fold (CARF) domains. Using a comparative genomics approach, and defining a Type III association score accounting for coevolution and specificity of flanking genes, we identified and classified 39 new Type III associated gene families. Most archaeal and bacterial Type III modules were seen to be flanked by several accessory genes, around half of which did not encode CARF domains and remain of unknown function. Northern blotting and interference assays in Synechocystis confirmed that one particular non-CARF accessory protein family was involved in crRNA maturation. Non-CARF accessory genes were generally diverse, encoding nuclease, helicase, protease, ATPase, transporter and transmembrane domains with some encoding no known domains. We infer that additional families of non-CARF accessory proteins remain to be found. The method employed is scalable for potential application to metagenomic data once automated pipelines for annotation of CRISPR-Cas systems have been developed. All accessory genes found in this study are presented online in a readily accessible and searchable format for researchers to audit their model organism of choice: http://accessory.crispr.dk .

Modularity of Plant Metabolic Gene Clusters: A Trio of Linked Genes That Are Collectively Required for Acylation of Triterpenes in Oat[W][OA

PubMed Central

Mugford, Sam T.; Louveau, Thomas; Melton, Rachel; Qi, Xiaoquan; Bakht, Saleha; Hill, Lionel; Tsurushima, Tetsu; Honkanen, Suvi; Rosser, Susan J.; Lomonossoff, George P.; Osbourn, Anne

2013-01-01

Operon-like gene clusters are an emerging phenomenon in the field of plant natural products. The genes encoding some of the best-characterized plant secondary metabolite biosynthetic pathways are scattered across plant genomes. However, an increasing number of gene clusters encoding the synthesis of diverse natural products have recently been reported in plant genomes. These clusters have arisen through the neo-functionalization and relocation of existing genes within the genome, and not by horizontal gene transfer from microbes. The reasons for clustering are not yet clear, although this form of gene organization is likely to facilitate co-inheritance and co-regulation. Oats (Avena spp) synthesize antimicrobial triterpenoids (avenacins) that provide protection against disease. The synthesis of these compounds is encoded by a gene cluster. Here we show that a module of three adjacent genes within the wider biosynthetic gene cluster is required for avenacin acylation. Through the characterization of these genes and their encoded proteins we present a model of the subcellular organization of triterpenoid biosynthesis. PMID:23532069

Detection with synthetic oligonucleotide probes of nucleotide sequence variations in the genes encoding enterotoxins of Escherichia coli.

PubMed Central

Nishibuchi, M; Murakami, A; Arita, M; Jikuya, H; Takano, J; Honda, T; Miwatani, T

1989-01-01

We examined variations in the genes encoding heat-stable enterotoxin (ST) and heat-labile enterotoxin (LT) in 88 strains of Escherichia coli isolated from individuals with traveler's diarrhea to find suitable sequences for use as oligonucleotide probes. Four oligonucleotide probes of the gene encoding ST of human origin (STIb or STh), one oligonucleotide probe of the gene encoding ST of porcine origin (STIa or STp), and three oligonucleotide probes of the gene encoding LT of human origin (LTIh) were used in DNA colony hybridization tests. In 15 of 22 strains possessing the STh gene and 28 of 42 strains producing LT, the sequences of all regions tested were identical to the published sequences. One region in the STh gene examined with a 18-mer probe was relatively well conserved and was shown to be closely associated with the enterotoxicity of the E. coli strains in suckling mice. This oligonucleotide, however, hybridized with strains of Vibrio cholerae O1, V. parahaemolyticus, and Yersinia enterocolitica that gave negative results in the suckling mouse assay. PMID:2685027

Cyclic stretch-induced the cytoskeleton rearrangement and gene expression of cytoskeletal regulators in human periodontal ligament cells.

PubMed

Wu, Yaqin; Zhuang, Jiabao; Zhao, Dan; Zhang, Fuqiang; Ma, Jiayin; Xu, Chun

2017-10-01

This study aimed to explore the mechanism of the stretch-induced cell realignment and cytoskeletal rearrangement by identifying several mechanoresponsive genes related to cytoskeletal regulators in human PDL cells. After the cells were stretched by 1, 10 and 20% strains for 0.5, 1, 2, 4, 6, 12 or 24 h, the changes of the morphology and content of microfilaments were recorded and calculated. Meanwhile, the expression of 84 key genes encoding cytoskeletal regulators after 6 and 24 h stretches with 20% strain was detected by using real-time PCR array. Western blot was applied to identify the protein expression level of several cytoskeletal regulators encoded by these differentially expressed genes. The confocal fluorescent staining results confirmed that stretch-induced realignment of cells and rearrangement of microfilaments. Among the 84 genes screened, one gene was up-regulated while two genes were down-regulated after 6 h stretch. Meanwhile, three genes were up-regulated while two genes were down-regulated after 24 h stretch. These genes displaying differential expression included genes regulating polymerization/depolymerization of microfilaments (CDC42EP2, FNBP1L, NCK2, PIKFYVE, WASL), polymerization/depolymerization of microtubules (STMN1), interacting between microfilaments and microtubules (MACF1), as well as a phosphatase (PPP1R12B). Among the proteins encoded by these genes, the protein expression level of Cdc42 effector protein-2 (encoded by CDC42EP2) and Stathmin-1 (encoded by STMN1) was down-regulated, while the protein expression level of N-WASP (encoded by WASL) was up-regulated. The present study confirmed the cyclic stretch-induced cellular realignment and rearrangement of microfilaments in the human PDL cells and indicated several force-sensitive genes with regard to cytoskeletal regulators.

A High-Resolution Gene Map of the Chloroplast Genome of the Red Alga Porphyra purpurea.

PubMed Central

Reith, M; Munholland, J

1993-01-01

Extensive DNA sequencing of the chloroplast genome of the red alga Porphyra purpurea has resulted in the detection of more than 125 genes. Fifty-eight (approximately 46%) of these genes are not found on the chloroplast genomes of land plants. These include genes encoding 17 photosynthetic proteins, three tRNAs, and nine ribosomal proteins. In addition, nine genes encoding proteins related to biosynthetic functions, six genes encoding proteins involved in gene expression, and at least five genes encoding miscellaneous proteins are among those not known to be located on land plant chloroplast genomes. The increased coding capacity of the P. purpurea chloroplast genome, along with other characteristics such as the absence of introns and the conservation of ancestral operons, demonstrate the primitive nature of the P. purpurea chloroplast genome. In addition, evidence for a monophyletic origin of chloroplasts is suggested by the identification of two groups of genes that are clustered in chloroplast genomes but not in cyanobacteria. PMID:12271072

Genome-Wide Architecture of Disease Resistance Genes in Lettuce

PubMed Central

Christopoulou, Marilena; Wo, Sebastian Reyes-Chin; Kozik, Alex; McHale, Leah K.; Truco, Maria-Jose; Wroblewski, Tadeusz; Michelmore, Richard W.

2015-01-01

Genome-wide motif searches identified 1134 genes in the lettuce reference genome of cv. Salinas that are potentially involved in pathogen recognition, of which 385 were predicted to encode nucleotide binding-leucine rich repeat receptor (NLR) proteins. Using a maximum-likelihood approach, we grouped the NLRs into 25 multigene families and 17 singletons. Forty-one percent of these NLR-encoding genes belong to three families, the largest being RGC16 with 62 genes in cv. Salinas. The majority of NLR-encoding genes are located in five major resistance clusters (MRCs) on chromosomes 1, 2, 3, 4, and 8 and cosegregate with multiple disease resistance phenotypes. Most MRCs contain primarily members of a single NLR gene family but a few are more complex. MRC2 spans 73 Mb and contains 61 NLRs of six different gene families that cosegregate with nine disease resistance phenotypes. MRC3, which is 25 Mb, contains 22 RGC21 genes and colocates with Dm13. A library of 33 transgenic RNA interference tester stocks was generated for functional analysis of NLR-encoding genes that cosegregated with disease resistance phenotypes in each of the MRCs. Members of four NLR-encoding families, RGC1, RGC2, RGC21, and RGC12 were shown to be required for 16 disease resistance phenotypes in lettuce. The general composition of MRCs is conserved across different genotypes; however, the specific repertoire of NLR-encoding genes varied particularly of the rapidly evolving Type I genes. These tester stocks are valuable resources for future analyses of additional resistance phenotypes. PMID:26449254

Cloning, characterization, expression analysis and inhibition studies of a novel gene encoding Bowman-Birk type protease inhibitor from rice bean

USDA-ARS?s Scientific Manuscript database

This paper presents the first study describing the isolation, cloning and characterization of a full length gene encoding Bowman-Birk protease inhibitor (RbTI) from rice bean (Vigna umbellata). A full-length protease inhibitor gene with complete open reading frame of 327bp encoding 109 amino acids w...

Cytochrome b5 gene and protein of Candida tropicalis and methods relating thereto

DOEpatents

Craft, David L.; Madduri, Krishna M.; Loper, John C.

2003-01-01

A novel gene has been isolated which encodes cytochrome b5 (CYTb5) protein of the .omega.-hydroxylase complex of C. tropicalis 20336. Vectors including this gene, and transformed host cells are provided. Methods of increasing the production of a CYTb5 protein are also provided which involve transforming a host cell with a gene encoding this protein and culturing the cells. Methods of increasing the production of a dicarboxylic acid are also provided which involve increasing in the host cell the number of genes encoding this protein.

Photodynamic activity of pyropheophorbide methyl ester and pyropheophorbide a in dimethylformamide solution.

PubMed

Al-Omari, Saleh; Ali, Ahmad

2009-03-01

Comparative spectroscopic study including the photosensitizers of pyropheophorbide methyl ester (PPME) and pyropheophorbide a (PPa) was performed to study their photodynamic activity. The investigated photosensitizers in a homogeneous system of dimethylformamide (DMF) are not photostable upon irradiation. The photobleaching efficiency of PPa is higher than that of PPME. Combining these results with the data obtained by measuring the singlet oxygen quantum yield and the hydroxyl group generation, it was revealed that the photobleaching efficiency could be correlated with the singlet oxygen quantum yield and the hydroxyl group production of the photosensitizer.

Genome complexity in the coelacanth is reflected in its adaptive immune system

USGS Publications Warehouse

Saha, Nil Ratan; Ota, Tatsuya; Litman, Gary W.; Hansen, John; Parra, Zuly; Hsu, Ellen; Buonocore, Francesco; Canapa, Adriana; Cheng, Jan-Fang; Amemiya, Chris T.

2014-01-01

We have analyzed the available genome and transcriptome resources from the coelacanth in order to characterize genes involved in adaptive immunity. Two highly distinctive IgW-encoding loci have been identified that exhibit a unique genomic organization, including a multiplicity of tandemly repeated constant region exons. The overall organization of the IgW loci precludes typical heavy chain class switching. A locus encoding IgM could not be identified either computationally or by using several different experimental strategies. Four distinct sets of genes encoding Ig light chains were identified. This includes a variant sigma-type Ig light chain previously identified only in cartilaginous fishes and which is now provisionally denoted sigma-2. Genes encoding α/β and γ/δ T-cell receptors, and CD3, CD4, and CD8 co-receptors also were characterized. Ig heavy chain variable region genes and TCR components are interspersed within the TCR α/δ locus; this organization previously was reported only in tetrapods and raises questions regarding evolution and functional cooption of genes encoding variable regions. The composition, organization and syntenic conservation of the major histocompatibility complex locus have been characterized. We also identified large numbers of genes encoding cytokines and their receptors, and other genes associated with adaptive immunity. In terms of sequence identity and organization, the adaptive immune genes of the coelacanth more closely resemble orthologous genes in tetrapods than those in teleost fishes, consistent with current phylogenomic interpretations. Overall, the work reported described herein highlights the complexity inherent in the coelacanth genome and provides a rich catalog of immune genes for future investigations.

The Bacillus subtilis ywjI (glpX) gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the class III Fbp enzyme.

PubMed

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-05-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions.

The Bacillus subtilis ywjI (glpX) Gene Encodes a Class II Fructose-1,6-Bisphosphatase, Functionally Equivalent to the Class III Fbp Enzyme▿

PubMed Central

Jules, Matthieu; Le Chat, Ludovic; Aymerich, Stéphane; Le Coq, Dominique

2009-01-01

We present here experimental evidence that the Bacillus subtilis ywjI gene encodes a class II fructose-1,6-bisphosphatase, functionally equivalent to the fbp-encoded class III enzyme, and constitutes with the upstream gene, murAB, an operon transcribed at the same level under glycolytic or gluconeogenic conditions. PMID:19270101

Molecular comparison of the structural proteins encoding gene clusters of two related Lactobacillus delbrueckii bacteriophages.

PubMed Central

Vasala, A; Dupont, L; Baumann, M; Ritzenthaler, P; Alatossava, T

1993-01-01

Virulent phage LL-H and temperate phage mv4 are two related bacteriophages of Lactobacillus delbrueckii. The gene clusters encoding structural proteins of these two phages have been sequenced and further analyzed. Six open reading frames (ORF-1 to ORF-6) were detected. Protein sequencing and Western immunoblotting experiments confirmed that ORF-3 (g34) encoded the main capsid protein Gp34. The presence of a putative late promoter in front of the phage LL-H g34 gene was suggested by primer extension experiments. Comparative sequence analysis between phage LL-H and phage mv4 revealed striking similarities in the structure and organization of this gene cluster, suggesting that the genes encoding phage structural proteins belong to a highly conservative module. Images PMID:8497043

KRAS Mutation Test in Korean Patients with Colorectal Carcinomas: A Methodological Comparison between Sanger Sequencing and a Real-Time PCR-Based Assay.

PubMed

Lee, Sung Hak; Chung, Arthur Minwoo; Lee, Ahwon; Oh, Woo Jin; Choi, Yeong Jin; Lee, Youn-Soo; Jung, Eun Sun

2017-01-01

Mutations in the KRAS gene have been identified in approximately 50% of colorectal cancers (CRCs). KRAS mutations are well established biomarkers in anti-epidermal growth factor receptor therapy. Therefore, assessment of KRAS mutations is needed in CRC patients to ensure appropriate treatment. We compared the analytical performance of the cobas test to Sanger sequencing in 264 CRC cases. In addition, discordant specimens were evaluated by 454 pyrosequencing. KRAS mutations for codons 12/13 were detected in 43.2% of cases (114/264) by Sanger sequencing. Of 257 evaluable specimens for comparison, KRAS mutations were detected in 112 cases (43.6%) by Sanger sequencing and 118 cases (45.9%) by the cobas test. Concordance between the cobas test and Sanger sequencing for each lot was 93.8% positive percent agreement (PPA) and 91.0% negative percent agreement (NPA) for codons 12/13. Results from the cobas test and Sanger sequencing were discordant for 20 cases (7.8%). Twenty discrepant cases were subsequently subjected to 454 pyrosequencing. After comprehensive analysis of the results from combined Sanger sequencing-454 pyrosequencing and the cobas test, PPA was 97.5% and NPA was 100%. The cobas test is an accurate and sensitive test for detecting KRAS -activating mutations and has analytical power equivalent to Sanger sequencing. Prescreening using the cobas test with subsequent application of Sanger sequencing is the best strategy for routine detection of KRAS mutations in CRC.

Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges.

PubMed

Tsapkini, Kyrana; Frangakis, Constantine; Gomez, Yessenia; Davis, Cameron; Hillis, Argye E

Primary progressive aphasia (PPA) is a neurodegenerative disease that primarily affects language functions and often begins in the fifth or sixth decade of life. The devastating effects on work and family life call for the investigation of treatment alternatives. In this article, we present new data indicating that neuromodulatory treatment, using transcranial direct current stimulation (tDCS) combined with a spelling intervention, shows some promise for maintaining or even improving language, at least temporarily, in PPA. The main aim of the present article is to determine whether tDCS plus spelling intervention is more effective than spelling intervention alone in treating written language in PPA. We also asked whether the effects of tDCS are sustained longer than the effects of spelling intervention alone. We present data from six PPA participants who underwent anodal tDCS or sham plus spelling intervention in a within-subject crossover design. Each stimulation condition lasted 3 weeks or a total of 15 sessions with a 2-month interval in between. Participants were evaluated on treatment tasks as well as on other language and cognitive tasks at 2-week and 2-month follow-up intervals after each stimulation condition. All participants showed improvement in spelling (with sham or tDCS). There was no difference in the treated items between the two conditions. There was, however, consistent and significant improvement for untrained items only in the tDCS plus spelling intervention condition. Furthermore, the improvement lasted longer in the tDCS plus spelling intervention condition compared to sham plus spelling intervention condition. Neuromodulation with tDCS offers promise as a means of augmenting language therapy to improve written language function at least temporarily in PPA. The consistent finding of generalisation of treatment benefits to untreated items and the superior sustainability of treatment effects with tDCS justifies further investigations. However, the small sample size still requires caution in interpretation. Present interventions need to be optimised, and particular challenges, such as ways to account for the variable effect of degeneration in each individual, are discussed.

Bacillus subtilis 168 Contains Two Differentially Regulated Genes Encoding l-Asparaginase

PubMed Central

Fisher, Susan H.; Wray, Lewis V.

2002-01-01

Expression of the two Bacillus subtilis genes encoding l-asparaginase is controlled by independent regulatory factors. The ansZ gene (formerly yccC) was shown by mutational analysis to encode a functional l-asparaginase, the expression of which is activated during nitrogen-limited growth by the TnrA transcription factor. Gel mobility shift and DNase I footprinting experiments indicate that TnrA regulates ansZ expression by binding to a DNA site located upstream of the ansZ promoter. The expression of the ansA gene, which encodes the second l-asparaginase, was found to be induced by asparagine. The ansA repressor, AnsR, was shown to negatively regulate its own expression. PMID:11914346

Bacillus subtilis 168 contains two differentially regulated genes encoding L-asparaginase.

PubMed

Fisher, Susan H; Wray, Lewis V

2002-04-01

Expression of the two Bacillus subtilis genes encoding L-asparaginase is controlled by independent regulatory factors. The ansZ gene (formerly yccC) was shown by mutational analysis to encode a functional L-asparaginase, the expression of which is activated during nitrogen-limited growth by the TnrA transcription factor. Gel mobility shift and DNase I footprinting experiments indicate that TnrA regulates ansZ expression by binding to a DNA site located upstream of the ansZ promoter. The expression of the ansA gene, which encodes the second L-asparaginase, was found to be induced by asparagine. The ansA repressor, AnsR, was shown to negatively regulate its own expression.

Recombinant DNA encoding a desulfurization biocatalyst

DOEpatents

Rambosek, John; Piddington, Chris S.; Kovacevich, Brian R.; Young, Kevin D.; Denome, Sylvia A.

1994-01-01

This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous.

A highly divergent gene cluster in honey bees encodes a novel silk family.

PubMed

Sutherland, Tara D; Campbell, Peter M; Weisman, Sarah; Trueman, Holly E; Sriskantha, Alagacone; Wanjura, Wolfgang J; Haritos, Victoria S

2006-11-01

The pupal cocoon of the domesticated silk moth Bombyx mori is the best known and most extensively studied insect silk. It is not widely known that Apis mellifera larvae also produce silk. We have used a combination of genomic and proteomic techniques to identify four honey bee fiber genes (AmelFibroin1-4) and two silk-associated genes (AmelSA1 and 2). The four fiber genes are small, comprise a single exon each, and are clustered on a short genomic region where the open reading frames are GC-rich amid low GC intergenic regions. The genes encode similar proteins that are highly helical and predicted to form unusually tight coiled coils. Despite the similarity in size, structure, and composition of the encoded proteins, the genes have low primary sequence identity. We propose that the four fiber genes have arisen from gene duplication events but have subsequently diverged significantly. The silk-associated genes encode proteins likely to act as a glue (AmelSA1) and involved in silk processing (AmelSA2). Although the silks of honey bees and silkmoths both originate in larval labial glands, the silk proteins are completely different in their primary, secondary, and tertiary structures as well as the genomic arrangement of the genes encoding them. This implies independent evolutionary origins for these functionally related proteins.

Sleep deprivation impairs object-selective attention: a view from the ventral visual cortex.

PubMed

Lim, Julian; Tan, Jiat Chow; Parimal, Sarayu; Dinges, David F; Chee, Michael W L

2010-02-05

Most prior studies on selective attention in the setting of total sleep deprivation (SD) have focused on behavior or activation within fronto-parietal cognitive control areas. Here, we evaluated the effects of SD on the top-down biasing of activation of ventral visual cortex and on functional connectivity between cognitive control and other brain regions. Twenty-three healthy young adult volunteers underwent fMRI after a normal night of sleep (RW) and after sleep deprivation in a counterbalanced manner while performing a selective attention task. During this task, pictures of houses or faces were randomly interleaved among scrambled images. Across different blocks, volunteers responded to house but not face pictures, face but not house pictures, or passively viewed pictures without responding. The appearance of task-relevant pictures was unpredictable in this paradigm. SD resulted in less accurate detection of target pictures without affecting the mean false alarm rate or response time. In addition to a reduction of fronto-parietal activation, attending to houses strongly modulated parahippocampal place area (PPA) activation during RW, but this attention-driven biasing of PPA activation was abolished following SD. Additionally, SD resulted in a significant decrement in functional connectivity between the PPA and two cognitive control areas, the left intraparietal sulcus and the left inferior frontal lobe. SD impairs selective attention as evidenced by reduced selectivity in PPA activation. Further, reduction in fronto-parietal and ventral visual task-related activation suggests that it also affects sustained attention. Reductions in functional connectivity may be an important additional imaging parameter to consider in characterizing the effects of sleep deprivation on cognition.

The effect of neck-specific exercise with, or without a behavioral approach, on pain, disability, and self-efficacy in chronic whiplash-associated disorders: a randomized clinical trial.

PubMed

Ludvigsson, Maria L; Peterson, Gunnel; O'Leary, Shaun; Dedering, Åsa; Peolsson, Anneli

2015-04-01

The aim of this study was to compare the effect on self-rated pain, disability, and self-efficacy of 3 interventions for the management of chronic whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE), physiotherapist-led NSE with the addition of a behavioral approach, or Prescription of Physical Activity (PPA). A total of 216 volunteers with chronic whiplash-associated disorders participated in this randomized, assessor blinded, clinical trial of 3 exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at 3 and 6 months. The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P<0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific groups and 28% in the PPA group reported substantial pain reduction. Reduction of disability was also larger in the 2 neck-specific exercise groups at both 3 and 6 months (P<0.02). Self-efficacy was only improved in the NSE group without a behavioral approach (P=0.02). However, there were no significant differences in any outcomes between the 2 physiotherapist-led NSE groups. NSE resulted in superior outcomes compared with PPA in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive.

Use of a physiological profile to document motor impairment in ageing and in clinical groups.

PubMed

Lord, S R; Delbaere, K; Gandevia, S C

2016-08-15

Ageing decreases exercise performance and is frequently accompanied by reductions in cognitive performance. Deterioration in the physiological capacity to stand, locomote and exercise can manifest itself as falling over and represents a significant deterioration in sensorimotor control. In the elderly, falling leads to serious morbidity and mortality with major societal costs. Measurement of a suite of physiological capacities that are required for successful motor performance (including vision, muscle strength, proprioception and balance) has been used to produce a physiological profile assessment (PPA) which has been tracked over the age spectrum and in different diseases (e.g. multiple sclerosis, Parkinson's disease). As well as measures of specific physiological capacities, the PPA generates an overall 'score' which quantitatively measures an individual's cumulative risk of falling. The present review collates data from the PPA (and the physiological capacities it measures) as well as its use in strategies to reduce falls in the elderly and those with different diseases. We emphasise that (i) motor impairment arises via reductions in a wide range of sensorimotor abilities; (ii) the PPA approach not only gives a snapshot of the physiological capacity of an individual, but it also gives insight into the deficits among groups of individuals with particular diseases; and (iii) deficits in seemingly restricted and disparate physiological domains (e.g. vision, strength, cognition) are funnelled into impairments in tasks requiring upright balance. Motor impairments become more prevalent with ageing but careful physiological measurement and appropriate interventions offer a way to maximise health across the lifespan. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Integrating the ODI-PPA scientific gateway with the QuickReduce pipeline for on-demand processing

NASA Astrophysics Data System (ADS)

Young, Michael D.; Kotulla, Ralf; Gopu, Arvind; Liu, Wilson

2014-07-01

As imaging systems improve, the size of astronomical data has continued to grow, making the transfer and processing of data a significant burden. To solve this problem for the WIYN Observatory One Degree Imager (ODI), we developed the ODI-Portal, Pipeline, and Archive (ODI-PPA) science gateway, integrating the data archive, data reduction pipelines, and a user portal. In this paper, we discuss the integration of the QuickReduce (QR) pipeline into PPA's Tier 2 processing framework. QR is a set of parallelized, stand-alone Python routines accessible to all users, and operators who can create master calibration products and produce standardized calibrated data, with a short turn-around time. Upon completion, the data are ingested into the archive and portal, and made available to authorized users. Quality metrics and diagnostic plots are generated and presented via the portal for operator approval and user perusal. Additionally, users can tailor the calibration process to their specific science objective(s) by selecting custom datasets, applying preferred master calibrations or generating their own, and selecting pipeline options. Submission of a QuickReduce job initiates data staging, pipeline execution, and ingestion of output data products all while allowing the user to monitor the process status, and to download or further process/analyze the output within the portal. User-generated data products are placed into a private user-space within the portal. ODI-PPA leverages cyberinfrastructure at Indiana University including the Big Red II supercomputer, the Scholarly Data Archive tape system and the Data Capacitor shared file system.

The Effect of Neck-specific Exercise With, or Without a Behavioral Approach, on Pain, Disability, and Self-Efficacy in Chronic Whiplash-associated Disorders

PubMed Central

Peterson, Gunnel; O’Leary, Shaun; Dedering, Åsa; Peolsson, Anneli

2015-01-01

Objectives: The aim of this study was to compare the effect on self-rated pain, disability, and self-efficacy of 3 interventions for the management of chronic whiplash-associated disorders: physiotherapist-led neck-specific exercise (NSE), physiotherapist-led NSE with the addition of a behavioral approach, or Prescription of Physical Activity (PPA). Materials and Methods: A total of 216 volunteers with chronic whiplash-associated disorders participated in this randomized, assessor blinded, clinical trial of 3 exercise interventions. Self-rated pain/pain bothersomeness (Visual Analogue Scale), disability (Neck Disability Index), and self-efficacy (Self-Efficacy Scale) were evaluated at baseline and at 3 and 6 months. Results: The proportion of patients reaching substantial reduction in pain bothersomness (at least 50% reduction) was more evident (P<0.01) in the 2 NSE groups (29% to 48%) compared with the PPA group (5%) at 3 months. At 6 months 39% to 44% of the patients in the 2 neck-specific groups and 28% in the PPA group reported substantial pain reduction. Reduction of disability was also larger in the 2 neck-specific exercise groups at both 3 and 6 months (P<0.02). Self-efficacy was only improved in the NSE group without a behavioral approach (P=0.02). However, there were no significant differences in any outcomes between the 2 physiotherapist-led NSE groups. Discussion: NSE resulted in superior outcomes compared with PPA in this study, but the observed benefits of adding a behavioral approach to the implementation of exercise in this study were inconclusive. PMID:24918474

Novel integrative virtual rehabilitation reduces symptomatology of primary progressive aphasia--a case report.

PubMed

Burdea, Grigore C; Polistico, Kevin; House, Gregory P; Liu, Richard R; Muñiz, Roberto; Macaro, Natalie A; Slater, Lisa M

2015-01-01

BrightBrainer™ integrative cognitive rehabilitation system evaluation in an Adult Day Program by a subject with Primary Progressive Aphasia (PPA) assumed to be of the mixed nonfluent/logopenic variant, and for determination of potential benefits. The subject was a 51-year-old Caucasian male diagnosed with PPA who had attended an Adult Day Program for 18 months prior to BrightBrainer training. The subject interacted with therapeutic games using a controller that measured 3D hand movements and flexion of both index fingers. The computer simulations adapted difficulty level based on task performance; results were stored on a remote server. The clinical trial consisted of 16 sessions, twice/week for 8 weeks. The subject was evaluated through neuropsychological measures, therapy notes and caregiver feedback forms. Neuropsychological testing indicated no depression (BDI 0) and severe dementia (BIMS 1 and MMSE 3). The 6.5 h of therapy consisted of games targeting Language comprehension; Executive functions; Focusing; Short-term memory; and Immediate/working memory. The subject attained the highest difficulty level in all-but-one game, while averaging 1300-arm task-oriented active movement repetitions and 320 index finger flexion movements per session. While neuropsychological testing showed no benefits, the caregiver reported strong improvements in verbal responses, vocabulary use, speaking in complete sentences, following one-step directions and participating in daily activities. This corroborated well with therapy notes. Preliminary findings demonstrate a meaningful reduction of PPA symptoms for the subject, suggesting follow-up imaging studies to detail neuronal changes induced by BrightBrainer system and controlled studies with a sufficiently large number of PPA subjects.

Proteomic profiling identifies the inorganic pyrophosphatase (PPA1) protein as a potential biomarker of metastasis in laryngeal squamous cell carcinoma.

PubMed

Bodnar, Magdalena; Luczak, Magdalena; Bednarek, Kinga; Szylberg, Lukasz; Marszalek, Andrzej; Grenman, Reidar; Szyfter, Krzysztof; Jarmuz-Szymczak, Malgorzata; Giefing, Maciej

2016-06-01

Relapse and metastasis are the main causes of unfavorable outcome in head and neck cancers. Whereas, understanding of the molecular background of these processes is far from being complete. Therefore, in this study we aimed to identify potential biomarker candidates of relapse and metastasis in laryngeal squamous cell carcinoma (LSCC) by combining the 2D electrophoresis based protein screen and immunohistochemical analysis of candidate proteins. We screened three groups of LSCC cell lines derived from primary tumors, recurrent tumors and metastases and identified seven proteins that differed significantly in relative abundance between the analyzed groups. Among the identified proteins were the heat shock proteins HSP60 and HSP70 that were significantly downregulated both in recurrences- and metastases-derived cell lines but not in primary tumor-derived cell lines. Moreover, we identified significant upregulation of the annexin V, calreticulin and the inorganic pyrophosphatase (PPA1) exclusively in the metastases-derived cell lines. As these upregulated proteins could potentially become novel biomarkers of metastasis, we have compared their abundance in primary tumor LSCC N(0) cases, primary tumor LSCC N(+) cases as well as in LSCC metastases N(+). Our results show an intense increase of cytoplasmic PPA1 abundance in the N(+) (p = 0.000042) compared to the N(0) group. In summary, we show a group of proteins deregulated in recurrences and metastases of LSCC. Moreover, we suggest the PPA1 protein as a potential new biomarker for metastasis in this cancer.

Differences in neural responses to ipsilateral stimuli in wide-view fields between face- and house-selective areas

PubMed Central

Li, Ting; Niu, Yan; Xiang, Jie; Cheng, Junjie; Liu, Bo; Zhang, Hui; Yan, Tianyi; Kanazawa, Susumu; Wu, Jinglong

2018-01-01

Category-selective brain areas exhibit varying levels of neural activity to ipsilaterally presented stimuli. However, in face- and house-selective areas, the neural responses evoked by ipsilateral stimuli in the peripheral visual field remain unclear. In this study, we displayed face and house images using a wide-view visual presentation system while performing functional magnetic resonance imaging (fMRI). The face-selective areas (fusiform face area (FFA) and occipital face area (OFA)) exhibited intense neural responses to ipsilaterally presented images, whereas the house-selective areas (parahippocampal place area (PPA) and transverse occipital sulcus (TOS)) exhibited substantially smaller and even negative neural responses to the ipsilaterally presented images. We also found that the category preferences of the contralateral and ipsilateral neural responses were similar. Interestingly, the face- and house-selective areas exhibited neural responses to ipsilateral images that were smaller than the responses to the contralateral images. Multi-voxel pattern analysis (MVPA) was implemented to evaluate the difference between the contralateral and ipsilateral responses. The classification accuracies were much greater than those expected by chance. The classification accuracies in the FFA were smaller than those in the PPA and TOS. The closer eccentricities elicited greater classification accuracies in the PPA and TOS. We propose that these ipsilateral neural responses might be interpreted by interhemispheric communication through intrahemispheric connectivity of white matter connection and interhemispheric connectivity via the corpus callosum and occipital white matter connection. Furthermore, the PPA and TOS likely have weaker interhemispheric communication than the FFA and OFA, particularly in the peripheral visual field. PMID:29451872

Verbal creativity in semantic variant primary progressive aphasia.

PubMed

Wu, Teresa Q; Miller, Zachary A; Adhimoolam, Babu; Zackey, Diana D; Khan, Baber K; Ketelle, Robin; Rankin, Katherine P; Miller, Bruce L

2015-02-01

Emergence of visual and musical creativity in the setting of neurologic disease has been reported in patients with semantic variant primary progressive aphasia (svPPA), also called semantic dementia (SD). It is hypothesized that loss of left anterior frontotemporal function facilitates activity of the right posterior hemispheric structures, leading to de novo creativity observed in visual artistic representation. We describe creativity in the verbal domain, for the first time, in three patients with svPPA. Clinical presentations are carefully described in three svPPA patients exhibiting verbal creativity, including neuropsychology, neurologic exam, and structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) was performed to quantify brain atrophy patterns in these patients against age-matched healthy controls. All three patients displayed new-onset creative writing behavior and produced extensive original work during the course of disease. Patient A developed interest in wordplay and generated a large volume of poetry. Patient B became fascinated with rhyming and punning. Patient C wrote and published a lifestyle guidebook. An overlap of their structural MR scans showed uniform sparing in the lateral portions of the language-dominant temporal lobe (superior and middle gyri) and atrophy in the medial temporal cortex (amygdala, limbic cortex). New-onset creativity in svPPA may represent a paradoxical functional facilitation. A similar drive for production is found in visually artistic and verbally creative patients. Mirroring the imaging findings in visually artistic patients, verbal preoccupation and creativity may be associated with medial atrophy in the language-dominant temporal lobe, but sparing of lateral dominant temporal and non-dominant posterior cortices.

Nonverbal oral apraxia in primary progressive aphasia and apraxia of speech.

PubMed

Botha, Hugo; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Whitwell, Jennifer L; Josephs, Keith A

2014-05-13

The goal of this study was to explore the prevalence of nonverbal oral apraxia (NVOA), its association with other forms of apraxia, and associated imaging findings in patients with primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). Patients with a degenerative speech or language disorder were prospectively recruited and diagnosed with a subtype of PPA or with PAOS. All patients had comprehensive speech and language examinations. Voxel-based morphometry was performed to determine whether atrophy of a specific region correlated with the presence of NVOA. Eighty-nine patients were identified, of which 34 had PAOS, 9 had agrammatic PPA, 41 had logopenic aphasia, and 5 had semantic dementia. NVOA was very common among patients with PAOS but was found in patients with PPA as well. Several patients exhibited only one of NVOA or apraxia of speech. Among patients with apraxia of speech, the severity of the apraxia of speech was predictive of NVOA, whereas ideomotor apraxia severity was predictive of the presence of NVOA in those without apraxia of speech. Bilateral atrophy of the prefrontal cortex anterior to the premotor area and supplementary motor area was associated with NVOA. Apraxia of speech, NVOA, and ideomotor apraxia are at least partially separable disorders. The association of NVOA and apraxia of speech likely results from the proximity of the area reported here and the premotor area, which has been implicated in apraxia of speech. The association of ideomotor apraxia and NVOA among patients without apraxia of speech could represent disruption of modules shared by nonverbal oral movements and limb movements.

Nonverbal oral apraxia in primary progressive aphasia and apraxia of speech

PubMed Central

Botha, Hugo; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Whitwell, Jennifer L.

2014-01-01

Objective: The goal of this study was to explore the prevalence of nonverbal oral apraxia (NVOA), its association with other forms of apraxia, and associated imaging findings in patients with primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). Methods: Patients with a degenerative speech or language disorder were prospectively recruited and diagnosed with a subtype of PPA or with PAOS. All patients had comprehensive speech and language examinations. Voxel-based morphometry was performed to determine whether atrophy of a specific region correlated with the presence of NVOA. Results: Eighty-nine patients were identified, of which 34 had PAOS, 9 had agrammatic PPA, 41 had logopenic aphasia, and 5 had semantic dementia. NVOA was very common among patients with PAOS but was found in patients with PPA as well. Several patients exhibited only one of NVOA or apraxia of speech. Among patients with apraxia of speech, the severity of the apraxia of speech was predictive of NVOA, whereas ideomotor apraxia severity was predictive of the presence of NVOA in those without apraxia of speech. Bilateral atrophy of the prefrontal cortex anterior to the premotor area and supplementary motor area was associated with NVOA. Conclusions: Apraxia of speech, NVOA, and ideomotor apraxia are at least partially separable disorders. The association of NVOA and apraxia of speech likely results from the proximity of the area reported here and the premotor area, which has been implicated in apraxia of speech. The association of ideomotor apraxia and NVOA among patients without apraxia of speech could represent disruption of modules shared by nonverbal oral movements and limb movements. PMID:24727315

Photocontrol of the expression of genes encoding chlorophyll a/b binding proteins and small subunit of ribulose-1,5-bisphosphate carboxylase in etiolated seedlings of Lycopersicon esculentum (L. ) and Nicotiana tabacum (L. )

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wehmeyer, B.; Cashmore, A.R.; Schaefer, E.

Phytochrome and the blue ultraviolet-A photoreceptor control light-induced expression of genes encoding the chlorophyll a/b binding protein of photosystem II and photosystem I and the genes for the small subunit of the ribulose-1,5-bisphosphate carboxylase in etiolated seedlings of Lycopersicon esculentum (tomato) and Nicotiana tabacum (tobacco). A high irradiance response also controls the induction of these genes. Genes encoding photosystem II- and I-associated chlorophyll a/b binding proteins both exhibit a transient rapid increase in expression in response to light pulse or to continuous irradiation. In contrast, genes encoding the small subunit exhibit a continuous increase in expression in response to light.more » These distinct expression characteristics are shown to reflect differences at the level of transcription.« less

The evolution of genes encoding for green fluorescent proteins: insights from cephalochordates (amphioxus)

NASA Astrophysics Data System (ADS)

Yue, Jia-Xing; Holland, Nicholas D.; Holland, Linda Z.; Deheyn, Dimitri D.

2016-06-01

Green Fluorescent Protein (GFP) was originally found in cnidarians, and later in copepods and cephalochordates (amphioxus) (Branchiostoma spp). Here, we looked for GFP-encoding genes in Asymmetron, an early-diverged cephalochordate lineage, and found two such genes closely related to some of the Branchiostoma GFPs. Dim fluorescence was found throughout the body in adults of Asymmetron lucayanum, and, as in Branchiostoma floridae, was especially intense in the ripe ovaries. Spectra of the fluorescence were similar between Asymmetron and Branchiostoma. Lineage-specific expansion of GFP-encoding genes in the genus Branchiostoma was observed, largely driven by tandem duplications. Despite such expansion, purifying selection has strongly shaped the evolution of GFP-encoding genes in cephalochordates, with apparent relaxation for highly duplicated clades. All cephalochordate GFP-encoding genes are quite different from those of copepods and cnidarians. Thus, the ancestral cephalochordates probably had GFP, but since GFP appears to be lacking in more early-diverged deuterostomes (echinoderms, hemichordates), it is uncertain whether the ancestral cephalochordates (i.e. the common ancestor of Asymmetron and Branchiostoma) acquired GFP by horizontal gene transfer (HGT) from copepods or cnidarians or inherited it from the common ancestor of copepods and deuterostomes, i.e. the ancestral bilaterians.

Identification and characterization of the gltK gene encoding a membrane-associated glucose transport protein of pseudomonas aeruginosa.

PubMed

Adewoye, L O; Worobec, E A

2000-08-08

The Pseudomonas aeruginosa oprB gene encodes the carbohydrate-selective OprB porin, which translocates substrate molecules across the outer membrane to the periplasmic glucose-binding protein. We identified and cloned two open reading frames (ORFs) flanking the oprB gene but are not in operonic arrangement with the oprB gene. The downstream ORF encodes a putative polypeptide homologous to members of a family of transcriptional repressors, whereas the oprB gene is preceded by an ORF encoding a putative product, which exhibits strong homology to several carbohydrate transport ATP-binding cassette (ABC) proteins. The genomic copy of the upstream ORF was mutagenized by homologous recombination. Analysis of the deletion mutant in comparison with the wild type revealed a significant reduction in [14C] glucose transport activity in the mutant strain, suggesting that this ORF likely encodes the inner membrane component of the glucose ABC transporter. It is thus designated gltK gene to reflect its homology to the Pseudomona fluorescens mtlK and its involvement in the high-affinity glucose transport system. Multiple alignment analysis revealed that the P. aeruginosa gltK gene product is a member of the MalK subfamily of ABC proteins.

Recombinant DNA encoding a desulfurization biocatalyst

DOEpatents

Rambosek, J.; Piddington, C.S.; Kovacevich, B.R.; Young, K.D.; Denome, S.A.

1994-10-18

This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous. 13 figs.

Structure, Function, Interaction, Co-evolution of Rice Blast Resistance Genes

USDA-ARS?s Scientific Manuscript database

Rice blast disease caused by the fungal pathogen Magnaporthe oryzae is one of the most destructive rice diseases worldwide. Resistance (R) genes to blast encode proteins that detect pathogen signaling molecules encoded by M. oryzae avirulence (AVR) genes. R genes can be a single or a member of clu...

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2007-11-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA). In this paper EC layered granules were used in addition to EC matrix. The relationship between release property and the concentration of PPA in plasma after administration using beagle dogs were examined. Then it was confirmed that the correlativity for EC layered granules and EC matrix were similar each other. Therefore, it was considered that the dissolution test is useful for prediction of changes in concentration of PPA in the blood with time. And it was suggested that EC layered granules were suitable as a controlled release system as well as EC matrix.

Plasma Pyrolysis Assembly Regeneration Evaluation

NASA Technical Reports Server (NTRS)

Medlen, Amber; Abney, Morgan B.; Miller, Lee A.

2011-01-01

In April 2010 the Carbon Dioxide Reduction Assembly (CRA) was delivered to the International Space Station (ISS). This technology requires hydrogen to recover oxygen from carbon dioxide. This results in the production of water and methane. Water is electrolyzed to provide oxygen to the crew. Methane is vented to space resulting in a loss of valuable hydrogen and unreduced carbon dioxide. This is not critical for ISS because of the water resupply from Earth. However, in order to have enough oxygen for long-term missions, it will be necessary to recover the hydrogen to maximize oxygen recovery. Thus, the Plasma Pyrolysis Assembly (PPA) was designed to recover hydrogen from methane. During operation, the PPA produces small amounts of carbon that can ultimately reduce performance by forming on the walls and windows of the reactor chamber. The carbon must be removed, although mechanical methods are highly inefficient, thus chemical methods are of greater interest. The purpose of this effort was to determine the feasibility of chemically removing the carbon from the walls and windows of a PPA reactor using a pure carbon dioxide stream.

Abstract and concrete categories? Evidences from neurodegenerative diseases.

PubMed

Catricalà, Eleonora; Della Rosa, Pasquale A; Plebani, Valentina; Vigliocco, Gabriella; Cappa, Stefano F

2014-11-01

We assessed the performance of patients with a diagnosis of Alzheimer׳s disease (AD) and of the semantic variant of primary progressive aphasia (sv-PPA) in a series of tasks involving both abstract and concrete stimuli, which were controlled for most of the variables that have been shown to affect performance on lexical-semantic tasks. Our aims were to compare the patients׳ performance on abstract and concrete stimuli and to assess category-effects within the abstract and concrete domains. The results showed: (i) a better performance on abstract than concrete concepts in sv-PPA patients. (ii) Category-related effects in the abstract domain, with emotion concepts being preserved in AD and social relations being selectively impaired in sv-PPA. In addition, a living-non living dissociation may be (infrequently) observed in individual AD patients after controlling for an extensive set of potential confounds. Thus, differences between and within the concrete or abstract domain may be present in patients with semantic memory disorders, mirroring the different brain regions involved by the different pathologies. Copyright © 2014 Elsevier Ltd. All rights reserved.

IRaPPA: Information retrieval based integration of biophysical models for protein assembly selection

PubMed Central

Moal, Iain H.; Barradas-Bautista, Didier; Jiménez-García, Brian; Torchala, Mieczyslaw; van der Velde, Arjan; Vreven, Thom; Weng, Zhiping; Bates, Paul A.; Fernández-Recio, Juan

2018-01-01

Motivation In order to function, proteins frequently bind to one another and form 3D assemblies. Knowledge of the atomic details of these structures helps our understanding of how proteins work together, how mutations can lead to disease, and facilitates the designing of drugs which prevent or mimic the interaction. Results Atomic modeling of protein-protein interactions requires the selection of near-native structures from a set of docked poses based on their calculable properties. By considering this as an information retrieval problem, we have adapted methods developed for Internet search ranking and electoral voting into IRaPPA, a pipeline integrating biophysical properties. The approach enhances the identification of near-native structures when applied to four docking methods, resulting in a near-native appearing in the top 10 solutions for up to 50% of complexes benchmarked, and up to 70% in the top 100. Availability IRaPPA has been implemented in the SwarmDock server (http://bmm.crick.ac.uk/~SwarmDock/), pyDock server (http://life.bsc.es/pid/pydockrescoring/) and ZDOCK server (http://zdock.umassmed.edu/), with code available on request. PMID:28200016

Operational Support for Instrument Stability through ODI-PPA Metadata Visualization and Analysis

NASA Astrophysics Data System (ADS)

Young, M. D.; Hayashi, S.; Gopu, A.; Kotulla, R.; Harbeck, D.; Liu, W.

2015-09-01

Over long time scales, quality assurance metrics taken from calibration and calibrated data products can aid observatory operations in quantifying the performance and stability of the instrument, and identify potential areas of concern or guide troubleshooting and engineering efforts. Such methods traditionally require manual SQL entries, assuming the requisite metadata has even been ingested into a database. With the ODI-PPA system, QA metadata has been harvested and indexed for all data products produced over the life of the instrument. In this paper we will describe how, utilizing the industry standard Highcharts Javascript charting package with a customized AngularJS-driven user interface, we have made the process of visualizing the long-term behavior of these QA metadata simple and easily replicated. Operators can easily craft a custom query using the powerful and flexible ODI-PPA search interface and visualize the associated metadata in a variety of ways. These customized visualizations can be bookmarked, shared, or embedded externally, and will be dynamically updated as new data products enter the system, enabling operators to monitor the long-term health of their instrument with ease.

Molecular genetics of Erwinia amylovora involved in the development of fire blight.

PubMed

Oh, Chang-Sik; Beer, Steven V

2005-12-15

The bacterial plant pathogen, Erwinia amylovora, causes the devastating disease known as fire blight in some Rosaceous plants like apple, pear, quince, raspberry and several ornamentals. Knowledge of the factors affecting the development of fire blight has mushroomed in the last quarter century. On the molecular level, genes encoding a Hrp type III secretion system, genes encoding enzymes involved in synthesis of extracellular polysaccharides and genes facilitating the growth of E. amylovora in its host plants have been characterized. The Hrp pathogenicity island, delimited by genes suggesting horizontal gene transfer, is composed of four distinct regions, the hrp/hrc region, the HEE (Hrp effectors and elicitors) region, the HAE (Hrp-associated enzymes) region, and the IT (Island transfer) region. The Hrp pathogenicity island encodes a Hrp type III secretion system (TTSS), which delivers several proteins from bacteria to plant apoplasts or cytoplasm. E. amylovora produces two exopolysaccharides, amylovoran and levan, which cause the characteristic fire blight wilting symptom in host plants. In addition, other genes, and their encoded proteins, have been characterized as virulence factors of E. amylovora that encode enzymes facilitating sorbitol metabolism, proteolytic activity and iron harvesting. This review summarizes our understanding of the genes and gene products of E. amylovora that are involved in the development of the fire blight disease.

The Drosophila pigmentation gene pink (p) encodes a homologue of human Hermansky-Pudlak syndrome 5 (HPS5).

PubMed

Falcón-Pérez, Juan M; Romero-Calderón, Rafael; Brooks, Elizabeth S; Krantz, David E; Dell'Angelica, Esteban C

2007-02-01

Lysosome-related organelles comprise a group of specialized intracellular compartments that include melanosomes and platelet dense granules (in mammals) and eye pigment granules (in insects). In humans, the biogenesis of these organelles is defective in genetic disorders collectively known as Hermansky-Pudlak syndrome (HPS). Patients with HPS-2, and two murine HPS models, carry mutations in genes encoding subunits of adaptor protein (AP)-3. Other genes mutated in rodent models include those encoding VPS33A and Rab38. Orthologs of all of these genes in Drosophila melanogaster belong to the 'granule group' of eye pigmentation genes. Other genes associated with HPS encode subunits of three complexes of unknown function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2 and -3, for which the Drosophila counterparts had not been characterized. Here, we report that the gene encoding the Drosophila ortholog of the HPS5 subunit of BLOC-2 is identical to the granule group gene pink (p), which was first studied in 1910 but had not been identified at the molecular level. The phenotype of pink mutants was exacerbated by mutations in AP-3 subunits or in the orthologs of VPS33A and Rab38. These results validate D. melanogaster as a genetic model to study the function of the BLOCs.

Chlorella viruses contain genes encoding a complete polyamine biosynthetic pathway

PubMed Central

Baumann, Sascha; Sander, Adrianne; Gurnon, James R.; Yanai-Balser, Giane; VanEtten, James L.; Piotrowski, Markus

2007-01-01

Two genes encoding the putative polyamine biosynthetic enzymes agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase (CPA) were cloned from the chloroviruses PBCV-1, NY-2A and MT325. They were expressed in Escherichia coli to form C-terminal (His)6-tagged proteins and the recombinant proteins were purified by Ni2+- binding affinity chromatography. The biochemical properties of the two enzymes are similar to AIH and CPA enzymes from Arabidopsis thaliana and Pseudomonas aeruginosa. Together with the previously known virus genes encoding ornithine/arginine decarboxlyase (ODC/ADC) and homospermidine synthase, the chloroviruses have genes that encode a complete set of functional enzymes that synthesize the rare polyamine homospermidine from arginine via agmatine, N-carbamoylputrescine and putrescine. The PBCV-1 aih and cpa genes are expressed early during virus infection together with the odc/adc gene, suggesting that biosynthesis of putrescine is important in early stages of viral replication. The aih and cpa genes are widespread in the chlorella viruses. PMID:17101165

A Comprehensive Analysis of Nuclear-Encoded Mitochondrial Genes in Schizophrenia.

PubMed

Gonçalves, Vanessa F; Cappi, Carolina; Hagen, Christian M; Sequeira, Adolfo; Vawter, Marquis P; Derkach, Andriy; Zai, Clement C; Hedley, Paula L; Bybjerg-Grauholm, Jonas; Pouget, Jennie G; Cuperfain, Ari B; Sullivan, Patrick F; Christiansen, Michael; Kennedy, James L; Sun, Lei

2018-05-01

The genetic risk factors of schizophrenia (SCZ), a severe psychiatric disorder, are not yet fully understood. Multiple lines of evidence suggest that mitochondrial dysfunction may play a role in SCZ, but comprehensive association studies are lacking. We hypothesized that variants in nuclear-encoded mitochondrial genes influence susceptibility to SCZ. We conducted gene-based and gene-set analyses using summary association results from the Psychiatric Genomics Consortium Schizophrenia Phase 2 (PGC-SCZ2) genome-wide association study comprising 35,476 cases and 46,839 control subjects. We applied the MAGMA method to three sets of nuclear-encoded mitochondrial genes: oxidative phosphorylation genes, other nuclear-encoded mitochondrial genes, and genes involved in nucleus-mitochondria crosstalk. Furthermore, we conducted a replication study using the iPSYCH SCZ sample of 2290 cases and 21,621 control subjects. In the PGC-SCZ2 sample, 1186 mitochondrial genes were analyzed, among which 159 had p values < .05 and 19 remained significant after multiple testing correction. A meta-analysis of 818 genes combining the PGC-SCZ2 and iPSYCH samples resulted in 104 nominally significant and nine significant genes, suggesting a polygenic model for the nuclear-encoded mitochondrial genes. Gene-set analysis, however, did not show significant results. In an in silico protein-protein interaction network analysis, 14 mitochondrial genes interacted directly with 158 SCZ risk genes identified in PGC-SCZ2 (permutation p = .02), and aldosterone signaling in epithelial cells and mitochondrial dysfunction pathways appeared to be overrepresented in this network of mitochondrial and SCZ risk genes. This study provides evidence that specific aspects of mitochondrial function may play a role in SCZ, but we did not observe its broad involvement even using a large sample. Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The ribosomal protein genes and Minute loci of Drosophila melanogaster

PubMed Central

Marygold, Steven J; Roote, John; Reuter, Gunter; Lambertsson, Andrew; Ashburner, Michael; Millburn, Gillian H; Harrison, Paul M; Yu, Zhan; Kenmochi, Naoya; Kaufman, Thomas C; Leevers, Sally J; Cook, Kevin R

2007-01-01

Background Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster, disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged development, short and thin bristles, and poor fertility and viability. While more than 50 Minute loci have been defined genetically, only 15 have so far been characterized molecularly and shown to correspond to RP genes. Results We combined bioinformatic and genetic approaches to conduct a systematic analysis of the relationship between RP genes and Minute loci. First, we identified 88 genes encoding 79 different cytoplasmic RPs (CRPs) and 75 genes encoding distinct mitochondrial RPs (MRPs). Interestingly, nine CRP genes are present as duplicates and, while all appear to be functional, one member of each gene pair has relatively limited expression. Next, we defined 65 discrete Minute loci by genetic criteria. Of these, 64 correspond to, or very likely correspond to, CRP genes; the single non-CRP-encoding Minute gene encodes a translation initiation factor subunit. Significantly, MRP genes and more than 20 CRP genes do not correspond to Minute loci. Conclusion This work answers a longstanding question about the molecular nature of Minute loci and suggests that Minute phenotypes arise from suboptimal protein synthesis resulting from reduced levels of cytoribosomes. Furthermore, by identifying the majority of haplolethal and haplosterile loci at the molecular level, our data will directly benefit efforts to attain complete deletion coverage of the D. melanogaster genome. PMID:17927810

Identifying metabolic enzymes with multiple types of association evidence

PubMed Central

Kharchenko, Peter; Chen, Lifeng; Freund, Yoav; Vitkup, Dennis; Church, George M

2006-01-01

Background Existing large-scale metabolic models of sequenced organisms commonly include enzymatic functions which can not be attributed to any gene in that organism. Existing computational strategies for identifying such missing genes rely primarily on sequence homology to known enzyme-encoding genes. Results We present a novel method for identifying genes encoding for a specific metabolic function based on a local structure of metabolic network and multiple types of functional association evidence, including clustering of genes on the chromosome, similarity of phylogenetic profiles, gene expression, protein fusion events and others. Using E. coli and S. cerevisiae metabolic networks, we illustrate predictive ability of each individual type of association evidence and show that significantly better predictions can be obtained based on the combination of all data. In this way our method is able to predict 60% of enzyme-encoding genes of E. coli metabolism within the top 10 (out of 3551) candidates for their enzymatic function, and as a top candidate within 43% of the cases. Conclusion We illustrate that a combination of genome context and other functional association evidence is effective in predicting genes encoding metabolic enzymes. Our approach does not rely on direct sequence homology to known enzyme-encoding genes, and can be used in conjunction with traditional homology-based metabolic reconstruction methods. The method can also be used to target orphan metabolic activities. PMID:16571130

[High gene conversion frequency between genes encoding 2-deoxyglucose-6-phosphate phosphatase in 3 Saccharomyces species].

PubMed

Piscopo, Sara-Pier; Drouin, Guy

2014-05-01

Gene conversions are nonreciprocal sequence exchanges between genes. They are relatively common in Saccharomyces cerevisiae, but few studies have investigated the evolutionary fate of gene conversions or their functional impacts. Here, we analyze the evolution and impact of gene conversions between the two genes encoding 2-deoxyglucose-6-phosphate phosphatase in S. cerevisiae, Saccharomyces paradoxus and Saccharomyces mikatae. Our results demonstrate that the last half of these genes are subject to gene conversions among these three species. The greater similarity and the greater percentage of GC nucleotides in the converted regions, as well as the absence of long regions of adjacent common converted sites, suggest that these gene conversions are frequent and occur independently in all three species. The high frequency of these conversions probably result from the fact that they have little impact on the protein sequences encoded by these genes.

Neologistic jargon aphasia and agraphia in primary progressive aphasia.

PubMed

Rohrer, Jonathan D; Rossor, Martin N; Warren, Jason D

2009-02-15

The terms 'jargon aphasia' and 'jargon agraphia' describe the production of incomprehensible language containing frequent phonological, semantic or neologistic errors in speech and writing, respectively. Here we describe two patients with primary progressive aphasia (PPA) who produced neologistic jargon either in speech or writing. We suggest that involvement of the posterior superior temporal-inferior parietal region may lead to a disconnection between stored lexical representations and language output pathways leading to aberrant activation of phonemes in neologistic jargon. Parietal lobe involvement is relatively unusual in PPA, perhaps accounting for the comparative rarity of jargon early in the course of these diseases.

Secretion Trap Tagging of Secreted and Membrane-Spanning Proteins Using Arabidopsis Gene Traps

Treesearch

Andrew T. Groover; Joseph R. Fontana; Juana M. Arroyo; Cristina Yordan; W. Richard McCombie; Robert A. Martienssen

2003-01-01

Secreted and membrane-spanning proteins play fundamental roles in plant development but pose challenges for genetic identification and characterization. We describe a "secretion trap" screen for gene trap insertions in genes encoding proteins routed through the secretory pathway. The gene trap transposon encodes a ß-glucuronidase reporter enzyme...

A deep auto-encoder model for gene expression prediction.

PubMed

Xie, Rui; Wen, Jia; Quitadamo, Andrew; Cheng, Jianlin; Shi, Xinghua

2017-11-17

Gene expression is a key intermediate level that genotypes lead to a particular trait. Gene expression is affected by various factors including genotypes of genetic variants. With an aim of delineating the genetic impact on gene expression, we build a deep auto-encoder model to assess how good genetic variants will contribute to gene expression changes. This new deep learning model is a regression-based predictive model based on the MultiLayer Perceptron and Stacked Denoising Auto-encoder (MLP-SAE). The model is trained using a stacked denoising auto-encoder for feature selection and a multilayer perceptron framework for backpropagation. We further improve the model by introducing dropout to prevent overfitting and improve performance. To demonstrate the usage of this model, we apply MLP-SAE to a real genomic datasets with genotypes and gene expression profiles measured in yeast. Our results show that the MLP-SAE model with dropout outperforms other models including Lasso, Random Forests and the MLP-SAE model without dropout. Using the MLP-SAE model with dropout, we show that gene expression quantifications predicted by the model solely based on genotypes, align well with true gene expression patterns. We provide a deep auto-encoder model for predicting gene expression from SNP genotypes. This study demonstrates that deep learning is appropriate for tackling another genomic problem, i.e., building predictive models to understand genotypes' contribution to gene expression. With the emerging availability of richer genomic data, we anticipate that deep learning models play a bigger role in modeling and interpreting genomics.

Molecular evolution of nitrogen assimilatory enzymes in marine prasinophytes.

PubMed

Ghoshroy, Sohini; Robertson, Deborah L

2015-01-01

Nitrogen assimilation is a highly regulated process requiring metabolic coordination of enzymes and pathways in the cytosol, chloroplast, and mitochondria. Previous studies of prasinophyte genomes revealed that genes encoding nitrate and ammonium transporters have a complex evolutionary history involving both vertical and horizontal transmission. Here we examine the evolutionary history of well-conserved nitrogen-assimilating enzymes to determine if a similar complex history is observed. Phylogenetic analyses suggest that genes encoding glutamine synthetase (GS) III in the prasinophytes evolved by horizontal gene transfer from a member of the heterokonts. In contrast, genes encoding GSIIE, a canonical vascular plant and green algal enzyme, were found in the Micromonas genomes but have been lost from Ostreococcus. Phylogenetic analyses placed the Micromonas GSIIs in a larger chlorophyte/vascular plant clade; a similar topology was observed for ferredoxin-dependent nitrite reductase (Fd-NiR), indicating the genes encoding GSII and Fd-NiR in these prasinophytes evolved via vertical transmission. Our results show that genes encoding the nitrogen-assimilating enzymes in Micromonas and Ostreococcus have been differentially lost and as well as recruited from different evolutionary lineages, suggesting that the regulation of nitrogen assimilation in prasinophytes will differ from other green algae.

Living colors in the gray mold pathogen Botrytis cinerea: codon-optimized genes encoding green fluorescent protein and mCherry, which exhibit bright fluorescence.

PubMed

Leroch, Michaela; Mernke, Dennis; Koppenhoefer, Dieter; Schneider, Prisca; Mosbach, Andreas; Doehlemann, Gunther; Hahn, Matthias

2011-05-01

The green fluorescent protein (GFP) and its variants have been widely used in modern biology as reporters that allow a variety of live-cell imaging techniques. So far, GFP has rarely been used in the gray mold fungus Botrytis cinerea because of low fluorescence intensity. The codon usage of B. cinerea genes strongly deviates from that of commonly used GFP-encoding genes and reveals a lower GC content than other fungi. In this study, we report the development and use of a codon-optimized version of the B. cinerea enhanced GFP (eGFP)-encoding gene (Bcgfp) for improved expression in B. cinerea. Both the codon optimization and, to a smaller extent, the insertion of an intron resulted in higher mRNA levels and increased fluorescence. Bcgfp was used for localization of nuclei in germinating spores and for visualizing host penetration. We further demonstrate the use of promoter-Bcgfp fusions for quantitative evaluation of various toxic compounds as inducers of the atrB gene encoding an ABC-type drug efflux transporter of B. cinerea. In addition, a codon-optimized mCherry-encoding gene was constructed which yielded bright red fluorescence in B. cinerea.

Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones

PubMed Central

Glass, Jennifer B.; Kretz, Cecilia B.; Ganesh, Sangita; Ranjan, Piyush; Seston, Sherry L.; Buck, Kristen N.; Landing, William M.; Morton, Peter L.; Moffett, James W.; Giovannoni, Stephen J.; Vergin, Kevin L.; Stewart, Frank J.

2015-01-01

Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes, but little is known about the metalloenyzme inventory of anaerobic marine microbial communities despite their importance to the nitrogen cycle. We compared dissolved O2, NO3−, NO2−, Fe and Cu concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in 21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time-series Station. Dissolved Fe concentrations increased sharply at upper oxic-anoxic transition zones, with the highest Fe:Cu molar ratio (1.8) occurring at the anoxic core of the Eastern Tropical North Pacific oxygen minimum zone and matching the predicted maximum ratio based on data from diverse ocean sites. The relative abundance of genes encoding Fe-binding proteins was negatively correlated with O2, driven by significant increases in genes encoding Fe-proteins involved in dissimilatory nitrogen metabolisms under anoxia. Transcripts encoding cytochrome c oxidase, the Fe- and Cu-containing terminal reductase in aerobic respiration, were positively correlated with O2 content. A comparison of the taxonomy of genes encoding Fe- and Cu-binding vs. bulk proteins in OMZs revealed that Planctomycetes represented a higher percentage of Fe genes while Thaumarchaeota represented a higher percentage of Cu genes, particularly at oxyclines. These results are broadly consistent with higher relative abundance of genes encoding Fe-proteins in the genome of a marine planctomycete vs. higher relative abundance of genes encoding Cu-proteins in the genome of a marine thaumarchaeote. These findings highlight the importance of metalloenzymes for microbial processes in oxygen minimum zones and suggest preferential Cu use in oxic habitats with Cu > Fe vs. preferential Fe use in anoxic niches with Fe > Cu. PMID:26441925

Meta-omic signatures of microbial metal and nitrogen cycling in marine oxygen minimum zones.

PubMed

Glass, Jennifer B; Kretz, Cecilia B; Ganesh, Sangita; Ranjan, Piyush; Seston, Sherry L; Buck, Kristen N; Landing, William M; Morton, Peter L; Moffett, James W; Giovannoni, Stephen J; Vergin, Kevin L; Stewart, Frank J

2015-01-01

Iron (Fe) and copper (Cu) are essential cofactors for microbial metalloenzymes, but little is known about the metalloenyzme inventory of anaerobic marine microbial communities despite their importance to the nitrogen cycle. We compared dissolved O2, NO[Formula: see text], NO[Formula: see text], Fe and Cu concentrations with nucleic acid sequences encoding Fe and Cu-binding proteins in 21 metagenomes and 9 metatranscriptomes from Eastern Tropical North and South Pacific oxygen minimum zones and 7 metagenomes from the Bermuda Atlantic Time-series Station. Dissolved Fe concentrations increased sharply at upper oxic-anoxic transition zones, with the highest Fe:Cu molar ratio (1.8) occurring at the anoxic core of the Eastern Tropical North Pacific oxygen minimum zone and matching the predicted maximum ratio based on data from diverse ocean sites. The relative abundance of genes encoding Fe-binding proteins was negatively correlated with O2, driven by significant increases in genes encoding Fe-proteins involved in dissimilatory nitrogen metabolisms under anoxia. Transcripts encoding cytochrome c oxidase, the Fe- and Cu-containing terminal reductase in aerobic respiration, were positively correlated with O2 content. A comparison of the taxonomy of genes encoding Fe- and Cu-binding vs. bulk proteins in OMZs revealed that Planctomycetes represented a higher percentage of Fe genes while Thaumarchaeota represented a higher percentage of Cu genes, particularly at oxyclines. These results are broadly consistent with higher relative abundance of genes encoding Fe-proteins in the genome of a marine planctomycete vs. higher relative abundance of genes encoding Cu-proteins in the genome of a marine thaumarchaeote. These findings highlight the importance of metalloenzymes for microbial processes in oxygen minimum zones and suggest preferential Cu use in oxic habitats with Cu > Fe vs. preferential Fe use in anoxic niches with Fe > Cu.

The Yersinia pestis gcvB gene encodes two small regulatory RNA molecules

PubMed Central

McArthur, Sarah D; Pulvermacher, Sarah C; Stauffer, George V

2006-01-01

Background In recent years it has become clear that small non-coding RNAs function as regulatory elements in bacterial virulence and bacterial stress responses. We tested for the presence of the small non-coding GcvB RNAs in Y. pestis as possible regulators of gene expression in this organism. Results In this study, we report that the Yersinia pestis KIM6 gcvB gene encodes two small RNAs. Transcription of gcvB is activated by the GcvA protein and repressed by the GcvR protein. The gcvB-encoded RNAs are required for repression of the Y. pestis dppA gene, encoding the periplasmic-binding protein component of the dipeptide transport system, showing that the GcvB RNAs have regulatory activity. A deletion of the gcvB gene from the Y. pestis KIM6 chromosome results in a decrease in the generation time of the organism as well as a change in colony morphology. Conclusion The results of this study indicate that the Y. pestis gcvB gene encodes two small non-coding regulatory RNAs that repress dppA expression. A gcvB deletion is pleiotropic, suggesting that the sRNAs are likely involved in controlling genes in addition to dppA. PMID:16768793

Screening for ATM Mutations in an African-American Population to Identify a Predictor of Breast Cancer Susceptibility

DTIC Science & Technology

2006-07-01

ATM genetic variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for each mutation examined. 15. SUBJECT...women without breast cancer. An additional objective is to determine the functional impact upon the protein encoded by the ATM gene for each mutation ...each ATM variant identified affects radiosensitivity and levels of the protein encoded by the ATM gene for mutations identified. Body STATEMENT

Isolation of a gene encoding a novel spectinomycin phosphotransferase from Legionella pneumophila.

PubMed

Suter, T M; Viswanathan, V K; Cianciotto, N P

1997-06-01

A gene capable of conferring spectinomycin resistance was isolated from Legionella pneumophila, the agent of Legionnaires' disease. The gene (aph) encoded a 36-kDa protein which has similarity to aminoglycoside phosphotransferases. Biochemical analysis confirmed that aph encodes a phosphotransferase which modifies spectinomycin but not hygromycin, kanamycin, or streptomycin. The strain that was the source of aph demonstrated resistance to spectinomycin, and Southern hybridizations determined that aph also exists in other legionellae.

Isolation of a gene encoding a novel spectinomycin phosphotransferase from Legionella pneumophila.

PubMed Central

Suter, T M; Viswanathan, V K; Cianciotto, N P

1997-01-01

A gene capable of conferring spectinomycin resistance was isolated from Legionella pneumophila, the agent of Legionnaires' disease. The gene (aph) encoded a 36-kDa protein which has similarity to aminoglycoside phosphotransferases. Biochemical analysis confirmed that aph encodes a phosphotransferase which modifies spectinomycin but not hygromycin, kanamycin, or streptomycin. The strain that was the source of aph demonstrated resistance to spectinomycin, and Southern hybridizations determined that aph also exists in other legionellae. PMID:9174205

Escherichia coli yjjPB genes encode a succinate transporter important for succinate production.

PubMed

Fukui, Keita; Nanatani, Kei; Hara, Yoshihiko; Yamakami, Suguru; Yahagi, Daiki; Chinen, Akito; Tokura, Mitsunori; Abe, Keietsu

2017-09-01

Under anaerobic conditions, Escherichia coli produces succinate from glucose via the reductive tricarboxylic acid cycle. To date, however, no genes encoding succinate exporters have been established in E. coli. Therefore, we attempted to identify genes encoding succinate exporters by screening an E. coli MG1655 genome library. We identified the yjjPB genes as candidates encoding a succinate transporter, which enhanced succinate production in Pantoea ananatis under aerobic conditions. A complementation assay conducted in Corynebacterium glutamicum strain AJ110655ΔsucE1 demonstrated that both YjjP and YjjB are required for the restoration of succinate production. Furthermore, deletion of yjjPB decreased succinate production in E. coli by 70% under anaerobic conditions. Taken together, these results suggest that YjjPB constitutes a succinate transporter in E. coli and that the products of both genes are required for succinate export.

Molecular cloning and expression of the gene encoding the kinetoplast-associated type II DNA topoisomerase of Crithidia fasciculata.

PubMed

Pasion, S G; Hines, J C; Aebersold, R; Ray, D S

1992-01-01

A type II DNA topoisomerase, topoIImt, was shown previously to be associated with the kinetoplast DNA of the trypanosomatid Crithidia fasciculata. The gene encoding this kinetoplast-associated topoisomerase has been cloned by immunological screening of a Crithidia genomic expression library with monoclonal antibodies raised against the purified enzyme. The gene CfaTOP2 is a single copy gene and is expressed as a 4.8-kb polyadenylated transcript. The nucleotide sequence of CfaTOP2 has been determined and encodes a predicted polypeptide of 1239 amino acids with a molecular mass of 138,445. The identification of the cloned gene is supported by immunoblot analysis of the beta-galactosidase-CfaTOP2 fusion protein expressed in Escherichia coli and by analysis of tryptic peptide sequences derived from purified topoIImt. CfaTOP2 shares significant homology with nuclear type II DNA topoisomerases of other eukaryotes suggesting that in Crithidia both nuclear and mitochondrial forms of topoisomerase II are encoded by the same gene.

Two pheromone precursor genes are transcriptionally expressed in the homothallic ascomycete Sordaria macrospora.

PubMed

Pöggeler, S

2000-06-01

In order to analyze the involvement of pheromones in cell recognition and mating in a homothallic fungus, two putative pheromone precursor genes, named ppg1 and ppg2, were isolated from a genomic library of Sordaria macrospora. The ppg1 gene is predicted to encode a precursor pheromone that is processed by a Kex2-like protease to yield a pheromone that is structurally similar to the alpha-factor of the yeast Saccharomyces cerevisiae. The ppg2 gene encodes a 24-amino-acid polypeptide that contains a putative farnesylated and carboxy methylated C-terminal cysteine residue. The sequences of the predicted pheromones display strong structural similarity to those encoded by putative pheromones of heterothallic filamentous ascomycetes. Both genes are expressed during the life cycle of S. macrospora. This is the first description of pheromone precursor genes encoded by a homothallic fungus. Southern-hybridization experiments indicated that ppg1 and ppg2 homologues are also present in other homothallic ascomycetes.

Arxula adeninivorans (Blastobotrys adeninivorans) — A Dimorphic Yeast of Great Biotechnological Potential

NASA Astrophysics Data System (ADS)

Böer, Erik; Steinborn, Gerhard; Florschütz, Kristina; Körner, Martina; Gellissen, Gerd; Kunze, Gotthard

The dimorphic ascomycetous yeast Arxula adeninivorans exhibits some unusual properties. Being a thermo- and halotolerant species it is able to assimilate and ferment many compounds as sole carbon and/or nitrogen source. It utilises n-alkanes and is capable of degrading starch. Due to these unusual biochemical properties A. adeninivorans can be exploited as a gene donor for the production of enzymes with attractive biotechnological characteristics. Examples of A. adeninivorans-derived genes that are overexpressed include the ALIP1 gene encoding a secretory lipase, the AINV encoding invertase, the AXDH encoding xylitol dehydrogenase and the APHY encoding a secretory phosphatase with phytase activity.

Distinct [18F]THK5351 binding patterns in primary progressive aphasia variants.

PubMed

Schaeverbeke, Jolien; Evenepoel, Charlotte; Declercq, Lieven; Gabel, Silvy; Meersmans, Karen; Bruffaerts, Rose; Adamczuk, Kate; Dries, Eva; Van Bouwel, Karen; Sieben, Anne; Pijnenburg, Yolande; Peeters, Ronald; Bormans, Guy; Van Laere, Koen; Koole, Michel; Dupont, Patrick; Vandenberghe, Rik

2018-06-26

To assess the binding of the PET tracer [ 18 F]THK5351 in patients with different primary progressive aphasia (PPA) variants and its correlation with clinical deficits. The majority of patients with nonfluent variant (NFV) and logopenic variant (LV) PPA have underlying tauopathy of the frontotemporal lobar or Alzheimer disease type, respectively, while patients with the semantic variant (SV) have predominantly transactive response DNA binding protein 43-kDa pathology. The study included 20 PPA patients consecutively recruited through a memory clinic (12 NFV, 5 SV, 3 LV), and 20 healthy controls. All participants received an extensive neurolinguistic assessment, magnetic resonance imaging and amyloid biomarker tests. [ 18 F]THK5351 binding patterns were assessed on standardized uptake value ratio (SUVR) images with the cerebellar grey matter as the reference using statistical parametric mapping. Whole-brain voxel-wise regression analysis was performed to evaluate the association between [ 18 F]THK5351 SUVR images and neurolinguistic scores. Analyses were performed with and without partial volume correction. Patients with NFV showed increased binding in the supplementary motor area, left premotor cortex, thalamus, basal ganglia and midbrain compared with controls and patients with SV. Patients with SV had increased binding in the temporal lobes bilaterally and in the right ventromedial frontal cortex compared with controls and patients with NFV. The whole-brain voxel-wise regression analysis revealed a correlation between agrammatism and motor speech impairment, and [ 18 F]THK5351 binding in the left supplementary motor area and left postcentral gyrus. Analysis of [ 18 F]THK5351 scans without partial volume correction revealed similar results. [ 18 F]THK5351 imaging shows a topography closely matching the anatomical distribution of predicted underlying pathology characteristic of NFV and SV PPA. [ 18 F]THK5351 binding correlates with the severity of clinical impairment.

Potentiation Effects of Half-Squats Performed in a Ballistic or Nonballistic Manner.

PubMed

Suchomel, Timothy J; Sato, Kimitake; DeWeese, Brad H; Ebben, William P; Stone, Michael H

2016-06-01

This study examined and compared the acute effects of ballistic and nonballistic concentric-only half-squats (COHSs) on squat jump performance. Fifteen resistance-trained men performed a squat jump 2 minutes after a control protocol or 2 COHSs at 90% of their 1 repetition maximum (1RM) COHS performed in a ballistic or nonballistic manner. Jump height (JH), peak power (PP), and allometrically scaled peak power (PPa) were compared using three 3 × 2 repeated-measures analyses of variance. Statistically significant condition × time interaction effects existed for JH (p = 0.037), PP (p = 0.041), and PPa (p = 0.031). Post hoc analysis revealed that the ballistic condition produced statistically greater JH (p = 0.017 and p = 0.036), PP (p = 0.031 and p = 0.026), and PPa (p = 0.024 and p = 0.023) than the control and nonballistic conditions, respectively. Small effect sizes for JH, PP, and PPa existed during the ballistic condition (d = 0.28-0.44), whereas trivial effect sizes existed during the control (d = 0.0-0.18) and nonballistic (d = 0.0-0.17) conditions. Large statistically significant relationships existed between the JH potentiation response and the subject's relative back squat 1RM (r = 0.520; p = 0.047) and relative COHS 1RM (r = 0.569; p = 0.027) during the ballistic condition. In addition, large statistically significant relationship existed between JH potentiation response and the subject's relative back squat strength (r = 0.633; p = 0.011), whereas the moderate relationship with the subject's relative COHS strength trended toward significance (r = 0.483; p = 0.068). Ballistic COHS produced superior potentiation effects compared with COHS performed in a nonballistic manner. Relative strength may contribute to the elicited potentiation response after ballistic and nonballistic COHS.

Sabatier Reactor System Integration with Microwave Plasma Methane Pyrolysis Post-Processor for Closed-Loop Hydrogen Recovery

NASA Technical Reports Server (NTRS)

Abney, Morgan B.; Miller, Lee A.; Williams, Tom

2010-01-01

The Carbon Dioxide Reduction Assembly (CRA) designed and developed for the International Space Station (ISS) represents the state-of-the-art in carbon dioxide reduction (CDRe) technology. The CRA produces water and methane by reducing carbon dioxide with hydrogen via the Sabatier reaction. The water is recycled to the Oxygen Generation Assembly (OGA) and the methane is vented overboard resulting in a net loss of hydrogen. The proximity to earth and the relative ease of logistics resupply from earth allow for a semi-closed system on ISS. However, long-term manned space flight beyond low earth orbit (LEO) dictates a more thoroughly closed-loop system involving significantly higher recovery of hydrogen, and subsequent recovery of oxygen, to minimize costs associated with logistics resupply beyond LEO. The open-loop ISS system for CDRe can be made closed-loop for follow-on missions by further processing methane to recover hydrogen. For this purpose, a process technology has been developed that employs a microwave-generated plasma to reduce methane to hydrogen and acetylene resulting in 75% theoretical recovery of hydrogen. In 2009, a 1-man equivalent Plasma Pyrolysis Assembly (PPA) was delivered to the National Aeronautics and Space Administration (NASA) for technical evaluation. The PPA has been integrated with a Sabatier Development Unit (SDU). The integrated process configuration incorporates a sorbent bed to eliminate residual carbon dioxide and water vapor in the Sabatier methane product stream before it enters the PPA. This paper provides detailed information on the stand-alone and integrated performance of both the PPA and SDU. Additionally, the integrated test stand design and anticipated future work are discussed.

Cognitive and anatomic double dissociation in the representation of concrete and abstract words in semantic variant and behavioral variant frontotemporal degeneration.

PubMed

Cousins, Katheryn A Q; York, Collin; Bauer, Laura; Grossman, Murray

2016-04-01

We examine the anatomic basis for abstract and concrete lexical representations in semantic memory by assessing patients with focal neurodegenerative disease. Prior evidence from healthy adult studies suggests that there may be an anatomical dissociation between abstract and concrete representations: abstract words more strongly activate the left inferior frontal gyrus relative to concrete words, while concrete words more strongly activate left anterior-inferior temporal regions. However, this double dissociation has not been directly examined. We test this dissociation in two patient groups with focal cortical atrophy in each of these regions, the behavioral variant of Frontotemporal Degeneration (bvFTD) and the semantic variant of Primary Progressive Aphasia (svPPA). We administered an associativity judgment task for abstract and concrete words, where subjects select which of two words is best associated with a given target word. Both bvFTD and svPPA patients were significantly impaired in their overall performance compared to controls. While controls treated concrete and abstract words equally, we found a category-specific double dissociation in patients' judgments: bvFTD patients showed a concreteness effect (CE), with significantly worse performance for abstract compared to concrete words, while svPPA patients showed reversal of the CE, with significantly worse performance for concrete over abstract words. Regression analyses also revealed an anatomic double dissociation: The CE is associated with inferior frontal atrophy in bvFTD, while reversal of the CE is associated with left anterior-inferior temporal atrophy in svPPA. These results support a cognitive and anatomic model of semantic memory organization where abstract and concrete representations are supported by dissociable neuroanatomic substrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia.

PubMed

Makaretz, Sara J; Quimby, Megan; Collins, Jessica; Makris, Nikos; McGinnis, Scott; Schultz, Aaron; Vasdev, Neil; Johnson, Keith A; Dickerson, Bradford C

2017-10-06

The semantic variant of primary progressive aphasia (svPPA) is typically associated with frontotemporal lobar degeneration (FTLD) with longTAR DNA-binding protein (TDP)-43-positive neuropil threads and dystrophic neurites (type C), and is only rarely due to a primary tauopathy or Alzheimer's disease. We undertook this study to investigate the localisation and magnitude of the presumed tau Positron Emission Tomography (PET) tracer [ 18 F]Flortaucipir (FTP; also known as T807 or AV1451) in patients with svPPA, hypothesising that most patients would not show tracer uptake different from controls. FTP and [ 11 C]Pittsburgh compound B PET imaging as well as MRI were performed in seven patients with svPPA and in 20 controls. FTP signal was analysed by visual inspection and by quantitative comparison to controls, with and without partial volume correction. All seven patients showed elevated FTP uptake in the anterior temporal lobe with a leftward asymmetry that was not observed in healthy controls. This elevated FTP signal, largely co-localised with atrophy, was evident on both visual inspection and quantitative cortical surface-based analysis. Five patients were amyloid negative, one was amyloid positive and one has an unknown amyloid status. In this series of patients with clinical profiles, structural MRI and amyloid PET imaging typical for svPPA, FTP signal was unexpectedly elevated with a spatial pattern localised to areas of atrophy. This raises questions about the possible off-target binding of this tracer to non-tau molecules associated with neurodegeneration. Further investigation with autopsy analysis will help illuminate the binding target(s) of FTP in cases of suspected FTLD-TDP neuropathology. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Development of a Microwave Regenerative Sorbent-Based Hydrogen Purifier

NASA Technical Reports Server (NTRS)

Wheeler, Richard R., Jr.; Dewberry, Ross H.; McCurry, Bryan D.; Abney, Morgan B.; Greenwood, Zachary W.

2016-01-01

This paper describes the design and fabrication of a Microwave Regenerative Sorbent-based Hydrogen Purifier (MRSHP). This unique microwave powered technology was developed for the purification of a hydrogen stream produced by the Plasma Pyrolysis Assembly (PPA). The PPA is a hydrogen recovery (from methane) post processor for NASA's Sabatier-based carbon dioxide reduction process. Embodied in the Carbon dioxide Reduction Assembly (CRA), currently aboard the International Space Station (ISS), the Sabatier reaction employs hydrogen to catalytically recover oxygen, in the form of water, from respiratory carbon dioxide produced by the crew. This same approach is base-lined for future service in the Air Revitalization system on extended missions into deep space where resupply is not practical. Accordingly, manned exploration to Mars may only become feasible with further closure of the air loop as afforded by the greater hydrogen recovery permitted by the PPA with subsequent hydrogen purification. By utilizing the well-known high sorbate loading capacity of molecular sieve 13x, coupled with microwave dielectric heating phenomenon, MRSHP technology is employed as a regenerative filter for a contaminated hydrogen gas stream. By design, freshly regenerated molecular sieve 13x contained in the MRSHP will remove contaminants from the effluent of a 1-CM scale PPA for several hours prior to breakthrough. By reversing flow and pulling a relative vacuum the MRSHP prototype then uses 2.45 GHz microwave power, applied through a novel coaxial antenna array, to rapidly heat the sorbent bed and drive off the contaminants in a short duration vacuum/thermal contaminant desorption step. Finally, following rapid cooling via room temperature cold plates, the MRSHP is again ready to serve as a hydrogen filter.

Montmorillonite catalysis of RNA oligomer formation in aqueous solution. A model for the prebiotic formation of RNA

NASA Technical Reports Server (NTRS)

Ferris, J. P.; Ertem, G.

1993-01-01

Oligomers of adenylic acid of up to the 11-mer in length are formed by the reaction of the phosphorimidazolide of adenosine (ImpA) in pH 8 aqueous solution at room temperature in the presence of Na(+)-montmorillonite. These oligomers are joined by phosphodiester bonds in which the 3',5'-linkage predominates over the 2',5'-linkage by a 2:1 ratio. Reaction of a 9:1 mixture of ImpA, A5'ppA results in the formation of oligomers with a 3:1 ratio of 3',5'- to 2',5'-linked phosphodiester bonds. A high proportion of these oligomers contain the A5'ppA grouping. A5'ppA reacts much more rapidly with ImpA than does 5'-ADP (ppA) or 5'-ATP (pppA). The exchangeable cation associated with the montmorillonite effects the observed catalysis with Li+, Na+, NH4+, and Ca2+ being the more effective while Mg2+ and Al3+ are almost ineffective catalysts. 2',5'-Linked oligomers, up to the tetramer in length, are formed using UO2(2+)-montmorillonite. The structure analysis of individual oligomer fractions was performed by selective enzymatic and KOH hydrolytic studies followed by HPLC analysis of the reaction products. It is concluded from the composition of the oligomers that the rate of addition ImpA to a 3'-terminus containing a 2',5'-linkage is slower than the addition to a nucleoside joined by a 3',5'-linked phosphodiester bond. The potential importance of mineral catalysis of the formation of RNA and other oligomers on primitive Earth is discussed.

Is "Learning" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts.

PubMed

Casaletto, K B; Marx, G; Dutt, S; Neuhaus, J; Saloner, R; Kritikos, L; Miller, B; Kramer, J H

2017-07-28

Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of "total learning" immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer's disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1-4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps>0.05). Multiple neurobehavioral systems are associated with "total learning" immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structure of the Elastin-Contractile Units in the Thoracic Aorta and How Genes That Cause Thoracic Aortic Aneurysms and Dissections Disrupt This Structure.

PubMed

Karimi, Ashkan; Milewicz, Dianna M

2016-01-01

The medial layer of the aorta confers elasticity and strength to the aortic wall and is composed of alternating layers of smooth muscle cells (SMCs) and elastic fibres. The SMC elastin-contractile unit is a structural unit that links the elastin fibres to the SMCs and is characterized by the following: (1) layers of elastin fibres that are surrounded by microfibrils; (2) microfibrils that bind to the integrin receptors in focal adhesions on the cell surface of the SMCs; and (3) SMC contractile filaments that are linked to the focal adhesions on the inner side of the membrane. The genes that are altered to cause thoracic aortic aneurysms and aortic dissections encode proteins involved in the structure or function of the SMC elastin-contractile unit. Included in this gene list are the genes encoding protein that are structural components of elastin fibres and microfibrils, FBN1, MFAP5, ELN, and FBLN4. Also included are genes that encode structural proteins in the SMC contractile unit, including ACTA2, which encodes SMC-specific α-actin and MYH11, which encodes SMC-specific myosin heavy chain, along with MYLK and PRKG1, which encode kinases that control SMC contraction. Finally, mutations in the gene encoding the protein linking integrin receptors to the contractile filaments, FLNA, also predispose to thoracic aortic disease. Thus, these data suggest that functional SMC elastin-contractile units are important for maintaining the structural integrity of the aorta. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Medicago truncatula contains a second gene encoding a plastid located glutamine synthetase exclusively expressed in developing seeds.

PubMed

Seabra, Ana R; Vieira, Cristina P; Cullimore, Julie V; Carvalho, Helena G

2010-08-19

Nitrogen is a crucial nutrient that is both essential and rate limiting for plant growth and seed production. Glutamine synthetase (GS), occupies a central position in nitrogen assimilation and recycling, justifying the extensive number of studies that have been dedicated to this enzyme from several plant sources. All plants species studied to date have been reported as containing a single, nuclear gene encoding a plastid located GS isoenzyme per haploid genome. This study reports the existence of a second nuclear gene encoding a plastid located GS in Medicago truncatula. This study characterizes a new, second gene encoding a plastid located glutamine synthetase (GS2) in M. truncatula. The gene encodes a functional GS isoenzyme with unique kinetic properties, which is exclusively expressed in developing seeds. Based on molecular data and the assumption of a molecular clock, it is estimated that the gene arose from a duplication event that occurred about 10 My ago, after legume speciation and that duplicated sequences are also present in closely related species of the Vicioide subclade. Expression analysis by RT-PCR and western blot indicate that the gene is exclusively expressed in developing seeds and its expression is related to seed filling, suggesting a specific function of the enzyme associated to legume seed metabolism. Interestingly, the gene was found to be subjected to alternative splicing over the first intron, leading to the formation of two transcripts with similar open reading frames but varying 5' UTR lengths, due to retention of the first intron. To our knowledge, this is the first report of alternative splicing on a plant GS gene. This study shows that Medicago truncatula contains an additional GS gene encoding a plastid located isoenzyme, which is functional and exclusively expressed during seed development. Legumes produce protein-rich seeds requiring high amounts of nitrogen, we postulate that this gene duplication represents a functional innovation of plastid located GS related to storage protein accumulation exclusive to legume seed metabolism.

Molecular cloning and expression of heteromeric ACCase subunit genes from Jatropha curcas.

PubMed

Gu, Keyu; Chiam, Huihui; Tian, Dongsheng; Yin, Zhongchao

2011-04-01

Acetyl-CoA carboxylase (ACCase) catalyzes the biotin-dependent carboxylation of acetyl-CoA to produce malonyl-CoA, which is the essential first step in the biosynthesis of long-chain fatty acids. ACCase exists as a multi-subunit enzyme in most prokaryotes and the chloroplasts of most plants and algae, while it is present as a multi-domain enzyme in the endoplasmic reticulum of most eukaryotes. The heteromeric ACCase of higher plants consists of four subunits: an α-subunit of carboxyltransferase (α-CT, encoded by accA gene), a biotin carboxyl carrier protein (BCCP, encoded by accB gene), a biotin carboxylase (BC, encoded by accC gene) and a β-subunit of carboxyltransferase (β-CT, encoded by accD gene). In this study, we cloned and characterized the genes accA, accB1, accC and accD that encode the subunits of heteromeric ACCase in Jatropha (Jatropha curcas), a potential biofuel plant. The full-length cDNAs of the four subunit genes were isolated from a Jatropha cDNA library and by using 5' RACE, whereas the genomic clones were obtained from a Jatropha BAC library. They encode a 771 amino acid (aa) α-CT, a 286-aa BCCP1, a 537-aa BC and a 494-aa β-CT, respectively. The single-copy accA, accB1 and accC genes are nuclear genes, while the accD gene is located in chloroplast genome. Jatropha α-CT, BCCP1, BC and β-CT show high identity to their homologues in other higher plants at amino acid level and contain all conserved domains for ACCase activity. The accA, accB1, accC and accD genes are temporally and spatially expressed in the leaves and endosperm of Jatropha plants, which are regulated by plant development and environmental factors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Gene Cluster Encoding Cholate Catabolism in Rhodococcus spp.

PubMed Central

Wilbrink, Maarten H.; Casabon, Israël; Stewart, Gordon R.; Liu, Jie; van der Geize, Robert; Eltis, Lindsay D.

2012-01-01

Bile acids are highly abundant steroids with important functions in vertebrate digestion. Their catabolism by bacteria is an important component of the carbon cycle, contributes to gut ecology, and has potential commercial applications. We found that Rhodococcus jostii RHA1 grows well on cholate, as well as on its conjugates, taurocholate and glycocholate. The transcriptome of RHA1 growing on cholate revealed 39 genes upregulated on cholate, occurring in a single gene cluster. Reverse transcriptase quantitative PCR confirmed that selected genes in the cluster were upregulated 10-fold on cholate versus on cholesterol. One of these genes, kshA3, encoding a putative 3-ketosteroid-9α-hydroxylase, was deleted and found essential for growth on cholate. Two coenzyme A (CoA) synthetases encoded in the cluster, CasG and CasI, were heterologously expressed. CasG was shown to transform cholate to cholyl-CoA, thus initiating side chain degradation. CasI was shown to form CoA derivatives of steroids with isopropanoyl side chains, likely occurring as degradation intermediates. Orthologous gene clusters were identified in all available Rhodococcus genomes, as well as that of Thermomonospora curvata. Moreover, Rhodococcus equi 103S, Rhodococcus ruber Chol-4 and Rhodococcus erythropolis SQ1 each grew on cholate. In contrast, several mycolic acid bacteria lacking the gene cluster were unable to grow on cholate. Our results demonstrate that the above-mentioned gene cluster encodes cholate catabolism and is distinct from a more widely occurring gene cluster encoding cholesterol catabolism. PMID:23024343

The prrF-Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

PubMed Central

Reinhart, Alexandria A.; Powell, Daniel A.; Nguyen, Angela T.; O'Neill, Maura; Djapgne, Louise; Wilks, Angela; Ernst, Robert K.

2014-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that requires iron to cause infection, but it also must regulate the uptake of iron to avoid iron toxicity. The iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs) are part of P. aeruginosa's iron regulatory network and affect the expression of at least 50 genes encoding iron-containing proteins. The genes encoding the PrrF1 and PrrF2 sRNAs are encoded in tandem in P. aeruginosa, allowing for the expression of a distinct, heme-responsive sRNA named PrrH that appears to regulate genes involved in heme metabolism. Using a combination of growth, mass spectrometry, and gene expression analysis, we showed that the ΔprrF1,2 mutant, which lacks expression of the PrrF and PrrH sRNAs, is defective for both iron and heme homeostasis. We also identified phuS, encoding a heme binding protein involved in heme acquisition, and vreR, encoding a previously identified regulator of P. aeruginosa virulence genes, as novel targets of prrF-mediated heme regulation. Finally, we showed that the prrF locus encoding the PrrF and PrrH sRNAs is required for P. aeruginosa virulence in a murine model of acute lung infection. Moreover, we showed that inoculation with a ΔprrF1,2 deletion mutant protects against future challenge with wild-type P. aeruginosa. Combined, these data demonstrate that the prrF-encoded sRNAs are critical regulators of P. aeruginosa virulence. PMID:25510881

CIP1 polypeptides and their uses

DOEpatents

Foreman, Pamela [Los Altos, CA; Van Solingen, Pieter [Naaldwijk, NL; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA

2011-04-12

Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

Paralogous ALT1 and ALT2 Retention and Diversification Have Generated Catalytically Active and Inactive Aminotransferases in Saccharomyces cerevisiae

PubMed Central

Peñalosa-Ruiz, Georgina; Aranda, Cristina; Ongay-Larios, Laura; Colon, Maritrini; Quezada, Hector; Gonzalez, Alicia

2012-01-01

Background Gene duplication and the subsequent divergence of paralogous pairs play a central role in the evolution of novel gene functions. S. cerevisiae possesses two paralogous genes (ALT1/ALT2) which presumably encode alanine aminotransferases. It has been previously shown that Alt1 encodes an alanine aminotransferase, involved in alanine metabolism; however the physiological role of Alt2 is not known. Here we investigate whether ALT2 encodes an active alanine aminotransferase. Principal Findings Our results show that although ALT1 and ALT2 encode 65% identical proteins, only Alt1 displays alanine aminotransferase activity; in contrast ALT2 encodes a catalytically inert protein. ALT1 and ALT2 expression is modulated by Nrg1 and by the intracellular alanine pool. ALT1 is alanine-induced showing a regulatory profile of a gene encoding an enzyme involved in amino acid catabolism, in agreement with the fact that Alt1 is the sole pathway for alanine catabolism present in S. cerevisiae. Conversely, ALT2 expression is alanine-repressed, indicating a role in alanine biosynthesis, although the encoded-protein has no alanine aminotransferase enzymatic activity. In the ancestral-like yeast L. kluyveri, the alanine aminotransferase activity was higher in the presence of alanine than in the presence of ammonium, suggesting that as for ALT1, LkALT1 expression could be alanine-induced. ALT2 retention poses the questions of whether the encoded protein plays a particular function, and if this function was present in the ancestral gene. It could be hypotesized that ALT2 diverged after duplication, through neo-functionalization or that ALT2 function was present in the ancestral gene, with a yet undiscovered function. Conclusions ALT1 and ALT2 divergence has resulted in delegation of alanine aminotransferase activity to Alt1. These genes display opposed regulatory profiles: ALT1 is alanine-induced, while ALT2 is alanine repressed. Both genes are negatively regulated by the Nrg1 repressor. Presented results indicate that alanine could act as ALT2 Nrg1-co-repressor. PMID:23049841

Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

PubMed

Auerbach, Raymond K; Chen, Bin; Butte, Atul J

2013-08-01

Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

Rudimentary expression of RYamide in Drosophila melanogaster relative to other Drosophila species points to a functional decline of this neuropeptide gene.

PubMed

Veenstra, Jan A; Khammassi, Hela

2017-04-01

RYamides are arthropod neuropeptides with unknown function. In 2011 two RYamides were isolated from D. melanogaster as the ligands for the G-protein coupled receptor CG5811. The D. melanogaster gene encoding these neuropeptides is highly unusual, as there are four RYamide encoding exons in the current genome assembly, but an exon encoding a signal peptide is absent. Comparing the D. melanogaster gene structure with those from other species, including D. virilis, suggests that the gene is degenerating. RNAseq data from 1634 short sequence read archives at NCBI containing more than 34 billion spots yielded numerous individual spots that correspond to the RYamide encoding exons, of which a large number include the intron-exon boundary at the start of this exon. Although 72 different sequences have been spliced onto this RYamide encoding exon, none codes for the signal peptide of this gene. Thus, the RNAseq data for this gene reveal only noise and no signal. The very small quantities of peptide recovered during isolation and the absence of credible RNAseq data, indicates that the gene is very little expressed, while the RYamide gene structure in D. melanogaster suggests that it might be evolving into a pseudogene. Yet, the identification of the peptides it encodes clearly shows it is still functional. Using region specific antisera, we could localize numerous neurons and enteroendocrine cells in D. willistoni, D. virilis and D. pseudoobscura, but only two adult abdominal neurons in D. melanogaster. Those two neurons project to and innervate the rectal papillae, suggesting that RYamides may be involved in the regulation of water homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis and Manipulation of Aspartate Pathway Genes for l-Lysine Overproduction from Methanol by Bacillus methanolicus▿

PubMed Central

Nærdal, Ingemar; Netzer, Roman; Ellingsen, Trond E.; Brautaset, Trygve

2011-01-01

We investigated the regulation and roles of six aspartate pathway genes in l-lysine overproduction in Bacillus methanolicus: dapG, encoding aspartokinase I (AKI); lysC, encoding AKII; yclM, encoding AKIII; asd, encoding aspartate semialdehyde dehydrogenase; dapA, encoding dihydrodipicolinate synthase; and lysA, encoding meso-diaminopimelate decarboxylase. Analysis of the wild-type strain revealed that in vivo lysC transcription was repressed 5-fold by l-lysine and induced 2-fold by dl-methionine added to the growth medium. Surprisingly, yclM transcription was repressed 5-fold by dl-methionine, while the dapG, asd, dapA, and lysA genes were not significantly repressed by any of the aspartate pathway amino acids. We show that the l-lysine-overproducing classical B. methanolicus mutant NOA2#13A52-8A66 has—in addition to a hom-1 mutation—chromosomal mutations in the dapG coding region and in the lysA promoter region. No mutations were found in its dapA, lysC, asd, and yclM genes. The mutant dapG gene product had abolished feedback inhibition by meso-diaminopimelate in vitro, and the lysA mutation was accompanied by an elevated (6-fold) lysA transcription level in vivo. Moreover, yclM transcription was increased 16-fold in mutant strain NOA2#13A52-8A66 compared to the wild-type strain. Overexpression of wild-type and mutant aspartate pathway genes demonstrated that all six genes are important for l-lysine overproduction as tested in shake flasks, and the effects were dependent on the genetic background tested. Coupled overexpression of up to three genes resulted in additive (above 80-fold) increased l-lysine production levels. PMID:21724876

Analysis and manipulation of aspartate pathway genes for L-lysine overproduction from methanol by Bacillus methanolicus.

PubMed

Nærdal, Ingemar; Netzer, Roman; Ellingsen, Trond E; Brautaset, Trygve

2011-09-01

We investigated the regulation and roles of six aspartate pathway genes in L-lysine overproduction in Bacillus methanolicus: dapG, encoding aspartokinase I (AKI); lysC, encoding AKII; yclM, encoding AKIII; asd, encoding aspartate semialdehyde dehydrogenase; dapA, encoding dihydrodipicolinate synthase; and lysA, encoding meso-diaminopimelate decarboxylase. Analysis of the wild-type strain revealed that in vivo lysC transcription was repressed 5-fold by L-lysine and induced 2-fold by dl-methionine added to the growth medium. Surprisingly, yclM transcription was repressed 5-fold by dl-methionine, while the dapG, asd, dapA, and lysA genes were not significantly repressed by any of the aspartate pathway amino acids. We show that the L-lysine-overproducing classical B. methanolicus mutant NOA2#13A52-8A66 has-in addition to a hom-1 mutation-chromosomal mutations in the dapG coding region and in the lysA promoter region. No mutations were found in its dapA, lysC, asd, and yclM genes. The mutant dapG gene product had abolished feedback inhibition by meso-diaminopimelate in vitro, and the lysA mutation was accompanied by an elevated (6-fold) lysA transcription level in vivo. Moreover, yclM transcription was increased 16-fold in mutant strain NOA2#13A52-8A66 compared to the wild-type strain. Overexpression of wild-type and mutant aspartate pathway genes demonstrated that all six genes are important for L-lysine overproduction as tested in shake flasks, and the effects were dependent on the genetic background tested. Coupled overexpression of up to three genes resulted in additive (above 80-fold) increased L-lysine production levels.

“Guilt by Association” Is the Exception Rather Than the Rule in Gene Networks

PubMed Central

Gillis, Jesse; Pavlidis, Paul

2012-01-01

Gene networks are commonly interpreted as encoding functional information in their connections. An extensively validated principle called guilt by association states that genes which are associated or interacting are more likely to share function. Guilt by association provides the central top-down principle for analyzing gene networks in functional terms or assessing their quality in encoding functional information. In this work, we show that functional information within gene networks is typically concentrated in only a very few interactions whose properties cannot be reliably related to the rest of the network. In effect, the apparent encoding of function within networks has been largely driven by outliers whose behaviour cannot even be generalized to individual genes, let alone to the network at large. While experimentalist-driven analysis of interactions may use prior expert knowledge to focus on the small fraction of critically important data, large-scale computational analyses have typically assumed that high-performance cross-validation in a network is due to a generalizable encoding of function. Because we find that gene function is not systemically encoded in networks, but dependent on specific and critical interactions, we conclude it is necessary to focus on the details of how networks encode function and what information computational analyses use to extract functional meaning. We explore a number of consequences of this and find that network structure itself provides clues as to which connections are critical and that systemic properties, such as scale-free-like behaviour, do not map onto the functional connectivity within networks. PMID:22479173

Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA.

PubMed

Queck, Shu Y; Khan, Burhan A; Wang, Rong; Bach, Thanh-Huy L; Kretschmer, Dorothee; Chen, Liang; Kreiswirth, Barry N; Peschel, Andreas; Deleo, Frank R; Otto, Michael

2009-07-01

Bacterial virulence and antibiotic resistance have a significant influence on disease severity and treatment options during bacterial infections. Frequently, the underlying genetic determinants are encoded on mobile genetic elements (MGEs). In the leading human pathogen Staphylococcus aureus, MGEs that contain antibiotic resistance genes commonly do not contain genes for virulence determinants. The phenol-soluble modulins (PSMs) are staphylococcal cytolytic toxins with a crucial role in immune evasion. While all known PSMs are core genome-encoded, we here describe a previously unidentified psm gene, psm-mec, within the staphylococcal methicillin resistance-encoding MGE SCCmec. PSM-mec was strongly expressed in many strains and showed the physico-chemical, pro-inflammatory, and cytolytic characteristics typical of PSMs. Notably, in an S. aureus strain with low production of core genome-encoded PSMs, expression of PSM-mec had a significant impact on immune evasion and disease. In addition to providing high-level resistance to methicillin, acquisition of SCCmec elements encoding PSM-mec by horizontal gene transfer may therefore contribute to staphylococcal virulence by substituting for the lack of expression of core genome-encoded PSMs. Thus, our study reveals a previously unknown role of methicillin resistance clusters in staphylococcal pathogenesis and shows that important virulence and antibiotic resistance determinants may be combined in staphylococcal MGEs.

Local entropy difference upon a substrate binding of a psychrophilic α-amylase and a mesophilic homologue

NASA Astrophysics Data System (ADS)

Kosugi, Takahiro; Hayashi, Shigehiko

2011-01-01

Psychrophilic α-amylase from the antarctic bacterium pseudoalteromonashaloplanktis (AHA) and its mesophilic homologue, porcine pancreatic α-amylase (PPA) are theoretically investigated with molecular dynamics (MD) simulations. We carried out 240-ns MD simulations for four systems, AHA and PPA with/without the bound substrate, and examined protein conformational entropy changes upon the substrate binding. We developed an analysis that decomposes the entropy changes into contributions of individual amino acids, and successfully identified protein regions responsible for the entropy changes. The results provide a molecular insight into the structural flexibilities of those enzymes related to the temperature dependences of the enzymatic activity.

Inspection applications with higher electron beam energies

NASA Astrophysics Data System (ADS)

Norman, D. R.; Jones, J. L.; Yoon, W. Y.; Haskell, K. J.; Sterbentz, J. W.; Zabriskie, J. M.; Hunt, A. W.; Harmon, F.; Kinlaw, M. T.

2005-12-01

The Idaho National Laboratory has developed prototype shielded nuclear material detection systems based on pulsed photonuclear assessment (PPA) techniques for the inspection of cargo containers. During this work, increased nuclear material detection capabilities have been demonstrated at higher electron beam energies than those allowed by federal regulations for cargo inspection. This paper gives a general overview of a nuclear material detection system, the PPA technique and discusses the benefits of using these higher energies. This paper also includes a summary of the numerical and test results from LINAC operations up to 24 MeV and discusses some of the federal energy limitations associated with cargo inspection.

Effects of alpha-amylase reaction mechanisms on analysis of resistant-starch contents.

PubMed

Moore, Samuel A; Ai, Yongfeng; Chang, Fengdan; Jane, Jay-lin

2015-01-22

This study aimed to understand differences in the resistant starch (RS) contents of native and modified starches obtained using two standard methods of RS content analysis: AOAC Method 991.43 and 2002.02. The largest differences were observed in native potato starch, cross-linked wheat distarch phosphate, and high-amylose corn starch stearic-acid complex (RS5) between using AOAC Method 991.43 with Bacillus licheniformis α-amylase (BL) and AOAC Method 2002.02 with porcine pancreatic α-amylase (PPA). To determine possible reasons for these differences, we hydrolyzed raw-starch granules with BL and PPA with equal activity at pH 6.9 and 37°C for up to 84 h and observed the starch granules displayed distinct morphological differences after the hydrolysis. Starches hydrolyzed by BL showed erosion on the surface of the granules; those hydrolyzed by PPA showed pitting on granule surfaces. These results suggested that enzyme reaction mechanisms, including the sizes of the binding sites and the reaction patterns of the two enzymes, contributed to the differences in the RS contents obtained using different methods of RS analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Targeted Nanoprobe Based on Carbon Nanotubes-Natural Biopolymer Chitosan Composites

PubMed Central

Wu, Baoyan; Zhao, Na

2016-01-01

A novel targeting theranostic nanoprobe based on single-walled carbon nanotubes (SWCNTs)-natural biopolymer chitosan composites was developed for cancer cell targeting imaging and fluorescence imaging-guided photodynamic therapy. First, chitosan was respectively conjugated with a tumor-homing molecule folic acid, or a photosensitizing drug pyropheophorbide a using a water-soluble carbodiimide coupling chemistry. Chitosan was fluorescently labeled by fluorescein isothiocyanate via the covalently linkage of the isothiocyanate group with the amino group. Second, SWCNTs were sonicated in the functional chitosan aqueous solution for 6 h at room temperature in order to obtain the nanoprobe (PPa/FITC-SWCNT-FA). The as-prepared nanoprobe has been characterized with transmission electron microscope, confocal microscopy, and cell cytotoxicity tests. Chitosan was decorated onto SWCNTs resulting in the water-dispersible PPa/FITC-SWCNT-FA, and can be selectively transported inside folate receptor-positive tumor cell with good targeting imaging. PPa/FITC-SWCNT-FA exhibited low dark toxicity about 7%–13%, and high phototoxicity about 60%–74% against HeLa cells upon a 635 nm laser irradiation, indicating satisfying biocompatibility and antitumor activity. These results suggest the study could offer a feasible alternative to presently available nanoparticle-based theranostic agents. PMID:28335344

Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public–Private Collaboration

PubMed Central

Surya, Asik; Setyaningsih, Budiarti; Suryani Nasution, Helmi; Gita Parwati, Cicilia; Yuzwar, Yullita E; Osberg, Mike; Hanson, Christy L; Hymoff, Aaron; Mingkwan, Pia; Makayova, Julia; Gebhard, Agnes; Waworuntu, Wiendra

2017-01-01

Abstract Background Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world’s “missing” TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. Methods A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. Results The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. Conclusions The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers. PMID:29117347

DNA Duplex-Based Photodynamic Molecular Beacon for Targeted Killing of Retinoblastoma Cell.

PubMed

Wei, Yanchun; Lu, Cuixia; Chen, Qun; Xing, Da

2016-11-01

Retinoblastoma (RB) is the most common primary intraocular malignancy of infancy. An alternative RB treatment protocol is proposed and tested. It is based on a photodynamic therapy (PDT) with a designed molecular beacon that specifically targets the murine double minute x (MDMX) high-expressed RB cells. A MDMX mRNA triggered photodynamic molecular beacon is designed by binding a photosensitizer molecule (pyropheophorbide-a, or PPa) and a black hole quencher-3 (BHQ3) through a complementary oligonucleotide sequence. Cells with and without MDMX high-expression are incubated with the beacon and then irradiated with a laser. The fluorescence and reactive oxygen species are detected in solution to verify the specific activation of PPa by the perfectly matched DNA targets. The cell viabilities are evaluated with CCK-8 and flow cytometry assay. The fluorescence and photo-cytoxicity of PPa is recovered and significantly higher in the MDMX high-expressed Y79 and WERI-Rb1 cells, compared to that with the MDMX low-expressed cells. The synthesized beacon exhibits high PDT efficiency toward MDMX high-expressed RB cells. The data suggest that the designed beacon may provide a potential alternative for RB therapy and secures the ground for future investigation.

Lexical decision with pseudohomophones and reading in the semantic variant of primary progressive aphasia: A double dissociation.

PubMed

Boukadi, Mariem; Potvin, Karel; Macoir, Joël; Jr Laforce, Robert; Poulin, Stéphane; Brambati, Simona M; Wilson, Maximiliano A

2016-06-01

The co-occurrence of semantic impairment and surface dyslexia in the semantic variant of primary progressive aphasia (svPPA) has often been taken as supporting evidence for the central role of semantics in visual word processing. According to connectionist models, semantic access is needed to accurately read irregular words. They also postulate that reliance on semantics is necessary to perform the lexical decision task under certain circumstances (for example, when the stimulus list comprises pseudohomophones). In the present study, we report two svPPA cases: M.F. who presented with surface dyslexia but performed accurately on the lexical decision task with pseudohomophones, and R.L. who showed no surface dyslexia but performed below the normal range on the lexical decision task with pseudohomophones. This double dissociation between reading and lexical decision with pseudohomophones is in line with the dual-route cascaded (DRC) model of reading. According to this model, impairments in visual word processing in svPPA are not necessarily associated with the semantic deficits characterizing this disease. Our findings also call into question the central role given to semantics in visual word processing within the connectionist account. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interactions between polyphenols in thinned young apples and porcine pancreatic α-amylase: Inhibition, detailed kinetics and fluorescence quenching.

PubMed

Sun, Lijun; Chen, Weiqi; Meng, Yonghong; Yang, Xingbin; Yuan, Li; Guo, Yurong; Warren, Frederick J; Gidley, Michael J

2016-10-01

Young apple polyphenols (YAP) and nine types of phenolic compounds were investigated regarding the inhibitory activity against porcine pancreatic α-amylase (PPA) in vitro. Tannic acid, chlorogenic acid and caffeic acid in YAP showed relatively high inhibition with the IC50 values of 0.30, 1.96 and 3.69mg/mL, respectively. A detailed kinetics of inhibition study revealed that YAP and tannic acid were competitive inhibitors of PPA, whereas chlorogenic acid and caffeic acid were mixed inhibitors, exhibiting both competitive and uncompetitive characteristics. The fluorescence of PPA could be significantly quenched by YAP and the three polyphenols, and their quenching constants were determined. The results showed that for the polyphenols investigated, the order of the apparent static quenching constants (KFQ) was in agreement with that of the reciprocal competitive inhibition constants (1/Kic) (tannic acid>chlorogenic acid>caffeic acid>epicatechin); both of the parameters were contrary to the order of the IC50 values. Thus, combining detailed kinetics and fluorescence quenching studies can be applied to characterise the interactions between polyphenols in young apples and α-amylase. Copyright © 2016 Elsevier Ltd. All rights reserved.

Written language impairments in primary progressive aphasia: a reflection of damage to central semantic and phonological processes.

PubMed

Henry, Maya L; Beeson, Pélagie M; Alexander, Gene E; Rapcsak, Steven Z

2012-02-01

Connectionist theories of language propose that written language deficits arise as a result of damage to semantic and phonological systems that also support spoken language production and comprehension, a view referred to as the "primary systems" hypothesis. The objective of the current study was to evaluate the primary systems account in a mixed group of individuals with primary progressive aphasia (PPA) by investigating the relation between measures of nonorthographic semantic and phonological processing and written language performance and by examining whether common patterns of cortical atrophy underlie impairments in spoken versus written language domains. Individuals with PPA and healthy controls were administered a language battery, including assessments of semantics, phonology, reading, and spelling. Voxel-based morphometry was used to examine the relation between gray matter volumes and language measures within brain regions previously implicated in semantic and phonological processing. In accordance with the primary systems account, our findings indicate that spoken language performance is strongly predictive of reading/spelling profile in individuals with PPA and suggest that common networks of critical left hemisphere regions support central semantic and phonological processes recruited for spoken and written language.

Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public-Private Collaboration.

PubMed

Surya, Asik; Setyaningsih, Budiarti; Suryani Nasution, Helmi; Gita Parwati, Cicilia; Yuzwar, Yullita E; Osberg, Mike; Hanson, Christy L; Hymoff, Aaron; Mingkwan, Pia; Makayova, Julia; Gebhard, Agnes; Waworuntu, Wiendra

2017-11-06

Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world's "missing" TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Assessment of Individuals with Primary Progressive Aphasia.

PubMed

Henry, Maya L; Grasso, Stephanie M

2018-07-01

Speech-language pathologists play a crucial role in the assessment and treatment of individuals with primary progressive aphasia (PPA). The speech-language evaluation is a critical aspect of the diagnostic and rehabilitative process, informing differential diagnosis as well as intervention planning and monitoring of cognitive-linguistic status over time. The evaluation should include a thorough case history and interview and a detailed assessment of speech-language and cognitive functions, with tasks designed to detect core and associated deficits outlined in current diagnostic criteria. In this paper, we review assessments that can be utilized to examine communication and cognition in PPA, including general aphasia batteries designed for stroke and/or progressive aphasia as well as tests of specific cognitive-linguistic functions, including naming, object/person knowledge, single-word and sentence comprehension, repetition, spontaneous speech/language production, motor speech, written language, and nonlinguistic cognitive domains. The comprehensive evaluation can inform diagnostic decision making and facilitate planning of interventions that are tailored to the patient's current status and likely progression of deficits. As such, the speech-language evaluation allows the medical team to provide individuals with PPA and their families with appropriate recommendations for the present and the future. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Potent α-amylase inhibitory activity of Indian Ayurvedic medicinal plants.

PubMed

P, Sudha; Zinjarde, Smita S; Bhargava, Shobha Y; Kumar, Ameeta R

2011-01-20

Indian medicinal plants used in the Ayurvedic traditional system to treat diabetes are a valuable source of novel anti-diabetic agents. Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post-prandial hyperglycemia via control of starch breakdown. In this study, seventeen Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on PPA (porcine pancreatic α-amylase). Preliminary phytochemical analysis of the lead extracts was performed in order to determine the probable constituents. Analysis of the 126 extracts, obtained from 17 plants (Aloe vera (L.) Burm.f., Adansonia digitata L., Allium sativum L., Casia fistula L., Catharanthus roseus (L.) G. Don., Cinnamomum verum Persl., Coccinia grandis (L.) Voigt., Linum usitatisumum L., Mangifera indica L., Morus alba L., Nerium oleander L., Ocimum tenuiflorum L., Piper nigrum L., Terminalia chebula Retz., Tinospora cordifolia (Willd.) Miers., Trigonella foenum-graceum L., Zingiber officinale Rosc.) for PPA inhibition was initially performed qualitatively by starch-iodine colour assay. The lead extracts were further quantified with respect to PPA inhibition using the chromogenic DNSA (3, 5-dinitrosalicylic acid) method. Phytochemical constituents of the extracts exhibiting≥ 50% inhibition were analysed qualitatively as well as by GC-MS (Gas chromatography-Mass spectrometry). Of the 126 extracts obtained from 17 plants, 17 extracts exhibited PPA inhibitory potential to varying degrees (10%-60.5%) while 4 extracts showed low inhibition (< 10%). However, strong porcine pancreatic amylase inhibitory activity (> 50%) was obtained with 3 isopropanol extracts. All these 3 extracts exhibited concentration dependent inhibition with IC50 values, viz., seeds of Linum usitatisumum (540 μgml-1), leaves of Morus alba (1440 μgml-1) and Ocimum tenuiflorum (8.9 μgml-1). Acarbose as the standard inhibitor exhibited an IC50 (half maximal inhibitory concentration)value of 10.2 μgml-1. Phytochemical analysis revealed the presence of alkaloids, tannins, cardiac glycosides, flavonoids, saponins and steroids with the major phytoconstituents being identified by GC-MS. This study endorses the use of these plants for further studies to determine their potential for type 2 diabetes management. Results suggests that extracts of Linum usitatisumum, Morus alba and Ocimum tenuiflorum act effectively as PPA inhibitors leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels.

Potent α-amylase inhibitory activity of Indian Ayurvedic medicinal plants

PubMed Central

2011-01-01

Background Indian medicinal plants used in the Ayurvedic traditional system to treat diabetes are a valuable source of novel anti-diabetic agents. Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post-prandial hyperglycemia via control of starch breakdown. In this study, seventeen Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on PPA (porcine pancreatic α-amylase). Preliminary phytochemical analysis of the lead extracts was performed in order to determine the probable constituents. Methods Analysis of the 126 extracts, obtained from 17 plants (Aloe vera (L.) Burm.f., Adansonia digitata L., Allium sativum L., Casia fistula L., Catharanthus roseus (L.) G. Don., Cinnamomum verum Persl., Coccinia grandis (L.) Voigt., Linum usitatisumum L., Mangifera indica L., Morus alba L., Nerium oleander L., Ocimum tenuiflorum L., Piper nigrum L., Terminalia chebula Retz., Tinospora cordifolia (Willd.) Miers., Trigonella foenum-graceum L., Zingiber officinale Rosc.) for PPA inhibition was initially performed qualitatively by starch-iodine colour assay. The lead extracts were further quantified with respect to PPA inhibition using the chromogenic DNSA (3, 5-dinitrosalicylic acid) method. Phytochemical constituents of the extracts exhibiting≥ 50% inhibition were analysed qualitatively as well as by GC-MS (Gas chromatography-Mass spectrometry). Results Of the 126 extracts obtained from 17 plants, 17 extracts exhibited PPA inhibitory potential to varying degrees (10%-60.5%) while 4 extracts showed low inhibition (< 10%). However, strong porcine pancreatic amylase inhibitory activity (> 50%) was obtained with 3 isopropanol extracts. All these 3 extracts exhibited concentration dependent inhibition with IC50 values, viz., seeds of Linum usitatisumum (540 μgml-1), leaves of Morus alba (1440 μgml-1) and Ocimum tenuiflorum (8.9 μgml-1). Acarbose as the standard inhibitor exhibited an IC50 (half maximal inhibitory concentration)value of 10.2 μgml-1. Phytochemical analysis revealed the presence of alkaloids, tannins, cardiac glycosides, flavonoids, saponins and steroids with the major phytoconstituents being identified by GC-MS. Conclusions This study endorses the use of these plants for further studies to determine their potential for type 2 diabetes management. Results suggests that extracts of Linum usitatisumum, Morus alba and Ocimum tenuiflorum act effectively as PPA inhibitors leading to a reduction in starch hydrolysis and hence eventually to lowered glucose levels. PMID:21251279

Comparison of pulse wave velocity and pulse pressure amplification in association with target organ damage in community-dwelling elderly: The Northern Shanghai Study.

PubMed

Bai, Bin; Teliewubai, Jiadela; Lu, Yuyan; Yu, Shikai; Xiong, Jing; Chi, Chen; Zhou, Yiwu; Ji, Hongwei; Fan, Ximin; Blacher, Jacques; Li, Jue; Zhang, Yi; Xu, Yawei

2018-05-01

This study aimed to investigate the discrepancy between pulse wave velocity (PWV) and pulse pressure amplification (PPA) in association with hypertensive target organ damage (TOD) in the elderly. From June 2014 to August 2015, 1599 participants aged >65 years old from communities located in northern Shanghai were recruited. Carotid-femoral pulse wave velocity (cfPWV), peripheral blood pressure (BP), central BP and other TOD indicators, including the ratio of the early ventricular filling velocity (E) to the peak velocity of the tissue Doppler velocity of septal mitral annulus (E/Ea), left ventricular mass index (LVMI), carotid intima-medium thickness (CIMT), estimated glomerular filtration rate (eGFR), and urinary albumin-creatinine ratio (ACR), were determined for each participant. PPA was defined as the peripheral-to-central pulse pressure ratio. In multivariable linear regression analysis, cfPWV was significantly associated with CIMT (β = 12.83 ± 4.28 μm per SD; P = 0.003) and eGFR (β = -1.85 ± 0.69 ml/min/1.73 m 2 per SD; P = 0.007), whereas PPA was significantly associated with E/Ea (β = -0.25 ± 0.10 per SD; P = 0.01) and LVMI (β = -3.00 ± 0.78 g/m 2 per SD; P < 0.001). Similarly, in multivariable logistic regression analysis, cfPWV was significantly associated with arterial plaque (odds ratio [OR], 1.21 [95% confidence interval [CI], 1.05-1.39]; P = 0.007), peripheral artery disease (OR, 1.22 [95% CI, 1.06-1.42]; P = 0.007), chronic kidney diseases (OR, 1.24 [95% CI, 1.01-1.54]; P = 0.04) and microalbuminuria (OR, 1.21 [95% CI, 1.07-1.37]; P = 0.002), while PPA was tightly associated with left ventricular hypertrophy (OR, 0.85 [95% CI, 0.72-0.99]; P = 0.04) and diastolic dysfunction (OR, 0.78 [95% CI, 0.64-0.96]; P = 0.02). In conclusion, cfPWV is a vessel-related and renal-related biomarker, while PPA is a cardiac-related biomarker in community-based elderly.

Staphylococcus aureus nasal carriage in Ukraine: antibacterial resistance and virulence factor encoding genes.

PubMed

Netsvyetayeva, Irina; Fraczek, Mariusz; Piskorska, Katarzyna; Golas, Marlena; Sikora, Magdalena; Mlynarczyk, Andrzej; Swoboda-Kopec, Ewa; Marusza, Wojciech; Palmieri, Beniamino; Iannitti, Tommaso

2014-03-05

The number of studies regarding the incidence of multidrug resistant strains and distribution of genes encoding virulence factors, which have colonized the post-Soviet states, is considerably limited. The aim of the study was (1) to assess the Staphylococcus (S.) aureus nasal carriage rate, including Methicillin Resistant S. aureus (MRSA) strains in adult Ukrainian population, (2) to determine antibiotic resistant pattern and (3) the occurrence of Panton Valentine Leukocidine (PVL)-, Fibronectin-Binding Protein A (FnBPA)- and Exfoliative Toxin (ET)-encoding genes. Nasal samples for S. aureus culture were obtained from 245 adults. The susceptibility pattern for several classes of antibiotics was determined by disk diffusion method according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The virulence factor encoding genes, mecA, lukS-lukF, eta, etb, etd, fnbA, were detected by Polymerase Chain Reaction (PCR). The S. aureus nasal carriage rate was 40%. The prevalence of nasal MRSA carriage in adults was 3.7%. LukS-lukF genes were detected in over 58% of the strains. ET-encoding genes were detected in over 39% of the strains and the most prevalent was etd. The fnbA gene was detected in over 59% of the strains. All MRSA isolates tested were positive for the mecA gene. LukS-lukF genes and the etd gene were commonly co-present in MRSA, while lukS-lukF genes and the fnbA gene were commonly co-present in Methicillin Sensitive S. aureus (MSSA) isolates. No significant difference was detected between the occurrence of lukS-lukF genes (P > 0.05) and the etd gene (P > 0.05) when comparing MRSA and MSSA. The occurrence of the fnbA gene was significantly more frequent in MSSA strains (P < 0.05). In Ukraine, S. aureus is a common cause of infection. The prevalence of S. aureus nasal carriage in our cohort of patients from Ukraine was 40.4%. We found that 9.1% of the strains were classified as MRSA and all MRSA isolates tested positive for the mecA gene. We also observed a high prevalence of PVL- and ET- encoding genes among S. aureus nasal carriage strains. A systematic surveillance system can help prevent transmission and spread of drug resistant toxin producing S. aureus strains.

Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome

PubMed Central

Kunieda, T; Fujiyuki, T; Kucharski, R; Foret, S; Ament, S A; Toth, A L; Ohashi, K; Takeuchi, H; Kamikouchi, A; Kage, E; Morioka, M; Beye, M; Kubo, T; Robinson, G E; Maleszka, R

2006-01-01

Carbohydrate-metabolizing enzymes may have particularly interesting roles in the honey bee, Apis mellifera, because this social insect has an extremely carbohydrate-rich diet, and nutrition plays important roles in caste determination and socially mediated behavioural plasticity. We annotated a total of 174 genes encoding carbohydrate-metabolizing enzymes and 28 genes encoding lipid-metabolizing enzymes, based on orthology to their counterparts in the fly, Drosophila melanogaster, and the mosquito, Anopheles gambiae. We found that the number of genes for carbohydrate metabolism appears to be more evolutionarily labile than for lipid metabolism. In particular, we identified striking changes in gene number or genomic organization for genes encoding glycolytic enzymes, cellulase, glucose oxidase and glucose dehydrogenases, glucose-methanol-choline (GMC) oxidoreductases, fucosyltransferases, and lysozymes. PMID:17069632

Novel Type V Staphylococcal Cassette Chromosome mec Driven by a Novel Cassette Chromosome Recombinase, ccrC

PubMed Central

Ito, Teruyo; Ma, Xiao Xue; Takeuchi, Fumihiko; Okuma, Keiko; Yuzawa, Harumi; Hiramatsu, Keiichi

2004-01-01

Staphylococcal cassette chromosome mec (SCCmec) is a mobile genetic element composed of the mec gene complex, which encodes methicillin resistance, and the ccr gene complex, which encodes the recombinases responsible for its mobility. The mec gene complex has been classified into four classes, and the ccr gene complex has been classified into three allotypes. Different combinations of mec gene complex classes and ccr gene complex types have so far defined four types of SCCmec elements. Now we introduce the fifth allotype of SCCmec, which was found on the chromosome of a community-acquired methicillin-resistant Staphylococcus aureus strain (strain WIS [WBG8318]) isolated in Australia. The element shared the same chromosomal integration site with the four extant types of SCCmec and the characteristic nucleotide sequences at the chromosome-SCCmec junction regions. The novel SCCmec carried mecA bracketed by IS431 (IS431-mecA-ΔmecR1-IS431), which is designated the class C2 mec gene complex; and instead of ccrA and ccrB genes, it carried a single copy of a gene homologue that encoded cassette chromosome recombinase. Since the open reading frame (ORF) was found to encode an enzyme which catalyzes the precise excision as well as site- and orientation-specific integration of the element, we designated the ORF cassette chromosome recombinase C (ccrC), and we designated the element type V SCCmec. Type V SCCmec is a small SCCmec element (28 kb) and does not carry any antibiotic resistance genes besides mecA. Unlike the extant SCCmec types, it carries a set of foreign genes encoding a restriction-modification system that might play a role in the stabilization of the element on the chromosome. PMID:15215121

Complete genome sequence of Nitrosospira multiformis, an ammonia-oxidizing bacterium from the soil environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norton, Jeanette M.; Klotz, Martin G; Stein, Lisa Y

2008-01-01

The complete genome of the ammonia-oxidizing bacterium, Nitrosospira multiformis (ATCC 25196T), consists of a circular chromosome and three small plasmids totaling 3,234,309 bp and encoding 2827 putative proteins. Of these, 2026 proteins have predicted functions and 801 are without conserved functional domains, yet 747 of these have similarity to other predicted proteins in databases. Gene homologs from Nitrosomonas europaea and N. eutropha were the best match for 42% of the predicted genes in N. multiformis. The genome contains three nearly identical copies of amo and hao gene clusters as large repeats. Distinguishing features compared to N. europaea include: the presencemore » of gene clusters encoding urease and hydrogenase, a RuBisCO-encoding operon of distinctive structure and phylogeny, and a relatively small complement of genes related to Fe acquisition. Systems for synthesis of a pyoverdine-like siderophore and for acyl-homoserine lactone were unique to N. multiformis among the sequenced AOB genomes. Gene clusters encoding proteins associated with outer membrane and cell envelope functions including transporters, porins, exopolysaccharide synthesis, capsule formation and protein sorting/export were abundant. Numerous sensory transduction and response regulator gene systems directed towards sensing of the extracellular environment are described. Gene clusters for glycogen, polyphosphate and cyanophycin storage and utilization were identified providing mechanisms for meeting energy requirements under substrate-limited conditions. The genome of N. multiformis encodes the core pathways for chemolithoautotrophy along with adaptations for surface growth and survival in soil environments.« less

Transcriptional Profiling of Caulobacter crescentus during Growth on Complex and Minimal Media

PubMed Central

Hottes, Alison K.; Meewan, Maliwan; Yang, Desiree; Arana, Naomi; Romero, Pedro; McAdams, Harley H.; Stephens, Craig

2004-01-01

Microarray analysis was used to examine gene expression in the freshwater oligotrophic bacterium Caulobacter crescentus during growth on three standard laboratory media, including peptone-yeast extract medium (PYE) and minimal salts medium with glucose or xylose as the carbon source. Nearly 400 genes (approximately 10% of the genome) varied significantly in expression between at least two of these media. The differentially expressed genes included many encoding transport systems, most notably diverse TonB-dependent outer membrane channels of unknown substrate specificity. Amino acid degradation pathways constituted the largest class of genes induced in PYE. In contrast, many of the genes upregulated in minimal media encoded enzymes for synthesis of amino acids, including incorporation of ammonia and sulfate into glutamate and cysteine. Glucose availability induced expression of genes encoding enzymes of the Entner-Doudoroff pathway, which was demonstrated here through mutational analysis to be essential in C. crescentus for growth on glucose. Xylose induced expression of genes encoding several hydrolytic exoenzymes as well as an operon that may encode a novel pathway for xylose catabolism. A conserved DNA motif upstream of many xylose-induced genes was identified and shown to confer xylose-specific expression. Xylose is an abundant component of xylan in plant cell walls, and the microarray data suggest that in addition to serving as a carbon source for growth of C. crescentus, this pentose may be interpreted as a signal to produce enzymes associated with plant polymer degradation. PMID:14973021

Molecular cloning and characterization of alpha - galactosidase gene from Glaciozyma antarctica

NASA Astrophysics Data System (ADS)

Moheer, Reyad Qaed Al; Bakar, Farah Diba Abu; Murad, Abdul Munir Abdul

2015-09-01

Psychrophilic enzymes are proteins produced by psychrophilic organisms which recently are the limelight for industrial applications. A gene encoding α-galactosidase from a psychrophilic yeast, Glaciozyma antarctica PI12 which belongs to glycoside hydrolase family 27, was isolated and analyzed using several bioinformatic tools. The cDNA of the gene with the size of 1,404-bp encodes a protein with 467 amino acid residues. Predicted molecular weight of protein was 48.59 kDa and hence we name the gene encoding α-galactosidase as GAL48. We found that the predicted protein sequences possessed signal peptide sequence and are highly conserved among other fungal α-galactosidase.

Isolation of Nicotiana plumbaginifolia cDNAs encoding isoforms of serine acetyltransferase and O-acetylserine (thiol) lyase in a yeast two-hybrid system with Escherichia coli cysE and cysK genes as baits.

PubMed

Liszewska, Frantz; Gaganidze, Dali; Sirko, Agnieszka

2005-01-01

We applied the yeast two-hybrid system for screening of a cDNA library of Nicotiana plumbaginifolia for clones encoding plant proteins interacting with two proteins of Escherichia coli: serine acetyltransferase (SAT, the product of cysE gene) and O-acetylserine (thiol)lyase A, also termed cysteine synthase (OASTL-A, the product of cysK gene). Two plant cDNA clones were identified when using the cysE gene as a bait. These clones encode a probable cytosolic isoform of OASTL and an organellar isoform of SAT, respectively, as indicated by evolutionary trees. The second clone, encoding SAT, was identified independently also as a "prey" when using cysK as a bait. Our results reveal the possibility of applying the two-hybrid system for cloning of plant cDNAs encoding enzymes of the cysteine synthase complex in the two-hybrid system. Additionally, using genome walking sequences located upstream of the sat1 cDNA were identified. Subsequently, in silico analyses were performed aiming towards identification of the potential signal peptide and possible location of the deduced mature protein encoded by sat1.

Characterization of white shrimp Litopenaeus vannamei integrin β and its role in immunomodulation by dsRNA-mediated gene silencing.

PubMed

Lin, Yong-Chin; Chen, Jiann-Chu; Chen, Yu-Yuan; Liu, Chun-Hung; Cheng, Winton; Hsu, Chih-Hung; Tsui, Wen-Ching

2013-06-01

The full sequence of white shrimp Litopenaeus vannamei integrin β (LV-B) is 2879bp which encodes 787 amino acids (aa) of the open reading frame (ORF). The mature protein (764 aa) contains (1) an extracellular domain (ED) of 692 aa, (2) a transmembrane domain (TD) of 23 aa, and (3) a cytoplasmic domain (CD) of 49 aa. The cloned LV-B grouped together with crayfish Pacifastacus leniusculus integrin β (PL-B1), but was far away from vertebrate integrin β1, β3, β5, β6, β7, and β8, and another L. vannamei integrin β (LV). A Southern blot analysis indicated that the cloned LV-B was a single copy of genomic DNA. LV-B mRNA was expressed in all tissues, and was highly expressed in haemocytes. LV-B was downregulated in shrimp 24 and 96h after having received white spot syndrome virus (WSSV). LV-B expression by haemocytes of shrimp was higher in the postmoult (A and B) stage, and lower in the premoult (D2/D3) stage. LV-B expression was significantly higher by shrimp reared in 2.5‰ and 5‰ salinities. Shrimp injected with integrin β dsRNA showed gene silencing of integrin β after 36h. LV-B-silenced shrimp showed decreased hyaline cells (HCs), granular cells (GCs, including semi-granular cells), the total haemocyte count (THC), respiratory bursts (RBs), and lysozyme activity, but showed increased RB/HC, superoxide dismutase (SOD) activity/HC, and the phenoloxidase (PO) activity/GC. LV-B-silenced shrimp showed upregulated expressions of lipopolysaccharide- and β-glucan-binding protein (LGBP), peroxinectin (PX), prophenoloxidase I (proPO I), proPO II, proPO-activating enzyme (ppA), α2-macroglobulin (α2-M), cytMnSOD, mtMnSOD, and heat shock protein 70 (HSP70). It was concluded that integrin β plays important roles in proPO activation, phagocytosis, and the antioxidant system for immunomodulation in shrimp. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic and functional properties of uncultivated thermophilic crenarchaeotes from a subsurface gold mine as revealed by analysis of genome fragments.

PubMed

Nunoura, Takuro; Hirayama, Hisako; Takami, Hideto; Oida, Hanako; Nishi, Shinro; Shimamura, Shigeru; Suzuki, Yohey; Inagaki, Fumio; Takai, Ken; Nealson, Kenneth H; Horikoshi, Koki

2005-12-01

Within a phylum Crenarchaeota, only some members of the hyperthermophilic class Thermoprotei, have been cultivated and characterized. In this study, we have constructed a metagenomic library from a microbial mat formation in a subsurface hot water stream of the Hishikari gold mine, Japan, and sequenced genome fragments of two different phylogroups of uncultivated thermophilic Crenarchaeota: (i) hot water crenarchaeotic group (HWCG) I (41.2 kb), and (ii) HWCG III (49.3 kb). The genome fragment of HWCG I contained a 16S rRNA gene, two tRNA genes and 35 genes encoding proteins but no 23S rRNA gene. Among the genes encoding proteins, several genes for putative aerobic-type carbon monoxide dehydrogenase represented a potential clue with regard to the yet unknown metabolism of HWCG I Archaea. The genome fragment of HWCG III contained a 16S/23S rRNA operon and 44 genes encoding proteins. In the 23S rRNA gene, we detected a homing-endonuclease encoding a group I intron similar to those detected in hyperthermophilic Crenarchaeota and Bacteria, as well as eukaryotic organelles. The reconstructed phylogenetic tree based on the 23S rRNA gene sequence reinforced the intermediate phylogenetic affiliation of HWCG III bridging the hyperthermophilic and non-thermophilic uncultivated Crenarchaeota.

Pulmonary Hypertension and Computed Tomography Measurement of Small Pulmonary Vessels in Severe Emphysema

PubMed Central

Matsuoka, Shin; Washko, George R.; Yamashiro, Tsuneo; Estepar, Raul San Jose; Diaz, Alejandro; Silverman, Edwin K.; Hoffman, Eric; Fessler, Henry E.; Criner, Gerard J.; Marchetti, Nathaniel; Scharf, Steven M.; Martinez, Fernando J.; Reilly, John J.; Hatabu, Hiroto

2010-01-01

Rationale: Vascular alteration of small pulmonary vessels is one of the characteristic features of pulmonary hypertension in chronic obstructive pulmonary disease. The in vivo relationship between pulmonary hypertension and morphological alteration of the small pulmonary vessels has not been assessed in patients with severe emphysema. Objectives: We evaluated the correlation of total cross-sectional area of small pulmonary vessels (CSA) assessed on computed tomography (CT) scans with the degree of pulmonary hypertension estimated by right heart catheterization. Methods: In 79 patients with severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), we measured CSA less than 5 mm2 (CSA<5) and 5 to 10 mm2 (CSA5−10), and calculated the percentage of total CSA for the lung area (%CSA<5 and %CSA5–10, respectively). The correlations of %CSA<5 and %CSA5–10 with pulmonary arterial mean pressure (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document}) obtained by right heart catheterization were evaluated. Multiple linear regression analysis using \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} as the dependent outcome was also performed. Measurements and Main Results: The %CSA<5 had a significant negative correlation with \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r = −0.512, P < 0.0001), whereas the correlation between %CSA5–10 and \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} did not reach statistical significance (r = −0.196, P = 0.083). Multiple linear regression analysis showed that %CSA<5 and diffusing capacity of carbon monoxide (DlCO) % predicted were independent predictors of \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} (r2 = 0.541): %CSA <5 (P < 0.0001), and DlCO % predicted (P = 0.022). Conclusions: The %CSA<5 measured on CT images is significantly correlated to \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}\\overline{Ppa}\\end{equation*}\\end{document} in severe emphysema and can estimate the degree of pulmonary hypertension. PMID:19875683

The genomic structure of the human Charcot-Leyden crystal protein gene is analogous to those of the galectin genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dyer, K.D.; Handen, J.S.; Rosenberg, H.F.

The Charcot-Leyden crystal (CLC) protein, or eosinophil lysophospholipase, is a characteristic protein of human eosinophils and basophils; recent work has demonstrated that the CLC protein is both structurally and functionally related to the galectin family of {beta}-galactoside binding proteins. The galectins as a group share a number of features in common, including a linear ligand binding site encoded on a single exon. In this work, we demonstrate that the intron-exon structure of the gene encoding CLC is analogous to those encoding the galectins. The coding sequence of the CLC gene is divided into four exons, with the entire {beta}-galactoside bindingmore » site encoded by exon III. We have isolated CLC {beta}-galactoside binding sites from both orangutan (Pongo pygmaeus) and murine (Mus musculus) genomic DNAs, both encoded on single exons, and noted conservation of the amino acids shown to interact directly with the {beta}-galactoside ligand. The most likely interpretation of these results suggests the occurrence of one or more exon duplication and insertion events, resulting in the distribution of this lectin domain to CLC as well as to the multiple galectin genes. 35 refs., 3 figs.« less

Recombination and mutation of class II histocompatibility genes in wild mice.

PubMed

Wakeland, E K; Darby, B R

1983-12-01

We have compared the tryptic peptide fingerprints of the A alpha, A beta, E alpha, and E beta subunits encoded by four wild-derived H-2 complexes expressing A molecules closely related to Ak. The A molecules encoded by these Ak-related mice have A alpha and A beta subunits that differ from A alpha k and A beta k by less than 10% of their tryptic peptides. Comparisons among the four wild-derived A molecules suggested that these contemporary A alpha and A beta alleles arose by sequential mutational events from common ancestor A alpha and A beta alleles. These results suggest that A alpha and A beta may co-evolve as an A beta A alpha gene duplex in wild mice. Tryptic peptide fingerprint comparisons of the E beta gene linked to these Ak-related A beta A alpha gene duplexes indicate that two encode E beta d-like subunits, whereas another encodes an E beta s-like subunit. These results strongly suggest that the A beta A alpha duplex and E beta recombine in wild mouse populations. The significantly different evolutionary patterns exhibited by the class II genes encoding A vs E molecules are discussed.

Multi-functional acetyl-CoA carboxylase from Brassica napus is encoded by a multi-gene family: indication for plastidic localization of at least one isoform.

PubMed

Schulte, W; Töpfer, R; Stracke, R; Schell, J; Martini, N

1997-04-01

Three genes coding for different multifunctional acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) isoenzymes from Brassica napus were isolated and divided into two major classes according to structural features in their 5' regions: class I comprises two genes with an additional coding exon of approximately 300 bp at the 5' end, and class II is represented by one gene carrying an intron of 586 bp in its 5' untranslated region. Fusion of the peptide sequence encoded by the additional first exon of a class I ACCase gene to the jellyfish Aequorea victoria green fluorescent protein (GFP) and transient expression in tobacco protoplasts targeted GFP to the chloroplasts. In contrast to the deduced primary structure of the biotin carboxylase domain encoded by the class I gene, the corresponding amino acid sequence of the class II ACCase shows higher identity with that of the Arabidopsis ACCase, both lacking a transit peptide. The Arabidopsis ACCase has been proposed to be a cytosolic isoenzyme. These observations indicate that the two classes of ACCase genes encode plastidic and cytosolic isoforms of multi-functional, eukaryotic type, respectively, and that B. napus contains at least one multi-functional ACCase besides the multi-subunit, prokaryotic type located in plastids. Southern blot analysis of genomic DNA from B. napus, Brassica rapa, and Brassica oleracea, the ancestors of amphidiploid rapeseed, using a fragment of a multi-functional ACCase gene as a probe revealed that ACCase is encoded by a multi-gene family of at least five members.

Characterization of GM-CSF-inhibitory factor and Uracil DNA glycosylase encoding genes from camel pseudocowpoxvirus.

PubMed

Nagarajan, G; Swami, Shelesh Kumar; Dahiya, Shyam Singh; Narnaware, S D; Mehta, S C; Singh, P K; Singh, Raghvendar; Tuteja, F C; Patil, N V

2015-06-01

The present study describes the PCR amplification of GM-CSF-inhibitory factor (GIF) and Uracil DNA glycosylase (UDG) encoding genes of pseudocowpoxvirus (PCPV) from the Indian Dromedaries (Camelus dromedarius) infected with contagious ecthyma using the primers based on the corresponding gene sequences of human PCPV and reindeer PCPV, respectively. The length of GIF gene of PCPV obtained from camel is 795 bp and due to the addition of one cytosine residue at position 374 and one adenine residue at position 516, the open reading frame (ORF) got altered, resulting in the production of truncated polypeptide. The ORF of UDG encoding gene of camel PCPV is 696 bp encoding a polypeptide of 26.0 kDa. Comparison of amino acid sequence homologies of GIF and UDG of camel PCPV revealed that the camel PCPV is closer to ORFV and PCPV (reference stains of both human and reindeer), respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

A mutation in a new gene bglJ, activates the bgl operon in Escherichia coli K-12

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giel, M.; Desnoyer, M.; Lopilato, J.

1996-06-01

A new mutation , bglJ4, has been characterized that results in the expression of the silent bgl operon. The bgl operon encodes proteins necessary for the transport and utilization of the aromatic {beta}-glucosides arbutin and salicin. A variety of mutations activate the operon and result in a Bgl{sup +} phenotype. Activating mutations are located upstream of the bgl promoter and in genes located elsewhere on the chromosome. Mutations outside of the bgl operon occur in the genes encoding DNA gyrase and in the gene encoding the nucleoid associated protein H-NS. The mutation described here, bglJ4, has been mapped to amore » new locus at min 99 on the Escherichia coli K-12 genetic map. The putative protein encoded by the bglJ gene has homology to a family of transcriptional activators. Evidence is presented that increased expression of the bglJ product is needed for activation of the bgl operon. 56 refs., 3 figs., 3 tabs.« less

Two Closely Related Genes of Arabidopsis Encode Plastidial Cytidinediphosphate Diacylglycerol Synthases Essential for Photoautotrophic Growth1[C

PubMed Central

Haselier, André; Akbari, Hana; Weth, Agnes; Baumgartner, Werner; Frentzen, Margrit

2010-01-01

Cytidinediphosphate diacylglycerol synthase (CDS) catalyzes the formation of cytidinediphosphate diacylglycerol, an essential precursor of anionic phosphoglycerolipids like phosphatidylglycerol or -inositol. In plant cells, CDS isozymes are located in plastids, mitochondria, and microsomes. Here, we show that these isozymes are encoded by five genes in Arabidopsis (Arabidopsis thaliana). Alternative translation initiation or alternative splicing of CDS2 and CDS4 transcripts can result in up to 10 isoforms. Most of the cDNAs encoding the various plant isoforms were functionally expressed in yeast and rescued the nonviable phenotype of the mutant strain lacking CDS activity. The closely related genes CDS4 and CDS5 were found to encode plastidial isozymes with similar catalytic properties. Inactivation of both genes was required to obtain Arabidopsis mutant lines with a visible phenotype, suggesting that the genes have redundant functions. Analysis of these Arabidopsis mutants provided further independent evidence for the importance of plastidial phosphatidylglycerol for structure and function of thylakoid membranes and, hence, for photoautotrophic growth. PMID:20442275

The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation.

PubMed

Henry, Romain; Bruneau, Emmanuelle; Gardan, Rozenn; Bertin, Stéphane; Fleuchot, Betty; Decaris, Bernard; Leblond-Bourget, Nathalie

2011-10-07

Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Δrgg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature.

Identification of an opd (organophosphate degradation) gene in an Agrobacterium isolate.

PubMed

Horne, Irene; Sutherland, Tara D; Harcourt, Rebecca L; Russell, Robyn J; Oakeshott, John G

2002-07-01

We isolated a bacterial strain, Agrobacterium radiobacter P230, which can hydrolyze a wide range of organophosphate (OP) insecticides. A gene encoding a protein involved in OP hydrolysis was cloned from A. radiobacter P230 and sequenced. This gene (called opdA) had sequence similarity to opd, a gene previously shown to encode an OP-hydrolyzing enzyme in Flavobacterium sp. strain ATCC 27551 and Brevundimonas diminuta MG. Insertional mutation of the opdA gene produced a strain lacking the ability to hydrolyze OPs, suggesting that this is the only gene encoding an OP-hydrolyzing enzyme in A. radiobacter P230. The OPH and OpdA proteins, encoded by opd and opdA, respectively, were overexpressed and purified as maltose-binding proteins, and the maltose-binding protein moiety was cleaved and removed. Neither protein was able to hydrolyze the aliphatic OP malathion. The kinetics of the two proteins for diethyl OPs were comparable. For dimethyl OPs, OpdA had a higher k(cat) than OPH. It was also capable of hydrolyzing the dimethyl OPs phosmet and fenthion, which were not hydrolyzed at detectable levels by OPH.

Detection of β-lactamase encoding genes in feces, soil and water from a Brazilian pig farm.

PubMed

Furlan, João Pedro Rueda; Stehling, Eliana Guedes

2018-01-10

β-lactam antibiotics are widely used for the treatment of different types of infections worldwide and the resistance to these antibiotics has grown sharply, which is of great concern. Resistance to β-lactams in gram-negative bacteria is mainly due to the production of β-lactamases, which are classified according to their functional activities. The aim of this study was to verify the presence of β-lactamases encoding genes in feces, soil, and water from a Brazilian pig farm. Different β-lactamases encoding genes were found, including bla CTX-M-Gp1 , bla CTX-M-Gp9 , bla SHV , bla OXA-1-like , bla GES , and bla VEB . The bla SHV and bla CTX-M-Gp1 genes have been detected in all types of samples, indicating the spread of β-lactam resistant bacteria among farm pigs and the environment around them. These results indicate that β-lactamase encoding genes belonging to the cloxacillinase, ESBL, and carbapenemase and they have high potential to spread in different sources, due to the fact that genes are closely related to mobile genetic elements, especially plasmids.

The molecular genetics of Usher syndrome.

PubMed

Ahmed, Z M; Riazuddin, S; Riazuddin, S; Wilcox, E R

2003-06-01

Association of sensorineural deafness and progressive retinitis pigmentosa with and without a vestibular abnormality is the hallmark of Usher syndrome and involves at least 12 loci among three different clinical subtypes. Genes identified for the more commonly inherited loci are USH2A (encoding usherin), MYO7A (encoding myosin VIIa), CDH23 (encoding cadherin 23), PCDH15 (encoding protocadherin 15), USH1C (encoding harmonin), USH3A (encoding clarin 1), and USH1G (encoding SANS). Transcripts from all these genes are found in many tissues/cell types other than the inner ear and retina, but all are uniquely critical for retinal and cochlear cell function. Many of these protein products have been demonstrated to have direct interactions with each other and perform an essential role in stereocilia homeostasis.

Cloning of the Pichia anomala SEC61 gene and its expression in a Saccharomyces cerevisiae sec61 mutant.

PubMed

Ruíz, Teresa; De la Rosa, José M; Domínguez, Angel; Rodríguez, Luis

2003-05-01

In several organisms, including Saccharomyces cerevisiae and other yeast species, the product encoded by the SEC61 gene is considered to be the core element of the translocation apparatus within the endoplasmic reticulum membrane through which translocation of secretory and membrane proteins occurs. In this study, we have cloned and characterized the homolog of the SEC61 gene from the yeast Pichia anomala. The cloned gene includes an ORF, interrupted after the first ten nucleotides by an intron of 131 bp, encoding a 479-amino acid putative polypeptide exhibiting homology to the products encoded by different eukaryotic SEC61 genes, particularly to those from other yeast species. We show that the P. anomala SEC61 gene is correctly processed (intron splicing) when expressed in S. cerevisiae and that it is able to complement the thermosensitive phenotype associated with a mutation in the S. cerevisiae SEC61 gene.

Identification of the gene for fly non-muscle myosin heavy chain: Drosophila myosin heavy chains are encoded by a gene family.

PubMed Central

Kiehart, D P; Lutz, M S; Chan, D; Ketchum, A S; Laymon, R A; Nguyen, B; Goldstein, L S

1989-01-01

In contrast to vertebrate species Drosophila has a single myosin heavy chain gene that apparently encodes all sarcomeric heavy chain polypeptides. Flies also contain a cytoplasmic myosin heavy chain polypeptide that by immunological and peptide mapping criteria is clearly different from the major thoracic muscle isoform. Here, we identify the gene that encodes this cytoplasmic isoform and demonstrate that it is distinct from the muscle myosin heavy chain gene. Thus, fly myosin heavy chains are the products of a gene family. Our data suggest that the contractile function required to power myosin based movement in non-muscle cells requires myosin diversity beyond that available in a single heavy chain gene. In addition, we show, that accumulation of cytoplasmic myosin transcripts is regulated in a developmental stage specific fashion, consistent with a key role for this protein in the movements of early embryogenesis. Images PMID:2498088

A novel chlorophyll a/b binding (Cab) protein gene from petunia which encodes the lower molecular weight Cab precursor protein.

PubMed

Stayton, M M; Black, M; Bedbrook, J; Dunsmuir, P

1986-12-22

The 16 petunia Cab genes which have been characterized are all closely related at the nucleotide sequence level and they encode Cab precursor polypeptides which are similar in sequence and length. Here we describe a novel petunia Cab gene which encodes a unique Cab precursor protein. This protein is a member of the smallest class of Cab precursor proteins for which no gene has previously been assigned in petunia or any other species. The features of this Cab precursor protein are that it is shorter by 2-3 amino acids than the formerly characterized Cab precursors, its transit peptide sequence is unrelated, and the mature polypeptide is significantly diverged at the functionally important N terminus from other petunia Cab proteins. Gene structure also discriminates this gene which is the only intron containing Cab gene in petunia genomic DNA.

Identification of chitinolytic bacteria isolated from shrimp pond sediment and characterization of their chitinase encoding gene

NASA Astrophysics Data System (ADS)

Triwijayani, A. U.; Puspita, I. D.; Murwantoko; Ustadi

2018-03-01

Chitinolytic bacteria are a group of bacteria owning enzymes that able to hydrolyze chitin. Previously, we isolated chitinolytic bacteria from shrimp pond sediment in Bantul, Yogyakarta, and obtained five isolates showing high chitinolytic index named as isolate PT1, PT2, PT5, PT6 and PB2. The aims of this study were to identify chitinolytic bacteria isolated from shrimp pond sediment and to characterize the chitinase encoding gene from each isolate. The molecular technique was performed by amplification of 16S rDNA, amplification of chitinase encoding gene and sequence analysis. Two chitinolytic bacteria of PT1 and PT2 were similar to Aeromonas bivalvium strain D15, PT5 to Pseudomonas stutzeri strain BD-2.2.1, PT6 to Serratia marcescens strain FZSF02 and PB2 to Streptomyces misionensis strain OsiRt-1. The comparison of chitinase encoding gene between three isolates with those in Gen Bank shows that PT1 had similar sequences with the chi1 gene in Aeromonas sp. 17m, PT2 with chi1 gene in A. caviae (CB101) and PT6 with chiB gene in S. Marcescens (BJL200).

Characterization of EhaJ, a New Autotransporter Protein from Enterohemorrhagic and Enteropathogenic Escherichia coli

PubMed Central

Easton, Donna M.; Totsika, Makrina; Allsopp, Luke P.; Phan, Minh-Duy; Idris, Adi; Wurpel, Daniël J.; Sherlock, Orla; Zhang, Bing; Venturini, Carola; Beatson, Scott A.; Mahony, Timothy J.; Cobbold, Rowland N.; Schembri, Mark A.

2011-01-01

Enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) are diarrheagenic pathotypes of E. coli that cause gastrointestinal disease with the potential for life-threatening sequelae. While certain EHEC and EPEC virulence mechanisms have been extensively studied, the factors that mediate host colonization remain to be properly defined. Previously, we identified four genes (ehaA, ehaB, ehaC, and ehaD) from the prototypic EHEC strain EDL933 that encode for proteins that belong to the autotransporter (AT) family. Here we have examined the prevalence of these genes, as well as several other AT-encoding genes, in a collection of EHEC and EPEC strains. We show that the complement of AT-encoding genes in EHEC and EPEC strains is variable, with some AT-encoding genes being highly prevalent. One previously uncharacterized AT-encoding gene, which we have termed ehaJ, was identified in 12/44 (27%) of EHEC and 2/20 (10%) of EPEC strains. The ehaJ gene lies immediately adjacent to a gene encoding a putative glycosyltransferase (referred to as egtA). Western blot analysis using an EhaJ-specific antibody indicated that EhaJ is glycosylated by EgtA. Expression of EhaJ in a recombinant E. coli strain, revealed EhaJ is located at the cell surface and in the presence of the egtA glycosyltransferase gene mediates strong biofilm formation in microtiter plate and flow cell assays. EhaJ also mediated adherence to a range of extracellular matrix proteins, however this occurred independent of glycosylation. We also demonstrate that EhaJ is expressed in a wild-type EPEC strain following in vitro growth. However, deletion of ehaJ did not significantly alter its adherence or biofilm properties. In summary, EhaJ is a new glycosylated AT protein from EPEC and EHEC. Further studies are required to elucidate the function of EhaJ in colonization and virulence. PMID:21687429

Targeted next-generation sequencing helps to decipher the genetic and phenotypic heterogeneity of hypertrophic cardiomyopathy

PubMed Central

Cecconi, Massimiliano; Parodi, Maria I.; Formisano, Francesco; Spirito, Paolo; Autore, Camillo; Musumeci, Maria B.; Favale, Stefano; Forleo, Cinzia; Rapezzi, Claudio; Biagini, Elena; Davì, Sabrina; Canepa, Elisabetta; Pennese, Loredana; Castagnetta, Mauro; Degiorgio, Dario; Coviello, Domenico A.

2016-01-01

Hypertrophic cardiomyopathy (HCM) is mainly associated with myosin, heavy chain 7 (MYH7) and myosin binding protein C, cardiac (MYBPC3) mutations. In order to better explain the clinical and genetic heterogeneity in HCM patients, in this study, we implemented a target-next generation sequencing (NGS) assay. An Ion AmpliSeq™ Custom Panel for the enrichment of 19 genes, of which 9 of these did not encode thick/intermediate and thin myofilament (TTm) proteins and, among them, 3 responsible of HCM phenocopy, was created. Ninety-two DNA samples were analyzed by the Ion Personal Genome Machine: 73 DNA samples (training set), previously genotyped in some of the genes by Sanger sequencing, were used to optimize the NGS strategy, whereas 19 DNA samples (discovery set) allowed the evaluation of NGS performance. In the training set, we identified 72 out of 73 expected mutations and 15 additional mutations: the molecular diagnosis was achieved in one patient with a previously wild-type status and the pre-excitation syndrome was explained in another. In the discovery set, we identified 20 mutations, 5 of which were in genes encoding non-TTm proteins, increasing the diagnostic yield by approximately 20%: a single mutation in genes encoding non-TTm proteins was identified in 2 out of 3 borderline HCM patients, whereas co-occuring mutations in genes encoding TTm and galactosidase alpha (GLA) altered proteins were characterized in a male with HCM and multiorgan dysfunction. Our combined targeted NGS-Sanger sequencing-based strategy allowed the molecular diagnosis of HCM with greater efficiency than using the conventional (Sanger) sequencing alone. Mutant alleles encoding non-TTm proteins may aid in the complete understanding of the genetic and phenotypic heterogeneity of HCM: co-occuring mutations of genes encoding TTm and non-TTm proteins could explain the wide variability of the HCM phenotype, whereas mutations in genes encoding only the non-TTm proteins are identifiable in patients with a milder HCM status. PMID:27600940

Characterization of two genes encoding the Mycobacterium tuberculosis ribonucleotide reductase small subunit.

PubMed Central

Yang, F; Curran, S C; Li, L S; Avarbock, D; Graf, J D; Chua, M M; Lu, G; Salem, J; Rubin, H

1997-01-01

Two nrdF genes, nrdF1 and nrdF2, encoding the small subunit (R2) of ribonucleotide reductase (RR) from Mycobacterium tuberculosis have 71% identity at the amino acid level and are both highly homologous with Salmonella typhimurium R2F. The calculated molecular masses of R2-1 and R2-2 are 36,588 (322 amino acids [aa]) and 36,957 (324 aa) Da, respectively. Western blot analysis of crude M. tuberculosis extracts indicates that both R2s are expressed in vivo. Recombinant R2-2 is enzymatically active when assayed with pure recombinant M. tuberculosis R1 subunit. Both ATP and dATP are activators for CDP reduction up to 2 and 1 mM, respectively. The gene encoding M. tuberculosis R2-1, nrdF1, is not linked to nrdF2, nor is either gene linked to the gene encoding the large subunit, M. tuberculosis nrdE. The gene encoding MTP64 was found downstream from nrdF1, and the gene encoding alcohol dehydrogenase was found downstream from nrdF2. A nrdA(Ts) strain of E. coli (E101) could be complemented by simultaneous transformation with M. tuberculosis nrdE and nrdF2. An M. tuberculosis nrdF2 variant in which the codon for the catalytically necessary tyrosine was replaced by the phenylalanine codon did not complement E101 when cotransformed with M. tuberculosis nrdE. Similarly, M. tuberculosis nrdF1 and nrdE did not complement E101. Activity of recombinant M. tuberculosis RR was inhibited by incubating the enzyme with a peptide corresponding to the 7 C-terminal amino acid residues of the R2-2 subunit. M. tuberculosis is a species in which a nrdEF system appears to encode the biologically active species of RR and also the only bacterial species identified so far in which class I RR subunits are not arranged on an operon. PMID:9335290

Cloning and sequence analysis of the LEU2 homologue gene from Pichia anomala.

PubMed

De la Rosa, J M; Pérez, J A; Gutiérrez, F; González, J M; Ruiz, T; Rodríguez, L

2001-11-01

The Pichia anomala LEU2 gene (PaLEU2) was isolated by complementation of a leu2 Saccharomyces cerevisiae mutant. The cloned gene also allowed growth of a Escherichia coli leuB mutant in leucine-lacking medium, indicating that it encodes a product able to complement the beta-isopropylmalate dehydrogenase deficiency of the mutants. The sequenced DNA fragment contains a complete ORF of 1092 bp, and the deduced polypeptide shares significant homologies with the products of the LEU2 genes from S. cerevisiae (84% identity) and other yeast species. A sequence resembling the GC-rich palindrome motif identified in the 5' region of S. cerevisiae LEU2 gene as the binding site for the transcription activating factor encoded by the LEU3 gene was found at the promoter region. In addition, upstream of the PaLEU2 the 3'-terminal half of a gene of the same orientation, encoding a homologue of the S. cerevisiae NFS1/SPL1 gene that encodes a mitochondrial cysteine desulphurase involved in both tRNA processing and mitochondrial metabolism, was found. The genomic organization of the PaNFS1-PaLEU2 gene pair is similar to that found in several other yeast species, including S. cerevisiae and Candida albicans, except that in some of them the LEU2 gene appears in the reverse orientation. Copyright 2001 John Wiley & Sons, Ltd.

A Different Microbiome Gene Repertoire in the Airways of Cystic Fibrosis Patients with Severe Lung Disease

PubMed Central

Bacci, Giovanni; Fiscarelli, Ersilia; Taccetti, Giovanni; Dolce, Daniela; Paganin, Patrizia; Morelli, Patrizia; Tuccio, Vanessa; De Alessandri, Alessandra; Lucidi, Vincenzina

2017-01-01

In recent years, next-generation sequencing (NGS) was employed to decipher the structure and composition of the microbiota of the airways in cystic fibrosis (CF) patients. However, little is still known about the overall gene functions harbored by the resident microbial populations and which specific genes are associated with various stages of CF lung disease. In the present study, we aimed to identify the microbial gene repertoire of CF microbiota in twelve patients with severe and normal/mild lung disease by performing sputum shotgun metagenome sequencing. The abundance of metabolic pathways encoded by microbes inhabiting CF airways was reconstructed from the metagenome. We identified a set of metabolic pathways differently distributed in patients with different pulmonary function; namely, pathways related to bacterial chemotaxis and flagellar assembly, as well as genes encoding efflux-mediated antibiotic resistance mechanisms and virulence-related genes. The results indicated that the microbiome of CF patients with low pulmonary function is enriched in virulence-related genes and in genes encoding efflux-mediated antibiotic resistance mechanisms. Overall, the microbiome of severely affected adults with CF seems to encode different mechanisms for the facilitation of microbial colonization and persistence in the lung, consistent with the characteristics of multidrug-resistant microbial communities that are commonly observed in patients with severe lung disease. PMID:28758937

Activation of Pathogenesis-related Genes by the Rhizobacterium, Bacillus sp. JS, Which Induces Systemic Resistance in Tobacco Plants.

PubMed

Kim, Ji-Seong; Lee, Jeongeun; Lee, Chan-Hui; Woo, Su Young; Kang, Hoduck; Seo, Sang-Gyu; Kim, Sun-Hyung

2015-06-01

Plant growth promoting rhizobacteria (PGPR) are known to confer disease resistance to plants. Bacillus sp. JS demonstrated antifungal activities against five fungal pathogens in in vitro assays. To verify whether the volatiles of Bacillus sp. JS confer disease resistance, tobacco leaves pre-treated with the volatiles were damaged by the fungal pathogen, Rhizoctonia solani and oomycete Phytophthora nicotianae. Pre-treated tobacco leaves had smaller lesion than the control plant leaves. In pathogenesis-related (PR) gene expression analysis, volatiles of Bacillus sp. JS caused the up-regulation of PR-2 encoding β-1,3-glucanase and acidic PR-3 encoding chitinase. Expression of acidic PR-4 encoding chitinase and acidic PR-9 encoding peroxidase increased gradually after exposure of the volatiles to Bacillus sp. JS. Basic PR-14 encoding lipid transfer protein was also increased. However, PR-1 genes, as markers of salicylic acid (SA) induced resistance, were not expressed. These results suggested that the volatiles of Bacillus sp. JS confer disease resistance against fungal and oomycete pathogens through PR genes expression.

Fusagene vectors: a novel strategy for the expression of multiple genes from a single cistron.

PubMed

Gäken, J; Jiang, J; Daniel, K; van Berkel, E; Hughes, C; Kuiper, M; Darling, D; Tavassoli, M; Galea-Lauri, J; Ford, K; Kemeny, M; Russell, S; Farzaneh, F

2000-12-01

Transduction of cells with multiple genes, allowing their stable and co-ordinated expression, is difficult with the available methodologies. A method has been developed for expression of multiple gene products, as fusion proteins, from a single cistron. The encoded proteins are post-synthetically cleaved and processed into each of their constituent proteins as individual, biologically active factors. Specifically, linkers encoding cleavage sites for the Golgi expressed endoprotease, furin, have been incorporated between in-frame cDNA sequences encoding different secreted or membrane bound proteins. With this strategy we have developed expression vectors encoding multiple proteins (IL-2 and B7.1, IL-4 and B7.1, IL-4 and IL-2, IL-12 p40 and p35, and IL-12 p40, p35 and IL-2 ). Transduction and analysis of over 100 individual clones, derived from murine and human tumour cell lines, demonstrate the efficient expression and biological activity of each of the encoded proteins. Fusagene vectors enable the co-ordinated expression of multiple gene products from a single, monocistronic, expression cassette.

Structure, Expression, Chromosomal Location and Product of the Gene Encoding Adh2 in Petunia

PubMed Central

Gregerson, R. G.; Cameron, L.; McLean, M.; Dennis, P.; Strommer, J.

1993-01-01

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes. PMID:8096485

Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence

PubMed Central

van der Ploeg, Jan R.

2005-01-01

In Streptococcus mutans, competence for genetic transformation and biofilm formation are dependent on the two-component signal transduction system ComDE together with the inducer peptide pheromone competence-stimulating peptide (CSP) (encoded by comC). Here, it is shown that the same system is also required for expression of the nlmAB genes, which encode a two-peptide nonlantibiotic bacteriocin. Expression from a transcriptional nlmAB′-lacZ fusion was highest at high cell density and was increased up to 60-fold following addition of CSP, but it was abolished when the comDE genes were interrupted. Two more genes, encoding another putative bacteriocin and a putative bacteriocin immunity protein, were also regulated by this system. The regions upstream of these genes and of two further putative bacteriocin-encoding genes and a gene encoding a putative bacteriocin immunity protein contained a conserved 9-bp repeat element just upstream of the transcription start, which suggests that expression of these genes is also dependent on the ComCDE regulatory system. Mutations in the repeat element of the nlmAB promoter region led to a decrease in CSP-dependent expression of nlmAB′-lacZ. In agreement with these results, a comDE mutant and mutants unable to synthesize or export CSP did not produce bacteriocins. It is speculated that, at high cell density, bacteriocin production is induced to liberate DNA from competing streptococci. PMID:15937160

Functional characterization of an apple (Malus x domestica) LysM domain receptor encoding gene for its role in defense response

USDA-ARS?s Scientific Manuscript database

Apple gene MDP0000136494 was identified as the only LysM containing protein encoding gene which was specifically up-regulated in P. ultimum infected apple root by a previous transcriptome analysis. In current study, the functional identity of MDP0000136494 was investigated using combined genomic, tr...

Cloning and sequencing the genes encoding goldfish and carp ependymin.

PubMed

Adams, D S; Shashoua, V E

1994-04-20

Ependymins (EPNs) are brain glycoproteins thought to function in optic nerve regeneration and long-term memory consolidation. To date, epn genes have been characterized in two orders of teleost fish. In this study, polymerase chain reactions (PCR) were used to amplify the complete 1.6-kb epn genes, gf-I and cc-I, from genomic DNA of Cypriniformes, goldfish and carp, respectively. Amplified bands were cloned and sequenced. Each gene consists of six exons and five introns. The exon portion of gf-I encodes a predicted 215-amino-acid (aa) protein previously characterized as GF-I, while cc-I encodes a predicted 215-aa protein 95% homologous to GF-I.

The complete mitochondrial genome sequence of Eimeria innocua (Eimeriidae, Coccidia, Apicomplexa).

PubMed

Hafeez, Mian Abdul; Vrba, Vladimir; Barta, John Robert

2016-07-01

The complete mitochondrial genome of Eimeria innocua KR strain (Eimeriidae, Coccidia, Apicomplexa) was sequenced. This coccidium infects turkeys (Meleagris gallopavo), Bobwhite quails (Colinus virginianus), and Grey partridges (Perdix perdix). Genome organization and gene contents were comparable with other Eimeria spp. infecting galliform birds. The circular-mapping mt genome of E. innocua is 6247 bp in length with three protein-coding genes (cox1, cox3, and cytb), 19 gene fragments encoding large subunit (LSU) rRNA and 14 gene fragments encoding small subunit (SSU) rRNA. Like other Apicomplexa, no tRNA was encoded. The mitochondrial genome of E. innocua confirms its close phylogenetic affinities to Eimeria dispersa.

Genes encoding novel lipid transporters and their use to increase oil production in vegetative tissues of plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Changcheng; Fan, Jilian; Yan, Chengshi

The present invention discloses a novel gene encoding a transporter protein trigalactosyldiacylglycerol-5 (TGD5), mutations thereof and their use to enhance TAG production and retention in plant vegetative tissue.

Isolation and characterization of polygalacturonase genes (pecA and pecB) from Aspergillus flavus.

PubMed Central

Whitehead, M P; Shieh, M T; Cleveland, T E; Cary, J W; Dean, R A

1995-01-01

Two genes, pecA and pecB, encoding endopolyglacturonases were cloned from a highly aggressive strain of Aspergillus flavus. The pecA gene consisted of 1,228 bp encoding a protein of 363 amino acids with a predicted molecular mass of 37.6 kDa, interrupted by two introns of 58 and 81 bp in length. Accumulation of pecA mRNA in both pectin- or glucose-grown mycelia in the highly aggressive strain matched the activity profile of a pectinase previously identified as P2c. Transformants of a weakly aggressive strain containing a functional copy of the pecA gene produced P2c in vitro, confirming that pecA encodes P2c. The coding region of pecB was determined to be 1,217 bp in length interrupted by two introns of 65 and 54 bp in length. The predicted protein of 366 amino acids had an estimated molecular mass of 38 kDa. Transcripts of this gene accumulated in mycelia grown in medium containing pectin alone, never in mycelia grown in glucose-containing medium, for both highly and weakly aggressive strains. Thus, pecB encodes the activity previously identified as P1 or P3. pecA and pecB share a high degree of sequence identity with polygalacturonase genes from Aspergillus parasiticus and Aspergillus oryzae, further establishing the close relationships between members of the A. flavus group. Conservation of intron positions in these genes also indicates that they share a common ancestor with genes encoding endopolyglacturonases of Aspergillus niger. PMID:7574642

Draft Genome Sequence of Ezakiella peruensis Strain M6.X2, a Human Gut Gram-Positive Anaerobic Coccus.

PubMed

Diop, Awa; Diop, Khoudia; Tomei, Enora; Raoult, Didier; Fenollar, Florence; Fournier, Pierre-Edouard

2018-03-01

We report here the draft genome sequence of Ezakiella peruensis strain M6.X2 T The draft genome is 1,672,788 bp long and harbors 1,589 predicted protein-encoding genes, including 26 antibiotic resistance genes with 1 gene encoding vancomycin resistance. The genome also exhibits 1 clustered regularly interspaced short palindromic repeat region and 333 genes acquired by horizontal gene transfer. Copyright © 2018 Diop et al.

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

PubMed Central

Ho, Joel R.; Chapeaublanc, Elodie; Kirkwood, Lisa; Nicolle, Remy; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Southgate, Jennifer; Radvanyi, François; Goud, Bruno

2012-01-01

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer. PMID:22724020

Differences in virulence genes and genome patterns of mastitis-associated Staphylococcus aureus among goat, cow, and human isolates in Taiwan.

PubMed

Chu, Chishih; Wei, Yajiun; Chuang, Shih-Te; Yu, Changyou; Changchien, Chih-Hsuan; Su, Yaochi

2013-03-01

A total of 117 mastitis-associated Staphylococcus aureus isolates from cow, goat, and human patients were analyzed for differences in antibiotic susceptibility, virulence genes, and genotypes using accessory gene regulator (agr) typing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Multidrug-resistant (MDR) S. aureus were commonly found in all sources, though they were predominantly found in human and goat isolates. Almost 70% of the isolates were resistant to ampicillin and penicillin. Host-associated virulence genes were identified as follows: tst, a gene encoding toxic shock syndrome toxin, was found in goat isolates; lukED and lukM, genes encoding leukocidin, found in cow isolates; lukPV, a gene encoding leukocidin, found in human isolates; and eta, a gene encoding for exfoliative toxin, found in both human and cow isolates. All four types of hemolysin, α, β, γ, and δ, were identified in human isolates, three types (α, γ, and δ), were identified in cow isolates, and two types (α and δ) were identified in goat isolates. Agr-typing determined agr1 to be the main subtype in human and cow isolates. PFGE and MLST analysis revealed the presence of diverse genotypes among the three sources. In conclusion, mastitis-associated, genetically diverse strains of MDR S. aureus differed in virulence genes among human, cow, and goat isolates.

Functions of the Magnaporthe oryzae Flb3p and Flb4p transcription factors in the regulation of conidiation.

PubMed

Matheis, S; Yemelin, A; Scheps, D; Andresen, K; Jacob, S; Thines, E; Foster, A J

2017-03-01

The Magnaporthe oryzae genes FLB3 and FLB4, orthologues of the Aspergillus nidulans regulators of conidiation FlbC and FlbD, were inactivated. These genes encode C2H2 zinc finger and Myb-like transcription factors, respectively, in A. nidulans. Analysis of the resultant mutants demonstrated that FLB4 is essential for spore formation and that strains lacking this gene are fluffy in their colony morphology due to an inability to complete conidiophore formation. Meanwhile, FLB3 is required for normal levels of aerial mycelium formation. We identified genes dependent on both transcription factors using microarray analysis. This analysis revealed that the transcription of several genes encoding proteins implicated in sporulation in Magnaporthe oryzae and other filamentous fungi are affected by FLB3 or FLB4 inactivation. Furthermore, the microarray analysis indicates that Flb3p may effectively reprogramme the cell metabolically by repressing transcription of genes encoding biosynthetic enzymes and inducing transcription of genes encoding catabolic enzymes. Additionally, qRT-PCR was employed and showed that FLB3 and FLB4 transcripts are enriched in synchronously sporulating cultures, as were the transcripts of other genes that are necessary for normal conidiation, consistent with a role for their gene products in this process. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Ornithorhynchus anatinus (platypus) links the evolution of immunoglobulin genes in eutherian mammals and nonmammalian tetrapods.

PubMed

Zhao, Yaofeng; Cui, Huiting; Whittington, Camilla M; Wei, Zhiguo; Zhang, Xiaofeng; Zhang, Ziding; Yu, Li; Ren, Liming; Hu, Xiaoxiang; Zhang, Yaping; Hellman, Lars; Belov, Katherine; Li, Ning; Hammarström, Lennart

2009-09-01

The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-omicron-gamma2-gamma1-alpha1-epsilon-alpha2 order, spanning a total of approximately 200 kb DNA, encoding six distinct isotypes. The omicron (omicron for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to upsilon (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.

The bglA Gene of Aspergillus kawachii Encodes Both Extracellular and Cell Wall-Bound β-Glucosidases

PubMed Central

Iwashita, Kazuhiro; Nagahara, Tatsuya; Kimura, Hitoshi; Takano, Makoto; Shimoi, Hitoshi; Ito, Kiyoshi

1999-01-01

We cloned the genomic DNA and cDNA of bglA, which encodes β-glucosidase in Aspergillus kawachii, based on a partial amino acid sequence of purified cell wall-bound β-glucosidase CB-1. The nucleotide sequence of the cloned bglA gene revealed a 2,933-bp open reading frame with six introns that encodes an 860-amino-acid protein. Based on the deduced amino acid sequence, we concluded that the bglA gene encodes cell wall-bound β-glucosidase CB-1. The amino acid sequence exhibited high levels of homology with the amino acid sequences of fungal β-glucosidases classified in subfamily B. We expressed the bglA cDNA in Saccharomyces cerevisiae and detected the recombinant β-glucosidase in the periplasm fraction of the recombinant yeast. A. kawachii can produce two extracellular β-glucosidases (EX-1 and EX-2) in addition to the cell wall-bound β-glucosidase. A. kawachii in which the bglA gene was disrupted produced none of the three β-glucosidases, as determined by enzyme assays and a Western blot analysis. Thus, we concluded that the bglA gene encodes both extracellular and cell wall-bound β-glucosidases in A. kawachii. PMID:10584016

Microarray analysis of toxicogenomic effects of Ortho-phenylphenol in Staphylococcus aureus

PubMed Central

Jang, Hyeung-Jin; Nde, Chantal; Toghrol, Freshteh; Bentley, William E

2008-01-01

Background Staphylococcus aureus (S. aureus), is responsible for many infectious diseases, ranging from benign skin infections to life-threatening endocarditis and toxic shock syndrome. Ortho-phenylphenol (OPP) is an antimicrobial agent and an active ingredient of EPA-registered disinfectants with wide human exposure in various agricultural, hospital and veterinary disinfectant products. Despite many uses, an understanding of a cellular response to OPP and it's mechanism of action, targeted genes, and the connectivity between targeted genes and the rest of cell metabolism remains obscure. Results Herein, we performed a genome-wide transcriptome analysis of the cellular responses of S. aureus when exposed to 0.82 mM of OPP for 20 and 60 min. Our data indicated that OPP downregulated the biosynthesis of many amino acids, which are required for protein synthesis. In particular, the genes encoding the enzymes of the diaminopimelate (DAP) pathway which results in lysine biosynthesis were significantly downregualted. Intriguingly, we revealed that the transcription of genes encoding ribosomal proteins was upregulated by OPP and at the same time, the genes encoding iron acquisition and transport were downregulated. The genes encoding virulence factors were upregulated and genes encoding phospholipids were downregulated upon 20 min exposure to OPP. Conclusion By using microarray analysis that enables us to simultaneously and globally examine the complete transcriptome during cellular responses, we have revealed novel information regarding the mode of action of OPP on Staphylococcus: OPP inhibits anabolism of many amino acids and highly downregulates the genes that encode the enzymes involved in the DAP pathway. Lysine and DAP are essential for building up the peptidoglycan cell wall. It was concluded that the mode of action of OPP is similar to the mechanism of action of some antibiotics. The discovery of this phenomenon provides useful information that will benefit further antimicrobial research on S. aureus. PMID:18793396

Degradation of triglycerides by a pseudomonad isolated from milk: molecular analysis of a lipase-encoding gene and its expression in Escherichia coli.

PubMed Central

Johnson, L A; Beacham, I R; MacRae, I C; Free, M L

1992-01-01

Psychrotrophic lipolytic bacteria represent a significant problem in the storage of refrigerated dairy products. A lipase-encoding gene has been cloned and characterized from a highly lipolytic strain of Pseudomonas. The nucleotide sequence of the gene predicts a polypeptide of M(r) 49,905, which was identified when the gene was expressed in Escherichia coli. Images PMID:1622251

Genes encoding giant danio and golden shiner ependymin.

PubMed

Adams, D S; Kiyokawa, M; Getman, M E; Shashoua, V E

1996-03-01

Ependymin (EPN) is a brain glycoprotein that functions as a neurotrophic factor in optic nerve regeneration and long-term memory consolidation in goldfish. To date, true epn genes have been characterized in one order of teleost fish, Cypriniformes. In the study presented here, polymerase chain reactions were used to analyze the complete epn genes, gd (1480 bp), and sh (2071 bp), from Cypriniformes giant danio and shiner, respectively. Southern hybridizations demonstrated the existence of one copy of each gene per corresponding haploid genome. Each gene was found to contain six exons and five introns. Gene gd encodes a predicted 218-amino acid (aa) protein GD 93 percent conserved to goldfish EPN, while sh encodes a predicted 214-aa protein SH 91 percent homologous to goldfish. Evidence is presented classifying proteins previously termed "EPNs" into two major categories: true EPNs and non-EPN cerebrospinal fluid glycoproteins. Proteins GD and SH contain all the hallmark, features of true EPNs.

Ti plasmid-encoded genes responsible for catabolism of the crown gall opine mannopine by Agrobacterium tumefaciens are homologs of the T-region genes responsible for synthesis of this opine by the plant tumor.

PubMed

Kim, K S; Farrand, S K

1996-06-01

Agrobacterium tumefaciens NT1 harboring pSaB4, which contains the 14-kb BamHI fragment 4 from the octopine/mannityl opine-type Ti plasmid pTi15955, grew well with agropine (AGR) but slowly with mannopine (MOP) as the sole carbon source. When a second plasmid encoding a dedicated transport system for MOP was introduced, these cells grew well with both AGR and MOP. Transposon insertion mutagenesis and subcloning identified a 5.7-kb region of BamHI fragment 4 that encodes functions required for the degradation of MOP. DNA sequence analysis revealed seven putative genes in this region: mocD (moc for mannityl opine catabolism) and mocE, oriented from right to left, and mocRCBAS, oriented from left to right. Significant identities exist at the nucleotide and derived amino acid sequence levels between these moc genes and the mas genes that are responsible for opine biosynthesis in crown gall tumors. MocD is a homolog of Mas2, the anabolic conjugase encoded by mas2'. MocE and MocC are related to the amino half and the carboxyl half, respectively, of Mas1 (MOP reductase), the second enzyme for MOP biosynthesis. These results indicate that the moc and mas genes evolved from a common origin. MocR and MocS are related to each other and to a putative repressor for the AGR degradation system encoded by the rhizogenic plasmid pRiA4. MocB and MocA are homologs of 6-phosphogluconate dehydratase and glucose-6-phosphate dehydrogenase, respectively. Mutations in mocD and mocE, but not mocC, are suppressed by functions encoded by the chromosome or the 450-kb megaplasmid present in many Agrobacterium isolates. We propose that moc genes derived from genes located elsewhere in the bacterial genome and that the tumor-expressed mas genes evolved from the bacterial moc genes.

Ti plasmid-encoded genes responsible for catabolism of the crown gall opine mannopine by Agrobacterium tumefaciens are homologs of the T-region genes responsible for synthesis of this opine by the plant tumor.

PubMed Central

Kim, K S; Farrand, S K

1996-01-01

Agrobacterium tumefaciens NT1 harboring pSaB4, which contains the 14-kb BamHI fragment 4 from the octopine/mannityl opine-type Ti plasmid pTi15955, grew well with agropine (AGR) but slowly with mannopine (MOP) as the sole carbon source. When a second plasmid encoding a dedicated transport system for MOP was introduced, these cells grew well with both AGR and MOP. Transposon insertion mutagenesis and subcloning identified a 5.7-kb region of BamHI fragment 4 that encodes functions required for the degradation of MOP. DNA sequence analysis revealed seven putative genes in this region: mocD (moc for mannityl opine catabolism) and mocE, oriented from right to left, and mocRCBAS, oriented from left to right. Significant identities exist at the nucleotide and derived amino acid sequence levels between these moc genes and the mas genes that are responsible for opine biosynthesis in crown gall tumors. MocD is a homolog of Mas2, the anabolic conjugase encoded by mas2'. MocE and MocC are related to the amino half and the carboxyl half, respectively, of Mas1 (MOP reductase), the second enzyme for MOP biosynthesis. These results indicate that the moc and mas genes evolved from a common origin. MocR and MocS are related to each other and to a putative repressor for the AGR degradation system encoded by the rhizogenic plasmid pRiA4. MocB and MocA are homologs of 6-phosphogluconate dehydratase and glucose-6-phosphate dehydrogenase, respectively. Mutations in mocD and mocE, but not mocC, are suppressed by functions encoded by the chromosome or the 450-kb megaplasmid present in many Agrobacterium isolates. We propose that moc genes derived from genes located elsewhere in the bacterial genome and that the tumor-expressed mas genes evolved from the bacterial moc genes. PMID:8655509

Comparative mapping of human alphoid centromeric sequences in great apes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Archidiacono, N.; Antonacci, R.; Marzella, R.

1994-09-01

Metaphase spreads from chimpanzees (Pan troglodytes and Pan paniscus) and gorilla (Gorilla gorilla) have been hybridized in situ with 27 alphoid DNA probes specific for the centromere of human chromosomes, to investigate the evolutionary relationship between centromeric regions of human and great apes. The results showed that most human probes do not recognize their corresponding homologs in great apes. Chromosome X is the only chromosome showing localization consistency in all the four species. Each suprachromosomal family (SCF) exhibits a distinct and peculiar evolutionary history. SCF1 (chromosomes 1, 3, 6, 7, 19, 12, 16) is very heterogeneous: some probes gave intensemore » signals, but always on non-homologous chromosomes; others did not produce any hybridization signal. All probes localized on SCF2 (chromosomes 2, 4, 8, 9, 13, 14, 15, 18, 20, 21, and 22) recognize a single chromosome: chromosome 11 (phylogenetic IX) in PTR and PPA; chromosome 4 (phylogenetic V) in GGO. SCF3 subsets (chromosomes 1, 11, 17, X) are substantially conserved in PTR and PPA, but not in GGO, with the exception restricted to chromosome X. No signals have been detected on PPA chromosomes I, III, IV, V, VI and in PTR chromosomes V, suggesting that the centromeric region of some chromsomes have probably lost homology with human alphoid sequences.« less

IRaPPA: information retrieval based integration of biophysical models for protein assembly selection.

PubMed

Moal, Iain H; Barradas-Bautista, Didier; Jiménez-García, Brian; Torchala, Mieczyslaw; van der Velde, Arjan; Vreven, Thom; Weng, Zhiping; Bates, Paul A; Fernández-Recio, Juan

2017-06-15

In order to function, proteins frequently bind to one another and form 3D assemblies. Knowledge of the atomic details of these structures helps our understanding of how proteins work together, how mutations can lead to disease, and facilitates the designing of drugs which prevent or mimic the interaction. Atomic modeling of protein-protein interactions requires the selection of near-native structures from a set of docked poses based on their calculable properties. By considering this as an information retrieval problem, we have adapted methods developed for Internet search ranking and electoral voting into IRaPPA, a pipeline integrating biophysical properties. The approach enhances the identification of near-native structures when applied to four docking methods, resulting in a near-native appearing in the top 10 solutions for up to 50% of complexes benchmarked, and up to 70% in the top 100. IRaPPA has been implemented in the SwarmDock server ( http://bmm.crick.ac.uk/∼SwarmDock/ ), pyDock server ( http://life.bsc.es/pid/pydockrescoring/ ) and ZDOCK server ( http://zdock.umassmed.edu/ ), with code available on request. moal@ebi.ac.uk. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2002-11-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.

Behavioral and language variants of frontotemporal dementia: a review of key symptoms.

PubMed

Laforce, Robert

2013-12-01

While recent advances in the development of neuroimaging and molecular biomarkers for studying neurodegenerative conditions have revolutionized the field, dementia remains a clinical diagnosis. No component of the diagnostic process is more crucial than obtaining a good history. Getting to know the first manifestations of the disease, tracking their evolution and functional impact, combined with a targeted neurological examination, further guides differential diagnosis. This paper summarizes the key symptoms of the behavioral and language variants of frontotemporal dementia. The behavioral variant of frontotemporal dementia (bvFTD) is characterized by severe changes in behavior and personality such as disinhibition, apathy, loss of empathy, or stereotypic behavior, leading to a loss of social competence. Executive functions are impaired, while memory and visuospatial skills are relatively better preserved. By contrast, the language variants or primary progressive aphasias (PPAs) are marked by prominent language disturbances that can be subclassified into a non-fluent/agrammatic variant (naPPA), a semantic variant (svPPA), and a logopenic variant (lvPPA). Although combined characterization of clinical, imaging, biological and genetic biomarkers is essential to establish a detailed diagnosis of such heterogeneous conditions, the author emphasizes the importance of accurate recognition of key symptoms that can lead to better identification of underlying neuropathology and appropriate treatment approaches.

Activation of PKC isoform beta(I) at the blood-brain barrier rapidly decreases P-glycoprotein activity and enhances drug delivery to the brain.

PubMed

Rigor, Robert R; Hawkins, Brian T; Miller, David S

2010-07-01

P-glycoprotein is an ATP (adenosine triphosphate)-driven drug efflux transporter that is highly expressed at the blood-brain barrier (BBB) and is a major obstacle to the pharmacotherapy of central nervous system diseases, including brain tumors, neuro-AIDS, and epilepsy. Previous studies have shown that P-glycoprotein transport activity in rat brain capillaries is rapidly reduced by the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha) acting through protein kinase C (PKC)-dependent signaling. In this study, we used isolated rat brain capillaries to show that the TNF-alpha-induced reduction of P-glycoprotein activity was prevented by a PKCbeta(I/II) inhibitor, LY333531, and mimicked by a PKCbeta(I/II) activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA). Western blotting of brain capillary extracts with phospho-specific antibodies showed that dPPA activated PKCbeta(I), but not PKCbeta(II). Moreover, in intact rats, intracarotid infusion of dPPA potently increased brain accumulation of the P-glycoprotein substrate, [(3)H]-verapamil without compromising tight junction integrity. Thus, PKCbeta(I) activation selectively reduced P-glycoprotein activity both in vitro and in vivo. Targeting PKCbeta(I) at the BBB may prove to be an effective strategy for enhancing the delivery of small molecule therapeutics to the brain.

Advanced Poincaré plot analysis differentiates between hypertensive pregnancy disorders.

PubMed

Seeck, A; Baumert, M; Fischer, C; Khandoker, A; Faber, R; Voss, A

2011-10-01

Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can result in severe complications for the mother and the foetus of which pre-eclampsia (PE) has the worst perinatal outcome. Several studies suggested that the autonomic nervous system plays an important role in the process of developing hypertensive pregnancy disorders, especially PE. The aim of this retrospective study was to investigate whether women with PE could be differentiated from women with various other hypertensive pregnancy disorders, by employing an enhanced Poincaré plot analysis (PPA), the segmented Poincaré plot analysis (SPPA), to their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension) were included. The SPPA as well as the traditional PPA found significant differences between PE and other hypertensive disorders of diastolic blood pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed significant differences (p < 0.001) also of the systolic blood pressure. Further on, linear discrimination analysis demonstrated that indices derived from SPPA are more suitable for differentiation between chronic and gestational hypertension and PE than those from traditional PPA (area under the ROC curve 0.85 versus 0.69). Therefore this procedure could contribute to the differential diagnosis of hypertensive pregnancy disorders.

How affective information from faces and scenes interacts in the brain

PubMed Central

Vandenbulcke, Mathieu; Sinke, Charlotte B. A.; Goebel, Rainer; de Gelder, Beatrice

2014-01-01

Facial expression perception can be influenced by the natural visual context in which the face is perceived. We performed an fMRI experiment presenting participants with fearful or neutral faces against threatening or neutral background scenes. Triangles and scrambled scenes served as control stimuli. The results showed that the valence of the background influences face selective activity in the right anterior parahippocampal place area (PPA) and subgenual anterior cingulate cortex (sgACC) with higher activation for neutral backgrounds compared to threatening backgrounds (controlled for isolated background effects) and that this effect correlated with trait empathy in the sgACC. In addition, the left fusiform gyrus (FG) responds to the affective congruence between face and background scene. The results show that valence of the background modulates face processing and support the hypothesis that empathic processing in sgACC is inhibited when affective information is present in the background. In addition, the findings reveal a pattern of complex scene perception showing a gradient of functional specialization along the posterior–anterior axis: from sensitivity to the affective content of scenes (extrastriate body area: EBA and posterior PPA), over scene emotion–face emotion interaction (left FG) via category–scene interaction (anterior PPA) to scene–category–personality interaction (sgACC). PMID:23956081

Two Distinct Scene-Processing Networks Connecting Vision and Memory.

PubMed

Baldassano, Christopher; Esteva, Andre; Fei-Fei, Li; Beck, Diane M

2016-01-01

A number of regions in the human brain are known to be involved in processing natural scenes, but the field has lacked a unifying framework for understanding how these different regions are organized and interact. We provide evidence from functional connectivity and meta-analyses for a new organizational principle, in which scene processing relies upon two distinct networks that split the classically defined parahippocampal place area (PPA). The first network of strongly connected regions consists of the occipital place area/transverse occipital sulcus and posterior PPA, which contain retinotopic maps and are not strongly coupled to the hippocampus at rest. The second network consists of the caudal inferior parietal lobule, retrosplenial complex, and anterior PPA, which connect to the hippocampus (especially anterior hippocampus), and are implicated in both visual and nonvisual tasks, including episodic memory and navigation. We propose that these two distinct networks capture the primary functional division among scene-processing regions, between those that process visual features from the current view of a scene and those that connect information from a current scene view with a much broader temporal and spatial context. This new framework for understanding the neural substrates of scene-processing bridges results from many lines of research, and makes specific functional predictions.

A Life Participation Approach to Primary Progressive Aphasia Intervention.

PubMed

Rogalski, Emily J; Khayum, Becky

2018-07-01

Primary progressive aphasia (PPA) is a clinical neurodegenerative dementia syndrome characterized by deficits in spoken and written word retrieval, word usage, and/or word comprehension. Currently, there are no effective treatments to reverse or halt the underlying disease process; however, speech-language therapy may be helpful. The Communication Bridge Care Model was developed to address the unique communication and quality of life needs of individuals living with PPA. The core elements include person-centered care with dyadic instruction for disease education, and counseling, along with tailored levels of impairment- and compensatory-based communication strategy training. Our multicomponent approach incorporates guidance from the Life Participation Approach for Aphasia, including client-directed assessment and interventions that aim to maximize functional communication and participation in desired life activities. The direct and indirect use of technology is integrated into our tailored model of care to facilitate achievement of the client's functional goals. Here, we describe how to practically apply the Communication Bridge Care Model across treatment settings, including case examples from the Communication Bridge research study. This approach to care provides an opportunity to maximize communication effectiveness and quality of life for individuals living with PPA throughout the course of disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Systematic Identification and Characterization of Novel Human Skin-Associated Genes Encoding Membrane and Secreted Proteins

PubMed Central

Buhren, Bettina Alexandra; Martinez, Cynthia; Schrumpf, Holger; Gasis, Marcia; Grether-Beck, Susanne; Krutmann, Jean

2013-01-01

Through bioinformatics analyses of a human gene expression database representing 105 different tissues and cell types, we identified 687 skin-associated genes that are selectively and highly expressed in human skin. Over 50 of these represent uncharacterized genes not previously associated with skin and include a subset that encode novel secreted and plasma membrane proteins. The high levels of skin-associated expression for eight of these novel therapeutic target genes were confirmed by semi-quantitative real time PCR, western blot and immunohistochemical analyses of normal skin and skin-derived cell lines. Four of these are expressed specifically by epidermal keratinocytes; two that encode G-protein-coupled receptors (GPR87 and GPR115), and two that encode secreted proteins (WFDC5 and SERPINB7). Further analyses using cytokine-activated and terminally differentiated human primary keratinocytes or a panel of common inflammatory, autoimmune or malignant skin diseases revealed distinct patterns of regulation as well as disease associations that point to important roles in cutaneous homeostasis and disease. Some of these novel uncharacterized skin genes may represent potential biomarkers or drug targets for the development of future diagnostics or therapeutics. PMID:23840300

Transgenic tomatoes express an antigenic polypeptide containing epitopes of the diphtheria, pertussis and tetanus exotoxins, encoded by a synthetic gene.

PubMed

Soria-Guerra, Ruth Elena; Rosales-Mendoza, Sergio; Márquez-Mercado, Crisóforo; López-Revilla, Rubén; Castillo-Collazo, Rosalba; Alpuche-Solís, Angel Gabriel

2007-07-01

A current priority of vaccinology is the development of multicomponent vaccines that protect against several pathogens. The diphtheria-pertussis-tetanus (DPT) vaccine prevents the symptoms of three serious and often fatal diseases due to the exotoxins produced by Corynebacterium diphteriae, Bordetella pertussis and Clostridium tetani. We are attempting to develop an edible DPT multicomponent vaccine in plants, based on the fusion of protective exotoxin epitopes encoded by synthetic genes. By means of Agrobacterium mediated transformation we generated transgenic tomatoes with a plant-optimised synthetic gene encoding a novel polypeptide containing two adjuvant and six DPT immunoprotective exotoxin epitopes joined by peptide linkers. In transformed tomato plants, integration of the synthetic DPT (sDPT) gene detected by PCR was confirmed by Southern blot, and specific transcripts of the expected molecular size were detected by RT-PCR. Expression of the putative polypeptide encoded by the sDPT gene was detected by immunoassay with specific antibodies to the diphtheria, pertussis and tetanus exotoxins. The sDPT gene is therefore integrated, transcribed and translated as the expected recombinant sDPT multiepitope polypeptide in transgenic tomatoes that constitute a potential edible vaccine.

Ubiquitin--conserved protein or selfish gene?

PubMed

Catic, André; Ploegh, Hidde L

2005-11-01

The posttranslational modifier ubiquitin is encoded by a multigene family containing three primary members, which yield the precursor protein polyubiquitin and two ubiquitin moieties, Ub(L40) and Ub(S27), that are fused to the ribosomal proteins L40 and S27, respectively. The gene encoding polyubiquitin is highly conserved and, until now, those encoding Ub(L40) and Ub(S27) have been generally considered to be equally invariant. The evolution of the ribosomal ubiquitin moieties is, however, proving to be more dynamic. It seems that the genes encoding Ub(L40) and Ub(S27) are actively maintained by homologous recombination with the invariant polyubiquitin locus. Failure to recombine leads to deterioration of the sequence of the ribosomal ubiquitin moieties in several phyla, although this deterioration is evidently constrained by the structural requirements of the ubiquitin fold. Only a few amino acids in ubiquitin are vital for its function, and we propose that conservation of all three ubiquitin genes is driven not only by functional properties of the ubiquitin protein, but also by the propensity of the polyubiquitin locus to act as a 'selfish gene'.

Alternative intronic promoters in development and disease.

PubMed

Vacik, Tomas; Raska, Ivan

2017-05-01

Approximately 20,000 mammalian genes are estimated to encode between 250 thousand and 1 million different proteins. This enormous diversity of the mammalian proteome is caused by the ability of a single-gene locus to encode multiple protein isoforms. Protein isoforms encoded by one gene locus can be functionally distinct, and they can even have antagonistic functions. One of the mechanisms involved in creating this proteome complexity is alternative promoter usage. Alternative intronic promoters are located downstream from their canonical counterparts and drive the expression of alternative RNA isoforms that lack upstream exons. These upstream exons can encode some important functional domains, and proteins encoded by alternative mRNA isoforms can be thus functionally distinct from the full-length protein encoded by canonical mRNA isoforms. Since any misbalance of functionally distinct protein isoforms is likely to have detrimental consequences for the cell and the whole organism, their expression must be precisely regulated. Misregulation of alternative intronic promoters is frequently associated with various developmental defects and diseases including cancer, and it is becoming increasingly clear that this phenomenon deserves more attention.

Amplification of Chromosome 1q Genes Encoding the Phosphoinositide Signalling Enzymes PI4KB, AKT3, PIP5K1A and PI3KC2B in Breast Cancer

PubMed Central

Waugh, Mark G.

2014-01-01

Little is known about the possible oncogenic roles of genes encoding for the phosphatidylinositol 4-kinases, a family of enzymes that regulate an early step in phosphoinositide signalling. To address this issue, the mutational status of all four human phosphatidylinositol 4-kinases genes was analyzed across 852 breast cancer samples using the COSMIC data resource. Point mutations in the phosphatidylinositol 4-kinase genes were uncommon and appeared in less than 1% of the patient samples however, 62% of the tumours had increases in gene copy number for PI4KB which encodes the phosphatidylinositol 4-kinase IIIbeta isozyme. Extending this analysis to subsequent enzymes in the phosphoinositide signalling cascades revealed that the only PIP5K1A, PI3KC2B and AKT3 genes exhibited similar patterns of gene copy number variation. By comparison, gene copy number increases for established oncogenes such as EGFR and HER2/Neu were only evident in 20% of the samples. The PI4KB, PIP5K1A, PI3KC2B and AKT3 genes are related in that they all localize to chromosome 1q which is often structurally and numerically abnormal in breast cancer. These results demonstrate that a gene quartet encoding a potential phosphoinositide signalling pathway is amplified in a subset of breast cancers. PMID:25368680

Bioinformatics analysis and detection of gelatinase encoded gene in Lysinibacillussphaericus

NASA Astrophysics Data System (ADS)

Repin, Rul Aisyah Mat; Mutalib, Sahilah Abdul; Shahimi, Safiyyah; Khalid, Rozida Mohd.; Ayob, Mohd. Khan; Bakar, Mohd. Faizal Abu; Isa, Mohd Noor Mat

2016-11-01

In this study, we performed bioinformatics analysis toward genome sequence of Lysinibacillussphaericus (L. sphaericus) to determine gene encoded for gelatinase. L. sphaericus was isolated from soil and gelatinase species-specific bacterium to porcine and bovine gelatin. This bacterium offers the possibility of enzymes production which is specific to both species of meat, respectively. The main focus of this research is to identify the gelatinase encoded gene within the bacteria of L. Sphaericus using bioinformatics analysis of partially sequence genome. From the research study, three candidate gene were identified which was, gelatinase candidate gene 1 (P1), NODE_71_length_93919_cov_158.931839_21 which containing 1563 base pair (bp) in size with 520 amino acids sequence; Secondly, gelatinase candidate gene 2 (P2), NODE_23_length_52851_cov_190.061386_17 which containing 1776 bp in size with 591 amino acids sequence; and Thirdly, gelatinase candidate gene 3 (P3), NODE_106_length_32943_cov_169.147919_8 containing 1701 bp in size with 566 amino acids sequence. Three pairs of oligonucleotide primers were designed and namely as, F1, R1, F2, R2, F3 and R3 were targeted short sequences of cDNA by PCR. The amplicons were reliably results in 1563 bp in size for candidate gene P1 and 1701 bp in size for candidate gene P3. Therefore, the results of bioinformatics analysis of L. Sphaericus resulting in gene encoded gelatinase were identified.

Role and Regulation of the Flp/Tad Pilus in the Virulence of Pectobacterium atrosepticum SCRI1043 and Pectobacterium wasabiae SCC3193

PubMed Central

Nykyri, Johanna; Mattinen, Laura; Niemi, Outi; Adhikari, Satish; Kõiv, Viia; Somervuo, Panu; Fang, Xin; Auvinen, Petri; Mäe, Andres; Palva, E. Tapio; Pirhonen, Minna

2013-01-01

In this study, we characterized a putative Flp/Tad pilus-encoding gene cluster, and we examined its regulation at the transcriptional level and its role in the virulence of potato pathogenic enterobacteria of the genus Pectobacterium. The Flp/Tad pilus-encoding gene clusters in Pectobacterium atrosepticum, Pectobacterium wasabiae and Pectobacterium aroidearum were compared to previously characterized flp/tad gene clusters, including that of the well-studied Flp/Tad pilus model organism Aggregatibacter actinomycetemcomitans, in which this pilus is a major virulence determinant. Comparative analyses revealed substantial protein sequence similarity and open reading frame synteny between the previously characterized flp/tad gene clusters and the cluster in Pectobacterium, suggesting that the predicted flp/tad gene cluster in Pectobacterium encodes a Flp/Tad pilus-like structure. We detected genes for a novel two-component system adjacent to the flp/tad gene cluster in Pectobacterium, and mutant analysis demonstrated that this system has a positive effect on the transcription of selected Flp/Tad pilus biogenesis genes, suggesting that this response regulator regulate the flp/tad gene cluster. Mutagenesis of either the predicted regulator gene or selected Flp/Tad pilus biogenesis genes had a significant impact on the maceration ability of the bacterial strains in potato tubers, indicating that the Flp/Tad pilus-encoding gene cluster represents a novel virulence determinant in Pectobacterium. Soft-rot enterobacteria in the genera Pectobacterium and Dickeya are of great agricultural importance, and an investigation of the virulence of these pathogens could facilitate improvements in agricultural practices, thus benefiting farmers, the potato industry and consumers. PMID:24040039

Role and regulation of the Flp/Tad pilus in the virulence of Pectobacterium atrosepticum SCRI1043 and Pectobacterium wasabiae SCC3193.

PubMed

Nykyri, Johanna; Mattinen, Laura; Niemi, Outi; Adhikari, Satish; Kõiv, Viia; Somervuo, Panu; Fang, Xin; Auvinen, Petri; Mäe, Andres; Palva, E Tapio; Pirhonen, Minna

2013-01-01

In this study, we characterized a putative Flp/Tad pilus-encoding gene cluster, and we examined its regulation at the transcriptional level and its role in the virulence of potato pathogenic enterobacteria of the genus Pectobacterium. The Flp/Tad pilus-encoding gene clusters in Pectobacterium atrosepticum, Pectobacterium wasabiae and Pectobacterium aroidearum were compared to previously characterized flp/tad gene clusters, including that of the well-studied Flp/Tad pilus model organism Aggregatibacter actinomycetemcomitans, in which this pilus is a major virulence determinant. Comparative analyses revealed substantial protein sequence similarity and open reading frame synteny between the previously characterized flp/tad gene clusters and the cluster in Pectobacterium, suggesting that the predicted flp/tad gene cluster in Pectobacterium encodes a Flp/Tad pilus-like structure. We detected genes for a novel two-component system adjacent to the flp/tad gene cluster in Pectobacterium, and mutant analysis demonstrated that this system has a positive effect on the transcription of selected Flp/Tad pilus biogenesis genes, suggesting that this response regulator regulate the flp/tad gene cluster. Mutagenesis of either the predicted regulator gene or selected Flp/Tad pilus biogenesis genes had a significant impact on the maceration ability of the bacterial strains in potato tubers, indicating that the Flp/Tad pilus-encoding gene cluster represents a novel virulence determinant in Pectobacterium. Soft-rot enterobacteria in the genera Pectobacterium and Dickeya are of great agricultural importance, and an investigation of the virulence of these pathogens could facilitate improvements in agricultural practices, thus benefiting farmers, the potato industry and consumers.

Morris County Improvement Authority, Morris County, New Jersey Renewable Energy Initiative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonanni, John

2013-05-01

The Morris County Improvement Authority (Authority), a public body corporate and politic of the State of New Jersey and created and controlled by the County, at the direction of the County and through the Program guaranteed by the County, financed 3.2 MW of solar projects (Solar Projects) at fifteen (15) sites for seven (7) local government units (Local Units) in and including the County. The Program uses a Power Purchase Agreement (PPA) structure, where the Solar Developer constructs, operates and maintains all of the Solar Projects, for the benefit of the Local Units and the Authority, for the maximum Statemore » law allowable PPA period of fifteen (15) years. Although all fifteen (15) sites were funded by the Authority, only the Mennen Arena site was considered for the purposes of the required local match funding for this grant. Specifically at the Mennen Arena site, the Authority financed 1.6 MW of solar panels. On October 18, 2013, the DOE Grant was drawn down following completion of the necessary application documents and final execution of an agreement memorializing the contemplated transaction by the Local Units, the County, The Authority and the solar developer. The proceeds of the DOE Grant were then applied to reduce the PPA price to all Local Units across the program and increase the savings from approximately 1/3 to almost half off the existing and forecasted utility pricing over the fifteen (15) year term, without adversely affecting all of the other benefits. With the application of the rate buy down, the price of electricity purchased under the PPA dropped from 10.9 to 7.7 cents/kWh. This made acquisition of renewable energy much more affordable for the Local Units, and it enhanced the success of the program, which will encourage other counties and local units to develop similar programs.« less

Energy Efficient Buildings, Salt Lake County, Utah

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnett, Kimberly

2012-04-30

Executive Summary Salt Lake County's Solar Photovoltaic Project - an unprecedented public/private partnership Salt Lake County is pleased to announce the completion of its unprecedented solar photovoltaic (PV) installation on the Calvin R. Rampton Salt Palace Convention Center. This 1.65 MW installation will be one the largest solar roof top installations in the country and will more than double the current installed solar capacity in the state of Utah. Construction is complete and the system will be operational in May 2012. The County has accomplished this project using a Power Purchase Agreement (PPA) financing model. In a PPA model amore » third-party solar developer will finance, develop, own, operate, and maintain the solar array. Salt Lake County will lease its roof, and purchase the power from this third-party under a long-term Power Purchase Agreement contract. In fact, this will be one of the first projects in the state of Utah to take advantage of the recent (March 2010) legislation which makes PPA models possible for projects of this type. In addition to utilizing a PPA, this solar project will employ public and private capital, Energy Efficiency and Conservation Block Grants (EECBG), and public/private subsidized bonds that are able to work together efficiently because of the recent stimulus bill. The project also makes use of recent changes to federal tax rules, and the recent re-awakening of private capital markets that make a significant public-private partnership possible. This is an extremely innovative project, and will mark the first time that all of these incentives (EECBG grants, Qualified Energy Conservation Bonds, New Markets tax credits, investment tax credits, public and private funds) have been packaged into one project. All of Salt Lake County's research documents and studies, agreements, and technical information is available to the public. In addition, the County has already shared a variety of information with the public through webinars, site tours, presentations, and written correspondence.« less

Mortality and cardiovascular events are best predicted by low central/peripheral pulse pressure amplification but not by high blood pressure levels in elderly nursing home subjects: the PARTAGE (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population) study.

PubMed

Benetos, Athanase; Gautier, Sylvie; Labat, Carlos; Salvi, Paolo; Valbusa, Filippo; Marino, Francesca; Toulza, Olivier; Agnoletti, Davide; Zamboni, Mauro; Dubail, Delphine; Manckoundia, Patrick; Rolland, Yves; Hanon, Olivier; Perret-Guillaume, Christine; Lacolley, Patrick; Safar, Michel E; Guillemin, Francis

2012-10-16

The aim of the longitudinal PARTAGE study was to determine the predictive value of blood pressure (BP) and pulse pressure amplification, a marker of arterial function, for overall mortality (primary endpoint) and major cardiovascular (CV) events, in subjects older than 80 years of age living in a nursing home. Assessment of pulse indexes may be important in the evaluation of the CV risk in very elderly frail subjects. A total of 1,126 subjects (874 women) who were living in French and Italian nursing homes were enrolled (mean age, 88 ± 5 years). Central (carotid) to peripheral (brachial) pulse pressure amplification (PPA) was calculated with the help of an arterial tonometer. Clinical and 3-day self-measurements of BP were conducted. During the 2-year follow-up, 247 subjects died, and 228 experienced major CV events. The PPA was a predictor of total mortality and major CV events in this population. A 10% increase in PPA was associated with a 24% (p < 0.0003) decrease in total mortality and a 17% (p < 0.01) decrease in major CV events. Systolic BP, diastolic BP, or pulse pressure were either not associated or inversely correlated with total mortality and major CV events. In very elderly individuals living in nursing homes, low PPA from central to peripheral arteries strongly predicts mortality and adverse effects. Assessment of this parameter could help in risk estimation and improve diagnostic and therapeutic strategies in very old, polymedicated persons. In contrast, high BP is not associated with higher risk of mortality or major CV events in this population. (Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population [PARTAGE]; NCT00901355). Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Permission to park: A statewide study of high school parking permits to determine compliance with graduated driver licensing law.

PubMed

Apanovitch, Audrey; Champany, Victoria; Wilson, Meghan; Emam, Hadeer; Ruiz, Kelly; Borrup, Kevin; Lapidus, Garry

2015-09-01

Motor vehicle crashes are the leading cause of fatality among teens in the United States. Beginning in the 1990s, many states enacted graduated driver licensing (GDL) systems to delay full licensure while allowing beginners to obtain experience under lower-risk conditions. Many high schools require parent and guardians of newly licensed teen drivers to complete a student parking pass application (PPA) for their son/daughter to drive, park, and transport themselves to and from school activities. The objective of this study was to describe the content of these PPAs for compliance with Connecticut's GDL law. PPAs were requested via e-mail, fax, or telephone from all Connecticut's high schools (n = 233). PPA variables included school demographics, parking rules, prohibitions and sanctions for violations, as well as reference to GDL law. Seventy-four schools were excluded because students were not allowed to park and schools did not require PPAs or declined to send us a copy of their PPAs. Of the remaining 159 schools, 122 (76.7%) sent us their PPAs. Responding schools were more likely to be suburban or rural. Most PPAs included a section on prohibitions and sanctions for driving misbehavior. Forty-three percent prohibited students from going to car during school hours, and 34% prohibited driving off campus/parking lot. Seventy percent warned of consequences for dangerous driving in parking lot, and 88% included the possibility of revocation for infractions. Only 14% had any reference to Connecticut's GDL law on their PPAs. A small percentage of Connecticut high schools include information about GDL laws on their PPAs. All states should examine their PPA content and adopt a uniform high school PPA that includes key provisions of their state's GDL laws in an effort to promote teen driving safety. Therapeutic study, level V.

Distribution and Evolution of Yersinia Leucine-Rich Repeat Proteins

PubMed Central

Hu, Yueming; Huang, He; Hui, Xinjie; Cheng, Xi; White, Aaron P.

2016-01-01

Leucine-rich repeat (LRR) proteins are widely distributed in bacteria, playing important roles in various protein-protein interaction processes. In Yersinia, the well-characterized type III secreted effector YopM also belongs to the LRR protein family and is encoded by virulence plasmids. However, little has been known about other LRR members encoded by Yersinia genomes or their evolution. In this study, the Yersinia LRR proteins were comprehensively screened, categorized, and compared. The LRR proteins encoded by chromosomes (LRR1 proteins) appeared to be more similar to each other and different from those encoded by plasmids (LRR2 proteins) with regard to repeat-unit length, amino acid composition profile, and gene expression regulation circuits. LRR1 proteins were also different from LRR2 proteins in that the LRR1 proteins contained an E3 ligase domain (NEL domain) in the C-terminal region or an NEL domain-encoding nucleotide relic in flanking genomic sequences. The LRR1 protein-encoding genes (LRR1 genes) varied dramatically and were categorized into 4 subgroups (a to d), with the LRR1a to -c genes evolving from the same ancestor and LRR1d genes evolving from another ancestor. The consensus and ancestor repeat-unit sequences were inferred for different LRR1 protein subgroups by use of a maximum parsimony modeling strategy. Structural modeling disclosed very similar repeat-unit structures between LRR1 and LRR2 proteins despite the different unit lengths and amino acid compositions. Structural constraints may serve as the driving force to explain the observed mutations in the LRR regions. This study suggests that there may be functional variation and lays the foundation for future experiments investigating the functions of the chromosomally encoded LRR proteins of Yersinia. PMID:27217422

Characterization of the Genes Encoding the Cytosolic and Plastidial Forms of ADP-Glucose Pyrophosphorylase in Wheat Endosperm1

PubMed Central

Burton, Rachel A.; Johnson, Philip E.; Beckles, Diane M.; Fincher, Geoffrey B.; Jenner, Helen L.; Naldrett, Mike J.; Denyer, Kay

2002-01-01

In most species, the synthesis of ADP-glucose (Glc) by the enzyme ADP-Glc pyrophosphorylase (AGPase) occurs entirely within the plastids in all tissues so far examined. However, in the endosperm of many, if not all grasses, a second form of AGPase synthesizes ADP-Glc outside the plastid, presumably in the cytosol. In this paper, we show that in the endosperm of wheat (Triticum aestivum), the cytosolic form accounts for most of the AGPase activity. Using a combination of molecular and biochemical approaches to identify the cytosolic and plastidial protein components of wheat endosperm AGPase we show that the large and small subunits of the cytosolic enzyme are encoded by genes previously thought to encode plastidial subunits, and that a gene, Ta.AGP.S.1, which encodes the small subunit of the cytosolic form of AGPase, also gives rise to a second transcript by the use of an alternate first exon. This second transcript encodes an AGPase small subunit with a transit peptide. However, we could not find a plastidial small subunit protein corresponding to this transcript. The protein sequence of the purified plastidial small subunit does not match precisely to that encoded by Ta.AGP.S.1 or to the predicted sequences of any other known gene from wheat or barley (Hordeum vulgare). Instead, the protein sequence is most similar to those of the plastidial small subunits from chickpea (Cicer arietinum) and maize (Zea mays) and rice (Oryza sativa) seeds. These data suggest that the gene encoding the major plastidial small subunit of AGPase in wheat endosperm has yet to be identified. PMID:12428011

Survival benefits of pelvic lymphadenectomy versus pelvic and para-aortic lymphadenectomy in patients with endometrial cancer

PubMed Central

Guo, Weina; Cai, Jing; Li, Min; Wang, Hongbo; Shen, Yi

2018-01-01

Abstract Background: Despite that pelvic and para-aortic lymphadenectomy (PPaLND) is recommended as part of accurate surgical staging by International Federation of Gynecology and Obstetrics (FIGO) in endometrial cancer, the impact of para-aortic lymphadenectomy on survival remains controversial. The aim of this work is to evaluate the survival benefits or risks in endometrial cancer patients who underwent surgical staging with or without para-aortic lymphadenectomy using meta-analysis. Methods: Literature search was undertaken using PubMed, Embase, and Cochrane Library databases for relevant articles published between January 1, 1990, and January 1, 2017, without language restriction. The primary outcome was overall survival (OS); progression-free survival (PFS)/recurrence-free survival (RFS)/disease-free survival (DFS)/disease-related survival (DRS) was also analyzed. Subgroup analysis and sensitivity analysis were conducted to investigate the source of heterogeneity. Quality assessments were performed by Newcastle–Ottawa Quality Assessment Scale (NOS). Publication bias was evaluated by using Begg and Egger tests. The hazard ratio (HR) was pooled with random-effects or fixed-effects model as appropriate. Results: Eight studies with a total of 2793 patients were included. OS was significantly longer in PPaLND group than in pelvic lymphadenectomy (PLND) group for patients with endometrial cancer [HR 0.68; 95% confidence interval (CI) 0.55–0.84, P < .001, I2 = 12.2%]. Subgroup analysis by recurrence risk explored the same association in patients at intermediate- or high-risk (HR 0.52; 95% CI 0.39–0.69, P < .001, I2 = 41.4%), but not for low-risk patients (HR 0.48; 95% CI 0.21–1.08, P = .077, I2 = 0). PPaLND with systematic resection of all para-aortic nodes up to renal vein also improved PFS/RFS/DFS/DRS, compared with PLND (HR 0.52, 95% CI 0.37–0.72, P < .001, I2 = 0). No publication bias was observed among included studies. Conclusion: PPaLND is associated with favorable survival outcomes in endometrial cancer patients with intermediate- or high-risk of recurrence compared with PLND, particularly with regards to OS. PPaLND with systematic resection of all para-aortic nodes up to renal vein also improve PFS compared with PLND. Further large-scale randomized clinical trials are required to validate our findings. PMID:29505525

Induction, immunochemical identity and immunofluorescence localization of an 80 000-molecular-weight peroxisome-proliferation-associated polypeptide (polypeptide PPA-80) and peroxisomal enoyl-CoA hydratase of mouse liver and renal cortex.

PubMed

Lalwani, N D; Reddy, M K; Mangkornkanok-Mark, M; Reddy, J K

1981-07-15

The hypolipidaemic drugs methyl clofenapate, BR-931, Wy-14643 and procetofen induced a marked proliferation of peroxisomes in the parenchymal cells of liver and the proximal-convoluted-tubular epithelium of mouse kidney. The proliferation of peroxisomes was associated with 6-12-fold increase in the peroxisomal palmitoyl-CoA oxidizing capacity of the mouse liver. Enhanced activity of the peroxisomal palmitoyl-CoA oxidation system was also found in the renal-cortical homogenates of hypolipidaemic-drug-treated mice. The activity of enoyl-CoA hydratase in the mouse liver increased 30-50-fold and in the kidney cortex 3-5-fold with hypolipidaemic-drug-induced peroxisome proliferation in these tissues, and over 95% of this induced activity was found to be heat-labile peroxisomal enzyme in both organs. Sodium dodecyl sulphate/polyacrylamide-gel-electrophoretic analysis of large-particle and microsomal fractions obtained from the liver and kidney cortex of mice treated with hypolipidaemic peroxisome proliferators demonstrated a substantial increase in the quantity of an 80000-mol.wt. peroxisome-proliferation-associated polypeptide (polypeptide PPA-80). The heat-labile peroxisomal enoyl-CoA hydratase was purified from the livers of mice treated with the hypolipidaemic drug methyl clofenapate; the antibodies raised against this electrophoretically homogeneous protein yielded a single immunoprecipitin band with purified mouse liver enoyl-CoA hydratase and with liver and kidney cortical extracts of normal and hypolipidaemic-drug-treated mice. These anti-(mouse liver enoyl-CoA hydratase) antibodies also cross-reacted with purified rat liver enoyl-CoA hydratase and with the polypeptide PPA-80 obtained from rat and mouse liver. Immunofluorescence studies with anti-(polypeptide PPA-80) and anti-(peroxisomal enoyl-CoA hydratase) provided visual evidence for the localization and induction of polypeptide PPA-80 and peroxisomal enoyl-CoA hydratase in the liver and kidney respectively of normal and hypolipidaemic-drug-treated mice. In the kidney, the distribution of these two proteins is identical and limited exclusively to the cytoplasm of proximal-convoluted-tubular epithelium. The immunofluorescence studies clearly complement the biochemical and ultrastructural observations of peroxisome induction in the liver and kidney cortex of mice fed on hypolipidaemic drugs. In addition, preliminary ultrastructural studies with the protein-A-gold-complex technique demonstrate that the heat-labile hepatic enoyl-CoA hydratase is localized in the peroxisome matrix.

Release of Water Soluble Drugs from Dynamically Swelling POLY(2-HYDROXYETHYL Methacrylate - CO - Methacrylic Acid) Hydrogels.

NASA Astrophysics Data System (ADS)

Kou, Jim Hwai-Cher

In this study, ionizable copolymers of HEMA and methacrylic acid (MA) are investigated for their potential use in developing pH dependent oral delivery systems. Because of the MA units, these gels swell extensively at high pH. Since solute diffusion in the hydrophilic polymers depends highly on the water content of the matrix, it is anticipated that the release rate will be modulated by this pH induced swelling. From a practical point of view, the advantage of the present system is that one can minimize drug loss in the stomach and achieve a programmed release in intestine. This approach is expected to improve delivery of acid labile drugs or drugs that cause severe gastrointestinal side effects. This work mainly focuses on the basic understanding of the mechanism involved in drug release from the poly(HEMA -co- MA) gels, especially under dynamic swelling conditions. Equilibrium swelling is first characterized since water content is the major determinant of transport properties in these gels. Phenylpropanolamine (PPA) is chosen as the model drug for the release study and its diffusion characteristics in the gel matrix determined. The data obtained show that the PPA diffusivity follows the free volume theory of Yasuda, which explains the accelerating effect of swelling on drug release. A mathematical model based on a diffusion mechanism has been developed to describe PPA release from the swelling gels. Based on this model, several significant conclusions can be drawn. First, the release rate can be modulated by the aspect ratio of the cylindrical geometry, and this has a practical implication in dosage form design. Second, the release rate can be lowered quite considerably if the dimensional increase due to swelling is significant. Consequently, it is the balance between the drug diffusivity increase and the gel dimensional growth that determines the release rate from the swelling matrix. Third, quasi-steady release kinetics, which are characteristic of swelling release systems, can also be predicted by this model. PPA release from initially dry poly(HEMA -co- MA) gels has also been studied. The data show that the release rate is mainly controlled by the PPA loading level and quite insensitive to the methacrylic acid composition of the gels. These phenomena can be adequately explained by analyzing the transport resistances in the gels. The overall time scale of release from these gels were shown to be in the range which was suitable for oral controlled release applications. (Abstract shortened with permission of author.).

Structural and transcriptional characterization of a novel member of the soybean urease gene family.

PubMed

Wiebke-Strohm, Beatriz; Ligabue-Braun, Rodrigo; Rechenmacher, Ciliana; De Oliveira-Busatto, Luisa Abruzzi; Carlini, Célia Regina; Bodanese-Zanettini, Maria Helena

2016-04-01

In plants, ureases have been related to urea degradation, to defense against pathogenic fungi and phytophagous insects, and to the soybean-Bradyrhizobium japonicum symbiosis. Two urease isoforms have been described for soybean: the embryo-specific, encoded by Eu1 gene, and the ubiquitous urease, encoded by Eu4. A third urease-encoding locus exists in the completed soybean genome. The gene was designated Eu5 and the putative product of its ORF as SBU-III. Phylogenetic analysis shows that 41 plant, moss and algal ureases have diverged from a common ancestor protein, but ureases from monocots, eudicots and ancient species have evolved independently. Genomes of ancient organisms present a single urease-encoding gene and urease-encoding gene duplication has occurred independently along the evolution of some eudicot species. SBU-III has a shorter amino acid sequence, since many gaps are found when compared to other sequences. A mutation in a highly conserved amino acid residue suggests absence of ureolytic activity, but the overall protein architecture remains very similar to the other ureases. The expression profile of urease-encoding genes in different organs and developmental stages was determined by RT-qPCR. Eu5 transcripts were detected in seeds one day after dormancy break, roots of young plants and embryos of developing seeds. Eu1 and Eu4 transcripts were found in all analyzed organs, but Eu4 expression was more prominent in seeds one day after dormancy break whereas Eu1 predominated in developing seeds. The evidence suggests that SBU-III may not be involved in nitrogen availability to plants, but it could be involved in other biological role(s). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Systems-level analysis of risk genes reveals the modular nature of schizophrenia.

PubMed

Liu, Jiewei; Li, Ming; Luo, Xiong-Jian; Su, Bing

2018-05-19

Schizophrenia (SCZ) is a complex mental disorder with high heritability. Genetic studies (especially recent genome-wide association studies) have identified many risk genes for schizophrenia. However, the physical interactions among the proteins encoded by schizophrenia risk genes remain elusive and it is not known whether the identified risk genes converge on common molecular networks or pathways. Here we systematically investigated the network characteristics of schizophrenia risk genes using the high-confidence protein-protein interactions (PPI) from the human interactome. We found that schizophrenia risk genes encode a densely interconnected PPI network (P = 4.15 × 10 -31 ). Compared with the background genes, the schizophrenia risk genes in the interactome have significantly higher degree (P = 5.39 × 10 -11 ), closeness centrality (P = 7.56 × 10 -11 ), betweeness centrality (P = 1.29 × 10 -11 ), clustering coefficient (P = 2.22 × 10 -2 ), and shorter average shortest path length (P = 7.56 × 10 -11 ). Based on the densely interconnected PPI network, we identified 48 hub genes and 4 modules formed by highly interconnected schizophrenia genes. We showed that the proteins encoded by schizophrenia hub genes have significantly more direct physical interactions. Gene ontology (GO) analysis revealed that cell adhesion, cell cycle, immune system response, and GABR-receptor complex categories were enriched in the modules formed by highly interconnected schizophrenia risk genes. Our study reveals that schizophrenia risk genes encode a densely interconnected molecular network and demonstrates the modular nature of schizophrenia. Copyright © 2018 Elsevier B.V. All rights reserved.

Cloning and expression of prion protein encoding gene of flounder ( Paralichthys olivaceus)

NASA Astrophysics Data System (ADS)

Zhang, Zhiwen; Sun, Xiuqin; Zhang, Jinxing; Zan, Jindong

2008-02-01

The prion protein (PrP) encoding gene of flounder ( Paralichthys olivaceus) was cloned. It was not interrupted by an intron. This gene has two promoters in its 5' upstream, indicating that its transcription may be intensive, and should have an important function. It was expressed in all 14 tissues tested, demonstrating that it is a house-keeping gene. Its expression in digestion and reproduction systems implies that the possible prions of fish may transfer horizontally.

Physiological roles of pyruvate ferredoxin oxidoreductase and pyruvate formate-lyase in Thermoanaerobacterium saccharolyticum JW/SL-YS485

DOE PAGES

Zhou, Jilai; Olson, Daniel G.; Lanahan, Anthony A.; ...

2015-09-15

We report that Thermoanaerobacter saccharolyticum is a thermophilic microorganism that has been engineered to produce ethanol at high titer (30–70 g/L) and greater than 90 % theoretical yield. However, few genes involved in pyruvate to ethanol production pathway have been unambiguously identified. In T. saccharolyticum, the products of six putative pfor gene clusters and one pfl gene may be responsible for the conversion of pyruvate to acetyl-CoA. To gain insights into the physiological roles of PFOR and PFL, we studied the effect of deletions of several genes thought to encode these activities. We found that that pyruvate ferredoxin oxidoreductase enzymemore » (PFOR) is encoded by the pforA gene and plays a key role in pyruvate dissimilation. We further demonstrated that pyruvate formate-lyase activity (PFL) is encoded by the pfl gene. Although the pfl gene is normally expressed at low levels, it is crucial for biosynthesis in T. saccharolyticum. In pforA deletion strains, pfl expression increased and was able to partially compensate for the loss of PFOR activity. Deletion of both pforA and pfl resulted in a strain that required acetate and formate for growth and produced lactate as the primary fermentation product, achieving 88 % theoretical lactate yield. PFOR encoded by Tsac_0046 and PFL encoded by Tsac_0628 are only two routes for converting pyruvate to acetyl-CoA in T. saccharolyticum. The physiological role of PFOR is pyruvate dissimilation, whereas that of PFL is supplying C1 units for biosynthesis.« less

Identification and Characterization of Three Differentially Expressed Genes, Encoding S-Adenosylhomocysteine Hydrolase, Methionine Aminopeptidase, and a Histone-Like Protein, in the Toxic Dinoflagellate Alexandrium fundyense†

PubMed Central

Taroncher-Oldenburg, Gaspar; Anderson, Donald M.

2000-01-01

Genes showing differential expression related to the early G1 phase of the cell cycle during synchronized circadian growth of the toxic dinoflagellate Alexandrium fundyense were identified and characterized by differential display (DD). The determination in our previous work that toxin production in Alexandrium is relegated to a narrow time frame in early G1 led to the hypothesis that transcriptionally up- or downregulated genes during this subphase of the cell cycle might be related to toxin biosynthesis. Three genes, encoding S-adenosylhomocysteine hydrolase (Sahh), methionine aminopeptidase (Map), and a histone-like protein (HAf), were isolated. Sahh was downregulated, while Map and HAf were upregulated, during the early G1 phase of the cell cycle. Sahh and Map encoded amino acid sequences with about 90 and 70% similarity to those encoded by several eukaryotic and prokaryotic Sahh and Map genes, respectively. The partial Map sequence also contained three cobalt binding motifs characteristic of all Map genes. HAf encoded an amino acid sequence with 60% similarity to those of two histone-like proteins from the dinoflagellate Crypthecodinium cohnii Biecheler. This study documents the potential of applying DD to the identification of genes that are related to physiological processes or cell cycle events in phytoplankton under conditions where small sample volumes represent an experimental constraint. The identification of an additional 21 genes with various cell cycle-related DD patterns also provides evidence for the importance of pretranslational or transcriptional regulation in dinoflagellates, contrary to previous reports suggesting the possibility that translational mechanisms are the primary means of circadian regulation in this group of organisms. PMID:10788388

Identification of a Novel Dioxygenase Involved in Metabolism of o-Xylene, Toluene, and Ethylbenzene by Rhodococcus sp. Strain DK17

PubMed Central

Kim, Dockyu; Chae, Jong-Chan; Zylstra, Gerben J.; Kim, Young-Soo; Kim, Seong-Ki; Nam, Myung Hee; Kim, Young Min; Kim, Eungbin

2004-01-01

Rhodococcus sp. strain DK17 is able to grow on o-xylene, benzene, toluene, and ethylbenzene. DK17 harbors at least two megaplasmids, and the genes encoding the initial steps in alkylbenzene metabolism are present on the 330-kb pDK2. The genes encoding alkylbenzene degradation were cloned in a cosmid clone and sequenced completely to reveal 35 open reading frames (ORFs). Among the ORFs, we identified two nearly exact copies (one base difference) of genes encoding large and small subunits of an iron sulfur protein terminal oxygenase that are 6 kb apart from each other. Immediately downstream of one copy of the dioxygenase genes (akbA1a and akbA2a) is a gene encoding a dioxygenase ferredoxin component (akbA3), and downstream of the other copy (akbA1b and akbA2b) are genes putatively encoding a meta-cleavage pathway. RT-PCR experiments show that the two copies of the dioxygenase genes are operonic with the downstream putative catabolic genes and that both operons are induced by o-xylene. When expressed in Escherichia coli, AkbA1a-AkbA2a-AkbA3 transformed o-xylene into 2,3- and 3,4-dimethylphenol. These were apparently derived from an unstable o-xylene cis-3,4-dihydrodiol, which readily dehydrates. This indicates a single point of attack of the dioxygenase on the aromatic ring. In contrast, attack of AkbA1a-AkbA2a-AkbA3 on ethylbenzene resulted in the formation of two different cis-dihydrodiols resulting from an oxidation at the 2,3 and the 3,4 positions on the aromatic ring, respectively. PMID:15574904

Discovery of Herpes B Virus-Encoded MicroRNAs▿

PubMed Central

Besecker, Michael I.; Harden, Mallory E.; Li, Guanglin; Wang, Xiu-Jie; Griffiths, Anthony

2009-01-01

Herpes B virus (BV) naturally infects macaque monkeys and is a close relative of herpes simplex virus. BV can zoonotically infect humans to cause a rapidly ascending encephalitis with ∼80% mortality. Therefore, BV is a serious danger to those who come into contact with these monkeys or their tissues and cells. MicroRNAs are regulators of gene expression, and there have been reports of virus-encoded microRNAs. We hypothesize that BV-encoded microRNAs are important for the regulation of viral and cellular genes. Herein, we report the discovery of three herpes B virus-encoded microRNAs. PMID:19144716

Gene encoding acetyl-coenzyme A carboxylase

DOEpatents

Roessler, Paul G.; Ohlrogge, John B.

1996-01-01

A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives thereof which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides.

Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis† †Electronic supplementary information (ESI) available: Containing all experimental details. See DOI: 10.1039/c3sc52911h Click here for additional data file.

PubMed Central

Fahad, Ahmed al; Abood, Amira; Fisch, Katja M.; Osipow, Anna; Davison, Jack; Avramović, Marija; Butts, Craig P.; Piel, Jörn; Simpson, Thomas J.

2014-01-01

An FAD-dependent monooxygenase encoding gene (SorbC) was cloned from Penicillium chrysogenum E01-10/3 and expressed as a soluble protein in Escherichia coli. The enzyme efficiently performed the oxidative dearomatisation of sorbicillin and dihydrosorbicillin to give sorbicillinol and dihydrosorbicillinol respectively. Bioinformatic examination of the gene cluster surrounding SorbC indicated the presence of two polyketide synthase (PKS) encoding genes designated sorbA and sorbB. The gene sorbA-encodes a highly reducing iterative PKS while SorbB encodes a non-reducing iterative PKS which features a reductive release domain usually involved in the production of polyketide aldehydes. Using these observations and previously reported results from isotopic feeding experiments a new and simpler biosynthetic route to the sorbicillin class of secondary metabolites is proposed which is consistent with all reported experimental results. PMID:25580210

A gene encoding the plant-like alternative oxidase is present in Phytomonas but absent in Leishmania spp.

PubMed

Van Hellemond, J J; Simons, B; Millenaar, F F; Tielens, A G

1998-01-01

The constituents of the respiratory chain are believed to differ among the trypanosomatids; bloodstream stages of African trypanosomes and Phytomonas promastigotes oxidize ubiquinol by a ubiquinol:oxygen oxidoreductase, also known as alternative oxidase, whereas Leishmania spp. oxidize ubiquinol via a classic cytochrome-containing respiratory chain. The molecular basis for this elementary difference in ubiquinol oxidation by the mitochondrial electron-transport chain in distinct trypanosomatids was investigated. The presence of a gene encoding the plant-like alternative oxidase could be demonstrated in Phytomonas and Trypanosoma brucei, trypanosomatids that are known to contain alternative oxidase activity. Our results further demonstrated that Leishmania spp. lack a gene encoding the plant-like alternative oxidase, and therefore, all stages of Leishmania spp. will lack the alternative oxidase protein. The observed fundamental differences between the respiratory chains of distinct members of the trypanosomatid family are thus caused by the presence or absence of a gene encoding the plant-like alternative oxidase.

Cloning of gene-encoded stem bromelain on system coming from Pichia pastoris as therapeutic protein candidate

NASA Astrophysics Data System (ADS)

Yusuf, Y.; Hidayati, W.

2018-01-01

The process of identifying bacterial recombination using PCR, and restriction, and then sequencing process was done after identifying the bacteria. This research aimed to get a yeast cell of Pichia pastoris which has an encoder gene of stem bromelain enzyme. The production of recombinant stem bromelain enzymes using yeast cells of P. pastoris can produce pure bromelain rod enzymes and have the same conformation with the enzyme’s conformation in pineapple plants. This recombinant stem bromelain enzyme can be used as a therapeutic protein in inflammatory, cancer and degenerative diseases. This study was an early stage of a step series to obtain bromelain rod protein derived from pineapple made with genetic engineering techniques. This research was started by isolating the RNA of pineapple stem which was continued with constructing cDNA using reserve transcriptase-PCR technique (RT-PCR), doing the amplification of bromelain enzyme encoder gene with PCR technique using a specific premiere couple which was designed. The process was continued by cloning into bacterium cells of Escherichia coli. A vector which brought the encoder gene of stem bromelain enzyme was inserted into the yeast cell of P. pastoris and was continued by identifying the yeast cell of P. pastoris which brought the encoder gene of stem bromelain enzyme. The research has not found enzyme gene of stem bromelain in yeast cell of P. pastoris yet. The next step is repeating the process by buying new reagent; RNase inhibitor, and buying liquid nitrogen.