Molecular characterization of chronic-type adult T-cell leukemia/lymphoma.

PubMed

Yoshida, Noriaki; Karube, Kennosuke; Utsunomiya, Atae; Tsukasaki, Kunihiro; Imaizumi, Yoshitaka; Taira, Naoya; Uike, Naokuni; Umino, Akira; Arita, Kotaro; Suguro, Miyuki; Tsuzuki, Shinobu; Kinoshita, Tomohiro; Ohshima, Koichi; Seto, Masao

2014-11-01

Adult T-cell leukemia/lymphoma (ATL) is a human T-cell leukemia virus type-1-induced neoplasm with four clinical subtypes: acute, lymphoma, chronic, and smoldering. Although the chronic type is regarded as indolent ATL, about half of the cases progress to acute-type ATL. The molecular pathogenesis of acute transformation in chronic-type ATL is only partially understood. In an effort to determine the molecular pathogeneses of ATL, and especially the molecular mechanism of acute transformation, oligo-array comparative genomic hybridization and comprehensive gene expression profiling were applied to 27 and 35 cases of chronic and acute type ATL, respectively. The genomic profile of the chronic type was nearly identical to that of acute-type ATL, although more genomic alterations characteristic of acute-type ATL were observed. Among the genomic alterations frequently observed in acute-type ATL, the loss of CDKN2A, which is involved in cell-cycle deregulation, was especially characteristic of acute-type ATL compared with chronic-type ATL. Furthermore, we found that genomic alteration of CD58, which is implicated in escape from the immunosurveillance mechanism, is more frequently observed in acute-type ATL than in the chronic-type. Interestingly, the chronic-type cases with cell-cycle deregulation and disruption of immunosurveillance mechanism were associated with earlier progression to acute-type ATL. These findings suggested that cell-cycle deregulation and the immune escape mechanism play important roles in acute transformation of the chronic type and indicated that these alterations are good predictive markers for chronic-type ATL. ©2014 American Association for Cancer Research.

Is the difference between right and left ATLs due to the distinction between general and social cognition or between verbal and non-verbal representations?

PubMed

Gainotti, Guido

2015-04-01

The present review aimed to check two proposals alternative to the original version of the 'semantic hub' hypothesis, based on semantic dementia (SD) data, which assumed that left and right anterior temporal lobes (ATLs) store in a unitary, amodal format all kinds of semantic representations. The first alternative proposal is that the right ATL might subsume non-verbal representations and the left ATL lexical-semantic representations and that only in the advanced stages of SD, when atrophy affects the ATLs bilaterally, the semantic impairment becomes 'multi-modal'. The second alternative suggestion is that right and left ATLs might underlie two different domains of knowledge, because general conceptual knowledge might be supported by the left ATL, and social cognition by the right ATL. Results of the review substantially support the first proposal, showing that the right ATL subsumes non-verbal representations and the left ATL lexical-semantic representations. They are less conclusive about the second suggestion, because the right ATL seems to play a more important role in behavioral and emotional functions than in higher level social cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional analysis of AtlA, the major N-acetylglucosaminidase of Enterococcus faecalis.

PubMed

Eckert, Catherine; Lecerf, Maxime; Dubost, Lionel; Arthur, Michel; Mesnage, Stéphane

2006-12-01

The major peptidoglycan hydrolase of Enterococcus faecalis, AtlA, has been identified, but its enzyme activity remains unknown. We have used tandem mass spectrometry analysis of peptidoglycan hydrolysis products obtained using the purified protein to show that AtlA is an N-acetylglucosaminidase. To gain insight into the regulation of its enzyme activity, the three domains of AtlA were purified alone or in combination following expression of truncated forms of the atlA gene in Escherichia coli or partial digestion of AtlA by proteinase K. The central domain of AtlA was catalytically active, but its activity was more than two orders of magnitude lower than that of the complete protein. Partial proteolysis of AtlA was detected in vivo: zymograms of E. faecalis extracts revealed two catalytically active protein bands of 62 and 72 kDa that were both absent in extracts from an atlA null mutant. Limited digestion of AtlA by proteinase K in vitro suggested that the proteolytic cleavage of AtlA in E. faecalis extracts corresponds to the truncation of the N-terminal domain, which is rich in threonine and glutamic acid residues. We show that the truncation of the N-terminal domain from recombinant AtlA has no impact on enzyme activity. The C-terminal domain of the protein, which contains six LysM modules bound to highly purified peptidoglycan, was required for optimal enzyme activity. These data indicate that AtlA is not produced as a proenzyme and that control of the AtlA glucosaminidase activity is likely to occur at the level of LysM-mediated binding to peptidoglycan.

Functional Analysis of AtlA, the Major N-Acetylglucosaminidase of Enterococcus faecalis▿

PubMed Central

Eckert, Catherine; Lecerf, Maxime; Dubost, Lionel; Arthur, Michel; Mesnage, Stéphane

2006-01-01

The major peptidoglycan hydrolase of Enterococcus faecalis, AtlA, has been identified, but its enzyme activity remains unknown. We have used tandem mass spectrometry analysis of peptidoglycan hydrolysis products obtained using the purified protein to show that AtlA is an N-acetylglucosaminidase. To gain insight into the regulation of its enzyme activity, the three domains of AtlA were purified alone or in combination following expression of truncated forms of the atlA gene in Escherichia coli or partial digestion of AtlA by proteinase K. The central domain of AtlA was catalytically active, but its activity was more than two orders of magnitude lower than that of the complete protein. Partial proteolysis of AtlA was detected in vivo: zymograms of E. faecalis extracts revealed two catalytically active protein bands of 62 and 72 kDa that were both absent in extracts from an atlA null mutant. Limited digestion of AtlA by proteinase K in vitro suggested that the proteolytic cleavage of AtlA in E. faecalis extracts corresponds to the truncation of the N-terminal domain, which is rich in threonine and glutamic acid residues. We show that the truncation of the N-terminal domain from recombinant AtlA has no impact on enzyme activity. The C-terminal domain of the protein, which contains six LysM modules bound to highly purified peptidoglycan, was required for optimal enzyme activity. These data indicate that AtlA is not produced as a proenzyme and that control of the AtlA glucosaminidase activity is likely to occur at the level of LysM-mediated binding to peptidoglycan. PMID:17041059

The atlA operon of Streptococcus mutans: role in autolysin maturation and cell surface biogenesis.

PubMed

Ahn, Sang-Joon; Burne, Robert A

2006-10-01

The Smu0630 protein (AtlA) was recently shown to be involved in cell separation, biofilm formation, and autolysis. Here, transcriptional studies revealed that atlA is part of a multigene operon under the control of at least three promoters. The morphology and biofilm-forming capacity of a nonpolar altA mutant could be restored to that of the wild-type strain by adding purified AtlA protein to the medium. A series of truncated derivatives of AtlA revealed that full activity required the C terminus and repeat regions. AtlA was cell associated and readily extractable from with sodium dodecyl sulfate. Of particular interest, the surface protein profile of AtlA-deficient strains was dramatically altered compared to the wild-type strain, as was the nature of the association of the multifunctional adhesin P1 with the cell wall. In addition, AtlA-deficient strains failed to develop competence as effectively as the parental strain. Mutation of thmA, which can be cotranscribed with atlA and encodes a putative pore-forming protein, resulted in a phenotype very similar to that of the AtlA-deficient strain. ThmA was also shown to be required for efficient processing of AtlA to its mature form, and treatment of the thmA mutant strain with full-length AtlA protein did not restore normal cell separation and biofilm formation. The effects of mutating other genes in the operon on cell division, biofilm formation, or AtlA biogenesis were not as profound. This study reveals that AtlA is a surface-associated protein that plays a critical role in the network connecting cell surface biogenesis, biofilm formation, genetic competence, and autolysis.

Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight.

PubMed

Aihara, Takatsugu; Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

2017-01-01

Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight.

Suppression of Arabidopsis RING E3 ubiquitin ligase AtATL78 increases tolerance to cold stress and decreases tolerance to drought stress.

PubMed

Kim, Soo Jin; Kim, Woo Taek

2013-08-19

AtATL78 is an Arabidopsis RING E3 ubiquitin ligase. RT-PCR and promoter-GUS assays revealed that AtATL78 was up-regulated by cold stress and down-regulated by drought. AtATL78 was localized at the plasma-membrane. Suppression of AtATL78 increased tolerance to cold stress but decreased tolerance to drought. Our data suggests that AtATL78 is a negative regulator of cold stress response and a positive regulator of drought stress response in Arabidopsis. These results further suggest that AtATL78 plays opposing roles in cold and drought stress responses. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma.

PubMed

Narita, Tomoko; Ishida, Takashi; Ito, Asahi; Masaki, Ayako; Kinoshita, Shiori; Suzuki, Susumu; Takino, Hisashi; Yoshida, Takashi; Ri, Masaki; Kusumoto, Shigeru; Komatsu, Hirokazu; Imada, Kazunori; Tanaka, Yuetsu; Takaori-Kondo, Akifumi; Inagaki, Hiroshi; Scholz, Arne; Lienau, Philip; Kuroda, Taruho; Ueda, Ryuzo; Iida, Shinsuke

2017-08-31

Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/P-TEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY 1143572 decreased c-Myc and Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)-transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1-transformed lines (n = 8), primary ATL cells (n = 11), and CD4 + cells from healthy volunteers (n = 5) were 0.535, 0.30, and 0.36 μM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572-treated ATL-bearing mice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n = 7 for both). Collectively, this study indicates that BAY 1143572 showed strong potential as a novel treatment of ATL. © 2017 by The American Society of Hematology.

Anodal transcranial direct current stimulation of the right anterior temporal lobe did not significantly affect verbal insight

PubMed Central

Ogawa, Takeshi; Shimokawa, Takeaki; Yamashita, Okito

2017-01-01

Humans often utilize past experience to solve difficult problems. However, if past experience is insufficient to solve a problem, solvers may reach an impasse. Insight can be valuable for breaking an impasse, enabling the reinterpretation or re-representation of a problem. Previous studies using between-subjects designs have revealed a causal relationship between the anterior temporal lobes (ATLs) and non-verbal insight, by enhancing the right ATL while inhibiting the left ATL using transcranial direct current stimulation (tDCS). In addition, neuroimaging studies have reported a correlation between right ATL activity and verbal insight. Based on these findings, we hypothesized that the right ATL is causally related to both non-verbal and verbal insight. To test this hypothesis, we conducted an experiment with 66 subjects using a within-subjects design, which typically has greater statistical power than a between-subjects design. Subjects participated in tDCS experiments across 2 days, in which they solved both non-verbal and verbal insight problems under active or sham stimulation conditions. To dissociate the effects of right ATL stimulation from those of left ATL stimulation, we used two montage types; anodal tDCS of the right ATL together with cathodal tDCS of the left ATL (stimulating both ATLs) and anodal tDCS of the right ATL with cathodal tDCS of the left cheek (stimulating only the right ATL). The montage used was counterbalanced across subjects. Statistical analyses revealed that, regardless of the montage type, there were no significant differences between the active and sham conditions for either verbal or non-verbal insight, although the finding for non-verbal insight was inconclusive because of a lack of statistical power. These results failed to support previous findings suggesting that the right ATL is the central locus of insight. PMID:28902872

Arabidopsis RING E3 ubiquitin ligase AtATL80 is negatively involved in phosphate mobilization and cold stress response in sufficient phosphate growth conditions.

PubMed

Suh, Ji Yeon; Kim, Woo Taek

2015-08-07

Phosphate (Pi) remobilization in plants is critical to continuous growth and development. AtATL80 is a plasma membrane (PM)-localized RING E3 ubiquitin (Ub) ligase that belongs to the Arabidopsis Tóxicos en Levadura (ATL) family. AtATL80 was upregulated by long-term low Pi (0-0.02 mM KH2PO4) conditions in Arabidopsis seedlings. AtATL80-overexpressing transgenic Arabidopsis plants (35S:AtATL80-sGFP) displayed increased phosphorus (P) accumulation in the shoots and lower biomass, as well as reduced P-utilization efficiency (PUE) under high Pi (1 mM KH2PO4) conditions compared to wild-type plants. The loss-of-function atatl80 mutant line exhibited opposite phenotypic traits. The atatl80 mutant line bolted earlier than wild-type plants, whereas AtATL80-overexpressors bloomed significantly later and produced lower seed yields than wild-type plants under high Pi conditions. Thus, AtATL80 is negatively correlated not only with P content and PUE, but also with biomass and seed yield in Arabidopsis. In addition, AtATL80-overexpressors were significantly more sensitive to cold stress than wild-type plants, while the atatl80 mutant line exhibited an increased tolerance to cold stress. Taken together, our results suggest that AtATL80, a PM-localized ATL-type RING E3 Ub ligase, participates in the Pi mobilization and cold stress response as a negative factor in Arabidopsis. Copyright © 2015 Elsevier Inc. All rights reserved.

AtlA functions as a peptidoglycan lytic transglycosylase in the Neisseria gonorrhoeae type IV secretion system.

PubMed

Kohler, Petra L; Hamilton, Holly L; Cloud-Hansen, Karen; Dillard, Joseph P

2007-08-01

Type IV secretion systems require peptidoglycan lytic transglycosylases for efficient secretion, but the function of these enzymes is not clear. The type IV secretion system gene cluster of Neisseria gonorrhoeae encodes two peptidoglycan transglycosylase homologues. One, LtgX, is similar to peptidoglycan transglycosylases from other type IV secretion systems. The other, AtlA, is similar to endolysins from bacteriophages and is not similar to any described type IV secretion component. We characterized the enzymatic function of AtlA in order to examine its role in the type IV secretion system. Purified AtlA was found to degrade macromolecular peptidoglycan and to produce 1,6-anhydro peptidoglycan monomers, characteristic of lytic transglycosylase activity. We found that AtlA can functionally replace the lambda endolysin to lyse Escherichia coli. In contrast, a sensitive measure of lysis demonstrated that AtlA does not lyse gonococci expressing it or gonococci cocultured with an AtlA-expressing strain. The gonococcal type IV secretion system secretes DNA during growth. A deletion of ltgX or a substitution in the putative active site of AtlA severely decreased DNA secretion. These results indicate that AtlA and LtgX are actively involved in type IV secretion and that AtlA is not involved in lysis of gonococci to release DNA. This is the first demonstration that a type IV secretion peptidoglycanase has lytic transglycosylase activity. These data show that AtlA plays a role in type IV secretion of DNA that requires peptidoglycan breakdown without cell lysis.

Controversies in targeted therapy of adult T cell leukemia/lymphoma: ON target or OFF target effects?

PubMed

Nasr, Rihab; El Hajj, Hiba; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-06-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL.

Effect of thinning on mixed-oak stem quality

Treesearch

David L. Sonderman; Everette D. Rast; Everette D. Rast

1988-01-01

Changes in limb-;elated stem defect were studied from 1977 to 1982 on 595 mixed-oak trees fbllowing a schedule of thinnings dating back to 1962. All of the thinnings were controlled by stocking goals rather than predetermined time intervals. Results show that heavy and moderate thinnings, as opposed to light thinnings,lhad an adverse effect on the number and size of...

Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia.

PubMed

Tada, Kohei; Kobayashi, Masayuki; Takiuchi, Yoko; Iwai, Fumie; Sakamoto, Takashi; Nagata, Kayoko; Shinohara, Masanobu; Io, Katsuhiro; Shirakawa, Kotaro; Hishizawa, Masakatsu; Shindo, Keisuke; Kadowaki, Norimitsu; Hirota, Kouji; Yamamoto, Junpei; Iwai, Shigenori; Sasanuma, Hiroyuki; Takeda, Shunichi; Takaori-Kondo, Akifumi

2015-04-01

Adult T cell leukemia (ATL) is an aggressive T cell malignancy caused by human T cell leukemia virus type 1 (HTLV-1) and has a poor prognosis. We analyzed the cytotoxic effects of various nucleoside analog reverse transcriptase inhibitors (NRTIs) for HIV-1 on ATL cells and found that abacavir potently and selectively kills ATL cells. Although NRTIs have minimal genotoxicities on host cells, the therapeutic concentration of abacavir induced numerous DNA double-strand breaks (DSBs) in the chromosomal DNA of ATL cells. DSBs persisted over time in ATL cells but not in other cell lines, suggesting impaired DNA repair. We found that the reduced expression of tyrosyl-DNA phosphodiesterase 1 (TDP1), a repair enzyme, is attributable to the cytotoxic effect of abacavir on ATL cells. We also showed that TDP1 removes abacavir from DNA ends in vitro. These results suggest a model in which ATL cells with reduced TDP1 expression are unable to excise abacavir incorporated into genomic DNA, leading to irreparable DSBs. On the basis of the above mechanism, we propose abacavir as a promising chemotherapeutic agent for ATL.

Anterior temporal face patches: a meta-analysis and empirical study

PubMed Central

Von Der Heide, Rebecca J.; Skipper, Laura M.; Olson, Ingrid R.

2013-01-01

Evidence suggests the anterior temporal lobe (ATL) plays an important role in person identification and memory. In humans, neuroimaging studies of person memory report consistent activations in the ATL to famous and personally familiar faces and studies of patients report resection or damage of the ATL causes an associative prosopagnosia in which face perception is intact but face memory is compromised. In addition, high-resolution fMRI studies of non-human primates and electrophysiological studies of humans also suggest regions of the ventral ATL are sensitive to novel faces. The current study extends previous findings by investigating whether similar subregions in the dorsal, ventral, lateral, or polar aspects of the ATL are sensitive to personally familiar, famous, and novel faces. We present the results of two studies of person memory: a meta-analysis of existing fMRI studies and an empirical fMRI study using optimized imaging parameters. Both studies showed left-lateralized ATL activations to familiar individuals while novel faces activated the right ATL. Activations to famous faces were quite ventral, similar to what has been reported in previous high-resolution fMRI studies of non-human primates. These findings suggest that face memory-sensitive patches in the human ATL are in the ventral/polar ATL. PMID:23378834

Clinical Trials and Treatment of ATL

PubMed Central

Tsukasaki, Kunihiro; Tobinai, Kensei

2012-01-01

ATL is a distinct peripheral T-lymphocytic malignancy associated with human T-cell lymphotropic virus type I (HTLV-1). The diversity in clinical features and prognosis of patients with this disease has led to its subtype-classification into four categories, acute, lymphoma, chronic, and smoldering types, defined by organ involvement, and LDH and calcium values. In case of acute, lymphoma, or unfavorable chronic subtypes (aggressive ATL), intensive chemotherapy like the LSG15 regimen (VCAP-AMP-VECP) is usually recommended if outside of clinical trials, based on the results of a phase 3 trial. In case of favorable chronic or smoldering ATL (indolent ATL), watchful waiting until disease progression has been recommended, although the long-term prognosis was inferior to those of, for instance, chronic lymphoid leukemia. Retrospective analysis suggested that the combination of interferon alpha and zidovudine was apparently promising for the treatment of ATL, especially for types with leukemic manifestation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is also promising for the treatment of aggressive ATL possibly reflecting graft versus ATL effect. Several new agent trials for ATL are ongoing and in preparation, including a defucosylated humanized anti-CC chemokine receptor 4 monoclonal antibody, IL2-fused with diphtheria toxin, histone deacetylase inhibitors, a purine nucleoside phosphorylase inhibitor, a proteasome inhibitor, and lenalidomide. PMID:23259064

Adult T-cell leukaemia/lymphoma can mimic other lymphomas in a non-endemic area: dilemmas in diagnosis and treatment.

PubMed

Huang, C-T; Lee, Y-H; Chow, K-C; Yang, C-F; Chen, P C-H; Hsiao, L-T; Gau, J-P; Tzeng, C-H; Liu, C-Y; Chiou, T-J

2014-04-01

The diagnosis of Adult T-cell leukaemia/lymphoma (ATL) in non-endemic regions is challenging. This study analyses the clinicopathologic features and diagnostic processes of ATL patients in Taiwan. ATL patients diagnosed and treated at Taipei Veterans General Hospital from 1998 through 2010 were retrospectively identified. The diagnosis of ATL was confirmed by in situ detection of human T-cell leukaemia virus type 1 (HTLV-1) when necessary. Patients' data were reviewed and analysed. Fourteen ATL patients were identified, among whom six (42.9%) had an antecedent diagnosis of other malignant lymphomas before the ATL diagnosis, including two diagnosed with Hodgkin disease (HD), one with peripheral T-cell lymphoma, two with chronic lymphocytic leukaemia and one with angioimmunoblastic T-cell lymphoma. Of the 14 patients, eight (57%) were subclassified as the acute type, three (21.4%) as the lymphoma type, and three (21.4%) as the chronic type ATL. Five of six (83.3%) patients with initial non-ATL misdiagnosis were diagnosed with non-acute type ATL. In particular, a patient with an antecedent diagnosis of HD presented with typical Reed-Sternberg (RS)-like cells harbouring Epstein-Barr virus genomes in affected lymph nodes. The patient progressed to acute type ATL 3 years after the initial diagnosis, and HTLV-1 genomes were identified in the previous RS-like cells. In non-endemic areas, such as Taiwan, ATL, particularly the non-acute type, may mimic other lymphomas and easily be misdiagnosed. HTLV-1 serology should be routinely screened in all malignant lymphoma patients. In situ detection of HTLV-1 is helpful in cases with diagnostic dilemmas. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection.

PubMed

Glover, D K; Ruiz, M; Takehana, K; Petruzella, F D; Riou, L M; Rieger, J M; Macdonald, T L; Watson, D D; Linden, J; Beller, G A

2001-09-04

Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)). ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

Phosphorylation of Arabidopsis ubiquitin ligase ATL31 is critical for plant carbon/nitrogen nutrient balance response and controls the stability of 14-3-3 proteins.

PubMed

Yasuda, Shigetaka; Sato, Takeo; Maekawa, Shugo; Aoyama, Shoki; Fukao, Yoichiro; Yamaguchi, Junji

2014-05-30

Ubiquitin ligase plays a fundamental role in regulating multiple cellular events in eukaryotes by fine-tuning the stability and activity of specific target proteins. We have previously shown that ubiquitin ligase ATL31 regulates plant growth in response to nutrient balance between carbon and nitrogen (C/N) in Arabidopsis. Subsequent study demonstrated that ATL31 targets 14-3-3 proteins for ubiquitination and modulates the protein abundance in response to C/N-nutrient status. However, the underlying mechanism for the targeting of ATL31 to 14-3-3 proteins remains unclear. Here, we show that ATL31 interacts with 14-3-3 proteins in a phosphorylation-dependent manner. We identified Thr(209), Ser(247), Ser(270), and Ser(303) as putative 14-3-3 binding sites on ATL31 by motif analysis. Mutation of these Ser/Thr residues to Ala in ATL31 inhibited the interaction with 14-3-3 proteins, as demonstrated by yeast two-hybrid and co-immunoprecipitation analyses. Additionally, we identified in vivo phosphorylation of Thr(209) and Ser(247) on ATL31 by MS analysis. A peptide competition assay showed that the application of synthetic phospho-Thr(209) peptide, but not the corresponding unphosphorylated peptide, suppresses the interaction between ATL31 and 14-3-3 proteins. Moreover, Arabidopsis plants overexpressing mutated ATL31, which could not bind to 14-3-3 proteins, showed accumulation of 14-3-3 proteins and growth arrest in disrupted C/N-nutrient conditions similar to wild-type plants, although overexpression of intact ATL31 resulted in repression of 14-3-3 accumulation and tolerance to the conditions. Together, these results demonstrate that the physiological role of phosphorylation at 14-3-3 binding sites on ATL31 is to modulate the binding ability and stability of 14-3-3 proteins to control plant C/N-nutrient response. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Enterococcus faecium biofilm formation: identification of major autolysin AtlAEfm, associated Acm surface localization, and AtlAEfm-independent extracellular DNA Release.

PubMed

Paganelli, Fernanda L; Willems, Rob J L; Jansen, Pamela; Hendrickx, Antoni; Zhang, Xinglin; Bonten, Marc J M; Leavis, Helen L

2013-04-16

Enterococcus faecium is an important multidrug-resistant nosocomial pathogen causing biofilm-mediated infections in patients with medical devices. Insight into E. faecium biofilm pathogenesis is pivotal for the development of new strategies to prevent and treat these infections. In several bacteria, a major autolysin is essential for extracellular DNA (eDNA) release in the biofilm matrix, contributing to biofilm attachment and stability. In this study, we identified and functionally characterized the major autolysin of E. faecium E1162 by a bioinformatic genome screen followed by insertional gene disruption of six putative autolysin genes. Insertional inactivation of locus tag EfmE1162_2692 resulted in resistance to lysis, reduced eDNA release, deficient cell attachment, decreased biofilm, decreased cell wall hydrolysis, and significant chaining compared to that of the wild type. Therefore, locus tag EfmE1162_2692 was considered the major autolysin in E. faecium and renamed atlAEfm. In addition, AtlAEfm was implicated in cell surface exposure of Acm, a virulence factor in E. faecium, and thereby facilitates binding to collagen types I and IV. This is a novel feature of enterococcal autolysins not described previously. Furthermore, we identified (and localized) autolysin-independent DNA release in E. faecium that contributes to cell-cell interactions in the atlAEfm mutant and is important for cell separation. In conclusion, AtlAEfm is the major autolysin in E. faecium and contributes to biofilm stability and Acm localization, making AtlAEfm a promising target for treatment of E. faecium biofilm-mediated infections. IMPORTANCE Nosocomial infections caused by Enterococcus faecium have rapidly increased, and treatment options have become more limited. This is due not only to increasing resistance to antibiotics but also to biofilm-associated infections. DNA is released in biofilm matrix via cell lysis, caused by autolysin, and acts as a matrix stabilizer. In this study, we identified and characterized the major autolysin in E. faecium, which we designated AtlAEfm. atlAEfm disruption resulted in resistance to lysis, reduced extracellular DNA (eDNA), deficient cell attachment, decreased biofilm, decreased cell wall hydrolysis, and chaining. Furthermore, AtlAEfm is associated with Acm cell surface localization, resulting in less binding to collagen types I and IV in the atlAEfm mutant. We also identified AtlAEfm-independent eDNA release that contributes to cell-cell interactions in the atlAEfm mutant. These findings indicate that AtlAEfm is important in biofilm and collagen binding in E. faecium, making AtlAEfm a promising target for treatment of E. faecium infections.

Frontotemporal correlates of impulsivity and machine learning in retired professional athletes with a history of multiple concussions.

PubMed

Goswami, R; Dufort, P; Tartaglia, M C; Green, R E; Crawley, A; Tator, C H; Wennberg, R; Mikulis, D J; Keightley, M; Davis, Karen D

2016-05-01

The frontotemporal cortical network is associated with behaviours such as impulsivity and aggression. The health of the uncinate fasciculus (UF) that connects the orbitofrontal cortex (OFC) with the anterior temporal lobe (ATL) may be a crucial determinant of behavioural regulation. Behavioural changes can emerge after repeated concussion and thus we used MRI to examine the UF and connected gray matter as it relates to impulsivity and aggression in retired professional football players who had sustained multiple concussions. Behaviourally, athletes had faster reaction times and an increased error rate on a go/no-go task, and increased aggression and mania compared to controls. MRI revealed that the athletes had (1) cortical thinning of the ATL, (2) negative correlations of OFC thickness with aggression and task errors, indicative of impulsivity, (3) negative correlations of UF axial diffusivity with error rates and aggression, and (4) elevated resting-state functional connectivity between the ATL and OFC. Using machine learning, we found that UF diffusion imaging differentiates athletes from healthy controls with significant classifiers based on UF mean and radial diffusivity showing 79-84 % sensitivity and specificity, and 0.8 areas under the ROC curves. The spatial pattern of classifier weights revealed hot spots at the orbitofrontal and temporal ends of the UF. These data implicate the UF system in the pathological outcomes of repeated concussion as they relate to impulsive behaviour. Furthermore, a support vector machine has potential utility in the general assessment and diagnosis of brain abnormalities following concussion.

ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation.

PubMed

Dassouki, Zeina; Sahin, Umut; El Hajj, Hiba; Jollivet, Florence; Kfoury, Youmna; Lallemand-Breitenbach, Valérie; Hermine, Olivier; de Thé, Hugues; Bazarbachi, Ali

2015-01-15

The human T-cell lymphotropic virus type I (HTLV-1) Tax transactivator initiates transformation in adult T-cell leukemia/lymphoma (ATL), a highly aggressive chemotherapy-resistant malignancy. The arsenic/interferon combination, which triggers degradation of the Tax oncoprotein, selectively induces apoptosis of ATL cell lines and has significant clinical activity in Tax-driven murine ATL or human patients. However, the role of Tax loss in ATL response is disputed, and the molecular mechanisms driving degradation remain elusive. Here we demonstrate that ATL-derived or HTLV-1-transformed cells are dependent on continuous Tax expression, suggesting that Tax degradation underlies clinical responses to the arsenic/interferon combination. The latter enforces promyelocytic leukemia protein (PML) nuclear body (NB) formation and partner protein recruitment. In arsenic/interferon-treated HTLV-1 transformed or ATL cells, Tax is recruited onto NBs and undergoes PML-dependent hyper-sumoylation by small ubiquitin-like modifier (SUMO)2/3 but not SUMO1, ubiquitination by RNF4, and proteasome-dependent degradation. Thus, the arsenic/interferon combination clears ATL through degradation of its Tax driver, and this regimen could have broader therapeutic value by promoting degradation of other pathogenic sumoylated proteins. © 2015 by The American Society of Hematology.

Adult T-cell leukemia-lymphoma in a pregnant woman diagnosed as a human T-cell lymphotropic virus type 1 carrier.

PubMed

Fuchi, Naoki; Miura, Kiyonori; Imaizumi, Yoshitaka; Hasegawa, Hiroo; Yanagihara, Katsunori; Miyazaki, Yasushi; Masuzaki, Hideaki

2016-03-01

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia-lymphoma (ATL), which is difficult to cure. In Japan, a nationwide HTLV-1 screening test in pregnant women has been recommended since 2011. A 30-year-old woman was diagnosed as being an HTLV-1 carrier in her previous pregnancy. During the current pregnancy, she had persistent fever and cough. Although she had treatment with antibiotics, peripheral white blood cell count remained high, with an abnormal lymphocyte count. Given that she was an HTLV-1 carrier, she was diagnosed with unfavorable chronic ATL (aggressive ATL) at 12 weeks gestation. After pregnancy termination, her ATL status became favorable chronic ATL (indolent ATL). Therefore, watchful waiting was performed until disease progression. This is the first case report of chronic ATL in early pregnancy, in a woman already diagnosed as an HTLV-1 carrier on screening test. © 2015 Japan Society of Obstetrics and Gynecology.

Controversies in Targeted Therapy of Adult T Cell Leukemia/Lymphoma: ON Target or OFF Target Effects?

PubMed Central

Nasr, Rihab; Hajj, Hiba El; Kfoury, Youmna; de Thé, Hugues; Hermine, Olivier; Bazarbachi, Ali

2011-01-01

Adult T cell leukemia/lymphoma (ATL) represents an ideal model for targeted therapy because of intrinsic chemo-resistance of ATL cells and the presence of two well identified targets: the HTLV-I retrovirus and the viral oncoprotein Tax. The combination of zidovudine (AZT) and interferon-alpha (IFN) has a dramatic impact on survival of ATL patients. Although the mechanism of action remains unclear, arguments in favor or against a direct antiviral effect will be discussed. Yet, most patients relapse and alternative therapies are mandatory. IFN and arsenic trioxide induce Tax proteolysis, synergize to induce apoptosis in ATL cells and cure Tax-driven ATL in mice through specific targeting of leukemia initiating cell activity. These results provide a biological basis for the clinical success of arsenic/IFN/AZT therapy in ATL patients and suggest that both extinction of viral replication (AZT) and Tax degradation (arsenic/IFN) are needed to cure ATL. PMID:21994752

Center-to-Limb Variability of Hot Coronal EUV Emissions During Solar Flares

NASA Astrophysics Data System (ADS)

Thiemann, E. M. B.; Chamberlin, P. C.; Eparvier, F. G.; Epp, L.

2018-02-01

It is generally accepted that densities of quiet-Sun and active region plasma are sufficiently low to justify the optically thin approximation, and this is commonly used in the analysis of line emissions from plasma in the solar corona. However, the densities of solar flare loops are substantially higher, compromising the optically thin approximation. This study begins with a radiative transfer model that uses typical solar flare densities and geometries to show that hot coronal emission lines are not generally optically thin. Furthermore, the model demonstrates that the observed line intensity should exhibit center-to-limb variability (CTLV), with flares observed near the limb being dimmer than those occurring near disk center. The model predictions are validated with an analysis of over 200 flares observed by the EUV Variability Experiment (EVE) on the Solar Dynamics Observatory (SDO), which uses six lines, with peak formation temperatures between 8.9 and 15.8 MK, to show that limb flares are systematically dimmer than disk-center flares. The data are then used to show that the electron column density along the line of sight typically increases by 1.76 × 10^{19} cm^{-2} for limb flares over the disk-center flare value. It is shown that the CTLV of hot coronal emissions reduces the amount of ionizing radiation propagating into the solar system, and it changes the relative intensities of lines and bands commonly used for spectral analysis.

Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity against glioblastoma by targeting IKKβ kinase activity and interrupting NF-κB/COX-2-mediated signaling cascades.

PubMed

Wang, Xun; Yu, Zhenlong; Wang, Chao; Cheng, Wei; Tian, Xiangge; Huo, Xiaokui; Wang, Yan; Sun, Chengpeng; Feng, Lei; Xing, Jinshan; Lan, Yulong; Sun, Dongdong; Hou, Qingjuan; Zhang, Baojing; Ma, Xiaochi; Zhang, Bo

2017-07-12

Glioblastoma multiforme (GBM) is one of the most refractory and palindromic central nervous system (CNS) neoplasms, and current treatments have poor effects in GBM patients. Hence, the identification of novel therapeutic targets and the development of effective treatment strategies are essential. Alantolactone (ATL) has a wide range of pharmacological activities, and its anti-tumor effect is receiving increasing attention. However, the molecular mechanism underlying the anti-GBM activity of ATL remains poorly understood. The biological functions of ATL in GBM cells were investigated using migration/invasion, colony formation and cell cycle/apoptosis assays. The localization of nuclear factor kappa B (NF-κB) p50/p65 and its binding to the cyclooxygenase 2 (COX-2) promoter were determined using confocal immunofluorescence, a streptavidin-agarose pulldown assay and a chromatin immunoprecipitation (ChIP) assay. IKKβ kinase activity was determined using a cell IKKβ kinase activity spectrophotometry quantitative detection kit and a molecular docking study. LC-MS/MS analysis was performed to determine the ability of ATL to traverse the blood-brain barrier (BBB). The in vivo anti-tumor efficacy of ATL was also analyzed in xenografted nude mice. Western blot analysis was performed to detect the protein expression levels. ATL significantly suppressed the growth of GBM in vivo and in vitro. ATL significantly reduced the expression of COX-2 by inhibiting the kinase activity of IKKβ by targeting the ATP-binding site and then attenuating the binding of NF-κB to the COX-2 promoter region. Furthermore, ATL induced apoptosis by activating the cytochrome c (cyt c)/caspase cascade signaling pathway. Moreover, ATL could penetrate the BBB. ATL exerts its anti-tumor effects in human GBM cells at least in part via NF-κB/COX-2-mediated signaling cascades by inhibiting IKKβ kinase activity. ATL, which is a natural small molecule inhibitor, is a promising candidate for clinical applications in the treatment of CNS tumors.

Evaluation of two prognostic indices for adult T cell leukemia/lymphoma in the subtropical endemic area, Okinawa, Japan.

PubMed

Tamaki, Keita; Morishima, Satoko; Nomura, Shogo; Nishi, Yukiko; Nakachi, Sawako; Kitamura, Sakiko; Uchibori, Sachie; Tomori, Shouhei; Hanashiro, Taeko; Shimabukuro, Natsuki; Tedokon, Iori; Morichika, Kazuho; Taira, Naoya; Tomoyose, Takeaki; Miyagi, Takashi; Karimata, Kaori; Ohama, Masayo; Yamanoha, Atsushi; Tamaki, Kazumitsu; Hayashi, Masaki; Uchihara, Jun-Nosuke; Ohshiro, Kazuiku; Asakura, Yoshitaka; Kuba-Miyara, Megumi; Karube, Kennosuke; Fukushima, Takuya; Masuzaki, Hiroaki

2018-05-17

Aggressive adult T-cell leukemia/lymphoma (ATL) has an extremely poor prognosis and is hyperendemic in Okinawa, Japan. This study evaluated two prognostic indices (PIs) for aggressive ATL, the ATL-PI and Japan Clinical Oncology Group (JCOG)-PI, in a cohort from Okinawa. The PIs were developed using two different Japanese cohorts that included few patients from Okinawa. The endpoint was overall survival (OS). Multivariable Cox regression analyses in the cohort of 433 patients revealed that all seven factors for calculating each PI were statistically significant prognostic predictors. Three-year OS rates for ATL-PI were 35.9% (low-risk, n=66), 10.4% (intermediate-risk, n=256), and 1.6% (high-risk, n=111), and those for JCOG-PI were 22.4% (moderate-risk, n=176) and 5.3% (high-risk, n=257). The JCOG-PI moderate-risk group included both the ATL-PI low- and intermediate-risk groups. ATL-PI more clearly identified the low-risk patient subgroup than JCOG-PI. To evaluate the external validity of the two PIs, we also assessed prognostic discriminability among 159 patients who loosely met the eligibility criteria of a previous clinical trial. Three-year OS rates for ATL-PI were 34.5% (low-risk, n=42), 9.2% (intermediate-risk, n=109), and 12.5% (high-risk, n = 8). Those for JCOG-PI were 22.4% (moderate-risk, n=95) and 7.6% (high-risk, n=64). The low-risk ATL-PI group had a better prognosis than the JCOG-PI moderate-risk group, suggesting that ATL-PI would be more useful than JCOG-PI for establishing and examining novel treatment strategies for ATL patients with a better prognosis. In addition, strongyloidiasis, previously suggested to be associated with ATL-related deaths in Okinawa, was not a prognostic factor in this study. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

T Cell Receptor Vβ Staining Identifies the Malignant Clone in Adult T cell Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells

PubMed Central

Witkover, Aviva; Tanaka, Yuetsu; Fields, Paul; Bangham, Charles R. M.

2016-01-01

There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can contribute to long-term remission of many malignancies. The etiological agent of adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1), contains highly immunogenic CTL epitopes, but ATL patients typically have low frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation. It remains unclear whether patients with ATL possess CTLs that can kill the malignant HTLV-1 infected clone. Here we used flow cytometric staining of TCRVβ and cell adhesion molecule-1 (CADM1) to identify monoclonal populations of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we quantified the rate of CD8+-mediated killing of the putative malignant clone in ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable to lyse autologous ATL clones when tested directly ex vivo. However, short in vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which expressed the viral sense strand gene products was significantly enhanced after in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene were most likely to make a detectable lytic CD8+ response to the ATL cells. We conclude that some patients with ATL possess functional tumour-specific CTLs which could be exploited to contribute to control of the disease. PMID:27893842

Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow.

PubMed

Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F; McEver, Rodger P

2015-10-15

A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain "swing-out," which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Multi-inhibitory effects of A2A adenosine receptor signaling on neutrophil adhesion under flow**

PubMed Central

Yago, Tadayuki; Tsukamoto, Hiroki; Liu, Zhenghui; Wang, Ying; Thompson, Linda F.; McEver, Rodger P.

2015-01-01

A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, β2 integrin-dependent slow rolling and chemokine-induced, β2 integrin-dependent arrest on ICAM-1. ATL313 inhibited selectin-induced β2 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain “swing-out”, which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti-β2 integrin antibody. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1 (Rap1), and β2 integrin-triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A (PKA) and its substrate C-terminal Src kinase (Csk), an inhibitor of SFKs. Treating neutrophils with a PKA inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-α challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases. PMID:26355151

Identification and characterization of an autolysin gene, atlA, from Streptococcus criceti.

PubMed

Tamura, Haruki; Yamada, Arisa; Kato, Hirohisa

2012-10-01

AtlA of Streptococcus mutans is a major autolysin and belongs to glycoside hydrolase family 25 with cellosyl of Streptomyces coelicolor. The autolysin gene (atlA) encoding AtlA was identified from S. criceti. AtlA of S. criceti comprises the signal sequence in the N-terminus, the putative cell-wall-binding domain in the middle, and the catalytic domain in the C-terminus. Homology modeling analysis of the catalytic domain of AtlA showed the resemblance of the spatial arrangement of five amino acids around the predicted catalytic cavity to that of cellosyl. Recombinant AtlA and its four point mutants, D655A, D747A, W831A, and D849A, were evaluated on zymogram of S. criceti cells. Lytic activity was destroyed in the mutants D655A and D747A and diminished in the mutants W831A and D849A. These results suggest that Asp655 and Asp747 residues are critical for lytic activity and Trp831 and Asp849 residues are also associated with enzymatic activity.

Discovery of ATL: an odyssey in restrospect.

PubMed

Yodoi, Junji; Maeda, Michiyuki

2011-11-01

Forty years have passed since our initial description of peculiar cases of adult-onset leukemia with abnormal cells having multi-convoluted nuclei and T cell properties, frequent in the southern regions of Japan in the early 1970s. Retrospectively, the study of adult T cell leukemia (ATL) and the related virus HTLV-I was a forerunner for all of human retrovirology, in which AIDS and the related retrovirus HIV were identified a few years later in the 1980s. Using the anti-TAC monoclonal antibody generated by the late Takashi Uchiyama during his stay in T. A. Waldmann's laboratory in NIH Bethesda, a cDNA encoding IL-2Rα chain was cloned by our group in Kyoto and by Waldmann's group in Bethesda. Abnormal IL-2Rα chain expression and the IL-2 dependency of ATL cell lines greatly contributed to the study of leukemogenesis of ATL. A new soluble factor named ADF/ATL-derived factor was also detected in ATL cell lines. After years of study, ADF proved to be a first human counterpart of thiol-related oxido-reductase thioredoxin/TRX, which opened the field of redox regulation of cell signaling involved in a variety of diseases. Close interaction among Drs. Kimishige Ishizaka, Kiyoshi Takastuki and T. A. Waldmanns before ATL and HTLV-I study was an essential base for our initiation of ATL research with Takashi Uchiyama and many other colleagues.

Unbalanced inflammatory reaction could increase tissue destruction and worsen skin infectious diseases - a comparative study of leishmaniasis and sporotrichosis.

PubMed

Morgado, F N; de Carvalho, L M V; Leite-Silva, J; Seba, A J; Pimentel, M I F; Fagundes, A; Madeira, M F; Lyra, M R; Oliveira, M M; Schubach, A O; Conceição-Silva, F

2018-02-13

The clinical presentations of skin diseases produced by different pathogens, as American tegumentary leishmaniasis (ATL) and sporotrichosis can be similar and possibly influenced by the skin immune system (SIS). The aim of the study was to understand the underlying mechanisms of skin inflammation produced by different pathogens. We used immunohistochemistry to analyze 96 patients: a- localized cutaneous leishmaniasis (LCL-ATL); b- sporotrichoid cutaneous leishmaniasis (SCL-ATL); c-lymphocutaneous (LC-SP); d- fixed (F-SP) sporotrichosis. LCL-ATL and SCL-ATL had a significantly higher percentage of CD8, FasL and NOS2 than sporotrichosis. In contrast, LC-SP had a substantially higher percentage of CD4, BCl2 and neutrophils than ATL lesions. These results indicated some differences in the profile of the in situ immune response suggesting that SIS is a complex, adaptable system capable of different responses to intracellular or extracellular pathogens. However, regardless of the etiological agents, the inflammatory reaction and clinical manifestations can be similar. SCL-ATL and LC-SP presented similarities in both clinical presentation and in situ inflammatory profile (CD3, CD22, neutrophils, macrophages). The clinical presentation of ATL and sporotrichosis could be explained by a combination of factors both of the host SIS and the etiological agent. The unbalanced host parasite relationship could result in atypical manifestations of skin disease.

Anti-ATLA (antibody to adult T-cell leukemia-lymphoma virus-associated antigen)-negative adult T-cell leukemia-lymphoma.

PubMed

Shimoyama, M; Minato, K; Tobinai, K; Nagai, M; Setoya, T; Watanabe, S; Hoshino, H; Miwa, M; Nagoshi, H; Ichiki, N; Fukushima, N; Sugiura, K; Funaki, N

1983-01-01

Five cases of adult T-cell leukemia-lymphoma (ATL) having typical clinicohematologic and morphologic features but negative for anti-ATLA [antibody to ATL virus (ATLV)-associated antigen (ATLA)] are presented. Some differences in immunologic, epidemiologic, and serologic data between anti-ATLA-positive and -negative ATLs are also described. Expression of ATLA in early primary cultured leukemic cells was found to be negative in three patients tested (Cases 1, 2 and 4), however, a long-term cultured cell line, ATL-6A, derived from peripheral blood leukemia cells from Case 1, was found to express ATLA. Mother of Case 1 and a daughter of Case 2 were anti-ATLA negative. These results indicate that ATLV was involved in certain anti-ATLA-negative ATL patients, at least in Case 1, and that the patient had no detectable immune response against ATLV and ATLA. However, in other cases in which no ATLA reactivity of serum and no ATLA expression in cultured leukemic cells were observed, another possibility such as activation of an unknown cellular oncogene specific for ATL without ATLV involvement may be considered. In order to prove these possibilities definitely, it is necessary to elucidate whether or not proviral DNA of ATLV is integrated into chromosomal DNA of ATL cells and to find a cellular oncogene specific for ATL in the future.

NASA Glenn's Acoustical Testing Laboratory Awarded Accreditation by the National Voluntary Laboratory Accreditation Program

NASA Technical Reports Server (NTRS)

Akers, James C.; Cooper, Beth A.

2004-01-01

NASA Glenn Research Center's Acoustical Testing Laboratory (ATL) provides a comprehensive array of acoustical testing services, including sound pressure level, sound intensity level, and sound-power-level testing per International Standards Organization (ISO)1 3744. Since its establishment in September 2000, the ATL has provided acoustic emission testing and noise control services for a variety of customers, particularly microgravity space flight hardware that must meet International Space Station acoustic emission requirements. The ATL consists of a 23- by 27- by 20-ft (height) convertible hemi/anechoic test chamber and a separate sound-attenuating test support enclosure. The ATL employs a personal-computer-based data acquisition system that provides up to 26 channels of simultaneous data acquisition with real-time analysis (ref. 4). Specialized diagnostic tools, including a scanning sound-intensity system, allow the ATL's technical staff to support its clients' aggressive low-noise design efforts to meet the space station's acoustic emission requirement. From its inception, the ATL has pursued the goal of developing a comprehensive ISO 17025-compliant quality program that would incorporate Glenn's existing ISO 9000 quality system policies as well as ATL-specific technical policies and procedures. In March 2003, the ATL quality program was awarded accreditation by the National Voluntary Laboratory Accreditation Program (NVLAP) for sound-power-level testing in accordance with ISO 3744. The NVLAP program is administered by the National Institutes of Standards and Technology (NIST) of the U.S. Department of Commerce and provides third-party accreditation for testing and calibration laboratories. There are currently 24 NVLAP-accredited acoustical testing laboratories in the United States. NVLAP accreditation covering one or more specific testing procedures conducted in accordance with established test standards is awarded upon successful completion of an intensive onsite assessment that includes proficiency testing and documentation review. The ATL NVLAP accreditation currently applies specifically to its ISO 3744 soundpower- level determination procedure (see the photograph) and supporting ISO 17025 quality system, although all ATL operations are conducted in accordance with its quality system. The ATL staff is currently developing additional procedures to adapt this quality system to the testing of space flight hardware in accordance with International Space Station acoustic emission requirements.<

Relationship between the occlusal plane corresponding to the lateral borders of the tongue and ala-tragus line in edentulous patients.

PubMed

Ghosn, Carole Abi; Zogheib, Carla; Makzoumé, Joseph E

2012-09-01

Definitions of the ala-tragus line (ATL) cause confusion, because the exact points of reference for this line do not agree. This study determined the relationship between the prosthetic occlusal plane (OP) corresponding to the lateral borders of the tongue and ATL which was established by using the inferior border of the ala of the nose and (1) the superior border of the tragus (ATL 1), (2) the tip (ATL 2) and (3) the inferior border of the tragus (ATL 3). Neutral zone moldings using phonation and autopolymerizing acrylic resin were recorded and leveled with the lateral borders of the tongue. Lateral cephalometric radiographs were taken of each subject by a standard method. Tracings were obtained on acetate paper to show the prosthetic OP and the three ATLs. The relationship between the prosthetic OP and each of ATL was measured for each subject. Mean and standard deviation values were then calculated for the relationship. Statistical analysis was performed using repeated measure analysis of variance followed by Bonferroni pairwise comparisons and Student's t-test (α = 0.05). Significant difference was found between the three mean angles (p = 0.001). There was no significant difference between the mean angle (5.00° ± 4.38) formed by OP and ATL 2, and the mean angle (4.90° ± 3.50) formed by OP and ATL 3 (p = 1.00) which revealed the smallest. The findings of this study indicated that ATLs, extending from the inferior border of the ala of the nose to (1) the tip of the tragus of the ear, and (2) the inferior border of the tragus presented the closest relationship to the prosthetic OP corresponding to the lateral borders of the tongue. When the ATL is used for orientation of the OP in denture construction, it would seem preferable to define it as running from the inferior border of the ala of the nose to the tip or to the inferior border of the tragus of the ear.

Comparison of HTLV-I Proviral Load in Adult T Cell Leukemia/Lymphoma (ATL), HTLV-I-Associated Myelopathy (HAM-TSP) and Healthy Carriers.

PubMed

Akbarin, Mohammad Mehdi; Rahimi, Hossein; Hassannia, Tahereh; Shoja Razavi, Ghazaleh; Sabet, Faezeh; Shirdel, Abbas

2013-03-01

Human T Lymphocyte Virus Type one (HTLV-I) is a retrovirus that infects about 10-20 million people worldwide. Khorasan province in Iran is an endemic area. The majority of HTLV-I-infected individuals sustain healthy carriers but small proportion of infected population developed two progressive diseases: HAM/TSP and ATL. The proviral load could be a virological marker for disease monitoring, therefore in the present study HTLV-I proviral load has been evaluated in ATL and compared to HAM/TSP and healthy carriers. In this case series study, 47 HTLV-I infected individuals including 13 ATL, 23 HAM/TSP and 11 asymptomatic subjects were studied. Peripheral blood mononuclear cells (PBMCs) were investigated for presence of HTLV-I DNA provirus by PCR using LTR and Tax fragments. Then in infected subjects, HTLV-I proviral load was measured using real time PCR TaqMan method. The average age of patients in ATL was 52±8, in HAM/TSP 45.52±15.17 and in carrier's 38.65±14.9 years which differences were not statistically significant. The analysis of data showed a significant difference in mean WBC among study groups (ATL vs HAM/TSP and carriers P=0.0001). Moreover, mean HTLV-I proviral load was 11967.2 ± 5078, 409 ± 71.3 and 373.6 ± 143.3 in ATL, HAM/TSP and Healthy Carriers, respectively. The highest HTLV-I proviral load was measured in ATL group that had a significant correlation with WBC count (R=0.495, P=0.001). The proviral load variations between study groups was strongly significant (ATL vs carrier P=0.0001; ATL vs HAM/TSP P= 0.0001 and HAM/TSP vs carriers P< 0.05). Conclusion : The present study demonstrated that HTLV-I proviral load was higher in ATL group in comparison with HAM/TSP and healthy carriers. Therefore, HTLV-I proviral load is a prognostic factor for development of HTLV-I associated diseases and can be used as a monitoring marker for the efficiency of therapeutic regime.

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis.

PubMed

Martin, Roy C; Kretzmer, Tracy; Palmer, Cheryl; Sawrie, Stephen; Knowlton, Robert; Faught, Edward; Morawetz, Richard; Kuzniecky, Ruben

2002-12-01

Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

PubMed Central

Dantzler, William H.; Pannabecker, Thomas L.

2012-01-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter.

PubMed

Layton, Anita T; Dantzler, William H; Pannabecker, Thomas L

2012-03-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na(+) or urea-Cl(-) cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na(+) or urea- Cl(-) cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

A genetic IFN/STAT1/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and Adult T-cell Leukemia patients.

PubMed

Khouri, Ricardo; Silva-Santos, Gilvanéia; Dierckx, Tim; Menezes, Soraya Maria; Decanine, Daniele; Theys, Kristof; Silva, Aline Clara; Farré, Lourdes; Bittencourt, Achiléa; Mangino, Massimo; Roederer, Mario; Vandamme, Anne-Mieke; Van Weyenbergh, Johan

2018-01-01

Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4 + CD25 + leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (T SCM ) Fas hi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied. In this study, we found significant ex vivo antiproliferative, antiviral and immunomodulatory effects of IFN-α treatment in short-term culture of primary mononuclear cells from ATL patients (n = 25). Bayesian Network analysis allowed us to integrate ex vivo IFN-α response with clinical, genetic and immunological data from ATL patients, thereby revealing a central role for FAS -670 polymorphism and apoptosis in the coordinated mechanism of action of IFN-α. FAS genotype-dependence of IFN-induced apoptosis was experimentally validated in an independent cohort of healthy controls (n = 20). The same FAS -670 polymorphism also determined CD4 T SCM levels in a genome-wide twin study (p = 7 × 10 -11 , n = 460), confirming a genetic link between apoptosis and T SCM levels. Transcriptomic analysis and cell type deconvolution confirmed the FAS genotype/T SCM link and IFN-α-induced downregulation of CD4 T SCM -specific genes in ATL patient cells. In conclusion, ex vivo IFN-α treatment exerts a pleiotropic effect on primary ATL cells, with a genetic IFN/STAT1/Fas axis determining apoptosis vs. proliferation and underscoring the CD4 T SCM model of ATL leukemogenesis.

Diversity in the architecture of ATLs, a family of plant ubiquitin-ligases, leads to recognition and targeting of substrates in different cellular environments.

PubMed

Aguilar-Hernández, Victor; Aguilar-Henonin, Laura; Guzmán, Plinio

2011-01-01

Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS) that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20-28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress.

Antibodies to adult T-cell leukemia-virus-associated antigen (ATLA) in sera from patients with ATL and controls in Japan: a nation-wide sero-epidemiologic study.

PubMed

Hinuma, Y; Komoda, H; Chosa, T; Kondo, T; Kohakura, M; Takenaka, T; Kikuchi, M; Ichimaru, M; Yunoki, K; Sato, I; Matsuo, R; Takiuchi, Y; Uchino, H; Hanaoka, M

1982-06-15

A nation-wide sero-epidemiologic survey of adult T-cell leukemia virus (ATLV), detected es anti-ATLA (ATLV-associated antigen), was made in Japan. Sera from adult donors in 15 different locations were screened for anti-ATLA. High incidences (6 to 37%) of antibody-positive donors were found in seven regions, one in northern Japan, and the others in southwestern regions. These areas are ATLV-endemic areas corresponding to ATL-endemic areas. Examination of sera from healthy donors aged 6 to 80 years in ATL-endemic areas showed an age-dependent increase of seropositive donors with a maximum of about 30% at 40 years of age. Anti-ATLA was found in all but two of 142 patients with ATL. Anti-ATLA-positive patients with ATL were mainly found in ATLV-endemic areas, and only a few in ATL-nonendemic areas. Six patients with cutaneous T-cell lymphoma in ATLV-nonendemic areas gave a negative reaction for anti-ATLA. The geometric mean titer of anti-ATLA of patients with ATL was higher than that of healthy donors.

Expression and regulation of ATL9, an E3 ubiquitin ligase involved in plant defense

PubMed Central

Lefebvre, Mitchell; Scaglione, Steven; Antico, Christopher J.; Jing, Tao; Yang, Xin; Shan, Weixing

2017-01-01

Plants are continually exposed to a variety of pathogenic organisms, including bacteria, fungi and viruses. In response to these assaults, plants have developed various defense pathways to protect themselves from pathogen invasion. An understanding of the expression and regulation of genes involved in defense signaling is essential to controlling plant disease. ATL9, an Arabidopsis RING zinc finger protein, is an E3 ubiquitin ligase that is induced by chitin and involved in basal resistance to the biotrophic fungal pathogen, Golovinomyces cichoracearum (G. cichoracearum). To better understand the expression and regulation of ATL9, we studied its expression pattern and the functions of its different protein domains. Using pATL9:GUS transgenic Arabidopsis lines we found that ATL9 is expressed in numerous tissues at various developmental stages and that GUS activity was induced rapidly upon wounding. Using a GFP control protein, we showed that ATL9 is a short-lived protein within plant cells and it is degraded via the ubiquitin-proteasome pathway. ATL9 contains two transmembrane domains (TM), a RING zinc-finger domain, and a PEST domain. Using a series of deletion mutants, we found that the PEST domain and the RING domain have effects on ATL9 degradation. Further infection assays with G. cichoracearum showed that both the RING domain and the TM domains are important for ATL9’s resistance phenotype. Interestingly, the PEST domain was also shown to be significant for resistance to fungal pathogens. This study demonstrates that the PEST domain is directly coupled to plant defense regulation and the importance of protein degradation in plant immunity. PMID:29161311

Individual memory change after anterior temporal lobectomy: a base rate analysis using regression-based outcome methodology.

PubMed

Martin, R C; Sawrie, S M; Roth, D L; Gilliam, F G; Faught, E; Morawetz, R B; Kuzniecky, R

1998-10-01

To characterize patterns of base rate change on measures of verbal and visual memory after anterior temporal lobectomy (ATL) using a newly developed regression-based outcome methodology that accounts for effects of practice and regression towards the mean, and to comment on the predictive utility of baseline memory measures on postoperative memory outcome. Memory change was operationalized using regression-based change norms in a group of left (n = 53) and right (n = 48) ATL patients. All patients were administered tests of episodic verbal (prose recall, list learning) and visual (figure reproduction) memory, and semantic memory before and after ATL. ATL patients displayed a wide range of memory outcome across verbal and visual memory domains. Significant performance declines were noted for 25-50% of left ATL patients on verbal semantic and episodic memory tasks, while one-third of right ATL patients displayed significant declines in immediate and delayed episodic prose recall. Significant performance improvement was noted in an additional one-third of right ATL patients on delayed prose recall. Base rate change was similar between the two ATL groups across immediate and delayed visual memory. Approximately one-fourth of all patients displayed clinically meaningful losses on the visual memory task following surgery. Robust relationships between preoperative memory measures and nonstandardized change scores were attenuated or reversed using standardized memory outcome techniques. Our results demonstrated substantial group variability in memory outcome for ATL patients. These results extend previous research by incorporating known effects of practice and regression to the mean when addressing meaningful neuropsychological change following epilepsy surgery. Our findings also suggest that future neuropsychological outcome studies should take steps towards controlling for regression-to-the-mean before drawing predictive conclusions.

A Bioimpedance Analysis Platform for Amputee Residual Limb Assessment.

PubMed

Sanders, Joan E; Moehring, Mark A; Rothlisberger, Travis M; Phillips, Reid H; Hartley, Tyler; Dietrich, Colin R; Redd, Christian B; Gardner, David W; Cagle, John C

2016-08-01

The objective of this research was to develop a bioimpedance platform for monitoring fluid volume in residual limbs of people with trans-tibial limb loss using prostheses. A customized multifrequency current stimulus profile was sent to thin flat electrodes positioned on the thigh and distal residual limb. The applied current signal and sensed voltage signals from four pairs of electrodes located on the anterior and posterior surfaces were demodulated into resistive and reactive components. An established electrical model (Cole) and segmental limb geometry model were used to convert results to extracellular and intracellular fluid volumes. Bench tests and testing on amputee participants were conducted to optimize the stimulus profile and electrode design and layout. The proximal current injection electrode needed to be at least 25 cm from the proximal voltage sensing electrode. A thin layer of hydrogel needed to be present during testing to ensure good electrical coupling. Using a burst duration of 2.0 ms, intermission interval of 100 μs, and sampling delay of 10 μs at each of 24 frequencies except 5 kHz, which required a 200-μs sampling delay, the system achieved a sampling rate of 19.7 Hz. The designed bioimpedance platform allowed system settings and electrode layouts and positions to be optimized for amputee limb fluid volume measurement. The system will be useful toward identifying and ranking prosthetic design features and participant characteristics that impact residual limb fluid volume.

The Dependence of Solar Flare Limb Darkening on Emission Peak Formation Temperature

NASA Astrophysics Data System (ADS)

Thiemann, Edward; Epp, Luke; Eparvier, Francis; Chamberlin, Phillip C.

2017-08-01

Solar limb effects are local brightening or darkening of an emission that depend on where in the Sun's atmosphere it forms. Near the solar limb, optically thick (thin) emissions will darken (brighten) as the column of absorbers (emitters) along the line-of-sight increases. Note that in limb brightening, emission sources are re-arranged whereas in limb darkening they are obscured. Thus, only limb darkening is expected to occur in disk integrated observations. Limb darkening also results in center-to-limb variations of disk-integrated solar flare spectra, with important consequences for how planetary atmospheres are affected by flares. Flares are typically characterized by their flux in the optically thin 0.1-0.8 nm band measured by the X-ray Sensor (XRS) on board the Geostationary Operational Environmental Satellite (GOES). On the other hand, Extreme Ultraviolet (EUV) line emissions can limb darken because they are sensitive to resonant scattering, resulting in a flare's location on the solar disk controlling the amount of ionizing radiation that reaches a planet. For example, an X-class flare originating from disk center may significantly heat a planet's thermosphere, whereas the same flare originating near the limb may have no effect because much of the effective emissions are scattered in the solar corona.To advance the relatively poor understanding of flare limb darkening, we use over 300 M-class or larger flares observed by the EUV Variability Experiment (EVE) onboard the Solar Dynamics Observatory (SDO) to characterize limb darkening as a function of emission peak formation temperature, Tf. For hot coronal emissions (Tf>2 MK), these results show a linear relationship between the degree of limb darkening and Tf where lines with Tf=2 MK darken approximately 7 times more than lines with Tf=16 MK. Because the extent of limb darkening is dependent on the height of the source plasma, we use simple Beer-Lambert radiative transfer analysis to interpret these results and characterize the average thermal structure of the flares considered. As such, these results can be used to constrain both empirical flare irradiance models and more sophisticated flare loop hydrodynamic models.

Impact of peptidoglycan O-acetylation on autolytic activities of the Enterococcus faecalis N-acetylglucosaminidase AtlA and N-acetylmuramidase AtlB.

PubMed

Emirian, Aurélie; Fromentin, Sophie; Eckert, Catherine; Chau, Françoise; Dubost, Lionel; Delepierre, Muriel; Gutmann, Laurent; Arthur, Michel; Mesnage, Stéphane

2009-09-17

Autolysins are potentially lethal enzymes that partially hydrolyze peptidoglycan for incorporation of new precursors and septum cleavage after cell division. Here, we explored the impact of peptidoglycan O-acetylation on the enzymatic activities of Enterococcus faecalis major autolysins, the N-acetylglucosaminidase AtlA and the N-acetylmuramidase AtlB. We constructed isogenic strains with various O-acetylation levels and used them as substrates to assay E. faecalis autolysin activities. Peptidoglycan O-acetylation had a marginal inhibitory impact on the activities of these enzymes. In contrast, removal of cell wall glycopolymers increased the AtlB activity (37-fold), suggesting that these polymers negatively control the activity of this enzyme.

Induction of apoptosis by HBI-8000 in adult T-cell leukemia/lymphoma is associated with activation of Bim and NLRP3.

PubMed

Hasegawa, Hiroo; Bissonnette, Reid P; Gillings, Mireille; Sasaki, Daisuke; Taniguchi, Hiroaki; Kitanosono, Hideaki; Tsuruda, Kazuto; Kosai, Kousuke; Uno, Naoki; Morinaga, Yoshitomo; Imaizumi, Yoshitaka; Miyazaki, Yasushi; Yanagihara, Katsunori

2016-08-01

Adult T-cell leukemia/lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell lymphotropic virus 1. Treatment options for acute ATL patients include chemotherapy, stem cell transplantation, and recently the anti-chemokine (C-C motif) receptor 4 antibody, although most patients still have a poor prognosis and there is a clear need for additional options. HBI-8000 is a novel oral histone deacetylase inhibitor with proven efficacy for treatment of T-cell lymphomas that recently received approval in China. In the present study, we evaluated the effects of HBI-8000 on ATL-derived cell lines and primary cells obtained from Japanese ATL patients. In most cases HBI-8000 induced apoptosis in both primary ATL cells and cell lines. In addition, findings obtained with DNA microarray suggested Bim activation and, interestingly, the contribution of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome pathway in HBI-8000-induced ATL cell death. Further investigations using siRNAs confirmed that Bim contributes to HBI-8000-induced apoptosis. Our results provide a rationale for a clinical investigation of the efficacy of HBI-8000 in patients with ATL. Although the role of NLRP3 inflammasome activation in ATL cell death remains to be verified, HBI-8000 may be part of a novel therapeutic strategy for cancer based on the NLRP3 pathway. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Tax-Independent Constitutive IκB Kinase Activation in Adult T-Cell Leukemia Cells1

PubMed Central

Hironaka, Noriko; Mochida, Kanako; Mori, Naoki; Maeda, Michiyuki; Yamamoto, Naoki; Yamaoka, Shoji

2004-01-01

Abstract Adult T-cell leukemia (ATL) is a fatal T-cell malignancy that arises long after infection with human T-cell leukemia virus type I (HTLV-I). We reported previously that nuclear factor-κB (NF-κB) was constitutively activated in ATL cells, although expression of the viral proteins was barely detectable, including Tax, which was known to persistently activate NF-κB. Here we demonstrate that ATL cells that do not express detectable Tax protein exhibit constitutive IκB kinase (IKK) activity. Transfection studies revealed that a dominant-negative form of IKK1, and not of IKK2 or NF-κB essential modulator (NEMO), suppressed constitutive NFκB activity in ATL cells. This IKK activity was accompanied by elevated expression of p52, suggesting that the recently described noncanonical pathway of NF-κB activation operates in ATL cells. We finally show that specific inhibition of NF-κB by a super-repressor form of IκBα (SR-IκBα) in HTLV-I-infected T cells results in cell death regardless of Tax expression, providing definitive evidence of an essential role for NF-κB in the survival of ATL cells. In conclusion, the IKK complex is constitutively activated in ATL cells through a cellular mechanism distinct from that of Tax-mediated IKK activation. Further elucidation of this cellular mechanism should contribute to establishing a rationale for treatment of ATL. PMID:15153339

Biofilm and toxin profile: A phenotypic and genotypic characterization of coagulase-negative staphylococci isolated from human bloodstream infections.

PubMed

Pedroso, S H S P; Sandes, S H C; Luiz, K C M; Dias, R S; Filho, R A T; Serufo, J C; Farias, L M; Carvalho, M A R; Bomfim, M R Q; Santos, S G

2016-11-01

Coagulase-negative staphylococci (CNS) represent one of the most prevalent microorganisms in nosocomial infections worldwide, nevertheless little is known about their pathogenicity features. Thus, our aim was to characterize virulence aspects of CNS isolated from patients with bloodstream infections assisted in hospitals of Belo Horizonte, MG, Brazil. Strains were identified using bioMérieuxVitek ® and for biofilm production evaluation, Congo Red Agar (CRA) and polystyrene plates were used. PCR was applied to detect icaA, icaB, icaC, atlE, sea, sec, sed, tsst-1 and agr. For statistical analyses were used hierarchical cluster, chi-square test and correspondence. 59 strains were analyzed, being S. haemolyticus the most prevalent. On CRA, 96.5% were biofilm producer, whereas on polystyrene plate, 100% showed adhesion at different times evaluated. Regarding genotypic analyses, 15.2%, 38.9%, 8.4%, 49.1%, 76.2%, 23.7%, 1.6%, 30.5% and 38.9% were positive for icaA, icaB, icaC, atlE, sea, sec, sed, tsst-1 and agr, respectively. Six clusters were formed and frequency distributions of agr, atlE, icaA, icaB, sea, sec, tsst-1 differed (P < 0.001). In conclusion, all strains were biofilm producer, with high prevalence of atlE, and had potential of toxin production, with high prevalence of sea. According to the group-analyses, icaB showed relationship with the strong adherence in samples. Copyright © 2016 Elsevier Ltd. All rights reserved.

Competition and enhancement effect in coremoval of atenolol and copper by an easily regenerative magnetic cation exchange resin.

PubMed

Li, Qimeng; Wang, Zheng; Li, Qiang; Shuang, Chendong; Zhou, Qing; Li, Aimin; Gao, Canzhu

2017-07-01

This paper aimed to investigate the removal of combined Cu 2+ and atenolol (ATL) in aqueous solution by using a newly synthesized magnetic cation exchange resin (MCER) as the adsorbent. The MCER exhibited efficient removal performance in sole, binary, pre-loading and saline systems. The adsorption kinetics of Cu 2+ and ATL fitted both pseudo-first-order and pseudo-second order model, while better described by pseudo-second order model in binary system. In mixed Cu 2+ and ATL solution, the adsorption of ATL was suppressed due to direct competition of carboxylic groups, while Cu 2+ adsorption was enhanced because of the formation of surface complexes. This increasing in heterogeneity was demonstrated by adsorption isotherms, which were more suitable for Freundlich model in binary system, while better described by Langmuir model in sole system. As proved by FTIR and XPS spectra, both amino and hydroxyl groups of ATL could form complexes with Cu 2+ . Decomplexing-bridging interaction was elucidated as the leading mechanism in coremoval of Cu 2+ and ATL, which involved [Cu-ATL] decomplexing and newly created Cu- or ATL sites for additional bridging. For saline system, the resulting competition and enhancement effects in mixed solution were amplified with the addition of co-existing cations. Moreover, the MCER could be effectively regenerated by 0.01 M HCl solution and maintain high stability over 5 adsorption-desorption cycles, which render it great potential for practical applications. Copyright © 2017. Published by Elsevier Ltd.

Development of an enzyme-linked immunosorbent assay and a beta-1 adrenergic receptor-based assay for monitoring the drug atenolol.

PubMed

Sapir, A; Shalev, A Hariton; Skalka, N; Bronshtein, A; Altstein, M

2013-03-01

Two approaches for monitoring atenolol (ATL) were applied: an immunochemical assay and a competitive-binding assay, based on the interaction between ATL and its target receptor, β1 adrenergic receptor (β1AR). Polyclonal antibodies (Abs) for ATL were generated, and a highly specific microplate immunochemical assay, that is, an enzyme-linked immunosorbent assay (ELISA), for its detection was developed. The ATL ELISA exhibited I50 and limit of detection (I20) values of 0.15 ± 0.048 and 0.032 ± 0.016 ng/ml, respectively, and the Abs did not cross-react with any of the tested beta-blocker drugs. Furthermore, a human β1AR (h-β1AR) was stably expressed in Spodoptera frugiperda cells (Sf9). The receptor was employed to develop a competitive-binding assay that monitored binding of ATL in the presence of isoproteranol by quantification of secondary messenger, cyclic adenosine monophosphate (cAMP), levels in the transfected cells. The assay showed that the recombinant h-β1AR was functional, could bind the agonistic ligand isoproterenol as well as the antagonist ATL, as indicated by a dose-dependent elevation of cAMP in the presence of isoproteranol, and decrease after ATL addition. The highly efficient and sensitive ELISA and the receptor assay represent two methods suitable for efficient and cost-effective large-scale, high-throughput monitoring of ATL in environmental, agricultural, and biological samples. Copyright © 2012 SETAC.

Vertical distribution of Martian aerosols from SPICAM/Mars-Express limb observations

NASA Astrophysics Data System (ADS)

Fedorova, A.; Korablev, O.; Bertaux, J.-L.; Rodin, A.; Perrier, S.; Moroz, V. I.

Limb spectroscopic observations provide invaluable information about vertical distribution of main atmospheric components in the Martian atmosphere, in particular vertical distribution and structure of aerosols, which play an important role in the heat balance of the planet. Only limited set of successful limb spectroscopic observations have been carried out on Mars so far, including those by MGS/TES spectrometer and Thermoscan and Auguste experiments of Phobos mission. Currently SPICAM instrument onboard Mars-Express spacecraft has accomplished several sequences of limb observations. First analysis of limb sounding data received by SPICAM IR and UV channels, which imply the presence of fine, deep, optically thin aerosol fraction extended over broad range of altitudes, is presented.

Quantification of HTLV-1 reverse transcriptase activity in ATL patients treated with zidovudine and interferon-α.

PubMed

Macchi, Beatrice; Balestrieri, Emanuela; Frezza, Caterina; Grelli, Sandro; Valletta, Elena; Marçais, Ambroise; Marino-Merlo, Francesca; Turpin, Jocelyn; Bangham, Charles R; Hermine, Olivier; Mastino, Antonio; Bazarbachi, Ali

2017-05-09

The therapeutic efficacy of the AZT and IFN combination in ATL presumably reflects the inhibition of RT-related functions.HTLV-1-RT activity from short-term cultured PBMCs may represent a predictive correlate of clinical response to AZT/IFN in ATL patients.

Anterior temporal lobes mediate semantic representation: Mimicking semantic dementia by using rTMS in normal participants

PubMed Central

Pobric, Gorana; Jefferies, Elizabeth; Ralph, Matthew A. Lambon

2007-01-01

Studies of semantic dementia and PET neuroimaging investigations suggest that the anterior temporal lobes (ATL) are a critical substrate for semantic representation. In stark contrast, classical neurological models of comprehension do not include ATL, and likewise functional MRI studies often fail to show activations in the ATL, reinforcing the classical view. Using a novel application of low-frequency, repetitive transcranial magnetic stimulation (rTMS) over the ATL, we demonstrate that the behavioral pattern of semantic dementia can be mirrored in neurologically intact participants: Specifically, we show that temporary disruption to neural processing in the ATL produces a selective semantic impairment leading to significant slowing in both picture naming and word comprehension but not to other equally demanding, nonsemantic cognitive tasks. PMID:18056637

Revealing the Dynamic Modulations That Underpin a Resilient Neural Network for Semantic Cognition: An fMRI Investigation in Patients With Anterior Temporal Lobe Resection.

PubMed

Rice, Grace E; Caswell, Helen; Moore, Perry; Lambon Ralph, Matthew A; Hoffman, Paul

2018-06-06

One critical feature of any well-engineered system is its resilience to perturbation and minor damage. The purpose of the current study was to investigate how resilience is achieved in higher cognitive systems, which we explored through the domain of semantic cognition. Convergent evidence implicates the bilateral anterior temporal lobes (ATLs) as a conceptual knowledge hub. While bilateral damage to this region produces profound semantic impairment, unilateral atrophy/resection or transient perturbation has a limited effect. Two neural mechanisms might underpin this resilience to unilateral ATL damage: 1) the undamaged ATL upregulates its activation in order to compensate; and/or 2) prefrontal regions involved in control of semantic retrieval upregulate to compensate for the impoverished semantic representations that follow from ATL damage. To test these possibilities, 34 postsurgical temporal lobe epilepsy patients and 20 age-matched controls were scanned whilst completing semantic tasks. Pictorial tasks, which produced bilateral frontal and temporal activation, showed few activation differences between patients and control participants. Written word tasks, however, produced a left-lateralized activation pattern and greater differences between the groups. Patients with right ATL resection increased activation in left inferior frontal gyrus (IFG). Patients with left ATL resection upregulated both the right ATL and right IFG. Consistent with recent computational models, these results indicate that 1) written word semantic processing in patients with ATL resection is supported by upregulation of semantic knowledge and control regions, principally in the undamaged hemisphere, and 2) pictorial semantic processing is less affected, presumably because it draws on a more bilateral network.

Effects of oxygen on biofilm formation and the AtlA autolysin of Streptococcus mutans.

PubMed

Ahn, Sang-Joon; Burne, Robert A

2007-09-01

The Streptococcus mutans atlA gene encodes an autolysin required for biofilm maturation and biogenesis of a normal cell surface. We found that the capacity to form biofilms by S. mutans, one of the principal causative agents of dental caries, was dramatically impaired by growth of the organism in an aerated environment and that cells exposed to oxygen displayed marked changes in surface protein profiles. Inactivation of the atlA gene alleviated repression of biofilm formation in the presence of oxygen. Also, the formation of long chains, a characteristic of AtlA-deficient strains, was less evident in cells grown with aeration. The SMu0629 gene is immediately upstream of atlA and encodes a product that contains a C-X-X-C motif, a characteristic of thiol-disulfide oxidoreductases. Inactivation of SMu0629 significantly reduced the levels of AtlA protein and led to resistance to autolysis. The SMu0629 mutant also displayed an enhanced capacity to form biofilms in the presence of oxygen compared to that of the parental strain. The expression of SMu0629 was shown to be under the control of the VicRK two-component system, which influences oxidative stress tolerance in S. mutans. Disruption of vicK also led to inhibition of processing of AtlA, and the mutant was hyperresistant to autolysis. When grown under aerobic conditions, the vicK mutant also showed significantly increased biofilm formation compared to strain UA159. This study illustrates the central role of AtlA and VicK in orchestrating growth on surfaces and envelope biogenesis in response to redox conditions.

Are Approaches to Learning in Kindergarten Associated with Academic and Social Competence Similarly?

ERIC Educational Resources Information Center

Razza, Rachel A.; Martin, Anne; Brooks-Gunn, Jeanne

2015-01-01

Background: Approaches to learning (ATL) is a key domain of school readiness with important implications for children's academic trajectories. Interestingly, however, the impact of early ATL on children's social competence has not been examined. Objective: This study examines associations between children's ATL at age 5 and academic achievement…

The incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type 1 carriers in Japan.

PubMed

Satake, Masahiro; Yamada, Yasuaki; Atogami, Sunao; Yamaguchi, Kazunari

2015-06-01

Human T-lymphotropic virus type 1 (HTLV-1) is highly endemic in the Kyushu/Okinawa region of Japan. A nationwide investigation verified the frequency of HTLV-1 carriers among first-time blood donors and the occurrence of newly diagnosed adult T-cell leukemia/lymphoma (ATL) cases from 2007 through 2008. After adjusting for differences in capture rate between areas, the age-, sex- and area-specific incidence of ATL among carriers was determined. Annual ATL incidence among 10 000 carriers was 7.7 and 8.7 for the Kyushu and non-Kyushu/Okinawa regions, respectively. The incidence increased sharply for men from their 40s to their 70s, but the rate in females remained unchanged through their 40s to 70s. ATL incidence in middle-aged females was still low, even if female carrier frequency was assumed to be identical to that of males. Patients with ATL in their 60s and 70s will comprise two-thirds of all patients with ATL for the next 15 years in Japan.

Sensory-Neuropathy-Causing Mutations in ATL3 Cause Aberrant ER Membrane Tethering.

PubMed

Krols, Michiel; Detry, Sammy; Asselbergh, Bob; Almeida-Souza, Leonardo; Kremer, Anna; Lippens, Saskia; De Rycke, Riet; De Winter, Vicky; Müller, Franz-Josef; Kurth, Ingo; McMahon, Harvey T; Savvides, Savvas N; Timmerman, Vincent; Janssens, Sophie

2018-05-15

The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro, these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity but are unable to promote membrane fusion, suggesting a defect in an intermediate step of the ATL3 functional cycle. Our data show that the effects of ATL3 mutations on ER network organization go beyond a loss of fusion and shed light on neuropathies caused by atlastin defects. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mapping the Multiple Graded Contributions of the Anterior Temporal Lobe Representational Hub to Abstract and Social Concepts: Evidence from Distortion-corrected fMRI.

PubMed

Binney, Richard J; Hoffman, Paul; Lambon Ralph, Matthew A

2016-09-06

A growing body of recent convergent evidence indicates that the anterior temporal lobe (ATL) has connectivity-derived graded differences in semantic function: the ventrolateral region appears to be the transmodal, omni-category center-point of the hub whilst secondary contributions come from the peripheries of the hub in a manner that reflects their differential connectivity to different input/output modalities. One of the key challenges for this neurocognitive theory is how different types of concept, especially those with less reliance upon external sensory experience (such as abstract and social concepts), are coded across the graded ATL hub. We were able to answer this key question by using distortion-corrected fMRI to detect functional activations across the entire ATL region and thus to map the neural basis of social and psycholinguistically-matched abstract concepts. Both types of concept engaged a core left-hemisphere semantic network, including the ventrolateral ATL, prefrontal regions and posterior MTG. Additionally, we replicated previous findings of weaker differential activation of the superior and polar ATL for the processing of social stimuli, in addition to the stronger, omni-category activation observed in the vATL. These results are compatible with the view of the ATL as a graded transmodal substrate for the representation of coherent concepts. © The Author 2016. Published by Oxford University Press.

Mapping the Multiple Graded Contributions of the Anterior Temporal Lobe Representational Hub to Abstract and Social Concepts: Evidence from Distortion-corrected fMRI

PubMed Central

Binney, Richard J.; Hoffman, Paul; Lambon Ralph, Matthew A.

2016-01-01

A growing body of recent convergent evidence indicates that the anterior temporal lobe (ATL) has connectivity-derived graded differences in semantic function: the ventrolateral region appears to be the transmodal, omni-category center-point of the hub whilst secondary contributions come from the peripheries of the hub in a manner that reflects their differential connectivity to different input/output modalities. One of the key challenges for this neurocognitive theory is how different types of concept, especially those with less reliance upon external sensory experience (such as abstract and social concepts), are coded across the graded ATL hub. We were able to answer this key question by using distortion-corrected fMRI to detect functional activations across the entire ATL region and thus to map the neural basis of social and psycholinguistically-matched abstract concepts. Both types of concept engaged a core left-hemisphere semantic network, including the ventrolateral ATL, prefrontal regions and posterior MTG. Additionally, we replicated previous findings of weaker differential activation of the superior and polar ATL for the processing of social stimuli, in addition to the stronger, omni-category activation observed in the vATL. These results are compatible with the view of the ATL as a graded transmodal substrate for the representation of coherent concepts. PMID:27600844

Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan.

PubMed

Iwanaga, Masako; Watanabe, Toshiki; Utsunomiya, Atae; Okayama, Akihiko; Uchimaru, Kaoru; Koh, Ki-Ryang; Ogata, Masao; Kikuchi, Hiroshi; Sagara, Yasuko; Uozumi, Kimiharu; Mochizuki, Manabu; Tsukasaki, Kunihiro; Saburi, Yoshio; Yamamura, Masaomi; Tanaka, Junji; Moriuchi, Yukiyoshi; Hino, Shigeo; Kamihira, Shimeru; Yamaguchi, Kazunari

2010-08-26

Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was significantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL.

Mapping Anterior Temporal Lobe Language Areas with FMRI: A Multi-Center Normative Study

PubMed Central

Binder, Jeffrey R.; Gross, William L.; Allendorfer, Jane B.; Bonilha, Leonardo; Chapin, Jessica; Edwards, Jonathan C.; Grabowski, Thomas J.; Langfitt, John T.; Loring, David W.; Lowe, Mark J.; Koenig, Katherine; Morgan, Paul S.; Ojemann, Jeffrey G.; Rorden, Christopher; Szaflarski, Jerzy P.; Tivarus, Madalina E.; Weaver, Kurt E.

2010-01-01

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series. PMID:20884358

Ubiquitin ligase ATL31 functions in leaf senescence in response to the balance between atmospheric CO2 and nitrogen availability in Arabidopsis.

PubMed

Aoyama, Shoki; Huarancca Reyes, Thais; Guglielminetti, Lorenzo; Lu, Yu; Morita, Yoshie; Sato, Takeo; Yamaguchi, Junji

2014-02-01

Carbon (C) and nitrogen (N) are essential elements for metabolism, and their availability, called the C/N balance, must be tightly coordinated for optimal growth in plants. Previously, we have identified the ubiquitin ligase CNI1/ATL31 as a novel C/N regulator by screening plants grown on C/N stress medium containing excess sugar and limited N. To elucidate further the effect of C/N balance on plant growth and to determine the physiological function of ATL31, we performed C/N response analysis using an atmospheric CO2 manipulation system. Under conditions of elevated CO2 and sufficient N, plant biomass and total sugar and starch dramatically increased. In contrast, elevated CO2 with limited N did not increase plant biomass but promoted leaf chlorosis, with anthocyanin accumulation and increased senescence-associated gene expression. Similar results were obtained with plants grown in medium containing excess sugar and limited N, suggesting that disruption of the C/N balance affects senescence progression. In ATL31-overexpressing plants, promotion of senescence under disrupted CO2/N conditions was repressed, whereas in the loss-of-function mutant it was enhanced. The ATL31 gene was transcriptionally up-regulated under N deficiency and in senescent leaves, and ATL31 expression was highly correlated with WRKY53 expression, a key regulator of senescence. Furthermore, transient protoplast analysis implicated the direct activation of ATL31 expression by WRKY53, which was in accordance with the results of WRKY53 overexpression experiments. Together, these results demonstrate the importance of C/N balance in leaf senescence and the involvement of ubiquitin ligase ATL31 in the process of senescence in Arabidopsis.

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia-lymphoma cells.

PubMed

Taniguchi, Hiroaki; Hasegawa, Hiroo; Sasaki, Daisuke; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Imaizumi, Yoshitaka; Hata, Tomoko; Tsukasaki, Kunihiro; Uno, Naoki; Morinaga, Yoshitomo; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-12-01

Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia–lymphoma cells

PubMed Central

Taniguchi, Hiroaki; Hasegawa, Hiroo; Sasaki, Daisuke; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Imaizumi, Yoshitaka; Hata, Tomoko; Tsukasaki, Kunihiro; Uno, Naoki; Morinaga, Yoshitomo; Yanagihara, Katsunori; Miyazaki, Yasushi

2014-01-01

Adult T-cell leukemia–lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. PMID:25263741

The adhesive properties of the Staphylococcus lugdunensis multifunctional autolysin AtlL and its role in biofilm formation and internalization.

PubMed

Hussain, Muzaffar; Steinbacher, Tim; Peters, Georg; Heilmann, Christine; Becker, Karsten

2015-01-01

Although it belongs to the group of coagulase-negative staphylococci, Staphylococcus lugdunensis has been known to cause aggressive courses of native and prosthetic valve infective endocarditis with high mortality similar to Staphylococcus aureus. In contrast to S. aureus, only little is known about the equipment of S. lugdunensis with virulence factors including adhesins and their role in mediating attachment to extracellular matrix and plasma proteins and host cells. In this study, we show that the multifunctional autolysin/adhesin AtlL of S. lugdunensis binds to the extracellular matrix and plasma proteins fibronectin, fibrinogen, and vitronectin as well as to human EA.hy926 endothelial cells. Furthermore, we demonstrate that AtlL also plays an important role in the internalization of S. lugdunensis by eukaryotic cells: The atlL-deficient mutant Mut17 adheres to and becomes internalized by eukaryotic cells to a lesser extent than the isogenic wild-type strain Sl253 and the complemented mutant Mut17 (pCUatlL) shows an increased internalization level in comparison to Mut17. Thus, surface localized AtlL that exhibits a broad binding spectrum also mediates the internalization of S. lugdunensis by eukaryotic cells. We therefore propose an internalization pathway for S. lugdunensis, in which AtlL plays a major role. Investigating the role of AtlL in biofilm formation of S. lugdunensis, Mut17 shows a significantly reduced ability for biofilm formation, which is restored in the complemented mutant. Thus, our data provide evidence for a significant role for AtlL in adherence and internalization processes as well as in biofilm formation of S. lugdunensis. Copyright © 2014 Elsevier GmbH. All rights reserved.

AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis

PubMed Central

Hsu, Ron-Bin; Shun, Chia-Tung; Hsu, Chih-Chieh

2017-01-01

ABSTRACT Host factors, such as platelets, have been shown to enhance biofilm formation by oral commensal streptococci, inducing infective endocarditis (IE), but how bacterial components contribute to biofilm formation in vivo is still not clear. We demonstrated previously that an isogenic mutant strain of Streptococcus mutans deficient in autolysin AtlA (ΔatlA) showed a reduced ability to cause vegetation in a rat model of bacterial endocarditis. However, the role of AtlA in bacterial biofilm formation is unclear. In this study, confocal laser scanning microscopy analysis showed that extracellular DNA (eDNA) was embedded in S. mutans GS5 floes during biofilm formation on damaged heart valves, but an ΔatlA strain could not form bacterial aggregates. Semiquantification of eDNA by PCR with bacterial 16S rRNA primers demonstrated that the ΔatlA mutant strain produced dramatically less eDNA than the wild type. Similar results were observed with in vitro biofilm models. The addition of polyanethol sulfonate, a chemical lysis inhibitor, revealed that eDNA release mediated by bacterial cell lysis is required for biofilm initiation and maturation in the wild-type strain. Supplementation of cultures with calcium ions reduced wild-type growth but increased eDNA release and biofilm mass. The effect of calcium ions on biofilm formation was abolished in ΔatlA cultures and by the addition of polyanethol sulfonate. The VicK sensor, but not CiaH, was found to be required for the induction of eDNA release or the stimulation of biofilm formation by calcium ions. These data suggest that calcium ion-regulated AtlA maturation mediates the release of eDNA by S. mutans, which contributes to biofilm formation in infective endocarditis. PMID:28674029

Technical Review of SRS Dose Reconstrruction Methods Used By CDC

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

Simpkins, Ali, A

2005-07-20

At the request of the Centers for Disease Control and Prevention (CDC), a subcontractor Advanced Technologies and Laboratories International, Inc.(ATL) issued a draft report estimating offsite dose as a result of Savannah River Site operations for the period 1954-1992 in support of Phase III of the SRS Dose Reconstruction Project. The doses reported by ATL differed than those previously estimated by Savannah River Site SRS dose modelers for a variety of reasons, but primarily because (1) ATL used different source terms, (2) ATL considered trespasser/poacher scenarios and (3) ATL did not consistently use site-specific parameters or correct usage parameters. Themore » receptors with the highest dose from atmospheric and liquid pathways were within about a factor of four greater than dose values previously reported by SRS. A complete set of technical comments have also been included.« less

Leishmania (Viannia) guyanensis in tegumentary leishmaniasis.

PubMed

Borges, Arissa Felipe; Gomes, Rodrigo Saar; Ribeiro-Dias, Fátima

2018-06-01

Leishmania (Viannia) guyanensis is a causal agent of American tegumentary leishmaniasis (ATL). This protozoan has been poorly investigated; however, it can cause different clinical forms of ATL, ranging from a single cutaneous lesion to severe lesions that can lead to destruction of the nasopharyngeal mucosa. L. (V.) guyanensis and the disease caused by this species can present unique aspects revealing the need to better characterize this parasite species to improve our knowledge of the immunopathological mechanisms and treatment options for ATL. The mechanisms by which some patients develop a more severe form of ATL remain unclear. It is known that the host immune profile and parasite factors may influence the clinical manifestations of the disease. Besides intrinsic parasite factors, Leishmaniavirus RNA 1 (LRV1) infecting L. guyanensis can contribute to ATL immunopathogenesis. In this review, general aspects of L. guyanensis infection in humans and mouse models are presented.

The Ventral Anterior Temporal Lobe has a Necessary Role in Exception Word Reading.

PubMed

Ueno, Taiji; Meteyard, Lotte; Hoffman, Paul; Murayama, Kou

2018-06-06

An influential account of reading holds that words with exceptional spelling-to-sound correspondences (e.g., PINT) are read via activation of their lexical-semantic representations, supported by the anterior temporal lobe (ATL). This account has been inconclusive because it is based on neuropsychological evidence, in which lesion-deficit relationships are difficult to localize precisely, and functional neuroimaging data, which is spatially precise but cannot demonstrate whether the ATL activity is necessary for exception word reading. To address these issues, we used a technique with good spatial specificity-repetitive transcranial magnetic stimulation (rTMS)-to demonstrate a necessary role of ATL in exception word reading. Following rTMS to left ventral ATL, healthy Japanese adults made more regularization errors in reading Japanese exception words. We successfully simulated these results in a computational model in which exception word reading was underpinned by semantic activations. The ATL is critically and selectively involved in reading exception words.

EPOCH regimen as salvage therapy for adult T-cell leukemia-lymphoma.

PubMed

Toriyama, Eo; Imaizumi, Yoshitaka; Taniguchi, Hiroaki; Taguchi, Jun; Nakashima, Jun; Itonaga, Hidehiro; Sato, Shinya; Ando, Koji; Sawayama, Yasushi; Hata, Tomoko; Fukushima, Takuya; Miyazaki, Yasushi

2018-04-12

Adult T-cell leukemia-lymphoma (ATL) is an intractable hematopoietic malignancy with a very poor prognosis. Although improved responses have been achieved through intensive chemotherapy in newly diagnosed patients with aggressive ATL, most patients suffer from relapse or disease recurrence, and an effective salvage therapy, especially for candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT), is yet to be established. The efficacy of the EPOCH regimen has been reported for several lymphoid malignancies; however, its efficacy for ATL has not been sufficiently evaluated. Here, we report results of a study of the EPOCH regimen as a salvage therapy for ATL. We retrospectively analyzed patients with relapsed or refractory ATL treated in our institution, with EPOCH as a first salvage therapy. Fourteen patients with a median age of 58 years were analyzed, among whom eight achieved a response, including a complete response in one patient and partial responses in seven. Seven patients underwent allo-HSCT after EPOCH therapy; however, the median overall survival (OS) could not be determined, whereas OS at 2 years after allo-HSCT was estimated to be 85.7%. These results suggest that EPOCH is an option for salvage therapy in patients with ATL, including candidates for allo-HSCT.

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.

High incidence of antibodies to HTLV-I tax in blood relatives of adult T cell leukemia patients.

PubMed

Okayama, A; Chen, Y M; Tachibana, N; Shioiri, S; Lee, T H; Tsuda, K; Essex, M

1991-01-01

Adult T cell leukemia (ATL) is caused by the human T cell leukemia virus type I (HTLV-I). Although the mechanisms of the leukemogenic process are unknown, the tax gene may have a role in this process. Because clustering occurs with HTLV-I and ATL, members of ATL families were examined for antibodies to the tax protein and compared with matched HTLV-I-positive blood donors. To investigate the antibody response to this protein, a plasmid, pBHX-4, was constructed to express a recombinant tax protein (r-tax). For ATL patients and their HTLV-I antibody-positive blood relatives, the rate of seroreactivity with the r-tax protein was 67.3% (35/52), compared with 51.6% (97/188) for HTLV-I antibody-positive control blood donors (P less than .05). The difference between direct offspring of ATL patients and matched HTLV-I blood donors was even greater (84.2% [16/91] vs. 44.2% [42/95]; P less than .005). Thus, tax antibody positivity in direct offspring of ATL patients may reflect differences in time or route of HTLV-I infection. Alternatively, it might reflect genetic differences in host susceptibility or virus strain.

The timing of anterior temporal lobe involvement in semantic processing.

PubMed

Jackson, Rebecca L; Lambon Ralph, Matthew A; Pobric, Gorana

2015-07-01

Despite indications that regions within the anterior temporal lobe (ATL) might make a crucial contribution to pan-modal semantic representation, to date there have been no investigations of when during semantic processing the ATL plays a critical role. To test the timing of the ATL involvement in semantic processing, we studied the effect of double-pulse TMS on behavioral responses in semantic and difficulty-matched control tasks. Chronometric TMS was delivered over the left ATL (10 mm from the tip of the temporal pole along the middle temporal gyrus). During each trial, two pulses of TMS (40 msec apart) were delivered either at baseline (before stimulus presentation) or at one of the experimental time points 100, 250, 400, and 800 msec poststimulus onset. A significant disruption to performance was identified from 400 msec on the semantic task but not on the control assessment. Our results not only reinforce the key role of the left ATL in semantic representation but also indicate that its contribution is especially important around 400 msec poststimulus onset. Together, these facts suggest that the ATL may be one of the neural sources of the N400 ERP component.

Relational vs. attributive interpretation of nominal compounds differentially engages angular gyrus and anterior temporal lobe

PubMed Central

Boylan, Christine; Trueswell, John C.; Thompson-Schill, Sharon L.

2018-01-01

The angular gyrus (AG) and anterior temporal lobe (ATL) have been found to respond to a number of tasks involving combinatorial processing. In this study, we investigate the conceptual combination of nominal compounds, and ask whether ATL/AG activity is modulated by the type of combinatorial operation applied to a nominal compound. We compare relational and attributive interpretations of nominal compounds and find that ATL and AG both discriminate these two types, but in distinct ways. While right AG demonstrated greater positive task-responsive activity for relational compounds, there was a greater negative deflection in the BOLD response in left AG for relational compounds. In left ATL, we found an earlier peak in subjects’ BOLD response curves for attributive interpretations. In other words, we observed dissociations in both AG and ATL between relational and attributive nominal compounds, with regard to magnitude in the former and to timing in the latter. These findings expand on prior studies that posit roles for both AG and ATL in conceptual processing generally, and in conceptual combination specifically, by indicating possible functional specializations of these two regions within a larger conceptual knowledge network. PMID:28236762

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions.

PubMed

Jackson, Rebecca L; Hoffman, Paul; Pobric, Gorana; Lambon Ralph, Matthew A

2016-02-03

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. Copyright © 2016 Jackson et al.

The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions

PubMed Central

Jackson, Rebecca L.; Hoffman, Paul; Pobric, Gorana

2016-01-01

The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. SIGNIFICANCE STATEMENT Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. PMID:26843633

Reaction time in pilots during intervals of high sustained g.

PubMed

Truszczynski, Olaf; Lewkowicz, Rafal; Wojtkowiak, Mieczyslaw; Biernacki, Marcin P

2014-11-01

An important problem for pilots is visual disturbances occurring under +Gz acceleration. Assessment of the degree of intensification of these disturbances is generally accepted as the acceleration tolerance level (ATL) criterion determined in human centrifuges. The aim of this research was to evaluate the visual-motor responses of pilots during rapidly increasing acceleration contained in cyclic intervals of +6 Gz to the maximum ATL. The study involved 40 male pilots ages 32-41 yr. The task was a quick and faultless response to the light stimuli presented on a light bar during exposure to acceleration until reaching the ATL. Simple response time (SRT) measurements were performed using a visual-motor analysis system throughout the exposures which allowed assessment of a pilot's ATL. There were 29 pilots who tolerated the initial phase of interval acceleration and achieved +6 Gz, completing the test at ATL. Relative to the control measurements, the obtained results indicate a significant effect of the applied acceleration on response time. SRT during +6 Gz exposure was not significantly longer compared with the reaction time between each of the intervals. SRT and erroneous reactions indicated no statistically significant differences between the "lower" and "higher" ATL groups. SRT measurements over the +6-Gz exposure intervals did not vary between "lower" and "higher" ATL groups and, therefore, are not useful in predicting pilot performance. The gradual exposure to the maximum value of +6 Gz with exposure to the first three intervals on the +6-Gz plateau effectively differentiated pilots.

The challenge of localizing the anterior temporal face area: a possible solution.

PubMed

Axelrod, Vadim; Yovel, Galit

2013-11-01

Humans recognize faces exceptionally well. However, the neural correlates of face recognition are still elusive. Accumulated evidence in recent years suggests that the anterior temporal lobe (ATL), in particular face-selective region in the ATL, is a probable locus of face recognition. Unfortunately, functional MRI (fMRI) studies encounter severe signal drop-out in the ventral ATL, where that ATL face area resides. Consequently, all previous studies localized this region in no more than half of the subjects and its volume was relatively small. Thus, a systematic exploration of the properties of the ATL face area is scarce. In the current high-resolution fMRI study we used coronal slice orientation, which permitted us to localize the ATL face area in all the subjects. Furthermore, the volume of the area was much larger than was reported in previous studies. Direct within subjects comparison with data collected with the commonly used axial slice orientation confirmed that the advantage of the coronal slice orientation in revealing a reliable and larger face-selective area in the ATL. Finally, by displaying the face-selective activations resultant from coronal and axial scanning together, we demonstrate an organization principle of a chain of face-selective regions along the posterior-anterior axis in the ventral temporal lobe that is highly reproducible across all subjects. By using the procedure proposed here, a significant progress can be made in studying the neural correlates of face recognition. Copyright © 2013 Elsevier Inc. All rights reserved.

Second messenger production in avian medullary nephron segments in response to peptide hormones.

PubMed

Goldstein, D L; Reddy, V; Plaga, K

1999-03-01

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy.

PubMed

Elliott, Cameron A; Broad, Andrew; Narvacan, Karl; Steve, Trevor A; Snyder, Thomas; Urlacher, Jordan; Wheatley, B Matt; Sinclair, D Barry

2018-06-22

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the initial operation was significantly more likely following ATL (47/61, 77%) than SelAH (8/18, 44%; p = 0.017, Fisher's exact test). There was no statistically significant difference in the proportion of patients with postoperative neuropsychological deficits following SelAH (8/18, 44%) or ATL (21/61, 34%). However, reoperation was significantly more likely following SelAH (8/18, 44%) than after ATL (7/61, 11%; p = 0.004) and was more likely to result in Engel I outcome for ATL after failed SelAH (7/8, 88%) than for posterior extension after failed ATL (1/7, 14%; p = 0.01). Reoperation was well tolerated without significant neuropsychological deterioration. Ultimately, including 15 reoperations, 58 of 79 (73%) patients were free from disabling seizures at the most recent follow-up. CONCLUSIONS SelAH among pediatric patients with medically refractory unilateral TLE yields significantly worse rates of seizure control compared with ATL. Reoperation is significantly more likely following SelAH, is not associated with incremental neuropsychological deterioration, and frequently results in freedom from disabling seizures. These results are significant in that they argue against using SelAH for pediatric TLE surgery.

Polarization from Thomson scattering of the light of a spherical, limb-darkened star

NASA Technical Reports Server (NTRS)

Rudy, R. J.

1979-01-01

The polarized flux produced by the Thomson scattering of the light of a spherical, limb-darkened star by optically thin, extrastellar regions of electrons is calculated and contrasted to previous models which treated the star as a point source. The point-source approximation is found to be valid for scattering by particles more than a stellar radius from the surface of the star but is inappropriate for those lying closer. The specific effect of limb darkening on the fractional polarization of the total light of a system is explored. If the principal source of light is the unpolarized flux of the star, the polarization is nearly independent of limb darkening.

Distinct neural substrates for semantic knowledge and naming in the temporoparietal network.

PubMed

Gesierich, Benno; Jovicich, Jorge; Riello, Marianna; Adriani, Michela; Monti, Alessia; Brentari, Valentina; Robinson, Simon D; Wilson, Stephen M; Fairhall, Scott L; Gorno-Tempini, Maria Luisa

2012-10-01

Patients with anterior temporal lobe (ATL) lesions show semantic and lexical retrieval deficits, and the differential role of this area in the 2 processes is debated. Functional neuroimaging in healthy individuals has not clarified the matter because semantic and lexical processes usually occur simultaneously and automatically. Furthermore, the ATL is a region challenging for functional magnetic resonance imaging (fMRI) due to susceptibility artifacts, especially at high fields. In this study, we established an optimized ATL-sensitive fMRI acquisition protocol at 4 T and applied an event-related paradigm to study the identification (i.e., association of semantic biographical information) of celebrities, with and without the ability to retrieve their proper names. While semantic processing reliably activated the ATL, only more posterior areas in the left temporal and temporal-parietal junction were significantly modulated by covert lexical retrieval. These results suggest that within a temporoparietal network, the ATL is relatively more important for semantic processing, and posterior language regions are relatively more important for lexical retrieval.

Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications.

PubMed

Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

2011-01-01

There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS). The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS. The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14-19 years) from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia), Bahrain, Dubai (United Arab Emirates), Kuwait, Amman (Jordan), Mosel (Iraq), Muscat (Oman), Tunisia (Tunisia) and Kenitra (Morocco). Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits. The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention.

Selective targeting of JAK/STAT signaling is potentiated by Bcl-xL blockade in IL-2–dependent adult T-cell leukemia

PubMed Central

Zhang, Meili; Mathews Griner, Lesley A.; Ju, Wei; Duveau, Damien Y.; Guha, Rajarshi; Petrus, Michael N.; Wen, Bernard; Maeda, Michiyuki; Shinn, Paul; Ferrer, Marc; Conlon, Kevin D.; Bamford, Richard N.; O’Shea, John J.; Thomas, Craig J.; Waldmann, Thomas A.

2015-01-01

Adult T-cell leukemia (ATL) develops in individuals infected with human T-cell lymphotropic virus-1 (HTLV-1). Presently there is no curative therapy for ATL. HTLV-1–encoded protein Tax (transactivator from the X-gene region) up-regulates Bcl-xL (B-cell lymphoma-extra large) expression and activates interleukin-2 (IL-2), IL-9, and IL-15 autocrine/paracrine systems, resulting in amplified JAK/STAT signaling. Inhibition of JAK signaling reduces cytokine-dependent ex vivo proliferation of peripheral blood mononuclear cells (PBMCs) from ATL patients in smoldering/chronic stages. Currently, two JAK inhibitors are approved for human use. In this study, we examined activity of multiple JAK inhibitors in ATL cell lines. The selective JAK inhibitor ruxolitinib was examined in a high-throughput matrix screen combined with >450 potential therapeutic agents, and Bcl-2/Bcl-xL inhibitor navitoclax was identified as a strong candidate for multicomponent therapy. The combination was noted to strongly activate BAX (Bcl-2-associated X protein), effect mitochondrial depolarization, and increase caspase 3/7 activities that lead to cleavage of PARP (poly ADP ribose polymerase) and Mcl-1 (myeloid cell leukemia 1). Ruxolitinib and navitoclax independently demonstrated modest antitumor efficacy, whereas the combination dramatically lowered tumor burden and prolonged survival in an ATL murine model. This combination strongly blocked ex vivo proliferation of five ATL patients’ PBMCs. These studies provide support for a therapeutic trial in patients with smoldering/chronic ATL using a drug combination that inhibits JAK signaling and antiapoptotic protein Bcl-xL. PMID:26396258

Effectiveness of an immunohistochemical protocol for Leishmania detection in different clinical forms of American tegumentary leishmaniasis.

PubMed

Marques, Fernanda A; Soares, Rodrigo P; Almeida, Gregório G; Souza, Carolina C; Melo, Maria N; Pinto, Sebastião A; Quixabeira, Valeria B; Pereira, Ledice I; Dorta, Miriam L; Ribeiro-Dias, Fatima; Silveira, Fernando T; Silva, Sydnei M; Gontijo, Celia M; Tafuri, Wagner L

2017-02-01

American tegumentary leishmaniasis (ATL) is a neglected disease widely distributed in Latin America. In Brazil, it is caused by different Leishmania species belonging to the Subgenera Viannia and Leishmania. ATL diagnosis is routinely based on clinical, epidemiological, parasitological and immunological (delayed-type hypersensitivity skin test-DTH) evidences. The main objective of this work was to determine the efficacy of a previous immunohistochemical (IHC) method developed by our group. Seventy eight skin biopsies from patients with different ATL clinical forms and origins were evaluated. The method was previously standardized in ATL patients from the municipality of Caratinga, Minas Gerais, Brazil, all infected with Leishmania (V.) braziliensis. Here, it is evaluated in patients from the North, Southeast and Midwest regions of Brazil. Clinical, parasitological (biopsy PCR) and immunological (Montenegro skin test-MST) diagnosis were performed prior to IHC procedure. The IHC procedure detected 70.5% of the cases having a high agreement with MST diagnosis (kappa=0.84). A distinguished contribution of this work is that IHC succeed in diagnosing some negative DTH patients. Those were infected with Leishmania (L.) amazonensis, commonly causing the anergic form of the disease. In conclusion, IHC succeed in detecting ATL caused by different Leishmania species from various geographic regions and clinical status. Although it was not able to detect ATL in all patients, it was better than MST providing an additional tool for the diagnosis of ATL patients. There was no significant correlation between clinical forms and histological features including the presence of necrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The course of language functions after temporal lobe epilepsy surgery: a prospective study.

PubMed

Giovagnoli, A R; Parente, A; Didato, G; Manfredi, V; Deleo, F; Tringali, G; Villani, F

2016-12-01

Anterior temporal lobectomy (ATL) within the language-dominant hemisphere can impair naming. This prospective study examined the pre-operative to post-operative course of different language components, clarifying which changes are relevant within the short-term and long-term outcome of language. Patients with drug-resistant temporal lobe epilepsy (TLE) were evaluated using the Token, Boston Naming and Word Fluency tests assessing sentence comprehension and word-finding on visual, semantic or phonemic cues. A total of 106 patients were evaluated before and 6 months, 1 and 2 years after ATL; 60 patients were also evaluated after 5 years and 38 controls were assessed at baseline. Seizure outcome was comparable between the left and right TLE patients. Before surgery, naming and word fluency were impaired in the left and right TLE patients, whereas sentence comprehension was normal. After left or right ATL, word fluency progressively improved, naming showed early worsening and late improvement after left ATL and progressive improvement after right ATL, and sentence comprehension did not change. At the 5-year follow-up, naming improvement was clinically significant in 31% and 71% of the left and right TLE patients, respectively. Pre-operative naming, ATL laterality, schooling, and post-operative seizure frequency and number of antiepileptic drugs predicted post-operative naming. Pre-operative word fluency and schooling predicted post-operative word fluency. Left or right TLE can impair word-finding but not sentence comprehension. After ATL, word-finding may improve for a long time, depending on TLE laterality, seizure control and mental reserve. These findings may clarify prognosis prior to treatment. © 2016 EAN.

The inferior, anterior temporal lobes and semantic memory clarified: novel evidence from distortion-corrected fMRI.

PubMed

Visser, M; Embleton, K V; Jefferies, E; Parker, G J; Ralph, M A Lambon

2010-05-01

The neural basis of semantic memory generates considerable debate. Semantic dementia results from bilateral anterior temporal lobe (ATL) atrophy and gives rise to a highly specific impairment of semantic memory, suggesting that this region is a critical neural substrate for semantic processing. Recent rTMS experiments with neurologically-intact participants also indicate that the ATL are a necessary substrate for semantic memory. Exactly which regions within the ATL are important for semantic memory are difficult to detect from these methods (because the damage in SD covers a large part of the ATL). Functional neuroimaging might provide important clues about which specific areas exhibit activation that correlates with normal semantic performance. Neuroimaging studies, however, have not consistently found anterior temporal lobe activation in semantic tasks. A recent meta-analysis indicates that this inconsistency may be due to a collection of technical limitations associated with previous studies, including a reduced field-of-view and magnetic susceptibility artefacts associated with standard gradient echo fMRI. We conducted an fMRI study of semantic memory using a combination of techniques which improve sensitivity to ATL activations whilst preserving whole-brain coverage. As expected from SD patients and ATL rTMS experiments, this method revealed bilateral temporal activation extending from the inferior temporal lobe along the fusiform gyrus to the anterior temporal regions, bilaterally. We suggest that the inferior, anterior temporal lobe region makes a crucial contribution to semantic cognition and utilising this version of fMRI will enable further research on the semantic role of the ATL. 2010 Elsevier Ltd. All rights reserved.

Degradation of atenolol via heterogeneous activation of persulfate by using BiOCl@Fe3O4 catalyst under simulated solar light irradiation.

PubMed

Shi, Yahong; Chen, Hongche; Wu, Yanlin; Dong, Wenbo

2018-01-01

Efficient oxidative degradation of pharmaceutical pollutants in aquatic environments is of great importance. This study used magnetic BiOCl@Fe 3 O 4 catalyst to activate persulfate (PS) under simulated solar light irradiation. This degradation system was evaluated using atenolol (ATL) as target pollutant. Four reactive species were identified in the sunlight/BiOCl@Fe 3 O 4 /PS system. The decreasing order of the contribution of each reactive species on ATL degradation was as follows: h +  ≈ HO ·  > O 2 ·-  > SO 4 ·- . pH significantly influenced ATL degradation, and an acidic condition favored the reaction. High degradation efficiencies were obtained at pH 2.3-5.5. ATL degradation rate increased with increased catalyst and PS contents. Moreover, ATL mineralization was higher in the sunlight/BiOCl@Fe 3 O 4 /PS system than in the sunlight/BiOCl@Fe 3 O 4 or sunlight/PS system. Nine possible intermediate products were identified through LC-MS analysis, and a degradation pathway for ATL was proposed. The BiOCl@Fe 3 O 4 nanomagnetic composite catalyst was synthesized in this work. This catalyst was easily separated and recovered from a treated solution by using a magnet, and it demonstrated a high catalytic activity. Increased amount of the BiOCl@Fe 3 O 4 catalyst obviously accelerated the efficiency of ATL degradation, and the reusability of the catalyst allowed the addition of a large dosage of BiOCl@Fe 3 O 4 to improve the degradation efficiency.

Prognostic index for chronic- and smoldering-type adult T-cell leukemia-lymphoma.

PubMed

Katsuya, Hiroo; Shimokawa, Mototsugu; Ishitsuka, Kenji; Kawai, Kazuhiro; Amano, Masahiro; Utsunomiya, Atae; Hino, Ryosuke; Hanada, Shuichi; Jo, Tatsuro; Tsukasaki, Kunihiro; Moriuchi, Yukiyoshi; Sueoka, Eisaburo; Yoshida, Shinichiro; Suzushima, Hitoshi; Miyahara, Masaharu; Yamashita, Kiyoshi; Eto, Tetsuya; Suzumiya, Junji; Tamura, Kazuo

2017-07-06

Adult T-cell leukemia-lymphoma (ATL) has been divided into 4 clinical subtypes: acute, lymphoma, chronic, and smoldering. The aim of this study is to develop a novel prognostic index (PI) for chronic and smoldering ATL. We conducted a nationwide retrospective survey on ATL patients, and 248 fully eligible individuals were used in this analysis. In the univariate analysis, sex, performance status, log 10 (soluble interleukin-2 receptor [sIL-2R]), neutrophils count, and lymphadenopathy showed values of P < .05 in training samples. A multivariate analysis was performed on these factors, and only log 10 (sIL-2R) was identified as an independent prognostic factor in training samples. Using a regression coefficient of this variable, a prognostic model was formulated to identify different levels of risk: indolent ATL-PI (iATL-PI) = 1.51 × log 10 (sIL-2R [U/mL]). The values calculated by iATL-PI were divided into 3 groups using a quartile point. In the validation sample, median survival times (MSTs) were 1.6 years, 5.5 years, and not reached for patients in the high-, intermediate-, and low-risk groups, respectively ( P < .0001). To make the scoring system clinically practicable, we simplified iATL-PI according to trichotomizing sIL-2R at 1000 and 6000 U/mL, using a quartile point. Patients with more than 6000 U/mL sIL-2R were categorized into the high-risk group, less than and equal to 1000 U/mL into the low-risk group, and the others into the intermediate-risk group, and MSTs were 1.6 years, not reached, and 5.5 years, respectively ( P < .0001). iATL-PI has potential as a novel tool for a risk-adapted therapeutic approach. © 2017 by The American Society of Hematology.

AtlA Mediates Extracellular DNA Release, Which Contributes to Streptococcus mutans Biofilm Formation in an Experimental Rat Model of Infective Endocarditis.

PubMed

Jung, Chiau-Jing; Hsu, Ron-Bin; Shun, Chia-Tung; Hsu, Chih-Chieh; Chia, Jean-San

2017-09-01

Host factors, such as platelets, have been shown to enhance biofilm formation by oral commensal streptococci, inducing infective endocarditis (IE), but how bacterial components contribute to biofilm formation in vivo is still not clear. We demonstrated previously that an isogenic mutant strain of Streptococcus mutans deficient in autolysin AtlA (Δ atlA ) showed a reduced ability to cause vegetation in a rat model of bacterial endocarditis. However, the role of AtlA in bacterial biofilm formation is unclear. In this study, confocal laser scanning microscopy analysis showed that extracellular DNA (eDNA) was embedded in S. mutans GS5 floes during biofilm formation on damaged heart valves, but an Δ atlA strain could not form bacterial aggregates. Semiquantification of eDNA by PCR with bacterial 16S rRNA primers demonstrated that the Δ atlA mutant strain produced dramatically less eDNA than the wild type. Similar results were observed with in vitro biofilm models. The addition of polyanethol sulfonate, a chemical lysis inhibitor, revealed that eDNA release mediated by bacterial cell lysis is required for biofilm initiation and maturation in the wild-type strain. Supplementation of cultures with calcium ions reduced wild-type growth but increased eDNA release and biofilm mass. The effect of calcium ions on biofilm formation was abolished in Δ atlA cultures and by the addition of polyanethol sulfonate. The VicK sensor, but not CiaH, was found to be required for the induction of eDNA release or the stimulation of biofilm formation by calcium ions. These data suggest that calcium ion-regulated AtlA maturation mediates the release of eDNA by S. mutans , which contributes to biofilm formation in infective endocarditis. Copyright © 2017 American Society for Microbiology.

Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions.

PubMed

Alvarez, Angela M; Mulla, Melissa J; Chamley, Lawrence W; Cadavid, Angela P; Abrahams, Vikki M

2015-02-01

Antiphospholipid antibodies (aPL) interfere with several physiologic functions of human trophoblasts, including reducing their ability to migrate, decreasing their production of angiogenic factors, and inducing an inflammatory response. This may provide the underlying mechanism by which aPL responses lead to recurrent pregnancy loss or preeclampsia in women with obstetric antiphospholipid syndrome (APS). Although treatment with heparin may reduce the rate of recurrent pregnancy loss, the risk of preeclampsia remains high. Therefore, alternative treatments are needed for the management of pregnant patients with APS. Since aspirin-triggered lipoxins (ATLs) have immune and angiogenic modulatory properties, the objective of this study was to determine the effects of the ATL 15-epi-lipoxin A4 on the function of aPL-altered human trophoblasts in the first trimester of pregnancy. A first-trimester human trophoblast cell line (HTR8) was treated with mouse anti-human β2 -glycoprotein I monoclonal antibodies (aPL) in the presence or absence of the ATL 15-epi-lipoxin A4 . Trophoblast migration and interactions with endometrial endothelial cells were measured using Transwell and coculture assays. Trophoblast secretion of cytokines and angiogenic factors was measured by enzyme-linked immunosorbent assay. Treatment of HTR8 cells with ATL reversed the aPL-induced decrease in trophoblast migration, an effect that appeared to be regulated through restoration of interleukin-6 production. Using a model of spiral artery transformation, aPL and sera from APS patients with pregnancy morbidity disrupted trophoblast-endothelial cell interactions, and treatment with ATL restored the stability of the cocultures. In contrast, ATL treatment did not resolve the proinflammatory and antiangiogenic responses of trophoblasts induced by aPL. These findings indicate that ATLs may have some benefits in terms of preventing the effects of aPL on trophoblast function, which raises the possibility of the use of ATLs as an adjuvant therapy in women with aPL. Copyright © 2015 by the American College of Rheumatology.

Arabitol Metabolism of Corynebacterium glutamicum and Its Regulation by AtlR

PubMed Central

Laslo, Tanja; von Zaluskowski, Philipp; Gabris, Christina; Lodd, Elisabeth; Rückert, Christian; Dangel, Petra; Kalinowski, Jörn; Auchter, Marc; Seibold, Gerd

2012-01-01

Expression profiling of Corynebacterium glutamicum in comparison to a derivative deficient in the transcriptional regulator AtlR (previously known as SucR or MtlR) revealed eight genes showing more than 4-fold higher mRNA levels in the mutant. Four of these genes are located in the direct vicinity of the atlR gene, i.e., xylB, rbtT, mtlD, and sixA, annotated as encoding xylulokinase, the ribitol transporter, mannitol 2-dehydrogenase, and phosphohistidine phosphatase, respectively. Transcriptional analysis indicated that atlR and the four genes are organized as atlR-xylB and rbtT-mtlD-sixA operons. Growth experiments with C. glutamicum and C. glutamicum ΔatlR, ΔxylB, ΔrbtT, ΔmtlD, and ΔsixA derivatives with sugar alcohols revealed that (i) wild-type C. glutamicum grows on d-arabitol but not on other sugar alcohols, (ii) growth in the presence of d-arabitol allows subsequent growth on d-mannitol, (iii) d-arabitol is cometabolized with glucose and preferentially utilized over d-mannitol, (iv) RbtT and XylB are involved in d-arabitol but not in d-mannitol metabolism, (v) MtlD is required for d-arabitol and d-mannitol metabolism, and (vi) SixA is not required for growth on any of the substrates tested. Furthermore, we show that MtlD confers d-arabitol and d-mannitol dehydrogenase activities, that the levels of these and also xylulokinase activities are generally high in the C. glutamicum ΔatlR mutant, whereas in the parental strain, they were high when cells were grown in the presence of d-arabitol and very low when cells were grown in its absence. Our results show that the XylB, RbtT, and MtlD proteins allow the growth of C. glutamicum on d-arabitol and that d-arabitol metabolism is subject to arabitol-dependent derepression by AtlR. PMID:22178972

CRISM Limb Observations of Aerosols and Water Vapor

NASA Technical Reports Server (NTRS)

Smith, Michael D.; Wolff, M.J.; Clancy, R.T.; Seelos, F.; Murchie, S.L.

2009-01-01

Near-infrared spectra taken in a limb-viewing geometry by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on-board the Mars Reconnaissance Orbiter (MRO) provide a useful tool for probing atmospheric structure. Here we describe preliminary work on the retrieval of vertical profiles of aerosols and water vapor from the CRISM limb observations. The first full set of CRISM limb observations was taken in July 2009, with subsequent limb observations planned once every two months. Each set of limb observations contains about four dozen scans across the limb giving pole-to-pole coverage for two orbits at roughly 100 and 290 W longitude. Radiative transfer modeling taking account of aerosol scattering in the limb-viewing geometry is used to model the observations. The retrievals show the height to which dust and water vapor extend and the location and height of water ice clouds. Results from the First set of CRISM limb observations (July 2009, Ls=300) show dust aerosol well-mixed to about three scale heights above the surface with thin water ice clouds above the dust near the equator and at mid-northern latitudes. Water vapor is concentrated at high southern latitudes.

Prefrontal cortex afferents to the anterior temporal lobe in the Macaca fascicularis monkey.

PubMed

Mohedano-Moriano, Alicia; Muñoz-López, Mónica; Sanz-Arigita, Ernesto; Pró-Sistiaga, Palma; Martínez-Marcos, Alino; Legidos-Garcia, María Ester; Insausti, Ana María; Cebada-Sánchez, Sandra; Arroyo-Jiménez, María Del Mar; Marcos, Pilar; Artacho-Pérula, Emilio; Insausti, Ricardo

2015-12-01

The anatomical organization of the lateral prefrontal cortex (LPFC) afferents to the anterior part of the temporal lobe (ATL) remains to be clarified. The LPFC has two subdivisions, dorsal (dLPFC) and ventral (vLPFC), which have been linked to cognitive processes. The ATL includes several different cortical areas, namely, the temporal polar cortex and rostral parts of the perirhinal, inferotemporal, and anterior tip of the superior temporal gyrus cortices. Multiple sensory modalities converge in the ATL. All of them (except the rostral inferotemporal and superior temporal gyrus cortices) are components of the medial temporal lobe, which is critical for long-term memory processing. We studied the LPFC connections with the ATL by placing retrograde tracer injections into the ATL: the temporal polar (n = 3), perirhinal (areas 35 and 36, n = 6), and inferotemporal cortices (area TE, n = 5), plus one additional deposit in the posterior parahippocampal cortex (area TF, n = 1). Anterograde tracer deposits into the dLPFC (A9 and A46, n = 2), the vLPFC (A46v, n = 2), and the orbitofrontal cortex (OF; n = 2) were placed for confirmation of those projections. The results showed that the vLPFC displays a moderate projection to rostral area TE and the dorsomedial portion of the temporal polar cortex; in contrast, the dLPFC connections with the ATL were weak. By comparison, the OFC and medial frontal cortices (MFC) showed dense connectivity with the ATL, namely, A13 with the temporopolar and perirhinal cortices. All areas of the MFC projected to the temporopolar cortex, albeit with a lower intensity. The functional significance of such paucity of LPFC afferents is unknown. © 2015 Wiley Periodicals, Inc.

Stair-shaped Achilles tendon lengthening in continuity - A new method to treat equinus deformity in patients with spastic cerebral palsy.

PubMed

Li, Zhengxun; Zhang, Ning; Wang, Yang; Cao, Songhua; Huang, Zheng; Hu, Yong

2017-10-27

Equinus of the ankle is a common deformity in spastic cerebral palsy. Achilles tendon lengthening is one of the effective options for the treatment of equinus deformity. In the study, a new stair-shaped Achilles tendon lengthening (ATL) procedure that preserves of the tendon continuity was performed in 28 tendons with equinus deformity (20 patients, mean age=10.5±2.6 years). The results were compared with a group of patients treated with the Z-lengthening procedure. During the latest follow-up visit, the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot scale score was much higher in the stair-shaped ATL group than in the Z-lengthening group (p<0.05). The two groups showed similar surgical correction angle after ATL(37.2±3.5° for stair-shaped ATL and 36.1±4.5° for Z-lengthening). During the latest follow-up visit, the correction angle in the Z-lengthening group decreased to 21.6±4.3°, which was lower than in the stair-shaped ATL group (29.0±3.1°; p<0.05). In addition, the data regarding the time required by each patient before being able to start rehabilitation and walking as well as gaining better stability for running indicated that the stair-shaped ATL group recovered significantly quicker than the Z-lengthening group. The stair-shaped ATL procedure resulted in a successful correction of the equinus deformity in spastic cerebral palsy, with the advantage of preserving a degree of continuity without a complete section of the tendon. This confers greater antigravity stability and quicker recovery in patients. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Mogamulizumab for relapsed adult T-cell leukemia-lymphoma: Updated follow-up analysis of phase I and II studies.

PubMed

Ishida, Takashi; Utsunomiya, Atae; Jo, Tatsuro; Yamamoto, Kazuhito; Kato, Koji; Yoshida, Shinichiro; Takemoto, Shigeki; Suzushima, Hitoshi; Kobayashi, Yukio; Imaizumi, Yoshitaka; Yoshimura, Kenichi; Kawamura, Kouichi; Takahashi, Takeshi; Tobinai, Kensei; Ueda, Ryuzo

2017-10-01

The present study sought to elucidate the prognosis of adult T-cell leukemia-lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti-CCR4 monoclonal antibody. Progression-free survival (PFS) and overall survival (OS) of ATL patients enrolled in two studies are herein updated, namely NCT00355472 (phase I study of mogamulizumab in relapsed patients with ATL and peripheral T-cell lymphoma) and NCT00920790 (phase II study for relapsed ATL). Of 13 patients with relapsed aggressive ATL in the phase I study, four (31%) survived >3 years. For 26 relapsed patients with aggressive ATL in the phase II study, median PFS was 5.2 months and 1-year PFS was 26%, whereas median OS was 14.4 months, and 3-year OS was 23%. For patients without a rash or who developed a grade 1 rash only, median PFS was 0.8 months, and 1-year PFS was zero, with a median OS of 6.0 months, and 3-year OS of 8%. In contrast, for patients who developed a rash ≥grade 2, median PFS was 11.7 months, and 1-year PFS was 50%, with a median OS of 25.6 months, and 3-year OS of 36%. Thus, we conclude that mogamulizumab monotherapy may improve PFS and OS in some patients with relapsed aggressive ATL, especially those who develop a skin rash as a moderate immune-related adverse event. Therefore, further investigation is warranted to validate the present observations and to clarify the mechanisms involved in the activity of mogamulizumab. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Lactococcus lactis Metabolism and Gene Expression during Growth on Plant Tissues

PubMed Central

Golomb, Benjamin L.

2014-01-01

Lactic acid bacteria have been isolated from living, harvested, and fermented plant materials; however, the adaptations these bacteria possess for growth on plant tissues are largely unknown. In this study, we investigated plant habitat-specific traits of Lactococcus lactis during growth in an Arabidopsis thaliana leaf tissue lysate (ATL). L. lactis KF147, a strain originally isolated from plants, exhibited a higher growth rate and reached 7.9-fold-greater cell densities during growth in ATL than the dairy-associated strain L. lactis IL1403. Transcriptome profiling (RNA-seq) of KF147 identified 853 induced and 264 repressed genes during growth in ATL compared to that in GM17 laboratory culture medium. Genes induced in ATL included those involved in the arginine deiminase pathway and a total of 140 carbohydrate transport and metabolism genes, many of which are involved in xylose, arabinose, cellobiose, and hemicellulose metabolism. The induction of those genes corresponded with L. lactis KF147 nutrient consumption and production of metabolic end products in ATL as measured by gas chromatography-time of flight mass spectrometry (GC-TOF/MS) untargeted metabolomic profiling. To assess the importance of specific plant-inducible genes for L. lactis growth in ATL, xylose metabolism was targeted for gene knockout mutagenesis. Wild-type L. lactis strain KF147 but not an xylA deletion mutant was able to grow using xylose as the sole carbon source. However, both strains grew to similarly high levels in ATL, indicating redundancy in L. lactis carbohydrate metabolism on plant tissues. These findings show that certain strains of L. lactis are well adapted for growth on plants and possess specific traits relevant for plant-based food, fuel, and feed fermentations. PMID:25384484

Nitrate-induced photodegradation of atenolol in aqueous solution: kinetics, toxicity and degradation pathways.

PubMed

Ji, Yuefei; Zeng, Chao; Ferronato, Corinne; Chovelon, Jean-Marc; Yang, Xi

2012-07-01

The extensive utilization of β-blockers worldwide led to frequent detection in natural water. In this study the photolysis behavior of atenolol (ATL) and toxicity of its photodegradation products were investigated in the presence of nitrate ions. The results showed that ATL photodegradation followed pseudo-first-order kinetics upon simulated solar irradiation. The photodegradation was found to be dependent on nitrate concentration and increasing the nitrate from 0.5 mML(-1) to 10 mML(-1) led to the enhancement of rate constant from 0.00101 min(-1) to 0.00716 min(-1). Hydroxyl radical was determined to play a key role in the photolysis process by using isopropanol as molecular probe. Increasing the solution pH from 4.8 to 10.4, the photodegradation rate slightly decreased from 0.00246 min(-1) to 0.00195 min(-1), probably due to pH-dependent effect of nitrate-induced .OH formation. Bicarbonate decreased the photodegradation of ATL in the presence of nitrate ions mainly through pH effect, while humic substance inhibited the photodegradation via both attenuating light and competing radicals. Upon irradiation for 240 min, only 10% reduction of total organic carbon (TOC) can be achieved in spite of 72% transformation rate of ATL, implying a majority of ATL transformed into intermediate products rather than complete mineralization. The main photoproducts of ATL were identified by using solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) techniques and possible nitrate-induced photodegradation pathways were proposed. The toxicity of the phototransformation products was evaluated using aquatic species Daphnia magna, and the results revealed that photodegradation was an effective mechanism for ATL toxicity reduction in natural waters. Copyright © 2012 Elsevier Ltd. All rights reserved.

Enterococcus faecium Biofilm Formation: Identification of Major Autolysin AtlAEfm, Associated Acm Surface Localization, and AtlAEfm-Independent Extracellular DNA Release

PubMed Central

Paganelli, Fernanda L.; Willems, Rob J. L.; Jansen, Pamela; Hendrickx, Antoni; Zhang, Xinglin; Bonten, Marc J. M.; Leavis, Helen L.

2013-01-01

ABSTRACT Enterococcus faecium is an important multidrug-resistant nosocomial pathogen causing biofilm-mediated infections in patients with medical devices. Insight into E. faecium biofilm pathogenesis is pivotal for the development of new strategies to prevent and treat these infections. In several bacteria, a major autolysin is essential for extracellular DNA (eDNA) release in the biofilm matrix, contributing to biofilm attachment and stability. In this study, we identified and functionally characterized the major autolysin of E. faecium E1162 by a bioinformatic genome screen followed by insertional gene disruption of six putative autolysin genes. Insertional inactivation of locus tag EfmE1162_2692 resulted in resistance to lysis, reduced eDNA release, deficient cell attachment, decreased biofilm, decreased cell wall hydrolysis, and significant chaining compared to that of the wild type. Therefore, locus tag EfmE1162_2692 was considered the major autolysin in E. faecium and renamed atlAEfm. In addition, AtlAEfm was implicated in cell surface exposure of Acm, a virulence factor in E. faecium, and thereby facilitates binding to collagen types I and IV. This is a novel feature of enterococcal autolysins not described previously. Furthermore, we identified (and localized) autolysin-independent DNA release in E. faecium that contributes to cell-cell interactions in the atlAEfm mutant and is important for cell separation. In conclusion, AtlAEfm is the major autolysin in E. faecium and contributes to biofilm stability and Acm localization, making AtlAEfm a promising target for treatment of E. faecium biofilm-mediated infections. PMID:23592262

Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells.

PubMed

Watanabe, Toshiki

2017-03-02

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemogenesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor-NF-κB signaling such as PLCG1 , PRKCB , and CARD11 and gain-of function mutations in CCR4 and CCR7 Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-κB. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1-infected CD4 + T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemogenesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated. © 2017 by The American Society of Hematology.

Arab Teens Lifestyle Study (ATLS): objectives, design, methodology and implications

PubMed Central

Al-Hazzaa, Hazzaa M; Musaiger, Abdulrahman O

2011-01-01

Background There is a lack of comparable data on physical activity, sedentary behavior, and dietary habits among Arab adolescents, which limits our understanding and interpretation of the relationship between obesity and lifestyle parameters. Therefore, we initiated the Arab Teens Lifestyle Study (ATLS). The ATLS is a multicenter collaborative project for assessing lifestyle habits of Arab adolescents. The objectives of the ATLS project were to investigate the prevalence rates for overweight and obesity, physical activity, sedentary activity and dietary habits among Arab adolescents, and to examine the interrelationships between these lifestyle variables. This paper reports on the objectives, design, methodology, and implications of the ATLS. Design/Methods The ATLS is a school-based cross-sectional study involving 9182 randomly selected secondary-school students (14–19 years) from major Arab cities, using a multistage stratified sampling technique. The participating Arab cities included Riyadh, Jeddah, and Al-Khobar (Saudi Arabia), Bahrain, Dubai (United Arab Emirates), Kuwait, Amman (Jordan), Mosel (Iraq), Muscat (Oman), Tunisia (Tunisia) and Kenitra (Morocco). Measured variables included anthropometric measurements, physical activity, sedentary behavior, sleep duration, and dietary habits. Discussion The ATLS project will provide a unique opportunity to collect and analyze important lifestyle information from Arab adolescents using standardized procedures. This is the first time a collaborative Arab project will simultaneously assess broad lifestyle variables in a large sample of adolescents from numerous urbanized Arab regions. This joint research project will supply us with comprehensive and recent data on physical activity/inactivity and eating habits of Arab adolescents relative to obesity. Such invaluable lifestyle-related data are crucial for developing public health policies and regional strategies for health promotion and disease prevention. PMID:22253540

Identification and characterization of an autolysin-encoding gene of Streptococcus mutans.

PubMed

Shibata, Yukie; Kawada, Miki; Nakano, Yoshio; Toyoshima, Kuniaki; Yamashita, Yoshihisa

2005-06-01

We identified a gene (atlA) encoding autolytic activity from Streptococcus mutans Xc. The AtlA protein predicted to be encoded by atlA is composed of 979 amino acids with a molecular weight of 107,279 and has a conserved beta-1,4-N-acetylmuramidase (lysozyme) domain in the C-terminal portion. Sodium dodecyl sulfate extracts of strain Xc showed two major bacteriolytic bands with molecular masses of 107 and 79 kDa, both of which were absent from a mutant with inactivated atlA. Western blot analysis revealed that the 79-kDa band was derived from the 107-kDa peptide by cleavage of its N-terminal portion. The inactivation of atlA resulted in a marked decrease in autolysis and the formation of very long chains of cells compared to the case for the parent strain. Although both the parent and mutant strains formed biofilms in the presence of sucrose, the biofilms formed by the mutant had a sponge-like architecture with large gaps and contained 30% less biomass than those formed by the parent strain. Furthermore, strain Xc formed glucose-dependent, loose biofilms in the absence of sucrose, but the mutant lost this ability. These results suggest that AtlA may play an important role in biofilm formation by S. mutans. The antibody produced against the C-terminal peptide containing the beta-1,4-N-acetylmuramidase domain drastically inhibited the autolytic activity of strain Xc. This inhibition was specific among the oral streptococci to S. mutans. These results indicate that the catalytic domain of AtlA is located at the C terminus, suggesting that further characterization of this domain may provide a means to control cariogenic dental plaque formation.

Early Birds in Korea: Exporting Defense AT and L Has Far Reaching Impact

DTIC Science & Technology

2015-11-01

studying the Defense AT&L magazine published for the U.S. Depart-ment of Defense (DoD) by the Defense Acquisition University (DAU). The study club’s...April Publications of the Early Birds Study group draw information and inspiration from Defense AT&L magazine . Collage of Early Birds Study Group...study club name. The club established two main objectives: (1) study the De- fense AT&L magazine published in English to learn advanced defense

Development of sugar chain-binding single-chain variable fragment antibody to adult T-cell leukemia cells using glyco-nanotechnology and phage display method.

PubMed

Muchima, Kaname; Todaka, Taro; Shinchi, Hiroyuki; Sato, Ayaka; Tazoe, Arisa; Aramaki, Rikiya; Kakitsubata, Yuhei; Yokoyama, Risa; Arima, Naomichi; Baba, Masanori; Wakao, Masahiro; Ito, Yuji; Suda, Yasuo

2018-04-01

Adult T-cell leukemia (ATL) is an intractable blood cancer caused by the infection of human T-cell leukemia virus type-1, and effective medical treatment is required. It is known that the structure and expression levels of cell surface sugar chains vary depending on cell states such as inflammation and cancer. Thus, it is expected that the antibody specific for ATL cell surface sugar chain would be an effective diagnostic tool and a strong candidate for the development of an anti-ATL drug. Here, we developed a stable sugar chain-binding single-chain variable fragment antibody (scFv) that can bind to ATL cells using a fibre-type Sugar Chip and phage display method. The fiber-type Sugar Chips were prepared using O-glycans released from ATL cell lines. The scFv-displaying phages derived from human B cells (diversity: 1.04 × 108) were then screened using the fiber-type Sugar Chips, and an O-glycan-binding scFv was obtained. The flow cytometry analysis revealed that the scFv predominantly bound to ATL cell lines. The sugar chain-binding properties of the scFv was evaluated by array-type Sugar Chip immobilized with a library of synthetic glycosaminoglycan disaccharide structures. Highly sulphated disaccharide structures were found to have high affinity to scFv.

Evidence for degraded low frequency verbal concepts in left resected temporal lobe epilepsy patients.

PubMed

Visser, M; Forn, C; Lambon Ralph, M A; Hoffman, P; Gómez Ibáñez, A; Sunajuán, Ana; Rosell Negre, P; Villanueva, V; Ávila, C

2018-06-01

According to a large neuropsychological and neuroimaging literature, the bilateral anterior temporal lobe (ATL) is a core region for semantic processing. It seems therefore surprising that semantic memory appears to be preserved in temporal lobe epilepsy (TLE) patients with unilateral ATL resection. However, recent work suggests that the bilateral semantic system is relatively robust against unilateral damage and semantic impairments under these circumstances only become apparent with low frequency specific concepts. In addition, neuroimaging studies have shown that the function of the left and right ATLs differ and therefore left or right ATL resection should lead to a different pattern of impairment. The current study investigated hemispheric differences in the bilateral semantic system by comparing left and right resected TLE patients during verbal semantic processing of low frequency concepts. Picture naming and semantic comprehension tasks with varying word frequencies were included to investigate the pattern of impairment. Left but not right TLE patients showed impaired semantic processing, which was particularly apparent on low frequency items. This indicates that, for verbal information, the bilateral semantic system is more sensitive to damage in the left compared to the right ATL, which is in line with theories that attribute a more prominent role to the left ATL due to connections with pre-semantic verbal regions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis.

PubMed

Jung, Chiau-Jing; Zheng, Quan-Hau; Shieh, Ya-Hsiung; Lin, Chi-Shuan; Chia, Jean-San

2009-11-01

Streptococcus mutans, a commensal of the human oral cavity, can survive in the bloodstream and cause infective endocarditis (IE). However, the virulence factors associated with this manifestation of disease are not known. Here, we demonstrate that AtlA, an autolysin of S. mutans is a newly identified fibronectin (Fn) binding protein and contributes to bacterial resistance to phagocytosis and survival in the bloodstream. Interestingly, prior exposure to plasma at low concentrations was sufficient to enhance bacterial survival in the circulation. Calcium ions at physiological plasma concentrations induced maturation of AtlA from the 104-90 kDa isoform resulting in increased Fn binding and resistance to phagocytosis. An isogenic mutant strain defective in AtlA expression exhibited reduced survival and virulence when tested in a rat model of IE compared with the wild-type and complemented strains. The data presented suggest that plasma components utilized by S. mutans enhanced survival in the circulation and AtlA is a virulence factor associated with infective endocarditis.

Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism

PubMed Central

Lei, Tianluo; Zhou, Lei; Layton, Anita T.; Zhou, Hong; Zhao, Xuejian; Bankir, Lise

2011-01-01

Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts. PMID:21849488

Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism.

PubMed

Lei, Tianluo; Zhou, Lei; Layton, Anita T; Zhou, Hong; Zhao, Xuejian; Bankir, Lise; Yang, Baoxue

2011-12-01

Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.

A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly.

PubMed

Trainer, Peter J; Newell-Price, John; Ayuk, John; Aylwin, Simon; Rees, D Aled; Drake, Wm; Chanson, Philippe; Brue, Thierry; Webb, Susan M; Montañana, Carmen Fajardo; Aller, Javier; McCormack, Ann I; Torpy, David J; Tachas, George; Atley, Lynne; Ryder, David; Bidlingmaier, Martin

2018-05-22

ATL1103 is a second-generation antisense oligomer targeting the human GH receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. 26 patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once- or twice-weekly for 13 weeks, and monitored for a further 8-week washout period. The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, ALS, GH, GHBP), comparison was between baseline and week 14. Safety was assessed by reported adverse events. Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups, respectivey. Compared to baseline, at week 14 twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (p=0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (p=0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and at week 21 remained lower than at baseline by a median of 18.7% (p=0.0005). Compared to baseline, by week 14 IGFBP3 and ALS had declined by a median of 8.9% (p=0.027) and 16.7% (p=0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (p=0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (p=0.027 and p=0.005), respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild to moderate injection-site reactions (ISR). This study provides proof-of-concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.

Identification and characterization of an autolysin gene, atlg, from Streptococcus sobrinus.

PubMed

Yamada, Arisa; Tamura, Haruki; Kato, Hirohisa

2009-02-01

AtlA is a major cell-lytic enzyme called autolysin in Streptococcus mutans. In this study, we identified the atlg gene-encoding autolysin (Atlg), consisting of 863 residues from Streptococcus sobrinus 6715DP, and confirmed lytic activity of recombinant Atlg by zymography of S. sobrinus cells. An atlA-inactivated mutant was constructed in S. mutans Xc, and the atlg gene product was characterized by plasmid complementation. Microscopic analysis, saliva-induced aggregation assay and autolysis assay of static cultures in air revealed that the atlg gene product partially complemented the role of AtlA. Furthermore, the capability of biofilm formation of the atlA-deficient mutant cultivated in air was restored by plasmid comprising the atlg gene. These findings suggest that Atlg may be involved in cell separation and biofilm formation in S. sobrinus.

Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism

PubMed Central

Chen, Jing; Petrus, Mike; Bryant, Bonita R.; Phuc Nguyen, Vinh; Stamer, Mindy; Goldman, Carolyn K.; Bamford, Richard; Morris, John C.; Janik, John E.

2008-01-01

The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including those of cytokines and their receptors, which plays an important role in early stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is activated by Tax via an NF-κB motif in its proximal promoter, whereas IL-9 receptor-α (IL-9Rα) expression is not induced by Tax. However, supporting a role for IL-9/IL-9Rα in ATL, a neutralizing monoclonal antibody directed toward IL-9Rα inhibited ex vivo spontaneous proliferation of primary ATL cells from several patients. Fluorescence-activated cell sorter analysis of freshly isolated peripheral blood mononuclear cells from these patients revealed high level expression of IL-9Rα on their CD14-expressing monocytes. Furthermore, purified T cells or monocytes alone from these patients did not proliferate ex vivo, whereas mixtures of these cell types manifested significant proliferation through a contact-dependent manner. Taken together, our data suggest that primary ATL cells, via IL-9, support the action of IL-9Rα/CD14-expressing monocytes, which subsequently support the ex vivo spontaneous proliferation of malignant T cells. In summary, these data support a role for IL-9 and its receptor in ATL by a paracrine mechanism. PMID:18339896

Impact of human T cell leukemia virus type 1 in living donor liver transplantation.

PubMed

Yoshizumi, T; Shirabe, K; Ikegami, T; Kayashima, H; Yamashita, N; Morita, K; Masuda, T; Hashimoto, N; Taketomi, A; Soejima, Y; Maehara, Y

2012-06-01

Human T cell leukemia virus type 1 (HTLV-1) is an endemic retrovirus in southwestern Japan, which causes adult T cell leukemia (ATL) or HTLV-1 associated myelopathy in a minority of carriers. Here, we investigated the impact of HTLV-1 status in living donor liver transplantation (LDLT). Twenty-six of 329 (7.9%) HTLV-1 carriers underwent primary LDLT. One recipient negative for HTLV-1 before LDLT received a graft from an HTLV-1 positive donor. Eight donors were HTLV-1 positive. Twenty-seven recipients (13 male and 14 female; mean age 52.5 years) were reviewed retrospectively. ATL developed in four recipients who ultimately died. The intervals between LDLT and ATL development ranged from 181 to 1315 days. Of the four ATL recipients, two received grafts from HTLV-1 positive donors and two from negative donors. The 1-, 3- and 5-year HTLV-1 carrier survival rates were 91.3%, 78.3% and 66.3%, respectively. Fulminant hepatic failure as a pretransplant diagnosis and a pretransplant MELD score ≥ 15 was identified as risk factors for ATL development in this study (p = 0.001 and p = 0.041, respectively). In conclusion, LDLT can be performed for HTLV-1 positive recipients. However, when fulminant hepatic failure is diagnosed, LDLT should not be performed until further studies have revealed the mechanisms of ATL development. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Seasonal variation of acute toxoplasmic lymphadenopathy in the United States.

PubMed

Contopoulos-Ioannidis, D; Talucod, J; Maldonado, Y; Montoya, J G

2015-07-01

We describe the seasonal variation of acute toxoplasmosis in the United States. Acute toxoplasmic lymphadenopathy (ATL) can be a surrogate of acute toxoplasmosis in patients in whom the date of onset of lymphadenopathy matches the window of acute infection predicted by serological tests performed at a reference laboratory. We used the electronic database of the Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMF-TSL) (1997-2011) to identify cases of ATL. We tested the uniformity of distribution of ATL cases per month, across the 12 calendar months, using circular statistics uniformity tests. We identified 112 consecutive cases of ATL. The distribution of cases was not uniform across the 12 calendar months. We observed the highest peak of cases in December and a second highest peak in September. Similar months were identified in patients with acute toxoplasmosis in rural areas in France. The results were similar when we performed weighted analyses, weighting for the total number of Toxoplasma gondii IgG tests performed per month in the PAMF-TSL laboratory. This is the largest study to date of the seasonal variation of ATL in the United States. Physicians should advise high-risk individuals to avoid risk factors associated with T. gondii infections especially around those months.

Limb-girdle muscular dystrophies

MedlinePlus

... diseases in which there is muscle weakness and wasting (muscular dystrophy). In most cases, both parents must ... which are not actually strong Loss of muscle mass, thinning of certain body parts Low back pain ...

Accuracy of qPCR for quantifying Leishmania kDNA in different skin layers of patients with American tegumentary leishmaniasis.

PubMed

Sevilha-Santos, L; Dos Santos Júnior, A C M; Medeiros-Silva, V; Bergmann, J O; da Silva, E F; Segato, L F; Arabi, A Y M; de Paula, N A; Sampaio, R N R; Lima, B D; Gomes, C M

2018-05-03

Superficial swab sampling of American tegumentary leishmaniasis (ATL) lesions shows higher amounts of Leishmania than those from biopsy. Subcutaneous involvement is also important in ATL, but parasite quantification according to lesion depth has not been evaluated. We aim to present the best depth at which sampling should be performed for molecular exams of ATL. Patients with a clinical presentation compatible with ATL were allocated to ATL and control groups. Qualitative and quantitative qPCR assays were performed using SYBR Green and primers amplifying the kDNA minicircle of Leishmania spp. in different skin layers, including the epidermis, the superior dermis, the inferior dermis, and the hypodermis. Fifty-nine patients were included in this study, including 40 who had been diagnosed with ATL and 19 controls. The number of parasites was greater in samples of the epidermis and superior dermis (159.1 × 10 6 , range 4.0-781.7, and 75.4 × 10 6 , range 8.0-244.5, mean Leishmania parasite equivalents per μg of tissue DNA, respectively) than those in samples of the inferior dermis and hypodermis (54.6, range 8.0-256.6, and 16.8 × 10 6 , range 8.0-24.1, mean Leishmania parasite equivalents per μg of tissue DNA, respectively). The best diagnostic accuracy was achieved in the superior dermis (77.9%) and was significantly greater than that in the hypodermis (63.3%; p 0.039). We conclude that superficial sampling can retrieve a greater quantity of parasites. Future studies of the role of transepidermal elimination as a mechanism of host defence in ATL must be performed as there is a considerable quantity of Leishmania kDNA in the epidermis. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Parahippocampectomy as a New Surgical Approach to Mesial Temporal Lobe Epilepsy Caused By Hippocampal Sclerosis: A Pilot Randomized Comparative Clinical Trial.

PubMed

Alonso-Vanegas, Mario Arturo; Freire Carlier, Iván D; San-Juan, Daniel; Martínez, Alma Rosa; Trenado, Carlos

2018-02-01

The parahippocampal gyrus plays an important role in the epileptogenic pathways of mesial temporal lobe epilepsy caused by hippocampal sclerosis (mTLE-HS); its resection could prevent epileptic seizures with fewer complications. This study evaluates the initial efficacy and safety of anterior temporal lobectomy (ATL), selective amygdalohipppocampectomy (SAH), and parahippocampectomy (PHC) surgical approaches in mTLE-HS. A randomized comparative pilot clinical trial (2008-2011) was performed that included patients with mTLE-HS who underwent ATL, trans-T3 SAH, and trans-T3 PHC. Their sociodemographic characteristics, visual field profiles, verbal and visual memory profiles, and Engel scale outcome at baseline and at 1 and 5 years are described, using descriptive statistics along with parametric and nonparametric tests. Forty-three patients with a mean age of 35.2 years (18-56 years), 65% female, were analyzed: 14 underwent PHC, 14 ATL, and 15 SAH. The following percentages refer to those patients who were seizure free (Engel class IA) at 1-year and 5-year follow-up, respectively: 42.9% PHC, 71.4% ATL, and 60% SAH (P = 0.304); 28.6% PHC, 50% ATL, and 53.3% SAH (P = 0.353). Postoperative visual field deficits were 0% PHC, 85.7% ATL, and 46.7% SAH (P = 0.001). Verbal and/or visual memory worsening were present in 21.3% PHC, 42.8% ATL, and 33.4% SAH (P = 0.488) and preoperative and postoperative visual memory scores were significantly different in the SAH group only (P = 0.046). PHC, ALT, and SAH show a preliminary similar efficacy in short-term seizure-free rates in patients with mTLE-HS. However, PHC efficacy in the long-term decreases compared with the other surgical techniques. PHC does not produce postoperative visual field deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapy-induced selective loss of leukemia-initiating activity in murine adult T cell leukemia

PubMed Central

El Hajj, Hiba; El-Sabban, Marwan; Hasegawa, Hideki; Zaatari, Ghazi; Ablain, Julien; Saab, Shahrazad T.; Janin, Anne; Mahfouz, Rami; Nasr, Rihab; Kfoury, Youmna; Nicot, Christophe; Hermine, Olivier; Hall, William

2010-01-01

Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates ATL in transgenic mice. In this study, we demonstrate that an As2O3 and IFN-α combination, known to trigger Tax proteolysis, cures Tax-driven ATL in mice. Unexpectedly, this combination therapy abrogated initial leukemia engraftment into secondary recipients, whereas the primary tumor bulk still grew in the primary hosts, only to ultimately abate later on. This loss of initial transplantability required proteasome function. A similar regimen recently yielded unprecedented disease control in human ATL. Our demonstration that this drug combination targeting Tax stability abrogates tumor cell immortality but not short-term growth may foretell a favorable long-term efficiency of this regimen in patients. PMID:21135137

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study.

PubMed

Takemoto, Shigeki; Iwanaga, Masako; Sagara, Yasuko; Watanabe, Toshiki

2015-01-01

Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.

Response Surface Methodology Optimization of Ultrasonic-Assisted Extraction of Acer Truncatum Leaves for Maximal Phenolic Yield and Antioxidant Activity.

PubMed

Yang, Lingguang; Yin, Peipei; Fan, Hang; Xue, Qiang; Li, Ke; Li, Xiang; Sun, Liwei; Liu, Yujun

2017-02-04

This study is the first to report the use of response surface methodology to improve phenolic yield and antioxidant activity of Acer truncatum leaves extracts (ATLs) obtained by ultrasonic-assisted extraction. The phenolic composition in ATLs extracted under the optimized conditions were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration ( X ₁), material-to-liquid ratio ( X ₂), ultrasonic temperature ( X ₃) and power ( X ₄) for an optimal total phenol yield ( Y ₁) and DPPH• antioxidant activity ( Y ₂). The results showed that the optimal combination was ethanol:water ( v : v ) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic bath temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent/100 g d.w. and a maximal DPPH• antioxidant activity of 74,241.61 μmol Trolox equivalent/100 g d.w. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic components in ATL. What's more, a gallotannins pathway existing in ATL from gallic acid to penta- O -galloylglucoside was proposed. All these results provide practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

Human T-cell leukemia virus type I Tax genotype analysis in Okinawa, the southernmost and remotest islands of Japan: Different distributions compared with mainland Japan and the potential value for the prognosis of aggressive adult T-cell leukemia/lymphoma.

PubMed

Sakihama, Shugo; Saito, Mineki; Kuba-Miyara, Megumi; Tomoyose, Takeaki; Taira, Naoya; Miyagi, Takashi; Hayashi, Masaki; Kinjo, Shigeko; Nakachi, Sawako; Tedokon, Iori; Nishi, Yukiko; Tamaki, Keita; Morichika, Kazuho; Uchihara, Jun-Nosuke; Morishima, Satoko; Karube, Ken-Nosuke; Tanaka, Yuetsu; Masuzaki, Hiroaki; Fukushima, Takuya

2017-10-01

Okinawa, comprising remote islands off the mainland of Japan, is an endemic area of human T-cell leukemia virus type I (HTLV-1), the causative virus of adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). We investigated the tax genotype of HTLV-1 among 29 HTLV-1 carriers, 74 ATL patients, and 33 HAM patients in Okinawa. The genotype distribution-60 (44%) taxA cases and 76 (56%) taxB cases-differed from that of a previous report from Kagoshima Prefecture in mainland Japan (taxA, 10%; taxB, 90%). A comparison of the clinical outcomes of 45 patients (taxA, 14; taxB, 31) with aggressive ATL revealed that the overall response and 1-year overall survival rates for taxA (50% and 35%, respectively) were lower than those for taxB (71% and 49%, respectively). In a multivariate analysis of two prognostic indices for aggressive ATL, Japan Clinical Oncology Group-Prognostic Index and Prognostic Index for acute and lymphoma ATL, with respect to age, performance status, corrected calcium, soluble interleukin-2 receptor, and tax genotype, the estimated hazard ratio of taxA compared with taxB was 2.68 (95% confidence interval, 0.87-8.25; P=0.086). Our results suggest that the tax genotype has clinical value as a prognostic factor for aggressive ATL. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of a checklist on advanced trauma life support task performance during pediatric trauma resuscitation.

PubMed

Kelleher, Deirdre C; Carter, Elizabeth A; Waterhouse, Lauren J; Parsons, Samantha E; Fritzeen, Jennifer L; Burd, Randall S

2014-10-01

Advanced Trauma Life Support (ATLS) has been shown to improve outcomes related to trauma resuscitation; however, omissions from this protocol persist. The objective of this study was to evaluate the effect of a trauma resuscitation checklist on performance of ATLS tasks. Video recordings of resuscitations of children sustaining blunt or penetrating injuries at a Level I pediatric trauma center were reviewed for completion and timeliness of ATLS primary and secondary survey tasks, with and without checklist use. Patient and resuscitation characteristics were obtained from the trauma registry. Data were collected during two 4-month periods before (n = 222) and after (n = 213) checklist implementation. The checklist contained 50 items and included four sections: prearrival, primary survey, secondary survey, and departure plan. Five primary survey ATLS tasks (cervical spine immobilization, oxygen administration, palpating pulses, assessing neurologic status, and exposing the patient) and nine secondary survey ATLS tasks were performed more frequently (p ≤ 0.01 for all) and vital sign measurements were obtained faster (p ≤ 0.01 for all) after the checklist was implemented. When controlling for patient and event-specific characteristics, primary and secondary survey tasks overall were more likely to be completed (odds ratio [OR] = 2.66, primary survey; OR = 2.47, secondary survey; p < 0.001 for both) and primary survey tasks were performed faster (p < 0.001) after the checklist was implemented. Implementation of a trauma checklist was associated with greater ATLS task performance and with increased frequency and speed of primary and secondary survey task completion. © 2014 by the Society for Academic Emergency Medicine.

Impaired expression of DICER and some microRNAs in HBZ expressing cells from acute adult T-cell leukemia patients

PubMed Central

Gazon, Hélène; Belrose, Gildas; Terol, Marie; Meniane, Jean-Come; Mesnard, Jean-Michel; Césaire, Raymond; Peloponese, Jean-Marie

2016-01-01

Global dysregulation of microRNAs (miRNAs), a class of non-coding RNAs that regulate genes expression, is a common feature of human tumors. Profiling of cellular miRNAs on Adult T cell Leukemia (ATL) cells by Yamagishi et al. showed a strong decrease in expression for 96.7% of cellular miRNAs in ATL cells. However, the mechanisms that regulate the expression of miRNAs in ATL cells are still largely unknown. In this study, we compared the expression of 12 miRs previously described for being overexpress by Tax and the expression of several key components of the miRNAs biogenesis pathways in different HBZ expressing cell lines as well as in primary CD4 (+) cells from acute ATL patients. We showed that the expression of miRNAs and Dicer1 were downregulated in cells lines expressing HBZ as well as in fresh CD4 (+) cells from acute ATL patients. Using qRT-PCR, western blotting analysis and Chromatin Immunoprecipitation, we showed that dicer transcription was regulated by c-Jun and JunD, two AP-1 transcription factors. We also demonstrated that HBZ affects the expression of Dicer by removing JunD from the proximal promoter. Furthermore, we showed that at therapeutic concentration of 1mM, Valproate (VPA) an HDAC inhibitors often used in cancer treatment, rescue Dicer expression and miRNAs maturation. These results might offer a rationale for clinical studies of new combined therapy in an effort to improve the outcome of patients with acute ATL. PMID:26849145

Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma

PubMed Central

Shindo, Takero

2016-01-01

Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP) results in a dismal clinical outcome, with a median overall survival of only around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to long-term remission in a proportion of patients with aggressive ATL, the clinical outcome in patients with refractory or relapsed ATL is unsatisfactory. The anti-CCR4 antibody mogamulizumab (moga) has been recently approved for ATL in Japan, and it is effective in a significant proportion of patients with refractory or relapsed ATL. However, there are major concerns about the harmful influences of pretransplant moga on the immune reconstitution after allo-HSCT. Specifically, moga depletes regulatory T cells (Tregs) for at least a few months, which may increase the risk of graft-versus-host disease (GVHD) after allo-HSCT. A recent retrospective study from Japan clearly showed that pretransplant moga increased the risk of severe and steroid-refractory GVHD, which led to increases in non-relapse mortality and overall mortality. To improve the overall clinical outcome in patients with relapsed or refractory ATL, more studies are needed to incorporate moga without increasing adverse effects on the clinical outcome after allo-HSCT. In this review, we aim to provide an updated summary of the research related to moga and allo-HSCT. PMID:27868052

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology.

PubMed

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît; Maldonado-Báez, Lymarie; Park, Seong Hee; Blackstone, Craig

2016-11-15

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. We have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. Published by Elsevier Inc.

Preparing for ICESat-2: Simulated Geolocated Photon Data for Cryospheric Data Products

NASA Astrophysics Data System (ADS)

Harbeck, K.; Neumann, T.; Lee, J.; Hancock, D.; Brenner, A. C.; Markus, T.

2017-12-01

ICESat-2 will carry NASA's next-generation laser altimeter, ATLAS (Advanced Topographic Laser Altimeter System), which is designed to measure changes in ice sheet height, sea ice freeboard, and vegetation canopy height. There is a critical need for data that simulate what certain ICESat-2 science data products will "look like" post-launch in order to aid the data product development process. There are several sources for simulated photon-counting lidar data, including data from NASA's MABEL (Multiple Altimeter Beam Experimental Lidar) instrument, and M-ATLAS (MABEL data that has been scaled geometrically and radiometrically to be more similar to that expected from ATLAS). From these sources, we are able to develop simulated granules of the geolocated photon cloud product; also referred to as ATL03. These simulated ATL03 granules can be further processed into the upper-level data products that report ice sheet height, sea ice freeboard, and vegetation canopy height. For ice sheet height (ATL06) and sea ice height (ATL07) simulations, both MABEL and M-ATLAS data products are used. M-ATLAS data use ATLAS engineering design cases for signal and background noise rates over certain surface types, and also provides large vertical windows of data for more accurate calculations of atmospheric background rates. MABEL data give a more accurate representation of background noise rates over areas of water (i.e., melt ponds, crevasses or sea ice leads) versus land or solid ice. Through a variety of data manipulation procedures, we provide a product that mimics the appearance and parameter characterization of ATL03 data granules. There are three primary goals for generating this simulated ATL03 dataset: (1) allowing end users to become familiar with using the large photon cloud datasets that will be the primary science data product from ICESat-2, (2) the process ensures that ATL03 data can flow seamlessly through upper-level science data product algorithms, and (3) the process ensures parameter traceability through ATL03 and upper-level data products. We will present a summary of how simulated data products are generated, the cryospheric data product applications for this simulated data (specifically ice sheet height and sea ice freeboard), and where these simulated datasets are available to the ICESat-2 data user community.

Three-dimensional contrast-enhanced magnetic resonance angiography for anterolateral thigh flap outlining: A retrospective case series of 68 patients.

PubMed

Jiang, Chunjing; Lin, Ping; Fu, Xiaoyan; Shu, Jiner; Li, Huimin; Hu, Xiaogang; He, Jianrong; Ding, Mingxing

2016-08-01

Flap transfer is increasingly used for repairing limb defects secondary to trauma or tumor, and appropriate preoperative planning plays a critical role. The present study aimed to examine the use of three-dimensional (3D) contrast-enhanced magnetic resonance angiography (CE-MRA) in evaluating the blood supply distribution and perforating branch pattern of anterolateral thigh (ALT) flaps. Bilateral donor lower limbs were scanned in 68 patients (136 limbs) using a Siemens Avanto 1.5 T magnetic resonance imaging scanner with a 3D fast low-angle shot sequence, following the thin-slab maximum intensity projection (TS-MIP) technique. The lateral femoral circumflex artery (LFCA) was visualized in all patients: 101 limbs (101/136, 74.3%) were type I; 20 limbs (20/136, 14.7%) were type II; 3 limbs (3/136, 2.2%) were type III; and 12 limbs (12/136, 8.8%) were type IV. Tertiary branches were identified in 94 limbs (94/136, 69.1%). Donor flaps were outlined according to MRA TS-MIP findings in 4 patients. All flaps survived uneventfully following the transfer. In donor flap outlining, 3D CE-MRA with the TS-MIP technique allowed an accurate, direct visualization of the branching pattern and distribution profile of the LFCA supplying the ALT flap.

Stand density-a factor affecting stem quality of young hardwoods

Treesearch

David L. Sonderman; David L. Sonderman

1985-01-01

A 14-year-old mixed oak stand was thinned in 1977 to stocking levels of 30, 50, and 60 percent and a control. From this stand, 117 trees were selected and their stem-related defects recorded. Six years later these same trees were reevaluated. The number of limb defects per square foot of surface area increased substantially more in the heavily thinned plots than in the...

Convergent Validity of the Arab Teens Lifestyle Study (ATLS) Physical Activity Questionnaire

PubMed Central

Al-Hazzaa, Hazzaa M.; Al-Sobayel, Hana I.; Musaiger, Abdulrahman O.

2011-01-01

The Arab Teens Lifestyle Study (ATLS) is a multicenter project for assessing the lifestyle habits of Arab adolescents. This study reports on the convergent validity of the physical activity questionnaire used in ATLS against an electronic pedometer. Participants were 39 males and 36 females randomly selected from secondary schools, with a mean age of 16.1 ± 1.1 years. ATLS self-reported questionnaire was validated against the electronic pedometer for three consecutive weekdays. Mean steps counts were 6,866 ± 3,854 steps/day with no significant gender difference observed. Questionnaire results showed no significant gender differences in time spent on total or moderate-intensity activities. However, males spent significantly more time than females on vigorous-intensity activity. The correlation of steps counts with total time spent on all activities by the questionnaire was 0.369. Relationship of steps counts was higher with vigorous-intensity (r = 0.338) than with moderate-intensity activity (r = 0.265). Pedometer steps counts showed higher correlations with time spent on walking (r = 0.350) and jogging (r = 0.383) than with the time spent on other activities. Active participants, based on pedometer assessment, were also most active by the questionnaire. It appears that ATLS questionnaire is a valid instrument for assessing habitual physical activity among Arab adolescents. PMID:22016718

Effect of Advanced Trauma Life Support program on medical interns' performance in simulated trauma patient management.

PubMed

Ahmadi, Koorosh; Sedaghat, Mohammad; Safdarian, Mahdi; Hashemian, Amir-Masoud; Nezamdoust, Zahra; Vaseie, Mohammad; Rahimi-Movaghar, Vafa

2013-01-01

Since appropriate and time-table methods in trauma care have an important impact on patients'outcome, we evaluated the effect of Advanced Trauma Life Support (ATLS) program on medical interns' performance in simulated trauma patient management. A descriptive and analytical study before and after the training was conducted on 24 randomly selected undergraduate medical interns from Imam Reza Hospital in Mashhad, Iran. On the first day, we assessed interns' clinical knowledge and their practical skill performance in confronting simulated trauma patients. After 2 days of ATLS training, we performed the same study and evaluated their score again on the fourth day. The two findings, pre- and post- ATLS periods, were compared through SPSS version 15.0 software. P values less than 0.05 were considered statistically significant. Our findings showed that interns'ability in all the three tasks improved after the training course. On the fourth day after training, there was a statistically significant increase in interns' clinical knowledge of ATLS procedures, the sequence of procedures and skill performance in trauma situations (P less than 0.001, P equal to 0.016 and P equal to 0.01 respectively). ATLS course has an important role in increasing clinical knowledge and practical skill performance of trauma care in medical interns.

Convergent validity of the Arab Teens Lifestyle Study (ATLS) physical activity questionnaire.

PubMed

Al-Hazzaa, Hazzaa M; Al-Sobayel, Hana I; Musaiger, Abdulrahman O

2011-09-01

The Arab Teens Lifestyle Study (ATLS) is a multicenter project for assessing the lifestyle habits of Arab adolescents. This study reports on the convergent validity of the physical activity questionnaire used in ATLS against an electronic pedometer. Participants were 39 males and 36 females randomly selected from secondary schools, with a mean age of 16.1 ± 1.1 years. ATLS self-reported questionnaire was validated against the electronic pedometer for three consecutive weekdays. Mean steps counts were 6,866 ± 3,854 steps/day with no significant gender difference observed. Questionnaire results showed no significant gender differences in time spent on total or moderate-intensity activities. However, males spent significantly more time than females on vigorous-intensity activity. The correlation of steps counts with total time spent on all activities by the questionnaire was 0.369. Relationship of steps counts was higher with vigorous-intensity (r = 0.338) than with moderate-intensity activity (r = 0.265). Pedometer steps counts showed higher correlations with time spent on walking (r = 0.350) and jogging (r = 0.383) than with the time spent on other activities. Active participants, based on pedometer assessment, were also most active by the questionnaire. It appears that ATLS questionnaire is a valid instrument for assessing habitual physical activity among Arab adolescents.

Analysis of Driver Behavior and Operations at Intersection Short Lanes

DOT National Transportation Integrated Search

2016-08-01

With the ever-increasing demand to add roadway capacity in a safe and efficient manner, the application of auxiliary through lanes (ATLs) at intersections has increased in recent years. ATL intersections exist when there is an added through lane intr...

Genes for ribitol and D-arabitol catabolism in Escherichia coli: their loci in C strains and absence in K-12 and B strains.

PubMed Central

Reiner, A M

1975-01-01

Escherichia coli C strains can grow at the expense of the two natural pentitols ribitol and D-arabitol, sugar alcohols previously thought not to be utilized by E. coli. E. coli strains K-12 and B cannot utilize either compound. The genetic loci responsible for pentitol catabolism in E. coli C, designated rtl and atl, are separate and closely linked. Each lies between metG and his and is highly co-transducible with metG and with a P2 prophage attachment site. rtl and atl readily can be transduced into E. coli K-12 or B strains, in which they integrate at, or very near, their E. coli C location. Transduction also can be used to insert rtl and atl into certain E. coli K-12 F' plasmids. No recombination between E. coli C strains and either K-12 or B strains occurs within the rtl-atl genetic region after interstrain conjugations or transductions. No cryptic rtl or atl genes in K-12 or B strains can be detected by complementation, recombination, or mutagenesis. These results are consistent with the view that the rtl-atl portion of the E. coli C chromosome has no counterpart in E. coli K-12 or B and may have been obtained from an extrageneric source. Detailed biochemical and genetic comparisons of penitol utilization in E. coli and Klebsiella aerogenes are in progress. The ability to catabolize xylitol is conferred upon E. coli C strains by a mutation at or adjacent to the rtl locus, whereas in E. coli K-12 or B strains harboring rtl an additional mutation at a separate locus is required for xylitol utilization. PMID:1097416

Oxidative degradation of atenolol by heat-activated persulfate: Kinetics, degradation pathways and distribution of transformation intermediates.

PubMed

Miao, Dong; Peng, Jianbiao; Zhou, Xiaohuan; Qian, Li; Wang, Mengjie; Zhai, Li; Gao, Shixiang

2018-05-17

Atenolol (ATL) has been widely detected in wastewater and aquatic environment. Although satisfactory removal of ATL from wastewater could be achieved, the mineralization ratio is usually low, which may result in the accumulation of its transformation products in the effluent and cause additional ecological risk to the environment. The aim of this study is to explore the effectiveness of heat activated persulfate (PS) in the removal of ATL from wastewater. Influencing factors including temperature, PS dosage, solution pH, existence of NO 3 - , Cl - , HCO 3 - and Suwannee river fulvic acid (SRFA) were examined. Complete removal of ATL was achieved within 40 min at pH 7.0 and 70 °C by using 0.5 mM PS. Inhibitive effects of HCO 3 - and FA had been observed on ATL oxidation, which was increased with the increase of their concentration. Sulfate radical (SO 4 - ) was determined as the main reactive species by quenching experiment. Eight intermediates produced in ATL degradation were identified, and four degradation pathways were proposed based on the analysis of mass spectrum and frontier electron densities. The distribution of major intermediates was influenced by reaction temperature. Hydroxylation intermediates and deamidation intermediate were the most prominent at 50 °C and 60 °C, respectively. All intermediates were completely degraded in 40 min except P134 at 70 °C. Effective removal of TOC (74.12%) was achieved with 0.5 mM PS, pH 7.0 and 70 °C after 240 min. The results proved that heat activation of PS is a promising method to remove organic pollutants in wastewater. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3.

PubMed

Kornak, Uwe; Mademan, Inès; Schinke, Marte; Voigt, Martin; Krawitz, Peter; Hecht, Jochen; Barvencik, Florian; Schinke, Thorsten; Gießelmann, Sebastian; Beil, F Timo; Pou-Serradell, Adolf; Vílchez, Juan J; Beetz, Christian; Deconinck, Tine; Timmerman, Vincent; Kaether, Christoph; De Jonghe, Peter; Hübner, Christian A; Gal, Andreas; Amling, Michael; Mundlos, Stefan; Baets, Jonathan; Kurth, Ingo

2014-03-01

Many neurodegenerative disorders present with sensory loss. In the group of hereditary sensory and autonomic neuropathies loss of nociception is one of the disease hallmarks. To determine underlying factors of sensory neurodegeneration we performed whole-exome sequencing in affected individuals with the disorder. In a family with sensory neuropathy with loss of pain perception and destruction of the pedal skeleton we report a missense mutation in a highly conserved amino acid residue of atlastin GTPase 3 (ATL3), an endoplasmic reticulum-shaping GTPase. The same mutation (p.Tyr192Cys) was identified in a second family with similar clinical outcome by screening a large cohort of 115 patients with hereditary sensory and autonomic neuropathies. Both families show an autosomal dominant pattern of inheritance and the mutation segregates with complete penetrance. ATL3 is a paralogue of ATL1, a membrane curvature-generating molecule that is involved in spastic paraplegia and hereditary sensory neuropathy. ATL3 proteins are enriched in three-way junctions, branch points of the endoplasmic reticulum that connect membranous tubules to a continuous network. Mutant ATL3 p.Tyr192Cys fails to localize to branch points, but instead disrupts the structure of the tubular endoplasmic reticulum, suggesting that the mutation exerts a dominant-negative effect. Identification of ATL3 as novel disease-associated gene exemplifies that long-term sensory neuronal maintenance critically depends on the structural organisation of the endoplasmic reticulum. It emphasizes that alterations in membrane shaping-proteins are one of the major emerging pathways in axonal degeneration and suggests that this group of molecules should be considered in neuroprotective strategies.

Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

PubMed

Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

2016-05-01

Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients.

Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice

PubMed Central

Ikebe, E; Kawaguchi, A; Tezuka, K; Taguchi, S; Hirose, S; Matsumoto, T; Mitsui, T; Senba, K; Nishizono, A; Hori, M; Hasegawa, H; Yamada, Y; Ueno, T; Tanaka, Y; Sawa, H; Hall, W; Minami, Y; Jeang, K T; Ogata, M; Morishita, K; Hasegawa, H; Fujisawa, J; Iha, H

2013-01-01

In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression. PMID:23955587

STATUS OF THE AMERICAN TEGUMENTARY LEISHMANIASIS IN THE STATE OF RIO DE JANEIRO , BRAZIL, FROM 2004 TO 2013

PubMed Central

VITA, Gilmar Ferreira; PEREIRA, Maria Angélica Vieira DA COSTA; FERREIRA, Ildemar; SANAVRIA, Argemiro; BARBOSA, Celso Guimarães; AURNHEIMER, Rita de Cássia Martins; de MELLO, Ericson Ramos; da SILVA, Claudia Bezerra; CABRAL, Rísia Brígida Gonçalves

2016-01-01

SUMMARY The aim of the present study was to analyze the status of the American Tegumentary Leishmaniasis (ATL) in the state of Rio de Janeiro, from 2004 to 2013, through its spatiotemporal distribution. We also described variables considered relevant to the epidemiology of the disease, such as the clinical form, gender, ethnic group, age group, and progression of disease. This is a descriptive study, which used notified secondary data from the Brazilian Information System of Notifiable Diseases (SINAN), Ministry of Health, Brazil, regarding confirmed diagnoses. To help the calculation of coefficients of detection and mortality, we used population data from the Brazilian Institute of Geography and Statistics (IBGE). We analyzed 1,470 cases of ATL with the predominance of the cutaneous clinical form (1,292/87.89%). The data has also revealed seven deaths, a predominance of males (922/62.72%), and a higher incidence of ATL in the white ethnic group (731/49.72%). We observed a high incidence of ATL in the group of 20 - 39 years old (477/32.44%). We concluded that there was a decrease in the number of ATL cases in the state of Rio de Janeiro, based on a coefficient of detection of 1.44/100.000 inhabitants in 2004 decreasing to 0.20/100.000 inhabitants in 2013. The localities with the highest occurrences of ATL were the metropolitan region (843 cases) and the municipality of Rio de Janeiro (740 cases). In 2005, the highest incidence of the disease was observed (351 cases) in the study. Among the variables selected to describe the epidemiology of the disease, the following categories: cutaneous clinical form, male patients, white ethnic group, and the age group of 20 - 39 years old were more affected than the others. PMID:27680176

Atl1 regulates choice between global genome and transcription-coupled repair of O(6)-alkylguanines.

PubMed

Latypov, Vitaly F; Tubbs, Julie L; Watson, Amanda J; Marriott, Andrew S; McGown, Gail; Thorncroft, Mary; Wilkinson, Oliver J; Senthong, Pattama; Butt, Amna; Arvai, Andrew S; Millington, Christopher L; Povey, Andrew C; Williams, David M; Santibanez-Koref, Mauro F; Tainer, John A; Margison, Geoffrey P

2012-07-13

Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O(6)-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O(6)-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O(6)-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparison of Cultivars and Seasonal Variation in Blueberry (Vaccinium Species) Leaf Extract on Adult T-Cell Leukemia Cell Line Growth Suppression.

PubMed

Kai, Hisahiro; Fuse, Takuichi; Kunitake, Hisato; Morishita, Kazuhiro; Matsuno, Koji

2014-06-30

The inhibitory effects of blueberry leaves on the proliferation of adult T-cell leukemia (ATL) cell lines have previously been reported. A comparison of blueberry leaf extracts from different cultivars and seasonal variation were investigated regarding their effects on ATL cell line proliferation. The inhibitory effects of 80% ethanol leaf extracts from different blueberry cultivars collected from April to December in 2006 or 2008 were evaluated using two ATL cell lines. The bioactivities of leaf extracts of rabbit-eye blueberry ( Vaccinium virgatum Aiton; RB species), southern highbush blueberry ( V. spp.; SB species), northern highbush blueberry ( V. corymbosum L.; NB species), and wild blueberry ( V. bracteatum Thunb.; WB species) were compared. Of these, leaves of the RB species collected in December showed a significantly stronger inhibitory effect in both cell lines than the SB, NB, or WB species. These results suggest elevated biosynthesis of ATL-preventative bioactive compounds in the leaves of the RB species before the defoliation season.

Comparison of Cultivars and Seasonal Variation in Blueberry (Vaccinium Species) Leaf Extract on Adult T-Cell Leukemia Cell Line Growth Suppression

PubMed Central

Kai, Hisahiro; Fuse, Takuichi; Kunitake, Hisato; Morishita, Kazuhiro; Matsuno, Koji

2014-01-01

The inhibitory effects of blueberry leaves on the proliferation of adult T-cell leukemia (ATL) cell lines have previously been reported. A comparison of blueberry leaf extracts from different cultivars and seasonal variation were investigated regarding their effects on ATL cell line proliferation. The inhibitory effects of 80% ethanol leaf extracts from different blueberry cultivars collected from April to December in 2006 or 2008 were evaluated using two ATL cell lines. The bioactivities of leaf extracts of rabbit-eye blueberry (Vaccinium virgatum Aiton; RB species), southern highbush blueberry (V. spp.; SB species), northern highbush blueberry (V. corymbosum L.; NB species), and wild blueberry (V. bracteatum Thunb.; WB species) were compared. Of these, leaves of the RB species collected in December showed a significantly stronger inhibitory effect in both cell lines than the SB, NB, or WB species. These results suggest elevated biosynthesis of ATL-preventative bioactive compounds in the leaves of the RB species before the defoliation season. PMID:28933373

Human T-Cell Lymphotropic Virus: A Model of NF-κB-Associated Tumorigenesis

PubMed Central

Qu, Zhaoxia; Xiao, Gutian

2011-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATL), whereas the highly related HTLV-2 is not associated with ATL or other cancers. In addition to ATL leukemogenesis, studies of the HTLV viruses also provide an exceptional model for understanding basic pathogenic mechanisms of virus-host interactions and human oncogenesis. Accumulating evidence suggests that the viral regulatory protein Tax and host inflammatory transcription factor NF-κB are largely responsible for the different pathogenic potentials of HTLV-1 and HTLV-2. Here, we discuss the molecular mechanisms of HTLV-1 oncogenic pathogenesis with a focus on the interplay between the Tax oncoprotein and NF-κB pro-oncogenic signaling. We also outline some of the most intriguing and outstanding questions in the fields of HTLV and NF-κB. Answers to those questions will greatly advance our understanding of ATL leukemogenesis and other NF-κB-associated tumorigenesis and will help us design personalized cancer therapies. PMID:21743832

VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation

PubMed Central

Shih, Yu-Tzu; Hsueh, Yi-Ping

2016-01-01

Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders. PMID:26984393

VCP and ATL1 regulate endoplasmic reticulum and protein synthesis for dendritic spine formation.

PubMed

Shih, Yu-Tzu; Hsueh, Yi-Ping

2016-03-17

Imbalanced protein homeostasis, such as excessive protein synthesis and protein aggregation, is a pathogenic hallmark of a range of neurological disorders. Here, using expression of mutant proteins, a knockdown approach and disease mutation knockin mice, we show that VCP (valosin-containing protein), together with its cofactor P47 and the endoplasmic reticulum (ER) morphology regulator ATL1 (Atlastin-1), regulates tubular ER formation and influences the efficiency of protein synthesis to control dendritic spine formation in neurons. Strengthening the significance of protein synthesis in dendritic spinogenesis, the translation blocker cyclohexamide and the mTOR inhibitor rapamycin reduce dendritic spine density, while a leucine supplement that increases protein synthesis ameliorates the dendritic spine defects caused by Vcp and Atl1 deficiencies. Because VCP and ATL1 are the causative genes of several neurodegenerative and neurodevelopmental disorders, we suggest that impaired ER formation and inefficient protein synthesis are significant in the pathogenesis of multiple neurological disorders.

Mapping Snow Depth with Automated Terrestrial Laser Scanning - Investigating Potential Applications

NASA Astrophysics Data System (ADS)

Adams, M. S.; Gigele, T.; Fromm, R.

2017-11-01

This contribution presents an automated terrestrial laser scanning (ATLS) setup, which was used during the winter 2016/17 to monitor the snow depth distribution on a NW-facing slope at a high-alpine study site. We collected data at high temporal [(sub-)daily] and spatial resolution (decimetre-range) over 0.8 km² with a Riegl LPM-321, set in a weather-proof glass fibre enclosure. Two potential ATLS-applications are investigated here: monitoring medium-sized snow avalanche events, and tracking snow depth change caused by snow drift. The results show the ATLS data's high explanatory power and versatility for different snow research questions.

The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma: analysis of 126 patients from the International Peripheral T-Cell Lymphoma Project.

PubMed

Suzumiya, J; Ohshima, K; Tamura, K; Karube, K; Uike, N; Tobinai, K; Gascoyne, R D; Vose, J M; Armitage, J O; Weisenburger, D D

2009-04-01

The International Peripheral T-cell Lymphoma Project was organized to better understand the T-cell and natural killer (NK) cell lymphomas, and our task is to present the clinicopathologic correlations and therapeutic results for adult T-cell leukemia/lymphoma (ATL). Among 1153 patients with T-cell or NK cell lymphomas, 126 patients (9.6%) with ATL were represented in this project. All were categorized as aggressive ATL, i.e. acute or lymphoma type, and 87% fell into the lymphoma type. The median age was 62 years and the male to female ratio was 1.2 : 1. Significant prognostic factors for overall survival (OS) by univariate analysis were the presence of B symptoms (P = 0.018), platelet count <150 x 10(9)/l (P = 0.065), and the International Prognostic Index (IPI; P = 0.019). However, multivariate analysis indicated that only the IPI was an independent predictor of OS. Combination chemotherapy including anthracyclines was given as the initial therapy in 109 of the 116 patients (94%) who received treatment, and the overall and complete response rates were 70% and 34%, respectively. However, there was no survival benefit for those receiving an anthracycline-containing regimen. Patients with aggressive ATL have a poor clinical outcome and the IPI is a useful model for predicting outcome in ATL of the lymphoma type.

Naming and recognizing famous faces in temporal lobe epilepsy.

PubMed

Glosser, G; Salvucci, A E; Chiaravalloti, N D

2003-07-08

To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy (ATL). Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy (TLE) either before or after ATL and to 10 healthy age- and education-matched controls. Spontaneous naming of photographed famous people was impaired in all patient groups, but was most abnormal in patients who had undergone left ATL. When allowed to demonstrate knowledge of the famous faces through verbal descriptions, rather than naming, patients with left TLE, left ATL, and right TLE improved to normal levels, but patients with right ATL were still impaired, suggesting a new deficit in identifying famous faces. Naming of famous people was related to naming of other common objects, verbal memory, and perceptual discrimination of faces. Recognition of the identity of pictured famous people was more related to visuospatial perception and memory. Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces, as well as the learning of new faces. Lesions in the left temporal lobe, especially in anterior regions, disrupt access to the names of known people, but do not affect recognition of the identities of famous faces. Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities.

Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation.

PubMed

Bose, Jeffrey L; Lehman, McKenzie K; Fey, Paul D; Bayles, Kenneth W

2012-01-01

The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.

Children's Early Approaches to Learning and Academic Trajectories through Fifth Grade

ERIC Educational Resources Information Center

Li-Grining, Christine P.; Votruba-Drzal, Elizabeth; Maldonado-Carreno, Carolina; Haas, Kelly

2010-01-01

Children's early approaches to learning (ATL) enhance their adaptation to the demands they experience with the start of formal schooling. The current study uses individual growth modeling to investigate whether children's early ATL, which includes persistence, emotion regulation, and attentiveness, explain individual differences in their academic…

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax301-309-Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients.

PubMed

Ishihara, Yuko; Tanaka, Yukie; Kobayashi, Seiichiro; Kawamura, Koji; Nakasone, Hideki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Uchimaru, Kaoru; Kanda, Yoshinobu

2017-10-01

We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax 301-309 -specific CD8 + cytotoxic T cells (Tax 301-309 -CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02 + ) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR + CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax 301-309 -CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax 301-309 -CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax 301-309 -CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax 301-309 -CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax 301-309 -CTLs, 1,458 Tax 301-309 -CTLs and 140 clones were identified in this cohort. Tax 301-309 -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR + CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02 + HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR + CTL response in the progression from carrier state to ATL. IMPORTANCE ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8 + CTLs. In our previous evaluation of Tax 301-309 -CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax 301-309 -CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR + Tax 301-309 -CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax 301-309 -CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax 301-309 -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection. Copyright © 2017 American Society for Microbiology.

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax301-309-Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients

PubMed Central

Ishihara, Yuko; Tanaka, Yukie; Kobayashi, Seiichiro; Kawamura, Koji; Nakasone, Hideki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-ichi; Tanihara, Aki; Kako, Shinichi; Uchimaru, Kaoru

2017-01-01

ABSTRACT We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax301-309-specific CD8+ cytotoxic T cells (Tax301-309-CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02+) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR+ CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax301-309-CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax301-309-CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax301-309-CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax301-309-CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax301-309-CTLs, 1,458 Tax301-309-CTLs and 140 clones were identified in this cohort. Tax301-309-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR+ CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02+ HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR+ CTL response in the progression from carrier state to ATL. IMPORTANCE ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the proliferation of HTLV-1-infected lymphocytes and is also a major target antigen for CD8+ CTLs. In our previous evaluation of Tax301-309-CTLs, we found that a unique amino acid sequence motif, PDR, in CDR3 of the TCR-β chain of Tax301-309-CTLs was conserved among ATL patients after allo-HSCT. Furthermore, the PDR+ Tax301-309-CTL clones selectively expanded and showed strong cytotoxic activities against HTLV-1. On the other hand, it remains unclear how Tax301-309-CTL repertoire exists in ACs. In this study, we comprehensively compared Tax-specific TCR repertoires at the single-cell level between ACs and ATL patients. Tax301-309-CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was conserved in all ACs and ATL patients, regardless of clinical subtype in HTLV-1 infection. PMID:28724766

Sustained Presence of Cutaneous Leishmaniasis in Urban Manaus, the Largest Human Settlement in the Amazon.

PubMed

Benício, Ednelza; Cordeiro, Mayara; Monteiro, Hannah; Saboia Moura, Marco Antônio; Oliveira, Cintia; Nunes Gadelha, Ellen Pricilla; Chrusciak-Talhari, Anette; Talhari, Carolina; de Lima Ferreira, Luiz Carlos; Mira, Marcelo Távora; Lima Machado, Paulo Roberto; Talhari, Sinésio; Schriefer, Albert

2015-12-01

The Amazon is responsible for approximately 40% of the American tegumentary leishmaniasis (ATL) in Brazil. Herein the sustained presence of ATL in Manaus, the largest settlement in the Amazon, was investigated. Records of notification of historic cases, and data from cases prospectively enrolled in the Tropical Medicine Foundation of the Amazonas State were used. Geographic coordinates of prospective patients' living sites were used to detect inner-city clusters of ATL. Infecting Leishmania species was determined by polymerase chain reaction. Among prospectively enrolled subjects, 94.8% were infected with Leishmania (Viannia) guyanensis, 76.7% were male, 30.2% were 0-20 years old, and 69.8% had an urban residence. Historic cases showed a profile similar to that of prospectively enrolled subjects. Several clusters of ATL, widely distributed within the city of Manaus, could be detected. In conclusion, there was a high frequency of disease in young age groups and cases clustered in urban neighborhoods. It cannot be determined from these data whether transmission of these cases occurred within or outside the city of Manaus. © The American Society of Tropical Medicine and Hygiene.

Sustained Presence of Cutaneous Leishmaniasis in Urban Manaus, the Largest Human Settlement in the Amazon

PubMed Central

Benício, Ednelza; Cordeiro, Mayara; Monteiro, Hannah; Moura, Marco Antônio Saboia; Oliveira, Cintia; Gadelha, Ellen Pricilla Nunes; Chrusciak-Talhari, Anette; Talhari, Carolina; de Lima Ferreira, Luiz Carlos; Mira, Marcelo Távora; Machado, Paulo Roberto Lima; Talhari, Sinésio; Schriefer, Albert

2015-01-01

The Amazon is responsible for approximately 40% of the American tegumentary leishmaniasis (ATL) in Brazil. Herein the sustained presence of ATL in Manaus, the largest settlement in the Amazon, was investigated. Records of notification of historic cases, and data from cases prospectively enrolled in the Tropical Medicine Foundation of the Amazonas State were used. Geographic coordinates of prospective patients' living sites were used to detect inner-city clusters of ATL. Infecting Leishmania species was determined by polymerase chain reaction. Among prospectively enrolled subjects, 94.8% were infected with Leishmania (Viannia) guyanensis, 76.7% were male, 30.2% were 0–20 years old, and 69.8% had an urban residence. Historic cases showed a profile similar to that of prospectively enrolled subjects. Several clusters of ATL, widely distributed within the city of Manaus, could be detected. In conclusion, there was a high frequency of disease in young age groups and cases clustered in urban neighborhoods. It cannot be determined from these data whether transmission of these cases occurred within or outside the city of Manaus. PMID:26483119

Concept typicality responses in the semantic memory network.

PubMed

Santi, Andrea; Raposo, Ana; Frade, Sofia; Marques, J Frederico

2016-12-01

For decades concept typicality has been recognized as critical to structuring conceptual knowledge, but only recently has typicality been applied in better understanding the processes engaged by the neurological network underlying semantic memory. This previous work has focused on one region within the network - the Anterior Temporal Lobe (ATL). The ATL responds negatively to concept typicality (i.e., the more atypical the item, the greater the activation in the ATL). To better understand the role of typicality in the entire network, we ran an fMRI study using a category verification task in which concept typicality was manipulated parametrically. We argue that typicality is relevant to both amodal feature integration centers as well as category-specific regions. Both the Inferior Frontal Gyrus (IFG) and ATL demonstrated a negative correlation with typicality, whereas inferior parietal regions showed positive effects. We interpret this in light of functional theories of these regions. Interactions between category and typicality were not observed in regions classically recognized as category-specific, thus, providing an argument against category specific regions, at least with fMRI. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Dog (Canis familiaris) infectivity to Lutzomyia youngi in Trujillo, Venezuela].

PubMed

Hernández, Dalila; Rojas, Elina; Scorza, José Vicente; Jorquera, Alicia

2006-10-01

In Trujillo, Venezuela the prevalence for American tegumentary leishmaniasis (ATL) is 38 per 100,000 inhabitants. In a periurban, rural settlement of the capital city Trujillo, we studied the potential capability of the domestic dog (Canis familiaris) as a source of infection for Lutzomyia youngi, a phlebotomine sand fly species abundant in the study area and whose domestic vectorial activity has been proven. Dogs with dermal lesions suggestive of ATL and parasitological confirmation of infection, were selected for xenodiagnosis by allowing sylvatic phlebotomines from a ATL free area, to feed ad libitum over each animal's entire body surface. The insects' intestinal tracts were dissected 5 days after the blood meal in order to look for flagellate forms. When these were found, parasitological identification was performed by the multiplex-PCR technique. Four hundred and fifty five sand flies engorged over two dogs in three different assays; promastigotes were found in 4 (0.88%) of the specimens on only one occasion. PCR identified DNA of the Leishmania Viannia subgenus. The household dog has the potential of being a domestic risk factor in the ATL transmission cycle.

Repression of tax expression is associated both with resistance of human T-cell leukemia virus type 1-infected T cells to killing by tax-specific cytotoxic T lymphocytes and with impaired tumorigenicity in a rat model.

PubMed

Nomura, Machiko; Ohashi, Takashi; Nishikawa, Keiko; Nishitsuji, Hironori; Kurihara, Kiyoshi; Hasegawa, Atsuhiko; Furuta, Rika A; Fujisawa, Jun-ichi; Tanaka, Yuetsu; Hanabuchi, Shino; Harashima, Nanae; Masuda, Takao; Kannagi, Mari

2004-04-01

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL). Although the viral transactivation factor, Tax, has been known to have apparent transforming ability, the exact function of Tax in ATL development is still not clear. To understand the role of Tax in ATL development, we introduced short-interfering RNAs (siRNAs) against Tax in a rat HTLV-1-infected T-cell line. Our results demonstrated that expression of siRNA targeting Tax successfully downregulated Tax expression. Repression of Tax expression was associated with resistance of the HTLV-1-infected T cells to Tax-specific cytotoxic-T-lymphocyte killing. This may be due to the direct effect of decreased Tax expression, because the Tax siRNA did not alter the expression of MHC-I, CD80, or CD86. Furthermore, T cells with Tax downregulation appeared to lose the ability to develop tumors in T-cell-deficient nude rats, in which the parental HTLV-1-infected cells induce ATL-like lymphoproliferative disease. These results indicated the importance of Tax both for activating host immune response against the virus and for maintaining the growth ability of infected cells in vivo. Our results provide insights into the mechanisms how the host immune system can survey and inhibit the growth of HTLV-1-infected cells during the long latent period before the onset of ATL.

Comparative histopathological study of sporotrichosis and American tegumentary leishmaniasis in dogs from Rio de Janeiro.

PubMed

Miranda, L H M; Quintella, L P; Santos, I B; Oliveira, R V C; Menezes, R C; Figueiredo, F B; Schubach, T M P

2010-07-01

Pyogranulomatous lesions from 80 dogs with sporotrichosis and 26 dogs with American tegumentary leishmaniasis (ATL) were compared microscopically in order to identify features that would support the diagnostic suspicion and direct the subsequent search for the aetiological agent of either infection. Odds ratios and their respective 95% confidence intervals were calculated in order to evaluate the impact of the microscopical findings on the diagnosis of either disease. Lesions with well-formed granulomata were 14 times more likely to be due to sporotrichosis than ATL. Marked neutrophil infiltration into granulomata was 12.26 times more likely to be associated with sporotrichosis when compared with lesions having mild neutrophilic infiltration. Absence of lymphocytes and macrophages in the peripheral infiltrate was associated with a 9.71 and 4.93 higher chance, respectively, of being sporotrichosis rather than ATL compared with lesions where these cells were present. Lesions with a perivascular, perifollicular and interstitial peripheral inflammatory infiltrate were 5.48 times more likely to be due to sporotrichosis than ATL when compared with lesions with a diffuse peripheral infiltrate. Histopathological analysis may therefore contribute to the diagnosis of sporotrichosis or ATL skin lesions in dogs since this method permits the identification of features that direct the diagnostic suspicion, thus facilitating the search for the aetiological agent in histological sections, permitting the precise request of subsequent tests and thereby reducing costs and time taken to achieve a definitive diagnosis and the initiation of appropriate therapy. (c) 2009 Elsevier Ltd. All rights reserved.

Effect of antibiotic prophylaxis on Coagulase-negative Staphylococcus virulence factor profiles in patients undergoing cataract surgery.

PubMed

López, Yolanda; Samudio, Margarita; Fariña, Norma; Castillo, Verónica; Abente, Sonia; Nentwich, Martin M; González-Britez, Nilsa; Laspina, Florentina; Carron, Agustín; Cibils, Diógenes; de Kaspar, Herminia Miño

2017-08-01

In this prospective study, multiplex polymerase chain reaction (PCR) was used to identify genes encoding virulence factors (ica, atlE and mecA) in Coagulase-negative Staphylococcus (CNS) isolates from the ocular microbiota of patients undergoing cataract surgery and to investigate possible changes in the CNS profile due to antibiotic prophylaxis. Between 09/2011 and 08/2013, patients undergoing cataract surgery were recruited at the Department of Ophthalmology, National University of Asuncion, Paraguay. In the eye to be operated on, patients received moxifloxacin 0.5 % eye drops four times at the day before surgery and a last drop 1 hour before surgery (T1). The other eye remained as control (T0). Conjunctival swabs were taken from both eyes 1 hour after the last drop. The presence of genes encoding biofilm formation (ica and atlE) and methicillin resistance (mecA) was detected by a multiplex PCR. Of the 162 patients (162 study eyes, 162 fellow eye as control group), 87 (53.7 %) eyes were positive for CNS at T0 yielding 96 CNS isolates; 70 eyes (43.2 %) were positive at T1 yielding 77 CNS isolates. For this study, 43 CNS isolates (44.8 %) from T0 and 45 (64.3 %) from T1 were used. Of the total isolates, 81.8 % (72/88) had at least one virulence factor gene (37/43 from T0 and 35/45 from T1) (p = 0.314). Simultaneous detection of ica and atlE genes was higher in T0 (58.0 %) than T1 (46.7 %), but the difference was not significant (p = 0.28). A high frequency of genes encoding virulence factors was observed in the coagulase-negative Staphylococcus isolates. The use of moxifloxacin did not significantly modify the CNS virulence factor profiles.

Different effects of anterior temporal lobectomy and selective amygdalohippocampectomy on verbal memory performance of patients with epilepsy.

PubMed

Boucher, Olivier; Dagenais, Emmanuelle; Bouthillier, Alain; Nguyen, Dang Khoa; Rouleau, Isabelle

2015-11-01

The advantage of selective amygdalohippocampectomy (SAH) over anterior temporal lobectomy (ATL) for the treatment of temporal lobe epilepsy (TLE) remains controversial. Because ATL is more extensive and involves the lateral and medial parts of the temporal lobe, it may be predicted that its impact on memory is more important than SAH, which involves resection of medial temporal structures only. However, several studies do not support this assumption. Possible explanations include task-specific factors such as the extent of semantic and syntactic information to be memorized and failure to control for main confounders. We compared preoperative vs. postoperative memory performance in 13 patients with SAH with 26 patients who underwent ATL matched on side of surgery, IQ, age at seizure onset, and age at surgery. Memory function was assessed using the Logical Memory subtest from the Wechsler Memory Scales - 3rd edition (LM-WMS), the Rey Auditory Verbal Learning Test (RAVLT), the Digit Span subtest from the Wechsler Adult Intelligence Scale, and the Rey-Osterrieth Complex Figure Test. Repeated measures analyses of variance revealed opposite effects of SAH and ATL on the two verbal learning memory tests. On the immediate recall trial of the LM-WMS, performance deteriorated after ATL in comparison with that after SAH. By contrast, on the delayed recognition trial of the RAVLT, performance deteriorated after SAH compared with that after ATL. However, additional analyses revealed that the latter finding was only observed when surgery was conducted in the right hemisphere. No interaction effects were found on other memory outcomes. The results are congruent with the view that tasks involving rich semantic content and syntactical structure are more sensitive to the effects of lateral temporal cortex resection as compared with mesiotemporal resection. The findings highlight the importance of task selection in the assessment of memory in patients undergoing TLE surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Measuring Approaches to Learning in Preschoolers: Validating the Structure of an Instrument for Teachers and Parents

ERIC Educational Resources Information Center

Barbu, Otilia C.; Marx, Ronald W.; Yaden, David B., Jr.; Levine-Donnerstein, Deborah

2016-01-01

This study examined a 13-item instrument measuring approaches to learning (AtL) as a component of school readiness in the context of early childhood socio-emotional development. Few instruments, limited to preschool teacher ratings, measure AtL among kindergarteners with short easy-to-use questionnaires. We investigated psychometric properties of…

Defense AT&L (Volume 37, Number 1, January-February 2008)

DTIC Science & Technology

2008-02-01

Protected vehicle onto a C-5 Galaxy aircraft. Photograph by Staff Sgt. Jason Robertson, USA In the News Defense AT&L: January-February 2008 54 “We have...saving costs and reducing the cycle time of the C20J Engine Line TH-57 Sea Ranger helicopter. Letterkenny’s power-generator maintenance operations have

Hypersensitivity reaction to β-lactam antibiotics in patients with adult T-cell leukemia/lymphoma treated with mogamulizumab
.

PubMed

Yasu, Takeo; Imai, Yoichi; Ohno, Nobuhiro; Uchimaru, Kaoru; Kurokawa, Yosuke; Tojo, Arinobu

2017-10-01

Mogamulizumab (MOG) is a humanized anti-CCR4 monoclonal antibody that is highly cytotoxic for adult T-cell leukemia/lymphoma (ATL) cells. Most non-hematological adverse events are cutaneous adverse reactions in ATL patients. We reviewed the medical records of 24 patients with CCR4-positive aggressive ATL who had received MOG treatment. The incidence of MOG-induced cutaneous adverse reactions (MCARs) was 25% (6 patients). Four patients with MCAR had an interesting clinical course, compared with MCARs reported in previous reports. The factors causing MCAR were suspected to be cefepime, cefozopran, and piperacillin/tazobactam. We consider that hypersensitivity reaction to β-lactam antibiotics is involved in a significant proportion of MCARs.
.

Upper limb malformations in chromosome 22q11 deletions

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

Shalev, S.A.; Dar, H.; Barel, H.

1996-03-29

We read with interest the report of Cormier-Daire et al. in a recent issue of the journal, describing upper limb malformations in DiGeorge syndrome. We observed a family with this group of rare clinical expression of chromosome 22q11 deletions. The proposita was examined in our clinic when she was 4 years old. She was mildly mentally retarded. Clinical evaluation showed normal growth, long thin nose with squared tip, nasal speech, and abundant scalp hair and no cardiac anomalies. The girl was accompanied by her mother. Facial similarities were noted between the two. The mother reported to be treated with oralmore » calcium due to hypoparathyroidism, diagnosed several years ago. Clinical evaluation showed wide flat face, short stature, mild mental retardation, slight hypertelorism, peculiar nose similar to her daughter`s, and nasal speech. No cardiac anomalies were found. Recently, a brother was born. Clinical examination documented large ventriculo-septal defect, retrognathia, narrow palpebral fissures, and long thin nose with squared tip. 1 ref.« less

Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation

PubMed Central

Green, Sophie; Lambon Ralph, Matthew A.; Moll, Jorge; Stamatakis, Emmanuel A.; Grafman, Jordan; Zahn, Roland

2010-01-01

It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. “critical” and “faultfinding”). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals. PMID:20493953

Myths and Misinformation About Gunshot Wounds may Adversely Affect Proper Treatment.

PubMed

Hafertepen, Stephen C; Davis, James W; Townsend, Ricard N; Sue, Lawrence P; Kaups, Krista L; Cagle, Kathleen M

2015-07-01

Poorly designed experiments and popular media have led to multiple myths about wound ballistics. Some of these myths have been incorporated into the trauma literature as fact and are included in Advanced Trauma Life Support (ATLS). We hypothesized that these erroneous beliefs would be prevalent, even among those providing care for patients with gunshot wounds (GSWs), but could be addressed through education. ATLS course content was reviewed. Several myths involving wound ballistics were identified. Clinically relevant myths were chosen including wounding mechanism, lead poisoning, debridement, and antibiotic use. Subsequently, surgery and emergency medicine services at three different trauma centers were studied. All three sites were busy, urban trauma centers with a significant amount of penetrating trauma. A pre-test was administered prior to a lecture on wound ballistics followed by a post-test. Pre- and post-test scores were compared and correlated with demographic data including ATLS course completion, firearm/ballistics experience, and years of post-graduate medical experience (PGME). One-hundred and fifteen clinicians participated in the study. A mean pre-test score of 34 % improved to 78 % on the post-test with associated improvements in all areas of knowledge (p < 0.001). Years of PGME correlated with higher pre-test score (p = 0.021); however, ATLS status did not (p = 0.774). Erroneous beliefs involving wound ballistics are prevalent even among clinicians who frequently treat victims of GSWs and could lead to inappropriate treatment. Focused education markedly improved knowledge. The ATLS course and manual promulgate some of these myths and should be revised.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

PubMed

Pauli, Carla; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; de Oliveira Thais, Maria Emilia Rodrigues; Kondageski, Charles; Linhares, Marcelo Neves; Guarnieri, Ricardo; de Lemos Zingano, Bianca; Ben, Juliana; Nunes, Jean Costa; Markowitsch, Hans Joachim; Wolf, Peter; Wiebe, Samuel; Lin, Katia; Walz, Roger

2017-05-01

To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Is there still a place for Achilles tendon lengthening?

PubMed

Tagoe, Mark T; Reeves, Neil D; Bowling, Frank L

2016-01-01

Patients with diabetes and ankle equinus are at particularly high risk for forefoot ulceration because of the development of high forefoot pressures. Stiffness in the triceps surae muscles and tendons are thought to be largely responsible for equinus in patients with diabetes and underpins the surgical rationale for Achilles tendon lengthening (ATL) procedures to alleviate this deformity and reduce ulcer risk. The established/traditional surgical approach is the triple hemisection along the length of the Achilles tendon. Although the percutaneous approach has been successful in achieving increases in ankle dorsiflexion >30°, the tendon rupture risk has led to some surgeons looking at alternative approaches. The gastrocnemius aponeurosis may be considered as an alternative because of the Achilles tendon's poor blood supply. ATL procedures are a balance between achieving adequate tendon lengthening and minimizing tendon rupture risk during or after surgery. After ATL surgery, the first 7 days should involve reduced loading and protected range of motion to avoid rupture, after which gradual reintroduction to loading should be encouraged to increase tendon strength. In summary, there is a moderate level of evidence to support surgical intervention for ankle joint equinus in patients with diabetes and forefoot ulceration that is non-responsive to other conservative treatments. Areas of caution for ATL procedures include the risk for overcorrection, tendon rupture and the tendon's poor blood supply. Further prospective randomized control trials are required to confirm the benefits of ATL procedures over conservative care and the most optimal anatomical sites for surgical intervention. Copyright © 2016 John Wiley & Sons, Ltd.

Contribution of the autolysin AtlA to the bactericidal activity of amoxicillin against Enterococcus faecalis JH2-2.

PubMed

Bravetti, Anne-Lise; Mesnage, Stéphane; Lefort, Agnès; Chau, Françoise; Eckert, Catherine; Garry, Louis; Arthur, Michel; Fantin, Bruno

2009-04-01

The bactericidal activity of amoxicillin was investigated against Enterococcus faecalis JH2-2 and against an isogenic mutant deficient in the production of the N-acetylglucosaminidase AtlA. Comparison of the two strains indicated that this autolysin contributes to killing by amoxicillin both in vitro and in a rabbit model of experimental endocarditis.

Characteristic patterns of relapse after allogeneic hematopoietic SCT for adult T-cell leukemia-lymphoma: a comparative study of recurrent lesions after transplantation and chemotherapy by the Nagasaki Transplant Group.

PubMed

Itonaga, H; Sawayama, Y; Taguchi, J; Honda, S; Taniguchi, H; Makiyama, J; Matsuo, E; Sato, S; Ando, K; Imanishi, D; Imaizumi, Y; Yoshida, S; Hata, T; Moriuchi, Y; Fukushima, T; Miyazaki, Y

2015-04-01

Allogeneic hematopoietic SCT (allo-SCT) is a promising therapy that may provide long-term durable remission for adult T-cell leukemia-lymphoma (ATL) patients; however, the incidence of relapse associated with ATL remains high. To determine the clinical features of these patients at relapse, we retrospectively analyzed tumor lesions in 30 or 49 patients who relapsed following allo-SCT or chemotherapy (CHT), respectively, at three institutions in Nagasaki prefecture between 1997 and 2011. A multivariate analysis revealed that the development of abnormal lymphocytes in the peripheral blood of patients at relapse was less frequent after allo-SCT than after CHT (P<0.001). Furthermore, relapse with a new lesion only in the absence of the primary lesion was more frequent in allo-SCT (P=0.014). Lesions were more frequently observed in the central nervous systems of patients who relapsed with new lesions only (P=0.005). Thus, the clinical manifestation of relapsed ATL was slightly complex, especially in post-transplant patients. Our results emphasized the need to develop adoptive modalities for early and accurate diagnoses of relapsed ATL.

Mouse Models of Human T Lymphotropic Virus Type-1–Associated Adult T-Cell Leukemia/Lymphoma

PubMed Central

Zimmerman, B.; Niewiesk, S.; Lairmore, M. D.

2011-01-01

Human T-lymphotropic virus type-1 (HTLV-1), the first human retrovirus discovered, is the causative agent of adult T-cell leukemia/lymphoma (ATL) and a number of lymphocyte-mediated inflammatory conditions including HTLV-1–associated myelopathy/tropical spastic paraparesis. Development of animal models to study the pathogenesis of HTLV-1–associated diseases has been problematic. Mechanisms of early infection and cell-to-cell transmission can be studied in rabbits and nonhuman primates, but lesion development and reagents are limited in these species. The mouse provides a cost-effective, highly reproducible model in which to study factors related to lymphoma development and the preclinical efficacy of potential therapies against ATL. The ability to manipulate transgenic mice has provided important insight into viral genes responsible for lymphocyte transformation. Expansion of various strains of immunodeficient mice has accelerated the testing of drugs and targeted therapy against ATL. This review compares various mouse models to illustrate recent advances in the understanding of HTLV-1–associated ATL development and how improvements in these models are critical to the future development of targeted therapies against this aggressive T-cell lymphoma. PMID:20442421

The Neural Bases of Taxonomic and Thematic Conceptual Relations: An MEG Study

PubMed Central

Lewis, Gwyneth A.; Poeppel, David; Murphy, Gregory L.

2015-01-01

Converging evidence from behavioral and neuroimaging studies of human concepts indicate distinct neural systems for taxonomic and thematic knowledge. A recent study of naming in aphasia found involvement of the anterior temporal lobe (ATL) during taxonomic (feature-based) processing, and involvement of the temporoparietal junction (TPJ) during thematic (function-based) processing. We conducted an online magnetoencephalography (MEG) study to examine the spatio-temporal nature of taxonomic and thematic relations. We measured participants’ brain responses to words preceded by either a taxonomically or thematically related item (e.g., cottage→castle, king→castle). In a separate experiment we collected relatedness ratings of the word pairs from participants. We examined effects of relatedness and relation type on activation in ATL and TPJ regions of interest (ROIs) using permutation t-tests to identify differences in ROI activation between conditions as well as single-trial correlational analyses to examine the millisecond-by-millisecond influence of the stimulus variables on the ROIs. Taxonomic relations strongly predicted ATL activation, and both kinds of relations influenced the TPJ. Our results further strengthen the view of the ATL's importance to taxonomic knowledge. Moreover, they provide a nuanced view of thematic relations as involving taxonomic knowledge. PMID:25582406

Forestry Expansion during the Last Decades in the Paraiba do Sul Basin - Brazil

NASA Astrophysics Data System (ADS)

Carriello, F.; Rezende, F. S.; Neves, O. M. S.; Rodriguez, D. A.

2016-06-01

from 1986 to 2010. In this region is situated the most important and largest extension of reminiscent of Mata Atlântica Biome reminiscent. This biome has been one the most exploited Brazilian biome since 1500, when Brazilian colonization begun. To achieve this goal, we use the GIS "SPRING" and images from Landsat 5 Satellite, TM sensor from 1986, 1990, 1995, 2000, 2005 and 2010, distributed by the Brazilian National Institute for Space Research - INPE. The non-supervised-classification was applied to images in order to produce land use and land cover maps. After that, we intersect each classification for each date with the precedent date, so we can analyze the paths of each land use change, focusing forestry expansion in native's Mata Atlântica areas. The results show that eucalyptus plantations in the region have expanded mostly over fragments of Mata Atlântica. About 99.389 hectares of Mata Atlântica were transformed into forestry in 25 years, an average rate of 4000 ha per year. Clear-cut was largest between 1990 and 1995, when 22810 hectares of rain forest were cut, and between 1995 and 2000, when 21430 hectares were cut.

Harvesting wood for energy.

Treesearch

Rodger A. Arola; Edwin W. Miyata

1981-01-01

Illustrates the potential of harvesting wood for industrial energy, based on the results of five harvesting studies. Presents information on harvesting operations, equipment costs, and productivity. Discusses mechanized thinning of hardwoods, clearcutting of low-value stands and recovery of hardwood tops and limbs. Also includes basic information on the physical and...

78 FR 28892 - Hazardous Fire Risk Reduction, East Bay Hills, CA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID FEMA 2010-0037] Hazardous Fire Risk Reduction, East Bay Hills, CA AGENCY: Federal Emergency Management Agency, DHS. ACTION..., limbing and mowing, thinning, and grazing techniques as appropriate to reduce the risk of fire hazard...

Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation.

PubMed

Yuen, Chun-Kit; Chan, Ching-Ping; Fung, Sin-Yee; Wang, Pei-Hui; Wong, Wan-Man; Tang, Hei-Man Vincent; Yuen, Kit-San; Chan, Chi-Ping; Jin, Dong-Yan; Kok, Kin-Hang

2016-04-01

Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-α combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-β was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKε, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-κB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKε, STING, and IRF3.In vitrokinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Suppression of Type I Interferon Production by Human T-Cell Leukemia Virus Type 1 Oncoprotein Tax through Inhibition of IRF3 Phosphorylation

PubMed Central

Yuen, Chun-Kit; Chan, Ching-Ping; Fung, Sin-Yee; Wang, Pei-Hui; Wong, Wan-Man; Tang, Hei-Man Vincent; Yuen, Kit-San; Chan, Chi-Ping

2016-01-01

ABSTRACT Infection with human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and tropical spastic paraparesis. Type I interferons (IFNs) are key effectors of the innate antiviral response, and IFN-α combined with the nucleoside reverse transcriptase inhibitor zidovudine is considered the standard first-line therapy for ATL. HTLV-1 oncoprotein Tax is known to suppress innate IFN production and response but the underlying mechanisms remain to be fully established. In this study, we report on the suppression of type I IFN production by HTLV-1 Tax through interaction with and inhibition of TBK1 kinase that phosphorylates IRF3. Induced transcription of IFN-β was severely impaired in HTLV-1-transformed ATL cells and freshly infected T lymphocytes. The ability to suppress IRF3 activation was ascribed to Tax. The expression of Tax alone sufficiently repressed the induction of IFN production by RIG-I plus PACT, cGAMP synthase plus STING, TBK1, IKKε, IRF3, and IRF7, but not by IRF3-5D, a dominant-active phosphomimetic mutant. This suggests that Tax perturbs IFN production at the step of IRF3 phosphorylation. Tax mutants deficient for CREB or NF-κB activation were fully competent in the suppression of IFN production. Coimmunoprecipitation experiments confirmed the association of Tax with TBK1, IKKε, STING, and IRF3. In vitro kinase assay indicated an inhibitory effect of Tax on TBK1-mediated phosphorylation of IRF3. Taken together, our findings suggested a new mechanism by which HTLV-1 oncoprotein Tax circumvents the production of type I IFNs in infected cells. Our findings have implications in therapeutic intervention of ATL. IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia (ATL), an aggressive and fatal blood cancer, as well as another chronic disabling disease of the spinal cord. Treatments are unsatisfactory, and options are limited. A combination of antiviral cellular protein alpha interferon and zidovudine, which is an inhibitor of a viral enzyme called reverse transcriptase, has been recommended as the standard first-line therapy for ATL. Exactly how HTLV-1 interacts with the cellular machinery for interferon production and action is not well understood. Our work sheds light on the mechanism of action for the inhibition of interferon production by an HTLV-1 oncogenic protein called Tax. Our findings might help to improve interferon-based anti-HTLV-1 and anti-ATL therapy. PMID:26819312

Tailoring and Critical Thinking - Key Principles for Acquisition Success

DTIC Science & Technology

2015-10-01

Defense AT&L: September–October 2015 6 Tailoring and Critical Thinking— Key Principles for Acquisition Success Mike Kotzian, D.M. n Michael Paul...well as program success . 7 Defense AT&L: September–October 2015 The Long Range Anti-Ship Missile Opportunity To ensure DARPA maintains its ability... successful flight demonstra- tions that initially proved the technical approach. Concurrent with these technical accomplishments came two important

Staff Specialist Survival Course

DTIC Science & Technology

2016-03-01

acquisition acumen and critical thinking . These areas of expertise add to the staff specialist’s tool box. We enhance the experience with the case study...learner to the documents’ intent and provides an understanding of the formats used. Building Critical Thinking Skills The ability to think ...specifically de- veloped for staff specialists—ATL 900. This course provides not Defense AT&L: March-April 2016 52 only problem-solving solutions, critical

2005 8th Annual Systems Engineering Conference. Volume 2, Wednesday Presentations

DTIC Science & Technology

2005-10-27

Acquisition Programs: An OSD Perspective, Col Warren Anderson, OUSD (AT&L) Defense Systems Implementation of Policy Requiring Systems Engineering Plans...Technical Excellence, Col Warren Anderson, OUSD (AT&L) Defense Systems Applying CMMI to System Safety, Mr. Tom Pfitzer, APT Research, Inc. System...to following pages for Tutorials Schedule) Buffett Lunch Tutorial Tracks (Please refer to following pages for Tutorials Schedule) Reception in

Student Attitudes toward Learning, Level of Pre-Knowledge and Instruction Type in a Computer-Simulation: Effects on Flow Experiences and Perceived Learning Outcomes

ERIC Educational Resources Information Center

Winberg, T. Mikael; Hedman, Leif

2008-01-01

Attitudes toward learning (ATL) have been shown to influence students' learning outcomes. However, there is a lack of knowledge about the ways in which the interaction between ATL, the learning situation, and the level of students' prior knowledge influence affective reactions and conceptual change. In this study, a simulation of acid-base…

Comprehension of Concrete and Abstract Words in Patients with Selective Anterior Temporal Lobe Resection and in Patients with Selective Amygdalo-Hippocampectomy

ERIC Educational Resources Information Center

Loiselle, Magalie; Rouleau, Isabelle; Nguyen, Dang Khoa; Dubeau, Francois; Macoir, Joel; Whatmough, Christine; Lepore, Franco; Joubert, Sven

2012-01-01

The role of the anterior temporal lobe (ATL) in semantic memory is now firmly established. There is still controversy, however, regarding the specific role of this region in processing various types of concepts. There have been reports of patients suffering from semantic dementia (SD), a neurodegenerative condition in which the ATL is damaged…

Mammalian knock out cells reveal prominent roles for atlastin GTPases in ER network morphology

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

Zhao, Guohua; Zhu, Peng-Peng; Renvoisé, Benoît

Atlastins are large, membrane-bound GTPases that participate in the fusion of endoplasmic reticulum (ER) tubules to generate the polygonal ER network in eukaryotes. They also regulate lipid droplet size and inhibit bone morphogenetic protein (BMP) signaling, though mechanisms remain unclear. Humans have three atlastins (ATL1, ATL2, and ATL3), and ATL1 and ATL3 are mutated in autosomal dominant hereditary spastic paraplegia and hereditary sensory neuropathies. Cellular investigations of atlastin orthologs in most yeast, plants, flies and worms are facilitated by the presence of a single or predominant isoform, but loss-of-function studies in mammalian cells are complicated by multiple, broadly-expressed paralogs. Wemore » have generated mouse NIH-3T3 cells lacking all three mammalian atlastins (Atl1/2/3) using CRISPR/Cas9-mediated gene knockout (KO). ER morphology is markedly disrupted in these triple KO cells, with prominent impairment in formation of three-way ER tubule junctions. This phenotype can be rescued by expression of distant orthologs from Saccharomyces cerevisiae (Sey1p) and Arabidopsis (ROOT HAIR DEFECTIVE3) as well as any one of the three human atlastins. Minimal, if any, changes are observed in the morphology of mitochondria and the Golgi apparatus. Alterations in BMP signaling and increased sensitivity to ER stress are also noted, though effects appear more modest. Finally, atlastins appear required for the proper differentiation of NIH-3T3 cells into an adipocyte-like phenotype. These findings have important implications for the pathogenesis of hereditary spastic paraplegias and sensory neuropathies associated with atlastin mutations. - Highlights: • NIH-3T3 cells lacking all three atlastin paralogs were generated using CRISPR/Cas9. • Cells lacking all atlastin GTPases exhibit far fewer 3-way ER tubule junctions. • ER morphology defects in atlastin knockout cells are rescued by distant plant and yeast orthologs. • Atlastin knock out cells also exhibit differences in ER stress and BMP signaling. • Atlastins appear important for adipocyte-like differentiation of NIH-3T3 cells.« less

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.

Enhanced muscular oxygen extraction in athletes exaggerates hypoxemia during exercise in hypoxia.

PubMed

Van Thienen, Ruud; Hespel, Peter

2016-02-01

High rate of muscular oxygen utilization facilitates the development of hypoxemia during exercise at altitude. Because endurance training stimulates oxygen extraction capacity, we investigated whether endurance athletes are at higher risk to developing hypoxemia and thereby acute mountain sickness symptoms during exercise at simulated high altitude. Elite athletes (ATL; n = 8) and fit controls (CON; n = 7) cycled for 20 min at 100 W (EX100W), as well as performed an incremental maximal oxygen consumption test (EXMAX) in normobaric hypoxia (0.107 inspired O2 fraction) or normoxia (0.209 inspired O2 fraction). Cardiorespiratory responses, arterial Po2 (PaO2), and oxygenation status in m. vastus lateralis [tissue oxygenation index (TOIM)] and frontal cortex (TOIC) by near-infrared spectroscopy, were measured. Muscle O2 uptake rate was estimated from change in oxyhemoglobin concentration during a 10-min arterial occlusion in m. gastrocnemius. Maximal oxygen consumption in normoxia was 70 ± 2 ml·min(-1·)kg(-1) in ATL vs. 43 ± 2 ml·min(-1·)kg(-1) in CON, and in hypoxia decreased more in ATL (-41%) than in CON (-25%, P < 0.05). Both in normoxia at PaO2 of ∼95 Torr, and in hypoxia at PaO2 of ∼35 Torr, muscle O2 uptake was twofold higher in ATL than in CON (0.12 vs. 0.06 ml·min(-1)·100 g(-1); P < 0.05). During EX100W in hypoxia, PaO2 dropped to lower (P < 0.05) values in ATL (27.6 ± 0.7 Torr) than in CON (33.5 ± 1.0 Torr). During EXMAX, but not during EX100W, TOIM was ∼15% lower in ATL than in CON (P < 0.05). TOIC was similar between the groups at any time. This study shows that maintenance of high muscular oxygen extraction rate at very low circulating PaO2 stimulates the development of hypoxemia during submaximal exercise in hypoxia in endurance-trained individuals. This effect may predispose to premature development of acute mountain sickness symptoms during exercise at altitude. Copyright © 2016 the American Physiological Society.

Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

PubMed

Becic, Tina; Kero, Darko; Vukojevic, Katarina; Mardesic, Snjezana; Saraga-Babic, Mirna

2018-04-01

The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development. Copyright © 2018 Elsevier GmbH. All rights reserved.

STS-45 Earth observation of the Aurora Australis or Southern Lights

NASA Image and Video Library

1992-04-02

STS-45 Earth observation taken onboard Atlantis, Orbiter Vehicle (OV) 104, is of the Aurora Australis or Southern Lights. The green appearing auroral activity engulfs the thin blue line on the Earth's limb. Aurorae were observed and photographed throughout the STS-45 nine-day mission.

STS-45 Earth observation of the Aurora Australis or Southern Lights

NASA Technical Reports Server (NTRS)

1992-01-01

STS-45 Earth observation taken onboard Atlantis, Orbiter Vehicle (OV) 104, is of the Aurora Australis or Southern Lights. The green appearing auroral activity engulfs the thin blue line on the Earth's limb. Aurorae were observed and photographed throughout the STS-45 nine-day mission.

Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma.

PubMed

Ogura, Michinori; Ishida, Takashi; Tsukasaki, Kunihiro; Takahashi, Takeshi; Utsunomiya, Atae

2016-07-01

Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL). The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively. A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment. These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.

Multi-Virulence-Locus Sequence Typing of Staphylococcus lugdunensis Generates Results Consistent with a Clonal Population Structure and Is Reliable for Epidemiological Typing

PubMed Central

Didi, Jennifer; Lemée, Ludovic; Gibert, Laure; Pons, Jean-Louis

2014-01-01

Staphylococcus lugdunensis is an emergent virulent coagulase-negative staphylococcus responsible for severe infections similar to those caused by Staphylococcus aureus. To understand its potentially pathogenic capacity and have further detailed knowledge of the molecular traits of this organism, 93 isolates from various geographic origins were analyzed by multi-virulence-locus sequence typing (MVLST), targeting seven known or putative virulence-associated loci (atlLR2, atlLR3, hlb, isdJ, SLUG_09050, SLUG_16930, and vwbl). The polymorphisms of the putative virulence-associated loci were moderate and comparable to those of the housekeeping genes analyzed by multilocus sequence typing (MLST). However, the MVLST scheme generated 43 virulence types (VTs) compared to 20 sequence types (STs) based on MLST, indicating that MVLST was significantly more discriminating (Simpson's index [D], 0.943). No hypervirulent lineage or cluster specific to carriage strains was defined. The results of multilocus sequence analysis of known and putative virulence-associated loci are consistent with a clonal population structure for S. lugdunensis, suggesting a coevolution of these genes with housekeeping genes. Indeed, the nonsynonymous to synonymous evolutionary substitutions (dN/dS) ratio, the Tajima's D test, and Single-likelihood ancestor counting (SLAC) analysis suggest that all virulence-associated loci were under negative selection, even atlLR2 (AtlL protein) and SLUG_16930 (FbpA homologue), for which the dN/dS ratios were higher. In addition, this analysis of virulence-associated loci allowed us to propose a trilocus sequence typing scheme based on the intragenic regions of atlLR3, isdJ, and SLUG_16930, which is more discriminant than MLST for studying short-term epidemiology and further characterizing the lineages of the rare but highly pathogenic S. lugdunensis. PMID:25078912

Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation.

PubMed

Green, Sophie; Ralph, Matthew A Lambon; Moll, Jorge; Stamatakis, Emmanuel A; Grafman, Jordan; Zahn, Roland

2010-10-01

It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. "critical" and "faultfinding"). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals. Copyright 2010 Elsevier Inc. All rights reserved.

Detection of human T lymphotropic virus type-I bZIP factor and tax in the salivary glands of Sjögren's syndrome patients.

PubMed

Nakamura, Hideki; Hasegawa, Hiroo; Sasaki, Daisuke; Takatani, Ayuko; Shimizu, Toshimasa; Kurushima, Shota; Horai, Yoshiro; Nakashima, Yoshikazu; Nakamura, Tatsufumi; Fukuoka, Junya; Kawakami, Atsushi

2018-03-20

To detect HTLV-I bZIP factor (HBZ), tax and relevant molecules in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS). The expressions of HBZ and tax in T cell lines and LSGs were analysed by in situ hybridization (ISH) or real time PCR. The expressions of forkhead box P3 (Foxp3) and p65 in immunohistochemistry were quantified. After specificity of ISH probes was determined in 5 T cell lines, in LSGs from an adult T-cell leukemia (ATL) patient and 3 HTLV-I-associated myelopathy (HAM)-SS patients, both HBZ and tax signals were detected in infiltrating mononuclear cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of ATL and HAM-SS, respectively. HBZ was dominantly observed in LSGs from 8 HTLV-I asymptomatic carrier (AC)-SS patients; faint expression of HBZ was observed in LSGs from 5 HTLV-I-seronegative SS patients. No cell adhesion molecule 1(CADM1) expressed in LSGs from the ATL patient. Although Foxp3 expression was observed in LSG MNCs of all of the SS patients, the ATL patient's expression was significantly greater than that of the AC-SS (p<0.01) and HTLV-I-seronegative SS (p<0.01) patients. The Foxp3 expression was similar in ATL and HAMSS, but significantly higher in HAM-SS than AC-SS (p<0.05). p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3. The expressions of Foxp3 in ducts differed according to HTLV-I infection. These results suggest that HBZ-mediated Foxp3 expression is partly associated with the pathogenesis of HTLV-I-seropositive SS.

Evaluation of focus laterality in temporal lobe epilepsy: a quantitative study comparing double inversion-recovery MR imaging at 3T with FDG-PET.

PubMed

Morimoto, Emiko; Okada, Tomohisa; Kanagaki, Mitsunori; Yamamoto, Akira; Fushimi, Yasutaka; Matsumoto, Riki; Takaya, Shigetoshi; Ikeda, Akio; Kunieda, Takeharu; Kikuchi, Takayuki; Paul, Dominik; Miyamoto, Susumu; Takahashi, Ryosuke; Togashi, Kaori

2013-12-01

To quantitatively compare the diagnostic capability of double inversion-recovery (DIR) with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE). This study was approved by the institutional review board, and written informed consent was obtained. Fifteen patients with TLE and 38 healthy volunteers were enrolled. All magnetic resonance (MR) images were acquired using a 3T-MRI system. Voxel-based analysis (VBA) was conducted for FDG-PET images and white matter segments of DIR images (DIR-WM) focused on the whole temporal lobe (TL) and the anterior part of the temporal lobe (ATL). Distribution of hypometabolic areas on FDG-PET and increased signal intensity areas on DIR-WM were evaluated, and their laterality was compared with clinically determined seizure focus laterality. Correct diagnostic rates of laterality were evaluated, and agreement between DIR-WM and FDG-PET was assessed using κ statistics. Increased signal intensity areas on DIR-WM were located at the vicinity of the hypometabolic areas on FDG-PET, especially in the ATL. Correct diagnostic rates of seizure focus laterality for DIR-WM (0.80 and 0.67 for the TL and the ATL, respectively) were slightly higher than those for FDG-PET (0.67 and 0.60 for the TL and the ATL, respectively). Agreement of laterality between DIR-WM and FDG-PET was substantial for the TL and almost perfect for the ATL (κ = 0.67 and 0.86, respectively). High agreement in localization between DIR-WM and FDG-PET and nearly equivalent detectability of them show us an additional role of MRI in TLE. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species.

PubMed

Sato, Camila Massae; Sanchez, Maria Carmen Arroyo; Celeste, Beatriz Julieta; Duthie, Malcolm S; Guderian, Jeffrey; Reed, Steven G; de Brito, Maria Edileuza Felinto; Campos, Marliane Batista; de Souza Encarnação, Helia Valeria; Guerra, Jorge; de Mesquita, Tirza Gabrielle Ramos; Pinheiro, Suzana Kanawati; Ramasawmy, Rajendranath; Silveira, Fernando Tobias; de Assis Souza, Marina; Goto, Hiro

2017-02-01

American tegumentary leishmaniasis (ATL) (also known as cutaneous leishmaniasis [CL]) is caused by various species of protozoa of the genus Leishmania The diagnosis is achieved on a clinical, epidemiological, and pathological basis, supported by positive parasitological exams and demonstration of leishmanin delayed-type hypersensitivity. Serological assays are not routinely used in the diagnosis because many are considered to have low sensitivity and the particular Leishmania species causing the disease can lead to variable performance. In the present study, we generated recombinant versions of two highly conserved Leishmania proteins, Leishmania (Viannia) braziliensis-derived Lb8E and Lb6H, and evaluated both in enzyme-linked immunosorbent assays (ELISA). Recombinant Lb6H (rLb6H) had better performance and reacted with 100.0% of the ATL and 89.4% of the VL samples. These reactions with rLb6H were highly specific (98.5%) when compared against those for samples from healthy control individuals. We then assessed rLb6H against sera from ATL patients infected with different species of Leishmania prevalent in Brazil [Leishmania (Leishmania) amazonensis, L (Viannia) braziliensis, and L (V) guyanensis] and samples from patients with other infectious diseases. In analyses of 500 sera, ELISA using rLb6H detected all 219 ATL samples (sensitivity of 100.0%) with an overall specificity of 93.9% (considering healthy individuals and other infectious diseases patients). Only a minority of samples from Chagas disease patients possessed antibodies against rLb6H, and all of these responses were low (with a highest reactivity index of 2.2). Taken together, our data support further evaluation of rLb6H and the potential for its routine use in the serological diagnosis of ATL. Copyright © 2017 Sato et al.

A conceptual lemon: theta burst stimulation to the left anterior temporal lobe untangles object representation and its canonical color.

PubMed

Chiou, Rocco; Sowman, Paul F; Etchell, Andrew C; Rich, Anina N

2014-05-01

Object recognition benefits greatly from our knowledge of typical color (e.g., a lemon is usually yellow). Most research on object color knowledge focuses on whether both knowledge and perception of object color recruit the well-established neural substrates of color vision (the V4 complex). Compared with the intensive investigation of the V4 complex, we know little about where and how neural mechanisms beyond V4 contribute to color knowledge. The anterior temporal lobe (ATL) is thought to act as a "hub" that supports semantic memory by integrating different modality-specific contents into a meaningful entity at a supramodal conceptual level, making it a good candidate zone for mediating the mappings between object attributes. Here, we explore whether the ATL is critical for integrating typical color with other object attributes (object shape and name), akin to its role in combining nonperceptual semantic representations. In separate experimental sessions, we applied TMS to disrupt neural processing in the left ATL and a control site (the occipital pole). Participants performed an object naming task that probes color knowledge and elicits a reliable color congruency effect as well as a control quantity naming task that also elicits a cognitive congruency effect but involves no conceptual integration. Critically, ATL stimulation eliminated the otherwise robust color congruency effect but had no impact on the numerical congruency effect, indicating a selective disruption of object color knowledge. Neither color nor numerical congruency effects were affected by stimulation at the control occipital site, ruling out nonspecific effects of cortical stimulation. Our findings suggest that the ATL is involved in the representation of object concepts that include their canonical colors.

The processing of semantic relatedness in the brain: Evidence from associative and categorical false recognition effects following transcranial direct current stimulation of the left anterior temporal lobe.

PubMed

Díez, Emiliano; Gómez-Ariza, Carlos J; Díez-Álamo, Antonio M; Alonso, María A; Fernandez, Angel

2017-08-01

A dominant view of the role of the anterior temporal lobe (ATL) in semantic memory is that it serves as an integration hub, specialized in the processing of semantic relatedness by way of mechanisms that bind together information from different brain areas to form coherent amodal representations of concepts. Two recent experiments, using brain stimulation techniques along with the Deese-Roediger-McDermott (DRM) paradigm, have found a consistent false memory reduction effect following stimulation of the ATL, pointing to the importance of the ATL in semantic/conceptual processing. To more precisely identify the specific process being involved, we conducted a DRM experiment in which transcranial direct current stimulation (anode/cathode/sham) was applied over the participants' left ATL during the study of lists of words that were associatively related to their non-presented critical words (e.g., rotten, worm, red, tree, liqueur, unripe, cake, food, eden, peel, for the critical item apple) or categorically related (e.g., pear, banana, peach, orange, cantaloupe, watermelon, strawberry, cherry, kiwi, plum, for the same critical item apple). The results showed that correct recognition was not affected by stimulation. However, an interaction between stimulation condition and type of relation for false memories was found, explained by a significant false recognition reduction effect in the anodal condition for associative lists that was not observed for categorical lists. Results are congruent with previous findings and, more importantly, they help to clarify the nature and locus of false memory reduction effects, suggesting a differential role of the left ATL, and providing critical evidence for understanding the creation of semantic relatedness-based memory illusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus.

PubMed

Olsen, Ansgar S; Sarras, Michael P; Intine, Robert V

2010-01-01

The zebrafish (Danio rerio) is an established model organism for the study of developmental processes, human disease, and tissue regeneration. We report that limb regeneration is severely impaired in our newly developed adult zebrafish model of type I diabetes mellitus. Intraperitoneal streptozocin injection of adult, wild-type zebrafish results in a sustained hyperglycemic state as determined by elevated fasting blood glucose values and increased glycation of serum protein. Serum insulin levels are also decreased and pancreas immunohistochemisty revealed a decreased amount of insulin signal in hyperglycemic fish. Additionally, the diabetic complications of retinal thinning and glomerular basement membrane thickening (early signs of retinopathy and nephropathy) resulting from the hyperglycemic state were evident in streptozocin-injected fish at 3 weeks. Most significantly, limb regeneration, following caudal fin amputation, is severely impaired in diabetic zebrafish and nonspecific toxic effects outside the pancreas were not found to contribute to impaired limb regeneration. This experimental system using adult zebrafish facilitates a broad spectrum of genetic and molecular approaches to study regeneration in the diabetic background. © 2010 by the Wound Healing Society.

Exploration of a Novel Persistent Reversal of Pathological Pain: Mechanisms and Mediators

DTIC Science & Technology

2015-04-01

ability of a single IT ATL313 dose to reverse neuropathic pain from traumatic peripheral neuropathy . Milestone 2 is complete. We determined that 1 pmol...cord injury; to prevent and reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ...ATL313 can reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ) injections. We also

Feasibility of cord blood transplantation in chemosensitive adult T-cell leukemia/lymphoma: a retrospective analysis of the Nagasaki Transplantation Network.

PubMed

Fukushima, Takuya; Itonaga, Hidehiro; Moriuchi, Yukiyoshi; Yoshida, Shinichiro; Taguchi, Jun; Imaizumi, Yoshitaka; Imanishi, Daisuke; Tsushima, Hideki; Sawayama, Yasushi; Matsuo, Emi; Hata, Tomoko; Miyazaki, Yasushi

2013-04-01

It has been reported that cord blood transplantation (CBT) for patients with aggressive adult T-cell leukemia/lymphoma (ATL) results in poorer outcomes than transplantation using other stem cell sources. To identify a subset of ATL in which CBT is feasible, we retrospectively analyzed 27 patients treated with CBT at three institutions in Nagasaki Prefecture, Japan. The estimated overall survival (OS) rate at 3 years was 27.4 %. Of 16 patients who received CBT during remission (complete, CR, or partial, PR), the OS rate at 3 years was 50 %, while during refractory periods (non-CR or non-PR), the OS rate was 9.1 %. Reduced intensity conditioning (RIC) was given to 18 patients, and myeloablative conditioning (MAC) was used in nine, with 3-year OS of 50.0 and 0 %, respectively. Of the 19 deaths, nine were due to progressive disease, eight (five MAC and three RIC) to infection, and two to multiple organ failure. These results suggest that CBT provides similar results with those in other transplantation procedures for selected ATL patients, such as those in CR or PR. Further studies are needed to evaluate the use of CBT in aggressive ATL.

The role of the left anterior temporal lobe in exception word reading: reconciling patient and neuroimaging findings.

PubMed

Wilson, Maximiliano A; Joubert, Sven; Ferré, Perrine; Belleville, Sylvie; Ansaldo, Ana Inés; Joanette, Yves; Rouleau, Isabelle; Brambati, Simona Maria

2012-05-01

Semantic dementia (SD) is a neurodegenerative disease that occurs following the atrophy of the anterior temporal lobes (ATLs). It is characterised by the degradation of semantic knowledge and difficulties in reading exception words (surface dyslexia). This disease has highlighted the role of the ATLs in the process of exception word reading. However, imaging studies in healthy subjects have failed to detect activation of the ATLs during exception word reading. The aim of the present study was to test whether the functional brain regions that mediate exception word reading in normal readers overlap those brain regions atrophied in SD. In Study One, we map the brain regions of grey matter atrophy in AF, a patient with mild SD and surface dyslexia profile. In Study Two, we map the activation pattern associated with exception word compared to pseudoword reading in young, healthy participants using fMRI. The results revealed areas of significant activation in healthy subjects engaged in the exception word reading task in the left anterior middle temporal gyrus, in a region observed to be atrophic in the patient AF. These results reconcile neuropsychological and functional imaging data, revealing the critical role of the left ATL in exception word reading. Copyright © 2012 Elsevier Inc. All rights reserved.

Airport Surface Movement Technologies: Atlanta Demonstrations Overview

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Young, Steven D.

1997-01-01

A flight demonstration was conducted in August 1997 at the Hartsfield Atlanta (ATL) International Airport as part of low visibility landing and surface operations (LVLASO) research activities. This research was aimed at investigating technology to improve the safety and efficiency of aircraft movements on the surface during the operational phases of roll-out, turnoff, and taxi in any weather condition down to a runway visual range of 300 feet. The system tested at ATL was composed of airborne and ground-based components that were integrated to provide both the flight crew and controllers with supplemental information to enable safe, expedient surface operations. Experimental displays were installed on a Boeing 757-200 research aircraft in both headup and head-down formats. On the ground, an integrated system maintained surveillance of the airport surface and a controller interface provided routing and control instructions. While at ATL, the research aircraft performed a series of flight and taxi operations to show the validity of the operational concept at a major airport facility, to validate simulation findings, and to assess each of the individual technologies performance in an airport environment. The concept was demonstrated to over 100 visitors from the Federal Aviation Administration (FAA) and the aviation community. This paper gives an overview of the LVLASO system and ATL test activities.

A Comparison of Two FMRI Methods for Predicting Verbal Memory Decline After Left Temporal Lobectomy: Language Lateralization vs. Hippocampal Activation Asymmetry

PubMed Central

Binder, Jeffrey R.; Swanson, Sara J.; Sabsevitz, David S.; Hammeke, Thomas A.; Raghavan, Manoj; Mueller, Wade M.

2010-01-01

Purpose Language lateralization measured by preoperative fMRI was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L-ATL) resection. The aim of this study was to determine whether language lateralization or hippocampal activation asymmetry is a better predictor of memory outcome in this setting. Methods Thirty L-ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre- and postoperative neuropsychological testing. A group of 37 right ATL surgery patients who underwent the same testing procedures was included for comparison. Results Verbal memory decline occurred in roughly half of the L-ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome. Discussion Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material-specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes. PMID:19817807

Secreted Immunomodulatory Proteins of Staphylococcus aureus Activate Platelets and Induce Platelet Aggregation.

PubMed

Binsker, Ulrike; Palankar, Raghavendra; Wesche, Jan; Kohler, Thomas P; Prucha, Josephine; Burchhardt, Gerhard; Rohde, Manfred; Schmidt, Frank; Bröker, Barbara M; Mamat, Uwe; Pané-Farré, Jan; Graf, Anica; Ebner, Patrick; Greinacher, Andreas; Hammerschmidt, Sven

2018-04-01

Staphylococcus aureus can cause bloodstream infections associated with infective endocarditis (IE) and disseminated intravascular coagulopathy (DIC). Both complications involve platelets. In view of an increasing number of antibiotic-resistant strains, new approaches to control systemic S. aureus infection are gaining importance. Using a repertoire of 52 recombinant S. aureus proteins in flow cytometry-based platelet activation and aggregation assays, we identified, in addition to the extracellular adherence protein Eap, three secreted staphylococcal proteins as novel platelet activating proteins. Eap and the chemotaxis inhibitory protein of S. aureus (CHIPS), the formyl peptide receptor-like 1 inhibitory protein (FLIPr) and the major autolysin Atl induced P-selectin expression in washed platelets and platelet-rich plasma. Similarly, AtlA, CHIPS and Eap induced platelet aggregation in whole blood. Fluorescence microscopy illustrated that P-selectin expression is associated with calcium mobilization and re-organization of the platelet actin cytoskeleton. Characterization of the functionally active domains of the major autolysin AtlA and Eap indicates that the amidase domain of Atl and the tandem repeats 3 and 4 of Eap are crucial for platelet activation. These results provide new insights in S. aureus protein interactions with platelets and identify secreted proteins as potential treatment targets in case of antibiotic-resistant S. aureus infection. Schattauer GmbH Stuttgart.

Defense AT&L (Volume 36, Number 5, September-October 2007)

DTIC Science & Technology

2007-10-01

requirements, providing security solutions, and manag- ing the security of information systems. 14 CAD/ PAD Require- ments Determination in the Air Force...be contacted at williams_peter@bah.com and steward_tiffani@bah.com. Defense AT&L: September-October 2007 14 Williams is director of the CAD/ PAD Joint...the U.S. House Science and Technology Subcommittee on Transportation, Aviation and Materials. Blair is the former head of the Air Force CAD/ PAD

Langley applications experiments data management system study. [for space shuttles

NASA Technical Reports Server (NTRS)

Lanham, C. C., Jr.

1975-01-01

A data management system study is presented that defines, in functional terms, the most cost effective ground data management system to support Advanced Technology Laboratory (ATL) flights of the space shuttle. Results from each subtask performed and the recommended system configuration for reformatting the experiment instrumentation tapes to computer compatible tape are examined. Included are cost factors for development of a mini control center for real-time support of the ATL flights.

AT&L Human Capital Strategic Plan v 3.0

DTIC Science & Technology

2007-07-01

as direct-hire and intern/mid- level lateral hiring programs. Recruiting strategies should focus on the unique advantages of employment that DoD AT&L...tailor our DoD AT&L strategies to ensure that we can sustain the level of personnel needed to accomplish our mission. 3 Accomplishments and Way Ahead... level of human capital strategies based on new knowledge and understanding. The USD(AT&L) encour- ages Components to work collaboratively to

Defense AT&L (Volume 36, Number 3, May-June 2007)

DTIC Science & Technology

2007-06-01

following five years. What are some of the biggest challenges you’ve dealt with? Photographs by SGT André Reynolds, USA A The biggest challenge is how...director of logistics operations (right); and Lt. Col. Robert Harney, DDAA commander (left). Photograph courtesy Anniston Army Depot Public Affairs Office...better A member of the DLA Contingency Support Team in Afghanistan checks an incoming subsistence shipment.DLA photograph Defense AT&L: May-June 2007 20

Defense AT&L (Volume 35, Number 4, July-August 2006)

DTIC Science & Technology

2006-08-01

solutions. Defense AT&L: July-August 2006 60 This is the first year of the JCTD business model , which will eventually replace the ACTD model . Building...foreign cultural skills in airmen. ARMY NEWS SERVICE (MARCH 7, 2006) SECARMY ORDERS ARMY-WIDE BUSINESS TRANSFORMATION Staff Sgt. Carmen L. Burgess, USA... business culture that is dedicated to con- tinuous improvement, focused on performance, and based on the enduring Army values. NAVY NEWSSTAND (MARCH 10

Evaluation of leadership skills during the simulation education course for the initial management of blunt trauma.

PubMed

Schott, Eric; Brautigam, Robert T; Smola, Jacqueline; Burns, Karyl J

2012-04-01

Leadership skills of senior residents, trauma fellows, and a nurse practitioner were assessed during simulation training for the initial management of blunt trauma. This was a pilot, observational study, that in addition to skill development and assessment also sought to determine the need for a dedicated leadership training course for surgical residents. The study evaluated the leadership skills and adherence to Advance Trauma Life Support (ATLS) guidelines of the team leaders during simulation training. The team leaders' performances on criteria regarding prearrival planning, critical actions based on ATLS, injury identification, patient management, and communication were evaluated for each of five blunt-trauma scenarios. Although there was a statistically significant increase in leadership skills for performing ATLS critical actions, P < 0.05, there were 10 adverse events. A structured simulation program dedicated to developing skills for team leadership willbe a worthwhile endeavor at our institution.

Activity of trypsin-like enzymes and gelatinases in rats with doxorubicin cardiomyopathy.

PubMed

Gordiienko, Iu A; Babets, Ya V; Kulinich, A O; Shevtsova, A I; Ushakova, G O

2014-01-01

Activity of trypsin-like enzymes (ATLE) and gelatinases A and B were studied in the blood plasma and extracts from cardiac muscle, cerebral cortex and cerebellum of rats with cardiomyopathy caused by anthracycline antibiotic doxorubicin against the background of preventive application of corvitin and α-ketoglutarate. ATLE significantly increased in blood plasma and extracts from cerebral cortex but decreased in extracts from cardiac muscle and cerebellum in doxorubicin cardiomyopathy (DCMP). In addition, a significant increase of activity of both gelatinases in plasma and tissue extracts was observed. Preventive administration of corvitin and α-ketoglutarate resulted in differently directed changes of activity of the above mentioned enzymes in heart and brain tissues. Obtained data confirm the hypothesis about activation of proteolysis under the influence of anthracycline antibiotics and testify to selective effect of corvitin and α-ketoglutarate on ATLE and gelatinases.

Functional impairment of Tax-specific but not cytomegalovirus-specific CD8+ T lymphocytes in a minor population of asymptomatic human T-cell leukemia virus type 1-carriers

PubMed Central

2011-01-01

Background Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+ T-cells in various clinical status of HTLV-1 infection. Results By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+ T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8+ T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+ T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+ T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8+ T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8+ T-cells. Conclusions These findings indicated that Tax-specific CD8+ T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8+ T-cells in early stages. PMID:22151736

Defense AT&L (Volume 35, Number 5, September-October 2006)

DTIC Science & Technology

2006-10-01

percent of production. The criti- Defense AT&L: September-October 2006 8 cal path elements driving the IOT &E schedule are not pro- duction hardware...reduced costs, and successful completion of work in the scheduled time. 30 The Commodity Approach to Aircraft Protection Systems Capt. Bill Chubb, USN The...piece of Littoral Combat Ship Two during the ship’s keel laying ceremony. The Navy’s second Littoral Combat Ship is scheduled for commissioning in

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

PubMed

Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-08-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.

PubMed

Suehiro, Youko; Hasegawa, Atsuhiko; Iino, Tadafumi; Sasada, Amane; Watanabe, Nobukazu; Matsuoka, Masao; Takamori, Ayako; Tanosaki, Ryuji; Utsunomiya, Atae; Choi, Ilseung; Fukuda, Tetsuya; Miura, Osamu; Takaishi, Shigeo; Teshima, Takanori; Akashi, Koichi; Kannagi, Mari; Uike, Naokuni; Okamura, Jun

2015-05-01

Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL. © 2015 John Wiley & Sons Ltd.

Use of Preoperative Functional MRI to Predict Verbal Memory Decline After Temporal Lobe Epilepsy Surgery

PubMed Central

Binder, Jeffrey R.; Sabsevitz, David S.; Swanson, Sara J.; Hammeke, Thomas A.; Raghavan, Manoj; Mueller, Wade M.

2010-01-01

Purpose Verbal memory decline is a frequent complication of left anterior temporal lobectomy (L-ATL). The goal of this study was to determine whether preoperative language mapping using functional magnetic resonance imaging (fMRI) is useful for predicting which patients are likely to experience verbal memory decline after L-ATL. Methods Sixty L-ATL patients underwent preoperative language mapping with fMRI, preoperative intracarotid amobarbital (Wada) testing for language and memory lateralization, and pre- and postoperative neuropsychological testing. Demographic, historical, neuropsychological, and imaging variables were examined for their ability to predict pre- to postoperative memory change. Results Verbal memory decline occurred in over 30% of patients. Good preoperative performance, late age at onset of epilepsy, left dominance on fMRI, and left dominance on the Wada test were each predictive of memory decline. Preoperative performance and age at onset together accounted for roughly 50% of the variance in memory outcome (p < .001), and fMRI explained an additional 10% of this variance (p ≤ .003). Neither Wada memory asymmetry nor Wada language asymmetry added additional predictive power beyond these noninvasive measures. Discussion Preoperative fMRI is useful for identifying patients at high risk for verbal memory decline prior to L-ATL surgery. Lateralization of language is correlated with lateralization of verbal memory, whereas Wada memory testing is either insufficiently reliable or insufficiently material-specific to accurately localize verbal memory processes. PMID:18435753

Description of a new species of the costata-group (Cladocera, Chydoridae, Aloninae) from Brazil.

PubMed

Sousa, Francisco Diogo R; Santos, Sandro; Güntzel, Adriana Maria; Diniz, Leidiane Pereira; De Melo Júnior, Mauro; Elmoor-Loureiro, Lourdes M A

2015-11-12

The aim of this study is to describe a new species of the costata-group from Brazil. Alona margipluma sp. nov. shares morphological traits with A. costata Sars, 1862, A. natalensis Sinev, 2008, and A. cheni Sinev, 1999, but differs from them in: (i) thin setulae between the marginal setae on the valves, (ii) setae 4-5 on the exopodite of limb III long and different in length, (iii) bottle-shaped sensillum on the basal endite of limb IV. For identification of Alona margipluma sp. nov. it is necessary to check carefully the main head pores and postabdomen characters since the former superficially resemble A. iheringula, A. setigera and Alona guttata.

Biomass estimators for thinned second-growth ponderosa pine trees.

Treesearch

P.H. Cochran; J.W. Jennings; C.T. Youngberg

1984-01-01

Usable estimates of the mass of live foliage and limbs of sapling and pole-sized ponderosa pine in managed stands in central Oregon can be obtained with equations using the logarithm of diameter as the only independent variable. These equations produce only slightly higher root mean square deviations than equations that include additional independent variables. A...

Influence of the nutritional status in the clinical and therapeutical evolution in adults and elderly with American Tegumentary Leishmaniasis.

PubMed

Oliveira, A G L; Brito, P D; Schubach, A O; Oliveira, R V C; Saheki, M N; Lyra, M R; Salgueiro, M M; Terceiro, B F; Pimentel, M I F; Vasconcellos, E C; Valete-Rosalino, C M

2013-10-01

The objective of this study is to describe the nutritional status of adult and elderly patients with American Tegumentary Leishmaniasis (ATL). It was conducted a longitudinal study in 68 adult and elderly patients with ATL treating at the Surveillance Leishmaniasis Laboratory at the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (Fiocruz), from 2009 to 2012. The nutritional assessment included the body mass index (BMI) and serum albumin levels. The clinical evolution (epithelialization and wound healing) was measured up to two years after ATL treatment. Most of the sample was composed of men (71%), adults (73%), with household income of 1-5 minimum wages (79%), and incomplete elementary school (48.5%). The predominant ATL form was cutaneous (72%), and 39% presented comorbidities, the most frequent was hypertension (30.8%). The most prevalent clinical and nutritional events were: recent decrease in food intake (23.9%); nasal obstruction (22.1%); oral ulcer (14.7%), anorexia and dysphagia (13.2% each) and odynophagia (10.3%). The total healing time was 115.00 (IR=80-230) days for skin lesions, and 120.00 (IR=104.50-223.50) days for mucous membrane lesions. Low body weight in 10%, and hypoalbuminemia in 12% of the patients have been observed. Low body weight was associated with age, mucosal leishmaniasis (ML), nasal obstruction, recent decrease in food intake and hypoalbuminemia. As for serum albumin depletion, association with the ML, dyspnea, dysphagia, odynophagia, recent decrease in food intake, absence of complete healing of the skin lesions, and increased healing time for mucous membrane lesions, was observed. The ML and their events that affect the alimentary intake have been related to the impairment of the nutritional status. Additionally, serum albumin depletion negatively affected the healing of the lesions, suggesting that a nutritional intervention can increase the effectiveness of the ATL treatment. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation.

PubMed

Tamai, Yotaro; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki-Ryang; Nakamae, Hirohisa; Suehiro, Youko; Kato, Koji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari

2013-04-15

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We previously reported that Tax-specific CD8(+) cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4(+) T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4(+) as well as CD8(+) T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4(+) T cell responses, we identified a novel HLA-DRB1*0101-restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4(+) Th1-like cells, a major population of HTLV-1-specific CD4(+) T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8(+) T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101(+) patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4(+) T cells were present in all HTLV-1-infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4(+) T cells in HLA-DRB1*0101(+)-infected individuals and that Tax-specific CD4(+) T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8(+) T cell responses.

Multi-virulence-locus sequence typing of Staphylococcus lugdunensis generates results consistent with a clonal population structure and is reliable for epidemiological typing.

PubMed

Didi, Jennifer; Lemée, Ludovic; Gibert, Laure; Pons, Jean-Louis; Pestel-Caron, Martine

2014-10-01

Staphylococcus lugdunensis is an emergent virulent coagulase-negative staphylococcus responsible for severe infections similar to those caused by Staphylococcus aureus. To understand its potentially pathogenic capacity and have further detailed knowledge of the molecular traits of this organism, 93 isolates from various geographic origins were analyzed by multi-virulence-locus sequence typing (MVLST), targeting seven known or putative virulence-associated loci (atlLR2, atlLR3, hlb, isdJ, SLUG_09050, SLUG_16930, and vwbl). The polymorphisms of the putative virulence-associated loci were moderate and comparable to those of the housekeeping genes analyzed by multilocus sequence typing (MLST). However, the MVLST scheme generated 43 virulence types (VTs) compared to 20 sequence types (STs) based on MLST, indicating that MVLST was significantly more discriminating (Simpson's index [D], 0.943). No hypervirulent lineage or cluster specific to carriage strains was defined. The results of multilocus sequence analysis of known and putative virulence-associated loci are consistent with a clonal population structure for S. lugdunensis, suggesting a coevolution of these genes with housekeeping genes. Indeed, the nonsynonymous to synonymous evolutionary substitutions (dN/dS) ratio, the Tajima's D test, and Single-likelihood ancestor counting (SLAC) analysis suggest that all virulence-associated loci were under negative selection, even atlLR2 (AtlL protein) and SLUG_16930 (FbpA homologue), for which the dN/dS ratios were higher. In addition, this analysis of virulence-associated loci allowed us to propose a trilocus sequence typing scheme based on the intragenic regions of atlLR3, isdJ, and SLUG_16930, which is more discriminant than MLST for studying short-term epidemiology and further characterizing the lineages of the rare but highly pathogenic S. lugdunensis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

ATLes: the strategic application of Web-based technology to address learning objectives and enhance classroom discussion in a veterinary pathology course.

PubMed

Hines, Stephen A; Collins, Peggy L; Quitadamo, Ian J; Brahler, C Jayne; Knudson, Cameron D; Crouch, Gregory J

2005-01-01

A case-based program called ATLes (Adaptive Teaching and Learning Environments) was designed for use in a systemic pathology course and implemented over a four-year period. Second-year veterinary students working in small collaborative learning groups used the program prior to their weekly pathology laboratory. The goals of ATLes were to better address specific learning objectives in the course (notably the appreciation of pathophysiology), to solve previously identified problems associated with information overload and information sorting that commonly occur as part of discovery-based processes, and to enhance classroom discussion. The program was also designed to model and allow students to practice the problem-oriented approach to clinical cases, thereby enabling them to study pathology in a relevant clinical context. Features included opportunities for students to obtain additional information on the case by requesting specific laboratory tests and/or diagnostic procedures. However, students were also required to justify their diagnostic plans and to provide mechanistic analyses. The use of ATLes met most of these objectives. Student acceptance was high, and students favorably reviewed the online ''Content Links'' that made useful information more readily accessible and level appropriate. Students came to the lab better prepared to engage in an in-depth and high-quality discussion and were better able to connect clinical problems to underlying changes in tissue (lesions). However, many students indicated that the required time on task prior to lab might have been excessive relative to what they thought they learned. The classroom discussion, although improved, was not elevated to the expected level-most likely reflecting other missing elements of the learning environment, including the existing student culture and the students' current discussion skills. This article briefly discusses the lessons learned from ATLes and how similar case-based exercises might be combined with other approaches to enhance and enliven classroom discussions in the veterinary curriculum.

Multidisciplinary insight into clonal expansion of HTLV-1-infected cells in adult T-cell leukemia via modeling by deterministic finite automata coupled with high-throughput sequencing.

PubMed

Farmanbar, Amir; Firouzi, Sanaz; Park, Sung-Joon; Nakai, Kenta; Uchimaru, Kaoru; Watanabe, Toshiki

2017-01-31

Clonal expansion of leukemic cells leads to onset of adult T-cell leukemia (ATL), an aggressive lymphoid malignancy with a very poor prognosis. Infection with human T-cell leukemia virus type-1 (HTLV-1) is the direct cause of ATL onset, and integration of HTLV-1 into the human genome is essential for clonal expansion of leukemic cells. Therefore, monitoring clonal expansion of HTLV-1-infected cells via isolation of integration sites assists in analyzing infected individuals from early infection to the final stage of ATL development. However, because of the complex nature of clonal expansion, the underlying mechanisms have yet to be clarified. Combining computational/mathematical modeling with experimental and clinical data of integration site-based clonality analysis derived from next generation sequencing technologies provides an appropriate strategy to achieve a better understanding of ATL development. As a comprehensively interdisciplinary project, this study combined three main aspects: wet laboratory experiments, in silico analysis and empirical modeling. We analyzed clinical samples from HTLV-1-infected individuals with a broad range of proviral loads using a high-throughput methodology that enables isolation of HTLV-1 integration sites and accurate measurement of the size of infected clones. We categorized clones into four size groups, "very small", "small", "big", and "very big", based on the patterns of clonal growth and observed clone sizes. We propose an empirical formal model based on deterministic finite state automata (DFA) analysis of real clinical samples to illustrate patterns of clonal expansion. Through the developed model, we have translated biological data of clonal expansion into the formal language of mathematics and represented the observed clonality data with DFA. Our data suggest that combining experimental data (absolute size of clones) with DFA can describe the clonality status of patients. This kind of modeling provides a basic understanding as well as a unique perspective for clarifying the mechanisms of clonal expansion in ATL.

Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

PubMed

Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

1999-12-01

Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

Effects of HD-tDCS on memory and metamemory for general knowledge questions that vary by difficulty

PubMed Central

Chua, Elizabeth F.; Ahmed, Rifat; Garcia, Sandry

2016-01-01

Background The ability to monitor one’s own memory is an important feature of normal memory and is an aspect of ‘metamemory’. Lesion studies have shown dissociations between memory and metamemory, but only single dissociations have been shown using transcranial direct current stimulation (tDCS). One potential reason that only single dissociations have been shown is that tDCS effects may be moderated by task difficulty. Objective/Hypothesis We used high definition (HD) tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC) and anterior temporal lobe (ATL) in semantic long-term memory and metamemory tasks. We also tested whether general knowledge question difficulty moderated the effects of HD-tDCS. Methods Across 3 sessions, participants received active HD-tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge recall and recognition tests, and a ‘feeling-of-knowing’ metamemory task. General knowledge questions were blocked by difficulty. Repeated measures ANOVAs were used to examine the effects of HD-tDCS on memory and metamemory tasks by memory question difficulty. Results HD-tDCS over the ATL led to improved recall compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to improved recognition accuracy and improved feeling-of-knowing accuracy compared to ATL and sham HD-tDCS, and this was not moderated by memory question difficulty. Conclusion(s) HD-tDCS can be used to dissociate the roles of the ATL and DLPFC in different memory and ‘metamemory’ tasks. The effects of HD-tDCS on task may be moderated by task difficulty, depending on the nature of the task and site of stimulation. PMID:27876306

Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder.

PubMed

Green, Sophie; Lambon Ralph, Matthew A; Moll, Jorge; Deakin, John F W; Zahn, Roland

2012-10-01

Proneness to overgeneralization of self-blame is a core part of cognitive vulnerability to major depressive disorder (MDD) and remains dormant after remission of symptoms. Current neuroanatomical models of MDD, however, assume general increases of negative emotions and are unable to explain biases toward emotions entailing self-blame (eg, guilt) relative to those associated with blaming others (eg, indignation). Recent functional magnetic resonance imaging (fMRI) studies in healthy participants have shown that moral feelings such as guilt activate representations of social meaning within the right superior anterior temporal lobe (ATL). Furthermore, this area was selectively coupled with the subgenual cingulate cortex and adjacent septal region (SCSR) during the experience of guilt compared with indignation. Despite its psychopathological importance, the functional neuroanatomy of guilt in MDD is unknown. To use fMRI to test the hypothesis that, in comparison with control individuals, participants with remitted MDD exhibit guilt-selective SCSR-ATL decoupling as a marker of deficient functional integration. Case-control study from May 1, 2008, to June 1, 2010. Clinical research facility. Twenty-five patients with remitted MDD (no medication in 16 patients) with no current comorbid Axis I disorders and 22 controls with no personal or family history of MDD. Between-group difference of ATL coupling with a priori SCSR region of interest for guilt vs indignation. We corroborated the prediction of a guilt-selective reduction in ATL-SCSR coupling in MDD vs controls (familywise error-corrected P=.001 over the region of interest) and revealed additional medial frontopolar, right hippocampal, and lateral hypothalamic areas of decoupling while controlling for medication status and intensity of negative emotions. Lower levels of ATL-SCSR coupling were associated with higher scores on a validated measure of overgeneralized self-blame (67-item Interpersonal Guilt Questionnaire). Vulnerability to MDD is associated with temporofrontolimbic decoupling that is selective for self-blaming feelings. This provides the first neural mechanism ofMDD vulnerability that accounts for self-blaming biases.

Effects of HD-tDCS on memory and metamemory for general knowledge questions that vary by difficulty.

PubMed

Chua, Elizabeth F; Ahmed, Rifat; Garcia, Sandry M

The ability to monitor one's own memory is an important feature of normal memory and is an aspect of 'metamemory'. Lesion studies have shown dissociations between memory and metamemory, but only single dissociations have been shown using transcranial direct current stimulation (tDCS). One potential reason that only single dissociations have been shown is that tDCS effects may be moderated by task difficulty. We used high definition (HD) tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC) and anterior temporal lobe (ATL) in semantic long-term memory and metamemory tasks. We also tested whether general knowledge question difficulty moderated the effects of HD-tDCS. Across 3 sessions, participants received active HD-tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge recall and recognition tests, and a 'feeling-of-knowing' metamemory task. General knowledge questions were blocked by difficulty. Repeated measures ANOVAs were used to examine the effects of HD-tDCS on memory and metamemory tasks by memory question difficulty. HD-tDCS over the ATL led to improved recall compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to improved recognition accuracy and improved feeling-of-knowing accuracy compared to ATL and sham HD-tDCS, and this was not moderated by memory question difficulty. HD-tDCS can be used to dissociate the roles of the ATL and DLPFC in different memory and 'metamemory' tasks. The effects of HD-tDCS on task may be moderated by task difficulty, depending on the nature of the task and site of stimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Ultrasonographic assessment of the proximal digital annular ligament in the equine forelimb.

PubMed

Dik, K J; Boroffka, S; Stolk, P

1994-01-01

Ultrasonography was used with 6 normal cadaver forelimbs of Dutch Warmblood horses to delineate the ultrasonographic anatomy of the palmar pastern region, with emphasis on the proximal digital annular ligament. Using a 5.5 MHz sector scanner, the thin proximal digital annular ligament was not visible on offset sonograms. Only if the digital sheath in the normal limb was distended was the distal border of this ligament outlined. In all normal limbs the palmarodistal thickness of the combined skin-proximal digital annular ligament layer in the mid-pastern region was 2 mm. The flexor tendons and distal sesamoidean ligaments were easily identified as hyperechoic structures. Distension of the digital sheath in the normal limbs clearly outlined the anechoic digital sheath pouches. In 4 lame horses ultrasonography aided the diagnosis of functional proximal digital annular ligament constriction. In all 4 diseased forelimbs ultrasonography demonstrated thickening of the skin-proximal digital annular ligament layer and distension of the digital sheath. In one of these limbs the distended digital sheath was also thickened. The flexor tendons and distal sesamoidean ligaments were normal. There was no radiographic evidence of additional bone or joint lesions.

Precision laser range finder system design for Advanced Technology Laboratory applications

NASA Technical Reports Server (NTRS)

Golden, K. E.; Kohn, R. L.; Seib, D. H.

1974-01-01

Preliminary system design of a pulsed precision ruby laser rangefinder system is presented which has a potential range resolution of 0.4 cm when atmospheric effects are negligible. The system being proposed for flight testing on the advanced technology laboratory (ATL) consists of a modelocked ruby laser transmitter, course and vernier rangefinder receivers, optical beacon retroreflector tracking system, and a network of ATL tracking retroreflectors. Performance calculations indicate that spacecraft to ground ranging accuracies of 1 to 2 cm are possible.

Defense AT&L Magazine A Publication of the Defense Acquisition University. Volume 33, Number 5, DAU 181

DTIC Science & Technology

2004-10-01

4 5 Defense AT&L: September-October 2004 tails with DAU offerings. We pride ourselves on keeping the CL program current with the ...indestructible.” Despite the weight of IBA, Moran said he has no doubt that the new body armor has saved lives . In the past 18 months, the Army has purchased...activities may deviate from the requirements in Federal Acquisition Regulation (FAR) 12.301(b)( 4 ), the clause at FAR 52.212- 5 , Defense FAR

CMOS array design automation techniques

NASA Technical Reports Server (NTRS)

Lombardi, T.; Feller, A.

1976-01-01

The design considerations and the circuit development for a 4096-bit CMOS SOS ROM chip, the ATL078 are described. Organization of the ATL078 is 512 words by 8 bits. The ROM was designed to be programmable either at the metal mask level or by a directed laser beam after processing. The development of a 4K CMOS SOS ROM fills a void left by available ROM chip types, and makes the design of a totally major high speed system more realizable.

Characterization of Used MIL-L-7808 Lubricants.

DTIC Science & Technology

1985-05-01

Gravimetric Finish 20 2.3.3 Separation of Mineral Oil by means of Sulphuric Acid 21 2.3.4 Rolls-Royce Method 1032 26 2.3.5 Conclusion 26 3 Minimum...and STM No. 1 i Application of Sulphuric Acid Method for MOC to:- IV Standards based upon ATL.9100 23 V Standards based upon ATL.9101 24 VI Standards...total acid numbers of the standards before, and after application of each technique. Considering firstly the volatile contaminant contents obtained by STM

Defense AT&L Magazine: A Publication of the Defense Acquisition University. Volume 33, Number 4, DAU 180

DTIC Science & Technology

2004-08-01

aircraft in flight and so saving money and time. Defense AT&L: July-August 2004 46 Haraburda is the deputy site project manager for operations at the...Certification for Government Oversight of Manufacturing Scott S. Haraburda and Jim Gary The Chemical Stockpile Disposal Program (CSDP)is a U.S. Army...The authors welcome comments and questions. Haraburda can be reached at scott.haraburda @us.army.mil and Gary at james.gary@necdf.necd. army.mil. final

Exercise CAPITAL SHIELD Towards Medical Response Integration in the National Capital Region

DTIC Science & Technology

2011-01-24

provided JTF the authority to develop Interagency partnerships  CY09/10: JTF CapMed executed (12) DSCA missions with Fed/State/Local partners...incident site at Lorton Youth Detention Center, VA – admin medical support 4-5 days  FY10, JTF CapMed inserted two-day MASCAL training (onsite only...Use exercise as test-bed for structure/tools: – Joint Critical Care ATLS Team: Modification of ATLS Team w/ attached triage and evac sections

Autolytic activity and molecular characteristics of Staphylococcus haemolyticus strains with induced vancomycin resistance.

PubMed

Kim, Jung Wook; Chung, Gyung Tae; Yoo, Jung Sik; Lee, Yeong Seon; Yoo, Jae Il

2012-10-01

The aim of this study was to investigate the molecular characteristics of induced vancomycin resistance in Staphylococcus haemolyticus. Autolytic properties and phenotypic characteristics of passage-selected vancomycin-resistant S. haemolyticus strains were examined. In addition, expression of autolysis-related genes (atl, lrgAB, sarA and lytS) was investigated using the RNase protection assay (RPA). The RPA results indicated that only the expression of the atl gene was significantly upregulated (2.5- to 6-fold increase) in vancomycin-intermediate and vancomycin-resistant strains. The vancomycin-resistant strains exhibited lower expression of murein hydrolase proteins and reduced autolytic activity compared with the parent strain. In addition, a reduced growth rate, cell wall thickening and higher survival rate in the presence of lysostaphin were observed in vancomycin-intermediate and vancomycin-resistant induced strains compared with the parent strain. In conclusion, altered autolytic properties, in particular upregulation of the atl gene, may contribute to vancomycin resistance in S. haemolyticus.

Dynamic neural architecture for social knowledge retrieval

PubMed Central

Wang, Yin; Collins, Jessica A.; Koski, Jessica; Nugiel, Tehila; Metoki, Athanasia; Olson, Ingrid R.

2017-01-01

Social behavior is often shaped by the rich storehouse of biographical information that we hold for other people. In our daily life, we rapidly and flexibly retrieve a host of biographical details about individuals in our social network, which often guide our decisions as we navigate complex social interactions. Even abstract traits associated with an individual, such as their political affiliation, can cue a rich cascade of person-specific knowledge. Here, we asked whether the anterior temporal lobe (ATL) serves as a hub for a distributed neural circuit that represents person knowledge. Fifty participants across two studies learned biographical information about fictitious people in a 2-d training paradigm. On day 3, they retrieved this biographical information while undergoing an fMRI scan. A series of multivariate and connectivity analyses suggest that the ATL stores abstract person identity representations. Moreover, this region coordinates interactions with a distributed network to support the flexible retrieval of person attributes. Together, our results suggest that the ATL is a central hub for representing and retrieving person knowledge. PMID:28289200

Improved Throughput with Cooperating Futuristic Airspace Management Components

NASA Technical Reports Server (NTRS)

Glaab, Patricia C.

2013-01-01

An experiment was conducted to integrate airspace management tools that would typically be confined to either the en route or the terminal airspace to explore the potential benefits of their communication to improve arrival capacity. A NAS-wide simulation was configured with a new concept component that used the information to reconfigure the terminal airspace to the capacity benefit of the airport. Reconfiguration included a dynamically expanding and contracting TRACON area and a varying number of active arrival runways, both automatically selected to accommodate predicted volume of traffic. ATL and DFW were selected for the study. Results showed significant throughput increase for scenarios that are considered to be over-capacity for current day airport configurations. During periods of sustained demand for ATL 2018, throughput increased by 26 operations per hour (30%) and average delay was reduced from 18 minutes to 8 minutes per flight when using the dynamic TRACON. Similar results were obtained for DFW with 2018 traffic levels and for ATL with 2006 traffic levels, but with lower benefits due to lower demand.

Automated terrestrial laser scanning with near-real-time change detection - monitoring of the Séchilienne landslide

NASA Astrophysics Data System (ADS)

Kromer, Ryan A.; Abellán, Antonio; Hutchinson, D. Jean; Lato, Matt; Chanut, Marie-Aurelie; Dubois, Laurent; Jaboyedoff, Michel

2017-05-01

We present an automated terrestrial laser scanning (ATLS) system with automatic near-real-time change detection processing. The ATLS system was tested on the Séchilienne landslide in France for a 6-week period with data collected at 30 min intervals. The purpose of developing the system was to fill the gap of high-temporal-resolution TLS monitoring studies of earth surface processes and to offer a cost-effective, light, portable alternative to ground-based interferometric synthetic aperture radar (GB-InSAR) deformation monitoring. During the study, we detected the flux of talus, displacement of the landslide and pre-failure deformation of discrete rockfall events. Additionally, we found the ATLS system to be an effective tool in monitoring landslide and rockfall processes despite missing points due to poor atmospheric conditions or rainfall. Furthermore, such a system has the potential to help us better understand a wide variety of slope processes at high levels of temporal detail.

Facilitation of Function and Manipulation Knowledge of Tools Using Transcranial Direct Current Stimulation (tDCS).

PubMed

Ishibashi, Ryo; Mima, Tatsuya; Fukuyama, Hidenao; Pobric, Gorana

2017-01-01

Using a variety of tools is a common and essential component of modern human life. Patients with brain damage or neurological disorders frequently have cognitive deficits in their recognition and manipulation of tools. In this study, we focused on improving tool-related cognition using transcranial direct current stimulation (tDCS). Converging evidence from neuropsychology, neuroimaging and non- invasive brain stimulation has identified the anterior temporal lobe (ATL) and inferior parietal lobule (IPL) as brain regions supporting action semantics. We observed enhanced performance in tool cognition with anodal tDCS over ATL and IPL in two cognitive tasks that require rapid access to semantic knowledge about the function or manipulation of common tools. ATL stimulation improved access to both function and manipulation knowledge of tools. The effect of IPL stimulation showed a trend toward better manipulation judgments. Our findings support previous studies of tool semantics and provide a novel approach for manipulation of underlying circuits.

Dynamic neural architecture for social knowledge retrieval.

PubMed

Wang, Yin; Collins, Jessica A; Koski, Jessica; Nugiel, Tehila; Metoki, Athanasia; Olson, Ingrid R

2017-04-18

Social behavior is often shaped by the rich storehouse of biographical information that we hold for other people. In our daily life, we rapidly and flexibly retrieve a host of biographical details about individuals in our social network, which often guide our decisions as we navigate complex social interactions. Even abstract traits associated with an individual, such as their political affiliation, can cue a rich cascade of person-specific knowledge. Here, we asked whether the anterior temporal lobe (ATL) serves as a hub for a distributed neural circuit that represents person knowledge. Fifty participants across two studies learned biographical information about fictitious people in a 2-d training paradigm. On day 3, they retrieved this biographical information while undergoing an fMRI scan. A series of multivariate and connectivity analyses suggest that the ATL stores abstract person identity representations. Moreover, this region coordinates interactions with a distributed network to support the flexible retrieval of person attributes. Together, our results suggest that the ATL is a central hub for representing and retrieving person knowledge.

Social cognition and the anterior temporal lobes: a review and theoretical framework

PubMed Central

McCoy, David; Klobusicky, Elizabeth; Ross, Lars A.

2013-01-01

Memory for people and their relationships, along with memory for social language and social behaviors, constitutes a specific type of semantic memory termed social knowledge. This review focuses on how and where social knowledge is represented in the brain. We propose that portions of the anterior temporal lobe (ATL) play a critical role in representing and retrieving social knowledge. This includes memory about people, their names and biographies and more abstract forms of social memory such as memory for traits and social concepts. This hypothesis is based on the convergence of several lines of research including anatomical findings, lesion evidence from both humans and non-human primates and neuroimaging evidence. Moreover, the ATL is closely interconnected with cortical nuclei of the amygdala and orbitofrontal cortex via the uncinate fasciculus. We propose that this pattern of connectivity underlies the function of the ATL in encoding and storing emotionally tagged knowledge that is used to guide orbitofrontal-based decision processes. PMID:23051902

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

PubMed

Limotai, Chusak; McLachlan, Richard S; Hayman-Abello, Susan; Hayman-Abello, Brent; Brown, Suzan; Bihari, Frank; Mirsattari, Seyed M

2018-06-19

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

The perirhinal cortex and conceptual processing: Effects of feature-based statistics following damage to the anterior temporal lobes.

PubMed

Wright, Paul; Randall, Billi; Clarke, Alex; Tyler, Lorraine K

2015-09-01

The anterior temporal lobe (ATL) plays a prominent role in models of semantic knowledge, although it remains unclear how the specific subregions within the ATL contribute to semantic memory. Patients with neurodegenerative diseases, like semantic dementia, have widespread damage to the ATL thus making inferences about the relationship between anatomy and cognition problematic. Here we take a detailed anatomical approach to ask which substructures within the ATL contribute to conceptual processing, with the prediction that the perirhinal cortex (PRc) will play a critical role for concepts that are more semantically confusable. We tested two patient groups, those with and without damage to the PRc, across two behavioural experiments - picture naming and word-picture matching. For both tasks, we manipulated the degree of semantic confusability of the concepts. By contrasting the performance of the two groups, along with healthy controls, we show that damage to the PRc results in worse performance in processing concepts with higher semantic confusability across both experiments. Further by correlating the degree of damage across anatomically defined regions of interest with performance, we find that PRc damage is related to performance for concepts with increased semantic confusability. Our results show that the PRc supports a necessary and crucial neurocognitve function that enables fine-grained conceptual processes to take place through the resolution of semantic confusability. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

ATLS Hypovolemic Shock Classification by Prediction of Blood Loss in Rats Using Regression Models.

PubMed

Choi, Soo Beom; Choi, Joon Yul; Park, Jee Soo; Kim, Deok Won

2016-07-01

In our previous study, our input data set consisted of 78 rats, the blood loss in percent as a dependent variable, and 11 independent variables (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse pressure, respiration rate, temperature, perfusion index, lactate concentration, shock index, and new index (lactate concentration/perfusion)). The machine learning methods for multicategory classification were applied to a rat model in acute hemorrhage to predict the four Advanced Trauma Life Support (ATLS) hypovolemic shock classes for triage in our previous study. However, multicategory classification is much more difficult and complicated than binary classification. We introduce a simple approach for classifying ATLS hypovolaemic shock class by predicting blood loss in percent using support vector regression and multivariate linear regression (MLR). We also compared the performance of the classification models using absolute and relative vital signs. The accuracies of support vector regression and MLR models with relative values by predicting blood loss in percent were 88.5% and 84.6%, respectively. These were better than the best accuracy of 80.8% of the direct multicategory classification using the support vector machine one-versus-one model in our previous study for the same validation data set. Moreover, the simple MLR models with both absolute and relative values could provide possibility of the future clinical decision support system for ATLS classification. The perfusion index and new index were more appropriate with relative changes than absolute values.

Influence of Silver-hydroxyapatite Nanocomposite Coating on Biofilm Formation of Joint Prosthesis and Its Mechanism.

PubMed

Zhao, L; Ashraf, M A

2015-12-01

The main reason for biomaterial related refractory infections is biofilm formation caused by bacterial adhesion on the surface of materials. Silver-hydroxyapatite (Ag/HA) nanocomposite coating can inhibit the formation of biofilm, but its mechanism is not clear. In order to clarify the mechanism, the amounts of biofilm on the Ag/HA composite coating and HA coating were determined, the release rates of silver nanoparticles in simulated body fluid (SBF) were detected by atomic absorption spectrometry, and the expression values of atlE , fbe , sap , iapB genes of Staphylococcus aureus were studied when they grew on Ag/HA composite coating and HA coating. The amount of the biofilm on the Ag/HA composite coating was significantly less than that on the HA coating, and the bacterial adhesion was decreased. The silver nanoparticles were released continuously in SBF and the release rate decreased gradually with time. The expression values of atlE , fbe and sap were high in the initial stage of adhesion and the expression value of iapB was high in the colonies-gathering stage in the control group, but they were all significantly inhibited in the presence of Ag. These results indicated that the main antibacterial effect of Ag/HA composite coating was achieved by the release of silver nanoparticles. The addition of Ag inhibited the expression of genes related to biofilm formation, which in turn inhibited the formation of biofilms. This provided theoretical support for the clinical application of Ag/HA composite coating.

HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling

PubMed Central

Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

2017-01-01

Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target. PMID:28881635

Outcome of temporal lobe epilepsy surgery evaluated with bitemporal intracranial electrode recordings.

PubMed

Massot-Tarrús, Andreu; Steven, David A; McLachlan, Richard S; Mirsattari, Seyed M; Diosy, David; Parrent, Andrew G; Blume, Warren T; Girvin, John P; Burneo, Jorge G

2016-11-01

Temporal lobe epilepsy (TLE) with unclear lateralization may require intracranial implantation of electrodes (IIE). We retrospectively assessed the association between the use of IIE and long-term outcomes in patients undergoing anterior temporal lobectomy (ATL). We retrospectively reviewed the records of 1,032 patients undergoing epilepsy surgery at our center from 1977 to 2006. Patients who underwent ATL were included. Seizure outcome was assessed through final follow-up. Those who underwent scalp and IIE (mostly evaluated with temporal subdural strip electrodes) were compared. From 497 patients who underwent ATL, 139 did so after IIE placement in the temporal lobes. Mean age at surgery was 32.3±12.3years and median duration of follow-up 24 months (range: 6-36). Fifty-three percent of those evaluated with IIE were seizure-free at their last available visit (vs. 68% evaluated with only scalp EEG, p=0.002). Patients with lesional TLE generally had a better outcome (65.5% seizure free) than those without lesions (56.3%, p=0.093), especially for unilateral TLE diagnosed with IIE. In a multivariate Cox regression analyses adjusted for gender, neuropsychological concordance, pathological findings, and post-operative seizures, bilateral TLE predicted seizure recurrence in IIE patients (HR=2.08, 95% CI: 1.08-4.0, p=0.029). More than a half of those who undergo IIE in suspected TLE are seizure free after ATL. IIE allows for the identification of surgical candidates. Copyright © 2016 Elsevier B.V. All rights reserved.

Individual prediction of change in delayed recall of prose passages after left-sided anterior temporal lobectomy.

PubMed

Jokeit, H; Ebner, A; Holthausen, H; Markowitsch, H J; Moch, A; Pannek, H; Schulz, R; Tuxhorn, I

1997-08-01

Prognostic variables for individual memory outcome after left anterior temporal lobectomy (ATL) were studied in 27 patients with refractory temporal lobe epilepsy. The difference between pre- and postoperative performance in the delayed recall of two prose passages (Story A and B) from the Wechsler Memory Scale served as measure of postoperative memory change. Fifteen independent clinical, neuropsychological, and electrophysiological variables were submitted to a multiple linear regression analysis. Preoperative immediate and delayed recall of story content and right hemisphere Wada memory performance for pictorial and verbal items explained very well postoperative memory changes in recall of Story B. Delayed recall of Story B, but not of Story A, had high concurrent validity to other measures of memory. Patients who became seizure-free did not differ in memory change from patients who continued to have seizures after ATL. The variables age at epilepsy onset and probable age at temporal lobe damage provided complementary information for individual prediction but with less effectiveness than Wada test data. Our model confirmed that good preoperative memory functioning and impaired right hemispheric Wada memory performance for pictorial items predict a high risk of memory loss after left ATL. The analyses demonstrate that the combination of independent measures delivers more information than Wada test performance or any other variable alone. The suggested function can be used routinely to estimate the individual severity of verbal episodic memory impairment that might occur after left-sided ATL and offers a rational basis for the counseling of patients.

Impact of miR-155 and miR-126 as novel biomarkers on the assessment of disease progression and prognosis in adult T-cell leukemia.

PubMed

Ishihara, Kaori; Sasaki, Daisuke; Tsuruda, Kazuto; Inokuchi, Naoko; Nagai, Kazuhiro; Hasegawa, Hiroo; Yanagihara, Katsunori; Kamihira, Shimeru

2012-12-01

Micro RNAs (miRNAs) provide new insight in the development of cancer, but little is known about their clinical relevance as biomarkers in the assessment of diagnosis, classification, progression and prognosis of various cancers. To explore a potential novel biomarker, we examined the cellular and plasma miRNA profiles in adult T-cell leukemia (ATL) characterized by diverse clinical features. Using CD4-positive cells isolated from 2 non-infected healthy individuals, 3 chronic ATL patients and 3 acute ATL patients, cellular miRNAs were profiled by microarray. The microarray screened 5 miRNAs namely miR-155, let-7g, miR-126, miR-130a and let-7b because of the large difference in their expression in diseased vs. that of healthy controls. The expression levels of before 5 miRNAs re-quantified by reverse transcription quantifiable polymerase chain reaction (RT-qPCR) were not always accordant in cells and plasma. The high and low plasma levels of miR-155 and miR-126 changed with ATL stage. The present study revealed that there is a quantitative discrepancy between cellular and plasma miRNAs. The elevation of plasma miR-155 and the reduction in miR-126 correlated with poor prognosis, indicating their usefulness as a novel biomarker for the assessment of disease stage. Copyright © 2012 Elsevier Ltd. All rights reserved.

WIP1 deficiency inhibits HTLV-1 Tax oncogenesis: novel therapeutic prospects for treatment of ATL?

PubMed Central

2012-01-01

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches. PMID:23256570

Pay for performance - motivation to succeed in Advanced Trauma Life Support courses - a question of background or funding?

PubMed

Klein, Roman; Armbruster, Wolfgang; Grotz, Martin; Höner, Bernd; Münzberg, Matthias; Grützner, Paul Alfred; Wölfl, Christoph Georg

2017-01-01

Objective: To correlate students' performance with their professional background and motivation to take part in Advanced Trauma Life Support (ATLS) courses. We base our analysis on the self-determination theory that differentiates intrinsic (ambition to perform by individual itself) from extrinsic motivation (incentive by external stimuli). Design: We present a non-blinded, monocentric, non-randomized descriptive study of 376 students taking part in an ATLS course at one course site in Germany. Part of a two-day ATLS course are two written tests; we correlate test scores with background information provided by the students in a questionnaire of 13 items (age, sex, adress, board certification, specialty, subspecialty, position, hospital level of care, hospital operator and hospital participation in trauma network, motivation, funding source, condition of funding). Setting: The students were recuited at the BG Trauma Center Ludwigshafen (Germany), a large 528-bed trauma center and one of 13 ATLS course sites in Germany. Participants: 449 ATLS course students taking part in ATLS courses at the above-mentioned course site from February 2009 to May 2010 were sent a questionnaire asking for their background. All 449 course students were eligible to participate. 376 (83.7%) questionnaires were returned, pre- and post-test results of all students aquired and included into our calculations. 312 (83%) were male and 64 (17%) female. The majority (59.3%) of recruited students came from trauma surgery, 21.8% from anesthesiology, 8% from general surgery, 4% from abdominal surgery, 0.5% from vascular or thoracic surgery each and 5.9% from other specialties. Results: Neither age, sex, subspecialty, hospital level of care, hospital operator, or hospital participation in trauma network played a role with respect to motivation or test results. The high degree of intrinsic motivation of consultants (92.3%) had no impact on their test results. Anesthesiologists were higher motivated (75.6% intrinsically motivated) in contrast to all surgical colleagues (63.6%), which showed significant differences in the pre- (89.8% vs. 85.3%, p=0.03) but not the post-test. Of all 13.6% students who were self-payers, 94.1% were intrinsically motivated; the 86.2% whose course fee was accounted for were less likely to be intrinsically motivated (63.9%). Sponsoring however did not have a negative impact on test results. Conditional funding (sponsored only on passing both tests) was detrimental to motivation: 0% of these individuals were intrinsically motivated and they scored significantly lower (82.5%) than all other students in the post-test (86.9%, p=0.002). Overall, intrinsically motivated students overtopped extrinsically motivated students in the post-test (88.0% vs. 83.4%, p<0.001). Conclusions: ATLS course participation is not compulsory for medical doctors in Germany. Intrinsic motivation to take part in these courses is a key prerequisite to increase performance, irrespective of the background of the students. Intrinsically motivated students are ready to invest into their education and vice versa. Conditional funding (course fee only sponsored on passing the course) evokes no intrinsic motivation at all and causes worse results.

Pay for performance – motivation to succeed in Advanced Trauma Life Support courses – a question of background or funding?

PubMed Central

Klein, Roman; Armbruster, Wolfgang; Grotz, Martin; Höner, Bernd; Münzberg, Matthias; Grützner, Paul Alfred; Wölfl, Christoph Georg

2017-01-01

Objective: To correlate students’ performance with their professional background and motivation to take part in Advanced Trauma Life Support (ATLS) courses. We base our analysis on the self-determination theory that differentiates intrinsic (ambition to perform by individual itself) from extrinsic motivation (incentive by external stimuli). Design: We present a non-blinded, monocentric, non-randomized descriptive study of 376 students taking part in an ATLS course at one course site in Germany. Part of a two-day ATLS course are two written tests; we correlate test scores with background information provided by the students in a questionnaire of 13 items (age, sex, adress, board certification, specialty, subspecialty, position, hospital level of care, hospital operator and hospital participation in trauma network, motivation, funding source, condition of funding). Setting: The students were recuited at the BG Trauma Center Ludwigshafen (Germany), a large 528-bed trauma center and one of 13 ATLS course sites in Germany. Participants: 449 ATLS course students taking part in ATLS courses at the above-mentioned course site from February 2009 to May 2010 were sent a questionnaire asking for their background. All 449 course students were eligible to participate. 376 (83.7%) questionnaires were returned, pre- and post-test results of all students aquired and included into our calculations. 312 (83%) were male and 64 (17%) female. The majority (59.3%) of recruited students came from trauma surgery, 21.8% from anesthesiology, 8% from general surgery, 4% from abdominal surgery, 0.5% from vascular or thoracic surgery each and 5.9% from other specialties. Results: Neither age, sex, subspecialty, hospital level of care, hospital operator, or hospital participation in trauma network played a role with respect to motivation or test results. The high degree of intrinsic motivation of consultants (92.3%) had no impact on their test results. Anesthesiologists were higher motivated (75.6% intrinsically motivated) in contrast to all surgical colleagues (63.6%), which showed significant differences in the pre- (89.8% vs. 85.3%, p=0.03) but not the post-test. Of all 13.6% students who were self-payers, 94.1% were intrinsically motivated; the 86.2% whose course fee was accounted for were less likely to be intrinsically motivated (63.9%). Sponsoring however did not have a negative impact on test results. Conditional funding (sponsored only on passing both tests) was detrimental to motivation: 0% of these individuals were intrinsically motivated and they scored significantly lower (82.5%) than all other students in the post-test (86.9%, p=0.002). Overall, intrinsically motivated students overtopped extrinsically motivated students in the post-test (88.0% vs. 83.4%, p<0.001). Conclusions: ATLS course participation is not compulsory for medical doctors in Germany. Intrinsic motivation to take part in these courses is a key prerequisite to increase performance, irrespective of the background of the students. Intrinsically motivated students are ready to invest into their education and vice versa. Conditional funding (course fee only sponsored on passing the course) evokes no intrinsic motivation at all and causes worse results. PMID:29214123

Physician staffed helicopter emergency medical systems can provide advanced trauma life support in mountainous and remote areas.

PubMed

Ausserer, Julia; Moritz, Elizabeth; Stroehle, Matthias; Brugger, Hermann; Strapazzon, Giacomo; Rauch, Simon; Mair, Peter

2017-01-01

In remote and mountainous areas, helicopter emergency medical systems (HEMS) are used to expedite evacuation and provide pre-hospital advanced trauma life support (ATLS) in major trauma victims. Aim of the study was to investigate feasibility of ATLS in HEMS mountain rescue missions and its influence on patient condition at hospital admission. 58 major trauma victims (Injury Severity Score ≥16), evacuated by physician staffed HEMS from remote and mountainous areas in the State of Tyrol, Austria between 1.1.2011 and 31.12.2013. Pre-hospital time exceeded 90min in 24 (44%) cases. 31 (53%) patients suffered critical impairment of at least one vital function (systolic blood pressure <90mmHg, GCS <10, or respiratory rate <10 or >30). 4 (6.9%) of 58 patients died prior to hospital admission. Volume resuscitation was restrictive: 18 (72%) of 25 hypotensive patients received ≤500ml fluids and blood pressure was increased >90mmHg at hospital admission in only 9 (36%) of these 25 patients. 8 (50%) of 16 brain trauma patients with a blood pressure <90mmHg remained hypotensive at hospital admission. Endotracheal intubation was accomplished without major complications in 15 (79%) of 19 patients with a Glasgow Coma Scale score <10. Rope operations were necessary in 40 (69%) of 58 cases and ATLS was started before hoist evacuation in 30 (75%) of them. The frequent combination of prolonged pre-hospital times, with critical impairment of vital functions, supports the need for early ATLS in HEMS mountain rescue missions. Pre-hospital endotracheal intubation is possible with a high success and low complication rate also in a mountain rescue scenario. Pre-hospital volume resuscitation is restrictive and hypotension is reversed at hospital admission in only one third of patients. Prolonged pre-hospital hypotension remains an unresolved problem in half of all brain trauma patients and indicates the difficulties to increase blood pressure to a desired level in a mountain rescue scenario. Despite technical considerations, on-site ATLS is feasible for an experienced emergency physician in the majority of rope rescue operations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reaction time in pilots at sustained acceleration of +4.5 G(z).

PubMed

Truszczynski, Olaf; Wojtkowiak, Mieczyslaw; Lewkowicz, Rafal; Biernacki, Marcin P; Kowalczuk, Krzysztof

2013-08-01

Pilots flying at very high speed are exposed to the effects of prolonged accelerations while changing their flight path. The aim of this research was to assess the impact of sustained accelerations on the visual-motor response times of pilots and the acceleration tolerance level (ATL) as a measure of pilots' endurance to applied +G(z). The study involved 18 young pilots, 23-25 yr of age. The subjects' task was to quickly and accurately respond to the light stimuli presented on a light bar during exposure to acceleration at +4.5 G(z) and until reaching the ATL. Simple response time (SRT) measurements were performed using a visual-motor analysis system throughout the exposures, which allowed the assessment of a pilot's ATL. The pilots' ATL ranged from 270 to 366 s (Mean = 317.7 +/- 26.15 SD). The analysis of the SRT indicated a significant effect of duration of acceleration on the visual response time. The results of the post hoc comparisons showed that SRT increased with longer durations of the same level of +G(z) load and then decreased, reaching values similar to the controls. Exposure to prolonged acceleration of +4.5 G(z) significantly increases SRT. There was no statistically significant difference in SRT between the pilots with "short" and "long" time exposures. A pilot's SRT during a prolonged +4.5 G(z) exposure could be a reliable indicator of pilot G performance in the fast jet. Deterioration of SRT may be used to predict imminent +G(z) endurance limits between pilots with widely varying endurance abilities.

Treatment and survival among 1594 patients with ATL.

PubMed

Katsuya, Hiroo; Ishitsuka, Kenji; Utsunomiya, Atae; Hanada, Shuichi; Eto, Tetsuya; Moriuchi, Yukiyoshi; Saburi, Yoshio; Miyahara, Masaharu; Sueoka, Eisaburo; Uike, Naokuni; Yoshida, Shinichiro; Yamashita, Kiyoshi; Tsukasaki, Kunihiro; Suzushima, Hitoshi; Ohno, Yuju; Matsuoka, Hitoshi; Jo, Tatsuro; Amano, Masahiro; Hino, Ryosuke; Shimokawa, Mototsugu; Kawai, Kazuhiro; Suzumiya, Junji; Tamura, Kazuo

2015-12-10

Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature T lymphocytes caused by human T-lymphotropic virus type I. Intensive combination chemotherapy and allogeneic hematopoietic stem cell transplantation have been introduced since the previous Japanese nationwide survey was performed in the late 1980s. In this study, we delineated the current features and management of ATL in Japan. The clinical data were collected retrospectively from the medical records of patients diagnosed with ATL between 2000 and 2009, and a total of 1665 patients' records were submitted to the central office from 84 institutions in Japan. Seventy-one patients were excluded; 895, 355, 187, and 157 patients with acute, lymphoma, chronic, and smoldering types, respectively, remained. The median survival times were 8.3, 10.6, 31.5, and 55.0 months, and 4-year overall survival (OS) rates were 11%, 16%, 36%, and 52%, respectively, for acute, lymphoma, chronic, and smoldering types. The number of patients with allogeneic hematopoietic stem cell transplantation was 227, and their median survival time and OS at 4 years after allogeneic hematopoietic stem cell transplantation was 5.9 months and 26%, respectively. This study revealed that the prognoses of the patients with acute and lymphoma types were still unsatisfactory, despite the recent progress in treatment modalities, but an improvement of 4-year OS was observed in comparison with the previous survey. Of note, one-quarter of patients who could undergo transplantation experienced long survival. It is also noted that the prognosis of the smoldering type was worse than expected. © 2015 by The American Society of Hematology.

Influence of Silver-hydroxyapatite Nanocomposite Coating on Biofilm Formation of Joint Prosthesis and Its Mechanism

PubMed Central

Zhao, L; Ashraf, MA

2015-01-01

ABSTRACT Background: The main reason for biomaterial related refractory infections is biofilm formation caused by bacterial adhesion on the surface of materials. Silver-hydroxyapatite (Ag/HA) nanocomposite coating can inhibit the formation of biofilm, but its mechanism is not clear. Material and Method: In order to clarify the mechanism, the amounts of biofilm on the Ag/HA composite coating and HA coating were determined, the release rates of silver nanoparticles in simulated body fluid (SBF) were detected by atomic absorption spectrometry, and the expression values of atlE, fbe, sap, iapB genes of Staphylococcus aureus were studied when they grew on Ag/HA composite coating and HA coating. Results: The amount of the biofilm on the Ag/HA composite coating was significantly less than that on the HA coating, and the bacterial adhesion was decreased. The silver nanoparticles were released continuously in SBF and the release rate decreased gradually with time. The expression values of atlE, fbe and sap were high in the initial stage of adhesion and the expression value of iapB was high in the colonies-gathering stage in the control group, but they were all significantly inhibited in the presence of Ag. Conclusion: These results indicated that the main antibacterial effect of Ag/HA composite coating was achieved by the release of silver nanoparticles. The addition of Ag inhibited the expression of genes related to biofilm formation, which in turn inhibited the formation of biofilms. This provided theoretical support for the clinical application of Ag/HA composite coating. PMID:27400164

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1.

PubMed

Manuel, Sharrón L; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K; Gardner, Jay; Betts, Michael R; Jain, Pooja

2013-10-01

The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. Quality of cytotoxic T lymphocytes (CTLs) is being increasingly associated with the outcome of persistent HTLV-1 infection. In this respect, a patient cohort (from HTLV-1 endemic region) consisting of seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8(+) T cells polyfunctionality in response to the viral antigen Tax. Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8(+) T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8(+) T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy / therapeutic vaccine against HTLV-mediated diseases.

Visual object naming in patients with small lesions centered at the left temporopolar region.

PubMed

Campo, Pablo; Poch, Claudia; Toledano, Rafael; Igoa, José Manuel; Belinchón, Mercedes; García-Morales, Irene; Gil-Nagel, Antonio

2016-01-01

Naming is considered a left hemisphere function that operates according to a posterior-anterior specificity gradient, with more fine-grained information processed in most anterior regions of the temporal lobe (ATL), including the temporal pole (TP). Word finding difficulties are typically assessed using visual confrontation naming tasks, and have been associated with selective damage to ATL resulting from different aetiologies. Nonetheless, the role of the ATL and, more specifically, of the TP in the naming network is not completely established. Most of the accumulated evidence is based on studies on patients with extensive lesions, often bilateral. Furthermore, there is a considerable variability in the anatomical definition of ATL. To better understand the specific involvement of the left TP in visual object naming, we assessed a group of patients with an epileptogenic lesion centered at the TP, and compared their performance with that of a strictly matched control group. We also administered a battery of verbal and non-verbal semantic tasks that was used as a semantic memory baseline. Patients showed an impaired naming ability, manifesting in a certain degree of anomia and semantically related naming errors, which was influenced by concept familiarity. This pattern took place in a context of mild semantic dysfunction that was evident in different types and modalities of semantic tasks. Therefore, current findings demonstrate that a restricted lesion to the left TP can cause a significant deficit in object naming. Of importance, the observed semantic impairment was far from the devastating degradation observed in semantic dementia and other bilateral conditions.

Lack of recall response to Tax in ATL and HAM/TSP patients but not in asymptomatic carriers of human T-cell leukemia virus type 1

PubMed Central

Manuel, Sharrón L.; Sehgal, Mohit; Connolly, John; Makedonas, George; Khan, Zafar K.; Gardner, Jay; Goedert, James J.; Betts, Michael R.; Jain, Pooja

2013-01-01

Purpose & methods The immunopathogenic mechanisms responsible for debilitating neurodegenerative and oncologic diseases associated with human T-cell leukemia virus type 1 (HTLV-1) are not fully understood. In this respect, a patient cohort from HTLV-1 endemic region that included seronegative controls (controls), asymptomatic carriers (ACs), and patients with adult T-cell leukemia (ATL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) was analyzed for CD8+ T cells polyfunctionality in response to the viral antigen Tax. Results Compared to ACs, ATL and HAM/TSP patients had lower frequency and polyfunctionality of CTLs in response to Tax suggesting dysfunction of CD8+ T cells in these individuals. As an underlying mechanism, programmed death-1 (PD-1) receptor was found to be highly unregulated in Tax-responsive as well as total CD8+ T cells from ATL and HAM/TSP but not from ACs and directly correlated with the lack of polyfunctionality in these individuals. Further, PD-1 expression showed a direct whereas MIP-1α expression had an indirect correlation with the proviral load providing new insights about the immunopathogenesis of HTLV-associated diseases. Additionally, we identified key cytokine signatures defining the immune activation status of clinical samples by the luminex assay. Conclusions Collectively, our findings suggest that reconstitution of fully functional CTLs, stimulation of MIP-1α expression, and/or blockade of the PD-1 pathway are potential approaches for immunotherapy and therapeutic vaccine against HTLV-mediated diseases. PMID:23888327

Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor

PubMed Central

Perretti, Mauro; Chiang, Nan; La, Mylinh; Fierro, Iolanda M.; Marullo, Stefano; Getting, Stephen J; Solito, Egle; Serhan, Charles N.

2009-01-01

Aspirin (ASA) and dexamethasone (DEX) are widely used anti-inflammatory agents yet their mechanism(s) for blocking polymorphonuclear neutrophil (PMN) accumulation at sites of inflammation remains unclear. Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A4 receptor (ALXR/FPRL1) to halt PMN diapedesis. These structurally diverse ligands specifically interact directly with recombinant human ALXR demonstrated by specific radioligand binding and function as well as immunoprecipitation of PMN receptors. In addition, the combination of both ATL and ANXA1-derived peptides limited PMN infiltration and reduced production of inflammatory mediators (that is, prostaglandins and chemokines) in vivo. Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci. PMID:12368905

Epidemiological and Clinical Changes in American Tegumentary Leishmaniasis in an Area of Leishmania (Viannia) braziliensis Transmission Over a 20-Year Period

PubMed Central

Jirmanus, Lara; Glesby, Marshall J.; Guimarães, Luiz H.; Lago, Ednaldo; Rosa, Maria Elisa; Machado, Paulo R.; Carvalho, Edgar M.

2012-01-01

The Health Post of Corte de Pedra is located in a region endemic for American tegumentary leishmaniasis (ATL) in the Brazilian state of Bahia, and it treats 500–1,300 patients annually. To describe temporal changes in the epidemiology of ATL, we reviewed a random sample of 10% of patient charts (N = 1,209) from 1988 to 2008. There was a twofold increase in the number of cases over the 20-year period, with fluctuations in 10-year cycles. Patients were most frequently male, between the ages of 10 and 30 years, and engaged in agricultural labor; 4.3% of patients had mucosal disease, and 2.4% of patients had disseminated disease. Over the study period, the number of disseminated cases increased threefold, the proportion of cases in younger patients and agricultural workers decreased, and the proportion of patients residing in coastal areas increased. ATL is on the rise in Bahia, with a 10-year periodicity and evolving changes in epidemiology and manifestations of disease. PMID:22403312

Adult T-cell leukemia on the east coast of Kii Peninsula--presentation of an anti-ATLA-negative case.

PubMed

Karitani, Y; Kobayashi, T; Koh, T; Iwata, Y; Tanaka, I; Minami, N; Shirakawa, S

1983-01-01

Nineteen patients with adult T-cell leukemia (ATL) have been found in the last seven years along the east coast of Kii Peninsula in Japan. The leukemic cells were of the immunologically inducer/helper T-cell phenotype. The prognosis was very poor (median survival time, 85 days), and most of the patients had fatal complications of pulmonary infections. Antibody against ATL-associated antigen (anti-ATLA) was detected in sera from 9 of 10 patients who were born along the coast. However, it was not detected in one patient who was born in a district surrounded by mountains. Although he had neither superficial lymphadenopathy nor skin lesions, he showed rapid clinical deterioration. His leukemic cells appeared to be extremely bizarre with marked nuclear deformation compared with those of the other patients. In surface marker studies the leukemic cells reacted positively with OKT3, OKT4 and OKIa-1 monoclonal antibodies. The characteristics of the anti-ATLA-negative case are discussed in comparison with the other ATL cases.

Precocity in a tiny titanosaur from the Cretaceous of Madagascar.

PubMed

Curry Rogers, Kristina; Whitney, Megan; D'Emic, Michael; Bagley, Brian

2016-04-22

Sauropod dinosaurs exhibit the largest ontogenetic size range among terrestrial vertebrates, but a dearth of very young individuals has hindered understanding of the beginning of their growth trajectory. A new specimen of Rapetosaurus krausei sheds light on early life in the smallest stage of one of the largest dinosaurs. Bones record rapid growth rates and hatching lines, indicating that this individual weighed ~3.4 kilograms at hatching. Just several weeks later, when it likely succumbed to starvation in a drought-stressed ecosystem, it had reached a mass of ~40 kilograms and was ~35 centimeters tall at the hip. Unexpectedly, Rapetosaurus limb bones grew isometrically throughout their development. Cortical remodeling, limb isometry, and thin calcified hypertrophic metaphyseal cartilages indicate an active, precocial growth strategy. Copyright © 2016, American Association for the Advancement of Science.

Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome

PubMed Central

De Pace, Raffaella; Damme, Markus; Mattera, Rafael; Jarnik, Michal; Hoffmann, Victoria; Morris, H. Douglas; Han, Tae-Un; Mancini, Grazia M. S.; Buonanno, Andrés

2018-01-01

The hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of disorders characterized by progressive lower limb spasticity. Mutations in subunits of the heterotetrameric (ε-β4-μ4-σ4) adaptor protein 4 (AP-4) complex cause an autosomal recessive form of complicated HSP referred to as “AP-4 deficiency syndrome”. In addition to lower limb spasticity, this syndrome features intellectual disability, microcephaly, seizures, thin corpus callosum and upper limb spasticity. The pathogenetic mechanism, however, remains poorly understood. Here we report the characterization of a knockout (KO) mouse for the AP4E1 gene encoding the ε subunit of AP-4. We find that AP-4 ε KO mice exhibit a range of neurological phenotypes, including hindlimb clasping, decreased motor coordination and weak grip strength. In addition, AP-4 ε KO mice display a thin corpus callosum and axonal swellings in various areas of the brain and spinal cord. Immunohistochemical analyses show that the transmembrane autophagy-related protein 9A (ATG9A) is more concentrated in the trans-Golgi network (TGN) and depleted from the peripheral cytoplasm both in skin fibroblasts from patients with mutations in the μ4 subunit of AP-4 and in various neuronal types in AP-4 ε KO mice. ATG9A mislocalization is associated with increased tendency to accumulate mutant huntingtin (HTT) aggregates in the axons of AP-4 ε KO neurons. These findings indicate that the AP-4 ε KO mouse is a suitable animal model for AP-4 deficiency syndrome, and that defective mobilization of ATG9A from the TGN and impaired autophagic degradation of protein aggregates might contribute to neuroaxonal dystrophy in this disorder. PMID:29698489

A Rare de novo Interstitial Duplication at 4p15.2 in a Boy with Severe Congenital Heart Defects, Limb Anomalies, Hypogonadism, and Global Developmental Delay.

PubMed

Liang, Liyang; Xie, Yingjun; Shen, Yiping; Yin, Qibin; Yuan, Haiming

2016-01-01

Proximal 4p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafe-au-lait spots, developmental delay, tall and thin habitus, and intellectual disability. At present, over 20 cases of this syndrome have been published. However, duplication of the same region in proximal 4p has never been reported. Here, we describe a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre- and postnatal developmental delay, and mild cognitive impairments. A de novo 4.5-Mb interstitial duplication at 4p15.2p15.1 was detected by chromosomal microarray analysis. Next-generation sequencing was employed and confirmed the duplication, but revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotype were identified, such as RBPJ, STIM2, CCKAR, and LGI2. The results suggest a novel contiguous gene duplication syndrome. © 2016 S. Karger AG, Basel.

Cross-sectional geometry of Pecos Pueblo femora and tibiae--a biomechanical investigation: II. Sex, age, side differences.

PubMed

Ruff, C B; Hayes, W C

1983-03-01

Intra-populational variation in cross-sectional geometric properties of the femur and tibia are investigated in the Pecos Pueblo skeletal sample. Sex differences in geometric parameters suggest that male lower limb bones are more adapted for A-P bending, females for M-L bending. Proposed explanations for this finding include sexual dimorphism in pelvic structure and culturally prescribed sex-related activities at Pecos. With aging, both males and females undergo endosteal resorption and cortical thinning, greater among females. Both sexes also demonstrate an increase with age in subperiosteal area and second moments of area, supporting results reported in some studies of modern population samples. Sex and site-specific remodeling of the femur and tibia with aging also occur. These localized remodeling changes appear to selectively conserve more compact cortical bone in areas of high mechanical stress. Side differences in cross-sectional geometric properties indicate that left lower limb bones are generally larger than right lower limb bones, with asymmetry greater among females. In particular, left femora and tibiae are relatively stronger in A-P bending, again more so in females.

Ultrasonographic analysis in vitro of parietal thickness of lower limb varicose veins.

PubMed

Bruschi, E; Como, G; Zuiani, C; Segatto, E; Rocco, M; Biasi, G; Bazzocchi, M

2006-09-01

The aim of this study was to evaluate the ability of ultrasound (US) to measure the parietal thickness of varicose veins. In a blind in vitro analysis, 28 great saphenous veins, obtained after stripping surgery from 28 patients with chronic venous insufficiency, were examined with a digital US scanner ATL-HDI5000, linear 5-1 to 2-MHz broadband probe, compound imaging technique and analogic-digital zooming. We obtained one to three progressive measurements for each vein wall (total 67 parietal thicknesses). The samples, fixed in formalin, were sent to the pathology laboratory: sections were obtained at the same level of the sonographic planes, and images were obtained by digital camera mounted on an optical microscope. Measurements obtained at histology were considered as the gold standard. K-statistic was applied to compare sonographic and histologic measurements. Considering only the hypoechoic wall portion, 29/29 (100%) diagnoses of hypotrophy (K=0.91), 19/22 (86%) diagnoses of normotrophy (K=0,47) and 12/16 (75%) diagnoses of hypertrophy (K=0.7) were obtained by sonography. In our preliminary experience, the in vitro study of varicose veins allows precise, at least morphological, detection of hypotrophic walls. If these preliminary data are confirmed in vivo, sonography could be used to discriminate patients eligible for conservative treatment instead of surgery.

Double control systems for human T-cell leukemia virus type 1 by innate and acquired immunity.

PubMed

Kannagi, Mari; Hasegawa, Atsuhiko; Kinpara, Shuichi; Shimizu, Yukiko; Takamori, Ayako; Utsunomiya, Atae

2011-04-01

Human T-cell leukemia virus type 1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-specific T-cell responses elicit antitumor and antiviral effects in experimental models, and are considered to be one of the most important determinants of the disease manifestation, since they are activated in HAM/TSP but not in ATL patients. The combination of low T-cell responses and elevated HTLV-1 proviral loads are features of ATL, and are also observed in a subpopulation of HTLV-1 carriers at the asymptomatic stage, suggesting that these features may be underlying risk factors. These risks may potentially be reduced by vaccination to activate HTLV-1-specific T-cell responses. HAM/TSP and ATL patients also differ in their levels of HTLV-1 mRNA expression, which are generally low in vivo but slightly higher in HAM/TSP patients. Our recent study indicated that viral expression in HTLV-1-infected T-cells is suppressed by stromal cells in culture through type-I IFNs. The suppression was reversible after isolation from the stromal cells, mimicking a long-standing puzzling phenomenon in HTLV-1 infection where the viral expression is very low in vivo and rapidly induced in vitro. Collectively, HTLV-1 is controlled by both acquired and innate immunity in vivo: HTLV-1-specific T-cells survey infected cells, and IFNs suppress viral expression. Both effects would contribute to a reduction in viral pathogenesis, although they may potentially influence or conflict with one another. The presence of double control systems for HTLV-1 infection provides a new concept for understanding the pathogenesis of HTLV-1-mediated malignant and inflammatory diseases. © 2011 Japanese Cancer Association.

The anterior-ventrolateral temporal lobe contributes to boosting visual working memory capacity for items carrying semantic information.

PubMed

Chiou, Rocco; Lambon Ralph, Matthew A

2018-04-01

Working memory (WM) is a buffer that temporarily maintains information, be it visual or auditory, in an active state, caching its contents for online rehearsal or manipulation. How the brain enables long-term semantic knowledge to affect the WM buffer is a theoretically significant issue awaiting further investigation. In the present study, we capitalise on the knowledge about famous individuals as a 'test-case' to study how it impinges upon WM capacity for human faces and its neural substrate. Using continuous theta-burst transcranial stimulation combined with a psychophysical task probing WM storage for varying contents, we provide compelling evidence that (1) faces (regardless of familiarity) continued to accrue in the WM buffer with longer encoding time, whereas for meaningless stimuli (colour shades) there was little increment; (2) the rate of WM accrual was significantly more efficient for famous faces, compared to unknown faces; (3) the right anterior-ventrolateral temporal lobe (ATL) causally mediated this superior WM storage for famous faces. Specifically, disrupting the ATL (a region tuned to semantic knowledge including person identity) selectively hinders WM accrual for celebrity faces while leaving the accrual for unfamiliar faces intact. Further, this 'semantically-accelerated' storage is impervious to disruption of the right middle frontal gyrus and vertex, supporting the specific and causative contribution of the right ATL. Our finding advances the understanding of the neural architecture of WM, demonstrating that it depends on interaction with long-term semantic knowledge underpinned by the ATL, which causally expands the WM buffer when visual content carries semantic information. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Adaptive thinking & leadership simulation game training for special forces officers.

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

Raybourn, Elaine Marie; Mendini, Kip; Heneghan, Jerry

Complex problem solving approaches and novel strategies employed by the military at the squad, team, and commander level are often best learned experimentally. Since live action exercises can be costly, advances in simulation game training technology offer exciting ways to enhance current training. Computer games provide an environment for active, critical learning. Games open up possibilities for simultaneous learning on multiple levels; players may learn from contextual information embedded in the dynamics of the game, the organic process generated by the game, and through the risks, benefits, costs, outcomes, and rewards of alternative strategies that result from decision making. Inmore » the present paper we discuss a multiplayer computer game simulation created for the Adaptive Thinking & Leadership (ATL) Program to train Special Forces Team Leaders. The ATL training simulation consists of a scripted single-player and an immersive multiplayer environment for classroom use which leverages immersive computer game technology. We define adaptive thinking as consisting of competencies such as negotiation and consensus building skills, the ability to communicate effectively, analyze ambiguous situations, be self-aware, think innovatively, and critically use effective problem solving skills. Each of these competencies is an essential element of leader development training for the U.S. Army Special Forces. The ATL simulation is used to augment experiential learning in the curriculum for the U.S. Army JFK Special Warfare Center & School (SWCS) course in Adaptive Thinking & Leadership. The school is incorporating the ATL simulation game into two additional training pipelines (PSYOPS and Civil Affairs Qualification Courses) that are also concerned with developing cultural awareness, interpersonal communication adaptability, and rapport-building skills. In the present paper, we discuss the design, development, and deployment of the training simulation, and emphasize how the multiplayer simulation game is successfully used in the Special Forces Officer training program.« less

Cell adhesion molecule-1 (CADM1) expressed on adult T-cell leukemia/lymphoma cells is not involved in the interaction with macrophages.

PubMed

Komohara, Yoshihiro; Ma, Chaoya; Yano, Hiromu; Pan, Cheng; Horlad, Hasita; Saito, Yoichi; Ohnishi, Koji; Fujiwara, Yukio; Okuno, Yutaka; Nosaka, Kisato; Shimosaki, Shunsuke; Morishita, Kazuhiro; Matsuoka, Masao; Wakayama, Tomohiko; Takeya, Motohiro

2017-07-05

Cell adhesion molecule 1 (CADM1) is a cell adhesion molecule that is expressed in brain, liver, lung, testis, and some kinds of cancer cells including adult T-cell leukemia/lymphoma (ATLL). Recent studies have indicated the involvement of CADM1 in cell-cell contact between cytotoxic T-lymphocytes and virus infected cells. We previously reported that cell-cell interaction between lymphoma cells and macrophages induces lymphoma cell proliferation. In the present study, we investigated whether CADM1 is associated with cell-cell interaction between several human lymphoma cell lines and macrophages.CADM1 expression was observed in the ATLL cell lines, ATN-1, ATL-T, and ATL-35T, and in the B cell lymphoma cell lines, TL-1, DAUDI, and SLVL, using western blotting. Significant cell-cell interaction between macrophages and ATN-1, ATL-T, ATL-35T and MT-2, DAUDI, and SLVL cells, as assessed by induction of cell proliferation, was observed. Immunohistochemical analysis of human biopsy samples indicated CADM1 expression in 10 of 14 ATLL cases; however, no case of follicular lymphoma or diffuse large B-cell lymphoma was positive for CADM1. Finally, the interaction of macrophages with cells of the CADM1-negative ED ATLL cell line and CADM1-transfected ED cells was tested. However, significant cell-cell interaction between macrophage and CADM1-transfected ED cells was not observed. We conclude that CADM1 was not associated with cell-cell interaction between lymphoma cells and macrophages, although CADM1 may be a useful marker of ATLL for diagnostic procedures.

Selective amygdalohippocampectomy versus standard temporal lobectomy in patients with mesiotemporal lobe epilepsy and unilateral hippocampal sclerosis: post-operative facial emotion recognition abilities.

PubMed

Wendling, Anne-Sophie; Steinhoff, Bernhard J; Bodin, Frédéric; Staack, Anke M; Zentner, Josef; Scholly, Julia; Valenti, Maria-Paula; Schulze-Bonhage, Andreas; Hirsch, Edouard

2015-03-01

Surgical treatment of mesial temporal lobe epilepsy (mTLE) patients involves the removal either of the left or the right hippocampus. Since the mesial temporal lobe is responsible for emotion recognition abilities, we aimed to assess facial emotion recognition (FER) in two homogeneous patient cohorts that differed only in the administered surgery design since anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH) were performed independently of the underlying electroclinical conditions. The patient selection for the two respective surgical procedures was carried out retrospectively between 2000 and 2009 by two independent epilepsy centres, the Kork Epilepsy Centre, Germany and the University Hospital of Strasbourg, France. All included patients had presented with unilateral hippocampus sclerosis (HS) without associated dysplasia or white matter blurring and had become seizure-free postoperatively. Psychometric evaluation was carried out with the Ekman 60 Faces Test and screened for depression and psychosomatic symptoms with the SCL-90 R and the BDI. Thirty healthy volunteers participated as control subjects. Sixty patients were included, 27 had undergone SAH and 33 ATL. Patients and controls obtained comparable scores in FER for surprise, happiness, anger and sadness. Concerning fear and disgust the patient group scored significantly worse. Left-sided operations led to the the most pronounced impairment. The ATL group scored significantly worse for recognition of fear compared with SAH patients. Inversely, after SAH scores for disgust were significantly lower than after ATL, independently of the side of resection. Unilateral temporal damage impairs FER. Different neurosurgical procedures may affect FER differently. Copyright © 2015 Elsevier B.V. All rights reserved.

Segregation of anterior temporal regions critical for retrieving names of unique and nonunique entities reflects underlying long-range connectivity

PubMed Central

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2015-01-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. PMID:26707082

Drug Uptake, Lipid Rafts, and Vesicle Trafficking Modulate Resistance to an Anticancer Lysophosphatidylcholine Analogue in Yeast*

PubMed Central

Cuesta-Marbán, Álvaro; Botet, Javier; Czyz, Ola; Cacharro, Luis M.; Gajate, Consuelo; Hornillos, Valentín; Delgado, Javier; Zhang, Hui; Amat-Guerri, Francisco; Acuña, A. Ulises; McMaster, Christopher R.; Revuelta, José Luis; Zaremberg, Vanina; Mollinedo, Faustino

2013-01-01

The ether-phospholipid edelfosine, a prototype antitumor lipid (ATL), kills yeast cells and selectively kills several cancer cell types. To gain insight into its mechanism of action, we performed chemogenomic screens in the Saccharomyces cerevisiae gene-deletion strain collection, identifying edelfosine-resistant mutants. LEM3, AGP2, and DOC1 genes were required for drug uptake. Edelfosine displaced the essential proton pump Pma1p from rafts, inducing its internalization into the vacuole. Additional ATLs, including miltefosine and perifosine, also displaced Pma1p from rafts to the vacuole, suggesting that this process is a major hallmark of ATL cytotoxicity in yeast. Radioactive and synthetic fluorescent edelfosine analogues accumulated in yeast plasma membrane rafts and subsequently the endoplasmic reticulum. Although both edelfosine and Pma1p were initially located at membrane rafts, internalization of the drug toward endoplasmic reticulum and Pma1p to the vacuole followed different routes. Drug internalization was not dependent on endocytosis and was not critical for yeast cytotoxicity. However, mutants affecting endocytosis, vesicle sorting, or trafficking to the vacuole, including the retromer and ESCRT complexes, prevented Pma1p internalization and were edelfosine-resistant. Our data suggest that edelfosine-induced cytotoxicity involves raft reorganization and retromer- and ESCRT-mediated vesicular transport and degradation of essential raft proteins leading to cell death. Cytotoxicity of ATLs is mainly dependent on the changes they induce in plasma membrane raft-located proteins that lead to their internalization and subsequent degradation. Edelfosine toxicity can be circumvented by inactivating genes that then result in the recycling of internalized cell-surface proteins back to the plasma membrane. PMID:23335509

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ.

PubMed

Giam, Chou-Zen; Semmes, Oliver John

2016-06-16

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10-20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%-5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

The influence of high-heeled shoes on strain and tension force of the anterior talofibular ligament and plantar fascia during balanced standing and walking.

PubMed

Yu, Jia; Wong, Duo Wai-Chi; Zhang, Hongtao; Luo, Zong-Ping; Zhang, Ming

2016-10-01

High-heeled shoes have the capability to alter the strain and tension of ligamentous structures between the foot and ankle, which may result in ankle instability. However, high-heeled shoes can also reduce the strain on plantar fascia, which may be beneficial for the treatment of plantar fasciitis. In this study, the influence of heel height on strain and tension force applied to the anterior talofibular ligament (ATL) and plantar fascia were investigated. A three-dimensional finite element model of coupled foot-ankle-shoe complex was constructed. Four heel heights were studied in balanced standing: 0 in. (0cm), 1 in. (2.54cm), 2 in. (5.08cm), and 3 in. (7.62cm). A walking analysis was performed using 2-in. (5.08cm) high-heeled shoes. During balanced standing, the tension force on the ATL increased from 14.8N to 97.0N, with a six-fold increase in strain from 0 in. to 3 in. (0-7.62cm). The tension force and the average strain on the plantar fascia decreased from 151.0N (strain: 0.74%) to 59.6N (strain: 0.28%) when the heel height increased from 0 in. to 2 in. (0-5.08cm). When heel height reached 3 in. (7.62cm), the force and average strain increased to 278.3N (strain: 1.33%). The walking simulation showed that the fascia stretched out while the ATL loading decreased during push off. The simulation outcome demonstrated the influence of heel height on ATL alteration and plantar fascia strain, which implies risks for ankle injury and suggests guidance for the treatment of plantar fasciitis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

PubMed Central

Giam, Chou-Zen; Semmes, Oliver John

2016-01-01

HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

A Novel Alternative Splicing Isoform of Human T-Cell Leukemia Virus Type 1 bZIP Factor (HBZ-SI) Targets Distinct Subnuclear Localization

PubMed Central

Murata, Ken; Hayashibara, Toshihisa; Sugahara, Kazuyuki; Uemura, Akiko; Yamaguchi, Taku; Harasawa, Hitomi; Hasegawa, Hiroo; Tsuruda, Kazuto; Okazaki, Toshiro; Koji, Takehiko; Miyanishi, Takayuki; Yamada, Yasuaki; Kamihira, Shimeru

2006-01-01

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type 1 (HTLV-1); however, the mechanism by which HTLV-1 causes adult T-cell leukemia has not been fully elucidated. Recently, a functional basic leucine zipper (bZIP) protein coded in the minus strand of HTLV-1 genome (HBZ) was identified. We report here a novel isoform of the HTLV-1 bZIP factor (HBZ), HBZ-SI, identified by means of reverse transcription-PCR (RT-PCR) in conjunction with 5′ and 3′ rapid amplification of cDNA ends (RACE). HBZ-SI is a 206-amino-acid-long protein and is generated by alternative splicing between part of the HBZ gene and a novel exon located in the 3′ long terminal repeat of the HTLV-1 genome. Consequently, these isoforms share >95% amino acid sequence identity, and differ only at their N termini, indicating that HBZ-SI is also a functional protein. Duplex RT-PCR and real-time quantitative RT-PCR analyses showed that the mRNAs of these isoforms were expressed at equivalent levels in all ATL cell samples examined. Nonetheless, we found by Western blotting that the HBZ-SI protein was preferentially expressed in some ATL cell lines examined. A key finding was obtained from the subcellular localization analyses of these isoforms. Despite their high sequence similarity, each isoform was targeted to distinguishable subnuclear structures. These data show the presence of a novel isoform of HBZ in ATL cells, and in addition, shed new light on the possibility that each isoform may play a unique role in distinct regions in the cell nucleus. PMID:16474156

Relocation of Alona manueli Sinev & Zawisza 2013 and a new closely related species from the Ecuadorian Andes to the new genus Alpinalona (Cladocera, Chydoridae, Aloninae).

PubMed

Alonso, Miguel; Sinev, Artem Y

2017-11-20

Alpinalona gen. nov. is described for two species found in high altitude localities of continental North America and South America: Alona manueli (Sinev & Zawisza, 2013) from the Neovolcanic Mexican Axis and Alpinalona cajasi gen. et sp. nov from El Cajas National Park (Ecuador). The new genus is separated from Hexalona and allies by the absence of limb VI and filter plate V;  from Anthalona, Coronatella and the elegans-group by having seven setae on exopodite III, and by the presence of a well-developed seta 1 on the IDL of limb III; from Alona s. str. (quadrangularis-group) and Ovalona, by two main head pores, lateral head pores located close to main pores, and by a bilobed exopodite V; from Ovalona by the presence of seta (i) and inner setae 2-3 on limb I, and setae 4-5 of exopodite III being of same size; and from Alona s. lato by weakly developed marginal denticles of postabdomen, clusters of thin setulae on ventral surface of limb I, and by plumose setae 5-6 of exopodite IV. Alpinalona cajasi sp. nov. can be easily distinguished from A. manueli by the following characteristics: prominent posterodorsal angle of carapace; broader headshield; longer PP distance; and postanal marginal denticles organized into groups.

Phenotypic and genotypic characterization of biofilm formation in Staphylococcus haemolyticus.

PubMed

Barros, Elaine M; Lemos, Moara; Souto-Padrón, Thais; Giambiagi-deMarval, Marcia

2015-06-01

Staphylococcus haemolyticus is one of the most frequently isolated coagulase-negative staphylococci. The ability to produce biofilm has contributed to its emergence as a nosocomial pathogen. In this study, some growth conditions were tested to determine their influence on biofilm formation. Brain-heart infusion (BHI) broth containing glucose was used to screen 64 clinical strains. A strong biofilm producer strain showed cells surrounded by a thick layer of extracellular matrix. The presence of atlE, fbp, bap, and icaA genes was analyzed. We concluded that S. haemolyticus biofilm production can be increased with cells grown in BHI, and highlighted that it could be an ica-independent process.

Distinct contributions of the fornix and inferior longitudinal fasciculus to episodic and semantic autobiographical memory.

PubMed

Hodgetts, Carl J; Postans, Mark; Warne, Naomi; Varnava, Alice; Lawrence, Andrew D; Graham, Kim S

2017-09-01

Autobiographical memory (AM) is multifaceted, incorporating the vivid retrieval of contextual detail (episodic AM), together with semantic knowledge that infuses meaning and coherence into past events (semantic AM). While neuropsychological evidence highlights a role for the hippocampus and anterior temporal lobe (ATL) in episodic and semantic AM, respectively, it is unclear whether these constitute dissociable large-scale AM networks. We used high angular resolution diffusion-weighted imaging and constrained spherical deconvolution-based tractography to assess white matter microstructure in 27 healthy young adult participants who were asked to recall past experiences using word cues. Inter-individual variation in the microstructure of the fornix (the main hippocampal input/output pathway) related to the amount of episodic, but not semantic, detail in AMs - independent of memory age. Conversely, microstructure of the inferior longitudinal fasciculus, linking occipitotemporal regions with ATL, correlated with semantic, but not episodic, AMs. Further, these significant correlations remained when controlling for hippocampal and ATL grey matter volume, respectively. This striking correlational double dissociation supports the view that distinct, large-scale distributed brain circuits underpin context and concepts in AM. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Acoustic emissions verification testing of International Space Station experiment racks at the NASA Glenn Research Center Acoustical Testing Laboratory

NASA Astrophysics Data System (ADS)

Akers, James C.; Passe, Paul J.; Cooper, Beth A.

2005-09-01

The Acoustical Testing Laboratory (ATL) at the NASA John H. Glenn Research Center (GRC) in Cleveland, OH, provides acoustic emission testing and noise control engineering services for a variety of specialized customers, particularly developers of equipment and science experiments manifested for NASA's manned space missions. The ATL's primary customer has been the Fluids and Combustion Facility (FCF), a multirack microgravity research facility being developed at GRC for the USA Laboratory Module of the International Space Station (ISS). Since opening in September 2000, ATL has conducted acoustic emission testing of components, subassemblies, and partially populated FCF engineering model racks. The culmination of this effort has been the acoustic emission verification tests on the FCF Combustion Integrated Rack (CIR) and Fluids Integrated Rack (FIR), employing a procedure that incorporates ISO 11201 (``Acoustics-Noise emitted by machinery and equipment-Measurement of emission sound pressure levels at a work station and at other specified positions-Engineering method in an essentially free field over a reflecting plane''). This paper will provide an overview of the test methodology, software, and hardware developed to perform the acoustic emission verification tests on the CIR and FIR flight racks and lessons learned from these tests.

Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki

PubMed Central

HINO, Shigeo

2011-01-01

In late 2010, the nation-wide screening of pregnant women for human T-lymphotropic virus type 1 (HTLV-1) infection was implemented in Japan to prevent milk-borne transmission of HTLV-1. In the late 1970s, recognition of the adult T-cell leukemia (ATL) cluster in Kyushu, Japan, led to the discovery of the first human retrovirus, HTLV-1. In 1980, we started to investigate mother-to-child transmission (MTCT) for explaining the peculiar endemicity of HTLV-1. Retrospective and prospective epidemiological data revealed the MTCT rate at ∼20%. Cell-mediated transmission of HTLV-1 without prenatal infection suggested a possibility of milk-borne transmission. Common marmosets were successfully infected by oral inoculation of HTLV-1 harboring cells. A prefecture-wide intervention study to refrain from breast-feeding by carrier mothers, the ATL Prevention Program Nagasaki, was commenced in July 1987. It revealed a marked reduction of HTLV-1 MTCT by complete bottle-feeding from 20.3% to 2.5%, and a significantly higher risk of short-term breast-feeding (<6 months) than bottle-feeding (7.4% vs. 2.5%, P < 0.001). PMID:21558754

Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity

PubMed Central

Azran, Inbal; Schavinsky-Khrapunsky, Yana; Aboud, Mordechai

2004-01-01

HTLV-1 is the etiological agent of adult T-cell leukemia (ATL), the neurological syndrome TSP/HAM and certain other clinical disorders. The viral Tax protein is considered to play a central role in the process leading to ATL. Tax modulates the expression of many viral and cellular genes through the CREB/ATF-, SRF- and NF-κB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process. Together, these capacities render Tax highly oncogenic as reflected by its ability to transform rodent fibroblasts and primary human T-cells and to induce tumors in transgenic mice. In this article we discuss these effects of Tax and their apparent contribution to the HTLV-1 associated leukemogenic process. Notably, however, shortly after infection the virus enters into a latent state, in which viral gene expression is low in most of the HTLV-1 carriers' infected T-cells and so is the level of Tax protein, although rare infected cells may still display high viral RNA. This low Tax level is evidently insufficient for exerting its multiple oncogenic effects. Therefore, we propose that the latent virus must be activated, at least temporarily, in order to elevate Tax to its effective level and that during this transient activation state the infected cells may acquire some oncogenic mutations which can enable them to further progress towards ATL even if the activated virus is re-suppressed after a while. We conclude this review by outlining an hypothetical flow of events from the initial virus infection up to the ultimate ATL development and comment on the risk factors leading to ATL development in some people and to TSP/HAM in others. PMID:15310405

Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity.

PubMed

Azran, Inbal; Schavinsky-Khrapunsky, Yana; Aboud, Mordechai

2004-08-13

HTLV-1 is the etiological agent of adult T-cell leukemia (ATL), the neurological syndrome TSP/HAM and certain other clinical disorders. The viral Tax protein is considered to play a central role in the process leading to ATL. Tax modulates the expression of many viral and cellular genes through the CREB/ATF-, SRF- and NF-kappaB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process. Together, these capacities render Tax highly oncogenic as reflected by its ability to transform rodent fibroblasts and primary human T-cells and to induce tumors in transgenic mice. In this article we discuss these effects of Tax and their apparent contribution to the HTLV-1 associated leukemogenic process. Notably, however, shortly after infection the virus enters into a latent state, in which viral gene expression is low in most of the HTLV-1 carriers' infected T-cells and so is the level of Tax protein, although rare infected cells may still display high viral RNA. This low Tax level is evidently insufficient for exerting its multiple oncogenic effects. Therefore, we propose that the latent virus must be activated, at least temporarily, in order to elevate Tax to its effective level and that during this transient activation state the infected cells may acquire some oncogenic mutations which can enable them to further progress towards ATL even if the activated virus is re-suppressed after a while. We conclude this review by outlining an hypothetical flow of events from the initial virus infection up to the ultimate ATL development and comment on the risk factors leading to ATL development in some people and to TSP/HAM in others.

Interictal scalp electroencephalography and intraoperative electrocorticography in magnetic resonance imaging-negative temporal lobe epilepsy surgery.

PubMed

Burkholder, David B; Sulc, Vlastimil; Hoffman, E Matthew; Cascino, Gregory D; Britton, Jeffrey W; So, Elson L; Marsh, W Richard; Meyer, Fredric B; Van Gompel, Jamie J; Giannini, Caterina; Wass, C Thomas; Watson, Robert E; Worrell, Gregory A

2014-06-01

Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging-negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging-negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging-negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (P = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (P = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging-negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy.

Heat exchanges in wet suits.

PubMed

Wolff, A H; Coleshaw, S R; Newstead, C G; Keatinge, W R

1985-03-01

Flow of water under foam neoprene wet suits could halve insulation that the suits provided, even at rest in cold water. On the trunk conductance of this flow was approximately 6.6 at rest and 11.4 W . m-2 . C-1 exercising; on the limbs, it was only 3.4 at rest and 5.8 W . m-2 . degrees C-1 exercising; but during vasoconstriction in the cold, skin temperatures on distal parts of limbs were lower than were those of the trunk, allowing adequate metabolic responses. In warm water, minor postural changes and movement made flow under suits much higher, approximately 60 on trunk and 30 W . m-2 . degrees C-1 on limbs, both at rest and at work. These changes in flow allowed for a wide range of water temperatures at which people could stabilize body temperature in any given suit, neither overheating when exercising nor cooling below 35 degrees C when still. Even thin people with 4- or 7- mm suits covering the whole body could stabilize their body temperatures in water near 10 degrees C in spite of cold vasodilatation. Equations to predict limits of water temperature for stability with various suits and fat thicknesses are given.

Impact of renal medullary three-dimensional architecture on oxygen transport.

PubMed

Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

2014-08-01

We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the high metabolic requirements of the thick limbs and raises NaCl reabsorption. Copyright © 2014 the American Physiological Society.

Results of a bone splint technique for the treatment of lower limb deformities in children with type I osteogenesis imperfecta

PubMed Central

Lin, Dasheng; Zhai, Wenliang; Lian, Kejian; Ding, Zhenqi

2013-01-01

Background: Children with osteogenesis imperfecta (OI) can suffer from frequent fractures and limb deformities, resulting in impaired ambulation. Osteopenia and thin cortices complicate orthopedic treatment in this group. This study evaluates the clinical results of a bone splint technique for the treatment of lower limb deformities in children with type I OI. The technique consists of internal plating combined with cortical strut allograft fixation. Materials and Methods: We prospectively followed nine children (five boys, four girls) with lower limb deformities due to type I OI, who had been treated with the bone splint technique (11 femurs, four tibias) between 2003 and 2006. The fracture healing time, deformity improvement, ambulation ability and complications were recorded to evaluate treatment effects. Results: At the time of surgery the average age in our study was 7.7 years (range 5-12 years). The average length of followup was 69 months (range 60-84 months). All patients had good fracture healing with an average healing time of 14 weeks (range 12-16 weeks) and none experienced further fractures, deformity, or nonunion. The fixation remained stable throughout the procedure in all cases, with no evidence of loosening or breakage of screws and the deformity and mobility significantly improved after surgery. Of the two children confined to bed before surgery, one was able to walk on crutches and the other needed a wheelchair. The other seven patients could walk without walking aids or support like crutches. Conclusions: These findings suggest that the bone splint technique provides good mechanical support and increases the bone mass. It is an effective treatment for children with OI and lower limb deformities. PMID:23960282

A combinaison of UV curing technology with ATL process

NASA Astrophysics Data System (ADS)

Balbzioui, I.; Hasiaoui, B.; Barbier, G.; L'hostis, G.; Laurent, F.; Ibrahim, A.; Durand, B.

2017-10-01

In order to reduce the time and the cost of manufacturing composite, UV curing technology combined with automated tape placement process (ATL) based on reverse approach by working with a fixed head was studied in this article. First, a brief description of the developed head placement is presented. Mechanical properties are then evaluated by varying process parameters, including compaction force and tape placement speed. Finally, a parametric study is carried out to identify suitable materials and process parameters to manufacture a photo composite material with high mechanical performances. The obtained results show that UV curing is a very good alternative for thermal polymerization because of its fast cure speed due to less dependency on temperature.

Use of Humanized RS-ATL8 Reporter System for Detection of Allergen-Specific IgE Sensitization in Human Food Allergy.

PubMed

Ali, Eman Ali; Nakamura, Ryosuke; Falcone, Franco H

2017-01-01

Allergen-specific Immunoglobulin E (IgE) determination lies at the heart of diagnosis of sensitization to food and other allergens. In the past few years, reporter systems capable of detecting the presence of allergen-specific IgE have been developed by several labs. These rely on humanized rat basophil leukemia cell lines stably transfected with reporter genes such as firefly luciferase. In this chapter, we describe protocols for the use of the RS-ATL8 cell line (IgE cross-linking-induced luciferase expression; EXiLE) in 96-well and 384-well formats. We also describe optional treatment steps for enveloped virus and complement inactivation.

Functional anatomy of gliding membrane muscles in the sugar glider (Petaurus breviceps).

PubMed

Endo, H; Yokokawa, K; Kurohmaru, M; Hayashi, Y

1998-02-01

In order to clarify the morphological adaptation for gliding behavior in the marsupial mammals, the gliding membrane muscles in the sugar glider (Petaurus breviceps) were observed. Unlike the styliform cartilage in flying squirrels, the sugar glider has a well-developed tibiocarpalis muscle in the most lateral area of the gliding membrane. The gliding membrane substantially consists of the humerodorsalis and tibioabdominalis muscle complex. We believe that the thick tibiocarpalis bundle and the humerodorsalis and tibioabdominalis muscle complex may serve as a membrane controller in the gliding behavior. A characteristic thin membranous structure between the cutaneous and deeper muscles was observed. In addition to the direct powerful control exerted by trunk and limb movement, we suggest that indirect power conduction by this thin membranous structure may contribute to gliding membrane control.

Open pneumothorax: the spectrum and outcome of management based on Advanced Trauma Life Support recommendations.

PubMed

Kong, V Y; Liu, M; Sartorius, B; Clarke, D L

2015-08-01

The current management of open pneumothorax (OPTX) is based on Advanced Trauma Life Support (ATLS) recommendations and consists of the application of a three-way occlusive dressing, followed by intercostal chest drain insertion. Very little is known regarding the spectrum and outcome of this approach, especially in the civilian setting. We conducted a retrospective review of 58 consecutive patients with OPTX over a four-year period managed in a high volume metropolitan trauma service in South Africa. Of the 58 patients included, 95% (55/58) were male, and the mean age for all patients was 21 years. Ninety-seven percent of all injuries were inflicted by knives and the remaining 3% (2/58) of injuries were inflicted by unknown weapons. 59% of injuries were left sided. In six patients (10%) a protocol violation was present in their management. Five of the six patients (83%) in whom protocol violation occurred developed a life-threatening event (tension PTX) compared to none amongst those where the protocol was followed (p < 0.001). There was no mortality as a direct result of management of OPTX following ATLS recommendations. ATLS recommendations for OPTX are safe and effective. Any deviation from this standard practice is associated with avoidable morbidity and potential mortality.

Experimental Infection of Lutzomyia (Nyssomyia) whitmani (Diptera: Psychodidae: Phlebotominae) With Leishmania (Viannia) braziliensis and Leishmania (L.) amazonensis, Etiological Agents of American Tugumentary Leishmaniasis.

PubMed

Fonteles, Raquel S; Pereira Filho, Adalberto A; Moraes, Jorge L P; Kuppinger, Oliver; Rebêlo, José M M

2016-01-01

Leishmania (L.) amazonensis (Lainson & Shaw, 1972) and Leishmania (Viannia) braziliensis (Vianna, 1911) are the principal causative agents of American tegumentary leishmaniasis (ATL) in Brazil. L. amazonensis also causes diffuse cutaneous leishmaniasis (DCL) vectored principally by Lutzomyia flaviscutellata and secondarily by Lutzomyia whitmani (Antunes & Coutinho, 1939). The latter is the most common phlebotomine in the state of Maranhão, and it is the focal species for potential ATL transmission. For this reason, we tested the ability of L. whitmani to become infected with Lutzomyia parasites. Phlebotomines were derived from a colony maintained in the laboratorial conditions. The first generation, uninfected females were offered a bloodmeal with mice infected with the strains of both parasites. We found that L. whitmani can become infected with both parasite species, with infection rates of 65.2% (L. braziliensis) and 47.4% (L. amazonensis). We conclude that in Maranhão, L. whitmani is likely an important vector in the transmission of ATL and may function as a vector of DCL. This possibility should be further investigated. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Induced seismicity closed-form traffic light system for actuarial decision-making during deep fluid injections.

PubMed

Mignan, A; Broccardo, M; Wiemer, S; Giardini, D

2017-10-19

The rise in the frequency of anthropogenic earthquakes due to deep fluid injections is posing serious economic, societal, and legal challenges to many geo-energy and waste-disposal projects. Existing tools to assess such problems are still inherently heuristic and mostly based on expert elicitation (so-called clinical judgment). We propose, as a complementary approach, an adaptive traffic light system (ATLS) that is function of a statistical model of induced seismicity. It offers an actuarial judgement of the risk, which is based on a mapping between earthquake magnitude and risk. Using data from six underground reservoir stimulation experiments, mostly from Enhanced Geothermal Systems, we illustrate how such a data-driven adaptive forecasting system could guarantee a risk-based safety target. The proposed model, which includes a linear relationship between seismicity rate and flow rate, as well as a normal diffusion process for post-injection, is first confirmed to be representative of the data. Being integrable, the model yields a closed-form ATLS solution that is both transparent and robust. Although simulations verify that the safety target is consistently ensured when the ATLS is applied, the model from which simulations are generated is validated on a limited dataset, hence still requiring further tests in additional fluid injection environments.

Aircrew fatigue in long-haul operations.

PubMed

Samel, A; Wegmann, H M; Vejvoda, M

1997-07-01

The studies were conducted on the transmeridian routes Düsseldorf (DUS)-Atlanta (ATL) and Hamburg (HAM)-Los Angeles (LAX), and on the north-south route Frankfurt (FRA)-Mahe (SEZ). Scheduled flight duration was between 8:50 hours (ATL-DUS) and 11:50 hours (HAM-LAX). In total, 25 rotations (50 flights) have been investigated by pre-, in- and post-flight data collection of sleep, taskload, fatigue and stress by electroencephalogram and electrocardiogram measurements and subjective ratings. Inflight ratings of taskload showed low perceived exertion during the Atlantic flights, and were moderate during the north-south transitions. Fatigue ratings increased with progressing flight duration. Towards the end of long U.S.-westcoast flights performed at day-time, and in all night flights, fatigue was elevated compared to the 'baseline' ratings collected during the day-time DUS-ATL flights. Fatigue was rated as being 'critical' by several pilots, particularly during the return flight SEZ-FRA when fatigue was severely pronounced. From the findings it is concluded that duty schedules, as performed on the route HAM-LAX (because of long duty hours), and particularly on the route FRA-SEZ (because of consecutive night work), may place excessive demands on mental and physiological capacity. With respect to legal aspects, the results are significant and should promote further deliberations for advanced schemes of flight duty time limitations and rest requirements.

Direct association of thioredoxin-1 (TRX) with macrophage migration inhibitory factor (MIF): regulatory role of TRX on MIF internalization and signaling.

PubMed

Son, Aoi; Kato, Noriko; Horibe, Tomohisa; Matsuo, Yoshiyuki; Mochizuki, Michika; Mitsui, Akira; Kawakami, Koji; Nakamura, Hajime; Yodoi, Junji

2009-10-01

Thioredoxin-1 (TRX) is a small (14 kDa) multifunctional protein with the redox-active site Cys-Gly-Pro-Cys. Macrophage migration inhibitory factor (MIF) is a 12 kDa cytokine belonging to the TRX family. Historically, when we purified TRX from the supernatant of ATL-2 cells, a 12 kDa protein was identified along with TRX, which was later proved to be MIF. Here, we show that TRX and MIF form a complex in the cell and the culture supernatant of ATL-2 cells. Using a BIAcore assay, we confirmed that TRX has a specific affinity with MIF. We also found that extracellular MIF was more effectively internalized into the ATL-2 cells expressing TRX on the cell surface, than the Jurkat T cells which do not express surface TRX. Moreover, anti-TRX antibody blocked the MIF internalization, suggesting that the cell surface TRX is involved in MIF internalization into the cells. Furthermore, anti-TRX antibody inhibited MIF-mediated enhancement of TNF-alpha production from macrophage RAW264.7 cells. These results suggest that the cell surface TRX serves as one of the MIF binding molecules or MIF receptor component and inhibits MIF-mediated inflammatory signals.

The discovery of HTLV-1, the first pathogenic human retrovirus.

PubMed

Coffin, John M

2015-12-22

After the discovery of retroviral reverse transcriptase in 1970, there was a flurry of activity, sparked by the "War on Cancer," to identify human cancer retroviruses. After many false claims resulting from various artifacts, most scientists abandoned the search, but the Gallo laboratory carried on, developing both specific assays and new cell culture methods that enabled them to report, in the accompanying 1980 PNAS paper, identification and partial characterization of human T-cell leukemia virus (HTLV; now known as HTLV-1) produced by a T-cell line from a lymphoma patient. Follow-up studies, including collaboration with the group that first identified a cluster of adult T-cell leukemia (ATL) cases in Japan, provided conclusive evidence that HTLV was the cause of this disease. HTLV-1 is now known to infect at least 4-10 million people worldwide, about 5% of whom will develop ATL. Despite intensive research, knowledge of the viral etiology has not led to improvement in treatment or outcome of ATL. However, the technology for discovery of HTLV and acknowledgment of the existence of pathogenic human retroviruses laid the technical and intellectual foundation for the discovery of the cause of AIDS soon afterward. Without this advance, our ability to diagnose and treat HIV infection most likely would have been long delayed.

Selective Attention to Semantic and Syntactic Features Modulates Sentence Processing Networks in Anterior Temporal Cortex

PubMed Central

Rogalsky, Corianne

2009-01-01

Numerous studies have identified an anterior temporal lobe (ATL) region that responds preferentially to sentence-level stimuli. It is unclear, however, whether this activity reflects a response to syntactic computations or some form of semantic integration. This distinction is difficult to investigate with the stimulus manipulations and anomaly detection paradigms traditionally implemented. The present functional magnetic resonance imaging study addresses this question via a selective attention paradigm. Subjects monitored for occasional semantic anomalies or occasional syntactic errors, thus directing their attention to semantic integration, or syntactic properties of the sentences. The hemodynamic response in the sentence-selective ATL region (defined with a localizer scan) was examined during anomaly/error-free sentences only, to avoid confounds due to error detection. The majority of the sentence-specific region of interest was equally modulated by attention to syntactic or compositional semantic features, whereas a smaller subregion was only modulated by the semantic task. We suggest that the sentence-specific ATL region is sensitive to both syntactic and integrative semantic functions during sentence processing, with a smaller portion of this area preferentially involved in the later. This study also suggests that selective attention paradigms may be effective tools to investigate the functional diversity of networks involved in sentence processing. PMID:18669589

What's Unique about Unique Entities? An fMRI Investigation of the Semantics of Famous Faces and Landmarks

PubMed Central

Olson, Ingrid R.

2012-01-01

Famous people and artifacts are referred to as “unique entities” (UEs) due to the unique nature of the knowledge we have about them. Past imaging and lesion experiments have indicated that the anterior temporal lobes (ATLs) as having a special role in the processing of UEs. It has remained unclear which attributes of UEs were responsible for the observed effects in imaging experiments. In this study, we investigated what factors of UEs influence brain activity. In a training paradigm, we systematically varied the uniqueness of semantic associations, the presence/absence of a proper name, and the number of semantic associations to determine factors modulating activity in regions subserving the processing of UEs. We found that a conjunction of unique semantic information and proper names modulated activity within a section of the left ATL. Overall, the processing of UEs involved a wider left-hemispheric cortical network. Within these regions, brain activity was significantly affected by the unique semantic attributes especially in the presence of a proper name, but we could not find evidence for an effect of the number of semantic associations. Findings are discussed in regard to current models of ATL function, the neurophysiology of semantics, and social cognitive processing. PMID:22021913

Detection of adult T-cell leukemia virus (ATLV) bearing lymphocytes in concentrated red blood cells derived from ATL associated antibody (ATLA-Ab) positive donors.

PubMed

Morishima, Y; Ohya, K; Ueda, R; Fukuda, T

1986-01-01

Adult T cell leukemia associated antibody (ATLA-Ab) positive persons were screened by indirect immunofluorescence (IF) testing. Their lymphocytes were collected from concentrated red blood cells (CRC), and cultured in vitro with and without phytohemagglutinin (PHA) for 10 days. The expression of ATL virus (ATLV) positive lymphocytes during the in vitro culture was then analyzed by IF assay using mouse monoclonal antibody ATL-19 reactive to p19 core protein of ATLV. 97% of ATLA-Ab positive CRC (36 cases) demonstrated ATLV positive lymphocytes after being cultured for more than 10 days with PHA, whereas, none of ATLA-Ab negative CRC (22 cases) demonstrated ATLV positive lymphocytes. All of the 10 ATLA-Ab positive CRC that were stored for 2, 4, and 7 days contained lymphocytes which expressed ATLV after in vitro culture, while 7 of 10 CRC stored for 14 days and only 1 of 10 CRCs stored for 20 days, expressed ATLV positive lymphocytes. This data indicates that almost all of the ATLA-Ab positive blood contained ATLV positive lymphocytes, and that the in vitro appearance of these ATLV positive lymphocytes was reduced by storing the CRC for more than 14 days.

Passive Wearable Skin Patch Sensor Measures Limb Hemodynamics Based on Electromagnetic Resonance.

PubMed

Cluff, Kim; Becker, Ryan; Jayakumar, Balakumar; Han, Kiyun; Condon, Ernie; Dudley, Kenneth; Szatkowski, George; Pipinos, Iraklis I; Amick, Ryan Z; Patterson, Jeremy

2018-04-01

The objectives of this study were to design and develop an open-circuit electromagnetic resonant skin patch sensor, characterize the fluid volume and resonant frequency relationship, and investigate the sensor's ability to measure limb hemodynamics and pulse volume waveform features. The skin patch was designed from an open-circuit electromagnetic resonant sensor comprised of a single baseline trace of copper configured into a square planar spiral which had a self-resonating response when excited by an external radio frequency sweep. Using a human arm phantom with a realistic vascular network, the sensor's performance to measure limb hemodynamics was evaluated. The sensor was able to measure pulsatile blood flow which registered as shifts in the sensor's resonant frequencies. The time-varying waveform pattern of the resonant frequency displayed a systolic upstroke, a systolic peak, a dicrotic notch, and a diastolic down stroke. The resonant frequency waveform features and peak systolic time were validated against ultrasound pulse wave Doppler. A statistical correlation analysis revealed a strong correlation () between the resonant sensor peak systolic time and the pulse wave Doppler peak systolic time. The sensor was able to detect pulsatile flow, identify hemodynamic waveform features, and measure heart rate with 98% accuracy. The open-circuit resonant sensor design leverages the architecture of a thin planar spiral which is passive (does not require batteries), robust and lightweight (does not have electrical components or electrical connections), and may be able to wirelessly monitor cardiovascular health and limb hemodynamics.

Active Immunization with an Octa-Valent Staphylococcus aureus Antigen Mixture in Models of S. aureus Bacteremia and Skin Infection in Mice

PubMed Central

van den Berg, Sanne; Koedijk, Dennis G. A. M.; Back, Jaap Willem; Neef, Jolanda; Dreisbach, Annette; van Dijl, Jan Maarten; Bakker-Woudenberg, Irma A. J. M.; Buist, Girbe

2015-01-01

Proteomic studies with different Staphylococcus aureus isolates have shown that the cell surface-exposed and secreted proteins IsaA, LytM, Nuc, the propeptide of Atl (pro-Atl) and four phenol-soluble modulins α (PSMα) are invariantly produced by this pathogen. Therefore the present study was aimed at investigating whether these proteins can be used for active immunization against S. aureus infection in mouse models of bacteremia and skin infection. To this end, recombinant His-tagged fusions of IsaA, LytM, Nuc and pro-Atl were isolated from Lactococcus lactis or Escherichia coli, while the PSMα1-4 peptides were chemically synthesized. Importantly, patients colonized by S. aureus showed significant immunoglobulin G (IgG) responses against all eight antigens. BALB/cBYJ mice were immunized subcutaneously with a mixture of the antigens at day one (5 μg each), and boosted twice (25 μg of each antigen) with 28 days interval. This resulted in high IgG responses against all antigens although the response against pro-Atl was around one log lower compared to the other antigens. Compared to placebo-immunized mice, immunization with the octa-valent antigen mixture did not reduce the S. aureus isolate P load in blood, lungs, spleen, liver, and kidneys in a bacteremia model in which the animals were challenged for 14 days with a primary load of 3 × 105 CFU. Discomfort scores and animal survival rates over 14 days did not differ between immunized mice and placebo-immunized mice upon bacteremia with S. aureus USA300 (6 × 105 CFU). In addition, this immunization did not reduce the S. aureus isolate P load in mice with skin infection. These results show that the target antigens are immunogenic in both humans and mice, but in the used animal models do not result in protection against S. aureus infection. PMID:25710376

Segregation of anterior temporal regions critical for retrieving names of unique and non-unique entities reflects underlying long-range connectivity.

PubMed

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2016-02-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category-specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus (UNC) was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus (ILF) was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

PubMed Central

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections. PMID:22768285

Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

PubMed

Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

2012-01-01

Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for Aaa in the pathogenesis of S. aureus infections.

Presurgery resting-state local graph-theory measures predict neurocognitive outcomes after brain surgery in temporal lobe epilepsy.

PubMed

Doucet, Gaelle E; Rider, Robert; Taylor, Nathan; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael; Tracy, Joseph I

2015-04-01

This study determined the ability of resting-state functional connectivity (rsFC) graph-theory measures to predict neurocognitive status postsurgery in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL). A presurgical resting-state functional magnetic resonance imaging (fMRI) condition was collected in 16 left and 16 right TLE patients who underwent ATL. In addition, patients received neuropsychological testing pre- and postsurgery in verbal and nonverbal episodic memory, language, working memory, and attention domains. Regarding the functional data, we investigated three graph-theory properties (local efficiency, distance, and participation), measuring segregation, integration and centrality, respectively. These measures were only computed in regions of functional relevance to the ictal pathology, or the cognitive domain. Linear regression analyses were computed to predict the change in each neurocognitive domain. Our analyses revealed that cognitive outcome was successfully predicted with at least 68% of the variance explained in each model, for both TLE groups. The only model not significantly predictive involved nonverbal episodic memory outcome in right TLE. Measures involving the healthy hippocampus were the most common among the predictors, suggesting that enhanced integration of this structure with the rest of the brain may improve cognitive outcomes. Regardless of TLE group, left inferior frontal regions were the best predictors of language outcome. Working memory outcome was predicted mostly by right-sided regions, in both groups. Overall, the results indicated our integration measure was the most predictive of neurocognitive outcome. In contrast, our segregation measure was the least predictive. This study provides evidence that presurgery rsFC measures may help determine neurocognitive outcomes following ATL. The results have implications for refining our understanding of compensatory reorganization and predicting cognitive outcome after ATL. The results are encouraging with regard to the clinical relevance of using graph-theory measures in presurgical algorithms in the setting of TLE. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Famous face identification in temporal lobe epilepsy: Support for a multimodal integration model of semantic memory

PubMed Central

Drane, Daniel L.; Ojemann, Jeffrey G.; Phatak, Vaishali; Loring, David W.; Gross, Robert E.; Hebb, Adam O.; Silbergeld, Daniel L.; Miller, John W.; Voets, Natalie L.; Saindane, Amit M.; Barsalou, Lawrence; Meador, Kimford J.; Ojemann, George A.; Tranel, Daniel

2012-01-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre-and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. PMID:23040175

Selectivity of recombinant human leukotriene D(4), leukotriene B(4), and lipoxin A(4) receptors with aspirin-triggered 15-epi-LXA(4) and regulation of vascular and inflammatory responses.

PubMed

Gronert, K; Martinsson-Niskanen, T; Ravasi, S; Chiang, N; Serhan, C N

2001-01-01

Aspirin-triggered lipoxin A(4) (ATL, 15-epi-LXA(4)) and leukotriene D(4) (LTD(4)) possess opposing vascular actions mediated via receptors distinct from the LXA(4) receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD(4) receptor (CysLT(1)) is induced in human vascular endothelia by interleukin-1beta. Recombinant CysLT(1) receptor gave stereospecific binding with both [(3)H]-LTD(4) and a novel labeled mimetic of ATL ([(3)H]-ATLa) that was displaced with LTD(4) and ATLa ( approximately IC(50) 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT(1) receptor antagonist, Singulair, showed a lower rank order for competition with [(3)H]-ATLa (IC(50) approximately 8.3 nmol/L). In contrast, LTD(4) was an ineffective competitive ligand for recombinant ALX receptor with [(3)H]-ATLa, and ATLa did not compete for [(3)H]-LTB(4) binding with recombinant LTB(4) receptor. Endogenous murine CysLT(1) receptors also gave specific [(3)H]-ATLa binding that was displaced with essentially equal affinity by LTD(4) or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT(1)-mediated vascular leakage in murine skin (200 microg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 microg/kg). These results indicate that ATL and LTD(4) bind and compete with equal affinity at CysLT(1), providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT(1) signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.

Famous face identification in temporal lobe epilepsy: support for a multimodal integration model of semantic memory.

PubMed

Drane, Daniel L; Ojemann, Jeffrey G; Phatak, Vaishali; Loring, David W; Gross, Robert E; Hebb, Adam O; Silbergeld, Daniel L; Miller, John W; Voets, Natalie L; Saindane, Amit M; Barsalou, Lawrence; Meador, Kimford J; Ojemann, George A; Tranel, Daniel

2013-06-01

This study aims to demonstrate that the left and right anterior temporal lobes (ATLs) perform critical but unique roles in famous face identification, with damage to either leading to differing deficit patterns reflecting decreased access to lexical or semantic concepts but not their degradation. Famous face identification was studied in 22 presurgical and 14 postsurgical temporal lobe epilepsy (TLE) patients and 20 healthy comparison subjects using free recall and multiple choice (MC) paradigms. Right TLE patients exhibited presurgical deficits in famous face recognition, and postsurgical deficits in both famous face recognition and familiarity judgments. However, they did not exhibit any problems with naming before or after surgery. In contrast, left TLE patients demonstrated both pre- and postsurgical deficits in famous face naming but no significant deficits in recognition or familiarity. Double dissociations in performance between groups were alleviated by altering task demands. Postsurgical right TLE patients provided with MC options correctly identified greater than 70% of famous faces they initially rated as unfamiliar. Left TLE patients accurately chose the name for nearly all famous faces they recognized (based on their verbal description) but initially failed to name, although they tended to rapidly lose access to this name. We believe alterations in task demands activate alternative routes to semantic and lexical networks, demonstrating that unique pathways to such stored information exist, and suggesting a different role for each ATL in identifying visually presented famous faces. The right ATL appears to play a fundamental role in accessing semantic information from a visual route, with the left ATL serving to link semantic information to the language system to produce a specific name. These findings challenge several assumptions underlying amodal models of semantic memory, and provide support for the integrated multimodal theories of semantic memory and a distributed representation of concepts. Copyright © 2012 Elsevier Ltd. All rights reserved.

Interictal Scalp Electroencephalography and Intraoperative Electrocorticography in Magnetic Resonance Imaging–Negative Temporal Lobe Epilepsy Surgery

PubMed Central

Burkholder, David B.; Sulc, Vlastimil; Hoffman, E. Matthew; Cascino, Gregory D.; Britton, Jeffrey W.; So, Elson L.; Marsh, W. Richard; Meyer, Fredric B.; Van Gompel, Jamie J.; Giannini, Caterina; Wass, C. Thomas; Watson, Robert E.; Worrell, Gregory A.

2014-01-01

IMPORTANCE Scalp electroencephalography (EEG) and intraoperative electrocorticography (ECoG) are routinely used in the evaluation of magnetic resonance imaging–negative temporal lobe epilepsy (TLE) undergoing standard anterior temporal lobectomy with amygdalohippocampectomy (ATL), but the utility of interictal epileptiform discharge (IED) identification and its role in outcome are poorly defined. OBJECTIVES To determine whether the following are associated with surgical outcomes in patients with magnetic resonance imaging–negative TLE who underwent standard ATL: (1) unilateral-only IEDs on preoperative scalp EEG; (2) complete resection of tissue generating IEDs on ECoG; (3) complete resection of opioid-induced IEDs recorded on ECoG; and (4) location of IEDs recorded on ECoG. DESIGN, SETTING, AND PARTICIPANTS Data were gathered through retrospective medical record review at a tertiary referral center. Adult and pediatric patients with TLE who underwent standard ATL between January 1, 1990, and October 15, 2010, were considered for inclusion. Inclusion criteria were magnetic resonance imaging–negative TLE, standard ECoG performed at the time of surgery, and a minimum follow-up of 12 months. Univariate analysis was performed using log-rank time-to-event analysis. Variables reaching significance with log-rank testing were further analyzed using Cox proportional hazards. MAIN OUTCOMES AND MEASURES Excellent or nonexcellent outcome at time of last follow-up. An excellent outcome was defined as Engel class I and a nonexcellent outcome as Engel classes II through IV. RESULTS Eighty-seven patients met inclusion criteria, with 48 (55%) achieving an excellent outcome following ATL. Unilateral IEDs on scalp EEG (P = .001) and complete resection of brain regions generating IEDs on baseline intraoperative ECoG (P = .02) were associated with excellent outcomes in univariate analysis. Both were associated with excellent outcomes when analyzed with Cox proportional hazards (unilateral-only IEDs, relative risk = 0.31 [95% CI, 0.16-0.64]; complete resection of IEDs on baseline ECoG, relative risk = 0.39 [95% CI, 0.20-0.76]). Overall, 25 of 35 patients (71%) with both unilateral-only IEDs and complete resection of baseline ECoG IEDs had an excellent outcome. CONCLUSIONS AND RELEVANCE Unilateral-only IEDs on preoperative scalp EEG and complete resection of IEDs on baseline ECoG are associated with better outcomes following standard ATL in magnetic resonance imaging–negative TLE. Prospective evaluation is needed to clarify the use of ECoG in tailoring temporal lobectomy. PMID:24781216

Colocalization of insulin-like growth factor-binding protein with insulin-like growth factor I.

PubMed

Kobayashi, S; Clemmons, D R; Venkatachalam, M A

1991-07-01

We report the localization of insulin-like growth factor I (IGF-I) and a 25-kDa form of insulin-like growth factor-binding protein (IGF-BP-1) in adult rat kidney. The antigens were localized using a rabbit anti-human IGF-I antibody, and a rabbit anti-human IGF-BP-1 antibody raised against human 25-kDa IGF-BP-1 purified from amniotic fluid. Immunohistochemistry by the avidin-biotin peroxidase conjugate technique showed that both peptides are located in the same nephron segments, in the same cell types. The most intense staining was in papillary collecting ducts. There was moderate staining also in cortical collecting ducts and medullary thick ascending limbs of Henle's loop. In collecting ducts the antigens were shown to be present in principal cells but not in intercalated cells. In distal convoluted tubules, cortical thick ascending limbs, and in structures presumptively identified as thin limbs of Henle's loops there was only modest staining. The macula densa, however, lacked immunoreactivity. Colocalization of IGF-I and IGF-BP-1 in the same cells supports the notion, derived from studies on cultured cells, that the actions of IGF-I may be modified by IGF-BPs that are present in the same location.

Post-Flare Giant Arches - Unanswered Questions

NASA Astrophysics Data System (ADS)

West, M. J.; Seaton, D. B.; Dennis, B. R.; Palmerio, E.; Savage, S. L.

2017-12-01

Recent observations from the SWAP EUV imager on-board PROBA2 and SXI X-ray observations from the GOES satellite have shown that post-flare giant arches and regular post-flare loops are one and the same thing. However, it is still not clear how certain loop systems are able to sustain prolonged growth to heights greater than half a solar-radii. In this presentation we further explore the energy deposition rate above post-flare loop systems through high-energy RHESSI observations. We also explore the difference between the growth of different loop systems through an epoch analysis. The epoch analysis is initially performed over the period when the STEREO satellites were in quadrature with PROBA2 allowing us to assess the difference between their on-disk and on-limb signatures. Giant arches are generally characterised by their height of growth when observed close to the solar limb, but due to the optically thin nature of the EUV solar atmosphere, projection effects and the scarcity of events occurring within 5 degrees of the limb it is not understood how common these events are. Using the analysis during the quadrature period we gain a better understanding of how rare these events are, and by determining characteristic on disk signatures we can combine our data set with magnetogram observations to better understand their magnetic evolution.

A Posteriori Comparison of Natural and Surgical Destabilization Models of Canine Osteoarthritis

PubMed Central

Pelletier, Jean-Pierre; d'Anjou, Marc-André; Blond, Laurent; Pelletier, Johanne-Martel; del Castillo, Jérôme R. E.

2013-01-01

For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA). Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought. PMID:24288664

The human T-cell leukemia virus type-1 p30II protein activates p53 and induces the TIGAR and suppresses oncogene-induced oxidative stress during viral carcinogenesis.

PubMed

Romeo, Megan; Hutchison, Tetiana; Malu, Aditi; White, Averi; Kim, Janice; Gardner, Rachel; Smith, Katie; Nelson, Katherine; Bergeson, Rachel; McKee, Ryan; Harrod, Carolyn; Ratner, Lee; Lüscher, Bernhard; Martinez, Ernest; Harrod, Robert

2018-05-01

In normal cells, aberrant oncogene expression leads to the accumulation of cytotoxic metabolites, including reactive oxygen species (ROS), which can cause oxidative DNA-damage and apoptosis as an intrinsic barrier against neoplastic disease. The c-Myc oncoprotein is overexpressed in many lymphoid cancers due to c-myc gene amplification and/or 8q24 chromosomal translocations. Intriguingly, p53 is a downstream target of c-Myc and hematological malignancies, such as adult T-cell leukemia/lymphoma (ATL), frequently contain wildtype p53 and c-Myc overexpression. We therefore hypothesized that p53-regulated pro-survival signals may thwart the cell's metabolic anticancer defenses to support oncogene-activation in lymphoid cancers. Here we show that the Tp53-induced glycolysis and apoptosis regulator (TIGAR) promotes c-myc oncogene-activation by the human T-cell leukemia virus type-1 (HTLV-1) latency-maintenance factor p30 II , associated with c-Myc deregulation in ATL clinical isolates. TIGAR prevents the intracellular accumulation of c-Myc-induced ROS and inhibits oncogene-induced cellular senescence in ATL, acute lymphoblastic leukemia, and multiple myeloma cells with elevated c-Myc expression. Our results allude to a pivotal role for p53-regulated antioxidant signals as mediators of c-Myc oncogenic functions in viral and non-viral lymphoid tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Developmental and sex-specific differences in expression of neuropeptides derived from allatotropin gene in the silkmoth Bombyx mori.

PubMed

Bednár, Branislav; Roller, Ladislav; Čižmár, Daniel; Mitrová, Diana; Žitňan, Dušan

2017-05-01

Allatotropin (AT) and related neuropeptides are widespread bioactive molecules that regulate development, food intake and muscle contractions in insects and other invertebrates. In moths, alternative splicing of the at gene generates three mRNA precursors encoding AT with different combinations of three structurally similar AT-like peptides (ATLI-III). We used in situ hybridization and immunohistochemistry to map the differential expression of these transcripts during the postembryonic development of Bombyx mori. Transcript encoding AT alone was expressed in numerous neurons of the central nervous system and frontal ganglion, whereas transcripts encoding AT with ATLs were produced by smaller specific subgroups of neurons in larval stages. Metamorphosis was associated with considerable developmental changes and sex-specific differences in the expression of all transcripts. The most notable was the appearance of AT/ATL transcripts (1) in the brain lateral neurosecretory cells producing prothoracicotropic hormone; (2) in the male-specific cluster of about 20 neurons in the posterior region of the terminal abdominal ganglion; (3) in the female-specific medial neurons in the abdominal ganglia AG2-7. Immunohistochemical staining showed that these neurons produced a mixture of various neuropeptides and innervated diverse peripheral organs. Our data suggest that AT/ATL neuropeptides are involved in multiple stage- and sex-specific functions during the development of B. mori.

Proximal dup(10q): Case report and literature review

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

Barritt, J.A.; Teague, K.E.; Bodurtha, J.N.

We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISHmore » with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.« less

The evolution of vertical climbing in primates: evidence from reaction forces.

PubMed

Hanna, Jandy B; Granatosky, Michael C; Rana, Pooja; Schmitt, Daniel

2017-09-01

Vertical climbing is an essential behavior for arboreal animals, yet limb mechanics during climbing are poorly understood and rarely compared with those observed during horizontal walking. Primates commonly engage in both arboreal walking and vertical climbing, and this makes them an ideal taxa in which to compare these locomotor forms. Additionally, primates exhibit unusual limb mechanics compared with most other quadrupeds, with weight distribution biased towards the hindlimbs, a pattern that is argued to have evolved in response to the challenges of arboreal walking. Here we test an alternative hypothesis that functional differentiation between the limbs evolved initially as a response to climbing. Eight primate species were recorded locomoting on instrumented vertical and horizontal simulated arboreal runways. Forces along the axis of, and normal to, the support were recorded. During walking, all primates displayed forelimbs that were net braking, and hindlimbs that were net propulsive. In contrast, both limbs served a propulsive role during climbing. In all species, except the lorisids, the hindlimbs produced greater propulsive forces than the forelimbs during climbing. During climbing, the hindlimbs tends to support compressive loads, while the forelimb forces tend to be primarily tensile. This functional disparity appears to be body-size dependent. The tensile loading of the forelimbs versus the compressive loading of the hindlimbs observed during climbing may have important evolutionary implications for primates, and it may be the case that hindlimb-biased weight support exhibited during quadrupedal walking in primates may be derived from their basal condition of climbing thin branches. © 2017. Published by The Company of Biologists Ltd.

Evidence of a significant rotational non-LTE effect in the CO2 4.3 µm PFS-MEX limb spectra

NASA Astrophysics Data System (ADS)

Kutepov, Alexander A.; Rezac, Ladislav; Feofilov, Artem G.

2017-01-01

Since January 2004, the planetary Fourier spectrometer (PFS) on board the Mars Express satellite has been recording near-infrared limb spectra of high quality up to the tangent altitudes ≈ 150 km, with potential information on density and thermal structure of the upper Martian atmosphere. We present first results of our modeling of the PFS short wavelength channel (SWC) daytime limb spectra for the altitude region above 90 km. We applied a ro-vibrational non-LTE model based on the stellar astrophysics technique of accelerated lambda iteration (ALI) to solve the multi-species and multi-level CO2 problem in the Martian atmosphere. We show that the long-standing discrepancy between observed and calculated spectra in the cores and wings of 4.3 µm region is explained by the non-thermal rotational distribution of molecules in the upper vibrational states 10011 and 10012 of the CO2 main isotope second hot (SH) bands above 90 km altitude. The redistribution of SH band intensities from band branch cores into their wings is caused (a) by intensive production of the CO2 molecules in rotational states with j > 30 due to the absorption of solar radiation in optically thin wings of 2.7 µm bands and (b) by a short radiative lifetime of excited molecules, which is insufficient at altitudes above 90 km for collisions to maintain rotation of excited molecules thermalized. Implications for developing operational algorithms for massive processing of PFS and other instrument limb observations are discussed.

[Outcome of patients with relapsed/refractory adult T-cell leukemia-lymphoma after salvage therapy].

PubMed

Taniguchi, Hiroaki; Imaizumi, Yoshitaka; Makiyama, Junya; Itonaga, Hidehiro; Ando, Koji; Sawayama, Yasushi; Imanishi, Daisuke; Taguchi, Jun; Tsushima, Hideki; Hata, Tomoko; Hasegawa, Hiroo; Hayashi, Tomayoshi; Niino, Daisuke; Ohshima, Koichi; Tsukasaki, Kunihiro; Miyazaki, Yasushi

2013-12-01

We retrospectively analyzed 81 relapsed or refractory adult T-cell leukemia-lymphoma (ATL) patients who received salvage therapy in our institution between 2000 and 2010. These patients had received chemotherapy, radiation, or hematopoietic stem cell transplantation (HSCT) as an initial treatment, and were then given chemotherapy, radiation, HSCT, or donor lymphocyte infusion (DLI) as salvage therapy. Median survival time was 3.9 months. Of 5 long-term survivors, who survived more than 2 years after the first salvage therapy, 4 patients received HSCT or DLI, and the other was given mogamulizumab as the salvage therapy. For patients with relapsed or refractory ATL, HSCT/DLI is a promising treatment for achieving long-term survival. Mogamulizumab may be the good choice for those who are ineligible for HSCT.

FMRI Is a Valid Noninvasive Alternative to Wada Testing

PubMed Central

Binder, Jeffrey R.

2010-01-01

Partial removal of the anterior temporal lobe (ATL) is a highly effective surgical treatment for intractable temporal lobe epilepsy, yet roughly half of patients who undergo left ATL resection show decline in language or verbal memory function postoperatively. Two recent studies demonstrate that preoperative fMRI can predict postoperative naming and verbal memory changes in such patients. Most importantly, fMRI significantly improves the accuracy of prediction relative to other noninvasive measures used alone. Addition of language and memory lateralization data from the intracarotid amobarbital (Wada) test did not improve prediction accuracy in these studies. Thus, fMRI provides patients and practitioners with a safe, non-invasive, and well-validated tool for making better-informed decisions regarding elective surgery based on a quantitative assessment of cognitive risk. PMID:20850386

Early and late fracture following extensive limb lengthening in patients with achondroplasia and hypochondroplasia.

PubMed

Kitoh, H; Mishima, K; Matsushita, M; Nishida, Y; Ishiguro, N

2014-09-01

Two types of fracture, early and late, have been reported following limb lengthening in patients with achondroplasia (ACH) and hypochondroplasia (HCH). We reviewed 25 patients with these conditions who underwent 72 segmental limb lengthening procedures involving the femur and/or tibia, between 2003 and 2011. Gender, age at surgery, lengthened segment, body mass index, the shape of the callus, the amount and percentage of lengthening and the healing index were evaluated to determine predictive factors for the occurrence of early (within three weeks after removal of the fixation pins) and late fracture (> three weeks after removal of the pins). The Mann‑Whitney U test and Pearson's chi-squared test for univariate analysis and stepwise regression model for multivariate analysis were used to identify the predictive factor for each fracture. Only one patient (two tibiae) was excluded from the analysis due to excessively slow formation of the regenerate, which required supplementary measures. A total of 24 patients with 70 limbs were included in the study. There were 11 early fractures in eight patients. The shape of the callus (lateral or central callus) was the only statistical variable related to the occurrence of early fracture in univariate and multivariate analyses. Late fracture was observed in six limbs and the mean time between removal of the fixation pins and fracture was 18.3 weeks (3.3 to 38.4). Lengthening of the tibia, larger healing index, and lateral or central callus were related to the occurrence of a late fracture in univariate analysis. A multivariate analysis demonstrated that the shape of the callus was the strongest predictor for late fracture (odds ratio: 19.3, 95% confidence interval: 2.91 to 128). Lateral or central callus had a significantly larger risk of fracture than fusiform, cylindrical, or concave callus. Radiological monitoring of the shape of the callus during distraction is important to prevent early and late fracture of lengthened limbs in patients with ACH or HCH. In patients with thin callus formation, some measures to stimulate bone formation should be considered as early as possible. ©2014 The British Editorial Society of Bone & Joint Surgery.

Interferon-α (IFN-α) suppresses HTLV-1 gene expression and cell cycling, while IFN-α combined with zidovudin induces p53 signaling and apoptosis in HTLV-1-infected cells

PubMed Central

2013-01-01

Background Human T-cell leukemia virus type-1 (HTLV-1) is the causative retrovirus of adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 gene expression is maintained at low levels in vivo by unknown mechanisms. A combination therapy of interferon-α (IFN-α) and zidovudin (AZT) shows therapeutic effects in ATL patients, although its mechanism is also obscure. We previously found that viral gene expression in IL-2-dependent HTLV-1-infected T-cells (ILTs) derived from ATL patients was markedly suppressed by stromal cells through a type I IFN response. Here, we investigated the effects of IFN-α with or without AZT on viral gene expression and cell growth in ILTs. Results ILTs expressed variable but lower amounts of HTLV-1 Tax protein than HTLV-1-transformed HUT102 cells. Following the addition of IFN-α, the amounts of HTLV-1 p19 in the supernatants of these cells decreased in three days, while HTLV-1 gene expression decreased only in ILTs but not HUT102 cells. IFN-α also suppressed the spontaneous HTLV-1 induction in primary ATL cells cultured for 24 h. A time course study using ILTs revealed that the levels of intracellular Tax proteins decreased in the first 24 h after addition of IFN-α, before the reduction in HTLV-1 mRNA levels. The initial decreases of Tax protein following IFN-α treatment were observed in 6 of 7 ILT lines tested, although the reduction rates varied among ILT lines. An RNA-dependent protein kinase (PKR)-inhibitor reversed IFN-mediated suppression of Tax in ILTs. IFN-α also induced cell cycle arrest at the G0/G1 phase and suppressed NF-κB activities in these cells. AZT alone did not affect HTLV-1 gene expression, cell viability or NF-κB activities. AZT combined with IFN-α markedly induced cell apoptosis associated with phosphorylation of p53 and induction of p53-responsive genes in ILTs. Conclusions IFN-α suppressed HTLV-1 gene expression at least through a PKR-mediated mechanism, and also induced cell cycle arrest in ILTs. In combination with AZT, IFN-α further induced p53 signaling and cell apoptosis in these cells. These findings suggest that HTLV-1-infected cells at an IL-2-dependent stage retain susceptibility to type I IFN-mediated regulation of viral expression, and partly explain how AZT/IFN-α produces therapeutic effects in ATL. PMID:23688327

The HTLV-1 basic leucine zipper factor (HBZ) attenuates repair of double-stranded DNA breaks via non-homologous end joining (NHEJ).

PubMed

Rushing, A W; Hoang, K; Polakowski, N; Lemasson, I

2018-05-16

Adult T-cell leukemia (ATL) is a fatal malignancy of CD4 + T-cells infected with human T-cell leukemia virus type I (HTLV-1). ATL cells often exhibit random gross chromosomal rearrangements that are associated with the induction and improper repair of double-stranded DNA breaks (DSBs). The viral oncoprotein Tax has been reported to impair DSB repair, but is not shown to be consistently expressed throughout all phases of infection. The viral oncoprotein HTLV-1 basic leucine zipper factor (HBZ) is consistently expressed prior to and throughout disease progression, but it is unclear whether it also influences DSB repair. We report that HBZ attenuates DSB repair by non-homologous end joining (NHEJ), in a manner dependent upon the basic leucine zipper (bZIP) domain. HBZ was found to interact with two vital members of the NHEJ core machinery, Ku70 and Ku80, and to be recruited to DSBs in a bZIP-dependent manner in vitro We observed that HBZ expression also resulted in a bZIP-dependent delay in DNA-PK activation following treatment with etoposide. Though Tax is reported to interact with Ku70, we did not find Tax expression to interfere with HBZ:Ku complex formation. However, as Tax was reported to saturate NHEJ, we found this effect masked the attenuation of NHEJ by HBZ. Overall, these data suggest that DSB repair mechanisms are impaired not only by Tax, but also by HBZ, and show that HBZ expression may significantly contribute to the accumulation of chromosomal abnormalities during HTLV-1 mediated oncogenesis. IMPORTANCE Human T-cell leukemia virus type 1 (HTLV-1) infects 15-20 million people worldwide. Approximately 90% of infected individuals are asymptomatic and may remain undiagnosed, increasing the risk that they will unknowingly transmit the virus. About 5% of the HTLV-1 positive population to develop Adult T-cell Leukemia (ATL), a fatal disease that is not highly responsive to treatment. Though ATL development remains poorly understood, two viral proteins, Tax and HBZ, have been implicated in driving disease progression by manipulating host cell signaling and transcriptional pathways. Unlike Tax, HBZ expression is consistently observed in all infected individuals, making it important to elucidate the specific role of HBZ in disease progression. Here, we present evidence that HBZ could promote the accumulation of double-stranded DNA breaks (DSBs) through the attenuation of the non-homologous end joining (NHEJ) repair pathway. This effect may lead to genome instability, ultimately contributing to the development of ATL. Copyright © 2018 American Society for Microbiology.

Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion

PubMed Central

Xing, Jihong; Li, Jianhua

2017-01-01

Background/Aims Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity (SNA) that regulates blood flow directed to the ischemic limb is exaggerated during exercise in this disease, and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic response. The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex. Methods A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues were obtained to examine the protein levels of PAR2 using western blot analysis. Current responses induced by activation of TRPA1 in skeletal muscle DRG neurons were characterized using whole-cell patch clamp methods. The blood pressure response to static exercise (i.e., muscle contraction) and stimulation of TRPA1 was also examined after a blockade of PAR2. Results The expression of PAR2 was amplified in DRG neurons of the occluded limb, and PAR2 activation with SL-NH2 (a PAR2 agonist) increased the amplitude of TRPA1 currents to a greater degree in DRG neurons of the occluded limb. Moreover, FSLLRY-NH2 (a PAR antagonist) injected into the arterial blood supply of the hindlimb muscles significantly attenuated the pressor response to muscle contraction and TRPA1 stimulation in rats with occluded limbs. Conclusions The PAR2 signal in muscle sensory nerves contributes to the amplified exercise pressor reflex via TRPA1 mechanisms in rats with femoral artery ligation. These findings provide a pathophysiological basis for autonomic responses during exercise activity in PAD, which may potentially aid in the development of therapeutic approaches for improvement of blood flow in this disease. PMID:29131007

Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy.

PubMed

Elliott, Cameron A; Gross, Donald W; Wheatley, B Matt; Beaulieu, Christian; Sankar, Tejas

2016-09-01

Determine the extent and time course of volumetric changes in the contralateral hippocampus following surgery for medically refractory temporal lobe epilepsy (TLE). Serial T1-weighted MRI brain scans were obtained in 26 TLE patients pre- and post-temporal lobe epilepsy surgery as well as in 12 control subjects of similar age. Patients underwent either anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SAH). Blinded, manual hippocampal volumetry (head, body, and tail) was performed in two groups: 1) two scan group [ATL (n=6); SAH (n=10)], imaged pre-surgery and on average at 5.4 years post-surgery; and 2) longitudinal group [ATL (n=8); SAH (n=2)] imaged pre-surgery and on post-operative day 1, 2, 3, 6, 60, 120 and a delayed time point (average 2.4 years). In the two scan group, there was atrophy by 12% of the unresected contralateral hippocampus (p<0.001), with atrophy being most pronounced (27%) in the hippocampal body (p<0.001) with no significant differences seen for the hippocampal head or tail. In the longitudinal group, significant atrophy was also observed for the whole hippocampus and the body with atrophy seen as early as post-operative day #1 which progressed significantly over the first post-operative week (1.3%/day and 3.0%./day, respectively) before stabilizing over the long-term to a 13% reduction in total volume. There was no significant difference in atrophy compared by surgical approach (ATL vs. SAH; p=0.94) or side (p=0.31); however, atrophy was significantly more pronounced in patients with ongoing post-operative seizures (hippocampal body, p=0.019; whole hippocampus, p=0.048). There were no detectable post-operative neuropsychological deficits attributable to contralateral hippocampal atrophy. Significant contralateral hippocampal atrophy occurs following TLE surgery, which begins immediately and progresses over the first post-operative week. The observation that seizure free patients had significantly less atrophy of the contralateral hippocampus after surgery suggests the possibility of an early post-operative imaging marker to predict surgical outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

ClinicalTrials.gov

2016-02-20

Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

Double triplex real-time PCR assay for simultaneous detection of Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, and Staphylococcus haemolyticus and determination of their methicillin resistance directly from positive blood culture bottles.

PubMed

Kilic, Abdullah; Basustaoglu, A Celal

2011-12-01

We developed and validated here a double triplex real-time PCR assay to simultaneously detect and identify Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus haemolyticus and their methicillin resistance in a single reaction directly from Gram-positive cocci-in-clusters (GPCs)-positive blood culture bottles. From August 15, 2009 through February 15, 2010, 238 GPC-positive samples were collected and identified by conventional methods as 11 methicillin-resistant S. aureus (MRSA), 28 methicillin-susceptible S. aureus (MSSA), 176 MR coagulase-negative staphylococci (MRCoNS), 21 MSCoNS and two Enterococcus faecalis. The double triplex real-time PCR assay was targeted and detected tuf, nuc and mecA genes in the first tube and atlE, gap and mvaA genes in the second tube which could be run simultaneously. The detection limit of the assay was found at 10(3) CFU/ml for the atleE gene, 10(4) CFU/ml for the mva gene and 10(5) CFU/ml for gap, nuc, mecA and tuf genes based on seeding experiments. All Staphylococcus species except two S. epidermidis were correctly identified by the assay. The double triplex real-time PCR assay quickly and accurately detects S. aureus, S. epidermidis, S. hominis and S. haemolyticus and their methicillin resistance in a single reaction directly from positive blood culture bottles within 83 min. Copyright © 2011 Institut Pasteur. All rights reserved.

Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

PubMed Central

Hoang, Kimson; Ankney, John A.; Nguyen, Stephanie T.; Rushing, Amanda W.; Polakowski, Nicholas; Miotto, Benoit; Lemasson, Isabelle

2016-01-01

Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples. PMID:26625199

Dissociable effects of prefrontal and anterior temporal cortical lesions on stereotypical gender attitudes.

PubMed

Gozzi, Marta; Raymont, Vanessa; Solomon, Jeffrey; Koenigs, Michael; Grafman, Jordan

2009-08-01

Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. In addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed.

[Advanced Trauma Life Support (ATLS) in the emergency room. Is it suitable as an SOP?].

PubMed

Shafizadeh, S; Tjardes, T; Steinhausen, E; Balke, M; Paffrath, T; Bouillon, B; Bäthis, H

2010-08-01

There is clinical evidence that a standardized management of trauma patients in the emergency room improves outcome. ATLS is a training course that teaches a systematic approach to the trauma patient in the emergency room. The aims are a rapid and accurate assessment of the patient's physiologic status, treatment according to priorities, and making decisions on whether the local resources are sufficient for adequate definitive treatment of the patient or if transfer to a trauma center is necessary. Above all it is important to prevent secondary injury, to realize timing as a relevant factor in the initial treatment, and to assure a high standard of care. A standard operating procedure (SOP) exactly regulates the approach to trauma patients and determines the responsibilities of the involved faculties. An SOP moreover incorporates the organizational structure in the treatment of trauma patients as well as the necessary technical equipment and staff requirements. To optimize process and result quality, priorities are in the fields of medical fundamentals of trauma care, education, and fault management. SOPs and training courses increase the process and result quality in the treatment of the trauma patient in the emergency room. These programs should be based on the special demands of the physiology of the trauma as well as the structural specifics of the hospital. ATLS does not equal an SOP but it qualifies as a standardized concept for management of trauma patients in the emergency room.

Dynamic semantic cognition: Characterising coherent and controlled conceptual retrieval through time using magnetoencephalography and chronometric transcranial magnetic stimulation.

PubMed

Teige, Catarina; Mollo, Giovanna; Millman, Rebecca; Savill, Nicola; Smallwood, Jonathan; Cornelissen, Piers L; Jefferies, Elizabeth

2018-06-01

Distinct neural processes are thought to support the retrieval of semantic information that is (i) coherent with strongly-encoded aspects of knowledge, and (ii) non-dominant yet relevant for the current task or context. While the brain regions that support readily coherent and more controlled patterns of semantic retrieval are relatively well-characterised, the temporal dynamics of these processes are not well-understood. This study used magnetoencephalography (MEG) and dual-pulse chronometric transcranial magnetic stimulation (cTMS) in two separate experiments to examine temporal dynamics during the retrieval of strong and weak associations. MEG results revealed a dissociation within left temporal cortex: anterior temporal lobe (ATL) showed greater oscillatory response for strong than weak associations, while posterior middle temporal gyrus (pMTG) showed the reverse pattern. Left inferior frontal gyrus (IFG), a site associated with semantic control and retrieval, showed both patterns at different time points. In the cTMS experiment, stimulation of ATL at ∼150 msec disrupted the efficient retrieval of strong associations, indicating a necessary role for ATL in coherent conceptual activations. Stimulation of pMTG at the onset of the second word disrupted the retrieval of weak associations, suggesting this site may maintain information about semantic context from the first word, allowing efficient engagement of semantic control. Together these studies provide converging evidence for a functional dissociation within the temporal lobe, across both tasks and time. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Global cloud top height retrieval using SCIAMACHY limb spectra: model studies and first results

NASA Astrophysics Data System (ADS)

Eichmann, Kai-Uwe; Lelli, Luca; von Savigny, Christian; Sembhi, Harjinder; Burrows, John P.

2016-03-01

Cloud top heights (CTHs) are retrieved for the period 1 January 2003 to 7 April 2012 using height-resolved limb spectra measured with the SCanning Imaging Absorption SpectroMeter for Atmospheric CHartographY (SCIAMACHY) on board ENVISAT (ENVIronmental SATellite). In this study, we present the retrieval code SCODA (SCIAMACHY cloud detection algorithm) based on a colour index method and test the accuracy of the retrieved CTHs in comparison to other methods. Sensitivity studies using the radiative transfer model SCIATRAN show that the method is capable of detecting cloud tops down to about 5 km and very thin cirrus clouds up to the tropopause. Volcanic particles can be detected that occasionally reach the lower stratosphere. Upper tropospheric ice clouds are observable for a nadir cloud optical thickness (COT) ≥ 0.01, which is in the subvisual range. This detection sensitivity decreases towards the lowermost troposphere. The COT detection limit for a water cloud top height of 5 km is roughly 0.1. This value is much lower than thresholds reported for passive cloud detection methods in nadir-viewing direction. Low clouds at 2 to 3 km can only be retrieved under very clean atmospheric conditions, as light scattering of aerosol particles interferes with the cloud particle scattering. We compare co-located SCIAMACHY limb and nadir cloud parameters that are retrieved with the Semi-Analytical CloUd Retrieval Algorithm (SACURA). Only opaque clouds (τN,c > 5) are detected with the nadir passive retrieval technique in the UV-visible and infrared wavelength ranges. Thus, due to the frequent occurrence of thin clouds and subvisual cirrus clouds in the tropics, larger CTH deviations are detected between both viewing geometries. Zonal mean CTH differences can be as high as 4 km in the tropics. The agreement in global cloud fields is sufficiently good. However, the land-sea contrast, as seen in nadir cloud occurrence frequency distributions, is not observed in limb geometry. Co-located cloud top height measurements of the limb-viewing Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on ENVISAT are compared for the period from January 2008 to March 2012. The global CTH agreement of about 1 km is observed, which is smaller than the vertical field of view of both instruments. Lower stratospheric aerosols from volcanic eruptions occasionally interfere with the cloud retrieval and inhibit the detection of tropospheric clouds. The aerosol impact on cloud retrievals was studied for the volcanoes Kasatochi (August 2008), Sarychev Peak (June 2009), and Nabro (June 2011). Long-lasting aerosol scattering is detected after these events in the Northern Hemisphere for heights above 12.5 km in tropical and polar latitudes. Aerosol top heights up to about 22 km are found in 2009 and the enhanced lower stratospheric aerosol layer persisted for about 7 months. In August 2009 about 82 % of the lower stratosphere between 30 and 70° N was filled with scattering particles and nearly 50 % in October 2008.

Two Coronal Mass Ejections Events Close to the Total Solar Eclipse Aug. 11, 1999

NASA Astrophysics Data System (ADS)

Churyumov, K. I.; Ivanchuk, V. I.

We present some results of exploration of the solar corona on the basis of analysis of its images obtained in Romania by K.I.Churyumov and in Bulgaria by V.Mormyl' and S.Kharchuk Aug. 11 1999. Structure of the corona is characterized by the presence of numerous power and thin rays which have mainly radial orientation in regard to the Sun. The high-latitude rays of the north hemisphere (especially in the NE sector) are inclined in the direction of the N-pole. The interesting peculiarity of the solar corona Aug. 11 1999 is the existence of the sabre-like thin double ray on the NE-limb, which goes from the solar limb region at p ~ 50o. It is close to the peculiar center of ``repulsion'', which is observed for the fan of rays of the E-limb. We proposed that the similar rays and the observed center of ``repulsion'' were an indicator (postcursor) which shows that in this place of the corona the phenomena of the coronal mass ejections (CME) of the coronal plasma occurred. This views was confirmed by observations of the solar corona with the help of the Lasco C2 coronograph of SOHO Aug. 10/11 1999. In the region of the NW-quadrant and near the W-equator the enough sharp transequatorial arc by height ~ 0.7Rsolar with the center at ϕo = +10 deg is detected. It is nonfull arcs which intersects set of rays structures and near its foundation on the altitude /~ 0.3Rsolar there is a coronal condensation with characteristic sizes Δ l ~ 0.1Rsolar. We think that it is tied with development of a coronal mass ejection (CME) detected by the coronograph Lasco C2 of SOHO Aug. 11/12, 1999. On the best pictures it is seen that CME had the angle sizes ~ 90 deg and filled in nearly the all NW quadrant as a not uniform buble. On the basis of the published data we determined several

Nervous systems in 3D: a comparison of Caridean, anomuran, and brachyuran zoea-I (Decapoda).

PubMed

Geiselbrecht, Hannes; Melzer, Roland R

2013-12-01

Using serial semi-thin sections and digital 3D-reconstructions we studied the nervous systems of zoea-I larvae in three decapod species, Hippolyte inermis (Leach, 1815), Porcellana platycheles (Pennant, 1777), and Pachygrapsus marmoratus (Fabricius, 1787). These taxa represent three decapod lineages, that is, Caridea, Anomura, and Brachyura, each characterized by specific zoea-I morphology. Special attention was paid to development of ganglia, neuropil composition, and segmental nerves. In all zoeae studied, the overall elements, for example, the segmental ganglia, their neuropils and most of the nerves of the adult decapod nervous system are present. Ongoing differentiation processes are observable as well, most obvious in segments with well-developed limbs the ganglia are in a more advanced stage of differentiation and more voluminous compared to segments with only limb buds or without externally visible limb anlagen. Intra- and interspecific comparisons indicate that neuromere differentiation thus deviates from a simple anterior-posterior gradient as, for example, posterior thoracic neuromeres are less developed than those of the pleon. In addition, the differences in the progress of the development of ganglia between the studied taxa can best be attributed to heterochronic mechanisms. Taxon and stage-specific morphologies indicate that neuronal architecture reflects both, morphogenesis to the adult stage and specific larval adaptions, and provides sets of characters relevant to understanding the corresponding phylogeny. © 2013 Wiley Periodicals, Inc.

Evidence for conductive Cl- pathways across the cell membranes of the thin ascending limb of Henle's loop.

PubMed Central

Yoshitomi, K; Kondo, Y; Imai, M

1988-01-01

To examine whether Cl- is transported via transcellular pathways in the thin ascending limb of Henle's loop (TAL), conventional microelectrode technique was applied in isolated TAL segments of hamsters perfused in vitro. The average basolateral membrane voltage (VB) was -24.5 +/- 1.5 mV (n = 18). Ouabain (10(-4) M) had no effect on VB. Sudden reduction of basolateral Cl- concentration from 165 to 5 mmol/liter caused a large depolarizing spike (+49.1 +/- 2.7 mV, n = 18), while the transepithelial potential (VT) showed lumen positive deflection by 33.4 +/- 1.2 mV, which indicates that a large Cl- conductance exists in the basolateral membrane. Reduction of luminal Cl- concentration caused sustained depolarization of luminal cell membrane from +24.5 +/- 2.1 to -9.7 +/- 3.4 mV (n = 6), which indicates that there is also a Cl- conductance in the luminal membrane. Since we have previously shown that acidification of ambient solution suppresses the transmural Cl- permeability, we tested whether acid pH also inhibits the Cl- conductance of the basolateral membrane. When pH of the bathing fluid was lowered to 5.8, the depolarizing spike of VB and the change of VT upon sudden reduction of basolateral Cl- were almost completely abolished. From these results we conclude: (a) both the luminal and the basolateral membrane of hamster TAL segments have Cl- conductances, and (b) Cl- transport in the TAL takes place, at least in part, via a transcellular route when a transepithelial Cl- gradient is present. PMID:2458388

48 CFR 250.102-1 - Delegation of authority.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT..., Technology, and Logistics (USD (AT&L)) under 10 U.S.C. 133, in addition to the Secretary of Defense and the...

Recording brain waves at the supermarket: what can we learn from a shopper's brain?

PubMed

Sands, Stephen F; Sands, J Andrew

2012-01-01

Communication and marketing campaigns have traditionally been divided into two lines: above the line (ATL) and below the line (BTL). ATL campaigns refer to communications such as TV, print, and outdoor displays that are intended to reach large audiences. The effects of ATL are inherently difficult to measure; we do not see the direct consequences of viewing an advertisement (i.e., a talking baby giving financial advice) and actual purchase of the product. ATL is intended to indirectly improve the impression of a brand. BTL campaigns refer to promotions and in-store displays and are designed to affect the point-of-purchase behavior. The effects of BTL are easier to measure; we see direct consequences of viewing a display (i.e., “Today Only, Two for the Price of One”) and eventual purchase of the product. BTL is intended to directly improve the impression of a brand. Neuroscience plays an important role in measuring the effects of marketing campaigns. Traditional methods of measurement (such as surveys and interviews) depend on the verbal ability of the consumer to articulate their motivations for purchasing a product. It is well known that participants are poor at introspective reasoning, leading to an eventual purchase that omits emotional elements. Recently, methods normally employed in cognitive neuroscience have been adapted for use in the evaluation of campaign effectiveness. These methods have increased our understanding of factors leading to economic decisions. The application of neuroscience in ATL campaigns is relatively straightforward. Participants view TV commercials, for example, seated in a comfortable setting with minimal movement while electroencephalogram (EEG) measures are monitored. These brain waves reveal cognitive events related to the media. Participants are exposed to a functional magnetic resonance imaging (fMRI) scanner to monitor changes in blood flow in various regions of the brain. Both of these methods are sensitive to underlying cognitive and emotional activity and are complimentary. EEG is more sensitive to time-locked events (i.e., story lines), whereas fMRI is more sensitive to the brain regions involved. The application of neuroscience in BTL campaigns is significantly more difficult to achieve. Participants move unconstrained in a shopping environment while EEG and eye movements are monitored. In this scenario, fMRI is not possible. fMRI can be used with virtual store mock-ups, but it is expensive and seldom used. We have developed a technology that allows for the measurement of EEG in an unobtrusive manner. The intent is to record the brain waves of participants during their day-to-day shopping experience. A miniaturized video recorder, EEG amplifiers, and eye-tracking systems are used. Digital signal processing is employed to remove the substantial artifact generated by eye movements and motion. Eye fixations identify specific viewings of products and displays, and they are used for synchronizing the behavior with EEG response. The location of EEG sources is determined by the use of a source reconstruction software.

Manufacturing Innovation and Technological Superiority

DTIC Science & Technology

2016-09-01

Defense AT&L: September-October 2016 2 From the Under Secretary of Defense for Acquisit ion, Technology, and Logist ics Manufacturing Innovation ...program to establish Manufacturing Innovation Institutes (MIIs) that would create incubators for advanced manufacturing technology in key

48 CFR 216.504 - Indefinite-quantity contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Deputy Director, Defense Procurement and Acquisition Policy (Contract Policy and International... Policy and International Contracting), OUSD (AT&L) DPAP (CPIC), 3060 Defense Pentagon, Washington, DC... contracts. 216.504 Section 216.504 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS...

[Companion diagnostics "POTELIGEO TEST IHC/FCM" used with "POTELIGEO" (mogamulizumab) for adult T-cell leukemia-lymphoma (ATL) treatment].

PubMed

Goami, Takeshi

2014-05-01

Personalized medicine offers the best treatment for individual patients, it is important for an IVD manufacturer to develop companion diagnostics in parallel with the development of new drugs through close cooperation with drug companies, and supply diagnostics companies with new drugs for physicians and patients. We received approval for a premarket approval application (PMA) for two in vitro diagnostic ("IVD") reagents, POTELIGEO TEST IHC and POTELIGEO TEST FCM ("POTELIGEO TEST"), in March 2012, and subsequently launched POTELIGEO TEST in May 2012. POTELIGEO TEST is a companion diagnostic used with POTELIGEO for which Kyowa Hakko Kirin has a new drug application (NDA) that was approved in March 2012, and is designed to help physicians identify appropriate subpopulations of adult T-cell leukemia-lymphoma(ATL) patients who are most likely to respond to POTELIGEO 20 mg (mogamulizumab) Injection ("POTELIGEO").

Limb flexion-induced axial compression and bending in human femoropopliteal artery segments.

PubMed

Poulson, William; Kamenskiy, Alexey; Seas, Andreas; Deegan, Paul; Lomneth, Carol; MacTaggart, Jason

2018-02-01

High failure rates of femoropopliteal artery (FPA) interventions are often attributed in part to severe mechanical deformations that occur with limb movement. Axial compression and bending of the FPA likely play significant roles in FPA disease development and reconstruction failure, but these deformations are poorly characterized. The goal of this study was to quantify axial compression and bending of human FPAs that are placed in positions commonly assumed during the normal course of daily activities. Retrievable nitinol markers were deployed using a custom-made catheter system into 28 in situ FPAs of 14 human cadavers. Contrast-enhanced, thin-section computed tomography images were acquired with each limb in the standing (180 degrees), walking (110 degrees), sitting (90 degrees), and gardening (60 degrees) postures. Image segmentation and analysis allowed relative comparison of spatial locations of each intra-arterial marker to determine axial compression and bending using the arterial centerlines. Axial compression in the popliteal artery (PA) was greater than in the proximal superficial femoral artery (SFA) or the adductor hiatus (AH) segments in all postures (P = .02). Average compression in the SFA, AH, and PA ranged from 9% to 15%, 11% to 19%, and 13% to 25%, respectively. The FPA experienced significantly more acute bending in the AH and PA segments compared with the proximal SFA (P < .05) in all postures. In the walking, sitting, and gardening postures, average sphere radii in the SFA, AH, and PA ranged from 21 to 27 mm, 10 to 18 mm, and 8 to 19 mm, whereas bending angles ranged from 150 to 157 degrees, 136 to 147 degrees, and 137 to 148 degrees, respectively. The FPA experiences significant axial compression and bending during limb flexion that occur at even modest limb angles. Moreover, different segments of the FPA appear to undergo significantly different degrees of deformation. Understanding the effects of limb flexion on axial compression and bending might assist with reconstructive device selection for patients requiring peripheral arterial disease intervention and may also help guide the development of devices with improved characteristics that can better adapt to the dynamic environment of the lower extremity vasculature. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Endemic and threatened tetrapods in the restingas of the biodiversity corridors of Serra do Mar and of the Central da Mata Atlântica in eastern Brazil.

PubMed

Rocha, C F D; Van Sluys, M; Bergallo, H G; Alves, M A S

2005-02-01

Biodiversity corridors comprise a mosaic of land uses connecting fragments of natural forest across a landscape. Two such corridors have been established along the eastern coast of Brazil: the Serra do Mar and the Central da Mata Atlântica corridors, along which most of the coastal plains are restinga areas. In this study, we analyze the present status of the endemic and endangered terrestrial vertebrates of both corridors. We sampled 10 restingas in both corridors, recording species of amphibians, reptiles, birds, and mammals. Some restingas harbor a relatively large number of endemic species,and two main regions of endemism can be identified along the restingas of both corridors: the coastal restingas from northern Espirito Santo State to southern Bahia State (between Linhares, ES, and Tarancoso, BA), and the coastal region between the restingas of Maricá and Jurubatiba, Rio de Janeiro State. Six species of terrestrial vertebrates considered threatened with extinction are found in the restingas of Serra do Mar and Central da Mata Atlântica biodiversity corridors (Liolaemus lutzae, Formicivora littoralis, Mimus gilvus, Schistochlamys melanopis, and Trinomys eliasi). The region located between the restinga of Maricá and that of Jurubatiba is of special relevance for the conservation of vertebrate species of the restingas of the corridors because a considerable number of threatened species of terrestrial vertebrates are found there. We strongly recommend efforts to develop checklists of threatened faunas for the States of Espirito Santo and Bahia.

Beyond the FFA: The Role of the Ventral Anterior Temporal Lobes in Face Processing

PubMed Central

Collins, Jessica A.; Olson, Ingrid R.

2014-01-01

Extensive research has supported the existence of a specialized face-processing network that is distinct from the visual processing areas used for general object recognition. The majority of this work has been aimed at characterizing the response properties of the fusiform face area (FFA) and the occipital face area (OFA), which together are thought to constitute the core network of brain areas responsible for facial identification. Although accruing evidence has shown that face-selective patches in the ventral anterior temporal lobes (vATLs) are interconnected with the FFA and OFA, and that they play a role in facial identification, the relative contribution of these brain areas to the core face-processing network has remained unarticulated. Here we review recent research critically implicating the vATLs in face perception and memory. We propose that current models of face processing should be revised such that the ventral anterior temporal lobes serve a centralized role in the visual face-processing network. We speculate that a hierarchically organized system of face processing areas extends bilaterally from the inferior occipital gyri to the vATLs, with facial representations becoming increasingly complex and abstracted from low-level perceptual features as they move forward along this network. The anterior temporal face areas may serve as the apex of this hierarchy, instantiating the final stages of face recognition. We further argue that the anterior temporal face areas are ideally suited to serve as an interface between face perception and face memory, linking perceptual representations of individual identity with person-specific semantic knowledge. PMID:24937188

The effect of aging on the brain network for exception word reading.

PubMed

Provost, Jean-Sebastien; Brambati, Simona M; Chapleau, Marianne; Wilson, Maximiliano A

2016-11-01

Cognitive and computational models of reading aloud agree on the existence of two procedures for reading. Pseudowords (e.g., atendier) are correctly read through subword processes only while exception words (e.g., pint) are only correctly read via whole-words processes. Regular words can be correctly read by means of either way. Previous behavioral studies showed that older adults relied more on whole-word processing for reading. The aim of the present fMRI study was to verify whether this larger whole-word reliance for reading in older adults was reflected by changes in the pattern of brain activation. Both young and elderly participants read aloud pseudowords, exception and regular words in the scanner. Behavioral results reproduced those of previous studies showing that older adults made significantly less errors when reading exception words. Neuroimaging results showed significant activation of the left anterior temporal lobe (ATL), a key region implicated in whole-word reading for exception word reading in both young and elderly participants. Critically, ATL activation was also found for regular word reading in the elderly. No differences were observed in the pattern of activation between regular and pseudowords in the young. In conclusion, these results extend evidence on the critical role of the left ATL for exception word reading to elderly participants. Additionally, our study shows for the first time from a developmental point of view that the behavioral changes found in reading during normal aging also have a brain counterpart in the reading network changes that sustain exception and regular word reading in the elderly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leishmania isoenzyme polymorphisms in Ecuador: Relationships with geographic distribution and clinical presentation

PubMed Central

Calvopina, Manuel; Armijos, Rodrigo X; Marco, Jorge D; Uezato, Hiroshi; Kato, Hirotomo; Gomez, Eduardo A; Korenaga, Masataka; Barroso, Paola A; Mimori, Tatsuyuki; Cooper, Philip J; Nonaka, Shigeo; Hashiguchi, Yoshihisa

2006-01-01

Background Determinants of the clinical presentation of the leishmaniases are poorly understood but Leishmania species and strain differences are important. To examine the relationship between clinical presentation, species and isoenzyme polymorphisms, 56 Leishmania isolates from distinct presentations of American tegumentary leishmaniasis (ATL) from Ecuador were analyzed. Methods Isolates were characterized by multilocus enzyme electrophoresis for polymorphisms of 11 isoenzymes. Patients were infected in four different ecologic regions: highland and lowland jungle of the Pacific coast, Amazonian lowlands and Andean highlands. Results Six Leishmania species constituting 21 zymodemes were identified: L. (Viannia) panamensis (21 isolates, 7 zymodemes), L. (V.) guyanensis (7 isolates, 4 zymodemes), L. (V.) braziliensis (5 isolates, 3 zymodemes), L. (Leishmania) mexicana (11 isolates, 4 zymodemes), L. (L.) amazonensis (10 isolates, 2 zymodemes) and L. (L.) major (2 isolates, 1 zymodeme). L. panamensis was the species most frequently identified in the Pacific region and was associated with several clinical variants of cutaneous disease (CL); eight cases of leishmaniasis recidiva cutis (LRC) found in the Pacific highlands were associated with 3 zymodemes of this species. Mucocutaneous leishmaniasis found only in the Amazonian focus was associated with 3 zymodemes of L. braziliensis. The papular variant of CL, Uta, found in the Andean highlands was related predominantly with a single zymodeme of L. mexicana. Conclusion Our data show a high degree of phenotypic variation within species, and some evidence for associations between specific variants of ATL (i.e. Uta and LRC) and specific Leishmania zymodemes. This study further defines the geographic distribution of Leishmania species and clinical variants of ATL in Ecuador. PMID:16968553

Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow–derived cells

PubMed Central

Day, Yuan-Ji; Huang, Liping; McDuffie, Marcia J.; Rosin, Diane L.; Ye, Hong; Chen, Jiang-Fan; Schwarzschild, Michael A.; Fink, J. Stephen; Linden, Joel; Okusa, Mark D.

2003-01-01

Activation of A2A adenosine receptors (A2ARs) protects kidneys from ischemia-reperfusion injury (IRI). A2ARs are expressed on bone marrow–derived (BM-derived) cells and renal smooth muscle, epithelial, and endothelial cells. To measure the contribution of A2ARs on BM-derived cells in suppressing renal IRI, we examined the effects of a selective agonist of A2ARs, ATL146e, in chimeric mice in which BM was ablated by lethal radiation and reconstituted with donor BM cells derived from GFP, A2AR-KO, or WT mice to produce GFP→WT, A2A-KO→WT, or WT→WT mouse chimera. We found little or no repopulation of renal vascular endothelial cells by donor BM with or without renal IRI. ATL146e had no effect on IRI in A2A-KO mice or A2A-KO→WT chimera, but reduced the rise in plasma creatinine from IRI by 75% in WT mice and by 60% in WT→WT chimera. ATL146e reduced the induction of IL-6, IL-1β, IL-1ra, and TGF-α mRNA in WT→WT mice but not in A2A-KO→WT mice. Plasma creatinine was significantly greater in A2A-KO than in WT mice after IRI, suggesting some renal protection by endogenous adenosine. We conclude that protection from renal IRI by A2AR agonists or endogenous adenosine requires activation of receptors expressed on BM-derived cells. PMID:12975473

A Critical Role for IL-17RB Signaling in HTLV-1 Tax-Induced NF-κB Activation and T-Cell Transformation

PubMed Central

Lavorgna, Alfonso; Matsuoka, Masao; Harhaj, Edward William

2014-01-01

Human T-cell leukemia virus type 1 (HTLV-1) infection is linked to the development of adult T-cell leukemia (ATL) and the neuroinflammatory disease HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 Tax protein functions as a potent viral oncogene that constitutively activates the NF-κB transcription factor to transform T cells; however, the underlying mechanisms remain obscure. Here, using next-generation RNA sequencing we identified the IL-25 receptor subunit IL-17RB as an aberrantly overexpressed gene in HTLV-1 immortalized T cells. Tax induced the expression of IL-17RB in an IκB kinase (IKK) and NF-κB-dependent manner. Remarkably, Tax activation of the canonical NF-κB pathway in T cells was critically dependent on IL-17RB expression. IL-17RB and IL-25 were required for HTLV-1-induced immortalization of primary T cells, and the constitutive NF-κB activation and survival of HTLV-1 transformed T cells. IL-9 was identified as an important downstream target gene of the IL-17RB pathway that drives the proliferation of HTLV-1 transformed cells. Furthermore, IL-17RB was overexpressed in leukemic cells from a subset of ATL patients and also regulated NF-κB activation in some, but not all, Tax-negative ATL cell lines. Together, our results support a model whereby Tax instigates an IL-17RB-NF-κB feed-forward autocrine loop that is obligatory for HTLV-1 leukemogenesis. PMID:25340344

In vivo immunogenicity of Tax 11-19 epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine

PubMed Central

Sagar, Divya; Masih, Shet; Schell, Todd; Jacobson, Steven; Comber, Joseph D.; Philip, Ramila; Wigdahl, Brian; Jain, Pooja; Khan, Zafar K.

2014-01-01

Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses. PMID:24739247

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013)

PubMed Central

Brahim, Lucia Regina; Valete-Rosalino, Cláudia Maria; Antônio, Liliane de Fátima; Pimentel, Maria Inês Fernandes; Lyra, Marcelo Rosandiski; Paes, Luiz Eduardo de Carvalho; da Costa, Ananda Dutra; Vieira, Iracema Forni; Dias, Cristina Maria Giordano; Duque, Maria Cristina de Oliveira; Marzochi, Mauro Celio de Almeida; Schubach, Armando de Oliveira

2017-01-01

BACKGROUND American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence. PMID:29211245

Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary leishmaniasis results in low lethality, low incidence of relapse, and low late mucosal involvement in a referral centre in Rio de Janeiro, Brazil (2001-2013).

PubMed

Brahim, Lucia Regina; Valete-Rosalino, Cláudia Maria; Antônio, Liliane de Fátima; Pimentel, Maria Inês Fernandes; Lyra, Marcelo Rosandiski; Paes, Luiz Eduardo de Carvalho; Costa, Ananda Dutra da; Vieira, Iracema Forni; Dias, Cristina Maria Giordano; Duque, Maria Cristina de Oliveira; Marzochi, Mauro Celio de Almeida; Schubach, Armando de Oliveira

2017-12-01

American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. Data were recovered from records of all ATL patients diagnosed during that period. Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.

Cross-modal integration of lexical-semantic features during word processing: evidence from oscillatory dynamics during EEG.

PubMed

van Ackeren, Markus J; Rueschemeyer, Shirley-Ann

2014-01-01

In recent years, numerous studies have provided converging evidence that word meaning is partially stored in modality-specific cortical networks. However, little is known about the mechanisms supporting the integration of this distributed semantic content into coherent conceptual representations. In the current study we aimed to address this issue by using EEG to look at the spatial and temporal dynamics of feature integration during word comprehension. Specifically, participants were presented with two modality-specific features (i.e., visual or auditory features such as silver and loud) and asked to verify whether these two features were compatible with a subsequently presented target word (e.g., WHISTLE). Each pair of features described properties from either the same modality (e.g., silver, tiny  =  visual features) or different modalities (e.g., silver, loud  =  visual, auditory). Behavioral and EEG data were collected. The results show that verifying features that are putatively represented in the same modality-specific network is faster than verifying features across modalities. At the neural level, integrating features across modalities induces sustained oscillatory activity around the theta range (4-6 Hz) in left anterior temporal lobe (ATL), a putative hub for integrating distributed semantic content. In addition, enhanced long-range network interactions in the theta range were seen between left ATL and a widespread cortical network. These results suggest that oscillatory dynamics in the theta range could be involved in integrating multimodal semantic content by creating transient functional networks linking distributed modality-specific networks and multimodal semantic hubs such as left ATL.

Early Intravascular Events are Associated with Development of ARDS.

PubMed

Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

2018-05-21

The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

SaeRS Is Responsive to Cellular Respiratory Status and Regulates Fermentative Biofilm Formation in Staphylococcus aureus.

PubMed

Mashruwala, Ameya A; Gries, Casey M; Scherr, Tyler D; Kielian, Tammy; Boyd, Jeffrey M

2017-08-01

Biofilms are multicellular communities of microorganisms living as a quorum rather than as individual cells. The bacterial human pathogen Staphylococcus aureus uses oxygen as a terminal electron acceptor during respiration. Infected human tissues are hypoxic or anoxic. We recently reported that impaired respiration elicits a p rogrammed c ell l ysis (PCL) phenomenon in S. aureus leading to the release of cellular polymers that are utilized to form biofilms. PCL is dependent upon the AtlA murein hydrolase and is regulated, in part, by the SrrAB two-component regulatory system (TCRS). In the current study, we report that the SaeRS TCRS also governs fermentative biofilm formation by positively influencing AtlA activity. The SaeRS-modulated factor fibronectin-binding protein A (FnBPA) also contributed to the fermentative biofilm formation phenotype. SaeRS-dependent biofilm formation occurred in response to changes in cellular respiratory status. Genetic evidence presented suggests that a high cellular titer of phosphorylated SaeR is required for biofilm formation. Epistasis analyses found that SaeRS and SrrAB influence biofilm formation independently of one another. Analyses using a mouse model of orthopedic implant-associated biofilm formation found that both SaeRS and SrrAB govern host colonization. Of these two TCRSs, SrrAB was the dominant system driving biofilm formation in vivo We propose a model wherein impaired cellular respiration stimulates SaeRS via an as yet undefined signal molecule(s), resulting in increasing expression of AtlA and FnBPA and biofilm formation. Copyright © 2017 American Society for Microbiology.

ATLa, an aspirin-triggered lipoxin A4 synthetic analog, prevents the inflammatory and fibrotic effects of bleomycin-induced pulmonary fibrosis.

PubMed

Martins, Vanessa; Valença, Samuel S; Farias-Filho, Francisco A; Molinaro, Raphael; Simões, Rafael L; Ferreira, Tatiana P T; e Silva, Patrícia M R; Hogaboam, Cory M; Kunkel, Steven L; Fierro, Iolanda M; Canetti, Claudio; Benjamim, Claudia F

2009-05-01

Despite an increase in the knowledge of mechanisms and mediators involved in pulmonary fibrosis, there are no successful therapeutics available. Lipoxins (LX) and their 15-epimers, aspirin-triggered LX (ATL), are endogenously produced eicosanoids with potent anti-inflammatory and proresolution effects. To date, few studies have been performed regarding their effect on pulmonary fibrosis. In the present study, using C57BL/6 mice, we report that bleomycin (BLM)-induced lung fibrosis was prevented by the concomitant treatment with an ATL synthetic analog, ATLa, which reduced inflammation and matrix deposition. ATLa inhibited BLM-induced leukocyte accumulation and alveolar collapse as evaluated by histology and morphometrical analysis. Moreover, Sirius red staining and lung hydroxyproline content showed an increased collagen deposition in mice receiving BLM alone that was decreased upon treatment with the analog. These effects resulted in benefits to pulmonary mechanics, as ATLa brought to normal levels both lung resistance and compliance. Furthermore, the analog improved mouse survival, suggesting an important role for the LX pathway in the control of disease establishment and progression. One possible mechanism by which ATLa restrained fibrosis was suggested by the finding that BLM-induced myofibroblast accumulation/differentiation in the lung parenchyma was also reduced by both simultaneous and posttreatment with the analog (alpha-actin immunohistochemistry). Interestingly, ATLa posttreatment (4 days after BLM) showed similar inhibitory effects on inflammation and matrix deposition, besides the TGF-beta level reduction in the lung, reinforcing an antifibrotic effect. In conclusion, our findings show that LX and ATL can be considered as promising therapeutic approaches to lung fibrotic diseases.

Intensity of emission lines of the quiescent solar corona: comparison between calculated and observed values

NASA Astrophysics Data System (ADS)

Krissinel, Boris

2018-03-01

The paper reports the results of calculations of the center-to-limb intensity of optically thin line emission in EUV and FUV wavelength ranges. The calculations employ a multicomponent model for the quiescent solar corona. The model includes a collection of loops of various sizes, spicules, and free (inter-loop) matter. Theoretical intensity values are found from probabilities of encountering parts of loops in the line of sight with respect to the probability of absence of other coronal components. The model uses 12 loops with sizes from 3200 to 210000 km with different values of rarefaction index and pressure at the loop base and apex. The temperature at loop apices is 1 400 000 K. The calculations utilize the CHIANTI database. The comparison between theoretical and observed emission intensity values for coronal and transition region lines obtained by the SUMER, CDS, and EIS telescopes shows quite satisfactory agreement between them, particularly for the solar disk center. For the data acquired above the limb, the enhanced discrepancies after the analysis refer to errors in EIS measurements.

Phantom Limb

NASA Image and Video Library

2017-09-25

The brightly lit limb of a crescent Enceladus looks ethereal against the blackness of space. The rest of the moon, lit by light reflected from Saturn, presents a ghostly appearance. Enceladus (313 miles or 504 kilometers across) is back-lit in this image, as is apparent by the thin crescent. However, the Sun-Enceladus-spacecraft (or phase) angle, at 141 degrees, is too low to make the moon's famous plumes easily visible. This view looks toward the Saturn-facing hemisphere of Enceladus. North on Enceladus is up. The above image is a composite of images taken with the Cassini spacecraft narrow-angle camera on March 29, 2017 using filters that allow infrared, green, and ultraviolet light. The image filter centered on 930 nm (IR) was is red in this image, the image filter centered on the green is green, and the image filter centered on 338 nm (UV) is blue. The view was obtained at a distance of approximately 110,000 miles (180,000 kilometers) from Enceladus. Image scale is 0.6 miles (1 kilometer) per pixel. The Cassini spacecraft ended its mission on Sept. 15, 2017. https://photojournal.jpl.nasa.gov/catalog/PIA21346

Reaction-diffusion systems and external morphogen gradients: the two-dimensional case, with an application to skeletal pattern formation.

PubMed

Glimm, Tilmann; Zhang, Jianying; Shen, Yun-Qiu; Newman, Stuart A

2012-03-01

We investigate a reaction-diffusion system consisting of an activator and an inhibitor in a two-dimensional domain. There is a morphogen gradient in the domain. The production of the activator depends on the concentration of the morphogen. Mathematically, this leads to reaction-diffusion equations with explicitly space-dependent terms. It is well known that in the absence of an external morphogen, the system can produce either spots or stripes via the Turing bifurcation. We derive first-order expansions for the possible patterns in the presence of an external morphogen and show how both stripes and spots are affected. This work generalizes previous one-dimensional results to two dimensions. Specifically, we consider the quasi-one-dimensional case of a thin rectangular domain and the case of a square domain. We apply the results to a model of skeletal pattern formation in vertebrate limbs. In the framework of reaction-diffusion models, our results suggest a simple explanation for some recent experimental findings in the mouse limb which are much harder to explain in positional-information-type models.

Growth of Fault-Cored Anticlines by Flexural Slip Folding: Analysis by Boundary Element Modeling

NASA Astrophysics Data System (ADS)

Johnson, Kaj M.

2018-03-01

Fault-related folds develop due to a combination of slip on the associated fault and distributed deformation off the fault. Under conditions that are sufficient for sedimentary layering to act as a stack of mechanical layers with contact slip, buckling can dramatically amplify the folding process. We develop boundary element models of fault-related folding of viscoelastic layers embedded with a reverse fault to examine the influence of such layering on fold growth. The strength of bedding contacts, the thickness and stiffness of layering, and fault geometry all contribute significantly to the resulting fold form. Frictional contact strength between layers controls the degree of localization of slip within fold limbs; high contact friction in relatively thin bedding tends to localize bedding slip within narrow kink bands on fold limbs, and low contact friction tends to produce widespread bedding slip and concentric fold form. Straight ramp faults tend to produce symmetric folds, whereas listric faults tend to produce asymmetric folds with short forelimbs and longer backlimbs. Fault-related buckle folds grow exponentially with time under steady loading rates. At early stages of folding, fold growth is largely attributed to slip on the fault, but as the fold increases amplitude, a larger portion of the fold growth is attributed to distributed slip across bedding contacts on the limbs of the fold. An important implication for geologic and earthquake studies is that not all surface deformation associated with blind reverse faults may be attributed to slip on the fault during earthquakes.

What are the Effects of Protest Fear?

DTIC Science & Technology

2014-06-01

Program AT&L Acquisition, Technology, and Logistics BPA blanket purchase agreement CONUS continental United States COR...they have awarded a task/delivery order against an IDIQ contract (or Blanket Purchase Agreement [ BPA ]) in order to avoid a bid protest. The data shows

Ice haze, snow, and the Mars water cycle

NASA Technical Reports Server (NTRS)

Kahn, Ralph

1990-01-01

Light curves and extinction profiles derived from Martian limb observations are used to constrain the atmospheric temperature structure in regions of the atmosphere with thin haze and to analyze the haze particle properties and atmospheric eddy mixing. Temperature between 170 and 190 K are obtained for three cases at levels in the atmosphere ranging from 20 to 50 km. Eddy diffusion coefficients around 100,000 sq cm/s, typical of a nonconvecting atmosphere, are derived in the haze regions at times when the atmosphere is relatively clear of dust. This parameter apparently changes by more than three orders of magnitude with season and local conditions. The derived particle size parameter varies systematically by more than an order of magnitude with condensation level, in such a way that the characteristic fall time is always about one Martian day. Ice hazes provide a mechanism for scavenging water vapor in the thin Mars atmosphere and may play a key role in the seasonal cycle of water on Mars.

Multiloculated solitary (unicameral) bone cyst in a young dog.

PubMed

Roode, Sarah C; Shive, Heather R; Hoorntje, Willemijn; Bernard, Jennifer; Stowe, Devorah M; Pool, Roy R; Grindem, Carol B

2018-05-21

A 20-month-old female spayed Staffordshire Terrier (22.3 kg) presented to the Orthopedic Surgery Service at North Carolina State University Veterinary Teaching Hospital for evaluation of a 6-week history of toe-touching to nonweight-bearing lameness in the right hind limb. Radiographs of the right stifle revealed a multiloculated lytic lesion of the distal femur, with a large open lytic zone centrally, numerous osseous septations peripherally, and focal areas of cortical thinning and loss. An aspirate of the right distal femoral lesion yielded mildly cloudy serosanguineous fluid. Cytologic examination of the fluid revealed a pleomorphic population of discrete cells that exhibited marked anisocytosis and anisokaryosis and a variable nucleus to cytoplasm (N:C) ratio, which were interpreted as probable neoplastic cells, with few macrophages, and evidence of hemorrhage. Given the clinical signs of pain, lesion size, and concern for malignant neoplasia, amputation of the right hind limb was performed. Histologically, the lesion had undulating walls 1-3 mm thick with a continuous outer layer of dense fibrous tissue and an inner layer composed of reactive cancellous bone with no cortical compacta remaining. Remnants of thin fibrous or fibro-osseous septa projected from the bony wall into the cyst lumen. The final histologic diagnosis was a benign multiloculated solitary (unicameral) bone cyst of the distal right femur. Based on the histopathologic findings, it was speculated that the cells identified on cytology were a mixture of developing osteoclasts, osteoblasts, endothelial, and stromal cells. This is the first report describing the cytologic examination of a solitary bone cyst in veterinary medicine. © 2018 American Society for Veterinary Clinical Pathology.

The Barrancas anticline in west-central Argentina: new geomorphic and geologic constraints on the geometry and activity of a fault-related fold

NASA Astrophysics Data System (ADS)

Rimando, J. M.; Schoenbohm, L. M.

2016-12-01

The Barrancas anticline in Mendoza Province, west-central Argentina is a N-NW-oriented, east-vergent fault-bend fold located in the transition from the mainly east-vergent, thin-skinned Argentine Precordillera to the mainly west-vergent, thick-skinned Sierras Pampeanas — one of the most active thrust zones on Earth. Previous studies of the Barrancas anticline interpreted its structure from 2-D and 3-D seismic data. The anticline is a fault-bend fold with multiple segments with different uplift histories and which linked only after 2.3Ma. This study aims to establish the temporal persistence of segmentation and to describe the role, extent and rates of deformation processes involved in the development of the Barrancas anticline from morphometric analyses, geologic and geomorphic mapping, and accurate dating of relevant geomorphic features. Longitudinal profile analysis of streams on the anticline reveals marked differences in normalized steepness index (ksn) between the western and eastern limbs as well as variation along strike. This distribution of ksn values reveals patterns consistent with asymmetry and segmentation of the Barrancas anticline. Swath profiles parallel to the fold axis resemble fault slip distribution profiles which was a basis for segmentation from previous studies. Drainage basin morphometric indices such as hypsometry, drainage density, and basin elongation were also measured. Hypsometric integral values were particularly higher on the west than on the east, possibly indicating younger folding on the western limb. This study will contribute to a better understanding of the nature, extent, timing, and rate of folding at the transition from thin- to thick-skinned thrust deformation in west-central Argentina. Additionally, this study will contribute to assessment of seismic hazards associated with fault-related folds in Argentina and in similar tectonic settings worldwide.

What are the Effects of Protest Fear?

DTIC Science & Technology

2014-06-17

Acquisition Professional Development Program AT&L Acquisition, Technology, and Logistics BPA blanket purchase agreement CONUS continental United States...Blanket Purchase Agreement [ BPA ]) in order to avoid a bid protest. The data shows that 88 respondents had done so throughout their career with 4,139

Military Throwaways Why Acquirers Should Go Disposable

DTIC Science & Technology

2016-02-01

Defense AT&L: January–February 2016 34 Military Throwaways? Why Acquirers Should Go Disposable Maj. Patrick Dugan, USAF Maj. Jon D. McComb...outdated they no longer are manufactured. Unfortunately, the military regularly deals with DMS issues. Going disposable would alleviate DMS concerns

Commercial aircraft engine emissions characterization of in-use aircraft at Hartsfield-Jackson Atlanta International Airport

DOT National Transportation Integrated Search

2008-01-31

The emissions from in-use commercial aircraft engines have been analyzed for selected gas-phase species and particulate characteristics using continuous extractive sampling 1-2 min downwind from operational taxi- and runways at Hartsfield-Jackson Atl...

Evaluation of concentrations of pharmaceuticals detected in sewage influents in Japan by using annual shipping and sales data.

PubMed

Azuma, Takashi; Nakada, Norihide; Yamashita, Naoyuki; Tanaka, Hiroaki

2015-11-01

A year-round monitoring survey of sewage flowing into sewage treatment plants located in urban Japan was conducted by targeting seven representative pharmaceutical components-atenolol (ATL), ciprofloxacin (CFX), clarithromycin (CTM), diclofenac (DCF), diltiazem (DTZ), disopyramide (DSP), and sulpiride (SPR)-detected in the river environment. For each of these components, two types of predicted concentration were estimated on the basis of two types of data (the shipping volume and sales volume of each component). The measured concentration of each component obtained through the survey and the two types of estimated predicted concentration of each component were then compared. The correspondence ratio between the predicted concentration estimated from the shipping volume of the component and the measured concentration (predicted concentration/measured concentration) was, for ATL, 3.1; CFX, 1.4; CTM, 1.4; DCF, 0.2; DTZ, 0.9; DSP, 11.6; and SPR, 1.1. The correspondence ratio between the predicted concentration estimated from the sales volume of the component and the measured concentration was, for ATL, 0.5; CFX, 1.1; CTM, 0.8; DCF, 0.1; DTZ, 0.2; DSP, 0.7; and SPR, 0.8. Although a generally corresponding trend was seen regardless of whether the prediction was based on shipping volume or sales volume, the predicted concentrations estimated from the shipping volumes of all components expect DSP were found, to our knowledge for the first time in Japan, to correspond better than those based on sales volumes to the measured concentrations. These findings should help to improve the prediction accuracy of concentrations of pharmaceutical components in river waters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of the Jonker-Volgenant-Castanon (JVC) assignment algorithm for track association

NASA Astrophysics Data System (ADS)

Malkoff, Donald B.

1997-07-01

The Jonker-Volgenant-Castanon (JVC) assignment algorithm was used by Lockheed Martin Advanced Technology Laboratories (ATL) for track association in the Rotorcraft Pilot's Associate (RPA) program. RPA is Army Aviation's largest science and technology program, involving an integrated hardware/software system approach for a next generation helicopter containing advanced sensor equipments and applying artificial intelligence `associate' technologies. ATL is responsible for the multisensor, multitarget, onboard/offboard track fusion. McDonnell Douglas Helicopter Systems is the prime contractor and Lockheed Martin Federal Systems is responsible for developing much of the cognitive decision aiding and controls-and-displays subsystems. RPA is scheduled for flight testing beginning in 1997. RPA is unique in requiring real-time tracking and fusion for large numbers of highly-maneuverable ground (and air) targets in a target-dense environment. It uses diverse sensors and is concerned with a large area of interest. Target class and identification data is tightly integrated with spatial and kinematic data throughout the processing. Because of platform constraints, processing hardware for track fusion was quite limited. No previous experience using JVC in this type environment had been reported. ATL performed extensive testing of the JVC, concentrating on error rates and run- times under a variety of conditions. These included wide ranging numbers and types of targets, sensor uncertainties, target attributes, differing degrees of target maneuverability, and diverse combinations of sensors. Testing utilized Monte Carlo approaches, as well as many kinds of challenging scenarios. Comparisons were made with a nearest-neighbor algorithm and a new, proprietary algorithm (the `Competition' algorithm). The JVC proved to be an excellent choice for the RPA environment, providing a good balance between speed of operation and accuracy of results.

Verbal memory outcome in patients with normal preoperative verbal memory and left mesial temporal sclerosis.

PubMed

LoGalbo, Anthony; Sawrie, Stephen; Roth, David L; Kuzniecky, Ruben; Knowlton, Robert; Faught, Edward; Martin, Roy

2005-05-01

Previous studies have shown that structural integrity (i.e., presence/absence of mesial temporal sclerosis (MTS)) of the left mesial temporal lobe is associated with verbal memory outcome following left anterior temporal lobectomy (ATL). However, the functional integrity of the left temporal lobe, as exemplified by preoperative verbal memory performance, has also been associated with verbal memory outcome following surgery. We investigated the risk of verbal memory loss in patients with known structural abnormality (i.e., left mesial temporal sclerosis by MRI) and normal preoperative verbal memory performance who undergo left ATL. Seventeen patients with left temporal lobe epilepsy, MRI-based exclusive left MTS, and normal preoperative verbal memory were identified. Normal verbal memory was defined as performance on both Acquisition (learning across trials 1-5) and Retrieval (long delayed free recall) portions of the California Verbal Learning Test (CVLT) above a T score of 40 (>16%ile). Postoperative verbal memory outcome was established by incorporating standardized regression-based (SRB) change scores. Postoperative declines across both CVLT Retrieval T scores and Acquisition T scores (average 20% and average 15% declines from baseline scores, respectively) were measured for the group. The average CVLT Retrieval SRB change score was -2.5, and the average CVLT Acquisition SRB change score was -1.0. A larger proportion of patients demonstrated postoperative declines on Retrieval scores than Acquisition scores (64.7% vs 17.6%, respectively). Even in the presence of left MTS, patients exhibiting normal presurgical verbal memory are at risk for verbal memory declines following ATL. These results suggest that the functional integrity of the left mesial temporal lobe may play an important role in the verbal memory outcome in this patient group.

In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP)

PubMed Central

Saito, Mineki; Matsuzaki, Toshio; Satou, Yorifumi; Yasunaga, Jun-ichirou; Saito, Kousuke; Arimura, Kimiyoshi; Matsuoka, Masao; Ohara, Yoshiro

2009-01-01

Background Recently, human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ), encoded from a minus strand mRNA was discovered and was suggested to play an important role in adult T cell leukemia (ATL) development. However, there have been no reports on the role of HBZ in patients with HTLV-1 associated inflammatory diseases. Results We quantified the HBZ and tax mRNA expression levels in peripheral blood from 56 HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, 10 ATL patients, 38 healthy asymptomatic carriers (HCs) and 20 normal uninfected controls, as well as human leukemic T-cell lines and HTLV-1-infected T-cell lines, and the data were correlated with clinical parameters. The spliced HBZ gene was transcribed in all HTLV-1-infected individuals examined, whereas tax mRNA was not transcribed in significant numbers of subjects in the same groups. Although the amount of HBZ mRNA expression was highest in ATL, medium in HAM/TSP, and lowest in HCs, with statistical significance, neither tax nor the HBZ mRNA expression per HTLV-1-infected cell differed significantly between each clinical group. The HTLV-1 HBZ, but not tax mRNA load, positively correlated with disease severity and with neopterin concentration in the cerebrospinal fluid of HAM/TSP patients. Furthermore, HBZ mRNA expression per HTLV-1-infected cell was decreased after successful immunomodulatory treatment for HAM/TSP. Conclusion These findings suggest that in vivo expression of HBZ plays a role in HAM/TSP pathogenesis. PMID:19228429

Telomere Length and the Risk of Atrial Fibrillation: Insights into the Role of Biological versus Chronological Aging

PubMed Central

Roberts, Jason D.; Dewland, Thomas A.; Longoria, James; Fitzpatrick, Annette L.; Ziv, Elad; Hu, Donglei; Lin, Jue; Glidden, David V.; Psaty, Bruce M.; Burchard, Esteban G.; Blackburn, Elizabeth H.; Olgin, Jeffrey E.; Heckbert, Susan R.; Marcus, Gregory M.

2014-01-01

Background Advanced age is the most important risk factor for atrial fibrillation (AF), however the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length (ATL) and LTL in cardiac surgery patients. Methods and Results Mean LTL and the TERT rs2736100 single nucleotide polymorphism (SNP) were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of ATL versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF prior to and after adjustment for potential confounders (adjusted hazard ratio [HR] 1.09; 95% CI: 0.92–1.29, p=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 SNP and incident AF (adjusted HR: 0.95; 95% CI: 0.88–1.04, p=0.265). In 35 cardiac surgery patients (26 with AF), ATL was longer than LTL (1.19 ± 0.20 versus 1.02 ± 0.25 [T/S ratio], p< 0.001), a finding that remained consistent within the AF subgroup. Conclusions Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF. PMID:25381796

The predictive value of FDG-PET with 3D-SSP for surgical outcomes in patients with temporal lobe epilepsy.

PubMed

Higo, Takuma; Sugano, Hidenori; Nakajima, Madoka; Karagiozov, Kostadin; Iimura, Yasushi; Suzuki, Masaru; Sato, Kiyoshi; Arai, Hajime

2016-10-01

We retrospectively evaluated the diagnostic value of (18)F-2-fluorodeoxy-d-glucose positron emission tomography (FDG-PET) with statistical analysis for the foci detection and predictive utility for postsurgical seizure outcome of patients with mesial temporal lobe epilepsy (mTLE). We evaluated 40 patients who were diagnosed mTLE and underwent selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) in our institute. Preoperative interictal FDG-PET with statistical analysis using three-dimensional stereotactic surface projection (3D-SSP) was detected with several clinical data including seizure semiology, MRI, scalp electroencephalography, surgical procedure with SAH or ATL and postsurgical outcome. The region of interest (ROI) was defined on 'Hippocampus & Amygdala', 'Parahippocampal gyrus & Uncus', 'T1 & T2', and 'T3 & Fusiform gyrus'. We obtained the ratio of hypometabolism difference (RHD) by 3D-SSP, and evaluated the relation among hypometabolic extent, surgical outcome and surgical procedure. The RHD in each ROIs ipsilateral to operative side was significantly higher than that of contralateral side in good outcome group. Hypometabolism of 'Hippocampus & Amygdala' was most reliable prognostic factor. Patients of discordant with presurgical examinations hardly showed obvious lateralized hypometabolism. Nevertheless, when they have significantly high RHD in mesial temporal lobe, good surgical outcome was expected. There was not significant difference of RHD distribution between SAH and ATL in good outcome group. Significant hypometabolism in mesial temporal lobe on FDG-PET with 3D-SSP is useful to predict good surgical outcome for patients with mTLE, particularly in discordant patients with hypometabolism in mesial temporal structure. However, FDG-PET is not indicative of surgical procedure. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy.

PubMed

Grammaldo, Liliana G; Di Gennaro, Giancarlo; Giampà, Teresa; De Risi, Marco; Meldolesi, Giulio N; Mascia, Addolorata; Sparano, Antonio; Esposito, Vincenzo; Quarato, Pier Paolo; Picardi, Angelo

2009-03-01

Memory decline is often observed after anterior temporal lobectomy (ATL), particularly in patients with dominant hemisphere resections. However, the follow-up length has been 1 year or less in most studies. Our aims were to examine postoperative memory changes over a longer period and to identify baseline demographic and clinical predictors of memory outcome. We administered material-specific memory tests at baseline, and 1 and 2 years after surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non-invasive presurgical protocol. Repeated measures multivariate analysis of variance (RM-MANOVA) was used to examine the relationship between changes in memory tests scores over time and side of TLE and pathology. Also, standardized residual change scores were calculated for each memory test and entered in multiple linear regression models aimed at identifying baseline predictors of better memory outcome. RM-MANOVA revealed a significant change in memory test scores over time, with an interaction between time and side of surgery, as 2 years after surgery patients with RTLE were improved while patients with LTLE were not worse as compared with baseline. Pathology was not associated with changes in memory scores. In multiple regression analysis, significant associations were found between right TLE and greater improvement in verbal memory, younger age and greater improvement in visuospatial memory, and male gender and greater improvement in both verbal and visuospatial memory. Our results suggest that the long-term memory outcome of TLE patients undergoing ATL without invasive presurgical assessment may be good in most cases not only for right-sided but also for left-sided resections.

Predictive factors of long-term outcomes of surgery for mesial temporal lobe epilepsy associated with hippocampal sclerosis.

PubMed

Mathon, Bertrand; Bielle, Franck; Samson, Séverine; Plaisant, Odile; Dupont, Sophie; Bertrand, Anne; Miles, Richard; Nguyen-Michel, Vi-Huong; Lambrecq, Virginie; Calderon-Garcidueñas, Ana Laura; Duyckaerts, Charles; Carpentier, Alexandre; Baulac, Michel; Cornu, Philippe; Adam, Claude; Clemenceau, Stéphane; Navarro, Vincent

2017-08-01

The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear. This retrospective study analyzed seizure, cognitive, and psychiatric outcomes, searching for factors associated with seizure relapse or cognitive and psychiatric deterioration after MTLE-HS surgery. Seizure, cognitive, and psychiatric outcomes were reviewed after 389 surgeries performed between 1990 and 2015 on patients aged 15-67 years at a tertiary center. Three surgical approaches were used: anterior temporal lobectomy (ATL; n = 209), transcortical selective amygdalohippocampectomy (SAH; n = 144), and transsylvian SAH (n = 36). With an average follow-up of 8.7 years (range = 1.0-25.2), seizure outcome was classified as Engel I in 83.7% and Engel Ia in 57.1% of patients. The histological classification of HS was type 1 for 75.3% of patients, type 2 for 18.7%, and type 3 for 1.2%. Two factors were significantly associated with seizure recurrence: past history of status epilepticus and preoperative intracranial electroencephalographic recording. In contrast, neither HS type, the presence of a dual pathology, nor surgical approach was associated with seizure outcome. Risk of cognitive impairment was 3.12 (95% confidence interval = 1.27-7.70), greater in patients after ATL than in patients after transcortical SAH. A presurgical psychiatric history and postoperative cognitive impairment were associated with poor psychiatric outcome. The SAH and ATL approaches have similar beneficial effects on seizure control, whereas transcortical SAH tends to minimize cognitive deterioration after surgery. Variation in postsurgical outcome with the class of HS should be investigated further. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

The Differential Contributions of Conceptual Representation Format and Language Structure to Levels of Semantic Abstraction Capacity.

PubMed

Gainotti, Guido

2017-06-01

This paper reviews some controversies concerning the original and revised versions of the 'hub-and-spoke' model of conceptual representations and their implication for abstraction capacity levels. The 'hub-and-spoke' model, which is based on data gathered in patients with semantic dementia (SD), is the most authoritative model of conceptual knowledge. Patterson et al.'s (Nature Reviews Neuroscience, 8(12), 976-987, 2007) classical version of this model maintained that conceptual representations are stored in a unitary 'amodal' format in the right and left anterior temporal lobes (ATLs), because in SD the semantic disorder cuts across modalities and categories. Several authors questioned the unitary nature of these representations. They showed that the semantic impairment is 'multi-modal'only in the advanced stages of SD, when atrophy affects the ATLs bilaterally, but that impariments can be modality-specific in lateralised (early) stages of the disease. In these cases, SD mainly affects lexical-semantic knowledge when atrophy predominates on the left side and pictorial representations when atrophy prevails on the right side. Some aspects of the model (i.e. the importance of spokes, the multimodal format of representations and the graded convergence of modalities within the ATLs), which had already been outlined by Rogers et al. (Psychological Review, 111(1), 205-235, 2004) in a computational model of SD, were strengthened by these results. The relevance of these theoretical problems and of empirical data concerning the neural substrate of concrete and abstract words is discussed critically. The conclusion of the review is that the highest levels of abstraction are due more to the structuring influence of language than to the format of representations.

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role.

PubMed

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4 + /CD25 + T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells1

PubMed Central

Kimura, Ryuichiro; Senba, Masachika; Cutler, Samuel J; Ralph, Stephen J; Xiao, Gutian; Mori, Naoki

2013-01-01

Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia (ATL) and various inflammatory disorders including HTLV-I-associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is known to cause permanent activation of many cellular transcription factors including nuclear factor-κB (NF-κB), cyclic adenosine 3′,5′-monophosphate response element-binding protein, and activator protein 1 (AP-1). Here, we show that NF-κB-binding cofactor inhibitor of NF-κB-ζ (IκB-ζ) is constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax transactivates the IκB-ζ gene, mainly through NF-κB. Microarray analysis of IκB-ζ-expressing uninfected T cells demonstrated that IκB-ζ induced the expression of NF-κB. and interferon-regulatory genes such as B cell CLL/lymphoma 3 (Bcl3), guanylate-binding protein 1, and signal transducer and activator of transcription 1. The transcriptional activation domain, nuclear localization signal, and NF-κB-binding domain of IκB-ζ were required for Bcl3 induction, and IκB-ζ synergistically enhanced Tax-induced Bcl3 transactivation in an NF-κB-dependent manner. Interestingly, IκB-ζ inhibited Tax-induced NF-κB, AP-1 activation, and HTLV-I transcription. Furthermore, IκB-ζ interacted with Tax in vitro and this interaction was also observed in an HTLV-I-transformed T cell line. These results suggest that IκB-ζ modulates Tax-dependent and Tax-independent gene transcription in T cells. The function of IκB-ζ may be of significance in ATL genesis and pathogenesis of HTLV-I-associated diseases. PMID:24027435

HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax.

PubMed

Ando, Satomi; Hasegawa, Atsuhiko; Murakami, Yuji; Zeng, Na; Takatsuka, Natsuko; Maeda, Yasuhiro; Masuda, Takao; Suehiro, Youko; Kannagi, Mari

2017-02-01

Adult T cell leukemia/lymphoma (ATL), a CD4 + T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8 + T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope-pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8 + T cells capable of proliferating and producing IFN-γ. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1-specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1-specific CTL responses, thereby reducing the risk of the development of ATL. Copyright © 2017 by The American Association of Immunologists, Inc.

Feeding preference of the shredder Phylloicus sp. for plant leaves of Chrysophyllum oliviforme or Miconia chartacea after conditioning in streams from different biomes.

PubMed

Reis, D F; Machado, M M D; Coutinho, N P; Rangel, J V; Moretti, M S; Morais, P B

2018-04-23

Macroinvertebrate shredders consume preferably leaves conditioned by fungi and bacteria which offer greater palatability to them. Plant species in Cerrado present high concentration of chemical elements such as lignin and cellulose, phenols and tanins thus making them less attractive for shredders consumption and limiting the palatability. This study aimed to evaluate the feeding preference of a macroinvertebrate shredder of the genus Phylloicus for plant material from two different biomes (Cerrado and Mata Atlântica), after conditioning in a stream of Mata Atlântica and observing their physical and chemical characteristics. Senescent leaves were collected, monthly from the litterfall of riparian vegetation in a 500 m stretch of a stream in each biome from August 2014 to January 201. The most abundant species in each stream was selected for the experiment. The experimental design consisted in with two treatments. The first (T1) comprised leaf discs from Chrysophyllum oliviforme (Cerrado species) together with leaf discs of Miconia chartacea (Atlantic Forest species) which were conditioned in the Atlantic Forest stream. The second treatment (T2) involved leaf discs of Miconia chartacea conditioned in Mata Altlântica and Cerrado streams. Both tests had showed significant differences between the two treatments (T1 and T2). For T1, there was consumption of M. chartacea leaf discs by Phylloicus sp., but there was no consumption of C. oliviforme discs. For T2, there was preference for M. chartaceae leaves conditioned in a stream of Mata Atlântica than in Cerrado stream. The results showed that Phylloicus sp., had presented preference for food detritus of the Mata Antlântica biome and rejection to the one from Cerrado biome.

Performance of advanced trauma life support procedures in microgravity

NASA Technical Reports Server (NTRS)

Campbell, Mark R.; Billica, Roger D.; Johnston, Smith L 3rd; Muller, Matthew S.

2002-01-01

BACKGROUND: Medical operations on the International Space Station will emphasize the stabilization and transport of critically injured personnel and so will need to be capable of advanced trauma life support (ATLS). METHODS: We evaluated the ATLS invasive procedures in the microgravity environment of parabolic flight using a porcine animal model. Included in the procedures evaluated were artificial ventilation, intravenous infusion, laceration closure, tracheostomy, Foley catheter drainage, chest tube insertion, peritoneal lavage, and the use of telemedicine methods for procedural direction. RESULTS: Artificial ventilation was performed and appeared to be unaltered from the 1-G environment. Intravenous infusion, laceration closure, percutaneous dilational tracheostomy, and Foley catheter drainage were achieved without difficulty. Chest tube insertion and drainage were performed with no more difficulty than in the 1-G environment due to the ability to restrain patient, operator and supplies. A Heimlich valve and Sorenson drainage system were both used to provide for chest tube drainage collection with minimal equipment, without the risk of atmospheric contamination, and with the capability to auto-transfuse blood drained from a hemothorax. The use of telemedicine in chest tube insertion was demonstrated to be useful and feasible. Peritoneal lavage using a percutaneous technique, although requiring less training to perform, was found to be dangerous in weightlessness due to the additional pressure of the bowel on the anterior abdominal wall creating a high risk of bowel perforation. CONCLUSIONS: The performance of ATLS procedures in microgravity appears to be feasible with the exception of diagnostic peritoneal lavage. Minor modifications to equipment and techniques are required in microgravity to effect surgical drainage in the presence of altered fluid dynamics, to prevent atmospheric contamination, and to provide for the restraint requirements. A parabolic simulation system was developed for equipment and procedure verification, physiological research, and possible crew medical officer training in the future.

Anticancer effects of phenoxazine derivatives revealed by inhibition of cell growth and viability, disregulation of cell cycle, and apoptosis induction in HTLV-1-positive leukemia cells.

PubMed

Miyano-Kurosaki, Naoko; Ikegami, Kou; Kurosaki, Kunihiko; Endo, Takahiko; Aoyagi, Hoshimi; Hanami, Mari; Yasumoto, Jun; Tomoda, Akio

2009-05-01

Adult T-cell leukemia (ATL) is a malignant tumor of human CD4(+) T cells infected with a human retrovirus, T lymphotropic virus type-1 (HTLV-1). The aim of the present study was to investigate the apoptotic effects of phenoxazines, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4alpha-dihydro-4alpha,8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on a T cell leukemia cell line from ATL patients, MT-1 cells; HTLV-1 transformed T-cell lines, HUT-102 cells and MT-2 cells; and an HTLV-1-negative rat sarcoma cell line, XC cells. Among these phenoxazines, Phx-3 at concentrations of less than 10 microg/ml extensively inhibited growth and cell viability; arrested cell cycles at sub G(0)/G(1) phase; and augmented apoptosis of MT-1, HUT-102, and MT-2 cells. However, these phenoxazines did not affect the cell viability of an HTLV-1-negative rat sarcoma cell line, XC cells, and phytohemaggutinin-activated human peripheral blood mononuclear cells, although they markedly inhibited the growth of these cells. The transmission of HTLV-1 from HTLV-1-positive cells (MT-2 cells) to HTLV-1-negative cells (XC cells) was considered to be prevented by Phx-1, Phx-2, or Phx-3 because the syncytium formation between these cells was inhibited markedly in the presence of these phenoxazines. The present results suggest that Phx-1, Phx-2, and, in particular, Phx-3 may be useful as therapeutic agents against ATL, which is extremely refractory to current therapies.

HTLV Deregulation of the NF-κB Pathway: An Update on Tax and Antisense Proteins Role

PubMed Central

Fochi, Stefania; Mutascio, Simona; Bertazzoni, Umberto; Zipeto, Donato; Romanelli, Maria G.

2018-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed toward the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins. PMID:29515558

[An epidemiologic study of anti-ATLA (antibody to adult T-cell leukemia-associated antigen) by category of disease in the Karatsu and Higashimatsuura districts of northern Kyusyu by enzymeimmunoassay].

PubMed

Morofuji, M; Kajiyama, W; Nakashima, K; Noguchi, A; Hayashi, J; Kashiwagi, S; Sumida, I; Hanada, M

1990-08-01

The Kyusyu district is known as an endemic area of HTLV-I. But the prevalence of anti-ATLA in Saga prefecture was reportedly relatively low. In this study, in order to determine the distribution of antibody to ATL-associated antigen (anti-ATLA) in the Karatsu and Higashimatsuura districts of the northern Kyusyu, the determination of anti-ATLA status of patients in Karatsu Red Cross Hospital was carried out from September to October, 1985. Sera from 757 patients were tested for presence of anti-ATLA by Enzyme immunoassay (EIA) prepared by Eisai Co., Ltd. Tokyo, Japan. Results obtained are as follows: 1) Overall prevalence of anti-ATLA was 13.7 per cent (104 of 757 individuals). Prevalence of anti-ATLA increased with age, reaching a maximum of 21.1 per cent for people from 60 to 69 years old. 2) Prevalence of anti-ATLA was 9.5 per cent (36 of 376) in males and 17.8 per cent (68 of 381) in females. A significant difference by sex was recognized. (p less than 0.001) 3) The positive rates of patients with non-malignant diseases were high in the Chinzei, Hizen, and Hamatama areas facing the Sea of Genkai. The positive rate of the seaside area was significantly higher than that of the mountain area. (p less than 0.001). 4) Anti-ATLA was most prevalent in the patients with neoplasms (26.1%). The positive rate of ATL patients was 100 per cent, and that of patients with malignancies other than ATL was 25.9 per cent. These results suggest that HTLV-I infection is likely to increase the incidence of other types of malignancy.

Histological evidence for muscle insertion in extant amniote femora: implications for muscle reconstruction in fossils.

PubMed

Petermann, Holger; Sander, Martin

2013-04-01

Since the 19th century, identification of muscle attachment sites on bones has been important for muscle reconstructions, especially in fossil tetrapods, and therefore has been the subject of numerous biological and paleontological studies. At the microscopic level, in histological thin sections, the only features that can be used reliably for identifying tendon-bone or muscle-tendon-bone interactions are Sharpey's fibers. Muscles, however, do not only attach to the bone indirectly with tendons, but also directly. Previous studies failed to provide new indicators for muscle attachment, or to address the question of whether muscles with direct attachment can be identified histologically. However, histological identification of direct muscle attachments is important because these attachments do not leave visible marks (e.g. scars and rugosities) on the bone surface. We dissected the right hind limb and mapped the muscle attachment sites on the femur of one rabbit (Oryctolagus cuniculus), one Alligator mississippiensis, and one turkey (Meleagris cuniculus). We then extracted the femur and prepared four histological thin sections for the rabbit and the turkey and five histological thin sections for the alligator. Sharpey's fibers, vascular canal orientation, and a frayed periosteal margin can be indicators for indirect but also direct muscle attachment. Sharpey's fibers can be oriented to the cutting plane of the thin section at high angles, and two Sharpey's fibers orientations can occur in one area, possibly indicating a secondary force axis. However, only about 60% of mapped muscle attachment sites could be detected in thin sections, and frequently histological features suggestive of muscle attachment occurred outside mapped sites. While these insights should improve our ability to successfully identify and reconstruct muscles in extinct species, they also show the limitations of this approach. © 2013 The Authors Journal of Anatomy © 2013 Anatomical Society.

Histological evidence for muscle insertion in extant amniote femora: implications for muscle reconstruction in fossils

PubMed Central

Petermann, Holger; Sander, Martin

2013-01-01

Since the 19th century, identification of muscle attachment sites on bones has been important for muscle reconstructions, especially in fossil tetrapods, and therefore has been the subject of numerous biological and paleontological studies. At the microscopic level, in histological thin sections, the only features that can be used reliably for identifying tendon–bone or muscle–tendon-bone interactions are Sharpey's fibers. Muscles, however, do not only attach to the bone indirectly with tendons, but also directly. Previous studies failed to provide new indicators for muscle attachment, or to address the question of whether muscles with direct attachment can be identified histologically. However, histological identification of direct muscle attachments is important because these attachments do not leave visible marks (e.g. scars and rugosities) on the bone surface. We dissected the right hind limb and mapped the muscle attachment sites on the femur of one rabbit (Oryctolagus cuniculus), one Alligator mississippiensis, and one turkey (Meleagris cuniculus). We then extracted the femur and prepared four histological thin sections for the rabbit and the turkey and five histological thin sections for the alligator. Sharpey's fibers, vascular canal orientation, and a frayed periosteal margin can be indicators for indirect but also direct muscle attachment. Sharpey's fibers can be oriented to the cutting plane of the thin section at high angles, and two Sharpey's fibers orientations can occur in one area, possibly indicating a secondary force axis. However, only about 60% of mapped muscle attachment sites could be detected in thin sections, and frequently histological features suggestive of muscle attachment occurred outside mapped sites. While these insights should improve our ability to successfully identify and reconstruct muscles in extinct species, they also show the limitations of this approach. PMID:23439026

Earth Observations taken by the Expedition 39 Crew

NASA Image and Video Library

2014-04-02

ISS039-E-009160 (2 April 2014) --- This nighttime view featuring the aurora borealis, the moon and Moscow was photographed by an Expedition 39 crew member on the International Space Station. A thin green line of the aurora borealis crosses the top of this image. The moon appears as a white disc just above the aurora. Airglow appears as a blue-white cusp on Earth's limb. Russia's capital city Moscow makes a splash of yellow (lower left), with its easily recognized radial pattern of highways. Other cities are Nizhni Novgorod (lower center) 400 kilometers from Moscow, St. Petersburg (left) 625 kilometers from Moscow, and Finland?s capital city Helsinki.

A new forest-dwelling Bent-toed Gecko (Squamata: Gekkonidae: Cyrtodactylus) from Doi Suthep, Chiang Mai Province, northern Thailand.

PubMed

Kunya, Kirati; Panmongkol, Aumporn; Pauwels, Olivier S G; Sumontha, Montri; Meewasana, Jiraporn; Bunkhwamdi, Woraphot; Dangsri, Siriwat

2014-06-03

We describe a new forest-dwelling Cyrtodactylus from Doi Suthep, Chiang Mai Province, northern Thailand. Cyrtodactylus doisuthep sp. nov. is characterized by a maximal known SVL of 90.5 mm; 19 or 20 longitudinal rows of dorsal tubercles; a continuous series of 34 or 35 enlarged femoro-precloacal scales, including six or seven pitted scales on each femur (male and females) separated by a diastema from six pitted (females) or pore-bearing (male) precloacal scales; no precloacal groove or depression; transversely enlarged subcaudal scales; and six or seven irregular thin beige dorsal bands between limb insertions. 

Defense AT&L (Volume 37, Number 3, May-June 2008)

DTIC Science & Technology

2008-06-01

which needs spectrum for consumer products such as cell phones and Blackberry ® devices. Q. Speaking of spectrum, the Defense Spectrum Organization...Modernism is arrogant, risk-averse, and ill-suited to a dynamic environment. Its tunnel vision inappropriately disregards inconvenient data and

Developing a Self-Sustaining Afghan National Army

DTIC Science & Technology

2009-12-03

Cordesman, Follow the Money : Why the US is Losing the War in Afghanistan, (Center For Strategic & International Studies, Washington DC: September 2008...Adrian Marsh. “Building an Army Program Management in Afghanistan,” Defense AT&L (July-August 2006). Cordesman, Anthony H. Follow the Money : Why

A survey of ATL-compatible radiometer antennas

NASA Technical Reports Server (NTRS)

Love, A. W.

1975-01-01

A survey was made of antennas suitable for remote sensing of the earth's surface, in particular the world ocean, by means of microwave radiometers operating in the 1 to 26 GHz frequency region and carried on board the shuttle-launched advanced technology laboratory. Array antennas are found to be unattractive and unsuited to the task. Reflectors, including Cassegrain and offset types, as well as horn-reflectors are possible candidates but all have shortcomings which impair the accuracy of measurement. Horns of the corrugated type have excellent electrical characteristics. Although they are physically very large and will require development of suitable deployment mechanisms, they appear to be valid candidates for the task. The evolution of the periscope antenna is outlined, and it is shown to possess nearly ideal electrical characteristics for the intended application. Its only shortcoming is that the feed horn creates aperture blocking; there is no blocking due to struts or any other source. The periscope antenna is recommended for ATL radiometry.

[Relationship between cognitive content and emotions following dilatory behavior: considering the level of trait procrastination].

PubMed

Hayashi, Junichiro

2009-02-01

The present study developed and evaluated the Automatic Thoughts List following Dilatory Behavior (ATL-DB) to explore the mediation hypothesis and the content-specificity hypothesis about the automatic thoughts with trait procrastination and emotions. In Study 1, data from 113 Japanese college students were used to choose 22 items to construct the ATL-DB. Two factors were indentified, I. Criticism of Self and Behavior, II. Difficulty in Achievement. These factors had high degrees of internal consistency and had positive correlations to trait procrastination. In Study 2, the relationships among trait procrastination, the automatic thoughts, depression, and anxiety were examined in 261 college students by using Structural Equation Modeling. The results showed that the influence of trait procrastination on depression was mainly mediated through Criticism of Self and Behavior only, while the influence of trait procrastination to anxiety was mediated through Criticism of Self and Behavior and Difficulty in Achievement. Therefore, the mediation hypothesis was supported and the content-specificity hypothesis was partially supported.

Divorce, approaches to learning, and children's academic achievement: a longitudinal analysis of mediated and moderated effects.

PubMed

Anthony, Christopher J; DiPerna, James Clyde; Amato, Paul R

2014-06-01

Data from the Early Childhood Longitudinal Study--Kindergarten Cohort (ECLS-K) were used to test the hypothesis that approaches to learning (ATL) mediates the link between parental divorce and academic achievement. Fixed effects regression was utilized to test for mediation, and subsequent moderation analyses examining gender and age at time of divorce also were conducted. Results indicated that divorce was associated with less growth in test scores and that ATL mediated 18% and 12% of this association in reading and mathematics respectively. Parental divorce also was associated with larger negative effects for children who experienced divorce at an older age as well as for girls' mathematics test scores. These findings contribute to the understanding of the impact of parental divorce on children's academic achievement and underscore the importance of focusing on the variability of child outcomes following parental divorce. Copyright © 2014 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Neural changes associated with semantic processing in healthy aging despite intact behavioral performance.

PubMed

Lacombe, Jacinthe; Jolicoeur, Pierre; Grimault, Stephan; Pineault, Jessica; Joubert, Sven

2015-10-01

Semantic memory recruits an extensive neural network including the left inferior prefrontal cortex (IPC) and the left temporoparietal region, which are involved in semantic control processes, as well as the anterior temporal lobe region (ATL) which is considered to be involved in processing semantic information at a central level. However, little is known about the underlying neuronal integrity of the semantic network in normal aging. Young and older healthy adults carried out a semantic judgment task while their cortical activity was recorded using magnetoencephalography (MEG). Despite equivalent behavioral performance, young adults activated the left IPC to a greater extent than older adults, while the latter group recruited the temporoparietal region bilaterally and the left ATL to a greater extent than younger adults. Results indicate that significant neuronal changes occur in normal aging, mainly in regions underlying semantic control processes, despite an apparent stability in performance at the behavioral level. Copyright © 2015 Elsevier Inc. All rights reserved.

Management and Oversight of Services Acquisition Within the United States Air Force

DTIC Science & Technology

2008-12-01

Air Mobility Command AFDW Air Force District of Washington AFSPC Air Force Space Command AT&L Acquisition Technologies and Logistics CPM ...were commonly performed in industry. The types of services included advertising for Navy recruitment, custodial services on Air Force bases, and on

A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation.

PubMed

Menezes, Soraya Maria; Leal, Fabio E; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

2017-01-01

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fas hi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fas hi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fas hi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased, but not defective Fas signaling in HAM/TSP. In silico analysis revealed biased Fas signaling toward proliferation and inflammation, driven by RelA/NF-κB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSP ex vivo transcriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fas hi lymphocyte phenotype in HAM/TSP, distinguishable from MS. Non-apoptotic Fas signaling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation, and early age of onset.

A Fashi Lymphoproliferative Phenotype Reveals Non-Apoptotic Fas Signaling in HTLV-1-Associated Neuroinflammation

PubMed Central

Menezes, Soraya Maria; Leal, Fabio E.; Dierckx, Tim; Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Schnitman, Saul V.; Kruschewsky, Ramon; López, Giovanni; Alvarez, Carolina; Talledo, Michael; Gotuzzo, Eduardo; Nixon, Douglas F.; Vercauteren, Jurgen; Brassat, David; Liblau, Roland; Vandamme, Anne Mieke; Galvão-Castro, Bernardo; Van Weyenbergh, Johan

2017-01-01

Human T-cell lymphotropic virus (HTLV)-1 was the first human retrovirus to be associated to cancer, namely adult T-cell leukemia (ATL), but its pathogenesis remains enigmatic, since only a minority of infected individuals develops either ATL or the neuroinflammatory disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). A functional FAS -670 polymorphism in an interferon (IFN)-regulated STAT1-binding site has been associated to both ATL and HAM/TSP susceptibility. Fashi T stem cell memory (Tscm) cells have been identified as the hierarchical apex of ATL, but have not been investigated in HAM/TSP. In addition, both FAS and STAT1 have been identified in an IFN-inducible HAM/TSP gene signature, but its pathobiological significance remains unclear. We comprehensively explored Fas expression (protein/mRNA) and function in lymphocyte activation, apoptosis, proliferation, and transcriptome, in PBMC from a total of 47 HAM/TSP patients, 40 asymptomatic HTLV-1-infected individuals (AC), and 58 HTLV-1 -uninfected healthy controls. Fas surface expression followed a two-step increase from HC to AC and from AC to HAM/TSP. In HAM/TSP, Fas levels correlated positively to lymphocyte activation markers, but negatively to age of onset, linking Fashi cells to earlier, more aggressive disease. Surprisingly, increased lymphocyte Fas expression in HAM/TSP was linked to decreased apoptosis and increased lymphoproliferation upon in vitro culture, but not to proviral load. This Fashi phenotype is HAM/TSP-specific, since both ex vivo and in vitro Fas expression was increased as compared to multiple sclerosis (MS), another neuroinflammatory disorder. To elucidate the molecular mechanism underlying non-apoptotic Fas signaling in HAM/TSP, we combined transcriptome analysis with functional assays, i.e., blocking vs. triggering Fas receptor in vitro with antagonist and agonist-, anti-Fas mAb, respectively. Treatment with agonist anti-Fas mAb restored apoptosis, indicating biased, but not defective Fas signaling in HAM/TSP. In silico analysis revealed biased Fas signaling toward proliferation and inflammation, driven by RelA/NF-κB. Correlation of Fas transcript levels with proliferation (but not apoptosis) was confirmed in HAM/TSP ex vivo transcriptomes. In conclusion, we demonstrated a two-step increase in Fas expression, revealing a unique Fashi lymphocyte phenotype in HAM/TSP, distinguishable from MS. Non-apoptotic Fas signaling might fuel HAM/TSP pathogenesis, through increased lymphoproliferation, inflammation, and early age of onset. PMID:28261198

Probable Earthquake Archaeological Effects in the ancient pyramids of Quetzalcóatl and Sun in Teotihuacán (Central Mexico)

NASA Astrophysics Data System (ADS)

Perez-Lopez, Raul; Rodríguez-Pascua, Miguel Angel; Garduño-Monroy, Victor Hugo; Oliveros, Arturo; Giner-Robles, Jorge L.; Silva, Pablo G.

2010-05-01

Teotihuacán was one of the blooming and greater cities of the Prehispanic cultural period within the central valley of México and one of the best archaeological findings of the Earth. During the period of splendour (Middle-Late Classic Period, 350-650 AD), almost 125.000 inhabitants lived in a vast city with more than 2000 stucco and block buildings, including the great religious and ceremonial pyramids: the Great Sun Pyramid, built between 1- 150 AD, the Moon Pyramid, built during a large time span (1-650 AD) and the outstanding Quetzalcóatl Pyramid (Feathered Snake Temple), built in two phases: the first original edifice built before 350 AD and the second one mainly are repairs of the west side and dated post-350 AD. The Quetzalcóatl Pyramid (Q- pyramid) shows a quadrangular base of ca. 3500 m2 with an extraordinary decoration of feathered snakes (attributed to the God Quetzalcóatl) and lizards. The second phase of construction consisted in a townhouse façade covering the west side of the pyramid (post 350AD), up to now with no evidence to justify such annexed wrapper of this west side. This ceremonial building was built within the Citadel, a complex area of Teotihuacán with residential and common zones as well (i.e. market). A detailed view of the steps of the west side stairs, displays different patterns of deformation affecting the blocks of the stair. The original and ancient stair exhibits rotated, overturned and displaced blocks, being stronger this deformation at the base of the pyramid. Moreover, the upper corners of the blocks appear broken in a similar form than the seismic-related feature defined as dipping broken corners or chipped corners. However, the horizontal disposition of the blocks suggests lateral vibration between them from horizontal shaking propagation. Besides, this feature appears lesser evident affecting the lower blocks of the annexed west façade, the only originally preserved ones. We have carried out a systematic measurement of this feature across the original west stairs of the Q- pyramid and the first stair level of the Sun pyramid. Furthermore, these horizontal dipping broken corners were also described affecting the new stairs of the annexed façade of the Q- pyramid. This suggests that seismic shaking could produce that deformation with a relative date of 350 AD post-quem. More data are necessary to properly test the earthquake occurrence and to bracket a probable intensity value.

Semantic retrieval during overt picture description: Left anterior temporal or the parietal lobe?

PubMed

Geranmayeh, Fatemeh; Leech, Robert; Wise, Richard J S

2015-09-01

Retrieval of semantic representations is a central process during overt speech production. There is an increasing consensus that an amodal semantic 'hub' must exist that draws together modality-specific representations of concepts. Based on the distribution of atrophy and the behavioral deficit of patients with the semantic variant of fronto-temporal lobar degeneration, it has been proposed that this hub is localized within both anterior temporal lobes (ATL), and is functionally connected with verbal 'output' systems via the left ATL. An alternative view, dating from Geschwind's proposal in 1965, is that the angular gyrus (AG) is central to object-based semantic representations. In this fMRI study we examined the connectivity of the left ATL and parietal lobe (PL) with whole brain networks known to be activated during overt picture description. We decomposed each of these two brain volumes into 15 regions of interest (ROIs), using independent component analysis. A dual regression analysis was used to establish the connectivity of each ROI with whole brain-networks. An ROI within the left anterior superior temporal sulcus (antSTS) was functionally connected to other parts of the left ATL, including anterior ventromedial left temporal cortex (partially attenuated by signal loss due to susceptibility artifact), a large left dorsolateral prefrontal region (including 'classic' Broca's area), extensive bilateral sensory-motor cortices, and the length of both superior temporal gyri. The time-course of this functionally connected network was associated with picture description but not with non-semantic baseline tasks. This system has the distribution expected for the production of overt speech with appropriate semantic content, and the auditory monitoring of the overt speech output. In contrast, the only left PL ROI that showed connectivity with brain systems most strongly activated by the picture-description task, was in the superior parietal lobe (supPL). This region showed connectivity with predominantly posterior cortical regions required for the visual processing of the pictorial stimuli, with additional connectivity to the dorsal left AG and a small component of the left inferior frontal gyrus. None of the other PL ROIs that included part of the left AG were activated by Speech alone. The best interpretation of these results is that the left antSTS connects the proposed semantic hub (specifically localized to ventral anterior temporal cortex based on clinical neuropsychological studies) to posterior frontal regions and sensory-motor cortices responsible for the overt production of speech. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Osteological histology of the Pan-Alcidae (Aves, Charadriiformes): correlates of wing-propelled diving and flightlessness.

PubMed

Smith, N Adam; Clarke, Julia A

2014-02-01

Although studies of osteological morphology, gross myology, myological histology, neuroanatomy, and wing-scaling have all documented anatomical modifications associated with wing-propelled diving, the osteohistological study of this highly derived method of locomotion has been limited to penguins. Herein we present the first osteohistological study of the derived forelimbs and hind limbs of wing-propelled diving Pan-Alcidae (Aves, Charadriiformes). In addition to detailing differences between wing-propelled diving charadriiforms and nondiving charadriiforms, microstructural modifications to the humeri, ulnae and femora of extinct flightless pan-alcids are contrasted with those of volant alcids. Histological thin-sections of four species of pan-alcids (Alca torda, †Alca grandis, †Pinguinus impennis, †Mancalla cedrosensis) and one outgroup charadriiform (Stercorarius longicaudus) were compared. The forelimb bones of wing-propelled diving charadriiforms were found to have significantly thicker (∼22%) cortical bone walls. Additionally, as in penguins, the forelimbs of flightless pan-alcids are found to be osteosclerotic. However, unlike the pattern documented in penguins that display thickened cortices in both forelimbs and hind limbs, the forelimb and hind limb elements of pan-alcids display contrasting microstructural morphologies with thickened forelimb cortices and relatively thinner femoral cortices. Additionally, the identification of medullary bone in the sampled †Pinguinus impennis specimen suggests that further osteohistological investigation could provide an answer to longstanding questions regarding sexual dimorphism of Great Auks. Finally, these results suggest that it is possible to discern volant from flightless wing-propelled divers from fragmentary fossil remains. Copyright © 2013 Wiley Periodicals, Inc.

Three-Dimensional Morphology of a Coronal Prominence Cavity

NASA Technical Reports Server (NTRS)

Gibson, S. E.; Kucera, T. A.; Rastawicki, D.; Dove, J.; deToma, G.; Hao, J.; Hill, S.; Hudson, H. S.; Marque, C.; McIntosh, P. S.;

Fermi -LAT Observations of High-energy Behind-the-limb Solar Flares

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

Ackermann, M.; Buehler, R.; Allafort, A.

2017-02-01

We report on the Fermi -LAT detection of high-energy emission from the behind-the-limb (BTL) solar flares that occurred on 2013 October 11, and 2014 January 6 and September 1. The Fermi -LAT observations are associated with flares from active regions originating behind both the eastern and western limbs, as determined by STEREO . All three flares are associated with very fast coronal mass ejections (CMEs) and strong solar energetic particle events. We present updated localizations of the >100 MeV photon emission, hard X-ray (HXR) and EUV images, and broadband spectra from 10 keV to 10 GeV, as well as microwavemore » spectra. We also provide a comparison of the BTL flares detected by Fermi -LAT with three on-disk flares and present a study of some of the significant quantities of these flares as an attempt to better understand the acceleration mechanisms at work during these occulted flares. We interpret the HXR emission to be due to electron bremsstrahlung from a coronal thin-target loop top with the accelerated electron spectra steepening at semirelativistic energies. The >100 MeV gamma-rays are best described by a pion-decay model resulting from the interaction of protons (and other ions) in a thick-target photospheric source. The protons are believed to have been accelerated (to energies >10 GeV) in the CME environment and precipitate down to the photosphere from the downstream side of the CME shock and landed on the front side of the Sun, away from the original flare site and the HXR emission.« less

Face-masks for facial atopic eczema: consider a hydrocolloid dressing.

PubMed

Rademaker, Marius

2013-08-01

Facial involvement of atopic eczema in young children can be difficult to manage. Chronic scratching and rubbing, combined with parental reluctance to use topical corticosteroids on the face, often results in recalcitrant facial eczema. While wet wraps are a useful management option for moderate/severe atopic eczema involving the trunk and limbs they are difficult to use on the face. We describe the use of a face-mask using a widely available adhesive hydrocolloid dressing (DuoDerm extra thin) in three children with recalcitrant facial atopic eczema. Symptomatic control of itch or soreness was obtained within hours and the facial atopic eczema was markedly improved by 7 days. The face-masks were easy to apply, each lasting 1-4 days. One patient had a single adjuvant application of a potent topical corticosteroid under the hydrocolloid dressing. All three patients had long remissions (greater than 3 months) of their facial eczema, although all continued to have significant eczema involving their trunk and limbs. Face-masks made from hydrocolloid dressings, with or without topical corticosteroids, are worth considering in children with recalcitrant facial eczema. © 2012 The Author. Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.

3D model of auroral emissions for Europa

NASA Astrophysics Data System (ADS)

Cessateur, G.; Barthelemy, M.; Rubin, M.; Lilensten, J.; Maggiolo, R.; De Keyser, J.; Gunell, H.; Loreau, J.

2017-12-01

As archetype of icy satellites, Europa will be one of the primary targets of the ESA JUICE and NASA Europa Clipper missions. Through surface sputtering, Europa does possess a thin neutral gas atmosphere, mainly composed of O2 and H2O. Valuable information can therefore be retrieved from auroral and airglow measurements. We present here a 3D electron-excitation-transport-emission coupled model of oxygen line emissions produced through precipitating electrons. The density and temperature of the electrons are first derived from the multifluid MHD model from Rubin et al. (2015). Oxygen emission lines in the UV have first been modelled, such as those at 130.5 and 135.6 nm, and there is a nonhomogenous distribution of the emission. For 135.6 nm, the line emission can be significant and reach 700 Rayleigh close to the surface for a polar limb viewing angle. Visible emissions with the red-doublet (630-636.4 nm) and green (577.7 nm) oxygen lines are also considered with emission intensities reaching 7150 R and 200 R, respectively, for limb polar viewing. Using different cross section data, a sensitivity study has also been performed to assess the impact of the uncertainties on the auroral emissions.

Hypertrophic osteopathy associated with mycotic pneumonia in two juvenile elk (Cervus elaphus).

PubMed

Ferguson, Nicole M; Lévy, Michel; Ramos-Vara, José A; Baird, Debra K; Wu, Ching Ching

2008-11-01

Two yearling bull elk (cervus claphus) from the same farm developed anorexia, weight loss, and lameness. On physical examination, both elk were thin and showed diffuse swelling of all lower limbs. Radiographs of the lower limbs showed periosteal thickening of the distal extremities, consistent with hypertrophic osteopathy. Thoracic radiographs indicated the presence of pulmonary nodules. Cytologic evaluations of tracheal washes on both elk were consistent with inflammation. Acid-fast stains on both samples were negative. Because of the poor prognosis, both elk were euthanized. At necropsy, the carpal, metacarpal, tarsal, and metatarsal bones, as well as the radius, ulna, and tibia had thickening of cortical bone. There were multiple encapsulated nodules throughout the lungs, lymph nodes, and kidney, and smaller nodules in the myocardium. On microscopic examination, these nodules contained myriads of hyphae, and immunohistochemistry for Aspergillus sp. was strongly positive. Aspergillus fumigatus was isolated from affected tissue in 1 elk. Necropsy findings in both elk were consistent with disseminated fungal granulomas and periosteal hyperostosis. This case presents the first description of hypertrophic osteopathy in elk. The source of infection was undetermined, but inhalation of spores from contaminated feed or bedding was suspected.

Predictors of Reading Achievement: Time on Reading Instruction and Approaches to Learning

ERIC Educational Resources Information Center

Puccioni, Jaime

2015-01-01

Policies increasing the amount of time allocated to reading instruction are popular initiatives to meet the demands of accountability testing. Research suggests that time on instruction and children's approaches to learning (ATL), which generally includes measures of attention, persistence, motivation, and flexibility, are positively associated…

Are You Experienced The Case for Acquisition Professional Qualification Standards

DTIC Science & Technology

2015-10-01

1, DAU 236), featuring a cover story on micro machines used in defense systems. The winners for Defense AT&L were managing edi - tor/senior editor of...Gonzalez, copy edi - tor and circulation manager; and Noelia Gamboa, editorial support. Defense AT&L’s sister DAU publication, the Defense Acquisition

78 FR 1742 - Amendment to Class B Airspace; Atlanta, GA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-09

... maneuvering room would be available for avoiding obstructions, clouds and turbulence, and for training... conflicts between commercial carriers and private flights and that changing the airspace would only impact private flights, making access into and out of the ATL Class B more difficult. The commenter is incorrect...

Data Availability to Support a Standardized Military Geographical Information System Database.

DTIC Science & Technology

1983-03-01

world. Camp Roberts, CA, is located on the edge of the GISs can be divided roughly into the manipulation Santa Lucia Mountains bordering the Salinas...ulsa 74102 Weterways Eoperiment Station 39180 Vicksburg 39180 FORSCOM ATlN: Library Walla della 99362 FORSCOM Engineer, ATN: AFEN-FE’dilmington 28401

Lidar Measurement of Exhaust Plume Characteristics from Commercial Jet Turbine Aircraft at the Denver International Airport.

DOT National Transportation Integrated Search

2008-04-01

This is the third in a series of measurements on this topic with the first two conducted at Los : Angeles International Airport (LAX) and Atlantas Hartsfield-Jackson International Airport (ATL). A major goal in all three studies has been to measur...

A Community Terrain-Following Ocean Modeling System (ROMS/TOMS)

DTIC Science & Technology

2013-09-30

workshop at the Windsor Atlântica Hotel, Rio de Janeiro , Brazil, October 22-25, 2012. As in the past, several tutorials were offered on basic and...from the European Centre For Medium-Range Weather Forecasts (ECMWF) ERA-Interim, 3-hour dataset. River runoff is included along the Alabama

Defense AT&L (Volume 35, Number 1, January-February 2006)

DTIC Science & Technology

2006-02-01

deletes restrictive re- quirements relating to the use of master agreements for vessel repair; deletes obsolete procedures for acquisition of bakery and...05-479, July 29, 2005 Interagency Contracting: Franchise Funds Provide Con- venience, but Value to DoD is Not Demonstrated, GAO- 05-456, July 29, 2005

Neural Mechanisms of Conceptual Relations

ERIC Educational Resources Information Center

Lewis, Gwyneth A.

2017-01-01

An over-arching goal in neurolinguistic research is to characterize the neural bases of semantic representation. A particularly relevant goal concerns whether we represent features and events (a) together in a generalized semantic hub or (b) separately in distinct but complementary systems. While the left anterior temporal lobe (ATL) is strongly…

MEG Evidence for Incremental Sentence Composition in the Anterior Temporal Lobe

ERIC Educational Resources Information Center

Brennan, Jonathan R.; Pylkkänen, Liina

2017-01-01

Research investigating the brain basis of language comprehension has associated the left anterior temporal lobe (ATL) with sentence-level combinatorics. Using magnetoencephalography (MEG), we test the parsing strategy implemented in this brain region. The number of incremental parse steps from a predictive left-corner parsing strategy that is…

Pilot instrumentation of a Superpave test section at the Kansas Accelerated Testing laboratory

DOT National Transportation Integrated Search

2003-04-01

Two Superpave test sections were constructed at the Kansas Accelerated Testing Laboratory (K-ATL) with 12.5 mm (2 in) nominal maximum size Superpave mixture (SM-2A) with varying percentages (15 and 30 percent) of river sand. A 150 kN (34 kip) tandem ...

Effect of six-month hypokinesia in dogs on mineral component, reconstruction and mechanical properties of bone tissue

NASA Technical Reports Server (NTRS)

Volozhin, A. I.; Pavlova, M. P.; Muradov, I. S.; Stupakov, G. P.; Korzhenyants, V. A.

1980-01-01

Ca45 incorporation into the bones of the limbs, particularly in the area of the muscle attachment increased in dogs as a result of 6 month hypokinesia. There were no phenomena of osteoporosis in the cortical layer of the diaphyses; however, changes in the form of osteons, an increase in the number of anastomoses between the channels and the thinning of the subperiosteal layer pointed to disturbances of the bone tissue reconstruction. Mineral saturation of the bone microstructures of the experimental dogs had a tendency to rise. No changes in the mechanical properties of the long bones occurred as a result of hypokinesia in dogs.

The Theory and Measurement of Interorganizational Collaborative Capacity in the Acquisition and Contracting Context

DTIC Science & Technology

2009-04-22

members) of some defined population” ( Thorndike , 1971, p. 533). Norms in this context would allow an organization to understand its relative standing on...theory. New York: McGraw-Hill. Thorndike , R.L. (1971). Educational measurement (2nd Ed.). Washington, DC: American Council on Education. USD (AT&L

Stress in air traffic controllers : comparison of two air route traffic control centers on different shift rotation patterns.

DOT National Transportation Integrated Search

1975-01-01

Stress in 23 air traffic controllers (ATCS) at Atlanta Air Route Traffic Control Center (ATL) on the straight 5-day shift rotation schedule was compared with stress in 23 ATCS's on the 2-2-1 shift rotation schedule at Fort Worth Air Route Traffic Con...

Analysis of Air Force Office of Special Investigations Agents Knowledge of the Contract Management Process

DTIC Science & Technology

2015-12-01

AND ABBREVIATIONS ACFE ACO AFFAR AFICA AFOSI AFMC AOR AT&L AUSA B BEP BPA BRAC BSIC C2 CEO CFE CFR CICA CID CITP CMMM CONUS COR...or blanket purchase agreements ( BPAs ), thereby providing flexibility to meet fluctuating government demands. c. Proposal Evaluation Criteria

An Analysis of Purchasing Systems at the Ship Level in the United States and Hellenic Navies

DTIC Science & Technology

2014-12-01

ABBREVIATIONS AT&L acquisition, technology, and logistics BPA blanket purchase agreement BBP better buying power DOD Department of Defense FC Fleet...the ships can also solicit and award formal contracts or blanket purchase agreements ( BPA )— BPA are charging accounts with selected suppliers for the

Ellsworth AFB, South Dakota. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1987-12-01

34. . . . . .. . . .. .1 ’’ 4 . .. 1~ ’ . ........ .. . .3.. . ’ ’.. 9,!.. 4.!o. . 8,3 4.3.° . . .. . L l4773, 𔃽’’’ 7$ (7Of 0 ’’,!Ř ATl3"’ V L );-AL CL1i’a7 [ LOLY 1,P

76 FR 71465 - Defense Federal Acquisition Regulations Supplement; Notification Requirements for Awards of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Procurement (Contract Policy and International Contracting), OUSD (AT&L) DPAP (CPIC), 3060 Defense Pentagon... International Contracting (CPIC). This enables a single office to oversee and manage the DoD-wide use of single... Delivery-Order Contracts (DFARS Case 2009-D036) AGENCY: Defense Acquisition Regulations System, Department...

Ohio-Based NREL Subcontractor Wins Major Small Business Award

Science.gov Websites

Ohio-Based NREL Subcontractor Wins Major Small Business Award For more information contact: e:mail alternative fuel vehicles has won a major award from the U.S. Small Business Administration (SBA). Automotive Testing Laboratories, Inc. (ATL) of East Liberty, Ohio was named the SBA's Midwest Regional Small Business

77 FR 30361 - Defense Federal Acquisition Regulation Supplement; Defense Trade Cooperation Treaty With the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... DEPARTMENT OF DEFENSE Defense Acquisitions Regulations System 48 CFR Parts 225 and 252 RIN 0750... United Kingdom (DFARS 2012-D034) AGENCY: Defense Acquisition Regulations System; Department of Defense... Acquisition Regulations System, Attn: (Insert case manager's name), OUSD (AT&L) DPAP/DARS, Room 3B855, 3060...

Dynamics of the Dermatologic Microbiome in U.S. Air Force Basic Training

DTIC Science & Technology

2017-04-05

PattersonATl @gmail.com 210-671 -9740 (330-701-5183) 16. AUTHORSHIP AND CO-AUTHOR(S) list In the order they will appear In the manuscript LAST NAME...epidemiologie changes tn the collective dermatologie microbiome are being compared based on shifts in miaoblota flora lrequoneies according to Gender

76 FR 8303 - Defense Federal Acquisition Regulation Supplement; Award-Fee Contracts (DFARS Case 2006-D021)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 216 and 252 RIN 0750...) AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION: Final rule. SUMMARY... Regulations System, OUSD (AT&L) DPAP/DARS, 3060 Defense Pentagon, Room 3B855, Washington, DC 20301-3060...

Memory Outcomes Following Selective versus Nonselective Temporal Lobe Removal: A Systematic Review

ERIC Educational Resources Information Center

Girgis, Fady

2012-01-01

The surgical removal of brain tissue for the treatment of temporal lobe epilepsy can be either nonselective, as with an anterior temporal lobectomy (ATL), or selective, as with a selective amygdalohippocampectomy (SAH). Although seizure outcomes are similar with both procedures, cognitive and memory outcomes remain a matter of debate. This study…

Studies on Phlebotominae (Diptera: Psychodidae) in the campus FIOCRUZ mata Atlântica, Jacarepaguá, in the City of Rio de Janeiro, Brazil.

PubMed

Souza, Nataly Araujo de; Silva, Juliana Bastos da; Godoy, Rodrigo Espíndola; Souza, Filipe Jonas Mattos de; Andrade-Coelho, Cláudia Alves de; Silva, Vanderlei Campos; Azevedo, Alfredo Carlos Rodrigues de; Rangel, Elizabeth Ferreira

2015-01-01

The presence of American cutaneous leishmaniasis (ACL) in the communities of the Campus FIOCRUZ Mata Atlântica (CFMA) in the City of Rio de Janeiro initiated the investigation of the Phlebotominae fauna in the Atlantic Forest to determine the occurrence of putative ACL vectors associated with the enzootic cycle. For 24 consecutive months, sand flies were captured inside the forest and in the border area near the communities. The following sand fly species were identified: Brumptomyia brumpti, Brumptomyia cunhai, Brumptomyia nitzulescui, Lutzomyia edwardsi, Lutzomyia pelloni, and Lutzomyia quinquefer. Other identified sand fly vectors, such as Lutzomyia intermedia (the predominant species), Lutzomyia migonei, Lutzomyia whitmani, Lutzomyia fischeri, and Lutzomyia hirsuta hirsuta, are associated with ACL transmission, and the vector for American visceral leishmaniases (AVL), Lutzomyia longipalpis, was also found. All sand fly vectors were found in both studied environments except for Lutzomyia whitmani, which was only identified in the forest. This study represents the first identification of Lutzomyia longipalpis in the CFMA, and the epidemiological implications are discussed.

A shared representation of order between encoding and recognition in visual short-term memory.

PubMed

Kalm, Kristjan; Norris, Dennis

2017-07-15

Many complex tasks require people to bind individual events into a sequence that can be held in short term memory (STM). For this purpose information about the order of the individual events in the sequence needs to be maintained in an active and accessible form in STM over a period of few seconds. Here we investigated how the temporal order information is shared between the presentation and response phases of an STM task. We trained a classification algorithm on the fMRI activity patterns from the presentation phase of the STM task to predict the order of the items during the subsequent recognition phase. While voxels in a number of brain regions represented positional information during either presentation and recognition phases, only voxels in the lateral prefrontal cortex (PFC) and the anterior temporal lobe (ATL) represented position consistently across task phases. A shared positional code in the ATL might reflect verbal recoding of visual sequences to facilitate the maintenance of order information over several seconds. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes

PubMed Central

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A.

2015-01-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. PMID:25491206

Geopan AT@S: a Brokering Based Gateway to Georeferenced Historical Maps for Risk Analysis

NASA Astrophysics Data System (ADS)

Previtali, M.

2017-08-01

Importance of ancient and historical maps is nowadays recognized in many applications (e.g., urban planning, landscape valorisation and preservation, land changes identification, etc.). In the last years a great effort has been done by different institutions, such as Geographical Institutes, Public Administrations, and collaborative communities, for digitizing and publishing online collections of historical maps. In spite of this variety and availability of data, information overload makes difficult their discovery and management: without knowing the specific repository where the data are stored, it is difficult to find the information required. In addition, problems of interconnection between different data sources and their restricted interoperability may arise. This paper describe a new brokering based gateway developed to assure interoperability between data, in particular georeferenced historical maps and geographic data, gathered from different data providers, with various features and referring to different historical periods. The developed approach is exemplified by a new application named GeoPAN Atl@s that is aimed at linking in Northern Italy area land changes with risk analysis (local seismicity amplification and flooding risk) by using multi-temporal data sources and historic maps.

Dynamics of human T-cell lymphotropic virus I (HTLV-I) infection of CD4+ T-cells.

PubMed

Katri, Patricia; Ruan, Shigui

2004-11-01

Stilianakis and Seydel (Bull. Math. Biol., 1999) proposed an ODE model that describes the T-cell dynamics of human T-cell lymphotropic virus I (HTLV-I) infection and the development of adult T-cell leukemia (ATL). Their model consists of four components: uninfected healthy CD4+ T-cells, latently infected CD4+ T-cells, actively infected CD4+ T-cells, and ATL cells. Mathematical analysis that completely determines the global dynamics of this model has been done by Wang et al. (Math. Biosci., 2002). In this note, we first modify the parameters of the model to distinguish between contact and infectivity rates. Then we introduce a discrete time delay to the model to describe the time between emission of contagious particles by active CD4+ T-cells and infection of pure cells. Using the results in Culshaw and Ruan (Math. Biosci., 2000) in the analysis of time delay with respect to cell-free viral spread of HIV, we study the effect of time delay on the stability of the endemically infected equilibrium. Numerical simulations are presented to illustrate the results.

Newly identified poor prognostic factors for adult T-cell leukemia-lymphoma treated with allogeneic hematopoietic stem cell transplantation.

PubMed

Tokunaga, Masahito; Uto, Hirofumi; Takeuchi, Shogo; Nakano, Nobuaki; Kubota, Ayumu; Tokunaga, Mayumi; Takatsuka, Yoshifusa; Seto, Masao; Ido, Akio; Utsunomiya, Atae

2017-01-01

To explore pre-transplantation prognostic factors for adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 70 patients at our institute (63 acute type and seven lymphoma type patients). Forty-five patients died after HSCT and the three-year overall survival (OS) rate was 35.2%. By univariate analysis, the adverse prognostic factors for OS were performance status ≥2, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score ≥3, European Group for Blood and Marrow Transplantation (EBMT) risk score ≥5, HSCT from an HLA-mismatched donor, serum soluble interleukin-2 receptor (sIL-2R) level ≥10,000 U/mL, lymphocyte count ≥4000/μL, and hemoglobin <9 g/dL at the time of HSCT. EBMT risk score and sIL-2R were identified as significant adverse prognostic factors using multivariate analysis. This analysis clearly demonstrates for the first time that HCT-CI and EBMT risk scores are reliable prognostic factors for ATL patients receiving allo-HSCT.

[Adult T-cell leukemia/lymphoma associated with unusual positivity of anti-ATLA (adult T-cell leukemia-cell-associated antigen) antibodies].

PubMed

Eto, T; Okamura, H; Okamura, T; Gondo, H; Kudo, J; Shibuya, T; Harada, M; Niho, Y

1990-03-01

A 56-year-old female was admitted because of generalized lymphadenopathy. Based upon histological findings of biopsied lymph node, malignant lymphoma, diffuse large cell type was diagnosed. The surface marker analysis showed that malignant cells were positive for CD4 and CD2 but negative for CD8. Although anti-ATLA (adult T-cell leukemia associated antigen) antibody was negative with the use of a gelatin particle agglutination method (P.A.), other methods such as an indirect immunofluorescence assay (I.F.), an enzyme-linked immunosorbent assay (E.I.A.) and a Western blotting assay revealed the positivity for anti-ATLA antibody. Adult T-cell leukemia/lymphoma (ATL/L) was confirmed by the presence of monoclonal integration of HTLV-I proviral DNA in biopsied specimen. This case, showing a pattern of P.A. (-) and I.F. (+), is extremely unusual, because I.F. and P.A. show highly close correlation. Thus, it is important to employ different methods for screening of anti-ATLA antibodies in the diagnosis of ATL/L.

Cognitive consequences of the left-right asymmetry of atrophy in semantic dementia.

PubMed

Woollams, Anna M; Patterson, Karalyn

2017-12-05

Semantic dementia (SD) is a condition in which atrophy to the anterior temporal lobes (ATL) produces a selective deterioration of conceptual knowledge. As this atrophy is always bilateral but usually asymmetrical, differences in performance of the two SD subgroups-with left > right (L > R) versus right > left (R > L) atrophy-constitute a major source of evidence regarding the roles of the left and right sides of this region. We explored this issue using large scale case-series methodology, with a pool of 216 observations of neuropsychological data from 72 patients with SD. Anomia was significantly more severe in the L > R subgroup, even when cases from the two subgroups were matched on severity of comprehension deficits. For subgroups matched on the degree of anomia, we show that asymmetry of atrophy also affected both the nature of the naming errors produced, and the degree of a semantic category effect (living things vs artefacts). A comparison across tasks varying in their loading on verbal and visual processing revealed a greater deficit in object naming for L > R cases and in a picture-based semantic association test for R > L cases; this held true whether severity across subgroups was controlled using pairwise matching or statistically via principal components analysis. Importantly, the size of our sample allowed us to demonstrate considerable individual variation within each of the L > R and R > L subgroups, with consequent overlap between them. Our results paint a clear picture of how asymmetry of atrophy affects cognitive performance in SD, and we discuss the results in terms of two mechanisms that could contribute to these differences: variation in the information involved in semantic representations in the left and right ATL, and preferential connectivity between each ATL and other more modality specific intra-hemispheric regions. Copyright © 2017. Published by Elsevier Ltd.

Human T-lymphotropic virus type 1 infection and disease in Spain.

PubMed

de Mendoza, Carmen; Caballero, Estrella; Aguilera, Antonio; Requena, Silvia; de Lejarazu, Raúl Ortiz; Pirón, María; González, Rocío; Jiménez, Ana; Roc, Lourdes; Treviño, Ana; Benito, Rafael; Fernández-Alonso, Miriam; Aguinaga, Aitziber; Rodríguez, Carmen; García-Costa, Juan; Blanco, Lidia; Ramos, José M; Calderón, Enrique; Eirós, José M; Sauleda, Silvia; Barreiro, Pablo; Soriano, Vicente

2017-07-31

: Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil asymptomatic unaware HTLV-1 carriers.

The discovery and geophysical response of the Atlántida Cu-Au porphyry deposit, Chile

NASA Astrophysics Data System (ADS)

Hope, Matthew; Andersson, Steve

2016-03-01

The discovery of the Atlántida Cu-Au-Mo porphyry deposit, which is unconformably overlain by 25-80 m of gravels, is a recent example of exploration success under cover in a traditional mining jurisdiction. Early acquisition of geophysics was a key tool in the discovery, and in later guiding further exploration drilling throughout the life of the project. Detailed review of the geophysical response of the deposit, with respect to the distribution of lithologies and alteration, coupled with their petrophysical properties has allowed full characterisation, despite no exposure at the surface of host rock nor porphyry-style mineralisation. Data acquired over the project include induced polarisation, magnetotellurics, ground and airborne magnetics, ground-based gravimetry, and petrophysical sampling. The distribution of the key geological features of the deposit has been inferred via acquisition of petrophysical properties and interpretation of surface geophysical datasets. Magnetic susceptibility is influenced strongly by both alteration and primary lithology, whilst density variations are dominated by primary lithological control. Several studies have shown that electrical properties may map the footprint of the hydrothermal system and associated mineralisation, via a combination of chargeability and resistivity. These properties are observed in geophysical datasets acquired at surface and allow further targeting and sterilisation at the deposit and project scale. By understanding these geophysical characteristics in a geological context, these data can be used to infer distribution of lithological units, depth to exploration targets and the potential for high grade mineralisation. Future exploration will likely be increasingly reliant on the understanding of the surface manifestations of buried deposits in remotely acquired data. This review summarises the application and results of these principles at the Atlántida project of northern Chile. Geophysical data can be used to improve the chances of discovery beneath post-mineral cover, and also improve drilling results throughout the advanced exploration of the program. The process of data review against geological control information is essential.

Interaction of HTLV-1 Tax protein with calreticulin: implications for Tax nuclear export and secretion.

PubMed

Alefantis, Timothy; Flaig, Katherine E; Wigdahl, Brian; Jain, Pooja

2007-05-01

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The HTLV-1 transcriptional transactivator protein Tax plays an integral role in virus replication and disease progression. Traditionally, Tax is described as a nuclear protein where it performs its primary role as a transcriptional transactivator. However, recent studies have clearly shown that Tax can also be localized to the cytoplasm where it has been shown to interact with a number of host transcription factors most notably NF-kappaB, constitutive expression of which is directly related to the T cell transforming properties of Tax in ATL patients. The presence of a functional nuclear export signal (NES) within Tax and the secretion of full-length Tax have also been demonstrated previously. Additionally, release of Tax from HTLV-1-infected cells and the presence of cell-free Tax was demonstrated in the CSF of HAM/TSP patients suggesting that the progression to HAM/TSP might be mediated by the ability of Tax to function as an extracellular cytokine. Therefore, in both ATL and HAM/TSP Tax nuclear export and nucleocytoplasmic shuttling may play a critical role, the mechanism of which remains unknown. In this study, we have demonstrated that the calcium binding protein calreticulin interacts with Tax by co-immunoprecipitation. This interaction was found to localize to a region at or near the nuclear membrane. In addition, differential expression of calreticulin was demonstrated in various cell types that correlated with their ability to retain cytoplasmic Tax, particularly in astrocytes. Finally, a comparison of a number of HTLV-1-infected T cell lines to non-infected T cells revealed higher expression of calreticulin in infected cells implicating a direct role for this protein in HTLV-1 infection.

Differing contributions of inferior prefrontal and anterior temporal cortex to concrete and abstract conceptual knowledge

PubMed Central

Hoffman, Paul; Binney, Richard J.; Lambon Ralph, Matthew A.

2015-01-01

Semantic cognition is underpinned by regions involved in representing conceptual knowledge and executive control areas that provide regulation of this information according to current task requirements. Using distortion-corrected fMRI, we investigated the contributions of these two systems to abstract and concrete word comprehension. We contrasted semantic decisions made either with coherent contextual support, which encouraged retrieval of a rich conceptual representation, or with irrelevant contextual information, which instead maximised demands on control processes. Inferior prefrontal cortex was activated more when decisions were made in the presence of irrelevant context, suggesting that this region is crucial for the semantic control functions required to select appropriate aspects of meaning in the face of competing information. It also exhibited greater activation for abstract words, which reflects the fact that abstract words tend to have variable, context-dependent meanings that place higher demands on control processes. In contrast, anterior temporal regions (ATL) were most active when decisions were made with the benefit of a coherent context, suggesting a representational role. There was a graded shift in concreteness effects in this region, with dorsolateral areas particularly active for abstract words and ventromedial areas preferentially activated by concrete words. This supports the idea that concrete concepts are closely associated with visual experience and abstract concepts with auditory-verbal information; and that sub-regions of the ATL display graded specialisation for these two types of knowledge. Between these two extremes, we identified significant activations for both word types in ventrolateral ATL. This area is known to be involved in representing knowledge for concrete concepts; here we established that it is also activated by abstract concepts. These results converge with data from rTMS and neuropsychological investigations in demonstrating that representational content and task demands influence recruitment of different areas in the semantic network. PMID:25303272

Effect of a checklist on advanced trauma life support workflow deviations during trauma resuscitations without pre-arrival notification.

PubMed

Kelleher, Deirdre C; Jagadeesh Chandra Bose, R P; Waterhouse, Lauren J; Carter, Elizabeth A; Burd, Randall S

2014-03-01

Trauma resuscitations without pre-arrival notification are often initially chaotic, which can potentially compromise patient care. We hypothesized that trauma resuscitations without pre-arrival notification are performed with more variable adherence to ATLS protocol and that implementation of a checklist would improve performance. We analyzed event logs of trauma resuscitations from two 4-month periods before (n = 222) and after (n = 215) checklist implementation. Using process mining techniques, individual resuscitations were compared with an ideal workflow model of 6 ATLS primary survey tasks performed by the bedside evaluator and given model fitness scores (range 0 to 1). Mean fitness scores and frequency of conformance (fitness = 1) were compared (using Student's t-test or chi-square test, as appropriate) for activations with and without notification both before and after checklist implementation. Multivariable linear regression, controlling for patient and resuscitation characteristics, was also performed to assess the association between pre-arrival notification and model fitness before and after checklist implementation. Fifty-five (12.6%) resuscitations lacked pre-arrival notification (23 pre-implementation and 32 post-implementation; p = 0.15). Before checklist implementation, resuscitations without notification had lower fitness (0.80 vs 0.90; p < 0.001) and conformance (26.1% vs 50.8%; p = 0.03) than those with notification. After checklist implementation, the fitness (0.80 vs 0.91; p = 0.007) and conformance (26.1% vs 59.4%; p = 0.01) improved for resuscitations without notification, but still remained lower than activations with notification. In multivariable analysis, activations without notification had lower fitness both before (b = -0.11, p < 0.001) and after checklist implementation (b = -0.04, p = 0.02). Trauma resuscitations without pre-arrival notification are associated with a decreased adherence to key components of the ATLS primary survey protocol. The addition of a checklist improves protocol adherence and reduces the effect of notification on task performance. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Structure-Function Analysis of Staphylococcus aureus Amidase Reveals the Determinants of Peptidoglycan Recognition and Cleavage*

PubMed Central

Büttner, Felix Michael; Zoll, Sebastian; Nega, Mulugeta; Götz, Friedrich; Stehle, Thilo

2014-01-01

The bifunctional major autolysin AtlA of Staphylococcus aureus cleaves the bacterium's peptidoglycan network (PGN) at two distinct sites during cell division. Deletion of the enzyme results in large cell clusters with disordered division patterns, indicating that AtlA could be a promising target for the development of new antibiotics. One of the two functions of AtlA is performed by the N-acetylmuramyl-l-alanine amidase AmiA, which cleaves the bond between the carbohydrate and the peptide moieties of PGN. To establish the structural requirements of PGN recognition and the enzymatic mechanism of cleavage, we solved the crystal structure of the catalytic domain of AmiA (AmiA-cat) in complex with a peptidoglycan-derived ligand at 1.55 Å resolution. The peptide stem is clearly visible in the structure, forming extensive contacts with protein residues by docking into an elongated groove. Less well defined electron density and the analysis of surface features indicate likely positions of the carbohydrate backbone and the pentaglycine bridge. Substrate specificity analysis supports the importance of the pentaglycine bridge for fitting into the binding cleft of AmiA-cat. PGN of S. aureus with l-lysine tethered with d-alanine via a pentaglycine bridge is completely hydrolyzed, whereas PGN of Bacillus subtilis with meso-diaminopimelic acid directly tethered with d-alanine is not hydrolyzed. An active site mutant, H370A, of AmiA-cat was completely inactive, providing further support for the proposed catalytic mechanism of AmiA. The structure reported here is not only the first of any bacterial amidase in which both the PGN component and the water molecule that carries out the nucleophilic attack on the carbonyl carbon of the scissile bond are present; it is also the first peptidoglycan amidase complex structure of an important human pathogen. PMID:24599952

Differing contributions of inferior prefrontal and anterior temporal cortex to concrete and abstract conceptual knowledge.

PubMed

Hoffman, Paul; Binney, Richard J; Lambon Ralph, Matthew A

2015-02-01

Semantic cognition is underpinned by regions involved in representing conceptual knowledge and executive control areas that provide regulation of this information according to current task requirements. Using distortion-corrected fMRI, we investigated the contributions of these two systems to abstract and concrete word comprehension. We contrasted semantic decisions made either with coherent contextual support, which encouraged retrieval of a rich conceptual representation, or with irrelevant contextual information, which instead maximised demands on control processes. Inferior prefrontal cortex was activated more when decisions were made in the presence of irrelevant context, suggesting that this region is crucial for the semantic control functions required to select appropriate aspects of meaning in the face of competing information. It also exhibited greater activation for abstract words, which reflects the fact that abstract words tend to have variable, context-dependent meanings that place higher demands on control processes. In contrast, anterior temporal regions (ATL) were most active when decisions were made with the benefit of a coherent context, suggesting a representational role. There was a graded shift in concreteness effects in this region, with dorsolateral areas particularly active for abstract words and ventromedial areas preferentially activated by concrete words. This supports the idea that concrete concepts are closely associated with visual experience and abstract concepts with auditory-verbal information; and that sub-regions of the ATL display graded specialisation for these two types of knowledge. Between these two extremes, we identified significant activations for both word types in ventrolateral ATL. This area is known to be involved in representing knowledge for concrete concepts; here we established that it is also activated by abstract concepts. These results converge with data from rTMS and neuropsychological investigations in demonstrating that representational content and task demands influence recruitment of different areas in the semantic network. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structure-function analysis of Staphylococcus aureus amidase reveals the determinants of peptidoglycan recognition and cleavage.

PubMed

Büttner, Felix Michael; Zoll, Sebastian; Nega, Mulugeta; Götz, Friedrich; Stehle, Thilo

2014-04-18

The bifunctional major autolysin AtlA of Staphylococcus aureus cleaves the bacterium's peptidoglycan network (PGN) at two distinct sites during cell division. Deletion of the enzyme results in large cell clusters with disordered division patterns, indicating that AtlA could be a promising target for the development of new antibiotics. One of the two functions of AtlA is performed by the N-acetylmuramyl-l-alanine amidase AmiA, which cleaves the bond between the carbohydrate and the peptide moieties of PGN. To establish the structural requirements of PGN recognition and the enzymatic mechanism of cleavage, we solved the crystal structure of the catalytic domain of AmiA (AmiA-cat) in complex with a peptidoglycan-derived ligand at 1.55 Å resolution. The peptide stem is clearly visible in the structure, forming extensive contacts with protein residues by docking into an elongated groove. Less well defined electron density and the analysis of surface features indicate likely positions of the carbohydrate backbone and the pentaglycine bridge. Substrate specificity analysis supports the importance of the pentaglycine bridge for fitting into the binding cleft of AmiA-cat. PGN of S. aureus with l-lysine tethered with d-alanine via a pentaglycine bridge is completely hydrolyzed, whereas PGN of Bacillus subtilis with meso-diaminopimelic acid directly tethered with d-alanine is not hydrolyzed. An active site mutant, H370A, of AmiA-cat was completely inactive, providing further support for the proposed catalytic mechanism of AmiA. The structure reported here is not only the first of any bacterial amidase in which both the PGN component and the water molecule that carries out the nucleophilic attack on the carbonyl carbon of the scissile bond are present; it is also the first peptidoglycan amidase complex structure of an important human pathogen.

Ultrasonography of the distal limbs in Nellore and Girolando calves 8 to 12 months of age

PubMed Central

2014-01-01

Background Ultrasonography can be used anywhere and allows rapid, noninvasive differentiation of soft tissue structures of the musculoskeletal system. The objectives of this study were to describe the ultrasonographic appearance of the structures of the metacarpo-/metatarsophalangeal and the interphalangeal joints, the appearance of the growth plates of the distal metacarpus/metatarsus and of the proximal phalanx and to measure the cross-sectional dimensions of the DDFT and SDFT in Nellore and Girolando calves eight to 12 months of age. Results In the longitudinal dorsal view the common digital extensor tendon and the digital extensor tendon were depicted as echogenic parallel fiber bundles located directly under the skin. The joint spaces appeared as anechoic interruptions of the hyperechogenic bone surfaces. The normal amount of synovial fluid could not be depicted. The growth plates were seen as anechoic interruptions of the bone surface proximal and distal to the fetlock joint space. In transverse sonograms of the distal palmar/plantar regions, the flexor tendons and branchs of the suspensory ligament were imaged as echogenic structures. The lumen of the digital flexor tendon sheath could not be imaged in these normal cattle. The thin digital distal annular ligament and the reversal of positions of the DDFT and SDFT could be appreciated. No significant differences were found between the cross-sectional measurements of the DDFT and the SDFT from Nellore and Girolando in any age, thoracic/pelvic limbs, right/left sides and lateral/medial digits. Conclusions The results of this study establish important ultrasonographic reference data of the normal structures of the distal limbs and the normal dimensions of the flexor tendons in Nellore and Girolando calves for use in clinical practice. PMID:24774582

Fermi-LAT Observations of High-energy Behind-the-limb Solar Flares

DOE PAGES

Ackermann, M.; Allafort, A.; Baldini, L.; ...

2017-01-31

In this paper, we report on the Fermi-LAT detection of high-energy emission from the behind-the-limb (BTL) solar flares that occurred on 2013 October 11, and 2014 January 6 and September 1. The Fermi-LAT observations are associated with flares from active regions originating behind both the eastern and western limbs, as determined by STEREO. All three flares are associated with very fast coronal mass ejections (CMEs) and strong solar energetic particle events. We present updated localizations of the >100 MeV photon emission, hard X-ray (HXR) and EUV images, and broadband spectra from 10 keV to 10 GeV, as well as microwavemore » spectra. We also provide a comparison of the BTL flares detected by Fermi-LAT with three on-disk flares and present a study of some of the significant quantities of these flares as an attempt to better understand the acceleration mechanisms at work during these occulted flares. We interpret the HXR emission to be due to electron bremsstrahlung from a coronal thin-target loop top with the accelerated electron spectra steepening at semirelativistic energies. The >100 MeV gamma-rays are best described by a pion-decay model resulting from the interaction of protons (and other ions) in a thick-target photospheric source. In conclusion, the protons are believed to have been accelerated (to energies >10 GeV) in the CME environment and precipitate down to the photosphere from the downstream side of the CME shock and landed on the front side of the Sun, away from the original flare site and the HXR emission.« less

A case report: a heterozygous deletion (2791_2805 del) in exon 18 of the filamin C gene causing filamin C-related myofibrillar myopathies in a Chinese family.

PubMed

Miao, Jing; Su, Fei-Fei; Liu, Xue-Mei; Wei, Xiao-Jing; Yuan, Yun; Yu, Xue-Fan

2018-06-04

Filamin C-related myofibrillar myopathies (MFM) are progressive skeletal myopathies with an autosomal dominant inheritance pattern. The conditions are caused by mutations of the filamin C gene (FLNC) located in the chromosome 7q32-q35 region. Genetic variations in the FLNC gene result in various clinical phenotypes. We describe a 43-year-old woman who suffered filamin C-related MFM, with symptoms first presenting in the proximal muscles of the lower limbs and eventually spreading to the upper limbs and distal muscles. The patient's serum level of creatine kinase was mildly increased. Mildy myopathic changes in the electromyographic exam and moderate lipomatous alterations in lower limb MRI were found. Histopathological examination revealed increased muscle fiber size variability, disturbances in oxidative enzyme activity, and the presence of abnormal protein aggregates and vacuoles in some muscle fibers. Ultrastructural analysis showed inclusions composed of thin filaments and interspersed granular densities. DNA sequencing analysis detected a novel 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the FLNC gene. The patient's father, sister, brother, three paternal aunts, one paternal uncle, and the uncle's son also had slowly progressive muscle weakness, and thus, we detected an autosomal dominant inheritance pattern of the disorder. A novel heterogeneous 15-nucleotide deletion (c.2791_2805del, p.931_935del) in the Ig-like domain 7 of the FLNC gene was found to cause filamin C-related MFM. This deletion in the FLNC gene causes protein aggregation, abnormalities in muscle structure, and impairment in muscle fiber function, which leads to muscle weakness.

X-ray Proper Motions and Shock Speeds along the Northwest Rim of SN1006

NASA Technical Reports Server (NTRS)

Katsuda, Satoru; Long, Knox S.; Petre, Robert; Reynolds, Stephen P.; Williams, Brian J.; Winkler, P. Frank

2012-01-01

We report the results of an X-ray proper motion measurement for the NW rim of SN 1006, carried out by comparing Chandra observations from 2001 and 2012. The NW limb has predominantly thermal X-ray emission, and it is the only location in SN 1006 with signi cant optical emission: a thin, Balmer-dominated lament. For most of the NW rim, the proper motion is approximately equal to 0.30"yr(exp -1), essentially the same as has been measured from the H alpha lament. Isolated regions of the NW limb are dominated by nonthermal emission, and here the proper motion is much higher, 0:49"yr(exp -1), close to the value measured in X-rays along the much brighter NE limb, where the X-rays are overwhelmingly nonthermal. At the 2.2 kpc distance to SN 1006, the proper motions imply shock velocities of approximately 3000 kms(exp -1) and approximately 5000 kms(exp -1) in the thermal and nonthermal regions, respectively. A lower velocity behind the H alpha filament is consistent with the picture that SN 1006 is encountering denser gas in the NW, as is also suggested by its overall morphology. In the thermally-dominated portion of the X-ray shell, we also see an o set in the radial profiles at different energies; the 0.5-0.6 keV peak dominated by O VII is closer to the shock front than that of the 0.8-3 keV emission|due to the longer times for heavier elements to reach ionization states where they produce strong X-ray emission.

A Jovian Hotspot in True and False Colors (Time set 3)

NASA Technical Reports Server (NTRS)

1997-01-01

True and false color views of an equatorial 'hotspot' on Jupiter. These images cover an area 34,000 kilometers by 11,000 kilometers. The top mosaic combines the violet (410 nanometers or nm) and near-infrared continuum (756 nm) filter images to create an image similar to how Jupiter would appear to human eyes. Differences in coloration are due to the composition and abundances of trace chemicals in Jupiter's atmosphere. The bottom mosaic uses Galileo's three near-infrared wavelengths (756 nm, 727 nm, and 889 nm displayed in red, green, and blue) to show variations in cloud height and thickness. Bluish clouds are high and thin, reddish clouds are low, and white clouds are high and thick. The dark blue hotspot in the center is a hole in the deep cloud with an overlying thin haze. The light blue region to the left is covered by a very high haze layer. The multicolored region to the right has overlapping cloud layers of different heights. Galileo is the first spacecraft to distinguish cloud layers on Jupiter.

North is at the top. The mosaics cover latitudes 1 to 10 degrees and are centered at longitude 336 degrees West. The planetary limb runs along the right edge of the image. Cloud patterns appear foreshortened as they approach the limb. The smallest resolved features are tens of kilometers in size. These images were taken on December 17, 1996, at a range of 1.5 million kilometers by the Solid State Imaging system aboard NASA's Galileo spacecraft.

The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.

This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

Effect of Ca sup 2+ on Cl sup minus transport in thin ascending limb of Henle's loop

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

Kondo, Yoshiaki; Yoshitomi, Koji; Imai, Masashi

1988-02-01

Effects of ambient Ca{sup 2+} concentration on Cl{sup {minus}} transport across the thin ascending limb of Henle's loop (TAL) were examined by the in vitro microperfusion technique. When Ca{sup 2+} concentration in the bathing fluid was decreased from 1.5 mM to nominally 0 mM at 37{degree}C, the relative permeability of Cl{sup {minus}} to Na{sup +} (P{sub Cl}/P{sub Na}) estimated from the NaCl diffusion voltage changed from 2.44 to 1.27. When Ca{sup 2+} concentration of the luminal fluid was reduced, P{sub Cl}/P{sub Na} was unchanged. When Ca{sup 2+} concentration in the bathing fluid was change from 4.5 to nominally 0 mM,more » the lumen-to-bath flux coefficient for {sup 36}Cl (K{sub 1{yields}b}{sup 36Cl}) was decreased, whereas the value of {sup 22}Na was unchanged, indicating that the reduction of Ca{sup 2+} concentration in the bathing fluid selectively inhibits Cl{sup {minus}} transport without affecting Na{sup +} transport. The pH titration curves of relative Cl{sup {minus}} permeability examined at three different Ca{sup 2+} concentrations at 37{degree}C revealed that the interaction between proton and Ca{sup +} was noncompetitive. Addition of quin 2-AM, which reduced intracellular Ca{sup 2+} concentration, to the bath caused an irreversible suppression of Cl{sup {minus}} permeability, suggesting that the decrease in intracellular Ca{sup 2+} concentration also inhibits the Cl{sup {minus}} transport across the TAL. From these observations the authors suggest: (1) Cl{sup {minus}} transport across the TAL is regulated by Ca{sup 2+} preferentially on the basolateral membrane; (2) this regulation depends on temperature; and (3) there is a noncompetitive interaction between Ca{sup 2+} and proton in the regulation of the conductive Cl{sup {minus}} pathway.« less

[Extravasation injuries in newborns: our experience about 15 cases].

PubMed

Nandiolo-Anelone, K R; Allah, K C; Cissé, L; Bankolé, S R; Oulaï, M; Aké, A Y L

2014-02-01

Extravasation injuries are common complications that occur during infusion for diagnostic or therapeutic purposes by the peripheral or central venous catheters. In pediatric settings, iatrogenic extravasations are serious. When they are viewed late, they are sources of functional sequelae. The purpose of this study was to report our experience with the management of iatrogenic extravasations for therapeutic purposes. Between January 2010 and December 2012, fifteen newborns were supported for accidents of infusion of the upper and the lower limbs. The male was mostly affected. The mean age was 3.6days, with extremes of one and nine days. The average birth weight was 2900g. The range was 1200g and 3550g. Serum 10 % glucose and calcium chloride were implicated in all cases. The lesions were seen in the late stages III in six cases and IV in nine cases. The upper limbs were frequently affected. Nine lesions were in the upper limbs and six in the lower limbs. The dorsal surfaces, feet and hands were frequently affected in six and five cases, respectively. Two lesions were in the anterior aspect of the forearm and elbow. Elbows lesions were circular and realized a tourniquet effect. Treatment was conservative in eleven cases: five pro-inflammatory fatty dressings and six alcoholic dressings. The surgery was delayed in four cases. It combined excision-full thickness skin graft, excision-dressing-thin skin grafting, debridement and two-full thickness skin graft for retractable wrist scars. Two deaths were related to associate pathologies. One patient was lost for follow-up. Our results were satisfactory in functional, aesthetic and psychological aspects. Extravasation injuries are serious iatrogenic lesions. If the lesions are seen at an early stage in usual circumstances, in extreme exercise, they are seen late, sometimes at the stage of functional, psychological and cosmetic sequelae. The difficulty of the therapeutic management of these lesions requires prevention through the development of protocols and the permanent training of nursing staff for an efficient practice of infusion. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Freedom of Information Act Requests: Six Keys to Handling Them

DTIC Science & Technology

2016-01-01

Defense AT&L: January–February 2016 50 Freedom of Information Act Requests Six Keys to Handling Them Michael A. Rodgers Rodgers is a professor of...crucial mission tasks. Understanding and using the six steps and keys provided above will free you from FOIA-induced distractions. The author can be contacted at michael.rodgers@dau.mil.

Caught in the (Education) Act: Tackling Michael Gove's Education Revolution. Report on 19th November 2011 Conference

ERIC Educational Resources Information Center

FORUM: for promoting 3-19 comprehensive education, 2012

2012-01-01

A number of significant campaigning organisations and education trades unions--the Anti-Academies Alliance, CASE, Comprehensive Future, Forum, ISCG and the Socialist Educational Association, along with ASCL, ATL, NASUWT and NUT--staged a conference in London on 19 November 2011, with the title 'Caught in the (Education) Act: tackling Michael…

Dynamic Gaming Platform (DGP)

DTIC Science & Technology

2009-04-01

GAMING PLATFORM (DGP) Lockheed Martin Corporation...YYYY) APR 09 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jul 07 – Mar 09 4. TITLE AND SUBTITLE DYNAMIC GAMING PLATFORM (DGP) 5a...CMU Carnegie Mellon University DGP Dynamic Gaming Platform GA Genetic Algorithm IARPA Intelligence Advanced Research Projects Activity LM ATL Lockheed Martin Advanced Technology Laboratories PAINT ProActive INTelligence

Economic and environmental effects of accelerated tariff liberalization in the forest products sector.

Treesearch

D.J. Brooks; J.A. Ferrante; J. Haverkamp; I. Bowles; W. Lange; D. Darr

2001-01-01

This study assesses the incremental economic and environmental impacts resulting from changes in the timing and scope of forest products tariff reductions as proposed in the Accelerated Tariff Liberalization (ATL) initiative in forest products. This initiative was proposed for agreement among member countries of the World Trade Organization. The analysis of...

Coyote and Raven (P)re-Visit Environmental Education, Sustainability, and Run-Away Capitalism

ERIC Educational Resources Information Center

Cole, Peter; O'Riley, Pat

2010-01-01

Together with ubiquitous agent evocateurs, Coyote and Raven, the authors engage trickster discourse and narrative shape shifting as they share research protocols and community conversations based on their research with the four Lower Stl'atl'imx communities (Xa'xtsa, N'Quat'qua, Skatin and Samahquam First Nations) of British Columbia, Canada, in…

Complex System Governance for Acquisition

DTIC Science & Technology

2016-04-30

2014, September–October). Cybersecurity challenges for program managers . Defense AT&L. Naphade, M., Banavar, G., Harrison, C., Paraszczak, J...the Acquisition Research Program of the Graduate School of Business & Public Policy at the Naval Postgraduate School. To request defense...Dickmann, Vice President, Sonalysts Inc. A Complex Systems Perspective of Risk Mitigation and Modeling in Development and Acquisition Programs Roshanak

Shining a Spotlight on the Defense Acquisition Workforce -- Again

DTIC Science & Technology

2009-01-01

Defense AT&L, January–February, 2008. Rostker, Bernard , A Call to Revitalize the Engines of Government, Santa Mon- ica, CA: RAND Corporation, OP-240...there are a large number of individuals in the 1101 series who are part of the AW, (3,816 in FY 2007), but they 13 Note that some FAI analyses have

Si III OV Bright Line of Scattering Polarized Light That Has Been Observed in the CLASP and Its Center-to-Limb Variation

NASA Technical Reports Server (NTRS)

Katsukawa, Yukio; Ishikawa, Ryoko; Kano, Ryohei; Kubo, Masahito; Noriyuki, Narukage; Kisei, Bando; Hara, Hirohisa; Yoshiho, Suematsu; Goto, Motouji; Ishikawa, Shinnosuke;

Earth limb views with greenish bands of airglow during STS-99

NASA Image and Video Library

2000-04-06

STS099-356-026 (11-22 February 2000) ---Because of its time exposure, this STS-99 35mm frame provides a view of several stars. The thin greenish band above the horizon is airglow; radiation emitted by the atmosphere from a layer about 30 kilometers thick and about 100 kilometers altitude. The predominant emission in airglow is the green 5577-Angstrom wavelength emission from atomic oxygen atoms. Airglow is always and everywhere present in the atmosphere; it results from the recombination of molecules that have been broken apart by solar radiation during the day. But airglow is so faint that it can only be seen at night by looking "edge on" at the emission layer, such as the view astronauts have in orbit.

New Developments in the SCIAMACHY Level 2 Ground Processor Towards Version 7

NASA Astrophysics Data System (ADS)

Meringer, Markus; Noël, Stefan; Lichtenberg, Günter; Lerot, Christophe; Theys, Nicolas; Fehr, Thorsten; Dehn, Angelika; Liebing, Patricia; Gretschany, Sergei

2016-07-01

SCIAMACHY (SCanning Imaging Absorption spectroMeter for Atmospheric ChartographY) aboard ESA's environmental satellite ENVISAT observed the Earth's atmosphere in limb, nadir, and solar/lunar occultation geometries covering the UV-Visible to NIR spectral range. It is a joint project of Germany, the Netherlands and Belgium and was launched in February 2002. SCIAMACHY doubled its originally planned in-orbit lifetime of five years before the communication to ENVISAT was severed in April 2012, and the mission entered its post-operational phase. In order to preserve the best quality of the outstanding data recorded by SCIAMACHY, data processors are still being updated. This presentation will highlight three new developments that are currently being incorporated into the forthcoming version 7 of ESA's operational level 2 processor: 1. Tropospheric BrO, a new retrieval based on the scientific algorithm of (Theys et al., 2011). This algorithm had originally been developed for the GOME-2 sensor and was later adapted for SCIAMACHY. The main principle of the new algorithm is to split BrO total columns, which are already an operational product, into stratospheric VCD_{strat} and tropospheric VCD_{trop} fractions. BrO VCD_{strat} is determined from a climatological approach, driven by SCIAMACHY O_3 and NO_2 observations. Tropospheric vertical column densities are then determined as difference VCD_{trop}=VCD_{total}-VCD_{strat}. 2. Improved cloud flagging using limb measurements (Liebing, 2015). Limb cloud flags are already part of the SCIAMACHY L2 product. They are currently calculated employing the scientific algorithm developed by (Eichmann et al., 2015). Clouds are categorized into four types: water, ice, polar stratospheric and noctilucent clouds. High atmospheric aerosol loadings, however, often lead to spurious cloud flags, when aerosols had been misidentified as clouds. The new algorithm will better discriminate between aerosol and clouds. It will also have a higher sensitivity w.r.t. thin clouds. 3. A new, future-proof file format for the level 2 product based on NetCDF. The data format will be aligned and harmonized with other missions, particularly GOME and Sentinels. The final concept for the new format is still under discussion within the SCIAMACHY Quality Working Group. References: K.-U. Eichmann et al.: Global cloud top height retrieval using SCIAMACHY limb spectra: model studies and first results, Atmos. Meas. Tech. Discuss., 8, 8295-8352, 2015. P. Liebing: New Limb Cloud Detection Algorithm Theoretical Basis Document, 2016. N. Theys et al.: Global observations of tropospheric BrO columns using GOME-2 satellite data, Atmos. Chem. Phys., 11, 1791-1811, 2011.

Thin Ice Clouds in Far IR Experiment: TICFIRE

NASA Astrophysics Data System (ADS)

Blanchet, Jean-Pierre

The TICFIRE mission concept developed with the support of the Canadian Space Agency aims: 1) to improve measurements of water-vapor concentration in the low limit, where cold regions are most sensitive and 2) to determine the contribution of Thin Ice Clouds (TIC) to the energy balance and the role of their microphysical properties on atmospheric cooling. TICFIRE is a process-oriented mission on a micro-satellite platform dedicated to observe key parameters of TIC forming in the cold regions of the Poles and globally, in the upper troposphere. It locates cloud top profiles at the limb and measures at nadir the corresponding upwelling radiance of the atmosphere directly in the thermal window and in the Far Infrared (FIR) spectrum over cold geographical regions, precisely where most of the atmospheric thermal cooling takes place. Due to technological limitations, the FIR spectrum (17 to 50 m) is not regularly monitored by conventional sensors despite its major importance. This deficiency in key data also impacts operational weather forecasting. TICFIRE will provide on a global scale a needed contribution in calibrated radiance assimilation near the IR maximum emission to improve weather forecast. Therefore, TICFIRE is a science-driven mission with a strong operational component.

Congenital heart defects in oculodentodigital dysplasia: Report of two cases.

PubMed

Izumi, Kosuke; Lippa, Andrew M; Wilkens, Alisha; Feret, Holly A; McDonald-McGinn, Donna M; Zackai, Elaine H

2013-12-01

Oculodentodigital dysplasia is caused by mutations in the GJA1 gene. Oculodentodigital dysplasia presents with a spectrum of clinical features including craniofacial, ocular, dental, and limb anomalies. Although recent findings implicate the major role of GJA1 during cardiac organogenesis, congenital heart defects are infrequently reported in oculodentodigital dysplasia. Here we report on two patients with GJA1 mutations presenting with cardiac malformations and type III syndactyly. Patient 1 presented with pulmonary atresia, an intact septum, right ventricular hypoplasia and tricuspid stenosis. The infant had a small nose, thin columella and bilateral 4-5 syndactyly of the fingers. A de novo c.226C>T (p.Arg76Cys) mutation was identified. Patient 2 presented at 6 months with a ventricular septal defect. The child had hypoplastic alae nasi with a thin columella and bilateral 4-5 syndactyly of the digits. A de novo missense mutation, c.145C>G (p.Gln49Glu) was found. Our two patients underscore the importance of cardiac evaluations as part of the initial workup for patients with findings of oculodentodigital dysplasia. Conversely, those patients with type III syndactyly and congenital heart defect should be screened for GJA1 mutations. © 2013 Wiley Periodicals, Inc.

A Review of Spatial and Seasonal Changes in Condensation Clouds Observed During Aerobraking by MGS TES

NASA Technical Reports Server (NTRS)

Pearl, J. C.; Smith, M. D.; Conrath, B. J.; Bandfield, J. L.; Christensen, P. R.

1999-01-01

Successful operation of the Mars Global Surveyor spacecraft beginning in September 1997, has permitted extensive infrared observations of condensation clouds during the martian southern summer and fall seasons (184 deg

[Progress on the Rule of Clavicle Epiphyseal Closure Using Multi-Imaging Technology].

PubMed

Fan, F; Tu, M; Luo, Y Z; Zhang, K; Chen, X G; Deng, Z H

2016-08-01

People aged 18 years could be punished lightly or diminished criminal responsibility, even be spared the death sentence, which has important meaning in Chinese judicatory adjudication. The epiphysis of long bones from human limbs and the secondary sexual characteristics almost have developed completely before 18 years old. Clavicle epiphysis is one of the articular metaphysis which has a late epiphyseal closure. The recent studies in exploring the rule of clavicle epiphyseal by multi-imaging technology shows that the development of clavicle epiphysis has some value in age estimation of 18 years old. CT, especially thin-section CT, is widely used at present. However, thin-section CT scanning has great net radiation, which is not ethically acceptable if it is not for diagnosis and treatment. MRI is nonradioactive tomographic imaging and easy to evaluate, which is one of the future research directions in forensic age estimation using the medial clavicle. This paper summarizes the progress on the rule of clavicle epiphyseal closure, and analyzes and summarizes the feasibility of rule of clavicle epiphyseal closure applies on age estimation. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Information Technology Program Management: Is There a Difference?

DTIC Science & Technology

2014-06-01

from the NAVAL POSTGRADUATE SCHOOL June 2014 Authors: James D. Allen Approved by: John Dillard, Lead Advisor Dr...Personnel and Management USD (AT&L) Under Secretary of Defense for Acquisition, Technology, & Logistics USDA Department of Agriculture xiv...interviews and questions via phone or email . E. ORGANIZATION This study is organized into five chapters. Chapter I presents an overview of the

Investigating Concurrency in Weapons Programs

DTIC Science & Technology

2010-10-01

manipulation. Defense AT&L: September-October 2010 20 acquisition’s Feb. 6, 2006, memorandum, “Design/Build Con - currency,” identified the high degree...We have consistently reported on the elevated risk of poor program outcomes from the substantial overlap of development, test, and production...rency a program can experience before significant cost increase is incurred rages on. Advantages and Disadvantages Intuitively, one can see the

Energy Input to the Auroral Ionosphere.

DTIC Science & Technology

1980-02-29

I s ionl ratev we (’tin-i Is too high; litl v lu, it woold kieep Ev itit t he ra tige of rl 40 tiV/ hi. :v.Itl!; et atl. 1 1911 1 anld (it la iI...to 170-km altitude. The Hall conductivity (solid line) is nearly always greater than the Pederson conductivity (dashed line). Fig. 6b. Calculated

Transforming the Future of Business Processes

DTIC Science & Technology

2008-04-01

Principal Deputy Under Secretary of Defense for Business Transformation Acquisition, finance and accounting, program management —Elizabeth McGrath has experi...executing the de- partment’s primary governance body for business trans- formation, the Defense Business Systems Management Committee (DBSMC... business transformation requires a num- ber of things—leadership commitment, strong investment 3 Defense AT&L: March-April 2008 management , an active

Academic Outcomes of the Chicago School Readiness Project in First Grade: Do Children's Approaches to Learning Mediate Treatment Effects on Academic Skills?

ERIC Educational Resources Information Center

Li-Grining, Christine; Haas, Kelly

2010-01-01

The Chicago School Readiness Project (CSRP), a randomized, classroom-based mental health intervention, aimed to improve teachers' behavior management of preschoolers' dysregulated behavior. The current follow-up study examines potential impacts on academic skills of first graders by enhancing their ATL. This investigation seeks to answer three…

Prehospital Nursing in Maryland - Legal Considerations

DTIC Science & Technology

1991-01-01

Certified CRTs’ scope of practice includes performing all phases of cardiopulmonary resuscitation including administration of drugs and intravenous solutions...who Prehospital Nursing 36 man the MedEvac helicopters, may perform all phases of prehospital advanced life support (ATLS), administer drugs and... midwifery . In Massachusetts, the Board of Registration in Nursing is authorized to establish conditions and regulations for nursing practice in the

Acquisition Environment, Safety, and Occupational Health: Lessons Learned From DoD Acquisition Systems Engineering Program Support Reviews

DTIC Science & Technology

2011-05-01

not integrated Lack of emphasis on implementing ESOH mitigations Failure to address USD (AT&L) hexavalent chrome policy 12 ODUSD(I&E) / CMRM Value of...4.1, Design Considerations Factor 4.1.4, ESOH Factor 4.1.7, Corrosion ( Hexavalent Chromium) 6 ODUSD(I&E) / CMRM 1. Mission Capabilities – Clarity and

Developing a Continuous Improvement System

DTIC Science & Technology

2016-09-16

disagree that continuous improvement is critical to an organization’s suc-cess, since conducting business using a status quo philosophy will not work...for implementing one of these processes include: better operational efficiency, increased customer satisfaction, improved employee morale ...when a problem in reliability or maintenance may become the greatest opportunity. As described in the January-February 2011 issue of Defense AT&L

The Extended Language Network: A Meta-Analysis of Neuroimaging Studies on Text Comprehension

PubMed Central

Ferstl, Evelyn C.; Neumann, Jane; Bogler, Carsten; von Cramon, D. Yves

2010-01-01

Language processing in context requires more than merely comprehending words and sentences. Important subprocesses are inferences for bridging successive utterances, the use of background knowledge and discourse context, and pragmatic interpretations. The functional neuroanatomy of these text comprehension processes has only recently been investigated. Although there is evidence for right-hemisphere contributions, reviews have implicated the left lateral prefrontal cortex, left temporal regions beyond Wernicke’s area, and the left dorso-medial prefrontal cortex (dmPFC) for text comprehension. To objectively confirm this extended language network and to evaluate the respective contribution of right hemisphere regions, meta-analyses of 23 neuroimaging studies are reported here. The analyses used replicator dynamics based on activation likelihood estimates. Independent of the baseline, the anterior temporal lobes (aTL) were active bilaterally. In addition, processing of coherent compared with incoherent text engaged the dmPFC and the posterior cingulate cortex. Right hemisphere activations were seen most notably in the analysis of contrasts testing specific subprocesses, such as metaphor comprehension. These results suggest task dependent contributions for the lateral PFC and the right hemisphere. Most importantly, they confirm the role of the aTL and the fronto-medial cortex for language processing in context. PMID:17557297

Spacecraft contamination programs within the Air Force Systems Command Laboratories

NASA Technical Reports Server (NTRS)

Murad, Edmond

1990-01-01

Spacecraft contamination programs exist in five independent AFSC organizations: Geophysics Laboratory (GL), Arnold Engineering and Development Center (AEDC), Rome Air Development Center (RADC/OSCE), Wright Research and Development Center (MLBT), Armament Laboratory (ATL/SAI), and Space Systems Division (SSD/OL-AW). In addition, a sizable program exists at Aerospace Corp. These programs are complementary, each effort addressing a specific area of expertise: GL's effort is aimed at addressing the effects of on-orbit contamination; AEDC's effort is aimed at ground simulation and measurement of optical contamination; RADC's effort addresses the accumulation, measurement, and removal of contamination on large optics; MLBT's effort is aimed at understanding the effect of contamination on materials; ATL's effort is aimed at understanding the effect of plume contamination on systems; SSD's effort is confined to the integration of some contamination experiments sponsored by SSD/CLT; and Aerospace Corp.'s effort is aimed at supporting the needs of the using System Program Offices (SPO) in specific areas, such as contamination during ground handling, ascent phase, laboratory measurements aimed at understanding on-orbit contamination, and mass loss and mass gain in on-orbit operations. These programs are described in some detail, with emphasis on GL's program.

RNAi-Based Suppressor Screens Reveal Genetic Interactions Between the CRL2LRR-1 E3-Ligase and the DNA Replication Machinery in Caenorhabditis elegans

PubMed Central

Ossareh-Nazari, Batool; Katsiarimpa, Anthi; Merlet, Jorge; Pintard, Lionel

2016-01-01

Cullin-RING E3-Ligases (CRLs), the largest family of E3 ubiquitin-Ligases, regulate diverse cellular processes by promoting ubiquitination of target proteins. The evolutionarily conserved Leucine Rich Repeat protein 1 (LRR-1) is a substrate-recognition subunit of a CRL2LRR-1 E3-ligase. Here we provide genetic evidence supporting a role of this E3-enzyme in the maintenance of DNA replication integrity in Caenorhabditis elegans. Through RNAi-based suppressor screens of lrr-1(0) and cul-2(or209ts) mutants, we identified two genes encoding components of the GINS complex, which is part of the Cdc45-MCM-GINS (CMG) replicative helicase, as well as CDC-7 and MUS-101, which drives the assembly of the CMG helicase during DNA replication. In addition, we identified the core components of the ATR/ATL-1 DNA replication checkpoint pathway (MUS-101, ATL-1, CLSP-1, CHK-1). These results suggest that the CRL2LRR-1 E3-ligase acts to modify or degrade factor(s) that would otherwise misregulate the replisome, eventually leading to the activation of the DNA replication checkpoint. PMID:27543292

Recent Improvements to the Acoustical Testing Laboratory at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Podboy, Devin M.; Mirecki, Julius H.; Walker, Bruce E.; Sutliff, Daniel L.

2014-01-01

The Acoustical Testing Laboratory (ATL) consists of a 27- by 23- by 20-ft (height) convertible hemi/anechoic chamber and separate sound-attenuating test support enclosure. Absorptive fiberglass wedges in the test chamber provide an anechoic environment down to 100 Hz. A spring-isolated floor system affords vibration isolation above 3 Hz. These specifications, along with very low design background levels, enable the acquisition of accurate and repeatable acoustical measurements on test articles that produce very low sound pressures. Removable floor wedges allow the test chamber to operate in either a hemi-anechoic or anechoic configuration, depending on the size of the test article and the specific test being conducted. The test support enclosure functions as a control room during normal operations. Recently improvements were accomplished in support of continued usage of the ATL by NASA programs including an analysis of the ultra-sonic characteristics. A 3-D traverse system inside the chamber was utilized for acquiring acoustic data for these tests. The traverse system drives a linear array of 13, 1/4 in.-microphones spaced 3 in. apart (36 in. span). An updated data acquisition system was also incorporated into the facility.

Recent Improvements to the Acoustical Testing Laboratory at the NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Podboy, Devin M.; Mirecki, Julius H.; Walker, Bruce E.; Sutliff, Daniel L.

2014-01-01

The Acoustical Testing Laboratory (ATL) consists of a 27 by 23 by 20 ft (height) convertible hemi/anechoic chamber and separate sound-attenuating test support enclosure. Absorptive fiberglass wedges in the test chamber provide an anechoic environment down to 100 Hz. A spring-isolated floor system affords vibration isolation above 3 Hz. These specifications, along with very low design background levels, enable the acquisition of accurate and repeatable acoustical measurements on test articles that produce very low sound pressures. Removable floor wedges allow the test chamber to operate in either a hemi-anechoic or anechoic configuration, depending on the size of the test article and the specific test being conducted. The test support enclosure functions as a control room during normal operations. Recently improvements were accomplished in support of continued usage of the ATL by NASA programs including an analysis of the ultra-sonic characteristics. A 3 dimensional traverse system inside the chamber was utilized for acquiring acoustic data for these tests. The traverse system drives a linear array of 13, 1/4"-microphones spaced 3" apart (36" span). An updated data acquisition system was also incorporated into the facility.

Reliability of trauma management videos on YouTube and their compliance with ATLS® (9th edition) guideline.

PubMed

Şaşmaz, M I; Akça, A H

2017-06-01

In this study, the reliability of trauma management scenario videos (in English) on YouTube and their compliance with Advanced Trauma Life Support (ATLS ® ) guidelines were investigated. The search was conducted on February 15, 2016 by using the terms "assessment of trauma" and ''management of trauma''. All videos that were uploaded between January 2011 and June 2016 were viewed by two experienced emergency physicians. The data regarding the date of upload, the type of the uploader, duration of the video and view counts were recorded. The videos were categorized according to the video source and scores. The search results yielded 880 videos. Eight hundred and thirteen videos were excluded by the researchers. The distribution of videos by years was found to be balanced. The scores of videos uploaded by an institution were determined to be higher compared to other groups (p = 0.003). The findings of this study display that trauma management videos on YouTube in the majority of cases are not reliable/compliant with ATLS-guidelines and can therefore not be recommended for educational purposes. These data may only be used in public education after making necessary arrangements.

Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes.

PubMed

Shimotake, Akihiro; Matsumoto, Riki; Ueno, Taiji; Kunieda, Takeharu; Saito, Satoru; Hoffman, Paul; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu; Takahashi, Ryosuke; Ikeda, Akio; Lambon Ralph, Matthew A

2015-10-01

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing. © The Author 2014. Published by Oxford University Press.

The Nature and Neural Correlates of Semantic Association versus Conceptual Similarity

PubMed Central

Jackson, Rebecca L.; Hoffman, Paul; Pobric, Gorana; Lambon Ralph, Matthew A.

2015-01-01

The ability to represent concepts and the relationships between them is critical to human cognition. How does the brain code relationships between items that share basic conceptual properties (e.g., dog and wolf) while simultaneously representing associative links between dissimilar items that co-occur in particular contexts (e.g., dog and bone)? To clarify the neural bases of these semantic components in neurologically intact participants, both types of semantic relationship were investigated in an fMRI study optimized for anterior temporal lobe (ATL) coverage. The clear principal finding was that the same core semantic network (ATL, superior temporal sulcus, ventral prefrontal cortex) was equivalently engaged when participants made semantic judgments on the basis of association or conceptual similarity. Direct comparisons revealed small, weaker differences for conceptual similarity > associative decisions (e.g., inferior prefrontal cortex) and associative > conceptual similarity (e.g., ventral parietal cortex) which appear to reflect graded differences in task difficulty. Indeed, once reaction time was entered as a covariate into the analysis, no associative versus category differences remained. The paper concludes with a discussion of how categorical/feature-based and associative relationships might be represented within a single, unified semantic system. PMID:25636912