bluuebunny/crossref_metadata_2025 huggingface dataset:
America's Uncounted Millions
Authors: Holden Constance
Published: May 2009

It is getting increasingly difficult to count a mobile population, but an “adjustment” based on postcensus sampling is politically unacceptable.
Evaluation of Oral Fluid Enzyme Immunoassay for Confirmation of a Positive Rapid Human Immunodeficiency Virus Test Result
Authors: Wesolowski L. G. , Sanchez T. , MacKellar D. A. , Branson B. M. , Ethridge S. F. , Constantine N. , Ketema F. , Sullivan P. S.
Published: May 2009

The CDC recommends that a reactive rapid human immunodeficiency virus (HIV) test be confirmed with an approved supplemental test; the performance of an intermediate enzyme immunoassay (EIA) is optional. In support of this recommendation, it was found that of 1,431 reactive rapid HIV test results, 2 (0.1%) had false-negative oral fluid Western blot results and both had false-negative EIA results.
Diminished Treatment Response of Periodontally Diseased Patients Infected with the JP2 Clone ofAggregatibacter(Actinobacillus)actinomycetemcomitans
Authors: Cortelli Sheila Cavalca , Costa Fernando Oliveira , Kawai Toshihisa , Aquino Davi Romeiro , Nobre Franco Gilson Cesar , Ohara Kazuhisa , Roman-Torres Caio Vinícius Gonçalves , Cortelli José Roberto
Published: May 2009

This longitudinal study evaluated the response to periodontal treatment by subjects infected with either JP2 (n= 25) or non-JP2 (n= 25)Aggregatibacter(Actinobacillus)actinomycetemcomitans. Participants were treated during the first 4 months by receiving (i) scaling and root planing, (ii) systemic antibiotic therapy, and (iii) periodontal surgery. Probing depth (PD), clinical attachment level (CAL), and gingival and plaque indices (GI and PI, respectively) were monitored at baseline and at 12 months, along with DNA-PCR-based subgingival detection of JP2 or non-JP2A. actinomycetemcomitans. At baseline, PD, CAL, and GI scores were statistically higher in the JP2 strain-positive group than the non-JP2-strain-positive group. At 12 months, PD, CAL, and GI scores had decreased significantly for both groups, but the reduction rates of PD and CAL were higher in the non-JP2-strain-positive group. Among JP2-strain-positive patients in the baseline, patients who remained JP2 strain positive at 12 months showed significantly higher GIs than did the patients who had lost the detectable JP2 clone. Patients who remained JP2 strain positive at 12 months appeared to be more resistant to mechanical-chemical therapy than did those who were still non-JP2 strain positive, while the elimination of JP2A. actinomycetemcomitansremarkably diminished gingival inflammation. Early identification and elimination of the JP2 clone ofA. actinomycetemcomitanswill enable practitioners to effectively predict the outcome of treatments applied to periodontal patients.
Prospective Universal Application of Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat Genotyping To CharacterizeMycobacterium tuberculosisIsolates for Fast Identification of Clustered and Orphan Cases
Authors: Alonso-Rodriguez Noelia , Martínez-Lirola Miguel , Sánchez M. Luisa , Herranz Marta , Peñafiel Teresa , Bonillo Magdalena del Carmen , Gonzalez-Rivera Milagros , Martínez Juan , Cabezas Teresa , Diez-García Luis Felipe , Bouza Emilio , García de Viedma Darío
Published: May 2009

The use of molecular tools for genotypingMycobacterium tuberculosisisolates in epidemiological surveys in order to identify clustered and orphan strains requires faster response times than those offered by the reference method, IS6110restriction fragment length polymorphism (RFLP) genotyping. A method based on PCR, the mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping technique, is an option for fast fingerprinting ofM. tuberculosis, although precise evaluations of correlation between MIRU-VNTR and RFLP findings in population-based studies in different contexts are required before the methods are switched. In this study, we evaluated MIRU-VNTR genotyping (with a set of 15 loci [MIRU-15]) in parallel to RFLP genotyping in a 39-month universal population-based study in a challenging setting with a high proportion of immigrants. For 81.9% (281/343) of theM. tuberculosisisolates, both RFLP and MIRU-VNTR types were obtained. The percentages of clustered cases were 39.9% (112/281) and 43.1% (121/281) for RFLP and MIRU-15 analyses, and the numbers of clusters identified were 42 and 45, respectively. For 85.4% of the cases, the RFLP and MIRU-15 results were concordant, identifying the same cases as clustered and orphan (kappa, 0.7). However, for the remaining 14.6% of the cases, discrepancies were observed: 16 of the cases clustered by RFLP analysis were identified as orphan by MIRU-15 analysis, and 25 cases identified as orphan by RFLP analysis were clustered by MIRU-15 analysis. When discrepant cases showing subtle genotypic differences were tolerated, the discrepancies fell from 14.6% to 8.6%. Epidemiological links were found for 83.8% of the cases clustered by both RFLP and MIRU-15 analyses, whereas for the cases clustered by RFLP or MIRU-VNTR analysis alone, links were identified for only 30.8% or 38.9% of the cases, respectively. The latter group of cases mainly comprised isolates that could also have been clustered, if subtle genotypic differences had been tolerated. MIRU-15 genotyping seems to be a good alternative to RFLP genotyping for real-time interventional schemes. The correlation between MIRU-15 andIS6110RFLP findings was reasonable, although some uncertainties as to the assignation of clusters by MIRU-15 analysis were identified.
Regulation of the ORF61 Promoter and ORF61 Functions in Varicella-Zoster Virus Replication and Pathogenesis
Authors: Wang Li , Sommer Marvin , Rajamani Jaya , Arvin Ann M.
Published: May 2009

Varicella-zoster virus (VZV) open reading frame 61 (ORF61) encodes a protein that transactivates viral and cellular promoters in transient-transfection assays and is the ortholog of herpes simplex virus ICP0. In this report, we mapped the ORF61 promoter and investigated its regulation by viral and cellular proteins in transient-expression experiments and by mutagenesis of the VZV genome (parent Oka strain). The 5′ boundary of the minimal ORF61 promoter required for IE62 transactivation was mapped to position −95 relative to the mRNA start site, and three noncanonical GT-rich Sp1-binding sites were documented to occur within the region comprising positions −95 to −45. Contributions of the three Sp1-binding-site motifs, designated Sp1a, Sp1b, and Sp1c, to ORF61 expression and viral replication were varied despite their similar sequences. Two sites, Sp1a and Sp1c, functioned synergistically. When both sites were mutated in the pOka genome to produce pOka-61proΔSp1ac, the mutant virus expressed significantly less ORF61 protein. Using this mutant to investigate ORF61 functions resulted in reductions in the expression levels of IE proteins, viral kinases ORF47 and ORF66, and the major glycoprotein gE, with the most impact on gE. Virion morphogenesis appeared to be intact despite minimal ORF61 expression. Pretreating melanoma cells with sodium butyrate enhanced titers of pOka-61proΔSp1ac but not pOka, suggesting that ORF61 has a role in histone deacetylase inhibition. Growth of pOka-61proΔSp1ac was impaired in SCIDhu skin xenografts, indicating that the regulation of the ORF61 promoter by Sp1 family proteins is important for ORF61 expression in vivo and that ORF61 contributes to VZV virulence at skin sites of replication.
Impaired Replication of Hepatitis C Virus Containing Mutations in a Conserved NS5B Retinoblastoma Protein-Binding Motif
Authors: McGivern David R. , Villanueva Rodrigo A. , Chinnaswamy Sreedhar , Kao C. Cheng , Lemon Stanley M.
Published: May 2009

Hepatitis C virus (HCV) downregulates the retinoblastoma tumor suppressor protein (Rb), a central cell cycle regulator which is also targeted by oncoproteins expressed by DNA tumor viruses. HCV genome replication is also enhanced in proliferating cells. Thus, it is possible that HCV interactions with host cell cycle regulators, such as Rb, have evolved to modify the intracellular environment to promote viral replication. To test this hypothesis and to determine the impact of viral regulation of Rb on HCV replication, we constructed infectious viral genomes containing mutations in the Rb-binding motif of NS5B which ablate the ability of HCV to regulate Rb. These genomes underwent replication in transfected cells but produced variably reduced virus yields. One mutant, L314A, was severely compromised for replication and rapidly mutated to L314V, thereby restoring both Rb regulation and replication competence. Another mutant, C316A, also failed to downregulate Rb abundance and produced virus yields that were about one-third that of virus with the wild-type (wt) NS5B sequence. Despite this loss of replication competence, purified NS5B-C316A protein was two- to threefold more active than wt NS5B in cell-free polymerase and replicase assays. Although small interfering RNA knockdown of Rb did not rescue the replication fitness of these mutants, we conclude that the defect in replication fitness is not due to defective polymerase or replicase function and is more likely to result from the inability of the mutated NS5B to optimally regulate Rb abundance and thereby modulate host gene expression.
Cryo-Electron Microscopy Structure of Adenovirus Type 2 Temperature-Sensitive Mutant 1 Reveals Insight into the Cell Entry Defect
Authors: Silvestry Mariena , Lindert Steffen , Smith Jason G. , Maier Oana , Wiethoff Christopher M. , Nemerow Glen R. , Stewart Phoebe L.
Published: May 2009

The structure of the adenovirus type 2 temperature-sensitive mutant 1 (Ad2
ts
1) was determined to a resolution of 10 Å by cryo-electron microscopy single-particle reconstruction. Ad2
ts
1 was prepared at a nonpermissive temperature and contains the precursor forms of the capsid proteins IIIa, VI, and VIII; the core proteins VII, X (mu), and terminal protein (TP); and the L1-52K protein. Cell entry studies have shown that although Ad2
ts
1 can bind the coxsackievirus and Ad receptor and undergo internalization via αv integrins, this mutant does not escape from the early endosome and is targeted for degradation. Comparison of the Ad2
ts
1 structure to that of mature Ad indicates that Ad2
ts
1 has a different core architecture. The Ad2
ts
1 core is closely associated with the icosahedral capsid, a connection which may be mediated by preproteins IIIa and VI. Density within hexon cavities is assigned to preprotein VI, and membrane disruption assays show that hexon shields the lytic activity of both the mature and precursor forms of protein VI. The internal surface of the penton base in Ad2
ts
1 appears to be anchored to the core by interactions with preprotein IIIa. Our structural analyses suggest that these connections to the core inhibit the release of the vertex proteins and lead to the cell entry defect of Ad2
ts
1.
Modulation of Human Immunodeficiency Virus Type 1 Protease Autoprocessing by Charge Properties of Surface Residue 69
Authors: Huang Liangqun , Sayer Jane M. , Swinford Marie , Louis John M. , Chen Chaoping
Published: May 2009

Mature, fully active human immunodeficiency virus protease (PR) is liberated from the Gag-Pol precursor via regulated autoprocessing. A chimeric protease precursor, glutathione
S
-transferase-transframe region (TFR)-PR-FLAG, also undergoes N-terminal autocatalytic maturation when it is expressed in
Escherichia coli
. Mutation of the surface residue H69 to glutamic acid, but not to several neutral or basic amino acids, impedes protease autoprocessing in bacteria and mammalian cells. Only a fraction of mature PR with an H69E mutation (PR
H69E
) folds into active enzymes, and it does so with an apparent

K
d

(dissociation constant) significantly higher than that of the wild-type protease, corroborating the marked retardation of the in vitro N-terminal autocatalytic processing of TFR-PR
H69E
and suggesting a folding defect in the precursor.
Strong Ability of Nef-Specific CD4+Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+T Cells and Macrophages
Authors: Zheng Nan , Fujiwara Mamoru , Ueno Takamasa , Oka Shinichi , Takiguchi Masafumi
Published: May 2009

A restricted number of studies have shown that human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic CD4+T cells are present in HIV-1-infected individuals. However, the roles of this type of CD4+T cell in the immune responses against an HIV-1 infection remain unclear. In this study, we identified novel Nef epitope-specific HLA-DRB1*0803-restricted cytotoxic CD4+T cells. The CD4+T-cell clones specific for Nef187-203 showed strong gamma interferon production after having been stimulated with autologous B-lymphoblastoid cells infected with recombinant vaccinia virus expressing Nef or pulsed with heat-inactivated virus particles, indicating the presentation of the epitope antigen through both exogenous and endogenous major histocompatibility complex class II processing pathways. Nef187-203-specific CD4+T-cell clones exhibited strong cytotoxic activity against both HIV-1-infected macrophages and CD4+T cells from an HLA-DRB1*0803+donor. In addition, these Nef-specific cytotoxic CD4+T-cell clones exhibited strong ability to suppress HIV-1 replication in both macrophages and CD4+T cells in vitro. Nef187-203-specific cytotoxic CD4+T cells were detected in cultures of peptide-stimulated peripheral blood mononuclear cells (PBMCs) and in ex vivo PBMCs from 40% and 20% of DRB1*0803+donors, respectively. These results suggest that HIV-1-specific CD4+T cells may directly control HIV-1 infection in vivo by suppressing virus replication in HIV-1 natural host cells.
Ocular Infection of Mice with Influenza A (H7) Viruses: a Site of Primary Replication and Spread to the Respiratory Tract
Authors: Belser Jessica A. , Wadford Debra A. , Xu Jianguo , Katz Jacqueline M. , Tumpey Terrence M.
Published: May 2009

Avian H7 influenza viruses have been responsible for poultry outbreaks worldwide and have resulted in numerous cases of human infection in recent years. The high rate of conjunctivitis associated with avian H7 subtype virus infections may represent a portal of entry for avian influenza viruses and highlights the need to better understand the apparent ocular tropism observed in humans. To study this, mice were inoculated by the ocular route with viruses of multiple subtypes and degrees of virulence. We found that in contrast to human (H3N2 and H1N1) viruses, H7N7 viruses isolated from The Netherlands in 2003 and H7N3 viruses isolated from British Columbia, Canada, in 2004, two subtypes that were highly virulent for poultry, replicated to a significant titer in the mouse eye. Remarkably, an H7N7 virus, as well as some avian H5N1 viruses, spread systemically following ocular inoculation, including to the brain, resulting in morbidity and mortality of mice. This correlated with efficient replication of highly pathogenic H7 and H5 subtypes in murine corneal epithelial sheets (ex vivo) and primary human corneal epithelial cells (in vitro). Influenza viruses were labeled to identify the virus attachment site in the mouse cornea. Although we found abundant H7 virus attachment to corneal epithelial tissue, this did not account for the differences in virus replication as multiple subtypes were able to attach to these cells. These findings demonstrate that avian influenza viruses within H7 and H5 subtypes are capable of using the eye as a portal of entry.
Is the Gut the Major Source of Virus in Early Simian Immunodeficiency Virus Infection?
Authors: Lay Matthew D. H. , Petravic Janka , Gordon Shari N. , Engram Jessica , Silvestri Guido , Davenport Miles P.
Published: May 2009

The acute phases of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection are characterized by rapid and profound depletion of CD4
+
T cells from the guts of infected individuals. The large number of CD4
+
T cells in the gut (a large fraction of which are activated and express the HIV/SIV coreceptor CCR5), the high level of infection of these cells, and the temporal coincidence of this CD4
+
T-cell depletion with the peak of virus in plasma in acute infection suggest that the intestinal mucosa may be the major source of virus driving the peak viral load. Here, we used data on CD4
+
T-cell proportions in the lamina propria of the rectums of SIV-infected rhesus macaques (which progress to AIDS) and sooty mangabeys (which do not progress) to show that in both species, the depletion of CD4
+
T cells from this mucosal site and its maximum loss rate are often observed several days before the peak in viral load, with few CD4
+
T cells remaining in the rectum by the time of peak viral load. In contrast, the maximum loss rate of CD4
+
T cells from bronchoalveolar lavage specimens and lymph nodes coincides with the peak in virus. Analysis of the kinetics of depletion suggests that, in both rhesus macaques and sooty mangabeys, CD4
+
T cells in the intestinal mucosa are a highly susceptible population for infection but not a major source of plasma virus in acute SIV infection.
On the Economics of Water Allocation and Pricing
Authors: Tsur Yacov
Published: May 2009

I present the economic principles of water allocation and pricing in a schematic water economy representing a wide range of real-world situations. The water policy has inter- and intratemporal components. The former determines extractions from the naturally replenished sources, given the stochastic nature of recharge processes. The latter is concerned mainly with the allocation of the extracted and produced water among the end users. The optimal water prices associated with the intratemporal allocation task are derived. Implementation of the optimal policy is discussed.
Effect of lowering uric acid on renal disease in the type 2 diabeticdb/dbmice
Authors: Kosugi Tomoki , Nakayama Takahiro , Heinig Marcelo , Zhang Li , Yuzawa Yukio , Sanchez-Lozada Laura Gabriela , Roncal Carlos , Johnson Richard J. , Nakagawa Takahiko
Published: May 2009

Hyperuricemia has recently been recognized to be a risk factor for nephropathy in the diabetic subject. We tested the hypothesis that lowering uric acid with a xanthine oxidase inhibitor might reduce renal injury in the diabetic mouse. Diabetic ( db/db) mice were treated with allopurinol or no treatment for 8 wk. Serum uric acid, renal function, and histology were assessed at death. The direct effect of uric acid in human proximal tubular epithelial cells was also evaluated under normal or high glucose condition. We found that db/db mice developed hyperuricemia, albuminuria, mesangial matrix expansion, and mild tubulointerstitial disease. Allopurinol treatment significantly lowered uric acid levels, reduced albuminuria, and ameliorated tubulointerstitial injury, but it did not prevent mesangial expansion. The mechanism for protection was shown to be due to a reduction in inflammatory cells mediated by a reduction in ICAM-1 expression by tubular epithelial cells. Interestingly, allopurinol did not reduce oxidative stress in the kidney. An inflammatory role of uric acid on tubular cells was also confirmed by our in vitro evidence that uric acid directly induced ICAM-1 expression in the human proximal tubular cell. In conclusion, hyperuricemia has a pathogenic role in the mild tubulointerstitial injury associated with diabetic nephropathy but not glomerular damage in db/db mice. Lowering uric acid may reduce tubulointerstitial injury in diabetes.
The proteasome inhibitor Bortezomib aggravates renal ischemia-reperfusion injury
Authors: Huber Julia M. , Tagwerker Andrea , Heininger Dorothea , Mayer Gert , Rosenkranz Alexander R. , Eller Kathrin
Published: May 2009

Bortezomib is a well-established treatment option for patients with multiple myeloma (MM). It is a selective and reversible inhibitor of the proteasome that is responsible for the degradation of many regulatory proteins that are involved in apoptosis, cell-cycle regulation, or transcription. Because patients with MM are prone to develop acute renal failure, we evaluated the influence of Bortezomib on renal ischemia-reperfusion injury (IRI). Mice were subjected to renal IRI by having the renal pedicles clamped for 30 min followed by reperfusion for 3, 24, and 48 h. Mice were either pretreated with 0.5 mg/kg body wt Bortezomib or vehicle intravenously 12 h before induction of IRI. Serum creatinine and tubular necrosis were significantly increased in Bortezomib compared with vehicle-treated mice. The inflammatory response was found to be significantly decreased in Bortezomib-treated mice as reflected by a decreased infiltration of CD4+T cells and a significantly decreased Th1 cytokine expression in the kidneys. In contrast, apoptosis was significantly increased in kidneys of Bortezomib-treated mice compared with vehicle-treated controls. Increased numbers of TUNEL-positive cells/mm2and increased mRNA expression of proapoptotic factors were detected in kidneys of Bortezomib-treated mice. Of note, p21, a cell senescence marker, was also significantly increased in kidneys of Bortezomib-treated mice. In summary, we provide evidence that Bortezomib worsens the outcome of renal IRI by leading to increased apoptosis of tubular cells despite decreased infiltrating T cells and proinflammatory mediators.
Training improves the response in glucose flux to exercise in postmenopausal women
Authors: Zarins Zinta A. , Johnson Matthew L. , Faghihnia Nastaran , Horning Michael A. , Wallis Gareth A. , Fattor Jill A. , Brooks George A.
Published: May 2009

We examined the effects of endurance training on parameters of glucose flux during rest and exercise in postmenopausal women. Ten sedentary, but healthy women (55 ± 1 yr) completed 12 wk of endurance exercise training on a cycle ergometer [5 days/wk, 1 h/day, 65% peak oxygen consumption (V̇o2peak)]. Flux rates were determined by primed continuous infusion of [6,6-2H]glucose (D2-glucose) during 90 min of rest and 60 min of cycle ergometer exercise during one pretraining exercise trial [65% V̇o2peak (PRE)] and two posttraining exercise trials [the power output that elicited 65% pretraining V̇o2peak (ABT) and 65% posttraining V̇o2peak (RLT)]. Training increased V̇o2peak by 16.3 ± 3.9% ( P < 0.05). Epinephrine and glucagon were lower during ABT and lactate was lower during ABT and RLT ( P < 0.05), but the apparent insulin response was unchanged. Whole body glucose rate of appearance decreased posttraining during exercise at a given power output (4.58 ± 0.39 mg·kg−1·min−1 during ABT compared with 5.21 ± 0.48 mg·kg−1·min−1 PRE, P < 0.05), but not at the same relative workload (5.85 ± 0.36 mg·kg−1·min−1). Training resulted in a 35% increase in glucose MCR during exercise at the same relative intensity (7.16 ± 0.42 ml·kg−1·min−1 during RLT compared with 5.28 ± 0.42 ml·kg−1·min−1 PRE, P < 0.05). Changes in parameters of glucose kinetics during exercise were accomplished without changes in dietary composition, body weight, or body composition. We conclude that despite changes in the hormonal milieu that occur at menopause, endurance training results in a similar magnitude in training-induced alterations of glucose flux as seen previously in younger women.
Sparse but Selective and Potent Synaptic Transmission From the Globus Pallidus to the Subthalamic Nucleus
Authors: Baufreton Jérôme , Kirkham Erin , Atherton Jeremy F. , Menard Ariane , Magill Peter J. , Bolam J. Paul , Bevan Mark D.
Published: May 2009

The reciprocally connected GABAergic globus pallidus (GP)-glutamatergic subthalamic nucleus (STN) network is critical for voluntary movement and an important site of dysfunction in movement disorders such as Parkinson's disease. Although the GP is a key determinant of STN activity, correlated GP-STN activity is rare under normal conditions. Here we define fundamental features of the GP-STN connection that contribute to poorly correlated GP-STN activity. Juxtacellular labeling of single GP neurons in vivo and stereological estimation of the total number of GABAergic GP-STN synapses suggest that the GP-STN connection is surprisingly sparse: single GP neurons maximally contact only 2% of STN neurons and single STN neurons maximally receive input from 2% of GP neurons. However, GP-STN connectivity may be considerably more selective than even these estimates imply. Light and electron microscopic analyses revealed that single GP axons give rise to sparsely distributed terminal clusters, many of which correspond to multiple synapses with individual STN neurons. Application of the minimal stimulation technique in brain slices confirmed that STN neurons receive multisynaptic unitary inputs and that these inputs largely arise from different sets of GABAergic axons. Finally, the dynamic-clamp technique was applied to quantify the impact of GP-STN inputs on STN activity. Small fractions of GP-STN input were sufficiently powerful to inhibit and synchronize the autonomous activity of STN neurons. Together these data are consistent with the conclusion that the rarity of correlated GP-STN activity in vivo is due to the sparsity and selectivity, rather than the potency, of GP-STN synaptic connections.
Recovery of Thumb and Finger Extension and Its Relation to Grasp Performance After Stroke
Authors: Lang Catherine E. , DeJong Stacey L. , Beebe Justin A.
Published: May 2009

This study investigated how the ability to extend the fingers and thumb recovers early after stroke and how the ability to extend all of the digits affects grasping performance. We studied 24 hemiparetic patients at 3 and 13 wk post stroke. At each visit, we tested the subjects' ability to actively extend all five digits of their contralesional, affected hand against gravity and to perform a grasp movement with the same hand. Three-dimensional motion analysis captured: 1) maximal voluntary extension excursion of each digit and 2) grasp performance variables of movement time, peak aperture, peak aperture rate, and aperture path ratio. We found that finger and thumb extension improved from 3 to 13 wk, with average improvements ranging from 12 to 19° across the five digits. Grasp performance improved on two of the four variables measured. Peak apertures and peak aperture rates improved from 3 to 13 wk, but self-selected movement time and aperture path ratio did not. Stepwise multiple regression models showed that the majority of variance in grasp performance at 13 wk could be predicted by the ability to extend the index or middle finger at 3 wk, plus the change in the ability to extend the index finger from 3 to 13 wk. R2values ranged from 0.55 to 0.89. Our data indicate that the amount of recovery in finger and thumb extension and grasping is small from 3 to 13 wk post stroke. In people with relatively pure motor hemiparesis, one important factor underlying deficits in hand shaping during grasping is the inability to extend the fingers and thumb. Without sufficient volitional control of finger and thumb extension, successful grasping of objects will not occur.
Narratives and Organizational Dynamics
Authors: Geiger Daniel , Antonacopoulou Elena
Published: May 2009

This article aims to demonstrate how narratives have the potential to bring about organizational inertia by creating self-reinforcing mechanisms and blind spots. Drawing on extensive interview data from a U.K. bio-manufacturing company, the empirical analysis shows how such narratives emerge by constructing a web of related, self-reinforcing narratives reflecting a consistent theme. The analysis demonstrates how the dominant (success) narrative remains vivid despite the existence of deviating narratives and severe crisis. In particular, the empirical findings illustrate how narratives construct a self-sustaining frame of reference, preventing the organization from questioning the principles underlying its past success. The discussion explains how narratives create self-reinforcing mechanisms and blind spots. It contributes to our understanding of the role of narratives in organizational change efforts and illustrates the way such self-reinforcing blind spots become a potential source of organizational inertia and path-dependence.
Using research
Authors: Wheeler Stephanie
Published: May 2009

Explores the importance of organizational research as a tool to support business change and improvement. Describes a tried and tested research methodology that has been used within public and private sector organizations and can be easily adapted by in-house research and information services. Demonstrates how research can be used to evaluate the effectiveness of learning and development products and services. Includes a case study from a central government department that investigates the role of the line manager in learning.
Real-time Motion Stabilization with B-mode Ultrasound Using Image Speckle Information and Visual Servoing
Authors: Krupa Alexandre , Fichtinger Gabor , Hager Gregory D.
Published: May 2009

We develop visual servo control to stabilize the image of moving soft tissue in B-mode ultrasound (US) imaging. We define the target region in a B-mode US image, and automatically control a robot to manipulate a an US probe by minimizing the difference between the target and the most recently acquired US image. We exploit tissue speckle information to compute the relative pose between the probe and the target region. In-plane motion is handled by image region tracking and out-of-plane motion recovered by speckle tracking using speckle decorrelation. A visual servo control scheme is then applied to manipulate the US probe to stabilize the target region in the live US image. In a first experiment involving only translational motion, an US phan-In a first experiment involving only translational motion, an US phan tom was moved by one robot while stabilizing the target with a second robot holding the US probe. In a second experiment, large six-degree-of-freedom (DOF) motions were manually applied to an US phantom while a six-DOF medical robot was controlled automatically to compensate for the probe displacement. The obtained results support the hypothesis that automated motion stabilization shows promise for a variety of US-guided medical procedures such as prostate cancer brachytherapy.
30-Year-old HIV-positive Female With Diffuse Alveolar Hemorrhage
Authors: Agarwal Vishal K. , Khurana Hargobind S. , Le Hai X. , Mathisen Glenn , Kamangar Nader
Published: May 2009

We present a case of Strongyloides stercoralis hyperinfection in a 30-year-old HIV positive female who presents with diffuse alveolar hemorrhage. We discuss the relevant differential diagnoses and characteristic imaging findings.
The Social Studies Education Discourse Community on Globalization: Exploring the Agenda of Preparing Citizens for the Global Age
Authors: Agbaria Ayman K.
Published: May 2009

The scholarship nexus between education and globalization provides limited insights into how global education has been framed and rendered. The purpose of this article is twofold. First, it seeks a better understanding of the nature of the mission of preparing citizens for the global age and what it entails in the context of learning and teaching social studies in the United States. Second, it aims at describing and characterizing the discourse community of social studies education as it relates to educating about and for globalization. Specifically, this article asks: What educational proposals are suggested in this discourse to prepare the students to meet the demands of globalization? What perspectives, skills, and values are emphasized? And what we can learn from this discourse’s selectivity of content and emphasis? All in all, the article reveals the enclosure of global education within the language and practices of multicultural education.
Neuronal Networks in Alzheimer's Disease
Authors: Yong He  , Zhang Chen  , Gaolang Gong  , Evans Alan
Published: May 2009

Alzheimer's disease (AD) is a progressive, neurodegenerative disease that can be clinically characterized by impaired memory and many other cognitive functions. Previous studies have demonstrated that the impairment is accompanied by not only regional brain abnormalities but also changes in neuronal connectivity between anatomically distinct brain regions. Specifically, using neurophysiological and neuroimaging techniques as well as advanced graph theory—based computational approaches, several recent studies have suggested that AD patients have disruptive neuronal integrity in large-scale structural and functional brain systems underlying high-level cognition, as demonstrated by a loss of small-world network characteristics. Small world is an attractive model for the description of complex brain networks because it can support both segregated and integrated information processing. The altered small-world organization thus reflects aberrant neuronal connectivity in the AD brain that is most likely to explain cognitive deficits caused by this disease. In this review, we will summarize recent advances in the brain network research on AD, focusing mainly on the large-scale structural and functional descriptions. The literature reviewed here suggests that AD patients are associated with integrative abnormalities in the distributed neuronal networks, which could provide new insights into the disease mechanism in AD and help us to uncover an imaging-based biomarker for the diagnosis and monitoring of the disease.
Open-Label Trial of Atomoxetine Hydrochloride in Adults With ADHD
Authors: Johnson Mats , Cederlund Mats , Råstam Maria , Areskoug Björn , Gillberg Christopher
Published: May 2009

Background: While atomoxetine is an established treatment for attention-deficit/hyperactivity disorder in children, few studies have examined its efficacy for adults. Methods: Open-label trial of atomoxetine in 20 individuals with ADHD, aged 19-47 years, for 10 weeks, and a total of one year for responders. Results: Ten patients met primary efficacy criteria at 10 weeks. Only one patient completed the whole study. Six patients discontinued before 10 weeks and thirteen at 10 weeks or later, mainly because of side-effects (aggression, depressed mood, raised liver enzymes, thyroid hormones, diastolic blood pressure), decreasing efficacy or non-compliance. Conclusion: Fifty percent responded to treatment, but only one patient (5%) felt sufficient improvement to continue for one year. Dosage may have been too low, and baseline impairment too high, for atomoxetine to have sufficient effect on ADHD symptoms in our group of adults. The majority had few side-effects, but several terminated treatment because of adverse effects.
Structure and properties of polypropylene/organic rectorite nanocomposites
Authors: Huang Yun , Ma Xiaoyan , Liang Guozheng , Yan Hongxia
Published: May 2009

Melt blending using a twin-screw extruder was used to prepare composites of polypropylene (PP)/organic rectorite (PR). The organic rectorite (OREC) was modified with dodecyl benzyl dimethyl ammonium bromide (1227). Wide-angle X-ray diffraction (WAXD) and transmission electron microscopy were used to investigate the dispersion of OREC in the composites. The d spacings of OREC in PR composites was greater than in OREC itself. The dispersion of OREC particles in the PP polymer matrix was fine and uniform when the clay content was small (2 wt.%). The rheology was characterized using a capillary rheometer. The processing behaviour of the PR system improved as the amount of OREC added increased. Non-isothermal crystallization kinetics were analysed using differential scanning calorimetry. It was shown that the addition of OREC had a heterogeneous nucleation effect on PP, and can accelerate the crystallization. However, only when fine dispersion was achieved, and at lower rates of temperature decrease, was the crystallinity greater. Wide-angle X-ray diffraction and polarized light microscopy were used to observe the crystalline form and crystallite size. The PP in the PR composites exhibited an a-monoclinic crystal form, as in pure PP, and in both cases a spherulite structure was observed. However, the smaller spherulite size in the PR systems indicated that addition of OREC can reduce the crystal size significantly, which might improve the ‘toughness’ of the PP. The mechanical properties (tensile and impact strength) improved when the amount of OREC added was appropriate. Dynamic mechanical analysis showed that the storage modulus (E′) and loss modulus (E″) of the nanocomposites were somewhat greater than those of pure PP when an appropriate amount of OREC was added. Finally, thermogravimetric analysis showed that the PR systems exhibited a greater thermal stability than was seen with pure PP.
Mineralogy, geochemistry and genesis of the Taşoluk kaolinite deposits in pre-Early Cambrian metamorphites and Neogene volcanites of Afyonkarahisar, Turkey
Authors: Kadir S. , Akbulut A.
Published: May 2009

The Taşoluk kaolinite deposits of Afyonkarahisar (western Anatolia) are hosted by both pre-Early Cambrian sericitic mica-chlorite schists and Neogene volcanites, the latter comprising tuffs and agglomerates. These units have been affected by hydrothermal alteration controlled by faults resulting in complex, irregular, lateral mineralogical zonation. The occurrence of a siliceous cap on altered schists and in claystone, of quartz veins in schists and tuffs, and the development of explosion cones and pit fillings indicate that alteration in both the schists and the volcanites is due to hydrothermal processes. Altered schists have generally large (locally small) Fe contents, and claystones are generally silicified and have small Fe contents. Kaolinite predominates south and west of Taşoluk, whereas high (Fe+Ti)-bearing illite + kaolinite predominate in other altered sections. The kaolinite exhibits a stacked micromorphology within altered schists, and the altered volcanites recordin situprecipitation, derived from a mechanism of paired dissolution and precipitation. Illite fibres coexist with kaolinite, smectite, chlorite, mica and sericitized feldspar in markedly altered schists, revealing that the illite formed either authigenically or by conversion of smectite to illite. A relative increase in Cr+Ni and decrease in Sr+Ba in the kaolinite deposits and their schistose host rock relative to the upper level of the kaolinite deposits and their volcanic parent rocks came about by the alteration of chlorite, mica and feldspar in the sericitic mica-chlorite schists, and feldspar, glass shards and schist fragments in the volcanites as a result of extensive faulting, fracturing and hydrothermal activity during Late Miocene-Pliocene volcanism, which contributed to the development of kaolinite deposits under acidic environmental conditions. With regard to industrial applications, the low-Fe kaolinized schists are suitable for use in refractories and paper coatings, while the claystone is suitable for use in ceramics and in the white-cement industry.
Metnase mediates chromosome decatenation in acute leukemia cells
Authors: Wray Justin , Williamson Elizabeth A. , Sheema Sheema , Lee Suk-Hee , Libby Edward , Willman Cheryl L. , Nickoloff Jac A. , Hromas Robert
Published: May 2009

After DNA replication, sister chromatids must be untangled, or decatenated, before mitosis so that chromatids do not tear during anaphase. Topoisomerase IIα (Topo IIα) is the major decatenating enzyme. Topo IIα inhibitors prevent decatenation, causing cells to arrest during mitosis. Here we report that acute myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint, and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain, and is a component of the nonhomologous end-joining DNA double-strand break repair pathway. Metnase interacts with Topo IIα and enhances its decatenation activity. Here we show that multiple types of acute leukemia cells have an attenuated mitotic arrest when decatenation is inhibited and that in an acute myeloid leukemia (AML) cell line this is mediated by Metnase. Of further importance, Metnase permits continued proliferation of these AML cells even in the presence of the clinical Topo IIα inhibitor VP-16. In vitro, purified Metnase prevents VP-16 inhibition of Topo IIα decatenation of tangled DNA. Thus, Metnase expression levels may predict AML resistance to Topo IIα inhibitors, and Metnase is a potential therapeutic target for small molecule interference.
Correction of murine hemophilia A following nonmyeloablative transplantation of hematopoietic stem cells engineered to encode an enhanced human factor VIII variant using a safety-augmented retroviral vector
Authors: Ramezani Ali , Hawley Robert G.
Published: May 2009

Insertional mutagenesis by retroviral vectors is a major impediment to the clinical application of hematopoietic stem cell gene transfer for the treatment of hematologic disorders. We recently developed an insulated self-inactivating gammaretroviral vector, RMSinOFB, which uses a novel enhancer-blocking element that significantly decreases genotoxicity of retroviral integration. In this study, we used the RMSinOFB vector to evaluate the efficacy of a newly bioengineered factor VIII (fVIII) variant (efVIII)—containing a combination of A1 domain point mutations (L303E/F309S) and an extended partial B domain for improved secretion plus A2 domain mutations (R484A/R489A/P492A) for reduced immunogenicity—toward successful treatment of murine hemophilia A. In cell lines, efVIII was secreted at up to 6-fold higher levels than an L303E/F309S A1 domain–only fVIII variant (sfVIIIΔB). Most important, when compared with a conventional gammaretroviral vector expressing sfVIIIΔB, lower doses of RMSin-efVIII-OFB–transduced hematopoietic stem cells were needed to generate comparable curative fVIII levels in hemophilia A BALB/c mice after reduced-intensity total body irradiation or nonmyeloablative chemotherapy conditioning regimens. These data suggest that the safety-augmented RMSin-efVIII-OFB platform represents an encouraging step in the development of a clinically appropriate gene addition therapy for hemophilia A.
Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain
Authors: Seth-Smith Helena MB , Harris Simon R , Persson Kenneth , Marsh Pete , Barron Andrew , Bignell Alexandra , Bjartling Carina , Clark Louise , Cutcliffe Lesley T , Lambden Paul R , Lennard Nicola , Lockey Sarah J , Quail Michael A , Salim Omar , Skilton Rachel J , Wang Yibing , Holland Martin J , Parkhill Julian , Thomson Nicholas R , Clarke Ian N
Published: May 2009

Background

Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis.

Results

The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor.

Conclusion

The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures.
Key role of the 3' untranslated region in the cell cycle regulated expression of the Leishmania infantum histone H2A genes: minor synergistic effect of the 5' untranslated region
Authors: Abanades Daniel R , Ramírez Laura , Iborra Salvador , Soteriadou Ketty , González Victor M , Bonay Pedro , Alonso Carlos , Soto Manuel
Published: May 2009

Background

Histone synthesis in Leishmania is tightly coupled to DNA replication by a post-transcriptional mechanism operating at the level of translation.

Results

In this work we have analyzed the implication of the 5' and 3' untranslated regions (UTR) in the cell cycle regulated expression of the histone H2A in Leishmania infantum. For that purpose, L. infantum promastigotes were stably transfected with different plasmid constructs in which the CAT coding region used as a reporter was flanked by the 5' and 3' UTR regions of the different H2A genes. We report that in spite of their sequence differences, histone H2A 5' and 3' UTRs conferred a cell cycle dependent pattern of expression on the CAT reporter since de novo synthesis of CAT increased when parasites enter the S phase. Using one established L. infantum cell line we showed that CAT expression is controlled by the same regulatory events that control the endogenous histone gene expression. Thus, although we did not detect changes in the level of CAT mRNAs during cell cycle progression, a drastic change in the polysome profiles of CAT mRNAs was observed during the progression from G1 to S phase. In the S phase CAT mRNAs were on polyribosomal fractions, but in the G1 phase the association of CAT transcripts with ribosomes was impaired. Furthermore, it was determined that the addition of just the H2A 3' UTR to the CAT reporter gene is sufficient to achieve a similar pattern of post-transcriptional regulation indicating that this region contains the major regulatory sequences involved in the cell cycle dependent expression of the H2A genes. On the other hand, although CAT transcripts bearing the H2A 5' alone were translated both in the G1 and S phase, higher percentages of transcripts were detected on polyribosomes in the S phase correlating with an increase in the de novo synthesis of CAT. Thus, it can be concluded that this region also contributes, although to a minor extent than the 3' UTR, in the enhancement of translation in the S phase relative to the G1 phase.

Conclusion

Our findings indicate that both, the 5' and the 3' UTRs contain sequence elements that contribute to the cell cycle expression of L. infantum H2A. The 3' UTR region is essential for cell cycle dependent translation of the L. infantum H2A transcripts whereas the 5' UTR has a minor contribution in their S phase dependent translation.