bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Simultaneous Botulinum Toxin Injections Into Several Muscles on Impairment, Activity, Participation, and Quality of Life Among Stroke Patients Presenting With a Stiff Knee Gait
Authors: Caty Gilles D. , Detrembleur Christine , Bleyenheuft Corinne , Deltombe Thierry , Lejeune Thierry M.
Published: July 2008

Background and Purpose—

Walking is an essential activity for daily life and social participation, and it is frequently limited after stroke. A lack of knee flexion during the swing phase (stiff knee) is one of the impairments that restrict walking ability among patients with hemiparetic spasticity. Our purpose was to study the effect of Botulinum toxin type A (BoNT A) injections in several spastic muscles on the impairment, activity, participation, and quality of life of patients with chronic stroke presenting with a stiff knee gait.

Methods—

Twenty chronic hemiparetic poststroke patients with stiff knee gait and ability to walk on a treadmill were recruited. BoNT A was injected into several spastic muscles: the rectus femoris (200 U), semitendinosus (100 U) and triceps surae (200 U). Patients’ neurological impairments (Ashworth scale, Duncan-Ely test, Stroke Impairment Assessment Set, and instrumented gait analysis), activity (ABILOCO and 10-m walking test), and participation (SATISPART-Stroke and 36-item Short-Form Health Survey) were assessed before and 2 months after the injection.

Results—

BoNT A injection reduced the impairments. It improved Stroke Impairment Assessment Set (56.5 [48–63] to 56.5 [52.5 to 63];
P
<0.001), reduced rectus femoris muscle tone (2 [1 to 2.5] to 0 [0 to 1];
P
<0.001), and reduced semitendinosus muscle tone (1 [1 to 1.5] to 1 [0 to 1];
P
<0.001). Gait analysis demonstrated increased knee flexion during the swing phase (22±19° to 27±16°;
P
=0.03), decreased external mechanical work (0.66±0.38 to 0.59±0.25 J kg
−1
m
−1
;
P
=0.04), and demonstrated a lower energy cost (5.8±1.9 to 4.9±1.9 J kg
−1
m
−1
;
P
=0.03). The patients’ locomotion ability was improved (2.2±1.9 to 3.2±2.1 logits;
P
=0.03). The participation and quality of life remained unchanged.

Conclusions—

BoNT A injections in several muscles improved the stiff knee gait and the locomotion ability in adult stroke patients.
A Composite View of Surface Signatures and Interior Properties of Nonlinear Internal Waves: Observations and Applications
Authors: Chang Ming-Huei , Lien Ren-Chieh , Yang Yiing Jang , Tang Tswen Yung , Wang Joe
Published: July 2008

Surface signatures and interior properties of large-amplitude nonlinear internal waves (NLIWs) in the South China Sea (SCS) were measured during a period of weak northeast wind (∼2 m s−1) using shipboard marine radar, an acoustic Doppler current profiler (ADCP), a conductivity–temperature–depth (CTD) profiler, and an echo sounder. In the northern SCS, large-amplitude NLIWs propagating principally westward appear at the tidal periodicity, and their magnitudes are modulated at the spring–neap tidal cycle. The surface scattering strength measured by the marine radar is positively correlated with the local wind speed when NLIWs are absent. When NLIWs approach, the surface scattering strength within the convergence zone is enhanced. The sea surface scattering induced by NLIWs is equivalent to that of a ∼6 m s−1 surface wind speed (i.e., 3 times greater than the actual surface wind speed). The horizontal spatial structure of the enhanced sea surface scattering strength predicts the horizontal spatial structure of the NLIW. The observed average half-amplitude full width of NLIWs λη/2 is 1.09 ± 0.2 km; the average half-amplitude full width of the enhanced scattering strength λI/2 is ∼0.57 λη/2. The average half-amplitude full width of the enhanced horizontal velocity convergence of NLIWs λ∂xu/2 is approximately equal to λI/2. The peak of the enhanced surface scattering leads the center of NLIWs by ∼0.46 λη/2. NLIW horizontal velocity convergence is positively correlated with the enhancement of the surface scattering strength. NLIW amplitude is positively correlated with the spatial integration of the enhancement of the surface scattering strength within the convergence zone of NLIWs. Empirical formulas are obtained for estimating the horizontal velocity convergence and the amplitude of NLIWs using radar measurements of surface scattering strength. The enhancement of the scattering strength exhibits strong asymmetry; the scattering strength observed from behind the propagating NLIW is 24% less than that observed ahead, presumably caused by the skewness and the breaking of surface waves induced by NLIWs. Above the center of NLIWs, the surface scattering strength is enhanced slightly, associated with isotropic surface waves presumably induced or modified by NLIWs. This analysis concludes that in low-wind conditions remote sensing measurements may provide useful predictions of horizontal velocity convergences, amplitudes, and spatial structures of NLIWs. Further applications and modification of the presented empirical formulas in different conditions of wind speed, surface waves, and NLIWs or with other remote sensing methods are encouraged.
Spatial Weighting and Iterative Projection Methods for EOFs
Authors: Baldwin Mark P. , Stephenson David B. , Jolliffe Ian T.
Published: July 2008

Often there is a need to consider spatial weighting in methods for finding spatial patterns in climate data. The focus of this paper is on techniques that maximize variance, such as empirical orthogonal functions (EOFs). A weighting matrix is introduced into a generalized framework for dealing with spatial weighting. One basic principal in the design of the weighting matrix is that the resulting spatial patterns are independent of the grid used to represent the data. A weighting matrix can also be used for other purposes, such as to compensate for the neglect of unrepresented subgrid-scale variance or, in the form of a prewhitening filter, to maximize the signal-to-noise ratio of EOFs. The new methodology is applicable to other types of climate pattern analysis, such as extended EOF analysis and maximum covariance analysis. The increasing availability of large datasets of three-dimensional gridded variables (e.g., reanalysis products and model output) raises special issues for data-reduction methods such as EOFs. Fast, memory-efficient methods are required in order to extract leading EOFs from such large datasets. This study proposes one such approach based on a simple iteration of successive projections of the data onto time series and spatial maps. It is also demonstrated that spatial weighting can be combined with the iterative methods. Throughout the paper, multivariate statistics notation is used, simplifying implementation as matrix commands in high-level computing languages.
Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA
Authors: Hasler F. , Studerus E. , Lindner K. , Ludewig S. , Vollenweider FX
Published: July 2008

Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT2Areceptors also contributes to the overall action of MDMA. The role of 5-HT1Areceptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT1Areceptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT1Aantagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment (‘positive derealization’ and ‘dreaminess’). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT1Areceptor system.
Risk of Late-Life Depression Across 10 European Union Countries: Deconstructing the Education Effect
Authors: Ladin Keren
Published: July 2008

Objective: Assess influence of education and noneducation-based measures of socioeconomic status on depression, illuminating the cumulative and income-adjusted effects cross-nationally. Method: Cross-sectional study of 22,777 men and women (50 to 104 years) from 10 European countries. Individual-level data were collected from the Survey of Health, Ageing and Retirement in Europe (SHARE). Results: Educational attainment was a strong predictor of late-life depression across all countries. Depression rates ranged from 18.10% in Denmark to 36.84% in Spain, reflecting a North— South gradient. Odds of depression were approximately twice as high among adults with less than a high school education compared with those of greater educational background ( p < .001). Inverse association between educational attainment and depression remained significant independent of all other sociodemographic variables. Discussion : Socioeconomic disparities in depression persist throughout later life. Variation in impact of education on depression cross-nationally illuminates need for future research into the protective effects of early-life education.
Data Consistency in Multiple Source Documents
Authors: Karch Debra L. , Logan Joseph E.
Published: July 2008

Data from the 2003-2004 National Violent Death Reporting System were used to compare consistency of homicide variables across multiple source documents. The NVDRS integrates death certificate, coroner/medical examiner and law enforcement data. Included in this analysis are 5,737 homicide incidents. Variables include victim demographics, manner of death, autopsy and pregnancy status, place, date and location of injury/death, and suspected use of alcohol. Demographic variables matched from lows of 70.9% for marital status to 99.9% for race. Injury/death variables matched from 72.6% for date of injury to 99.5% for state of injury. Situational variables ranged from 75.6% for suspected alcohol use to 97.5% for pregnancy status. Overall, data collected across multiple source documents matched at greater than 70%; however inconsistencies have implications for analyzing data from systems with multiple source documents. Understanding and mitigating data mismatches will increase the consistency of data on which violence prevention programs are developed.
Impaired nuclear import and viral incorporation of Vpr derived from a HIV long-term non-progressor
Authors: Caly Leon , Saksena Nitin K , Piller Sabine C , Jans David A
Published: July 2008

We previously reported an epidemiologically linked HIV-1 infected patient cohort in which a long-term non-progressor (LTNP) infected two recipients who then exhibited normal disease progression. Expression of patient-derived vpr sequences from each of the three cohort members in mammalian cells tagged with GFP revealed a significant reduction in Vpr nuclear import and virion incorporation uniquely from the LTNP, whereas Vpr from the two progressing recipients displayed normal localisation and virion incorporation, implying a link between efficient Vpr nuclear import and HIV disease progression. Importantly, an F72L point mutation in the LTNP was identified for the first time as being uniquely responsible for decreased Vpr nuclear import.
Antibodies to the CD4-binding site of HIV-1 gp120 suppress gp120-specific CD4 T cell response while enhancing antibody response
Authors: Visciano Maria Luisa , Tuen Michael , Chen Pei-de , Hioe Catarina E
Published: July 2008

Background

The binding of Abs to the CD4-binding site (CD4bs) of HIV-1 envelope gp120 has been shown to obstruct the processing and generation of helper epitopes from this antigen, resulting in poor presentation of various gp120 epitopes by MHC class II to CD4 T cells. However, the physiologic significance of these inhibitory anti-CD4bs Absin vivohas remained unclear. In this study, we evaluated the immunologic effects of anti-CD4bs Absin vivousing a murine model.

Results

Animals were immunized with recombinant envelope proteins with or without CD4-binding activity (designated CD4bs+Env and CD4bs–Env, respectively). As expected, anti-CD4bs Abs were generated only after immunization with CD4bs+ Env and not with CD4bs–Env. The presence of anti-CD4bs Abs was associated with lower levels of envelope-specific lymphoproliferation in animals immunized with CD4bs+ Env. To further determine the specific role of the anti-CD4bs Abs, we immunized mice with gp120 in the presence of an inhibitory anti-CD4bs mAb or a non-inhibitory anti-gp120 mAb. The data show that the presence of anti-CD4bs mAb reduced CD4 T cell responses to gp120. However, we also detected significantly higher titers of anti-gp120 Abs following immunization with gp120 and the anti-CD4bs mAb.

Conclusion

Anti-CD4bs Abs can exert discordant effects on the gp120-specific CD4 T cell and Ab responsesin vivo, indicating the importance of these particular Abs in influencing both the cellular and the humoral immune responses against HIV-1.
Mycobacterium tuberculosis aortic graft infection with recurrent hemoptysis: a case report
Authors: Clerc Olivier , Jaton Katia , Prod'hom Guy , Von Segesser Ludwig , Greloz Vincent , Greub Gilbert
Published: July 2008

Introduction

Mycobacterium tuberculosis may cause a large variety of clinical presentations due to its ability to disseminate by contiguity or hematogenously. Tuberculosis may remain undiagnosed for years due to the chronic course of the disease, with potentially life-threatening long-term complications.

Case presentation

In this case report, we describe a tuberculous aortic graft infection in a 72-year-old man documented by polymerase chain reaction and cultures. The patient presented with three episodes of hemoptysis following a remote history of miliary tuberculosis. The infection was treated by graft replacement and prolonged antimycobacterial therapy.

Conclusion

Tuberculous infection of a vascular graft is an uncommon complication, but should be considered in patients with an intravascular device and a history of previous tuberculosis, especially when hematogenous spread may have occurred a few months after surgery, or when an active mycobacterial infection is present in close proximity to the graft.
Different serological cross-reactivity of Trypanosoma rangeli forms in Trypanosoma cruzi-infected patients sera
Authors: de Moraes Milene H , Guarneri Alessandra A , Girardi Fabiana P , Rodrigues Juliana B , Eger Iriane , Tyler Kevin M , Steindel Mário , Grisard Edmundo C
Published: July 2008

Background

American Trypanosomiasis or Chagas disease is caused by Trypanosoma cruzi which currently infects approximately 16 million people in the Americas causing high morbidity and mortality. Diagnosis of American trypanosomiasis relies on serology, primarily using indirect immunofluorescence assay (IFA) with T. cruzi epimastigote forms. The closely related but nonpathogenic Trypanosoma rangeli has a sympatric distribution with T. cruzi and is carried by the same vectors. As a result false positives are frequently generated. This confounding factor leads to increased diagnostic test costs and where false positives are not caught, endangers human health due to the toxicity of the drugs used to treat Chagas disease.

Results

In the present study, serologic cross-reactivity between the two species was compared for the currently used epimastigote form and the more pathologically relevant trypomastigote form, using IFA and immunoblotting (IB) assays. Our results reveal an important decrease in cross reactivity when T. rangeli culture-derived trypomastigotes are used in IFA based diagnosis of Chagas disease. Western blot results using sera from both acute and chronic chagasic patients presenting with cardiac, indeterminate or digestive disease revealed similar, but not identical, antigenic profiles.

Conclusion

This is the first study addressing the serological cross-reactivity between distinct forms and strains of T. rangeli and T. cruzi using sera from distinct phases of the Chagasic infection. Several T. rangeli-specific proteins were detected, which may have potential as diagnostic tools.
Environmental-Like Exposure to Low Levels of Estrogen Affects Sexual Behavior and Physiology of Female Rats
Authors: Della Seta Daniele , Farabollini Francesca , Dessì-Fulgheri Francesco , Fusani Leonida
Published: July 2008

Xenoestrogens are endocrine-disrupting chemicals that mimic the action of endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are well documented, whereas the experimental evidence for impairment of reproductive behavior and physiology in mammals after exposure to xenoestrogens has been debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure and that the chemicals tested have additional nonestrogenic toxic effects, hindering generalization of actual xenoestrogenic effects. Here we show that environmental-like exposure to the pure estrogen 17α-ethinylestradiol during development alters reproductive behavior and physiology in adult female Sprague-Dawley rats. We simulated environmental exposure by giving low doses (0.4 and 0.004 μg/kg·d) of 17α-ethinylestradiol orally to pregnant females from conception to weaning of the pups, which continued to receive the treatment until puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma levels of intact female rats when they reached 3 months of age. Exposure to the higher dose strongly affected female sexual behavior and physiology, with suppression of lordosis and the estrous cycle and enhanced aggression toward males. The lower dose disrupted appetitive components of sexual behavior that influence the rate of copulation. Estradiol plasma levels were not affected by the treatment. Our study revealed that exposure to low oral doses of a pure estrogen during development alters female sexual behavior and physiology. These results suggest potential risks of reproductive failure from xenoestrogen exposure in realistic ecological conditions.
Regulation of Bone Mass, Osteoclast Function, and Ovariectomy-Induced Bone Loss by the Type 2 Cannabinoid Receptor
Authors: Idris Aymen I. , Sophocleous Antonia , Landao-Bassonga Euphemie , van't Hof Robert J. , Ralston Stuart H.
Published: July 2008

The endocannabinoid system has recently been shown to play a role in the regulation of bone metabolism. The type 2 cannabinoid receptor (CB2) has been reported to regulate bone mass, but conflicting results have been reported with regard to its effects on bone resorption and osteoclast function. Here we investigated the role that CB2 plays in regulating bone mass and osteoclast function using a combination of pharmacological and genetic approaches. The CB2-selective antagonist/inverse agonist AM630 inhibited osteoclast formation and activity in vitro, whereas the CB2-selective agonists JWH133 and HU308 stimulated osteoclast formation. Osteoclasts generated from CB2 knockout mice (CB2−/−) were resistant to the inhibitory effects of AM630 in vitro, consistent with a CB2-mediated effect. There was no significant difference in peak bone mass between CB2−/− mice and wild-type littermates, but after ovariectomy, bone was lost to a greater extent in wild-type compared with CB2−/− mice. Furthermore, AM630 protected against bone loss in wild-type mice, but the effect was blunted in CB2−/− mice. We conclude that CB2 regulates osteoclast formation and bone resorption in vitro and that under conditions of increased bone turnover, such as after ovariectomy, CB2 regulates bone loss. These observations indicate that CB2 regulates osteoclast formation and contributes to ovariectomy-induced bone loss and demonstrate that cannabinoid receptor antagonists/inverse agonists may be of value in the treatment of bone diseases characterized by increased osteoclast activity.
Leptin Regulates Peripheral Lipid Metabolism Primarily through Central Effects on Food Intake
Authors: Prieur Xavier , Tung Y. C. Loraine , Griffin Julian L. , Farooqi I. Sadaf , O'Rahilly Stephen , Coll Anthony P.
Published: July 2008

The metabolic effects of leptin may involve both centrally and peripherally mediated actions with a component of the central actions potentially independent of alterations in food intake. Ob/ob mice have significant abnormalities in lipid metabolism, correctable by leptin administration. We used ob/ob mice to study the relative importance of the subtypes of actions of leptin (central vs. peripheral; food intake dependent vs. independent) on lipid metabolism. Mice were treated for 3 d with leptin, either centrally [intracerebroventricular (icv)] or peripherally (ip), and compared with mice pair-fed to the leptin-treated mice (PF) and with ad libitum-fed controls (C). All treatment groups (icv, ip, PF) showed indistinguishable changes in liver weight; hepatic steatosis; hepatic lipidemic profile; and circulating free fatty acids, triglycerides, and cholesterol lipoprotein profile. Changes in the expression of genes involved in lipogenesis and fatty acid oxidation in liver, muscle, and white fat were broadly similar in ip, icv, and PF groups. Leptin (both icv and ip) stimulated expression of both mitochondrial and peroxisomal acyl-coenzyme A oxidase (liver) and peroxisomal proliferator-activated receptor-α (skeletal muscle) to an extent not replicated by pair feeding. Leptin had profound effects on peripheral lipid metabolism, but the majority were explained by its effects on food intake. Leptin had additional centrally mediated effects to increase the expression of a limited number of genes concerned with fatty acid oxidation. Whereas we cannot exclude direct peripheral effects of leptin on certain aspects of lipid metabolism, we were unable to detect any such effects on the parameters measured in this study.
Conditional ablation of Notch signaling in pancreatic development
Authors: Nakhai Hassan , Siveke Jens T. , Klein Bettina , Mendoza-Torres Lidia , Mazur Pawel K. , Algül Hana , Radtke Freddy , Strobl Lothar , Zimber-Strobl Ursula , Schmid Roland M.
Published: July 2008

The role of the Notch signaling members Notch1, Notch2 and Rbpj in exocrine pancreatic development is not well defined. We therefore analyzed conditional pancreas-specific Rbpj and combined Notch1/Notch2 knockout mice using Ptf1a+/Cre(ex1)mice crossed with floxed Rbpj or Notch1/Notch2mice. Mice were analyzed at different embryonic stages for pancreatic exocrine and endocrine development. The absence of Rbpj in pancreatic progenitor cells impaired exocrine pancreas development up to embryonic day 18.5 and led to premature differentiation of pancreatic progenitors into endocrine cells. In Rbpj-deficient pancreata, amylase-expressing acini and islets formed during late embryonic and postnatal development,suggesting an essential role of Rbpj in early but not late development. Contrary to this severe phenotype, the concomitant inactivation of Notch1 and Notch2 only moderately disturbed the proliferation of pancreatic epithelial cells during early embryonic development, and did not inhibit pancreatic development. Our results show that, in contrast to Rbpj, Notch1 and Notch2 are not essential for pancreatogenesis. These data favor a Notch-independent role of Rbpj in the development of the exocrine pancreas. Furthermore, our findings suggest that in late stages of pancreatic development exocrine cell differentiation and maintenance are independent of Rbpj.
Approaches to Finding the Molecular Basis of Mitochondrial Oxidative Phosphorylation Disorders
Authors: Kirby Denise M. , Thorburn David R.
Published: July 2008

Inherited disorders of mitochondrial oxidative phosphorylation are the most common group of inborn errors of metabolism and cause a wide range of clinical presentations. Mitochondrial DNA encodes 13 protein subunits required for oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and mutations in most of these genes cause human disease. Nuclear genes encode most of the protein subunits and all other proteins required for mitochondrial biogenesis and mitochondrial DNA replication and expression. Mutations in 64 nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial disease and many novel mitochondrial disease genes await discovery. The genetic complexity of oxidative phosphorylation means that maternal, autosomal recessive, autosomal dominant and X-linked modes of inheritance can occur, along with de novo mutations. This complexity presents a challenge in planning efficient molecular genetic diagnosis of patients with suspected mitochondrial disease. In some situations, clinical phenotype can be strongly predictive of the underlying genotype. However, more often this is not the case and it is usually helpful, particularly with pediatric patients, to determine whether the activity of one or more of the individual oxidative phosphorylation enzymes is deficient before proceeding with mutation analysis. In this review we will summarize the genetic bases of mitochondrial disease and discuss some approaches to integrate information from clinical presentation, laboratory findings, family history, and imaging to guide molecular investigation.
“Beyond This World of Transiency and Impermanence”: Japanese Americans, Dharma Bums, and the Making of American Buddhism during the Early Cold War Years
Authors: Masatsugu Michael K.
Published: July 2008

This article examines the growing interest in Buddhism in the United States during the Cold War, analyzing discussions and debates around the authenticity of various Buddhist teachings and practices that emerged in an interracial Buddhist study group and its related publications. Japanese American Buddhists had developed a modified form of Jōdo Shinshū devotional practice as a strategy for building ethnic community and countering racialization as religious and racial Others. The authenticity of these practices was challenged by European and European American scholars and artists, especially the Beats, who drew upon Orientalist representations of Buddhism as ancient, exotic, and mysterious. In response, Japanese American Buddhists crafted their own definition of “tradition” by drawing from institutional and devotional developments dating back to fourteenth-century Japan as well as more recent Japanese American history. The article contextualizes these debates within the broader discussion of cultural pluralism and race relations during the Cold War.
Effect of Inflammatory Cytokines on Major Histocompatibility Complex Expression and Differentiation of Human Neural Stem/Progenitor Cells
Authors: Johansson Saga , Price Jack , Modo Michel
Published: July 2008

To develop transplantation of neural stem/progenitor cells (NSPCs) as a successful treatment of neurodegenerative disorders, the possible induction of an inflammatory response following implantation needs to be taken into consideration. Inflammatory cytokines can upregulate major histocompatibility complex (MHC) expression on transplanted cells, thereby rendering them more susceptible to graft rejection. Furthermore, cytokines also have a profound effect on cell differentiation, migration, and proliferation, which can greatly affect the outcome of transplantation. Here we studied the effect of three inflammatory cytokines, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), from three different species (human, monkey, rat) on expression of MHC molecules and differentiation of two human NSPC lines derived from striatum and hippocampus. Human and monkey IFN-γ strongly upregulate MHC expression in both NSPC lines in a dose-dependent manner, whereas rat IFN-γ has an effect on MHC expression only in hippocampal cells. Furthermore, TNF-α, but not IL-6, upregulates MHC expression in both NSPC lines. Differentiation of NSPCs in the presence of cytokines showed that IFN-γ increased the neuronal yield threefold in striatal NSPC cultures and increased the number of oligodendrocytes twofold in hippocampal NSPC cultures. Addition of TNF-α enhanced gliogenesis in both cell lines, whereas IL-6 stimulated neurogenesis. Human NSPC lines' response to cytokines is therefore species specific and also dependent on the NSPCs' region of origin. The successful translation of different cell lines from animal models to clinical trials could be substantially influenced by the species-specific regulation of MHC and differentiation as reported here.

Disclosure of potential conflicts of interest is found at the end of this article.
Adult Germ Line Stem Cells as a Source of Functional Neurons and Glia
Authors: Glaser Tamara , Opitz Thoralf , Kischlat Thomas , Konang Rachel , Sasse Philipp , Fleischmann Bernd K. , Engel Wolfgang , Nayernia Karim , Brüstle Oliver
Published: July 2008

The derivation of autologous pluripotent cells has become a central goal in translational stem cell research. Although somatic cell nuclear transfer and transcription factor-based reprogramming enable the generation of pluripotent cells from adult tissue, both methodologies depend on complex epigenetic alterations. Recent data suggest that the adult germ line may represent an alternative and natural source of pluripotent stem cells. Multipotent adult germ line stem cells (maGSCs) with properties similar to those of embryonic stem cells have been derived from mouse spermatogonial stem cells. These cells exhibit extensive self-renewal, expression of pluripotency markers, and differentiation into derivatives of all three germ layers. Here we report the derivation of multipotent neural and glial precursors as well as adherently proliferating neural stem cells from maGSCs. Characterization of maGSC-derived neurons revealed segregation into GABAergic, glutamatergic, serotonergic, and tyrosine hydroxylase-positive phenotypes. On a functional level, maGSC-derived neurons generate spontaneously active functional networks, which use both glutamatergic and GABAergic synaptic transmission and engage in synchronized oscillatory activity. maGSC-derived oligodendrocytes undergo full maturation and ensheathe host axons in myelin-deficient tissue. Our data suggest that neural stem and precursor cells derived from maGSCs could provide a versatile and potentially autologous source of functional neurons and glia.

Disclosure of potential conflicts of interest is found at the end of this article.
Directed Evolution of Motor Neurons from Genetically Engineered Neural Precursors
Authors: Bohl Delphine , Liu Song , Blanchard Stéphane , Hocquemiller Michaël , Haase Georg , Heard Jean-Michel
Published: July 2008

Stem cell-based therapies hold therapeutic promise for degenerative motor neuron diseases, such as amyotrophic lateral sclerosis, and for spinal cord injury. Fetal neural progenitors present less risk of tumor formation than embryonic stem cells but inefficiently differentiate into motor neurons, in line with their low expression of motor neuron-specific transcription factors and poor response to soluble external factors. To overcome this limitation, we genetically engineered fetal rat spinal cord neurospheres to express the transcription factors HB9, Nkx6.1, and Neurogenin2. Enforced expression of the three factors rendered neural precursors responsive to Sonic hedgehog and retinoic acid and directed their differentiation into cholinergic motor neurons that projected axons and formed contacts with cocultured myotubes. When transplanted in the injured adult rat spinal cord, a model of acute motor neuron degeneration, the engineered precursors transiently proliferated, colonized the ventral horn, expressed motor neuron-specific differentiation markers, and projected cholinergic axons in the ventral root. We conclude that genetic engineering can drive the differentiation of fetal neural precursors into motor neurons that efficiently engraft in the spinal cord. The strategy thus holds promise for cell replacement in motor neuron and related diseases.

Disclosure of potential conflicts of interest is found at the end of this article.
Safety Aspect concerning Radiolytic Gas Generation in Reactors
Authors: Ramshesh V.
Published: July 2008

In water cooled and water moderated reactors (H2O in boiling water reactors/pressurised water reactors, D2O in pressurised heavy water reactors) during normal operation, radiolysis is a source of production of hydrogen/deuterium and oxygen. During the progress of a nuclear accident, while there are other important sources of hydrogen/deuterium, the oxygen availability can occur only through radiolysis or direct contact with air. In air saturated with water vapour at room temperature and pressure when H2/D2 concentration exceeds 4 vol % (a conservative estimate), a combustible mixture with oxygen can be formed. It is proposed to examine the basic principles of water radiolysis as far as they pertain to generation of H2/D2 and O2 and try to apply these concepts to reactors both under operating conditions and in accident situations. It is concluded that the possibility of an accident taking place through radiolysis is highly unlikely.
Lethal Effects of Heat on Bacterial Physiology and Structure
Authors: Russell A.D.
Published: July 2008

High temperatures have profound effects on the structural and physiological properties of sporulating and non-sporulating bacteria, with membranes, RNA, DNA, ribosomes, protein and enzymes all affected. Nevertheless, it is apparent that no one single event is responsible for cell death. The induction of intracellular heat-shock proteins and the activation of extracellular alarmones in vegetative cells exposed to mildly lethal temperatures are important cell responses. In bacterial spores, several factors contribute to the overall resistance to moist (wet) and dry heat; the latter, but not the former, induces mutations. Heat resistance develops during sporulation, when spore-specific heat-shock proteins are also produced. Heat sensitivity is regained during germination of spores.
Two-Component Signal Transduction Systems as Key Players in Stress responses of Lactic Acid Bacteria
Authors: El-Sharoud Walid M.
Published: July 2008

Lactic acid bacteria (LAB) continue as an important group of gram-positive bacteria that have been extensively exploited in food industries and various biotechnological applications. Some LAB species are, however, opportunistic pathogens and were reported to be associated with overwhelming number of human infections. During the use of LAB in industry or over the course of human infection, these bacteria are exposed to environmental stress. While LAB display adaptive mechanisms to cope with adverse conditions, the regulation of these mechanisms remains to be elucidated. Recent completion of genome sequencing of various LAB strains combined with the development of advanced molecular techniques have enabled the identification of a number of putative two-component signal transduction systems, also known as two-component regulatory systems (2CRS), in LAB. Examining the effect of deleting genes specifying putative 2CRS proteins in these organisms has revealed the involvement of 2CRS in the responses of LAB to different stresses. There are lines of evidence indicating that certain 2CRS may mediate a general stress response in Enterococcus faecalis and Streptococcus pyogenes. This review highlights the influence of 2CRS on the physiology of LAB during optimal growth and survival/growth on exposure to environmental stress.
An Introduction to Rna-Mediated Gene Silencing
Authors: Geanacopoulos Mark
Published: July 2008

Careful analysis of cases where introduction of additional copies of endogenous genes caused coordinate silencing of both the transgene and the endogenous gene laid the ground work for the discovery of RNA-mediated silencing. Silencing begins with the expression and recognition of double-stranded RNA, which is cleaved into short RNAs that recognize, by complementarity, sequences that are targets for down regulation. An RNA target can be regarded (post-transcriptional gene silencing), but the small RNAs can also direct the sequence-specific modification of DNA and chromatin. RNA-mediated gene silencing in eukaryotes may have originated as surveillance mechanism to protect the organism from transposable elements and viruses and then evolved to specify chromosomal modifications and to regulate expression of a significant fraction of endogenous genes by microRNAs. This review seeks to furnish the student and non-expert with some idea of how RNA-mediated silencing was discovered and a broad overview of the present state of knowledge.
Concepts of Renormalization in Physics
Authors: Alexandre Jean
Published: July 2008

A non technical introduction to the concept of renormalization is given, with an emphasis on the energy scale dependence in the description of a physical system. We first describe the idea of scale dependence in the study of a ferromagnetic phase transition, and then show how similar ideas appear in particle physics. This short review is written for non-particle physicists and/or students aiming at studying Particle Physics.
Deciphering a Complex Genetic Regulatory Network: The Bacillus Subtilis σW Protein and Intrinsic Resistance to Antimicrobial Compounds
Authors: Helmann John D.
Published: July 2008

Bacillus subtilis, a spore-forming soil bacterium, is the preeminent model system for the analysis of gene regulation in Gram-positive bacteria. Early genetic analyses established that this organism uses alternative sigma (σ) subunits to reprogram RNA polymerase to activate genes required for growth phase transitions, motility, general stress response, and sporulation. Unexpectedly, the genome sequence predicts the presence of an additional seven a subunits: all members of the extracytoplasmic function (ECF) a subfamily of regulators that typically respond to cell envelope stresses. Here, we review our current understanding of one of these a factors, a with an emphasis on experimental strategies and approaches. Exposure to cell envelope active antibiotics and toxic peptides triggers a signaling cascade that releases σW from its cognate anti-σ thereby allowing transcription of ∼60 σW-dependent genes. These genes encode proteins that inactivate, sequester, or eliminate toxic compounds from the cell.
Dna Supercoiling and Bacterial Gene Expression
Authors: Dorman Charles J.
Published: July 2008

DNA in bacterial cells is maintained in a negatively supercoiled state. This contributes to the organization of the bacterial nucleoid and also influences the global gene expression pattern in the cell through modulatory effects on transcription. Supercoiling arises as a result of changes to the linking number of the relaxed double-stranded DNA molecule and is set and reset by the action of DNA topoisomerases. This process is subject to a multitude of influences that are usually summarized as environmental stress. Responsiveness of linking number change to stress offers the promise of a mechanism for the wholesale adjustment of the transcription programme of the cell as the bacterium experiences different environments. Recent data from DNA microarray experiments support this proposition. The emerging picture is one of DNA supercoiling acting at or near the apex of a regulatory hierarchy where it collaborates with nucleoid-associated proteins and transcription factors to determine the gene expression profile of the cell.
Variations on a Theme: Diverse N-Acyl Homoserine Lactone-Mediated Quorum Sensing Mechanisms in Gram-Negative Bacteria
Authors: Smith Debra , Wang Jin-Hong , Swatton Jane E. , Davenport Peter , Price Bianca , Mikkelsen Helga , Stickland Hannah , Nishikawa Kahoko , Gardiol NoéMie , Spring David R. , Welch Martin
Published: July 2008

Many Gram-negative bacteria employ a mechanism of cell–cell communication known as quorum sensing (QS). The role of QS is to enable the cells in a culture to coordinate their gene expression profile with changes in the population cell density. The best characterized mechanisms of QS employ N-acylated homoserine lactones (AHLs) as signalling molecules. These AHLs are made by enzymes known as Luxl homologs, and accumulate in the culture supernatant at a rate proportional to the increase in cell density. Once the AHL concentration exceeds a certain threshold value, these ligands bind to intracellular receptors known as LuxR homologs. The latter are transcriptional regulators, whose activity alters upon binding the AHL ligand, thereby eliciting a change in gene transcription. Over the last five years, it has become increasingly obvious that this is a rather simplistic view of AHL-dependent QS, and that in fact, there is considerable diversity in the way in which Luxl-R homologs operate. The aim of the current review is to describe these variations on the basic theme, and to show how functional genomics is revolutionizing our understanding of QS-controlled regulons.
Remediation Strategies for Historical Mining and Smelting Sites
Authors: Dybowska Agnieszka , Farago Margaret , Valsami-Jones Eugenia , Thornton Iain
Published: July 2008

The environmental, social and economic problems associated with abandoned mine sites are serious and global. Environmental damage arising from polluted waters and dispersal of contaminated waste is a feature characteristic of many old mines in North America, Australia, Europe and elsewhere. Today, because of the efficiency of mining operations and legal requirements in many countries for prevention of environmental damage from mining operations, the release of metals to the environment from modern mining is low. However, many mineralized areas that were extensively worked in the 18th and 19th centuries and left abandoned after mining had ceased, have left a legacy of metal contaminated land.

Unlike organic chemicals and plastics, metals cannot be degraded chemically or biologically into non-toxic and environmentally neutral constituents. Thus sites contaminated with toxic metals present a particular challenge for remediation. Soil remediation has been the subject of a significant amount of research work in the past decade; this has resulted in a number of remediation options currently available or being developed.

Remediation strategies for metal/metalloid contaminated historical mining sites are reviewed and summarized in this article. It focuses on the current applications of in situ remediation with the use of soil amendments (adsorption and precipitation based methods are discussed) and phytoremediation fin situ plant based technology for environmental clean up and restoration). These are promising alternative technologies to traditional options of excavation and ex situ treatment, offering an advantage of being non-invasive and low cost. In particular, they have been shown to be effective in remediation of mining and smelting contaminated sites, although the long-term durability of these treatments cannot be predicted.
The nature of Language
Authors: Abler William L.
Published: July 2008

Sentences share with equations properties of discrete, linear infinities; distinct symbol types; alternation of symbol types in the signal; deep-structure with a main verb and recursion; associative, commutative, and distributive properties; autonomous levels of organization; paraphrase, ellipsis, and ambiguity; powers of assertion, truth and falsity; modification of an entire statement; and a blank proxy element. Sentences are derived from the symmetrical equation by applying a single asymmetry transformation. The self-regulated, autonomous nature of the symmetrical equation is the antithesis of natural selection, which is contingent upon local conditions. The dependence of the sentence upon the equation means that the idea of language evolution presents numerous obstacles. For the most part, ideas contained in this paper are adapted from the author's book, Structure of Matter, Structure of Mind1.
Current Molecular Techniques for the detection of Microbial Pathogens
Authors: Galluzzi Luca , Magnani Mauro , Saunders Nick , Harms Carsten , Bruce Ian James
Published: July 2008

Traditionally the detection of microbial pathogens in clinical, environmental or food samples has commonly needed the prelevation of cells by culture before the application of the detectionstrategy. This is done to increase cellnumber thereby overcoming problems associated with the sensitivity of classical detection strategies. However, culture-based methods have the disadvantages of taking longer, usually are more complex and require skilled personnel as well as not being able to detect viable but non cultivable microbial species. A number of molecular methods have been developed in the last 10 to 15 years to overcome these issues and to facilitate the rapid, accurate, sensitive and cost effective identification and enumeration of microorganisms which are designed to replace and/or support classical approaches to microbial detection. Amongst these new methods, ones based on the polymerase chain reaction and nucleic acid hybridization have been shown to be particularly suitable for this purpose. This review generally summarizes some of the current and emerging nucleic acid basedmolecular approaches for the detection, discrimination and quantification of microbes in environmental, food and clinical samples andincludes reference to the recently developing areas of microfluidics and nanotechnology “Lab-on-a-chip”.
Cold Shock Proteins Aid coupling of Transcription and Translation in Bacteria
Authors: El-Sharoud Walid M. , Graumann Peter L.
Published: July 2008

Transcription and translation are tightly coupled in bacterial cells. However, the transcription machinery and ribosomes generally occupy different subcellular regions in bacteria such as Escherichia coli and Bacillus subtilis, indicating the need for (a) mechanism(s) coupling these processes. A prime function of this mechanism(s) would be ensuring the transfer of unfolded mKNA from the nucleoid to ribosomes, which require linear mRNA for the initiation of translation. During conditions of a sudden decrease in temperature (cold shock), secondary structures in mRNA would pose an even greater problem for the initiation process. Two conserved classes of proteins, cold shock proteins (CSPs) and cold induced RNA helicases (CSHs), appear to be major players in the prevention of secondary mRNA structures and in transcription/translation coupling. CSPs are general mRNA-binding proteins, and like CSH-type RNA helicases, the presence of at least one csp gene in the cell is essential for viability. Members of both protein families have recently been shown to interact, suggesting that a two-step process achieves the coupling process, removal of secondary mRNA structures through CSHs and prevention of reformation through CSPs.