bluuebunny/crossref_metadata_2025 huggingface dataset:
The Transmural Activation Sequence in Porcine and Canine Left Ventricle Is Markedly Different During Long‐Duration Ventricular Fibrillation
Authors: ALLISON J. SCOTT , QIN HAO , DOSDALL DEREK J. , HUANG JIAN , NEWTON JONATHAN C. , ALLRED JAMES D. , SMITH WILLIAM M. , IDEKER RAYMOND E.
Published: October 2007

Background: Humans are more similar in transmural Purkinje and cardiac ion channel distributions to dogs than pigs. The Purkinje network in pigs is transmural but confined to the endocardium in dogs. Little is known about intramural activation during long‐duration ventricular fibrillation (LDVF) given these differences. We tested the hypothesis that the transmural activation sequence is similar in sinus rhythm (SR) and LDVF in dogs as well as pigs, but different between species.

Methods and Results: In six pigs and seven dogs, 50–60 plunge needles (six electrodes, 2‐mm spacing) were placed throughout the left ventricle. Unipolar recordings were made for >10 minutes of LDVF. SR and LDVF activation times were grouped into waves by linking activations along each needle. Origin (earliest activation) and propagation direction were determined for each wave. The mean wave origin was significantly more endocardial in dogs than pigs for SR and 1 through 10 minutes of LDVF. Predominant propagation direction in LDVF and SR was endocardial to epicardial in dogs, but the opposite or equal in both directions in pigs. Fastest activation rate was epicardial in pigs, but endocardial in dogs with an increasing endocardial‐to‐epicardial activation rate gradient as LDVF progressed in dogs but not pigs.

Conclusions: The transmural activation sequence in SR and LDVF is markedly different between pigs and dogs. These differences may be related to differences in Purkinje fiber and ion channel distributions and suggest that dogs are a better model for investigating activation sequences during LDVF, given the similarities with humans.
Clinical Significance of Macroscopic T‐Wave Alternans After Sodium Channel Blocker Administration in Patients with Brugada Syndrome
Authors: TADA TAKESHI , KUSANO KENGO FUKUSHIMA , NAGASE SATOSHI , BANBA KIMIKAZU , MIURA DAIJI , NISHII NOBUHIRO , WATANABE ATSUYUKI , NAKAMURA KAZUFUMI , MORITA HIROSHI , OHE TOHRU
Published: October 2007

Introduction: Macroscopic T‐wave alternans (TWA) is sometimes observed after sodium channel blocker administration in patients with Brugada syndrome (BS), but little is known about the association between occurrence of TWA and clinical characteristics in BS patients. We investigated the association between spontaneous ventricular fibrillation (VF) occurrence and TWA after pilsicainide, a sodium channel blocker administration in BS patients.

Methods and Results: We administered pilsicainide at a dose of 1 mg/kg to 77 BS patients (76 males and one female; mean age, 48.4 years) and examined the association between TWA after pilsicainide administration and clinical characteristics, including age, spontaneous VF, syncope, family history of sudden death, spontaneous coved ST elevation, late potentials (LP), induction of VF by programmed electrical stimulation, and SCN5A mutation. None of the patients had TWA before pilsicainide administration, but TWA became apparent in 17 (22.1%) of the patients after pilsicainide administration. Patients with TWA had a significantly higher incidence of spontaneous VF (52.9% vs 8.3%, P < 0.001) and syncope (58.8% vs 26.7%, P < 0.05) than did patients without TWA. Then, we focused on the association between spontaneous VF and clinical characteristics. Patients with spontaneous VF had a significantly higher incidence of TWA (64.3% vs 12.7%, P < 0.001) and LP positive (92.9% vs 56.5%, P < 0.01) than did patients without spontaneous VF. In multivariate analysis, TWA (P = 0.001) and LP (P = 0.047) appeared as the independent predictor for spontaneous VF.

Conclusion: TWA after pilsicainide administration is associated with a high risk of clinical VF in patients with BS.
Description of Deviata rositae n. sp., a New Ciliate Species (Ciliophora, Stichotrichia) from Argentina
Authors: KÜPPERS GABRIELA C. , LOPRETTO ESTELA C. , CLAPS MARÍA C.
Published: September 2007

ABSTRACT. Soil samples were taken from a temporary pond located in Buenos Aires province, Argentina, during the dry phase in the summer of 2005. The ciliates were studied alive and after staining with protargol. Deviata rositae n. sp. measures 112–154 μm in length and 21–28 μm in width in vivo and has a vermiform body. The contractile vacuole is located in the mid‐body on the left. The macronucleus is moniliform and there are 1–3 micronuclei. The oral apparatus is composed of 14–18 adoral membranelles and straight paroral and endoral membranes that never intersect each other. The somatic ciliature is arranged in four frontal cirri, one buccal cirrus, six long and slightly spiraled rows of cirri with the first right row extending up to the equatorial or sub‐equatorial region, and two dorsal rows of dikinetids. This new species of Deviata primarily differs from its congeners by the number of macronuclear nodules and the number and disposition of the dorsal rows of dikinetids.
Human Serum Lyses Trypanosoma brucei by Triggering Uncontrolled Swelling of the Parasite Lysosome
Authors: VANHOLLEBEKE BENOIT , LECORDIER LAURENCE , PEREZ‐MORGA DAVID , AMIGUET‐VERCHER AMELIA , PAYS ETIENNE
Published: September 2007

ABSTRACT. Trypanosoma brucei brucei infects a wide range of mammals, but is unable to infect humans because this subspecies is lysed by normal human serum (NHS). The phenotype of cellular lysis is debated. For some authors the lysosome undergoes osmotic swelling due to massive influx of chloride ions from the cytoplasmic compartment, but others describe multiple small cytoplasmic vacuoles and general swelling of the cellular body. Using population‐level imaging of live immobilized trypanosomes throughout the lysis process, we report that specific swelling of the lysosome is a genuine and major characteristic of NHS‐mediated lysis and that this phenotype is independent of the strain of trypanosomes and of NHS aging or damaging. Thus, irrespective of experimental conditions NHS reproducibly induced the swelling of the parasite lysosome.
The Influence of Polyethylene Imine on the Gelcasting of SiC With Two Different Initiators
Authors: Zhang Tao , Zhang Zhaoquan , Dong Manjiang , Zhang Jingxian , Lin Qingling , Jiang Dongliang
Published: September 2007

In the present work, polyethylene imine (PEI) is used as dispersant to prepare SiC slurry for aqueous gelcasting. When ammonium persulfate (APS) is used as initiator, PEI accelerates the polymerization of monomers and the solidification of gelcasting slurry at 25°C. The reason is that tertiary amine in the structure of PEI and APS form a redox system as initiator. SiC gelcating slurry with PEI and APS solidifies in 2 min at 25°C, which makes the operation of casting impossible. However, when another initiator, 2, 2′‐azobis [2‐(2‐imidazolin‐2‐yl) propane] dihydrochloride (AZIP·2HCl), is used, PEI does not accelerate but delays the polymerization of monomers because of the chain transfer. SiC gelcasting slurry in the presence of PEI and AZIP·2HCl has good fluidity and long idle time at 25°C. The slurry can be poured into the mold easily and solidifies in 5 min at 45°C. Therefore, PEI can be used as dispersant with the initiator of AZIP·2HCl in the gelcasting process, while PEI cannot act as dispersant when the initiator is APS.
Sol–Gel Synthesis and Characterization of Ytterbium Silicate Powders
Authors: Wen Haiming , Dong Shaoming , He Ping , Wang Zhen , Zhou Haijun , Zhang Xiangyu
Published: September 2007

Ytterbium silicate (Yb2SiO5) is a promising environmental barrier coating material for SiC‐based ceramic matrix composites. Yb2SiO5 powders were prepared by the sol–gel process using tetraethyl orthosilicate and ytterbium nitrate as starting materials. The Yb2SiO5 gel was characterized by Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis–differential scanning calorimetry (TGA–DSC). After calcining the gel at 1200°C for 1 h, Yb2SiO5 powders were obtained, which were examined by X‐ray diffraction, FTIR, transmission electron microscope, and scanning electron microscope. The results showed that single‐phase Yb2SiO5 powders of 200–300 nm in size were successfully synthesized.
Double Precursor Solution Coating Approach for Low‐Temperature Sintering of [Pb(Mg1/3Nb2/3)O3]0.63[PbTiO3]0.37 Solids
Authors: Luo Hongyu , Shih Wan Y. , Shih Wei‐Heng
Published: September 2007

Lead‐based piezoelectric ceramics typically require sintering temperatures higher than 1000°C at which significant lead loss can occur. Here, we report a double precursor solution coating (PSC) method for fabricating low‐temperature sinterable polycrystalline [Pb(Mg1/3Nb2/3)O3]0.63‐[PbTiO3]0.37 (PMN–PT) ceramics. In this method, submicrometer crystalline PMN powder was first obtained by dispersing Mg(OH)2‐coated Nb2O5 particles in a lead acetate/ethylene glycol solution (first PSC), followed by calcination at 800°C. The crystalline PMN powder was subsequently suspended in a PT precursor solution containing lead acetate and titanium isopropoxide in ethylene glycol to form the PMN–PT precursor powder (second PSC) that could be sintered at a temperature as low as 900°C. The resultant d33 for samples sintered at 900°, 1000°, and 1100°C for 2 h were 600, 620, and 700 pm/V, respectively, comparable with the known value. We attributed the low sintering temperature to the reactive sintering nature of the present PMN–PT precursor powder. The reaction between the nanosize PT and the submicrometer‐size PMN occurred roughly in the same temperature range as the densification, 850°–900°C, thereby significantly accelerating the sintering process. The present PSC technique is very general and should be readily applicable to other multicomponent systems.
Effect of Calcination on Crystallinity for Nanostructured Development of Wormhole‐Like Mesoporous Tungsten Oxide
Authors: Lai Wei Hao , Teoh Lay Gaik , Su Yen Hsun , Shieh Jiann , Hon Min Hsiung
Published: September 2007

The effects of calcination on the crystallinity and grain growth model for microstructure development of wormhole‐like mesoporous tungsten oxide are investigated in this study. We found that residual mesopores of wormhole‐like tungsten oxide can be seen calcined above 500°C, as evidenced by retention of a wormhole‐like mesostructure of tungsten oxide. A model was proposed to combine grain growth with wormhole‐like mesoporous behavior and to investigate whether the formation of wormhole‐like mesoporous tungsten oxide can retard the collapse rate of mesopores during the calcination process.
Gemtuzumab ozogamicin in combination with attenuated doses of standard induction chemotherapy can successfully induce complete remission without increasing toxicity in patients with acute myeloid leukemia aged 55 or older
Authors: Eom Ki‐Seong , Kim Hee‐Je , Min Woo‐Sung , Lee Seok , Min Chang‐Ki , Cho Byung‐Sik , Kim Sung‐Yong , Kim Yoo‐Jin , Lee Dong‐Gun , Choi Su‐Mi , Cho Seok‐Goo , Kim Dong‐Wook , Lee Jong‐Wook , Shin Wan‐Shik , Kim Chun‐Choo
Published: October 2007

Background:  In this study, the effectiveness and safety of combining gemtuzumab ozogamicin (GO) with an abbreviated schedule of standard induction chemotherapy were assessed in 37 patients (aged ≥55) yr with previously untreated acute myeloid leukemia (AML).

Methods:  GO was administered at a dose of 6 mg/m2 as a single 2‐h intravenous infusion on day 1. Following GO, an abbreviated schedule of induction chemotherapy consisting of idarubicin (12 mg/m2/d, days 2–4), and N4‐behenoyl‐1‐β‐arabinofuranosyl cytosine (300 mg/m2/d, days 2–6) was given.

Results:  Thirty‐seven patients were treated with GO in combination with chemotherapy. Complete remission (CR) and CR with incomplete platelet recovery were achieved in 28 patients (75.7%) and one patient (2.7%) respectively. Two patients (5.4%) died during induction and two patients (5.4%) with grade 4 treatment emergent adverse effects during chemotherapy did not complete induction chemotherapy. The majority of toxicities were mild and manageable. Severe myelosuppresion was universal with significantly prolonged thrombocytopenic period. In total, 25 patients who received consolidation treatment, 19 patients remain alive at the time of analysis. Thirteen patients had undergone hematopoietic stem cell transplantation, three are preparing for transplantation and seven are receiving their consolidation chemotherapy course.

Conclusion:  Although only a relatively small number of cases were included in this preliminary study and the follow‐up duration was short, frontline GO in combination with attenuated conventional chemotherapy was found to be effective and feasible in elderly patients with AML.
Zoledronate has an antitumor effect and induces actin rearrangement in dexamethasone‐resistant myeloma cells
Authors: Koizumi Masayuki , Nakaseko Chiaki , Ohwada Chikako , Takeuchi Masahiro , Ozawa Shinichi , Shimizu Naomi , Cho Ryuko , Nishimura Miki , Saito Yasushi
Published: September 2007

New strategies are needed to overcome the resistance of multiple myeloma (MM) to dexamethasone (Dex). Several recent in vitro studies demonstrated the antitumor effect of nitrogen‐containing amino‐bisphosphonates (N‐BPs) in various tumor cell lines. Inhibition of the prenylation of small G proteins is assumed to be one of the principal mechanisms by which N‐BPs exert their effects. There have been few reports on N‐BP treatment of MM cells that are resistant to Dex. Additionally, it is not known how small G proteins are altered in N‐BP‐treated MM cells. In this study, we evaluated the effect of the most potent N‐BP, zoledronate (ZOL), on a Dex‐resistant human MM cell subline (Dex‐R) that we established from the well‐documented RPMI8226 cell line. ZOL reduced the viability and induced apoptosis of Dex‐R cells. Some of the ZOL‐treated RPMI8226 cells and ZOL‐treated Dex‐R cells were elongated; however, elongated cells were not seen among the Dex‐treated RPMI8226 cells. Furthermore, we found that portions of the small G proteins, Rho and Rap1A, were unprenylated in the ZOL‐treated MM cells. Geranylgeraniol reduced the above‐mentioned ZOL‐induced effects. These findings suggest that ZOL may be beneficial for the treatment of Dex‐resistant MM by suppressing the processing of RhoA and Rap1A.
The clinical significance of the spectrum of interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians
Authors: Garewal Gurjeewan , Das Reena , Awasthi Anshu , Ahluwalia Jasmina , Marwaha Ram Kumar
Published: September 2007

Objectives: To assess the clinical significance of the interactions of CAP+1 (A→C), a silent β‐globin gene mutation, with other β‐thalassemia mutations and globin gene modifiers in north Indians. Methods: The clinical phenotypes associated with compound heterozygosity for the CAP+1 (A→C) mutation with other β‐thalassemia mutations, together with the potential effect of the genetic modifiers α‐thalassemia and the Xmn‐1Gγ C→T polymorphism were studied in 30 patients. The frequency of the CAP+1 (A→C) polymorphism was determined and an analysis of the red cell indices, HbA2 levels, iron status, and α‐globin genes was carried out in 35 heterozygotes. Results: Based on an analysis of 1075 β‐thalassemia alleles the CAP+1 (A→C) mutation constituted 3.2% of north Indians. There was a wide spectrum of phenotypic severity in compound heterozygotes; 18 of 30 were transfusion dependent. There was a very high frequency of the −/− genotype of the Xmn‐1Gγ polymorphism in compound heterozygotes. Analysis of 35 heterozygotes indicated that approximately half were hematologically normal and therefore genuine ‘silent’ carriers. Conclusions: Compound heterozygotes for CAP+1 (A→C) and other severe β‐thalassemia alleles are phenotypically severe enough to necessitate appropriate therapy and counseling. The unexpected severity of these interactions may be due, in part, to the high frequency of β‐thalassemia alleles associated with the Xmn‐1Gγ− allele in Indian populations. It is concluded that the CAP+1 (A→C) mutation can pose serious difficulties in screening and counseling programs in populations in which it occurs at a significant frequency.
Partial splenic embolization in children with hereditary spherocytosis
Authors: Pratl Barbara , Benesch Martin , Lackner Herwig , Portugaller Horst Rupert , Pusswald Bernadette , Sovinz Petra , Schwinger Wolfgang , Moser Andrea , Urban Christian
Published: October 2007

Objectives:  Although total splenectomy is able to reduce clinical symptoms in patients with hereditary spherocytosis (HS), splenectomized patients are at risk to develop overwhelming bacterial infections and, to a lesser extent, thromboembolic complications. In contrast, partial splenectomy or partial splenic embolization (PSE) may also decrease the rate of hemolytic complications while maintaining residual splenic function. The aim of this study was to investigate the benefit of PSE in children with moderate to severe HS.

Patients and methods:  We performed PSE via retrograde transfemoral access in eight children (four female, four male) with moderate to severe HS at a median age of 8 yr. HS‐related complications before PSE included gallstones in six and aplastic crises in four children. One patient was transfusion‐dependent.

Results:  No acute side effects were seen during or after PSE. Median hemoglobin increased significantly from levels between 7.5 g/dL and 11.65 g/dL before PSE to levels between 8.4 g/dL and 13.35 g/dL after PSE (P = 0.012). Median splenic sizes before PSE ranged from 9.7 cm/m2 to 19.0 cm/m2 and significantly decreased to values between 4.4 cm/m2 and 15.65 cm/m2 during follow‐up (P = 0.012).

Conclusions:  PSE appears to be a safe, effective and feasible treatment option for the management of children with moderate to severe HS.
Dominant‐Negative Behavior of Mammalian Vps35 in Yeast Requires a Conserved PRLYL Motif Involved in Retromer Assembly
Authors: Zhao Xiang , Nothwehr Steven , Lara‐Lemus Roberto , Zhang Bao‐yan , Peter Harald , Arvan Peter
Published: October 2007

The retromer protein complex assists in recycling selected integral membrane proteins from endosomes to the trans Golgi network. One protein subcomplex (Vps35p, Vps26p and Vps29p) combines with a second (Vps17p and Vps5p) to form a coat involved in sorting and budding of endosomal vesicles. Yeast Vps35p (yVps35) exhibits similarity to human Vps35 (hVps35), especially in a completely conserved PRLYL motif contained within an amino‐terminal domain. Companion studies indicate that an R98W mutation in yVps35 causes defective retromer assembly in Saccharomyces cerevisiae. Herein, we find that the expression of hVps35 in yeast confers dominant‐negative vacuolar proenzyme secretion and defective secretory proprotein processing. The mutant phenotype appears to be driven by hVps35 competing with endogenous yVps35, becoming incorporated into defective retromer complexes and causing proteasomal degradation of endogenous Vps26 and Vps29. Increased expression of yVps35 displaces some hVps35 to a 100 000 × g supernatant and suppresses the dominant‐negative phenotype. Remarkably, mutation of the conserved R107W of hVps35 displaces some of the protein to the 100 000 × g supernatant, slows protein turnover and restores stability of Vps26p and Vps29p and completely abrogates dominant‐negative trafficking behavior. We show that hVps35 coprecipitates Vps26, whereas the R107W mutant does not. In pancreatic beta cells, the R107W mutant shifts hVps35 from peripheral endosomes to a juxtanuclear compartment, affecting both mannose phosphate receptors and insulin. These data underscore importance of the Vps35 PRLYL motif in retromer subcomplex interactions and function.
Dual effect of echinomycin on hypoxia‐inducible factor‐1 activity under normoxic and hypoxic conditions
Authors: Vlaminck Benoit , Toffoli Sebastien , Ghislain Benjamin , Demazy Catherine , Raes Martine , Michiels Carine
Published: October 2007

Hypoxia‐inducible factor‐1 (HIF‐1) is now recognized as a possible target for cancer treatment. This transcription factor is responsible for the overexpression of several genes favouring cancer cell survival and inducing neo‐angiogenesis. Echinomycin has recently been described to inhibit HIF‐1 DNA binding and transcriptional activity. In this work, it is shown that echinomycin strongly inhibits the activity of HIF‐1 under hypoxic conditions, and also interferes with the activity of other transcription factors. These results demonstrate the lack of specificity of this molecule. Moreover, it is demonstrated that echinomycin induces an increase in HIF‐1 activity under normoxic conditions, parallel to an increase in the expression of HIF‐1 target genes. This effect is caused by an increase in HIF‐1α protein level, resulting from an increase in the transcription of the HIF‐1A gene in the presence of a low concentration of echinomycin. Transfection experiments with HIF‐1α promoter constructs revealed the presence of an Sp1 binding element responsive to echinomycin. Furthermore, echinomycin enhanced Sp1 activity, as measured by the use of a specific reporter system. These findings show, for the first time, that echinomycin has a dual effect on HIF‐1 activity under normoxic and hypoxic conditions, demonstrating that this molecule cannot be used in cancer treatment.
Discovery of a galactic wind in the central region of M100
Authors: Jiménez-Vicente J. , Castillo-Morales A. , Mediavilla E. , Battaner E.
Published: October 2007

We report the discovery of a galactic wind in the central region of the galaxy M100. This result is based on a careful 2D spectroscopic study performed on observations made with the fibre system INTEGRAL on the William Herschel Telescope. The primary evidence of the wind is the presence of blueshifted interstellar NaD absorption lines. The velocity field of the absorbers show a clear rotation pattern but which is globally blueshifted (∼−115 km s−1) with respect to the systemic velocity of the galaxy. The emission lines also present a blueward component arising from the ionized gas phase of the galactic wind. The velocity field of the ionized gas wind component shows no evidence of rotation but exhibits a pattern that can be interpreted in terms of the projection of an outflowing cone or shell. The wind component has [N ii]/Hα ratios of about 1.8, typical of shock ionization. The ionized component of the wind can be identified with an expanding shell of shocked gas, and the neutral component with disc gas entrained in the wind at the interface of the expanding shell with the galactic interstellar medium. The galactic wind seems to be driven uniquely by the nuclear starburst. Our analysis indicates that a non-negligible fraction of the wind material might escape to the intergalactic medium (IGM). In this case, if the wind detected in M100 were representative of similar phenomena in other galaxies with low to moderate activity, the current estimates of metal and dust content of the IGM might be drastically underestimated.
Mouse Behavioral Assays Relevant to the Symptoms of Autism*
Authors: Crawley Jacqueline N.
Published: October 2007

While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T‐maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism.
The Neurobiology of Autism
Authors: Pardo Carlos A. , Eberhart Charles G.
Published: October 2007

Improving clinical tests are allowing us to more precisely classify autism spectrum disorders and diagnose them at earlier ages. This raises the possibility of earlier and potentially more effective therapeutic interventions. To fully capitalize on this opportunity, however, will require better understanding of the neurobiological changes underlying this devastating group of developmental disorders. It is becoming clear that the normal trajectory of neurodevelopment is altered in autism, with aberrations in brain growth, neuronal patterning and cortical connectivity. Changes to the structure and function of synapses and dendrites have also been strongly implicated in the pathology of autism by morphological, genetic and animal modeling studies. Finally, environmental factors are likely to interact with the underlying genetic profile, and foster the clinical heterogeneity seen in autism spectrum disorders. In this review we attempt to link the molecular pathways altered in autism to the neurodevelopmental and clinical changes that characterize the disease. We focus on signaling molecules such as neurotrophin, Reelin, PTEN and hepatocyte growth factor, neurotransmitters such as serotonin and glutamate, and synaptic proteins such as neurexin, SHANK and neuroligin. We also discuss evidence implicating oxidative stress, neuroglial activation and neuroimmunity in autism.
Modeling Parent and Metabolite Fate and Transport in Subsurface Drained Fields With Directly Connected Macropores1
Authors: Fox Garey A. , Sabbagh George J. , Malone Robert W. , Rojas Ken
Published: September 2007

Abstract:  Few studies exist that evaluate or apply pesticide transport models based on measured parent and metabolite concentrations in fields with subsurface drainage. Furthermore, recent research suggests pesticide transport through exceedingly efficient direct connections, which occur when macropores are hydrologically connected to subsurface drains, but this connectivity has been simulated at only one field site in Allen County, Indiana. This research evaluates the Root Zone Water Quality Model (RZWQM) in simulating the transport of a parent compound and its metabolite at two subsurface drained field sites. Previous research used one of the field sites to test the original modification of the RZWQM to simulate directly connected macropores for bromide and the parent compound, but not for the metabolite. This research will evaluate RZWQM for parent/metabolite transformation and transport at this first field site, along with evaluating the model at an additional field site to evaluate whether the parameters for direct connectivity are transferable and whether model performance is consistent for the two field sites with unique soil, hydrologic, and environmental conditions. Isoxaflutole, the active ingredient in BALANCE® herbicide, was applied to both fields. Isoxaflutole rapidly degrades into a metabolite (RPA 202248). This research used calibrated RZWQM models for each field based on observed subsurface drain flow and/or edge of field conservative tracer concentrations in subsurface flow. The calibrated models for both field sites required a portion (approximately 2% but this fraction may require calibration) of the available water and chemical in macropore flow to be routed directly into the subsurface drains to simulate peak concentrations in edge of field subsurface drain flow shortly after chemical applications. Confirming the results from the first field site, the existing modification for directly connected macropores continually failed to predict pesticide concentrations on the recession limbs of drainage hydrographs, suggesting that the current strategy only partially accounts for direct connectivity. Thirty‐year distributions of annual mass (drainage) loss of parent and metabolite in terms of percent of isoxaflutole applied suggested annual simulated percent losses of parent and metabolite (3.04 and 1.31%) no greater in drainage than losses in runoff on nondrained fields as reported in the literature.
The Structure of Instrumental Practical Reasoning
Authors: MILLER CHRISTIAN
Published: October 2007

Standard views of instrumental practical reasoning often appeal just to an end‐directed desire and a means‐end belief. I argue that such accounts are insufficient when it comes to the practical lives of agents. Instead I offer a novel view of such reasoning, the heart of which is the addition of a normative belief concerning the desirability of the agent's end.
Is This a World Where Knowledge Has to Include Justification?
Authors: HETHERINGTON STEPHEN
Published: October 2007

If any thesis is all‐but‐universally accepted by contemporary epistemologists, it is justificationism—the thesis that being an instance of knowledge has to include being epistemically justified in some appropriate way. If there is to be any epistemological knowledge about knowledge, a paradigm candidate would seem to be our knowledge that justificationism is true. This is a conception of a way in which knowledge has to berobust. Nevertheless, this paper provides reason to doubt the truth of that conception. Even epistemology’s supposed conceptual core is not as epistemically unchallengeable as we might have assumed to be the case.
Competition and species diversity: removal of dominant species increases diversity in Costa Rican butterfly communities
Authors: Kunte Krushnamegh
Published: October 2007

Biological communities are usually dominated by a few species and show characteristically skewed species abundance distributions. Although niche apportionment and resource competition are sometimes implicated in such patterns, few experimental studies have shown direct links between resource limitation, competition with dominant species and their impacts on the overall diversity and composition of large natural communities. Here I report the results of an experiment in which I first studied species diversity and composition in two Costa Rican nectar‐feeding butterfly communities numerically dominated by two species of Anartia butterflies. Then I removed Anartia from these communities to study changes in resource availability, species abundance relationships, community diversity and composition as an outcome of the removal of the dominant competitors. In the face of competition with Anartia, nectar was scarce, species abundance distributions were highly skewed, and species diversity was low in both communities. Within two weeks after the removal of Anartia, there were parallel changes in both communities: competition for nectar reduced and the nectar quantity increased substantially, which facilitated increase in community diversity and resulted in significantly less skewed species abundance distributions. Higher nectar quantity also enabled the distribution of body size and proboscis length of constituent species in the communities to expand at both ends. This study thus experimentally showed that resource competition with the dominant species was excluding many species from the communities, lowering their diversity and skewing relative species abundance relationships. These findings are of fundamental importance for competition theory and community ecology because they indicate ways in which diverse communities may be affected by and recover from competition with dominant species.
Design, Fabrication, and Characterization of a Micro Vapor-Jet Vacuum Pump
Authors: Doms Marco , Müller Jörg
Published: October 2007

A microelectromechanical system (MEMS) vapor-jet pump for vacuum generation in miniaturized analytical systems, e.g., micro-mass-spectrometers (Wapelhorst, E., Hauschild, J., and Mueller, J., 2005, “A Fully Integrated Micro Mass Spectrometer,” in Fifth Workshop on Harsh-Environment Mass Spectrometry;Hauschild, J., Wapelhorst, E., and Mueller, J., 2005, “A Fully Integrated Plasma Electron Source for Micro Mass Spectrometers,” in Ninth International Conference on Miniaturized Systems for Chemistry and Life Sciences (μTAS), pp. 476–478), is presented. A high velocity nitrogen or water vapor jet is used for vacuum generation. Starting from atmospheric pressure, a high throughput of more than 23ml∕min and an ultimate pressure of 495mbars were obtained with this new type of micropump. An approach for the full integration of all components of the pump is presented and validated by experimental results. The pump is fabricated from silicon and glass substrates using standard MEMS fabrication techniques including deep reactive ion etching, trichlorosilane molecular vapor deposition, and metal-assisted chemical etching for porous silicon fabrication. Micromachined pressure sensors based on the Pirani principle have been developed and integrated into the pump for monitoring.
Development-Length Requirements for Fully Developed Laminar Pipe Flow of Inelastic Non-Newtonian Liquids
Authors: Poole R. J. , Ridley B. S.
Published: October 2007

In the current study, we report the results of a detailed and systematic numerical investigation of developing pipe flow of inelastic non-Newtonian fluids obeying the power-law model. We are able to demonstrate that a judicious choice of the Reynolds number allows the development length at high Reynolds number to collapse onto a single curve (i.e., independent of the power-law index n). Moreover, at low Reynolds numbers, we show that the development length is, in contrast to existing results in the literature, a function of power-law index. Using a simple modification to the recently proposed correlation for Newtonian fluid flows (Durst, F. et al., 2005, “The Development Lengths of Laminar Pipe and Channel Flows,” J. Fluids Eng., 127, pp. 1154–1160) to account for this low Re behavior, we propose a unified correlation for XD∕D, which is valid in the range 0.4<n<1.5 and 0<Re<1000.
Response to Comment on "Top-Down Versus Bottom-Up Control of Attention in the Prefrontal and Posterior Parietal Cortices"
Authors: Miller Earl K. , Buschman Timothy J.
Published: October 2007

We reported latencies for target selection based on the earliest neurons to show effects, which Schall
et al
. mistakenly compare to latencies based on population averages. We show that there are actually no discrepancies across studies and also discuss the relative merits of single-electrode versus multiple-electrode approaches.
On Sickness and Surroundings
Authors: Anker Peder
Published: October 2007

Breathing Space
. How Allergies Shape Our Lives and Landscapes.
By Gregg Mitman
. Yale University Press, New Haven, CT, 2007. 330 pp. $30. ISBN 9780300110357.

Toxic Exposures
. Contested Illnesses and the Environmental Health Movement.
By Phil Brown
. Columbia University Press, New York, 2007. 392 pp. $29.50, £19. ISBN 9780231129480.

Mitman considers how the changing environment in the United States has fed the surge of allergic disease. Brown explores the consequences of medical and political debates over environmentally induced illnesses.
Odor-Mediated Push-Pull Pollination in Cycads
Authors: Terry Irene , Walter Gimme H. , Moore Chris , Roemer Robert , Hull Craig
Published: October 2007

The reproductive organs of some plants self-heat, release scent, and attract pollinators. The relations among these processes are not well understood, especially in the more ancient, nonflowering gymnosperm lineages. We describe the influence of plant volatiles in an obligate pollination mutualism between an Australian Macrozamia cycad (a gymnosperm with male and female individuals) and its specialist thrips pollinator, Cycadothrips chadwicki. Pollen-laden thrips leave male cycad cones en masse during the daily thermogenic phase, when cone temperatures and volatile emissions increase dramatically and thrips are repelled. As thermogenesis declines, total volatile emissions diminish and cones attract thrips, resulting in pollination of female cones. Behavioral and electrophysiological tests on thrips reveal that variations in b-myrcene and ocimene emissions by male and female cones are sufficient to explain the observed sequential thrips' repellence (push) and attraction (pull). These dynamic interactions represent complex adaptations that enhance the likelihood of pollination and may reflect an intermediate state in the evolution of biotic pollination.
Advances in Cytokinin Signaling
Authors: Müller Bruno , Sheen Jen
Published: October 2007

Cytokinins are essential plant hormones that control various processes in plants' development and response to external stimuli. The
Arabidopsis
cytokinin signal transduction pathway involves hybrid histidine protein kinase sensors, phosphotransfer proteins, and regulators as transcription activators and repressors in a phosphorelay system. Each step is executed by components encoded by multigene families. Recent findings have revealed new functions, new feedback loops, and connections to other signaling pathways.
Polymer Gate Dielectric Surface Viscoelasticity Modulates Pentacene Transistor Performance
Authors: Kim Choongik , Facchetti Antonio , Marks Tobin J.
Published: October 2007

Nanoscopically confined polymer films are known to exhibit substantially depressed glass transition temperatures (
L
g
's) as compared to the corresponding bulk materials. We report here that pentacene thin films grown on polymer gate dielectrics at temperatures well below their bulk
T
g
's exhibit distinctive and abrupt morphological and microstructural transitions and thin-film transistor (TFT) performance discontinuities at well-defined growth temperatures. The changes reflect the higher chain mobility of the dielectric in its rubbery state and are independent of dielectric film thickness. Optimization of organic TFT performance must recognize this fundamental buried interface viscoelasticity effect, which is detectable in the current-voltage response.
Variations on a Theorem
Authors: Whiteley Louise
Published: October 2007

A Disappearing Number
.
Conceived and directed by Simon McBurney, devised by Complicite
. Co-produced by Complicite, barbicanbite07, Wiener Festwochen, Holland Festival, Ruhrfestspiele, in association with Theatre Royal Plymouth. Barbican Theatre, London. Through 6 October 2007.
www.complicite.org/productions/detail.html?id=43

The play, which takes as its starting point the collaboration between the mathematicians Srinivasa Ramanujan (a poor Brahmin from South India) and G. H. Hardy (a Cambridge don), explores our relentless compulsion to understand.
Development of an Internal Control for Evaluation and Standardization of a Quantitative PCR Assay for Detection of
Helicobacter pylori
in Drinking Water
Authors: Sen Keya , Schable Nancy A. , Lye Dennis J.
Published: September 2007

Due to metabolic and morphological changes that can prevent
Helicobacter pylori
cells in water from growing on conventional media, an
H. pylori
-specific TaqMan quantitative PCR (qPCR) assay was developed that uses a 6-carboxyfluorescein-labeled probe (A. E. McDaniels, L. Wymer, C. Rankin, and R. Haugland, Water Res. 39:4808-4816, 2005). However, proper internal controls are needed to provide an accurate estimate of low numbers of
H. pylori
in drinking water. In this study, the 135-bp amplicon described by McDaniels et al. was modified at the probe binding region, using PCR mutagenesis. The fragment was incorporated into a single-copy plasmid to serve as a PCR-positive control and cloned into
Escherichia coli
to serve as a matrix spike. It was shown to have a detection limit of five copies, using a VIC dye-labeled probe. A DNA extraction kit was optimized that allowed sampling of an entire liter of water. Water samples spiked with the recombinant
E. coli
cells were shown to behave like
H. pylori
cells in the qPCR assay. The recombinant
E. coli
cells were optimized to be used at 10 cells/liter of water, where they were shown not to compete with 5 to 3,000 cells of
H. pylori
in a duplex qPCR assay. Four treated drinking water samples spiked with
H. pylori
(100 cells) demonstrated similar cycle threshold values if the chlorine disinfectant was first neutralized by sodium thiosulfate.
Environmental Monitoring of
Mycobacterium bovis
in Badger Feces and Badger Sett Soil by Real-Time PCR, as Confirmed by Immunofluorescence, Immunocapture, and Cultivation
Authors: Sweeney F. P. , Courtenay O. , Hibberd V. , Hewinson R. G. , Reilly L. A. , Gaze W. H. , Wellington E. M. H.
Published: September 2007

Real-time PCR was used to detect and quantify
Mycobacterium bovis
cells in naturally infected soil and badger feces. Immunomagnetic capture, immunofluorescence, and selective culture confirmed species identification and cell viability. These techniques will prove useful for monitoring
M. bovis
in the environment and for elucidating transmission routes between wildlife and cattle.
Evaluation of the
Staphylococcus aureus
Class C Nonspecific Acid Phosphatase (SapS) as a Reporter for Gene Expression and Protein Secretion in Gram-Negative and Gram-Positive Bacteria
Authors: du Plessis Erika , Theron Jacques , Berger Eldie , Louw Maureen
Published: September 2007

A phosphatase secreted by
Staphylococcus aureus
strain 154 has previously been characterized and classified as a new member of the bacterial class C family of nonspecific acid phosphatases. As the acid phosphatase activity can be easily detected with a cost-effective plate screen assay, quantitatively measured by a simple enzyme assay, and detected by zymography, its potential use as a reporter system was investigated. The
S. aureus
acid phosphatase (
sapS
) gene has been cloned and expressed from its own regulatory sequences in
Escherichia coli
,
Bacillus subtilis
, and
Bacillus halodurans
. Transcriptional and translational fusions of the
sapS
gene with selected heterologous promoters and signal sequences were constructed and expressed in all three of the host strains. From the range of promoters evaluated, the strongest promoter for heterologous protein production in each of the host strains was identified, i.e., the
E. coli lacZ
promoter in
E. coli
, the
B. halodurans
alkaline protease promoter in
B. subtilis
, and the
B. halodurans
σ
D
promoter in
B. halodurans
. This is the first report on the development of a class C acid phosphatase gene as a reporter gene with the advantage of being able to function in both gram-positive and gram-negative host strains.
Prevalence of EnterotoxigenicClostridium perfringensIsolates in Pittsburgh (Pennsylvania) Area Soils and Home Kitchens
Authors: Li Jihong , Sayeed Sameera , McClane Bruce A.
Published: September 2007

In the United States and Europe, food poisoning due toClostridium perfringenstype A is predominantly caused byC. perfringensisolates carrying a chromosomal enterotoxin gene (cpe). Neither the reservoir for these isolates nor the point in the food chain where these bacteria contaminate foods is currently understood. Therefore, the current study investigated whether type A isolates carrying a chromosomalcpegene are present in two potential reservoirs, i.e., soil and home kitchen surfaces. NoC. perfringensisolates were recovered from home kitchen surfaces, but most surveyed soil samples containedC. perfringens. The recovered soil isolates were predominantly type A, but some type C, D, and E soil isolates were also identified. Allcpe-positive isolates recovered from soil were genotyped as type A, with theircpegenes oncpeplasmids rather than the chromosome. However, twocpe-positive soil isolates did not carry a classicalcpeplasmid. Both of those atypicalcpe-positive soil isolates were sporulation capable yet failed to produceC. perfringensenterotoxin, possibly because of differences in their upstream promoter regions. Collectively these results suggest that neither soil nor home kitchen surfaces represent major reservoirs for type A isolates with chromosomalcpethat cause food poisoning, although soil does appear to be a reservoir forcpe-positive isolates causing non-food-borne gastrointestinal diseases.
Design and Performance of a 16S rRNA-Targeted Oligonucleotide Probe for Detection of Members of the Genus
Bdellovibrio
by Fluorescence In Situ Hybridization
Authors: Mahmoud Khaled K. , McNeely Damian , Elwood Chelsea , Koval Susan F.
Published: September 2007

A 16S rRNA-targeted, Cy3-labeled oligonucleotide probe was designed to detect members of the genus
Bdellovibrio
by fluorescence in situ hybridization. Specific hybridization conditions were established; however, the detection of bdellovibrios in environmental samples required enrichment, confirming that
Bdellovibrio
spp. are not present in large numbers in the environment.
Analysis of the Mycosamine Biosynthesis and Attachment Genes in the Nystatin Biosynthetic Gene Cluster of
Streptomyces noursei
ATCC 11455
Authors: Nedal Aina , Sletta Håvard , Brautaset Trygve , Borgos Sven E. F. , Sekurova Olga N. , Ellingsen Trond E. , Zotchev Sergey B.
Published: September 2007

The polyene macrolide antibiotic nystatin produced by
Streptomyces noursei
contains a deoxyaminosugar mycosamine moiety attached to the C-19 carbon of the macrolactone ring through the β-glycosidic bond. The nystatin biosynthetic gene cluster contains three genes,
nysDI, nysDII
, and
nysDIII
, encoding enzymes with presumed roles in mycosamine biosynthesis and attachment as glycosyltransferase, aminotransferase, and GDP-mannose dehydratase, respectively. In the present study, the functions of these three genes were analyzed. The recombinant NysDIII protein was expressed in
Escherichia coli
and purified, and its in vitro GDP-mannose dehydratase activity was demonstrated. The
nysDI
and
nysDII
genes were inactivated individually in
S. noursei
, and analyses of the resulting mutants showed that both genes produced nystatinolide and 10-deoxynystatinolide as major products. Expression of the
nysDI
and
nysDII
genes in
trans
in the respective mutants partially restored nystatin biosynthesis in both cases, supporting the predicted roles of these two genes in mycosamine biosynthesis and attachment. Both antifungal and hemolytic activities of the purified nystatinolides were shown to be strongly reduced compared to those of nystatin, confirming the importance of the mycosamine moiety for the biological activity of nystatin.
Nisin-Controlled Extracellular Production of Interleukin-2 inLactococcus lactisStrains, without the Requirement for a Signal Peptide Sequence
Authors: Fernández Antonio , Rodríguez Juan M. , Bongaerts Roy J. , Gasson Michael J. , Horn Nikki
Published: September 2007

Secretion of the cytokine interleukin-2 (IL-2) was investigated inLactococcus lactisusing the secretory machinery of the bacteriocin lactococcin A. Surprisingly, thelcnCDtransport genes were not essential for mouse IL-2 secretion. Furthermore, expression of a mature mouse IL-2 gene resulted in interleukin secretion without the requirement for a leader sequence.