bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary Neuroendocrine Cell Hyperplasia: Identification, Diagnostic Criteria and Incidence in Untreated Ageing Rats of Different Strains
Authors: Haworth Richard , Woodfine Jennie , McCawley Sean , Pilling Andrew M. , Lewis David J. , Williams Tom C.
Published: September 2007

Pulmonary Neuroendocrine Cells (PNEC) are found as clusters called neuroepithelial bodies (NEB) or as single cells scattered in the respiratory epithelium. Pulmonary neuroendocrine cell hyperplasia is recorded in humans and experimentally manipulated rodents. The objectives of this work were to identify the optimal immunohistochemical markers for PNEC in the rat for use on paraffin-embedded, formalin-fixed material and to provide the first comparative incidence of PNEC hyperplasia in untreated 2-year-old rats of different strains. Calcitonin-gene related peptide (CGRP) and protein G product 9.5 (PGP9.5) antibodies identified PNEC consistently and selectively. In contrast, PNEC did not express chromogranin-A or S-100. PNEC hyperplasia was defined as foci of PNEC with greater than 40 nuclei, excluding overlying respiratory epithelium and submucosal PNEC. PNEC hyperplasia was observed at low incidence (0–7%) in untreated 2-year-old Sprague-Dawley, Han Wistar and Wistar rats but not Fischer 344 rats. This is the first report of spontaneous PNEC hyperplasia in rats. The cause of this hyperplasia is unknown, but experimental models that induce PNEC hyperplasia by causing bronchiolar cell injury are discussed. PNEC neoplasia in the rat is unreported in the literature and was not observed in animals examined in this study.
Adenine Nucleotide (ADP/ATP) Translocase 3 Participates in the Tumor Necrosis Factor–induced Apoptosis of MCF-7 Cells
Authors: Yang Ziqiang , Cheng Wei , Hong Lixin , Chen Wanze , Wang Yanhai , Lin Shengcai , Han Jiahuai , Zhou Huamin , Gu Jun
Published: September 2007

Mitochondrial adenine nucleotide translocase (ANT) is believed to be a component or a regulatory component of the mitochondrial permeability transition pore (mtPTP), which controls mitochondrial permeability transition during apoptosis. However, the role of ANT in apoptosis is still uncertain, because hepatocytes isolated from ANT knockout and wild-type mice are equally sensitive to TNF- and Fas-induced apoptosis. In a screen for genes required for tumor necrosis factor α (TNF-α)-induced apoptosis in MCF-7 human breast cancer cells using retrovirus insertion–mediated random mutagenesis, we discovered that the ANT3 gene is involved in TNF-α–induced cell death in MCF-7 cells. We further found that ANT3 is selectively required for TNF- and oxidative stress–induced cell death in MCF-7 cells, but it is dispensable for cell death induced by several other inducers. This data supplements previous data obtained from ANT knockout studies, indicating that ANT is involved in some apoptotic processes. We found that the resistance to TNF-α–induced apoptosis observed in ANT3 mutant (ANT3mut) cells is associated with a deficiency in the regulation of the mitochondrial membrane potential and cytochrome c release. It is not related to intracellular ATP levels or survival pathways, supporting a previous model in which ANT regulates mtPTP. Our study provides genetic evidence supporting a role of ANT in apoptosis and suggests that the involvement of ANT in cell death is cell type– and stimulus-dependent.
Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to Metastasis
Authors: Hashimoto Yosuke , Parsons Maddy , Adams Josephine C.
Published: September 2007

Recurrence of carcinomas due to cells that migrate away from the primary tumor is a major problem in cancer treatment. Immunohistochemical analyses of human carcinomas have consistently correlated up-regulation of the actin-bundling protein fascin with a clinically aggressive phenotype and poor prognosis. To understand the functional and mechanistic contributions of fascin, we undertook inducible short hairpin RNA (shRNA) knockdown of fascin in human colon carcinoma cells derived from an aggressive primary tumor. Fascin-depletion led to decreased numbers of filopodia and altered morphology of cell protrusions, decreased Rac-dependent migration on laminin, decreased turnover of focal adhesions, and, in vivo, decreased xenograft tumor development and metastasis. cDNA rescue of fascin shRNA-knockdown cells with wild-type green fluorescent protein-fascin or fascins mutated at the protein kinase C (PKC) phosphorylation site revealed that both the actin-bundling and active PKC-binding activities of fascin are required for the organization of filopodial protrusions, Rac-dependent migration, and tumor metastasis. Thus, fascin contributes to carcinoma migration and metastasis through dual pathways that impact on multiple subcellular structures needed for cell migration.
AVIS: AJAX viewer of interactive signaling networks
Authors: Berger Seth I. , Iyengar Ravi , Ma’ayan Avi
Published: September 2007

Motivation: Increasing complexity of cell signaling network maps requires sophisticated visualization technologies. Simple web-based visualization tools can allow for improved data presentation and collaboration. Researchers studying cell signaling would benefit from having the ability to embed dynamic cell signaling maps in web pages.

Summary: AVIS is a Google gadget compatible web-based viewer of interactive cell signaling networks. AVIS is an implementation of AJAX (Asynchronous JavaScript with XML) with the usage of the libraries GraphViz, ImageMagic (PerlMagic) and overLib. AVIS provides web-based visualization of text-based signaling networks with dynamical zooming, panning and linking capabilities. AVIS is a cross-platform web-based tool that can be used to visualize network maps as embedded objects in any web page. AVIS was implemented for visualization of PathwayGenerator, a tool that displays over 4000 automatically generated mammalian cell signaling maps; NodeNeighborhood a tool to visualize first and second interacting neighbors of yeast and mammalian proteins; and for Genes2Networks, a tool to connect lists of genes and protein using background protein interaction networks.

Availability: A demo page of AVIS and links to applications and distributions can be found at http://actin.pharm.mssm.edu/AVIS2. Detailed instructions for using and configuring AVIS can be found in the user manual at http://actin.pharm.mssm.edu/AVIS2/manual.pdf

Contact:  avi.maayan@mssm.edu
Safety of Acupuncture Practice in Japan: Patient Reactions, Therapist Negligence and Error Reduction Strategies
Authors: Yamashita Hitoshi , Tsukayama Hiroshi
Published: September 2007

Evidence‐based approach on the safety of acupuncture had been lagging behind both in the West and the East, but reliable data based on some prospective surveys were published after the late 1990s. In the present article, we, focusing on ‘Japanese acupuncture’, review relevant case reports and prospective surveys on adverse events in Japan, assess the safety of acupuncture practice in this country, and suggest a strategy for reducing the therapists’ error. Based on the prospective surveys, it seems reasonable to suppose that serious adverse events are rare in standard practice by adequately trained acupuncturists, regardless of countries or modes of practice. Almost all of adverse reactions commonly seen in acupuncture practice—such as fatigue, drowsiness, aggravation, minor bleeding, pain on insertion and subcutaneous hemorrhage—are mild and transient, although we should be cautious of secondary injury following drowsiness and needle fainting. After demonstrating that acupuncture is inherently safe, we have been focusing on how to reduce the risk of negligence in Japan, as well as educating acupuncturists more about safe depth of insertion and infection control. Incident reporting and feedback system is a useful strategy for reducing therapist errors such as forgotten needles. For the benefit of acupuncture patients in Japan, it is important to establish mandatory postgraduate clinical training and continued education system.
The 5th I. E. Melhus Graduate Student Symposium: Today's Students Preparing to Meet Tomorrow's Challenges in Epidemiology and Plant Disease Management
Authors: Nutter Forrest W.
Published: September 2007

The Irving E. Melhus Graduate Student Symposium is a prestigious annual event that takes place as part of the American Phytopathology Society (APS) annual meeting and is co-sponsored by the APS Epidemiology Committee and the APS Foundation. The I.E. Melhus symposia feature graduate students competitively chosen to present their thesis research results. Criteria for selection include evaluation of the significance of the contribution towards improving our understanding of plant pathology, their communication skills, and letters of nomination.

Accepted for publication 24 April 2007. Published 26 July 2007.
An Application of Space-Time Analysis to Improve the Epidemiological Understanding of the Papaya-Papaya Yellow Crinkle Pathosystem
Authors: Esker Paul D. , Gibb Karen S. , Dixon Philip M. , Nutter Forrest W.
Published: September 2007

Yellow crinkle disease of papaya is a serious threat to papaya production in Australia. Space-time point pattern analysis was used to study the spatial and temporal dependence of two phytoplasma strains that cause yellow crinkle: tomato big bud (TBB) and sweet potato little leaf V4 (SPLL-V4). Incidence data for both phytoplasma strains were obtained from a field study conducted in Katherine, NT, Australia, between January 1996 and May 1999. The primary ecological and epidemiological question of interest was to elucidate the scale of spatial or spatio-temporal aggregation of phytoplasma-infected papaya plants. The hypothesis was that there would be a contagion process, where TBB- and SPLL-V4-infected papaya would be aggregated and not random. To test this hypothesis, a point pattern spatial analysis using Monte Carlo simulation was initially applied to the incidence data. Results of this analysis suggested that SPLL-V4 infected papaya plants displayed aggregation with spatial dependence up to 30 m (10 to 15 plants along or across rows), whereas there was not strong evidence to suggest that TBB-infected papaya plants were aggregated. However, when a space-time point pattern analysis was subsequently used to simultaneously test for the interaction between space and time, there was strong evidence (P < 0.01 for SPLL-V4 and P < 0.10 for TBB) to suggest a space-time interaction for both SPLL-V4 and TBB. For SPLL-V4, a space-time risk window of approximately 10 months and 20 m was detected, whereas for TBB, this risk window was 5 months and 10 m. The results of these studies support the hypothesis that papaya infection by both phytoplasma strains appears to be the result of a contagion process, providing support for the contention that insect vectors are the most likely mechanism for acquisition, dispersal, and transmission.

Accepted for publication 26 April 2007. Published 26 July 2007.
Addressing the Gaps in our Knowledge of Grapevine Downy Mildew for Improved Forecasting and Management
Authors: Kennelly Megan M. , Gadoury David M. , Wilcox Wayne F. , Magarey Peter A. , Seem Robert C.
Published: September 2007

The complex interactions of Plasmopara viticola with environment and host make grapevine downy mildew an ideal candidate for disease forecasting. However, a forecasting model is only as good as the knowledge used to build it, and DMCast is no exception. We addressed some knowledge gaps concerning this disease: (i) initial timing and span of primary infection; (ii) survival of the lesions and sporangia; and (iii) critical period of fruit susceptibility. Experiments revealed that, though emerging shoots are susceptible earlier than previously thought, primary infection frequently occurs near the confluence of a specific host phenological stage and certain weather conditions. Primary infection also may trigger new epidemics later in the season than was traditionally hypothesized. Lesions declined with repeated sporulation cycles but, contrary to prior reports, not age alone. Sporangia died within 8 h on dry, warm days but retained high viability on cooler days. With controlled inoculations, we determined that in the New York climate, fruit of several cultivars (Chardonnay, Riesling, Concord, and Niagara) become resistant to infection by 2 to 3 weeks post-bloom. These studies have clarified several knowledge gaps and long-held assumptions that have direct implications for improving disease forecasting and disease management.

Accepted for publication 14 March 2007. Published 26 July 2007.
Temporal Dynamics of Septoria Leaf Spot of Blueberry and its Relationship to Defoliation and Yield
Authors: Ojiambo Peter S. , Scherm Harald , Brannen Phillip M.
Published: September 2007

In field trials on Premier rabbiteye blueberry in Georgia, onset of Septoria leaf spot (caused by Septoria albopunctata) occurred between late April and mid-June. Average disease severity increased sigmoidally until late September, after which it declined due to the abscission of severely affected leaves. Disease severity was highest on early-emerging leaves and on those located on shoots closer to the ground. Pycnidiospore inoculum was present throughout the season, and leaves became infected by S. albopunctata season-long. Disease severity, defoliation, flower bud set, and next season's yield were interrelated; severely affected leaves abscised earlier in the fall than those with low disease severity, and shoots with severely diseased leaves and/or high levels of defoliation had reduced flower bud set. Furthermore, such shoots consistently had low yields the following year. The results form the basis for identifying disease levels that can be tolerated during specific periods of crop development without negatively impacting flower bud set and yield.

Accepted for publication 15 March 2007. Published 26 July 2007.
Plant Pathogens at Work: Progress and Possibilities for Weed Biocontrol Classical versus Bioherbicidal Approach
Authors: Yandoc-Ables C. B. , Rosskopf E. N. , Charudattan R.
Published: September 2007

Weed biological control using plant pathogens has been successfully implemented for a number of important invasive weeds. Both the classical and bioherbicide approaches have shown promise depending on the characteristics of the target weed. Bioherbicidal activity can be improved with research on formulation and application technology. Other approaches that have improved weed control efficacy for both classical biological control agents and bioherbicides include using a combination of pathogens and insects.

Accepted for publication 9 April 2007. Published 22 August 2007.
Comparative Host Susceptibility and Sporulation Potential of Phytophthora ramorum
Authors: Linderman Robert G. , Davis E. Anne
Published: September 2007

Phytophthora ramorum, causal agent of ramorum blight of woody shrub species, has caused serious damage to cultivars and species of camellia in commercial nurseries. Reports of relative susceptibility of camellia to P. ramorum have indicated a range from high to low susceptibility, both in nurseries and under experimental conditions. We inoculated a series of cultivars of camellia to determine their relative susceptibility to infection, and then compared lesion size to the capacity of the pathogen to produce sporangia on the lesions. We found, as did others, a wide range of susceptibility among cultivars, but lack of correlation between susceptibility (lesion size) and potential to produce sporangia that might spread the pathogen within the nursery. These results indicate that on some cultivars the pathogen might produce small or inconspicuous lesions, yet still produce copious numbers of sporangia that could spread the disease, both within the nursery and from nursery to nursery.

Accepted for publication 10 April 2007. Published 22 August 2007.
Age-related shapes of the cost of reproduction in vertebrates
Authors: Proaktor G , Milner-Gulland E.J , Coulson T
Published: September 2007

The shape of the association between age and the cost of reproduction varies across species. However, it is unclear whether there are any general patterns in the way the cost of reproduction varies with life history, taxon or ecological function. Using a simple theoretical method, we identified three characteristic patterns to describe the age-related survival cost of reproduction. The most frequent pattern is an approximately exponential decay (ED) with increasing age. Two additional u-shaped patterns were identified, where the cost of reproduction was higher for young and old individuals compared with intermediate-aged individuals. The majority of these u-shaped curves suggested higher costs of reproduction at older ages (RQ), with the rest suggesting a higher cost at young ages (LQ). While predators were most likely to exhibit ED-shaped cost curves, herbivores were equally likely to exhibit ED and RQ curves; birds were likely to exhibit ED-shaped curves and mammals were split equally between ED and RQ curves. These findings suggest that there may be predictable differences in the age-related shape of the cost of reproduction between species, but further research is required to identify the mechanisms generating such differences.
Premature deactivation of soleus during the propulsive phase of cat jumping
Authors: Kaya Motoshi , Leonard Tim R , Herzog Walter
Published: September 2007

It has been shown that cat soleus (SOL) forces remain nearly constant despite increases in electromyography (EMG) activity for increasing speeds of locomotion, while medial gastrocnemius (MG) forces and EMG activity increase in parallel. Furthermore, during jumping, average cat SOL forces decrease, while average EMG activity increases dramatically compared with walking conditions. Finally, during rapid paw-shake movements, SOL forces and EMG activities are nearly zero. Based on these results, we hypothesized that the SOL is deactivated, despite ankle extensor requirements, if the contractile conditions limit SOL force potential severely. The purposes of this study were to (i) investigate SOL EMG activity and force as a function of its contractile conditions during jumping, (ii) test whether SOL EMG activity is associated with SOL contractile conditions, and (iii) determine the functional implications of SOL EMG activity during jumping. It was found that the SOL was prematurely deactivated in two distinct phases during the propulsive phase of jumping, in which shortening speeds approached or even exceeded the maximal speed of muscle shortening. We concluded that the SOL was prematurely deactivated to save energy because its mechanical work output approached zero, and speculated that the first phase of deactivation might be caused by a decrease in group Ia firing associated with active shortening and the second by a pre-programmed response inherent to the central pattern generator.
A beetle-inspired solution for underwater adhesion
Authors: Varenberg M , Gorb S
Published: September 2007

Glue-free reversible adhesion was achieved underwater using a beetle-inspired mushroom-shaped fibrillar microstructure. Structured surfaces reveal a 25% increase in pull-off force when immersed in water and their underwater attachment is 20 times more effective than that of flat surfaces. The van der Waals interaction that underlies the adhesion of the mushroom-shaped fibrillar microstructure is significantly enhanced by a suction effect when underwater. This results in a higher adhesive capability of the material, with potential in medicine, bio- and marine technologies and a range of applications in liquid-dominated environments.
The learnability of quantum states
Authors: Aaronson Scott
Published: September 2007

Traditional quantum state tomography requires a number of measurements that grows exponentially with the number of qubitsn. But using ideas from computational learning theory, we show that one can do exponentially better in a statistical setting. In particular, to predict the outcomes ofmostmeasurements drawn from an arbitrary probability distribution, one needs only a number of sample measurements that grows linearly withn. This theorem has the conceptual implication that quantum states, despite being exponentially long vectors, are nevertheless ‘reasonable’ in a learning theory sense. The theorem also has two applications to quantum computing: first, a new simulation of quantum one-way communication protocols and second, the use of trusted classical advice to verify untrusted quantum advice.
Bats respond to polarity of a magnetic field
Authors: Wang Yinan , Pan Yongxin , Parsons Stuart , Walker Michael , Zhang Shuyi
Published: September 2007

Bats have been shown to use information from the Earth's magnetic field during orientation. However, the mechanism underlying this ability remains unknown. In this study we investigated whether bats possess a polarity- or inclination-based compass that could be used in orientation. We monitored the hanging position of adultNyctalus plancyiin the laboratory in the presence of an induced magnetic field of twice Earth-strength. When under the influence of a normally aligned induced field the bats showed a significant preference for hanging at the northern end of their roosting basket. When the vertical component of the field was reversed, the bats remained at the northern end of the basket. However, when the horizontal component of the field was reversed, the bats changed their positions and hung at the southern end of the basket. Based on these results, we conclude thatN. plancyi, unlike all other non-mammalian vertebrates tested to date, uses a polarity-based compass during orientation in the roost, and that the same compass is also likely to underlie bats' long-distance navigation abilities.
The effect of energy reserves and food availability on optimal immune defence
Authors: Houston Alasdair I , McNamara John M , Barta Zoltán , Klasing Kirk C
Published: September 2007

In order to avoid both starvation and disease, animals must allocate resources between energy reserves and immune defence. We investigate the optimal allocation. We find that animals with low reserves choose to allocate less to defence than animals with higher reserves because when reserves are low it is more important to increase reserves to reduce the risk of starvation in the future. In general, investment in immune defence increases monotonically with energy reserves. An exception is when the animal can reduce its probability of death from disease by reducing its foraging rate. In this case, allocation to immune defence can peak at intermediate reserves. When food changes over time, the optimal response depends on the frequency of changes. If the environment is relatively stable, animals forage most intensively when the food is scarce and invest more in immune defence when the food is abundant than when it is scarce. If the environment changes quickly, animals forage at low intensity when the food is scarce, but at high intensity when the food is abundant. As the rate of environmental change increases, immune defence becomes less dependent on food availability. We show that the strength of selection on reserve-dependent immune defence depends on how foraging intensity and immune defence determine the probability of death from disease.
α3-Integrins are required for hippocampal long-term potentiation and working memory
Authors: Chan Chi-Shing , Levenson Jonathan M. , Mukhopadhyay Partha S. , Zong Lin , Bradley Allan , Sweatt J. David , Davis Ronald L.
Published: September 2007

Integrins comprise a large family of heterodimeric, transmembrane cell adhesion receptors that mediate diverse neuronal functions in the developing and adult CNS. Recent pharmacological and genetic studies have suggested that β1-integrins are critical in synaptic plasticity and memory formation. To further define the role of integrins in these processes, we generated a postnatal forebrain and excitatory neuron-specific knockout of α3-integrin, one of several binding partners for β1 subunit. At hippocampal Schaffer collateral-CA1 synapses, deletion of α3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of α3-integrin. Behavioral studies demonstrated that the mutant mice were selectively defective in a hippocampus-dependent, nonmatch-to-place working memory task, but were normal in other hippocampusdependent spatial tasks. The impairment in LTP and working memory is similar to that observed in β1-integrin conditional knockout mice, suggesting that α3-integrin is the functional binding partner for β1 for these processes in the forebrain.
Overcoming interference: An fMRI investigation of pattern separation in the medial temporal lobe
Authors: Kirwan C. Brock , Stark Craig E.L.
Published: September 2007

The medial temporal lobe (MTL) supports the formation and retrieval of long-term declarative memories, or memories for facts and everyday events. One challenge posed for this type of memory stems from the highly overlapping nature of common episodes. Within cognitive psychology, it is widely accepted that interference between information learned at different times is a major limitation on memory. In spite of several decades of intense research in the fields of interference theory and the neurobiological underpinnings of declarative memory, there is little direct evidence bearing on how the MTL resolves this interference to form accurate memories of everyday facts and events. Computational models of MTL function have proposed a mechanism in which the MTL, specifically the hippocampus, performs pattern separation, whereby overlapping representations are made less similar. However, there is little evidence bearing on how this process is carried out in the intact human MTL. Using high-resolution fMRI, we conducted a set of experiments that taxed behavioral pattern separation by using highly similar, interfering stimuli in a modified continuous recognition task. Regions within the parahippocampal gyrus demonstrated activity consistent with a “recall to reject” strategy. In contrast and critical to performing the task, activity within the hippocampus distinguished between correctly identified true stimulus repetitions, correctly rejected presentations of similar lure stimuli, and false alarms to similar lures. These data support the computational models’ assertion that the hippocampus plays a key role in pattern separation.
Escherichia coli phage‐shock protein A (PspA) binds to membrane phospholipids and repairs proton leakage of the damaged membranes
Authors: Kobayashi Ryuji , Suzuki Toshiharu , Yoshida Masasuke
Published: September 2007

Escherichia coli phage‐shock protein A (PspA), a 25.3 kDa peripheral membrane protein, is induced under the membrane stress conditions and is assumed to help maintain membrane potential. Here, we report that purified PspA, existing as a large oligomer, is really able to suppress proton leakage of the membranes. This was demonstrated for membrane vesicles prepared from the PspA‐lacking E. coli mutants, and for membrane vesicles damaged by ethanol and Triton X‐100 prepared from the mutant and the wild‐type cells. PspA also suppressed proton leakage of damaged liposomes made from E. coli total lipids. Furthermore, we found that PspA bound preferentially to liposomes containing phosphatidylserine and phosphatidylglycerol. All these effects were not observed for monomer PspA that was prepared by refolding of urea‐denatured PspA. These results indicate that oligomers of PspA bind to membrane phospholipids and suppress proton leakage.
Transcriptional control of nmrA by the bZIP transcription factor MeaB reveals a new level of nitrogen regulation in Aspergillus nidulans
Authors: Wong Koon Ho , Hynes Michael J. , Todd Richard B. , Davis Meryl A.
Published: September 2007

Fungi can use a diverse range of nitrogen sources. Some nitrogen sources sustain a rapid growth rate and are used in preference to less readily metabolized nitrogen sources. The mechanisms involved in this control of nitrogen utilization have been studied in the model filamentous ascomycete, Aspergillus nidulans. The GATA transcription factor AreA is necessary for the expression of nitrogen‐catabolic permeases and enzymes. AreA activity is controlled by multiple mechanisms including regulated areA transcript levels and regulated AreA nuclear export. During nitrogen sufficiency, AreA activation is also prevented by the co‐repressor NmrA. We have investigated nitrogen signalling to NmrA. NmrA overexpression prevents AreA function irrespective of the nitrogen status. The mRNA levels of areA and nmrA are inversely regulated, suggesting that the relative levels of AreA and NmrA are critical in determining AreA activation. The bZIP transcription factor MeaB was found to activate nmrA expression and a conserved element, TTGCACCAT, bound by MeaB in vitro is present in the promoters of NmrA homologues in other filamentous ascomycetes. Expression of meaB was not strongly regulated suggesting that transcriptional activation by MeaB is modulated by the nitrogen status. This work highlights a new level of complexity in the regulation of nitrogen catabolism.
Factors shaping genetic variation in the MHC of natural non‐human primate populations
Authors: Bonhomme M. , Blancher A. , Jalil M. F. , Crouau‐Roy B.
Published: September 2007

Across a large distribution range, population‐specific factors as well as pathogen‐mediated selection may shape species genetic diversity in the major histocompatibility complex (MHC). We have studied genetic diversity and population differentiation in the MHC region of the Southeast Asian cynomolgus macaque (Macaca fascicularis fascicularis), a species with large and discontinuous range, in order to investigate the role of demography vs selection. Genetic variation was assessed at seven MHC microsatellites on 272 individuals from five populations (Indochina, Java, Borneo, Philippines, and Mauritius). A high genetic diversity was observed in all populations and the Philippines but also the Mauritius populations were the most genetically differentiated. The strength and extent of linkage disequilibrium (LD) (up to 4 Mb) varies across populations mainly because of demographic factors. In Indochina, the complete lack of LD could be the signature of ancient hybridization between cynomolgus and rhesus macaques in the Indochinese peninsula. With the additional support of seven autosomal microsatellites, tests for outlier loci based on intrapopulation diversity and interpopulation differentiation (using F‐statistic) allowed to dissociate demographic from selective histories: (i) demographic history may itself explain levels of MHC variability in the Mauritius populations and (ii) positive selection could be responsible for the Philippines population differentiation, especially in the MHC class II region. Among various pathogens, Plasmodium knowlesi and Plasmodium coatneyi are two likely candidates to explain the higher frequency of some MHC haplotypes. Indeed, literature describes low parasitemia in the Philippines individuals, contrasting with fatal infections provoked by these parasites in other cynomolgus macaque populations.
Dissociation of sad facial expressions and autonomic nervous system responding in boys with disruptive behavior disorders
Authors: Marsh Penny , Beauchaine Theodore P. , Williams Bailey
Published: September 2007

Although deficiencies in emotional responding have been linked to externalizing behaviors in children, little is known about how discrete response systems (e.g., expressive, physiological) are coordinated during emotional challenge among these youth. We examined time‐linked correspondence of sad facial expressions and autonomic reactivity during an empathy‐eliciting task among boys with disruptive behavior disorders (n=31) and controls (n=23). For controls, sad facial expressions were associated with reduced sympathetic (lower skin conductance level, lengthened cardiac preejection period [PEP]) and increased parasympathetic (higher respiratory sinus arrhythmia [RSA]) activity. In contrast, no correspondence between facial expressions and autonomic reactivity was observed among boys with conduct problems. Furthermore, low correspondence between facial expressions and PEP predicted externalizing symptom severity, whereas low correspondence between facial expressions and RSA predicted internalizing symptom severity.
The burden of caesarean section refusal in a developing country setting
Authors: Chigbu CO , Iloabachie GC
Published: September 2007

Objective  To investigate the prevalence, aetiology and outcomes of caesarean section refusal in pregnant women.

Design  A prospective controlled study.

Setting  University of Nigeria Teaching Hospital and Aghaeze Hospital, Enugu, Nigeria.

Population  A total of 62 Nigerian women who declined elective caesarean section.

Method  Interviewer‐administered questionnaires at the time of caesarean section refusal and postdelivery. The delivery outcomes of the subjects were compared with that of a matched control group of women who accepted caesarean section.

Main outcome measures  Prevalence, maternal reasons for caesarean section refusal and the resultant maternal and perinatal mortality.

Results  The prevalence of caesarean section refusal was 11.6% of all caesarean deliveries. Maternal reasons for refusing caesarean section include fear of death, economic reasons, desire to experience vaginal delivery and inadequate counselling. Outcomes were significantly worse among women who refused elective caesarean section than in the controls with a maternal mortality of 15% (versus 2%, P = 0.008) and a perinatal mortality of 34% (versus 5%, P < 0.001).

Conclusion  There is a high prevalence of caesarean section refusal in south‐eastern Nigeria. Women declining caesareans have very poor maternal and perinatal outcomes and need extra support.
Centralisation of services for the management of ovarian cancer: arguments for
Authors: Olaitan A , McCormack M
Published: September 2007

The recommendation in 1999, by the National Health Service Executive (NHSE) that the management of gynaecological cancer be centralised, led to a reorganisation of services for women with gynaecological malignancies. Debate has continued about the feasibility and benefits of ovarian cancer centralisation particularly because its insidious presentation can make it difficult to identify women with ovarian cancer before surgery. Despite this, there is clear evidence that centralisation is advantageous to women in terms of quality of life, morbidity and survival.
Urological and colorectal complications following surgery for rectovaginal endometriosis
Authors: Slack A , Child T , Lindsey I , Kennedy S , Cunningham C , Mortensen N , Koninckx P , McVeigh E
Published: September 2007

Objectives  To report the short‐ and medium‐term complications of laparoscopic laser excisional surgery for rectovaginal endometriosis.

Design  Retrospective cohort study.

Setting  University teaching hospital, UK.

Population  A total of 128 women with histologically confirmed rectovaginal endometriosis who underwent laparoscopic laser surgery between May 1999 and September 2006.

Methods  Women were identified from operative database, and a case note review was performed. Data for surgical outcome and surgical complications were collected.

Main outcome measures  Rates of urinary tract and colorectal complications.

Results  A total of 128 women underwent surgery. Of these, 32 required intraoperative closure of a rectal wall defect, including 3 segmental rectosigmoid resections. There were three rectovaginal fistulae and one ureterovaginal fistula. Ureteric damage occurred in two women, and five women suffered postoperative urinary retention. The risk of intraoperative bowel intervention was increased in women who complained of cyclical rectal bleeding.

Conclusion  Laparoscopic laser excision of rectovaginal endometriosis is a safe procedure with similar, if not lower, complication rates to other published surgical series.
Squamous cell carcinoma arising in a dermoid cyst of the ovary: a case series
Authors: Hurwitz JL , Fenton A , McCluggage WG , McKenna S
Published: September 2007

Objective  Malignant transformation in a dermoid cyst of the ovary is a rare complication, occurring in only 1–2% of cases, with squamous cell carcinoma being the most common type. Preoperative diagnosis is difficult because of the lack of specific symptoms and signs to suggest malignancy. Because of the small numbers of women involved, our knowledge of this rare tumour type is limited. This study aims to further characterise the population of women affected, the disease itself and the most appropriate management strategy.

Design  We identified 14 women with this diagnosis between 1989 and 2006. This is a descriptive study, looking at the patient characteristics, mode of presentation and the role of tumour markers and radiological imaging in diagnosis. We also examined the stage and pathological features of the tumour at presentation and the subsequent course of the disease. We have also described our experiences using surgery, chemotherapy and radiotherapy in the management of these women.

Results  We found that these tumours present at an age older than that of mature teratomas and that there are no reliable diagnostic tools or prognostic indicators. The behaviour of these tumours is unpredictable, and the role of chemotherapy and radiotherapy remains unclear. We suggest that repeated surgical resection of disease at the time of relapse could give a very durable response in selected women.
Response of Spores to High‐Pressure Processing
Authors: Black Elaine P. , Setlow Peter , Hocking Ailsa D. , Stewart Cynthia M. , Kelly Alan L. , Hoover Dallas G.
Published: September 2007

ABSTRACT:  This review focuses on the responses of microbial spores to food processes that incorporate high hydrostatic pressures. While the majority of information deals with spores of Bacillus species, spores of Clostridium and Alicyclobacillus species are also discussed, and a section of the review surveys the responses of fungal spores to high‐pressure processing. The mechanisms of the germination of bacterial spores are outlined in detail with regard to spore physiology and structure, along with molecular aspects of germinants and the interaction with spore receptors. Use of treatments combining pressure and temperature for a range of different food products is reviewed, including examples of hurdle technology employing high hydrostatic pressure. Pressure‐assisted thermal sterilization is also discussed.
Larvicidal efficacy of Aloe barbadensis and Cannabis sativa against the malaria vector Anopheles stephensi (Diptera: Culicidae)
Authors: MAURYA Prejwltta , MOHAN Lalit , SHARMA Preeti , BATABYAL Lata , SRIVASTAVA C. N.
Published: September 2007

Anopheles stephensi is the primary vector of malaria, an endemic disease in India. An effort to control An. stephensi larvae by leaf extracts of Aloe barbadensis (Liliaceae) and Cannabis sativa (Moraceae) was made under laboratory conditions. A carbon tetrachloride extract of A. barbadensis was the most effective of all the extracts tested for larvicidal activity against the anopheline larvae, with LC50 15.58 and 8.04 p.p.m. after 24 and 48 h of exposure, respectively. Thus, the leaf extract of A. barbadensis has active components that could be useful as a larvicide of ecocongenial nature against malaria vectors.
Clinical, laboratory and therapeutic aspects of platelet‐type von Willebrand disease
Authors: FRANCHINI M. , MONTAGNANA M. , LIPPI G.
Published: September 2007

Platelet‐type von Willebrand disease (PT‐VWD), or pseudo‐VWD, is a rare inherited platelet disorder characterized by an increased affinity of the platelet membrane glycoprotein Ibα receptor for normal von Willebrand factor leading to characteristic platelet hyperaggregability. As PT‐VWD shares most of the clinical and laboratory features of subtype 2B VWD, the differential diagnosis between these two inherited bleeding disorders requires either platelet‐mixing or molecular genetic studies. In this review, the main clinical, laboratory and therapeutic characteristics of PT‐VWD are concisely reported.
Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS‐II toxin
Authors: Wang Zhuren , Robertson Brian , Fedida David
Published: September 2007

Kv3 channels have a major role in determining neuronal excitability, and are characterized by ultra‐rapid kinetics of gating and a high activation threshold. However, the gating currents, which occur as a result of positional changes of the charged elements in the channel structure during activation, are not well understood. Here we report a study of gating currents from wild‐type Kv3.2b channels, expressed in human embryonic kidney (HEK) cells to facilitate high time‐resolution recording. On‐gating currents (Ig,on) had extremely rapid kinetics such that at +80 mV, the time constant for the decay of Ig,on was only ∼0.3 ms. Decay of Ig,on appeared mono‐exponential at all potentials studied, and in support of this, the charge–voltage (Q–V) relationship was fitted with a single Boltzmann function, supporting the idea that only one charge system is required to account for the time course of Ig,on and the voltage dependence of Qon. The voltage (V½) for half movement of gating charge was −8.4 ± 4.0 mV (n= 6), which closely matches the voltage dependence of activation of Kv3.2b ionic currents reported before. Depolarizations to more positive potentials than 0 mV decreased the amplitude and slowed the decay of the off‐gating currents (Ig,off), suggesting that a rate‐limiting step in opening was present in Kv3 channels as in Shaker and other Kv channels. Return of charge was negatively shifted along the potential axis with a V½ of Qoff of −80.9 ± 0.8 mV (n= 3), which allowed ∼90% charge return upon repolarization to −100 mV. BDS‐II toxin apparently reduced Ig,on, and greatly slowed the kinetics of Ig,on, while shifting the Q–V relationship in the depolarizing direction. However, the Q–V relationship remained well fitted by a single Boltzmann function. These data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels.
Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance
Authors: Pierno Sabata , Desaphy Jean‐François , Liantonio Antonella , De Luca Annamaria , Zarrilli Antonia , Mastrofrancesco Lisa , Procino Giuseppe , Valenti Giovanna , Conte Camerino Diana
Published: September 2007

Muscle disuse produced by hindlimb unloading (HU) induces severe atrophy and slow‐to‐fast fibre type transition of the slow‐twitch soleus muscle (Sol). After 2 weeks HU, the resting ClC‐1 chloride conductance (gCl) of sarcolemma, which controls muscle excitability, increases in Sol toward a value typical of the fast‐twitch EDL muscle. After 3 days of HU, the gCl increases as well before initiation of fibre type transition. Since ClC‐1 channels are acutely silenced by PKC‐dependent phosphorylation, we studied the modulation of gCl by PKC and serine–threonine phosphatase in Sol during HU, using a number of pharmacological tools. We show that a fraction of ClC‐1 channels of control Sol are maintained in an inactive state by PKC basal activity, which contributes to the lower gCl in control Sol compared to EDL. After 14 days of HU, PKC/phosphatase manipulation produces effects on Sol gCl that corroborate the partial slow‐to‐fast transition. After 3 days of HU, the early increase of gCl in Sol is entirely attributable to a reduction of PKC activity and/or activation of phosphatase, maintaining ClC‐1 channels in a fully active state. Accordingly, we found that HU reduces expression of PKCα, ɛ, and θ isoenzymes in Sol and EDL muscles and reduces total PKC activity. Moreover, we show that the rheobase current is increased in Sol muscle fibres as soon as after 3 days of HU, most probably in relation to the increased gCl. In conclusion, Sol muscle disuse is characterized by a rapid reduction of PKC activity, which reduces muscle excitability and is likely to contribute to disuse‐induced muscle impairment.
Modal Analysis of Nonviscously Damped Beams
Authors: Adhikari S. , Friswell M. I. , Lei Y.
Published: September 2007

Linear dynamics of Euler–Bernoulli beams with nonviscous nonlocal damping is considered. It is assumed that the damping force at a given point in the beam depends on the past history of velocities at different points via convolution integrals over exponentially decaying kernel functions. Conventional viscous and viscoelastic damping models can be obtained as special cases of this general damping model. The equation of motion of the beam with such a general damping model results in a linear partial integro-differential equation. Exact closed-form equations of the natural frequencies and mode shapes of the beam are derived. Numerical examples are provided to illustrate the new results.
Magnetic Force and Thermal Expansion as Failure Mechanisms of Electrothermal MEMS Actuators Under Electrostatic Discharge Testing
Authors: Weiss Jonathan D.
Published: September 2007

Like microelectronic circuits, microelectromechanical systems (MEMS) devices are susceptible to damage by electrostatic discharge (ESD). At Sandia National Laboratories, polysilicon electrothermal MEMS actuators have been subjected to ESD pulses to examine that susceptibility. Failures, in the form of cracks at points of high stress concentration, occurred that could not be explained by thermal degradation of the polysilicon caused by excessive heating, or by excessive displacement of the legs of the actuator of the same nature that occur in normal operation. One hypothesis presented in this paper is that the internal magnetic forces between the legs of the actuator, resulting from the ESD-associated high current pulses, might produce vibrations of amplitude sufficient to produce these cracks. However, a dynamic analysis based on simple beam theory indicated that such cracks are unlikely to occur, except under rather extreme conditions. On the other hand, these same current pulses also cause resistive heating of the legs and, therefore, thermally induced compression that can lead to buckling. Buckling stresses, particularly when augmented by magnetic forces, can readily explain failure. Both the magnetic and thermal analyses were performed using the human body model and the machine model of ESD. A justification for ignoring shuttle motion and eddy currents induced in the substrate during the ESD pulse is presented, as well.
Coactivation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies
Authors: Stommel Jayne M. , Kimmelman Alec C. , Ying Haoqiang , Nabioullin Roustem , Ponugoti Aditya H. , Wiedemeyer Ruprecht , Stegh Alexander H. , Bradner James E. , Ligon Keith L. , Brennan Cameron , Chin Lynda , DePinho Ronald A.
Published: September 2007

Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anticancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are coactivated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple concomitantly activated RTKs. Combinations of RTK inhibitors and/or RNA interference, but not single agents, decreased signaling, cell survival, and anchorage-independent growth even in glioma cells deficient in PTEN, a frequently inactivated inhibitor of PI3K. Thus, effective GBM therapy may require combined regimens targeting multiple RTKs.