Gastrointestinal effects following acupuncture at Pericardium-6 and Stomach-36 in healthy dogs: a pilot study.

OBJECTIVES: To quantify changes in gastric and intestinal emptying times in the conscious dog following gastrointestinal acupoint stimulation. MATERIALS AND METHODS: In a randomised, blinded crossover study, six dogs were fed 30×1.5 mm barium-impregnated polyethylene spheres and underwent: (1) no acupuncture (Control); (2) stimulation of target points PC6 and ST36 (Target) and (3) stimulation of non-target points LU7 and BL55 (Sham). Abdominal radiographs were assessed immediately after feeding the spheres and every hour for 12 hours and their number in the stomach and large intestines was counted. RESULTS: The number of barium-impregnated polyethylene spheres found distal to the stomach was less in the Target group compared to the Control and Sham groups between hours 2 and 4, but no differences between groups were seen for the remainder of the treatment period. The number of spheres found within the colon/rectum was less in the Target group compared to the Control and Sham groups between hours 4 and 6, and compared to the Sham group only at hour 7 but no differences between groups were seen after hour 8. CLINICAL SIGNIFICANCE: Acupuncture targeted at the gastrointestinal tract of dogs was associated briefly with slowed gastric emptying and gastrointestinal transit time. This foundational study lays the groundwork for additional studies of acupuncture effects associated with altered physiologic states.

Significant Excess of Electronlike Events in the MiniBooNE Short-Baseline Neutrino Experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions.

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

In vivo imaging of tau pathology using multi-parametric quantitative MRI.

As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.

Neither serotonin nor adenosine-dependent mechanisms preserve ventilatory capacity in ALS rats.

In rats over-expressing SOD1G93A, ventilation is preserved despite significant loss of respiratory motor neurons. Thus, unknown forms of compensatory respiratory plasticity may offset respiratory motor neuron cell death. Although mechanisms of such compensation are unknown, other models of respiratory motor plasticity may provide a conceptual guide. Multiple cellular mechanisms give rise to phrenic motor facilitation; one mechanism requires spinal serotonin receptor and NADPH oxidase activity whereas another requires spinal adenosine receptor activation. Here, we studied whether these mechanisms contribute to compensatory respiratory plasticity in SOD1G93A rats. Using plethysmography, we assessed ventilation in end-stage SOD1G93A rats after: (1) serotonin depletion with parachlorophenylalanine (PCPA), (2) serotonin (methysergide) and A2A (MSX-3) receptor inhibition, (3) NADPH oxidase inhibition (apocynin), and (4) combined treatments. The ability to increase ventilation was not decreased by individual or combined treatments; thus, these mechanisms do not maintain breathing capacity at end-stage motor neuron disease. Possible mechanisms giving rise to enhanced breathing capacity with combined treatment in end-stage SOD1G93A rats are discussed.

Improved search for ν¯(µ)→ν¯(e) oscillations in the MiniBooNE experiment.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν[over ¯](e) appearance data from 11.27×10(20) protons on target in the antineutrino mode, an increase of approximately a factor of 2 over the previously reported results. An event excess of 78.4±28.5 events (2.8σ) is observed in the energy range 200

Cervical spinal demyelination with ethidium bromide impairs respiratory (phrenic) activity and forelimb motor behavior in rats.

Although respiratory complications are a major cause of morbidity/mortality in many neural injuries or diseases, little is known concerning mechanisms whereby deficient myelin impairs breathing, or how patients compensate for such changes. Here, we tested the hypothesis that respiratory and forelimb motor functions are impaired in a rat model of focal dorsolateral spinal demyelination (ethidium bromide, EB). Ventilation, phrenic nerve activity and horizontal ladder walking were performed 7-14 days post-C2 injection of EB or vehicle (SHAM). EB caused dorsolateral demyelination at C2-C3 followed by significant spontaneous remyelination at 14 days post-EB. Although ventilation did not differ between groups, ipsilateral integrated phrenic nerve burst amplitude was significantly reduced versus SHAM during chemoreceptor activation at 7 days post-EB but recovered by 14 days. The ratio of ipsi- to contralateral phrenic nerve amplitude correlated with cross-sectional lesion area. This ratio was significantly reduced 7 days post-EB versus SHAM during baseline conditions, and versus SHAM and 14-day groups during chemoreceptor activation. Limb function ipsilateral to EB was impaired 7 days post-EB and partially recovered by 14 days post-EB. EB provides a reversible model of focal, spinal demyelination, and may be a useful model to study mechanisms of functional impairment and recovery via motor plasticity, or the efficacy of new therapeutic interventions to reduce severity or duration of disease.

Nondestructive sampling of insect DNA from defensive secretion.

Nondestructive techniques to obtain DNA from organisms can further genetic analyses such as estimating genetic diversity, dispersal and lifetime fitness, without permanently removing individuals from the population or removing body parts. Possible DNA sources for insects include frass, exuviae, and wing and leg clippings. However, these are not feasible approaches for organisms that cannot be removed from their natural environment for long periods or when adverse effects of tissue removal must be avoided. This study evaluated the impacts and efficacy of extracting haemolymph from a defensive secretion to obtain DNA for amplification of microsatellites using a nondestructive technique. A secretion containing haemolymph was obtained from Bolitotherus cornutus (the forked fungus beetle) by perturbation of the defensive gland with a capillary tube. A laboratory experiment demonstrated that the sampling methodology had no impact on mortality, reproductive success or gland expression. To evaluate the quality of DNA obtained in natural samples, haemolymph was collected from 187 individuals in the field and successfully genotyped at nine microsatellite loci for 95.7% of samples. These results indicate that haemolymph-rich defensive secretions contain DNA and can be sampled without negative impacts on the health or fitness of individual insects.

A transient assay for recombination demonstrates that Arabidopsis SNM1 and XRCC3 enhance non-homologous recombination.

Replacement of endogenous genes by homologous recombination is rare in plants; the majority of genetic modifications are the result of transforming DNA molecules undergoing random genomic insertion by way of non-homologous recombination. Factors that affect chromatin remodeling and DNA repair are thought to have the potential to enhance the frequency of homologous recombination in plants. Conventional tools to study the frequencies of genetic recombination often rely on stable transformation-based approaches, with these systems being rarely capable of high-throughput or combinatorial analysis. We developed a series of vectors that use chemiluminescent (LUC and REN) reporter genes to assay the relative frequency of homologous and non-homologous recombination in plants. These transient assay vectors were used to screen 14 candidate genes for their effects on recombination frequencies in Nicotiana benthamiana plants. Over-expression of Arabidopsis genes with sequence similarity to SNM1 from yeast and XRCC3 from humans enhanced the frequency of non-homologous recombination when assayed using two different donor vectors. Transient N. benthamiana leaf systems were also used in an alternative assay for preliminary measurements of homologous recombination frequencies, which were found to be enhanced by over-expression of RAD52, MIM and RAD51 from yeast, as well as CHR24 from Arabidopsis. The findings for the assays described here are in line with previous studies that analyzed recombination frequencies using stable transformation. The assays we report have revealed functions in non-homologous recombination for the Arabidopsis SNM1 and XRCC3 genes, so the suppression of these genes' expression offers a potential means to enhance the gene targeting frequency in plants. Furthermore, our findings also indicate that plant gene targeting frequencies could be enhanced by over-expression of RAD52, MIM, CHR24, and RAD51 genes.

Ventilatory impairment in the dysmyelinated Long Evans shaker rat.

Although respiratory complications significantly contribute to morbidity/mortality in advanced myelin disorders, little is known concerning mechanisms whereby dysmyelination impairs ventilation, or how patients compensate (i.e. plasticity). To establish a model for studies concerning mechanisms of ventilatory impairment/compensation, we tested the hypotheses that respiratory function progressively declines in a model of CNS dysmyelination, the Long Evans shaker rat (les). The observed impairment is associated with abnormal inspiratory neural output. Minimal myelin staining was found throughout the CNS of les rats, including the brainstem and cervical bulbospinal tracts. Ventilation (via whole-body plethysmography) and phrenic motor output were assessed in les and wild-type (WT) rats during baseline, hypoxia (11% O(2)) and hypercapnia (7% CO(2)). Hypercapnic ventilatory responses were similar in young adult les and WT rats (2 months old); in hypoxia, rats exhibited seizure-like activity with sustained apneas. However, 5-6 month old les rats exhibited decreased breathing frequencies, mean inspiratory flow (V(T)/T(I)) and ventilation (V (E)) during baseline and hypercapnia. Although phrenic motor output exhibited normal burst frequency and amplitude in 5-6 month old les rats, intra-burst activity was abnormal. In WT rats, phrenic activity was progressive and augmenting; in les rats, phrenic activity was decrementing with asynchronized, multipeaked activity. Thus, although ventilatory capacity is maintained in young, dysmyelinated rats, ventilatory impairment develops with age, possibly through discoordination in respiratory motor output. This study is the first reporting age-related breathing abnormalities in a rodent dysmyelination model, and provides the foundation for mechanistic studies of respiratory insufficiency and therapeutic interventions.

Event excess in the MiniBooNE search for ¯νµâ†’¯νe oscillations.

The MiniBooNE experiment at Fermilab reports results from a search for ¯ν_{µ}→¯ν_{e} oscillations, using a data sample corresponding to 5.66×10²° protons on target. An excess of 20.9±14.0 events is observed in the energy range 475

Search for electron antineutrino appearance at the deltam(2) approximately 1 eV(2) Scale.

The MiniBooNE Collaboration reports initial results from a search for nu(mu)-->nu(e) oscillations. A signal-blind analysis was performed using a data sample corresponding to 3.39x10(20) protons on target. The data are consistent with background prediction across the full range of neutrino energy reconstructed assuming quasielastic scattering, 200

Search for muon neutrino and antineutrino disappearance in MiniBooNE.

The MiniBooNE Collaboration reports a search for nu_{micro} and nu[over]_{micro} disappearance in the Deltam;{2} region of 0.5-40 eV;{2}. These measurements are important for constraining models with extra types of neutrinos, extra dimensions, and CPT violation. Fits to the shape of the nu_{micro} and nu[over]_{micro} energy spectra reveal no evidence for disappearance at the 90% confidence level (C.L.) in either mode. The test of nu[over]_{micro} disappearance probes a region below Deltam;{2} = 40 eV;{2} never explored before.

Measurement of the ratio of the numu charged-current single-pion production to quasielastic scattering with a 0.8 GeV neutrino beam on mineral oil.

Using high statistics samples of charged-current numu interactions, the MiniBooNE [corrected] Collaboration reports a measurement of the single-charged-pion production to quasielastic cross section ratio on mineral oil (CH2), both with and without corrections for hadron reinteractions in the target nucleus. The result is provided as a function of neutrino energy in the range 0.4 GeV

Measurement of numicro and nue events in an off-axis horn-focused neutrino beam.

We report the first observation of off-axis neutrino interactions in the MiniBooNE detector from the NuMI beam line at Fermilab. The MiniBooNE detector is located 745 m from the NuMI production target, at 110 mrad angle (6.3 degrees) with respect to the NuMI beam axis. Samples of charged-current quasielastic numicro and nue interactions are analyzed and found to be in agreement with expectation. This provides a direct verification of the expected pion and kaon contributions to the neutrino flux and validates the modeling of the NuMI off-axis beam.

Unexplained excess of electronlike events from a 1-GeV neutrino beam.

The MiniBooNE Collaboration observes unexplained electronlike events in the reconstructed neutrino energy range from 200 to 475 MeV. With 6.46x10;{20} protons on target, 544 electronlike events are observed in this energy range, compared to an expectation of 415.2+/-43.4 events, corresponding to an excess of 128.8+/-20.4+/-38.3 events. The shape of the excess in several kinematic variables is consistent with being due to either nu_{e} and nu[over ]_{e} charged-current scattering or nu_{mu} neutral-current scattering with a photon in the final state. No significant excess of events is observed in the reconstructed neutrino energy range from 475 to 1250 MeV, where 408 events are observed compared to an expectation of 385.9+/-35.7 events.

Measurement of muon neutrino quasielastic scattering on carbon.

The observation of neutrino oscillations is clear evidence for physics beyond the standard model. To make precise measurements of this phenomenon, neutrino oscillation experiments, including MiniBooNE, require an accurate description of neutrino charged current quasielastic (CCQE) cross sections to predict signal samples. Using a high-statistics sample of nu_(mu) CCQE events, MiniBooNE finds that a simple Fermi gas model, with appropriate adjustments, accurately characterizes the CCQE events observed in a carbon-based detector. The extracted parameters include an effective axial mass, M_(A)(eff)=1.23+/-0.20 GeV, that describes the four-momentum dependence of the axial-vector form factor of the nucleon, and a Pauli-suppression parameter, kappa=1.019+/-0.011. Such a modified Fermi gas model may also be used by future accelerator-based experiments measuring neutrino oscillations on nuclear targets.

Search for electron neutrino appearance at the Delta m2 approximately 1 eV2 scale.

The MiniBooNE Collaboration reports first results of a search for nu e appearance in a nu mu beam. With two largely independent analyses, we observe no significant excess of events above the background for reconstructed neutrino energies above 475 MeV. The data are consistent with no oscillations within a two-neutrino appearance-only oscillation model.

Measurement of the nucleon strange-antistrange asymmetry at next-to-leading order in QCD from NuTeV Dimuon data.

We present a new measurement of the difference between the nucleon strange and antistrange quark distributions from dimuon events recorded by the NuTeV experiment at Fermilab. This analysis is the first to use a complete next to leading order QCD description of charm production from neutrino scattering. Dimuon events in neutrino deep inelastic scattering allow direct and independent study of the strange and antistrange content of the nucleon. We find a positive strange asymmetry with a significance of 1.6sigma. We also report a new measurement of the charm mass.

Occurrence of infected amoebae in cooling towers compared with natural aquatic environments: implications for emerging pathogens.

Many species of bacteria pathogenic to humans, such as Legionella, are thought to have evolved in association with amoebal hosts. Several novel unculturable bacteria related to Legionella have also been found in amoebae, a few of which have been thought to be causes of nosocomial infections in humans. Because amoebae can be found in cooling towers, we wanted to know whether cooling tower environments might enhance the association between amoebae and bacterial pathogens of amoebae in order to identify potential "hot spots" for emerging human pathogens. To compare occurrence of infected amoebae in natural environments with those in cooling towers, 40 natural aquatic environments and 40 cooling tower samples were examined. Logistic regression analysis determined variables that were significant predictors of the occurrence of infected amoebae, which were found in 22 of 40 cooling tower samples but in only 3 of the 40 natural samples. An odds ratio showed that it is over 16 times more likely to encounter infected amoebae in cooling towers than in natural environments. Environmental data from cooling towers and natural habitats combined revealed dissolved organic carbon (DOC) and pH were predictors of the occurrence of the pathogens, however, when cooling tower data alone were analyzed, no variables accounted for the occurrence. Several bacteria have novel rRNA sequences, and most strains were not culturable outside of amoebae. Such pathogens of amoebae may spread to the environment via aerosols from cooling towers. Studies of emerging infectious diseases should strongly consider cooling towers as a source of amoeba-associated pathogens.