Ten-Hour Exposure to Low-Dose Ketamine Enhances Corticostriatal Cross-Frequency Coupling and Hippocampal Broad-Band Gamma Oscillations

Introduction: Treatment-resistant depression, post-traumatic stress disorder, chronic pain, and L-DOPA-induced dyskinesia in Parkinson’s disease are characterized by hypersynchronous neural oscillations. Sub-anesthetic ketamine is effective at treating these conditions, and this may relate to ketamine’s capacity to reorganize oscillatory activity throughout the brain. For example, a single ketamine injection increases gamma (∼40 Hz) and high-frequency oscillations (HFOs, 120–160 Hz) in the cortex, hippocampus, and striatum. While the effects of single injections have been investigated, clinical ketamine treatments can involve 5-h up to 3-day sub-anesthetic infusions. Little is known about the effects of such prolonged exposure on neural synchrony. We hypothesized that hours-long exposure entrains circuits that generate HFOs so that HFOs become sustained after ketamine’s direct effects on receptors subside.Methods: Local-field recordings were acquired from motor cortex (M1), striatum, and hippocampus of behaving rats (n = 8), and neural responses were measured while rats received 5 ketamine injections (20 mg/kg, i.p., every 2 h, 10-h exposure). In a second experiment, the same animals received injections of D1-receptor antagonist (SCH-23390, 1 mg/kg, i.p.) prior to ketamine injection to determine if D1 receptors were involved in producing HFOs.Results: Although HFOs remained stable throughout extended ketamine exposure, broad-band high-frequency activity (40–140 Hz) in the hippocampus and delta-HFO cross-frequency coupling (CFC) in dorsal striatum increased with the duration of exposure. Furthermore, while ketamine-triggered HFOs were not affected by D1 receptor blockade, ketamine-associated gamma in motor cortex was suppressed, suggesting involvement of D1 receptors in ketamine-mediated gamma activity in motor cortex.Conclusion: Prolonged ketamine exposure does not enhance HFOs in corticostriatal circuits, but, instead, enhances coordination between low and high frequencies in the striatum and reduces synchrony in the hippocampus. Increased striatal CFC may facilitate spike-timing dependent plasticity, resulting in lasting changes in motor activity. In contrast, the observed wide-band high-frequency “noise” in the hippocampus suggests that ketamine disrupts action-potential timing and reorganizes connectivity in this region. Differential restructuring of corticostriatal and limbic circuits may contribute to ketamine’s clinical benefits

Comparison of different wheelchair seating on thermoregulation and perceptual responses in thermoneutral and hot conditions in children

We examined the effects of 4 different wheelchair seatings on physiological and perceptual measures in 21 healthy, pre-pubertal children (9 ± 2 years). Participants were able-bodied and did not regularly use a wheelchair. Participants sat for 2 h in Neutral (∼22.5 °C, ∼40%RH) and Hot (∼35 °C, ∼37%RH) conditions. Four seating technologies were: standard incontinent cover and cushion (SEAT1); standard incontinent cover with new cushion (SEAT2) were tested in Neutral and Hot; new non-incontinent cover with new cushion (SEAT3); new incontinent cover and new cushion (SEAT4) were tested in Neutral only. Measurements included skin blood flow (SkBF), sweating rate (SR) and leg skin temperature (TlegB) on the bottom of the leg (i.e. skin-seat interface), heart rate (HR), mean skin temperature, tympanic temperature, thermal comfort, and thermal sensation. During Neutral, SkBF and TlegB were lower (∼50% and ∼1 °C, respectively) and SR higher (∼0.5 mg cm−2·min−1) (p  0.05). During Hot, HR and temperatures were higher than in Neutral but there were no differences (p > 0.05) between SEATs. New cover and cushion improved thermoregulatory responses during Neutral but not Hot. An impermeable incontinent cover negated improvements from cushion design. Seat cover appears more important than seat cushion during typical room conditions

Combining the [ABA] and net photosynthesis-based model equations of stomatal conductance

Stomatal conductance gs is variously depicted as being dependent on environmental conditions ( Jarvis, 976), transpiration ( Monteith, 1995), net photosynthesis ( Leuning, 1995) or chemical signalling arriving in the xylem ( Tardieu and Davies, 1993). Accurate descriptions of gs are being increasingly demanded in the large-scale land surface model components of General Circulation Models (GCMs) to predict future land-atmospheric fluxes of water vapour, heat and carbon dioxide. The JULES model, for instance, uses the net photosynthesis description combined with a relatively simple semi-linear dependence on soil moisture content that modulates the photosynthesis dependence ( Cox et al., 1998). Dewar (2002) combines the Leuning (1995) and Tardieu and Davies (1993) models. We revisit that combination, and discuss whether the Vapour Pressure Deficit (VPD) implicit in both components is different or in common. Further, we show a potential re-arrangement of the combined equations reveals that this model for gs can be considered as being dependent on only four variables: evaporative flux JwJw, net photosynthesis an, soil moisture content θ and ambient CO2 concentration ca. Expressed this way, gs is influenced by two relatively slowly varying stores of the hydrological and carbon cycles (soil water content and atmospheric CO2) and two more rapidly fluctuating fluxes from both cycles (evaporation and net photosynthesis). We consider how the modelling structure and its response to both canopy-level and soil environmental controls may make it suitable for inclusion in GCMs, and what this entails in terms of parameterisation

Muon anomalous magnetic dipole moment in supersymmetric theories

We study the muon anomalous magnetic dipole moment in supersymmetric theories. The impact of the recent Brookhaven E821 experimental measurement on both model-independent and model-dependent supersymmetric parameter spaces is discussed in detail. We find that values of tan\beta as low as 3 can be obtained while remaining within the E821 one-sigma bound. This requires a light smuon; however, we show that, somewhat surprisingly, no model-independent bound can be placed on the mass of the lightest chargino for any tan\beta greater than or equal to 3. We also show that the maximum contributions to the anomalous magnetic moment are insensitive to CP-violating phases. We provide analyses of the supersymmetric contribution to the muon anomalous magnetic moment in dilaton-dominated supergravity models and gauge-mediated supersymmetry-breaking models. Finally, we discuss how other phenomena, such as $B(b\to s\gamma)$, relic abundance of the lightest superpartner, and the Higgs mass may be correlated with the anomalous magnetic moment, but do not significantly impact the viability of a supersymmetric explanation, or the mass limits obtainable on smuons and charginos.Comment: 28 page

The genome of ε15, a serotype-converting, Group E1 Salmonella enterica-specific bacteriophage

AbstractThe genome sequence of the Salmonella enterica serovar Anatum-specific, serotype-converting bacteriophage ε15 has been completed. The nonredundant genome contains 39,671 bp and 51 putative genes. It most closely resembles the genome of φV10, an Escherichia coli O157:H7-specific temperate phage, with which it shares 36 related genes. More distant relatives include the Burkholderia cepacia-specific phage, BcepC6B (8 similar genes), the Bordetella bronchiseptica-specific phage, BPP-1 (8 similar genes) and the Photobacterium profundum prophage, P Pφpr1 (6 similar genes).ε15 gene identifications based on homologies with known gene families include the terminase small and large subunits, integrase, endolysin, two holins, two DNA methylase enzymes (one adenine-specific and one cytosine-specific) and a RecT-like enzyme. Genes identified experimentally include those coding for the serotype conversion proteins, the tail fiber, the major capsid protein and the major repressor. ε15's attP site and the Salmonella attB site with which it interacts during lysogenization have also been determined

Caldera resurgence during the 2018 eruption of Sierra Negra volcano, Galápagos Islands.

Recent large basaltic eruptions began after only minor surface uplift and seismicity, and resulted in caldera subsidence. In contrast, some eruptions at Galápagos Island volcanoes are preceded by prolonged, large amplitude uplift and elevated seismicity. These systems also display long-term intra-caldera uplift, or resurgence. However, a scarcity of observations has obscured the mechanisms underpinning such behaviour. Here we combine a unique multiparametric dataset to show how the 2018 eruption of Sierra Negra contributed to caldera resurgence. Magma supply to a shallow reservoir drove 6.5 m of pre-eruptive uplift and seismicity over thirteen years, including an Mw5.4 earthquake that triggered the eruption. Although co-eruptive magma withdrawal resulted in 8.5 m of subsidence, net uplift of the inner-caldera on a trapdoor fault resulted in 1.5 m of permanent resurgence. These observations reveal the importance of intra-caldera faulting in affecting resurgence, and the mechanisms of eruption in the absence of well-developed rift systems

Gefitinib and <i>EGFR</i> Gene Copy Number Aberrations in Esophageal Cancer

Purpose: The cancer esophagus gefitinib (COG) trial demonstrated improved progression free survival with the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib relative to placebo in advanced esophageal cancer patients with disease progression after chemotherapy. Rapid and durable responses were observed in a minority. We hypothesised that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Patients and Methods: A pre-specified blinded molecular analysis of COG trial tumours was conducted to compare efficacy of gefitinib to placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF and PIK3CA mutation status. EGFR CNG was determined by fluorescent insitu hybridisation (FISH) using pre-specified criteria and EGFR FISH positive defined as high polysomy or amplification. Results: Biomarker data were available for 340 patients. In EGFR FISH positive tumours (20.2%) overall survival was improved with gefitinib compared to placebo (hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.35, 1.00 p=0.05). In EGFR FISH negative tumours there was no difference in overall survival with gefitinib compared to placebo (HR for death, 0.90, 95% CI 0.69, 1.18 p=0.46). EGFR amplification (7.2%) patients gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI 0.07-0.64; p=0.006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF and PIK3CA mutations, or for any mutation versus none. Conclusion: EGFR CNG assessed by FISH appears to identify a subgroup of esophageal cancer patients who may benefit from gefitinib as a second line treatment, and suggests that anti-EGFR 3 therapies should be investigated in prospective clinical trials in different settings in EGFR FI SH positive, and in particular EGFR amplified, esophageal cancer

Barrett's esophagus: prevalence–incidence and etiology–origins

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86957/1/j.1749-6632.2011.06042.x.pd