To serve as a robust internal circadian clock, the cell‐autonomous molecular and electrophysiological activities of the individual neurons of the mammalian suprachiasmatic nucleus (SCN) are ...coordinated in time and neuroanatomical space. Although the contributions of the chemical and electrical interconnections between neurons are essential to this circuit‐level orchestration, the features upon which they operate to confer robustness to the ensemble signal are not known. To address this, we applied several methods to deconstruct the interactions between the spatial and temporal organisation of circadian oscillations in organotypic slices from mice with circadian abnormalities. We studied the SCN of mice lacking Cryptochrome genes (Cry1 and Cry2), which are essential for cell‐autonomous oscillation, and the SCN of mice lacking the vasoactive intestinal peptide receptor 2 (VPAC2‐null), which is necessary for circuit‐level integration, in order to map biological mechanisms to the revealed oscillatory features. The SCN of wild‐type mice showed a strong link between the temporal rhythm of the bioluminescence profiles of PER2::LUC and regularly repeated spatially organised oscillation. The Cry‐null SCN had stable spatial organisation but lacked temporal organisation, whereas in VPAC2‐null SCN some specimens exhibited temporal organisation in the absence of spatial organisation. The results indicated that spatial and temporal organisation were separable, that they may have different mechanistic origins (cell‐autonomous vs. interneuronal signaling) and that both were necessary to maintain robust and organised circadian rhythms throughout the SCN. This study therefore provided evidence that the coherent emergent properties of the neuronal circuitry, revealed in the spatially organised clusters, were essential to the pacemaking function of the SCN.
We study the cellular and network organisation of the suprachiasmatic nucleus (SCN) in wild type and mutant mice using patterns of PER2 oscillations across the tissue in a slice preparation. Results in wild type mice, Cryptochrome‐null mice, and animals lacking the receptor for VIP reveal that spatial and temporal organisations are separable and may have different mechanistic origins. Coupling of the two is necessary to maintain robust and organised circadian rhythmicity throughout the SCN.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Managing pelagic shark stocks requires information about the movement patterns and fisheries interactions of all age classes, including young-of-the-year (YOY; age-0), which, for many species, is ...particularly scant. This study investigated the vertical and horizontal movements of YOY blue sharks Prionace glauca and shortfin makos Isurus oxyrinchus in the Southern California Bight (SCB) ecoregion using pop-up satellite archival tags (PSATs) and fishery data. Geolocation estimates from PSATs (n = 5 for each species) occurred entirely within the SCB ecoregion and exclusive economic zones of the USA and México (mean tracking period: 46.1 ± 24.8 d). YOY blue sharks spent 96.4% of their time at <40 m depth (60.4% <2 m) and exhibited reverse diel vertical migration (greater nighttime depths). YOY shortfin makos spent 97.0% of their time at <40 m (24.8% <2 m) and exhibited a ‘midday dip’ of 5–10 m below the surface, centered around solar noon. These differences in vertical movements likely reflect foraging tactics. Additionally, observer data from the California drift gillnet fishery suggest juvenile blue sharks and shortfin makos move seasonally along the coast, northward from late summer to early fall and southward from late autumn to early winter. Age classes for both species exhibited latitudinal segregation, with smaller blue sharks and larger shortfin makos found farther north. The SCB ecoregion has long been regarded as a nursery area for both species; however, our data, in combination with previous studies, suggest this important habitat is much more extensive, comprising the highly productive continental margins spanning approximately 27.7–46.2°N for blue sharks and 23.4–34.5°N for shortfin makos.
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Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to ...rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electron laser sources.
Traditional approaches to the study of food webs emphasize the transfer of local primary productivity in the form of living plant organic matter across trophic levels. However, dead organic matter, ...or detritus, a common feature of most ecosystems plays a frequently overlooked role as a dynamic heterogeneous resource and habitat for many species. We develop an integrative framework for understanding the impact of detritus that emphasizes the ontogeny and heterogeneity of detritus and the various ways that explicit inclusion of detrital dynamics alters generalizations about the structure and functioning of food webs. Through its influences on food web composition and dynamics, detritus often increases system stability and persistence, having substantial effects on trophic structure and biodiversity. Inclusion of detrital heterogeneity in models of food web dynamics is an essential new direction for ecological research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid ...overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.
Opioids are powerful analgesic drugs that are used clinically to treat pain. However, chronic opioid use causes compensatory neuroadaptations that result in greater pain sensitivity during ...withdrawal, known as opioid withdrawal-induced hyperalgesia (OWIH). Cold nociception tests are commonly used in humans, but preclinical studies often use mechanical and heat stimuli to measure OWIH. Thus, further characterization of cold nociception stimuli is needed in preclinical models. We assessed three cold nociception tests-thermal gradient ring (5-30 °C, 5-50 °C, 15-40 °C, and 25-50 °C), dynamic cold plate (4 °C to -1 °C at -1 °C/min, -1 °C to 4 °C at +1 °C/min), and stable cold plate (10 °C, 6 °C, and 2 °C)-to measure hyperalgesia in a mouse protocol of heroin dependence. On the thermal gradient ring, mice in the heroin withdrawal group preferred warmer temperatures, and the results depended on the ring's temperature range. On the dynamic cold plate, heroin withdrawal increased the number of nociceptive responses, with a temperature ramp from 4 °C to -1 °C yielding the largest response. On the stable cold plate, heroin withdrawal increased the number of nociceptive responses, and a plate temperature of 2 °C yielded the most significant increase in responses. Among the three tests, the stable cold plate elicited the most robust change in behavior between heroin-dependent and nondependent mice and had the highest throughput. To pharmacologically characterize the stable cold plate test, we used μ-opioid and non-opioid receptor-targeting drugs that have been previously shown to reverse OWIH in mechanical and heat nociception assays. The full μ-opioid receptor agonist methadone and μ-opioid receptor partial agonist buprenorphine decreased OWIH, whereas the preferential μ-opioid receptor antagonist naltrexone increased OWIH. Two N-methyl-d-aspartate receptor antagonists (ketamine, MK-801), a corticotropin-releasing factor 1 receptor antagonist (R121919), a β
-adrenergic receptor antagonist (butoxamine), an α
-adrenergic receptor agonist (lofexidine), and a 5-hydroxytryptamine-3 receptor antagonist (ondansetron) had no effect on OWIH. These data demonstrate that the stable cold plate at 2 °C yields a robust, reliable, and concise measure of OWIH that is sensitive to opioid agonists.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
7.
The T2K fine-grained detectors Amaudruz, P.-A.; Barbi, M.; Bishop, D. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2012, Volume:
696
Journal Article
Peer reviewed
Open access
T2K is a long-baseline neutrino oscillation experiment searching for νe appearance in a νμ beam. The beam is produced at the J-PARC accelerator complex in Tokai, Japan, and the neutrinos are detected ...by the Super-Kamiokande detector located 295km away in Kamioka. A suite of near detectors (ND280) located 280 m downstream of the production target is used to characterize the components of the beam before they have had a chance to oscillate and to better understand various neutrino interactions on several nuclei. This paper describes the design and construction of two massive fine-grained detectors (FGDs) that serve as active targets in the ND280 tracker. One FGD is composed solely of scintillator bars while the other is partly scintillator and partly water. Each element of the FGDs is described, including the wavelength shifting fiber and Multi-Pixel Photon Counter used to collect the light signals, the readout electronics, and the calibration system. Initial tests and in situ results of the FGDs' performance are also presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The common thresher shark Alopias vulpinus constitutes an important commercial fishery on the Pacific coasts of both the USA and Mexico. However, little is known about the juvenile phase of this ...species. This study used a combination of pop-up archival satellite tagging, tag-recapture, and fishery catch data to investigate the movement patterns, habitat preferences, ecology, and geographic distribution of juvenile common thresher sharks along the Pacific coast of the USA and Mexico. Juvenile threshers primarily utilized continental shelf waters, with a geographic range extending from Punta Eugenia in Baja California, Mexico (27.8° N) north to Morro Bay, California (35.3° N). Within this range, sharks were found at significantly lower latitudes in March and April. Satellite-tagged juvenile threshers exhibited diel patterns of vertical distribution, primarily inhabiting the upper 20 m of the water column by night, and significantly greater depths by day. In addition, juvenile threshers made frequent daytime dives to depths exceeding 50 m, with a maximum recorded dive depth of 192 m. Tracked sharks were most commonly associated with ambient water temperatures between 14 and 17°C, and inhabited significantly warmer temperatures at night than during the day. No tidal or lunar influence on vertical distribution was found, and vertical habitat utilization did not increase concomitantly with shark size. This study is the first to document movements of juvenile threshers between US and Mexican waters, highlighting the need for bi-national management strategies for this shared fishery resource.
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We report a measurement of the flux-integrated cross section for inclusive muon neutrino charged-current interactions on carbon. The double-differential measurements are given as a function of the ...muon momentum and angle. Relative to our previous publication on this topic, these results have an increased angular acceptance and higher statistics. The data sample presented here corresponds to 5.7×1020 protons on target. The total flux-integrated cross section is measured to be (6.950±0.662)×10−39 cm2 nucleon−1 and is consistent with our simulation.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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