bluuebunny/crossref_metadata_2025_split huggingface dataset:
The photovoltage of rods and cones in the dark‐adapted mouse retina
Authors: Cangiano Lorenzo , Asteriti Sabrina , Cervetto Luigi , Gargini Claudia 
Published: May 2012

Key points
The mouse retina has become a key model for research on the function and dysfunction of the early stages of vision, but its photoreceptors have proven difficult to access with whole‐cell recording techniques.
We have optimized the mouse retinal slice preparation to the degree required for studying photoreceptors with a reasonably high yield.
We find that single photon processing in rods is considerably more efficient than previously thought, implying a more favourable transmission at the rod–rod bipolar cell synapse.
Cones were recorded much more frequently than their numeric proportion of ∼3% allowing us to obtain direct functional evidence suggestive of rod–cone coupling in the mouse.
This study opens the way for further investigations into mammalian photoreceptor function by exploiting the powerful molecular genetic approaches available in the mouse.
Abstract  Research on photoreceptors has led to important insights into how light signals are detected and processed in the outer retina. Most information about photoreceptor function, however, comes from lower vertebrates. The large majority of mammalian studies are based on suction pipette recordings of outer segment currents, a technique that doesn't allow examination of phenomena occurring downstream of phototransduction. Only a small number of whole‐cell recordings have been made, mainly in the macaque. Due to the growing importance of the mouse in vision research, we have optimized a retinal slice preparation that allows the reliable collection of perforated‐patch recordings from light responding rods and cones. Unexpectedly, the frequency of cone recordings was much higher than their numeric proportion of ∼3%. This allowed us to obtain direct functional evidence suggestive of rod–cone coupling in the mouse. Moreover, rods had considerably larger single photon responses than previously published for mammals (3.44 mV, SD 1.37, n= 19 at 24°C; 2.46 mV, SD 1.08, n= 10 at 36°C), and a relatively high signal/noise ratio (6.4, SD 1.8 at 24°C; 6.8, SD 2.8 at 36°C). Both findings imply a more favourable transmission at the rod–rod bipolar cell synapse. Accordingly, relatively few photoisomerizations were sufficient to elicit a half‐maximal response (6.7, SD 2.7, n= 5 at 24°C; 10.6, SD 1.7, n= 3 at 36°C), leading to a narrow linear response range. Our study demonstrates new features of mammalian photoreceptors and opens the way for further investigations into photoreceptor function using retinas from mutant mouse models.
Interneuron‐mediated inhibition synchronizes neuronal activity during slow oscillation
Authors: Chen Jen‐Yung , Chauvette Sylvain , Skorheim Steven , Timofeev Igor , Bazhenov Maxim 
Published: May 2012

Key points
A signature of deep sleep in the EEG is large‐amplitude fluctuation of field potential, which reflects alternating periods of activity and silence in the thalamocortical network.
Transitions between active and silent states of sleep slow oscillation are well synchronous between remote populations of neurons with the onsets of silent states synchronized better than the onsets of activity.
We found that synaptic inhibition plays a major role in terminating active cortical states; strong synaptic inhibition is necessary to synchronize onsets of silent states during normal sleep slow oscillation.
We further show that when synaptic inhibition is significantly reduced, active state termination is mediated by intrinsic hyperpolarizing conductances.
Our study suggests that inhibitory interaction in the cortical network actively mediates the patterns of neural activity during slow‐wave sleep and may, therefore, contribute to various brain functions developed during deep sleep.
Abstract  The signature of slow‐wave sleep in the electroencephalogram (EEG) is large‐amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron‐mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure‐like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms.
The Arabidopsis central vacuole as an expression system for intracellular transporters: functional characterization of the Cl−/H+ exchanger CLC‐7
Authors: Costa Alex , Gutla Paul Vijay Kanth , Boccaccio Anna , Scholz‐Starke Joachim , Festa Margherita , Basso Barbara , Zanardi Ilaria , Pusch Michael , Schiavo Fiorella Lo , Gambale Franco , Carpaneto Armando 
Published: May 2012

Key points
Ion transport proteins in intracellular membranes of eukaryotic cells play key roles in many physiological and pathological processes.
The function of many of these transporters is poorly understood, because their intracellular localization makes them difficult to study.
Here, we used the large organelle of plant cells, the central vacuole, as a novel system to study an intracellular transporter from animal cells.
Our data showed that the lysosomal chloride transporter CLC‐7 from rat constitutes a functional transport protein in the central vacuole of the model plant Arabidopsis thaliana (thale cress).
This novel approach has the potential to elucidate the transport properties of further, poorly studied intracellular ion channels and transporters.
Abstract  Functional characterization of intracellular transporters is hampered by the inaccessibility of animal endomembranes to standard electrophysiological techniques. Here, we used Arabidopsis mesophyll protoplasts as a novel heterologous expression system for the lysosomal chloride–proton exchanger CLC‐7 from rat. Following transient expression of a rCLC‐7:EGFP construct in isolated protoplasts, the fusion protein efficiently targeted to the membrane of the large central vacuole, the lytic compartment of plant cells. Membrane currents recorded from EGFP‐positive vacuoles were almost voltage independent and showed time‐dependent activation at elevated positive membrane potentials as a hallmark. The shift in the reversal potential of the current induced by a decrease of cytosolic pH was compatible with a 2Cl−/1H+ exchange stoichiometry. Mutating the so‐called gating glutamate into alanine (E245A) uncoupled chloride fluxes from the movement of protons, transforming the transporter into a chloride channel‐like protein. Importantly, CLC‐7 transport activity in the vacuolar expression system was recorded in the absence of the auxiliary subunit Ostm1, differently to recent data obtained in Xenopus oocytes using a CLC‐7 mutant with partial plasma membrane expression. We also show that plasma membrane‐targeted CLC‐7E245A is non‐functional in Xenopus oocytes when expressed without Ostm1. In summary, our data suggest the existence of an alternative CLC‐7 operating mode, which is active when the protein is not in complex with Ostm1. The vacuolar expression system has the potential to become a valuable tool for functional studies on intracellular ion channels and transporters from animal cells.
Rhythmic dendritic Ca2+ oscillations in thalamocortical neurons during slow non‐REM sleep‐related activity in vitro
Authors: Errington Adam C. , Hughes Stuart W. , Crunelli Vincenzo 
Published: May 2012

Key points
Sensory thalamocortical (TC) neurons are thought to play a crucial role in oscillatory brain activity typical of slow wave sleep.
Intrinsic oscillations in TC neurons rely upon expression of T‐type voltage gated Ca2+ channels.
We show that during sleep like firing patterns in TC neurons in brain slices, low threshold spikes mediated by T‐type channels produce global and rhythmic dendritic Ca2+ signals. In particular we show Ca2+ elevations in dendritic spine like structures during slow oscillatory activity.
We find that the duration of dendritic Ca2+ signals and the mean level of Ca2+ in TC neuron dendrites varies with oscillation frequency.
This global repetitive Ca2+ entry in to TC cells during oscillations could have significant implications for synaptic signalling and biochemical processes in these important sensory neurons.
Abstract  The distribution of T‐type Ca2+ channels along the entire somatodendritic axis of sensory thalamocortical (TC) neurons permits regenerative propagation of low threshold spikes (LTS) accompanied by global dendritic Ca2+ influx. Furthermore, T‐type Ca2+ channels play an integral role in low frequency oscillatory activity (<1–4 Hz) that is a defining feature of TC neurons. Nonetheless, the dynamics of T‐type Ca2+ channel‐dependent dendritic Ca2+ signalling during slow sleep‐associated oscillations remains unknown. Here we demonstrate using patch clamp recording and two‐photon Ca2+ imaging of dendrites from cat TC neurons undergoing spontaneous slow oscillatory activity that somatically recorded δ (1–4 Hz) and slow (<1 Hz) oscillations are associated with rhythmic and sustained global oscillations in dendritic Ca2+. In addition, our data reveal the presence of LTS‐dependent Ca2+ transients (Δ[Ca2+]) in dendritic spine‐like structures on proximal TC neuron dendrites during slow (<1 Hz) oscillations whose amplitudes are similar to those observed in the dendritic shaft. We find that the amplitude of oscillation associated Δ[Ca2+] do not vary significantly with distance from the soma whereas the decay time constant (τdecay) of Δ[Ca2+] decreases significantly in more distal dendrites. Furthermore, τdecay of dendritic Δ[Ca2+] increases significantly as oscillation frequency decreases from δ to slow frequencies where pronounced depolarised UP states are observed. Such rhythmic dendritic Ca2+ entry in TC neurons during sleep‐related firing patterns could be an important factor in maintaining the oscillatory activity and associated biochemical signalling processes, such as synaptic downscaling, that occur in non‐REM sleep.
Disease‐causing mutations C277R and C277Y modify gating of human ClC‐1 chloride channels in myotonia congenita
Authors: Weinberger Sebastian , Wojciechowski Daniel , Sternberg Damien , Lehmann‐Horn Frank , Jurkat‐Rott Karin , Becher Toni , Begemann Birgit , Fahlke Christoph , Fischer Martin 
Published: May 2012

Key points
ClC channels are double‐barrelled channels with two ion conduction pathways per individual channel.
Substituting cysteine 277 by serine constitutively opens the common gate suggesting that this residue plays a major role in joint openings/closings of both protopores of ClC‐1.
We studied here the functional consequences of two novel myotonia‐associated mutations, C277R and C277Y, of human ClC‐1 chloride channels.
C277Y not only modified the common gate, but also protopore gating.
C277Y inverts the voltage dependence and reduces the open probabilities of protopore and common gates and thus decreases the absolute open probabilities of homodimeric hClC‐1 channels to values below 3%.
C277Y reduces single protopore current amplitudes to about two‐thirds of wild‐type values, and inverts the anion permeability sequence.
Our results explain the disease‐causing effects and provide novel insights into the molecular processes underlying normal and pathologically altered function of muscle chloride channels.
Abstract  Myotonia congenita is a genetic condition that is caused by mutations in the muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation and muscle stiffness. We here investigate the functional consequences of two novel disease‐causing missense mutations, C277R and C277Y, using heterologous expression in HEK293T cells and patch clamp recording. Both mutations reduce macroscopic anion currents in transfected cells. Since hClC‐1 is a double‐barrelled anion channel, this reduction in current amplitude might be caused by altered gating of individual protopores or of joint openings and closing of both protopores. We used non‐stationary noise analysis and single channel recordings to separate the mutants’ effects on individual and common gating processes. We found that C277Y inverts the voltage dependence and reduces the open probabilities of protopore and common gates resulting in decreases of absolute open probabilities of homodimeric channels to values below 3%. In heterodimeric channels, C277R and C277Y also reduce open probabilities and shift the common gate activation curve towards positive potentials. Moreover, C277Y modifies pore properties of hClC‐1. It reduces single protopore current amplitudes to about two‐thirds of wild‐type values, and inverts the anion permeability sequence to I−= NO3− > Br− > Cl−. Our findings predict a dramatic reduction of the muscle fibre resting chloride conductance and thus fully explain the disease‐causing effects of mutations C277R and C277Y. Moreover, they provide additional insights into the function of C277, a residue recently implicated in common gating of ClC channels.
Proof of concept for low‐dose molecular breast imaging with a dual‐head CZT gamma camera. Part I. Evaluation in phantoms
Authors: Hruska Carrie B. , Weinmann Amanda L. , O'Connor Michael K. 
Published: May 2012

Purpose:Molecular breast imaging (MBI) is a nuclear medicine technology that uses dual‐head cadmium zinc telluride (CZT) gamma cameras to image functional uptake of a radiotracer, Tc‐99m sestamibi, in the breast. An important factor in adoption of MBI in the screening setting is reduction of the necessary administered dose of Tc‐99m sestamibi from the typically used dose of 740 MBq to approximately 148 MBq, such that MBI's whole‐body effective dose is comparable to that of screening mammography. Methods that increase MBI count sensitivity may allow a proportional reduction in the necessary administered dose. Our objective was to evaluate the impact of two count sensitivity improvement methods on image quality by evaluating count sensitivity, spatial resolution, and lesion contrast in phantom simulations.Methods:Two dual‐head CZT‐based MBI systems were studied: LumaGem and Discovery NM 750b. Two count sensitivity improvement methods were implemented: registered collimators optimized for dedicated breast imaging and widened energy acceptance window optimized for use with CZT. System sensitivity, spatial resolution, and tumor contrast‐to‐noise ratio (CNR) were measured comparing standard collimation and energy window setting [126–154 keV (+10%, −10%)] with optimal collimation and a wide energy window [110–154 keV (+10%, −21%)].Results:Compared to the standard collimator designs and energy windows for these two systems, use of registered optimized collimation and wide energy window increased system sensitivity by a factor of 2.8–3.6. Spatial resolution decreased slightly for both systems with new collimation. At 3 cm from the collimator face, LumaGem's spatial resolution was 4.8 and 5.6 mm with standard and optimized collimation; Discovery NM 750b's spatial resolution was 4.4 and 4.6 mm with standard and optimized collimation, respectively. For both systems, at tumor depths of 1 and 3 cm, use of optimized collimation and wide energy window significantly improved CNR compared to standard settings for tumors 8.0 and 9.2 mm in diameter. At the closer depth of 1 cm, optimized collimation and wide energy window also significantly improved CNR for 5.9 mm tumors on Discovery NM 750b.Conclusions:Registered optimized collimation and wide energy window yield a substantial gain in count sensitivity and measurable gain in CNR, with some loss in spatial resolution compared to the standard collimator designs and energy windows used on these two systems. At low‐count densities calculated to represent doses of 148 MBq, this tradeoff results in adequate count density and lesion contrast for detection of lesions ≥8 mm in the middle of a typical breast (3 cm deep) and lesions ≥6 mm close to the collimator (1 cm deep).
X‐ray spectral measurements for tungsten‐anode from 20 to 49 kVp on a digital breast tomosynthesis system
Authors: Zhang Da , Li Xinhua , Liu Bob 
Published: May 2012

Purpose:This paper presents new spectral measurements of a tungsten‐target digital breast tomosynthesis (DBT) system, including spectra of 43–49 kVp.Methods:Raw x‐ray spectra of 20–49 kVp were directly measured from the tube port of a Selenia Dimensions DBT system using a CdTe based spectrometer. Two configurations of collimation were employed: one with two tungsten pinholes of and diameters, and the other with a single pinhole of diameter, for acquiring spectra from the focal spot and from the focal spot as well as its vicinity. Stripping correction was applied to the measured spectra to compensate distortions due to escape events. The measured spectra were compared with the existing mammographic spectra of the TASMIP model in terms of photon fluence per exposure, spectral components, and half‐value layer (HVL). HVLs were calculated from the spectra with a numerical filtration of 0.7 mm aluminum and were compared against actual measurements on the DBT system using W/Al (target‐filter) combination, without paddle in the beam.Results:The spectra from the double‐pinhole configuration, in which the acceptance aperture pointed right at the focal spot, were harder than the single‐pinhole spectra which include both primary and off‐focus radiation. HVL calculated from the single‐pinhole setup agreed with the measured HVL within 0.04 mm aluminum, while the HVL values from the double‐pinhole setup were larger than the single‐pinhole HVL by at most 0.1 mm aluminum. The spectra from single‐pinhole setup agreed well with the TASMIP mammographic spectra, and are more relevant for clinical purpose.Conclusions:The spectra data would be useful for future research on DBT system with tungsten targets.
Comparison of measured with calculated dose distribution from a 120‐MeV electron beam from a laser‐plasma accelerator
Authors: Lundh O. , Rechatin C. , Faure J. , Ben‐Ismaïl A. , Lim J. , De Wagter C. , De Neve W. , Malka V. 
Published: May 2012

Purpose:To evaluate the dose distribution of a 120‐MeV laser‐plasma accelerated electron beam which may be of potential interest for high‐energy electron radiation therapy.Methods:In the interaction between an intense laser pulse and a helium gas jet, a well collimated electron beam with very high energy is produced. A secondary laser beam is used to optically control and to tune the electron beam energy and charge. The potential use of this beam for radiation treatment is evaluated experimentally by measurements of dose deposition in a polystyrene phantom. The results are compared to Monte Carlo simulations using thegeant4 code.Results:It has been shown that the laser‐plasma accelerated electron beam can deliver a peak dose of more than 1 Gy at the entrance of the phantom in a single laser shot by direct irradiation, without the use of intermediate magnetic transport or focusing. The dose distribution is peaked on axis, with narrow lateral penumbra. Monte Carlo simulations of electron beam propagation and dose deposition indicate that the propagation of the intense electron beam (with large self‐fields) can be described by standard models that exclude collective effects in the response of the material.Conclusions:The measurements show that the high‐energy electron beams produced by an optically injected laser‐plasma accelerator can deliver high enough dose at penetration depths of interest for electron beam radiotherapy of deep‐seated tumors. Many engineering issues must be resolved before laser‐accelerated electrons can be used for cancer therapy, but they also represent exciting challenges for future research.
Development of a randomized 3D cell model for Monte Carlo microdosimetry simulations
Authors: Douglass Michael , Bezak Eva , Penfold Scott 
Published: May 2012

Purpose:The objective of the current work was to develop an algorithm for growing a macroscopic tumor volume from individual randomized quasi‐realistic cells. The major physical and chemical components of the cell need to be modeled. It is intended to import the tumor volume intoGEANT4 (and potentially other Monte Carlo packages) to simulate ionization events within the cell regions.Methods:AMATLAB© code was developed to produce a tumor coordinate system consisting of individual ellipsoidal cells randomized in their spatial coordinates, sizes, and rotations. An eigenvalue method using a mathematical equation to represent individual cells was used to detect overlapping cells. GEANT4 code was then developed to import the coordinate system into GEANT4 and populate it with individual cells of varying sizes and composed of the membrane, cytoplasm, reticulum, nucleus, and nucleolus. Each region is composed of chemically realistic materials.Results:The in‐house developedMATLAB© code was able to grow semi‐realistic cell distributions (∼2 × 108 cells in 1 cm3) in under 36 h. The cell distribution can be used in any number of Monte Carlo particle tracking toolkits including GEANT4, which has been demonstrated in this work.Conclusions:Using the cell distribution andGEANT4, the authors were able to simulate ionization events in the individual cell components resulting from 80 keV gamma radiation (the code is applicable to other particles and a wide range of energies). This virtual microdosimetry tool will allow for a more complete picture of cell damage to be developed.
Draft Genome Sequence of the Yeast Pachysolen tannophilus CBS 4044/NRRL Y-2460
Authors: Liu Xiaoying , Kaas Rolf Sommer , Jensen Peter Ruhdal , Workman Mhairi 
Published: May 2012

ABSTRACT

A draft genome sequence of the yeast
Pachysolen tannophilus
CBS 4044/NRRL Y-2460 is presented. The organism has the potential to be developed as a cell factory for biorefineries due to its ability to utilize waste feedstocks. The sequenced genome size was 12,238,196 bp, consisting of 34 scaffolds. A total of 4,463 genes from 5,346 predicted open reading frames were annotated with function.
BASELINE FINDINGS OF A PROSPECTIVE STUDY ON PRO-OFFENDING ATTITUDES AND SELF-REPORTED PROBLEMS AMONG JUVENILE PROBATIONERS
Authors: CHUI WING HONG , CHAN HENG CHOON (OLIVER) 
Published: May 2012

Although there are scholarly articles and government reports published over the years (Chui, 2004, 2006; Lo et al., 1997), little is known about the effectiveness of the current Hong Kong probation system in reducing juvenile probationers' recidivism risk and easing their community reintegration process. Thus, this Phase One study of an ongoing three-phase longitudinal project aims to set a baseline to measure the pro-offending attitudes and self-reported problems of 77 male juvenile offenders (aged 14 to 20) who recently started their probation period at a residential home using CRIME-PICS II. Phases Two and Three will be conducted upon the completion of their probation and eventual release into their community. Within-programme changes will be measured to examine the effectiveness of the current juvenile probation practice. Sample demographic characteristics, offender criminal history, and CRIME-PICS II descriptive findings are presented. This project is imperative in several aspects with implications for both public policy and social work practice.