Transient Appearance Research Articles

NuSTAR DISCOVERY OF A CYCLOTRON LINE IN THE ACCRETING X-RAY PULSAR IGR J16393-4643

ABSTRACT The high-mass X-ray binary and accreting X-ray pulsar IGR J16393-4643 was observed by the Nuclear Spectroscope Telescope Array in the 3–79 keV energy band for a net exposure time of 50 ks. We present the results of this observation which enabled the discovery of a cyclotron resonant scattering feature with a centroid energy of keV. This allowed us to measure the magnetic field strength of the neutron star for the first time: B = (2.5 ± 0.1) × 1012 G. The known pulsation period is now observed at 904.0 ± 0.1 s. Since 2006, the neutron star has undergone a long-term spin-up trend at a rate of s s−1 (−0.6 s per year, or a frequency derivative of Hz s−1). In the power density spectrum, a break appears at the pulse frequency which separates the zero slope at low frequency from the steeper slope at high frequency. This addition of angular momentum to the neutron star could be due to the accretion of a quasi-spherical wind, or it could be caused by the transient appearance of a prograde accretion disk that is nearly in corotation with the neutron star whose magnetospheric radius is around 2 × 108 cm.

Pleural Effusion after Percutaneous Radiofrequency Ablation for Hepatic Malignancies

Background and AimsRadiofrequency ablation (RFA) can play an important role in the treatment of primary or metastatic liver tumors. Currently, percutaneous RFA is generally regarded as a safe, effective, and minimally invasive procedure. This study aimed to evaluate the presence and course of pleural effusion after monopolar RFA. MethodsFrom October 2008 to July 2013, a total of 54 patients (28 male and 26 female, mean age 65.2) treated with monopolar RFA were included in our study. 47 patients were diagnosed with hepatocellular carcinoma, 4 patients with hepatic metastasis, and 3 patients had other diagnoses. There were a total of 115 sessions of treatment and 199 liver tumors to be treated (1.73 ± 1.02 tumors treated per session). The tumor size ranged from 0.8 cm to 5.0 cm (mean 2.31 cm, standard deviation 1.04 cm). Thereafter, a follow-up ultrasound was performed within 24 hours subsequent to ablation to evaluate the presence of pleural effusion. The degree of pleural effusion was assessed by chest X-ray. ResultsFifteen (13.0%) treatment sessions in 14 patients showed right-sided pleural effusion after ablations. One patient had a large amount of effusion, while other patients manifested a minimal to small amount of effusion. There were 5 patients that experienced delayed resolution of pleural effusion; one patient (0.87%) had a minimal amount of pleural effusion even after one month. Overall, there was no pneumothorax, or periprocedural morality. Age, gender, tumor numbers, tumor sizes, and complete ablation of target tumors were similar among groups presenting with or without pleural effusion. Tumor locations associated with S78 segments abutting the diaphragm or right lobe of the liver were not associated with development of pleural effusion. Only the duration of ablation time had a marginal trend toward significance (p = 0.051). ConclusionsThe transient appearance of right-sided pleural effusion after percutaneous RFA for hepatic malignancies was not infrequent. However, refractory pleural effusion was rare.

Thermal behaviour of Al-rich tobermorite

The tobermorite supergroup is composed by a number of calcium-silicate-hydrate (C-S-H) minerals characterized by different hydration states and sub-cell symmetries. Taking into account their basal spacing, closely related to the hydration state, phases having a 14 A (plombierite), 11 A (tobermorite, kenotobermorite, and clinotobermorite), and 9 A (riversideite) basal spacing have been described. Tobermorite and kenotobermorite belong to the so-called tobermorite group and differ for their thermal behaviour which can be “normal” (the phase shrinks to a 9 A phase at 300 °C) or “anomalous” (the phase preserves its 11 A basal spacing at 300 °C). Specimens of Al-rich tobermorite from Montalto di Castro and Vallerano, Latium, Central Italy, showing a “normal” thermal behaviour, were studied in order to describe the transition from the 11 A to the 9 A phase by means of thermo-gravimetric–differential scanning calorimetry (TG-DSC) analyses as well as in situ and ex situ X-ray diffraction experiments. The TG-DSC analyses showed a continuous mass loss from 100 °C up to 700 °C, with different mass loss gradients between 100 °C up to 300 °C and between 300 °C up to 700 °C, corresponding to the dehydration of tobermorite and dehydroxylation of “tobermorite 9 A”, respectively. Above 700 °C, “tobermorite 9 A” is replaced by wollastonite. The X-ray powder diffraction data were collected at the GILDA beamline of the ESRF, Grenoble, France, from room temperature up to ca. 840 °C. Tobermorite is completely replaced by the 9 A phase at ca. 300 °C, whereas the latter is transformed into wollastonite at ca. 700 °C. The transition from the 11 A to the 9 A phase seems to be favoured by the transient appearance of a clinotobermorite-like compound.

Successful Treatment of Segmental Vitiligo in Children with the Combination of 1-mm Minigrafts and Phototherapy

Background: Minigrafts using a 1-mm biopsy punch (1-mm minigrafts) are being increasingly used to treat vitiligo. However, there have been few reports of the use of 1-mm minigrafts in pediatric patients. Objective: To examine the effectiveness of combination therapy with 1-mm minigrafts and phototherapy in children with segmental vitiligo. Methods: Minigrafts were placed in 13 patients aged ≤16 years with segmental vitiligo. Following surgery, 11 patients underwent irradiation with excimer laser light and 2 with narrow-band ultraviolet B light. Results: A mean repigmentation of 81.6% was obtained. A particularly high mean repigmentation of 87.9% was seen in patients aged ≤12 years, indicating greater efficacy in these patients than in patients aged ≥13 years (mean, 67.5%). Although a transient cobblestone appearance occurred as an adverse effect, it improved over time. Conclusions: Combined treatment of segmental vitiligo with 1-mm minigrafts and phototherapy can be performed safely and is highly effective in young patients.

Jianshuiite in oceanic manganese nodules at the Paleocene-Eocene boundary

Synchrotron powder X-ray diffraction and scanning electron microscopy examinations of manganese oxide concretions/nodules (~0.3–1.0 mm diameter) from ODP Site 1262 on Walvis Ridge in the Southeastern Atlantic Ocean revealed that they consist primarily of the layered Mn oxide phase jianshuiite [(Mg,Mn,Ca)Mn34+O7·3H2O]. The nodules are from an interval with severe carbonate dissolution that represents the Paleocene/Eocene (P/E) thermal maximum (~55.8 Ma). Most nodules from the middle of the carbonate dissolution interval contain internal open space, and consist almost entirely of euhedral plate-like jianshuiite crystals, 2–4 μm in diameter and ~0.1–0.5 μm thick. Backscattered electron images and energy-dispersive X-ray analyses revealed stacks of interleaved Al-rich and Al-poor jianshuiite crystals in some nodules. The crystals in other nodules contain predominantly Mg (with trace K and Al) in addition to Mn and O, making them near “end-member” jianshuiite. Rietveld refinements in space group R 3 confirmed the isostructural relationship between jianshuiite and chalcophanite, with Mg occupying the interlayer position above and below the vacant sites in the Mn/O octahedral sheet, and coordinated to 3 octahedral layer O atoms (1.94 A) and 3 interlayer water O atoms (2.13 A). Final refined occupancy factors suggest that small quantities of Ni and possibly Mn2+ are located on the Mg site. The transient appearance of the Mg-rich birnessite-like phase jianshuiite, probably abiotically produced, must indicate an exceptional transient change in the chemistry of the pore fluids within deep ocean sediments directly following the P/E boundary, possibly as a result of decreasing oxygen levels and pH, followed by a return to pre-event conditions.

Neutral lipid production in Dunaliella salina during osmotic stress and adaptation

The salt-tolerant green microalga Dunaliella salina can survive both hyper- and hypo-osmotic shock. Upon osmotic shock, the cells transiently and rapidly decreased or increased in size within minutes and slowly over hours acquired their original cell size and volume. Cell size distribution differs significantly in the cultures grown in the salinity range from 1.5 to 15 % NaCl. By using Nile Red fluorescence to detect neutral lipids, it became clear that only hyper-osmotic shock on cells induced transient neutral lipid appearance in D. salina, while those transferred from 9 to 15 % NaCl stimulated the most neutral lipid accumulation. These cells grew well in 9 % NaCl, but they cannot recover a shift to 15 % NaCl and cell division is accordingly slowed down. The transient appearance of neutral lipid could be dependent on the inhibition of cell division experiencing the NaCl shift. Moreover, the effect of nutrient limitation slows down cell division and photosynthesis as a secondary result, which triggers the cells to accumulate neutral storage lipids when they entered the stationary phase, which is seen in all the batch cultures of D. salina grown in the salinity range of 3–15 %. The changes in salt concentration did not significantly influence the overall fatty acid composition in D. salina cells. Although there shows both increased amounts of total lipids and neutral lipids in the cells grown in salinity higher than 9 % NaCl, lipid productivity is however compromised by the slower cell growth rate and lower cell density under this condition.

Prognostic Significance of Late Potentials in Outpatients with Type 2 Brugada Electrocardiogram.

Brugada syndrome is characterized by distinguishing electrocardiogram (ECG) patterns (coved and saddle-back types with day-to-day variation) and occurrence of lethal tachy-arrhythmias. The appearance of coved type ECG (type 1) is required for the diagnosis of Brugada syndrome, whereas the significance of saddle-back type ECG (type 2), which is inadequate for the diagnosis, has not been fully established. We enrolled 34 consecutive patients with type 2 ECG on outpatient-clinic. Among them, 7 patients were ventricular fibrillation (VF) survivors who were diagnosed as Brugada syndrome with transient appearance of type 1 ECG, and showed type 2 ECG on their first outpatient-clinic visit after the VF event (VF group). The remaining 27 were asymptomatic and never showed type 1 ECG on repeated ECG examinations (control group). The VF group showed significantly longer RJ intervals in leads V1 and V2 and QTc intervals in lead V2 compared with the control group (P < 0.030, P < 0.017, and P < 0.030, respectively). Late potentials, detected on the signal-averaged ECG (SA-ECG), reflect conduction abnormalities and are known as one of the risk markers of arrhythmic events. Among the 34 patients, late potentials were negative in 12 patients belonging to the control group. In conclusion, the SA-ECG could be helpful to identify high-risk patients for its high negative predictive value as the first step, and ECG parameters, including RJ intervals in leads V1 and V2 and QTc interval in lead V2, could be useful for further risk stratification in patients with type 2 Brugada ECG.

Transient and periodic spatiotemporal structures in a reaction-diffusion-mechanics system.

We study transient spatiotemporal structures induced by a weak space-time localized stimulus in an excitable contractile fiber within a two-component globally coupled reaction-diffusion model. The model which we develop allows us to analyze various regimes of excitation spreading and determine origin of the induced structures for various contraction types (defined by the fiber fixation) and global coupling strengths. One of the most notable effects we observed is the after-excitation effect. It leads to emergence of multiple excitation pulses excited by a single external stimulus and can result in long-lasting transient activity and appearance of new oscillatory attractor regimes, including the ones with multiple phase clusters.

NIMG-16PSEUDOPROGRESSION AND IMMUNOTHERAPY IN GLIOBLASTOMA: A CASE SERIES FROM COHORT 1 OF CHECKMATE-143 (NCT02017717)

BACKGROUND: In CHECKMATE-143, safety and tolerability of nivolumab and ipilimumab were evaluated in patients with first recurrence of glioblastoma. One of the challenges with immune targeting therapies is the accurate assessment of changes in disease progression with neuroimaging. Immune-related treatment effects presenting as temporary increases in target or non-target lesions or a transient appearance of a new lesion are observed in ∼10% of patients. These changes can result from influx of inflammatory cells leading to temporary appearances of increased mass. Here, we present neuroimaging results that meet RANO criteria for progressive disease, and the corresponding histopathology findings. METHODS: In cohort 1, eligible patients were randomized 1:1 to nivolumab 3mg/kg Q2W or nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W followed by nivolumab 3 mg/kg Q2W. Responses were assessed using RANO criteria at Weeks 6, 12, and Q8W onward. Treatment beyond progression was permitted until a second radiologic confirmation of progression 8 weeks later. At the time of imaging progression, if biopsy/resection was feasible, pathological evaluation was performed and histopathologic findings were correlated with imaging changes. RESULTS: A total of 20 patients were treated in cohort 1. In some cases, immune-related treatment effects presenting as target lesion growth or appearance of new lesions were observed on imaging. A variety of histopathologic patterns were observed with radiographic progression. Imaging and the correlated histopathological findings will be presented in detail. CONCLUSIONS: Immune-related treatment effects can occur in patients with glioblastoma receiving checkpoint inhibitors. Tissue acquisition and pathologic assessment can clarify the etiology of progression imaging findings preventing premature discontinuation of potentially beneficial therapy.

Interacting Multiview Tracker.

A robust algorithm is proposed for tracking a target object in dynamic conditions including motion blurs, illumination changes, pose variations, and occlusions. To cope with these challenging factors, multiple trackers based on different feature representations are integrated within a probabilistic framework. Each view of the proposed multiview (multi-channel) feature learning algorithm is concerned with one particular feature representation of a target object from which a tracker is developed with different levels of reliability. With the multiple trackers, the proposed algorithm exploits tracker interaction and selection for robust tracking performance. In the tracker interaction, a transition probability matrix is used to estimate dependencies between trackers. Multiple trackers communicate with each other by sharing information of sample distributions. The tracker selection process determines the most reliable tracker with the highest probability. To account for object appearance changes, the transition probability matrix and tracker probability are updated in a recursive Bayesian framework by reflecting the tracker reliability measured by a robust tracker likelihood function that learns to account for both transient and stable appearance changes. Experimental results on benchmark datasets demonstrate that the proposed interacting multiview algorithm performs robustly and favorably against state-of-the-art methods in terms of several quantitative metrics.

Glucocorticoid Receptor Transcriptional Activation via the BRG1-Dependent Recruitment of TOP2β and Ku70/86

BRG1, the central ATPase of the human SWI/SNF complex, is critical for biological functions, including nuclear receptor (NR)-regulated transcription. Analysis of BRG1 mutants demonstrated that functional motifs outside the ATPase domain are important for transcriptional activity. In the course of experiments examining protein interactions mediated through these domains, Ku70 (XRCC6) was found to associate with a BRG1 fragment encompassing the conserved helicase-SANT-associated (HSA) and BRK domains of BRG1. Subsequent transcriptional activation assays and chromatin immunoprecipitation studies showed that Ku70/86 and components of the topoisomerase IIβ (TOP2β)/poly(ADP ribose) polymerase 1 (PARP1) complex are necessary for NR-mediated SWI/SNF-dependent transcriptional activation from endogenous promoters. In addition to establishing Ku-BRG1 binding and TOP2β/PARP1 recruitment by nuclear receptor transactivation, we demonstrate that the transient appearance of glucocorticoid receptor (GR)/BRG1-dependent, TOP2β-mediated double-strand DNA breaks is required for efficient GR-stimulated transcription. Taken together, these results suggest that a direct interaction between Ku70/86 and BRG1 brings together SWI/SNF remodeling capabilities and TOP2β activity to enhance the transcriptional response to hormone stimulation.

Modeling the high-energy electronic state manifold of adenine: Calibration for nonlinear electronic spectroscopy.

Pump-probe electronic spectroscopy using femtosecond laser pulses has evolved into a standard tool for tracking ultrafast excited state dynamics. Its two-dimensional (2D) counterpart is becoming an increasingly available and promising technique for resolving many of the limitations of pump-probe caused by spectral congestion. The ability to simulate pump-probe and 2D spectra from ab initio computations would allow one to link mechanistic observables like molecular motions and the making/breaking of chemical bonds to experimental observables like excited state lifetimes and quantum yields. From a theoretical standpoint, the characterization of the electronic transitions in the visible (Vis)/ultraviolet (UV), which are excited via the interaction of a molecular system with the incoming pump/probe pulses, translates into the determination of a computationally challenging number of excited states (going over 100) even for small/medium sized systems. A protocol is therefore required to evaluate the fluctuations of spectral properties like transition energies and dipole moments as a function of the computational parameters and to estimate the effect of these fluctuations on the transient spectral appearance. In the present contribution such a protocol is presented within the framework of complete and restricted active space self-consistent field theory and its second-order perturbation theory extensions. The electronic excited states of adenine have been carefully characterized through a previously presented computational recipe [Nenov et al., Comput. Theor. Chem. 1040-1041, 295-303 (2014)]. A wise reduction of the level of theory has then been performed in order to obtain a computationally less demanding approach that is still able to reproduce the characteristic features of the reference data. Foreseeing the potentiality of 2D electronic spectroscopy to track polynucleotide ground and excited state dynamics, and in particular its expected ability to provide conformational dependent fingerprints in dimeric systems, the performances of the selected reduced level of calculations have been tested in the construction of 2D electronic spectra for the in vacuo adenine monomer and the unstacked adenine homodimer, thereby exciting the Lb/La transitions with the pump pulse pair and probing in the Vis to near ultraviolet spectral window.

Efficient and accurate set-based registration of time-separated aerial images

This paper addresses the task of time-separated aerial image registration. The ability to solve this problem accurately and reliably is important for a variety of subsequent image understanding applications. The principal challenge lies in the extent and nature of transient appearance variation that a land area can undergo, such as that caused by the change under illumination conditions, seasonal variations, or the occlusion by non-persistent objects (people, cars). Our work introduces several major novelties (i) unlike previous work on aerial image registration, we approach the problem using a set-based paradigm; (ii) we show how image space local, pair-wise constraints can be used to enforce a globally good registration using a constraints graph structure; (iii) we show how a simple holistic representation derived from raw aerial images can be used as a basic building block of the constraints graph in a manner which achieves both high registration accuracy and speed; (iv) lastly, we introduce a new and, to the best of our knowledge, the only data corpus suitable for the evaluation of set-based aerial image registration algorithms. Using this data set, we demonstrate (i) that the proposed method outperforms the state-of-the-art for pair-wise registration already, achieving greater accuracy and reliability, while at the same time reducing the computational cost of the task and (ii) that the increase in the number of available images in a set consistently reduces the average registration error, with a major difference already for a single additional image.

Emergence of drug tolerance in cancer cell populations: an evolutionary outcome of selection, nongenetic instability, and stress-induced adaptation.

In recent experiments on isogenetic cancer cell lines, it was observed that exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells, which display markers associated with stem cell-like cancer cells. After a period of time, some of the surviving cells were observed to change their phenotype to resume normal proliferation and eventually repopulate the sample. Furthermore, the drug-tolerant cells could be drug resensitized following drug washout. Here, we propose a theoretical mechanism for the transient emergence of such drug tolerance. In this framework, we formulate an individual-based model and an integro-differential equation model of reversible phenotypic evolution in a cell population exposed to cytotoxic drugs. The outcomes of both models suggest that nongenetic instability, stress-induced adaptation, selection, and the interplay between these mechanisms can push an actively proliferating cell population to transition into a weakly proliferative and drug-tolerant state. Hence, the cell population experiences much less stress in the presence of the drugs and, in the long run, reacquires a proliferative phenotype, due to phenotypic fluctuations and selection pressure. These mechanisms can also reverse epigenetic drug tolerance following drug washout. Our study highlights how the transient appearance of the weakly proliferative and drug-tolerant cells is related to the use of high-dose therapy. Furthermore, we show how stem-like characteristics can act to stabilize the transient, weakly proliferative, and drug-tolerant subpopulation for a longer time window. Finally, using our models as in silico laboratories, we propose new testable hypotheses that could help uncover general principles underlying the emergence of cancer drug tolerance.

Mitochondrial Protein in the Nucleus

Other than the respiratory chain components, most mitochondrial proteins are synthesized in the cytosol and imported into the mitochondria. Many mitochondrial proteins therefore have at least a transient cytosolic appearance, and several have a dual mitochondrial-cytosol functional localization. However, recent work has revealed several proteins, one of which is a large protein complex, with dual mitochondrial and nuclear localizations. The enzyme fumarase which catalyzes the reversible hydration/dehydration of fumarate to malate is part of the mitochondria matrix tricarboxylic acid (TCA) cycle. It could, however, be recruited from the cytosol to the nucleus in response to DNA damage, where it is important for DNA repair. The pyruvate dehydrogenase complex (PDC) generates acetyl-CoA from pyruvate, and is recently shown to translocate from the mitochondrial matrix into the nuclear under mitogenic and stress conditions to generate acetyl–CoA within the nucleus. The mitochondrial monooxygenase CLK-1/COQ7 responsible for the synthesis of ubiquinone is most recently found to have a nuclear isoform with an uncleaved amino terminus, where it affects transcriptional changes associated with mitochondrial reactive oxygen species (ROS) generation. In this review, we highlight these unusual cases of nuclear localization of classically mitochondrial proteins, and discuss their possible functions in the nucleus.

Stoichiometry and assembly of mTOR complexes revealed by single-molecule pulldown.

The mammalian target of rapamycin (mTOR) kinase is a master regulator of cellular, developmental, and metabolic processes. Deregulation of mTOR signaling is implicated in numerous human diseases including cancer and diabetes. mTOR functions as part of either of the two multisubunit complexes, mTORC1 and mTORC2, but molecular details about the assembly and oligomerization of mTORCs are currently lacking. We use the single-molecule pulldown (SiMPull) assay that combines principles of conventional pulldown assays with single-molecule fluorescence microscopy to investigate the stoichiometry and assembly of mTORCs. After validating our approach with mTORC1, confirming a dimeric assembly as previously reported, we show that all major components of mTORC2 exist in two copies per complex, indicating that mTORC2 assembles as a homodimer. Interestingly, each mTORC component, when free from the complexes, is present as a monomer and no single subunit serves as the dimerizing component. Instead, our data suggest that dimerization of mTORCs is the result of multiple subunits forming a composite surface. SiMPull also allowed us to distinguish complex disassembly from stoichiometry changes. Physiological conditions that abrogate mTOR signaling such as nutrient deprivation or energy stress did not alter the stoichiometry of mTORCs. On the other hand, rapamycin treatment leads to transient appearance of monomeric mTORC1 before complete disruption of the mTOR-raptor interaction, whereas mTORC2 stoichiometry is unaffected. These insights into assembly of mTORCs may guide future mechanistic studies and exploration of therapeutic potential.

Role of Hydrogen in Cavitation Degradation of Iron in Water Solutions

Hydrogen ingress into a metal has been observed at cavitation in distilled water and in 3% NaCl solution at open circuit potential. The measurements of hydrogen permeation rate have been made using an ultrasonic cavitation facility with an attached Devanathan-Stachurski double cell. Increase in vibration amplitude has been associated with the increase in amplitude of electrochemical voltage and current pulses and with the modification of hydrogen permeation rate. Hydrogen behavior within the metal has been affected by the cavitation induced dynamic stresses and metal deformation hardening, ascertained on the basis of the appearance of hydrogen permeation transients at cavitation in comparison with those recorded for the unstressed state. Metal damage has been a resultof associated effects of cavitation and hydrogen.

Transient appearance of the epithelial invagination in the olfactory pit of chick embryos.

In this study, immunohistochemical analysis has been performed using neuronal markers (GAP43, NCAM and PGP 9.5) to characterize the epithelial invagination in the medial wall of the olfactory pit in the chick embryos. At stages 26–27, the epithelial invagination was primarily composed of characteristic round-shaped cells, which were negative for neuronal markers. These cells were also found in the medial wall of the olfactory pit at stage 24, whereas the epithelial invagination was not observed at any stages other than stages 26–27. The possible relationship between the round-shaped cells and the migratory cells is discussed.

Retinal dendritic cell recruitment, but not function, was inhibited in MyD88 and TRIF deficient mice.

BackgroundImmune system cells are known to affect loss of neurons due to injury or disease. Recruitment of immune cells following retinal/CNS injury has been shown to affect the health and survival of neurons in several models. We detected close, physical contact between dendritic cells and retinal ganglion cells following an optic nerve crush, and sought to understand the underlying mechanisms.MethodsCD11c-DTR/GFP mice producing a chimeric protein of diphtheria toxin receptor (DTR) and GFP from a transgenic CD11c promoter were used in conjunction with mice deficient in MyD88 and/or TRIF. Retinal ganglion cell injury was induced by an optic nerve crush, and the resulting interactions of the GFPhi cells and retinal ganglion cells were examined.ResultsRecruitment of GFPhi dendritic cells to the retina was significantly compromised in MyD88 and TRIF knockout mice. GFPhi dendritic cells played a significant role in clearing fluorescent-labeled retinal ganglion cells post-injury in the CD11c-DTR/GFP mice. In the TRIF and MyD88 deficient mice, the resting level of GFPhi dendritic cells was lower, and their influx was reduced following the optic nerve crush injury. The reduction in GFPhi dendritic cell numbers led to their replacement in the uptake of fluorescent-labeled debris by GFPlo microglia/macrophages. Depletion of GFPhi dendritic cells by treatment with diphtheria toxin also led to their displacement by GFPlo microglia/macrophages, which then assumed close contact with the injured neurons.ConclusionsThe contribution of recruited cells to the injury response was substantial, and regulated by MyD88 and TRIF. However, the presence of these adaptor proteins was not required for interaction with neurons, or the phagocytosis of debris. The data suggested a two-niche model in which resident microglia were maintained at a constant level post-optic nerve crush, while the injury-stimulated recruitment of dendritic cells and macrophages led to their transient appearance in numbers equivalent to or greater than the resident microglia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0143-1) contains supplementary material, which is available to authorized users.

THEMIS observations of the current sheet dynamics in response to the intrusion of the high‐velocity plasma flow into the near‐Earth magnetotail

AbstractA small separation between Time History of Events and Macroscale Interactions during Substorms (THEMIS) probes allows us to analyze a sudden activation in the near‐Earth current sheet (CS) at microscales. The start of the activation coincides with the appearance of an earthward plasma flow and dipolarization front (DF) at THEMIS location. The time sequence of observations of the fast plasma flow and the associated DF by three THEMIS probes denotes their dawnward displacement and the localization of the flow channel in the dawn‐dusk direction. The onset of kink perturbations of the CS was generated on the dawn side of the flow. These fluctuations also propagated dawnward and were followed by the CS thinning (L ~ ρi) and by the development of tearing instability with transient appearance of a magnetic null point. The region of the unstable CS with a magnetic null point was localized in the X and, possibly, in the Y directions. The CS perturbations were most likely triggered by the intrusion of the fast flow into the ambient plasma in the course of the global dawnward displacement of the flow structure. Although no substorm onset was observed during the CS activation, a ground signature of a pseudobreakup was detected just after the excitement of the tearing mode in the near‐Earth tail. Probably the pseudobreakup was caused by a localized diversion of the current, which could result from the disruption of the cross‐tail current in a localized region of the near‐Earth CS.