Acetylation of c-Myc at Lysine 148 Protects Neurons After Ischemia.

This study focuses on understanding the role of c-Myc, a cancer-associated transcription factor, in the penumbra following ischemic stroke. While its involvement in cell death and survival is recognized, its post-translational modifications, particularly acetylation, remain understudied in ischemia models. Investigating these modifications could have significant clinical implications for controlling c-Myc activity in the central nervous system. Although previous studies on c-Myc acetylation have been limited to non-neuronal cells, our research examines its expression in perifocal cells during stroke recovery to explore regulatory mechanisms via acetylation. We found that in peri-infarct neurons, c-Myc is upregulated with acetylation at K148 but not K323 during the acute phase of stroke, with SIRT2 deacetylase primarily affecting K148 acetylation. Molecular dynamics simulations suggest that lysine 148 plays a crucial role in stabilizing c-Myc spatial structure. Increased acetylation at K148 reduces c-Myc compaction, potentially limiting its nuclear penetration, promoting calpain-mediated cleavage, and decreasing nuclear localization. Additionally, cytoplasmic acetylation at K148 may alter c-Myc's interaction with unidentified proteins, potentially influencing its pro-apoptotic effects and promoting cytoplasmic accumulation. Targeting SIRT2 with selective inhibitors could be a promising avenue for future stroke therapy strategies.

Acetylation of p53 in the Cerebral Cortex after Photothrombotic Stroke.

p53 expression and acetylation are crucial for the survival and death of neurons in penumbra. At the same time, the outcome of ischemia for penumbra cells depends largely on the histone acetylation status, but the effect of histone acetyltransferases and deacetylases on non-histone proteins like p53 is largely understudied. With combined in silico and in vitro approach, we have identified enzymes capable of acetylation/deacetylation, distribution, stability, and pro-apoptotic activity of p53 in ischemic penumbra in the course of post-stroke recovery, and also detected involved loci of acetylation in p53. The dynamic regulation of the acetylation of p53 at lysine 320 is controlled by acetyltransferase PCAF and histone deacetylases HDAC1 and HDAC6. The in silico simulation have made it possible to suggest the acetylation of p53 at lysine 320 acetylation may facilitate the shuttling of p53 between the nucleus and cytoplasm in penumbra neurons. Acetylation of p53 at lysine 320 is more preferable than acetylation at lysine 373 and probably promotes survival and repair of penumbra neurons after stroke. Strategies to increase p53 acetylation at lysine 320 via increasing PCAF activity, inhibiting HDAC1 or HDAC6, inhibiting p53, or a combination of these interventions may have therapeutic benefits for stroke recovery and would be promising for neuroprotective therapy of stroke.

Bottom-Up Gold Filling in New Geometries and Yet Higher Aspect Ratio Gratings for Hard X-Ray Interferometry.

An extreme bottom-up filling variant of superconformal Au electrodeposition yielding void-free filling of recessed features is demonstrated with diffraction gratings composed of a two-dimensional patterned "chessboard" array of square vias of aspect ratio (depth/width) ≈ 23 as well as one-dimensional arrays of trenches having aspect ratios exceeding 50 and 65. Deposition on planar and patterned substrates is examined in several near-neutral x mol·L-1 Na3Au(SO3)2 + 0.64 mol·L-1 Na2SO3 electrolytes (x = [0.08, 0.16, 0.32]) containing ≈ 50 µmol·L-1 Bi3+ additive. The electrolytes are similar to those used in earlier work, although the upper bound on Au(SO3)2 concentration is twofold greater than previously described. Filling results are complemented by associated current and deposition charge transients whose features, particularly with well controlled pH, exhibit repeatable behaviors and timescales for incubation of passive deposition followed by bottom-up, void-free filling. While incompletely filled features can exhibit substantial via-to-via variation in fill height, self-passivation that follows complete bottom-up filling results in highly uniform filling profiles across the substrates. Visibility measurements capture the quality and uniformity of the as-formed wafer scale gratings. X-ray phase contrast imaging demonstrates their potential for imaging applications.

Author Correction: Nanofocusing of hard X-ray free electron laser pulses using diamond based Fresnel zone plates.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tunable kinoform x-ray beam splitter.

We demonstrate an x-ray beam splitter with high performances for multi-kilo-electron-volt photons. The device is based on diffraction on kinoform structures, which overcome the limitations of binary diffraction gratings. This beam splitter achieves a dynamical splitting ratio in the range 0-99.1% by tilting the optics and is tunable, here shown in a photon energy range of 7.2-19 keV. High diffraction efficiency of 62.6%, together with an extinction ratio of 0.6%, is demonstrated at 12.4 keV, with angular separation for the split beam of 0.5 mrad. This device can find applications in beam monitoring at synchrotrons, at x-ray free electron lasers for online diagnostics and beamline multiplexing and, possibly, as key elements for delay lines or ultrashort x-ray pulses manipulation.

Model-independent particle species disentanglement by X-ray cross-correlation scattering.

Mixtures of different particle species are often investigated using the angular averages of the scattered X-ray intensity. The number of species is deduced by singular value decomposition methods. The full disentanglement of the data into per-species contributions requires additional knowledge about the system under investigation. We propose to exploit higher-order angular X-ray intensity correlations with a new computational protocol, which we apply to synchrotron data from two-species mixtures of two-dimensional static test nanoparticles. Without any other information besides the correlations, we demonstrate the assessment of particle species concentrations in the measured data sets, as well as the full ab initio reconstruction of both particle structures. The concept extends straightforwardly to more species and to the three-dimensional case, whereby the practical application will require the measurements to be performed at an X-ray free electron laser.

Magnetic Field Tuning and Quantum Interference in a Cooper Pair Splitter.

Cooper pair splitting (CPS) is a process in which the electrons of the naturally occurring spin-singlet pairs in a superconductor are spatially separated using two quantum dots. Here, we investigate the evolution of the conductance correlations in an InAs CPS device in the presence of an external magnetic field. In our experiments the gate dependence of the signal that depends on both quantum dots continuously evolves from a slightly asymmetric Lorentzian to a strongly asymmetric Fano-type resonance with increasing field. These experiments can be understood in a simple three-site model, which shows that the nonlocal CPS leads to symmetric line shapes, while the local transport processes can exhibit an asymmetric shape due to quantum interference. These findings demonstrate that the electrons from a Cooper pair splitter can propagate coherently after their emission from the superconductor and how a magnetic field can be used to optimize the performance of a CPS device. In addition, the model calculations suggest that the estimate of the CPS efficiency in the experiments is a lower bound for the actual efficiency.

Gigahertz Quantized Charge Pumping in Bottom-Gate-Defined InAs Nanowire Quantum Dots.

Semiconducting nanowires (NWs) are a versatile, highly tunable material platform at the heart of many new developments in nanoscale and quantum physics. Here, we demonstrate charge pumping, that is, the controlled transport of individual electrons through an InAs NW quantum dot (QD) device at frequencies up to 1.3 GHz. The QD is induced electrostatically in the NW by a series of local bottom gates in a state of the art device geometry. A periodic modulation of a single gate is enough to obtain a dc current proportional to the frequency of the modulation. The dc bias, the modulation amplitude and the gate voltages on the local gates can be used to control the number of charges conveyed per cycle. Charge pumping in InAs NWs is relevant not only in metrology as a current standard, but also opens up the opportunity to investigate a variety of exotic states of matter, for example, Majorana modes, by single electron spectroscopy and correlation experiments.

Two-dimensional structure from random multiparticle X-ray scattering images using cross-correlations.

Knowledge of the structure of biological macromolecules, especially in their native environment, is crucial because of the close structure-function relationship. X-ray small-angle scattering is used to determine the shape of particles in solution, but the achievable resolution is limited owing to averaging over particle orientations. In 1977, Kam proposed to obtain additional structural information from the cross-correlation of the scattering intensities. Here we develop the method in two dimensions, and give a procedure by which the single-particle diffraction pattern is extracted in a model-independent way from the correlations. We demonstrate its application to a large set of synchrotron X-ray scattering images on ensembles of identical, randomly oriented particles of 350 or 200 nm in size. The obtained 15 nm resolution in the reconstructed shape is independent of the number of scatterers. The results are discussed in view of proposed 'snapshot' scattering by molecules in the liquid phase at X-ray free-electron lasers.

Imprinting magnetic information in manganites with x rays.

The effect of x rays on an orbital and charge ordered epitaxial film of a Pr0.5Ca0.5MnO3 is presented. As the film is exposed to x rays, the antiferromagnetic response increases and concomitantly the conductivity of the film improve. These results are discussed in terms of a persistent x-ray induced doping, leading to a modification of the magnetic structure. This effect allows writing electronic and magnetic information in the film and represents a novel way of manipulating magnetism.

True reference nanosensor realized with silicon nanowires.

Conventional gate oxide layers (e.g., SiO(2), Al(2)O(3), or HfO(2)) in silicon field-effect transistors (FETs) provide highly active surfaces, which can be exploited for electronic pH sensing. Recently, great progress has been achieved in pH sensing using compact integrateable nanowire FETs. However, it has turned out to be much harder to realize a true reference electrode, which--while sensing the electrostatic potential--does not respond to the proton concentration. In this work, we demonstrate a highly effective reference sensor, a so-called reference FET, whose proton sensitivity is suppressed by as much as 2 orders of magnitude. To do so, the Al(2)O(3) surface of a nanowire FET was passivated with a self-assembled monolayer of silanes with a long alkyl chain. We have found that a full passivation can be achieved only after an extended period of self-assembling lasting several days at 80 °C. We use this slow process to measure the number of active proton binding sites as a function of time by a quantitative comparison of the measured nonlinear pH-sensitivities to a theoretical model (site-binding model). Furthermore, we have found that a partially passivated surface can sense small changes in the number of active binding sites reaching a detection limit of δN(s) ≈ 170 µm(-2) Hz(-1/2) at 10 Hz and pH 3.

Nanofocusing of hard X-ray free electron laser pulses using diamond based Fresnel zone plates.

A growing number of X-ray sources based on the free-electron laser (XFEL) principle are presently under construction or have recently started operation. The intense, ultrashort pulses of these sources will enable new insights in many different fields of science. A key problem is to provide x-ray optical elements capable of collecting the largest possible fraction of the radiation and to focus into the smallest possible focus. As a key step towards this goal, we demonstrate here the first nanofocusing of hard XFEL pulses. We developed diamond based Fresnel zone plates capable of withstanding the full beam of the world's most powerful x-ray laser. Using an imprint technique, we measured the focal spot size, which was limited to 320 nm FWHM by the spectral band width of the source. A peak power density in the focal spot of 4×10(17)W/cm(2) was obtained at 70 fs pulse length.

[The morphofunctional changes in the kidneys of patients with staghorn nephrolithiasis operated on using a block of the renal blood flow]. / Morfofunktsional'nye izmeneniia pochek u bol'nykh s korallovidnym nefrolitiazom, operirovannykh s primeneniem blokady pochechnogo krovotoka.

A study was made of morphofunctional changes in the kidneys depending on duration of ischemia and use of the drug combination proposed by the contributors to the article, for pharmacological protection of the kidney. The examination of intraoperative renal biopsy specimens revealed the hystological structure of the kidney to be more intact, with its functional capacity tending to restore more readily than in control, in those patients in whom pharmacological protection had been embarked on. Constricting the renal artery and carrying on pharmacological protection of kidney we succeeded in effecting a complete elimination of the coral-like calculus fragments in favourable conditions on a "dry" organ, being able to manage with almost non-traumatic nephrotomy associated with minimum loss of blood, which fact resulted in the reduction of the lithogenesis recurrence rate by 17 %.

[Results of surgical treatment of patients with coral-shaped kidney stones]. / Rezultaty operativnogo lecheniia bolnykh s korallovidnymi kamniami pochek.

The results of treatment of 140 patients with coral-like renal calculus operated on with blockade of the renal blood flow and performance of pharmacologic protection of a kidney have been analysed. The possibility to remove all the fragments of a coral-like calculus under favourable conditions (on a "dry" organ, performance of nephrotomy with low traumaticity and minimal blood loss) was noted. This allowed early restoration of renal function and 17% decrease in the incidence of the development of recurrent calculus formation.

[One-stage operations in bilateral nephrolithiasis]. / Odnomomentnye operatsii pri dvustoronnem nefrolitiaze.

The results of treatment of 60 patients with bilateral nephrolithiasis undergoing one-stage operations are presented.

[Primary hyperparathyroidism in patients with bilateral nephrolithiasis]. / Pervichnyi giperparatireoz u bol'nykh dvustoronnim nefrolitiazom.

Experience in the diagnosis and treatment of the renal form of primary hyperparathyroidism in 57 patients with bilateral nephrolithiasis was summed up. The main diagnostic criterion was the detection of biochemical changes in the blood and urine (hypercalcemia, hypophosphatemia, hypercalciuria) and the use of some tests (Howard's test and parathyroidin test). Parathyroidectomy was performed after establishing diagnosis. A new stage in therapy of such patients was a study of renal function and phosphocalcium metabolism after parathyroidectomy. The improvement of some indices (an increase in glomerular filtration, urea excretion with urine and relative urine density, and a decrease in hypercalciuria and hyperphosphaturia) indicated the effectiveness of surgical intervention for primary hyperparathyroidism in patients with bilateral nephrolithiasis. It was also confirmed by a decrease in lithogenic relapse after parathyroidectomy.