H3K9me3 loss and ERVs activation as hallmarks for osteoarthritis progression and knee joint aging.

OBJECTIVE: This study aims to link aberrant endogenous retroviruses (ERVs) activation and osteoarthritis (OA) progression by comparing the chromatin accessibility and transcriptomic landscapes of diseased or intact joint tissues of OA patients. METHOD: We performed ERVs-centric analysis on published ATAC-seq and RNA-seq data from OA patients' cartilage tissues. Here, we compared the outer region of the lateral tibial plateau, representing intact cartilage, to the inner region of the medial tibial plateau, representing damaged cartilage. In addition, cartilage tissue sections from OA patients and post-traumatic OA mouse models were assayed for global H3K9me3 abundance through immunohistochemistry staining. RESULTS: Chromatin accessibility and transcription of ERVs, particularly from evolutionarily "intermediate age" ERVs families (ERV1 and ERVL), were enriched and elevated in OA cartilage. This integrative analysis suggests that H3K9me3-related heterochromatin loss might be mechanistically connected to ERV activation in OA tissue. We further verified that global H3K9me3 levels were reduced in diseased cartilage relative to intact tissue in OA patients and injury-induced OA mice. CONCLUSION: The findings suggest a compelling hypothesis that the loss of H3K9me3, either due to aging or cellular stressors, may lead to ERVs reactivation that contributes to tissue inflammation and OA progression. This study unveils the intricate relationship between epigenetic alterations, ERVs activation, and OA, paving the way for potential therapeutic interventions targeting these pathogenic mechanisms.

Phase-tuned acousto-optic spatial filter.

An acousto-optic (AO) tunable filter with a phase-controlled dual-section piezoelectric transducer is designed and created for laser beam shaping (LBS). Owing to the acoustic beam steering effect, we experimentally observe splitting of the two-dimensional transfer function. As a result, we demonstrate generation of tunable bottle laser beams and dual-ring intensity distributions for the diffracted beam.

De-cluttering Scatterplots with Integral Images.

Scatterplots provide a visual representation of bivariate data (or 2D embeddings of multivariate data) that allows for effective analyses of data dependencies, clusters, trends, and outliers. Unfortunately, classical scatterplots suffer from scalability issues, since growing data sizes eventually lead to overplotting and visual clutter on a screen with a fixed resolution, which hinders the data analysis process. We propose an algorithm that compensates for irregular sample distributions by a smooth transformation of the scatterplot's visual domain. Our algorithm evaluates the scatterplot's density distribution to compute a regularization mapping based on integral images of the rasterized density function. The mapping preserves the samples' neighborhood relations. Few regularization iterations suffice to achieve a nearly uniform sample distribution that efficiently uses the available screen space. We further propose approaches to visually convey the transformation that was applied to the scatterplot and compare them in a user study. We present a novel parallel algorithm for fast GPU-based integral-image computation, which allows for integrating our de-cluttering approach into interactive visual data analysis systems.

Independent multicolored bottle-beam generation using acousto-optic spatial shaping of a femtosecond laser beam.

We report on the development of a tunable spectral and spatial frequency shaping system for ultrashort laser pulses using acousto-optic filters. The system enables the creation of arbitrary axially symmetric multi-wavelength field configurations in the Ti:sapphire laser emission range near 800 nm and controlling them at a multi-kilohertz rate. We experimentally demonstrate independent generation of two-colored annular intensity distributions from a single femtosecond laser beam and a bottle beam having the hollow cylindrical volume with the aspect ratio of 9:1. This laser beam shaping system can be useful in creating advanced setups for an optical control of cold atoms.

Naphthalene-Based Polymers as Catalytic Supports for Suzuki Cross-Coupling.

In this work, for the first time, naphthalene (NA)-based polymers were synthesized by one-stage Friedel-Crafts crosslinking. The influence of NA functionalization by -OH, -SO3H, and -NO2 groups on the polymers' porosity and distribution of the catalytically active phase (Pd) was studied. Synthesized catalytic systems containing 1 wt.% of Pd either in the form of Pd(II) species or Pd(0) nanoparticles supported on NA-based polymers were tested in a model reaction of Suzuki cross-coupling between 4-bromoanisole and phenylboronic acid under mild reaction conditions (60 °C, ethanol-water mixture as a solvent). These novel catalysts demonstrated high efficiency with more than 95% of 4-bromoanisole conversion and high selectivity (>97%) for the target 4-methoxybiphenyl.

An Integrated View of Stressors as Causative Agents in OA Pathogenesis.

Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell's response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage can be repaired, and sometimes, even worse, the stress response can overtax the system itself, further aggravating homeostasis and leading to its loss. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance. The consequence of the accumulation of stress on articular chondrocytes is aberrant mitogenesis and differentiation, defective extracellular matrix production and turnover, cellular senescence, and cell death. The most severe form of stress-induced chondrocyte dysfunction in the joints is osteoarthritis (OA). Here, we summarize studies on the cellular effects of stressors on articular chondrocytes and demonstrate that the molecular effectors of the stress pathways connect to amplify articular joint dysfunction and OA development.

TRIM28 secures skeletal stem cell fate during skeletogenesis by silencing neural gene expression and repressing GREM1/AKT/mTOR signaling axis.

Long bones are generated by mesoderm-derived skeletal progenitor/stem cells (SSCs) through endochondral ossification, a process of sequential chondrogenic and osteogenic differentiation tightly controlled by the synergy between intrinsic and microenvironment cues. Here, we report that loss of TRIM28, a transcriptional corepressor, in mesoderm-derived cells expands the SSC pool, weakens SSC osteochondrogenic potential, and endows SSCs with properties of ectoderm-derived neural crest cells (NCCs), leading to severe defects of skeletogenesis. TRIM28 preferentially enhances H3K9 trimethylation and DNA methylation on chromatin regions more accessible in NCCs; loss of this silencing upregulates neural gene expression and enhances neurogenic potential. Moreover, TRIM28 loss causes hyperexpression of GREM1, which is an extracellular signaling factor promoting SSC self-renewal and SSC neurogenic potential by activating AKT/mTORC1 signaling. Our results suggest that TRIM28-mediated chromatin silencing establishes a barrier for maintaining the SSC lineage trajectory and preventing a transition to ectodermal fate by regulating both intrinsic and microenvironment cues.

Analysis of Acousto-Optic Figure of Merit in KGW and KYW Crystals.

Monoclinic potassium rare-earth crystals are known as efficient materials for solid-state lasers and acousto-optic modulators. A number of specific configurations for acousto-optic devices based on those crystals have recently been proposed, but the acousto-optic effect of those crystals has only been analyzed fragmentarily for some interaction directions. In this work, we numerically searched for the global maxima of an acousto-optic figure of merit for isotropic diffraction in KGd(WO4)2 and KY(WO4)2 crystals. It was demonstrated that the global maxima of the acousto-optic figure of merit in those crystals occur in the slow optical mode propagating along the crystal's twofold symmetry axis and in the acoustic wave propagating orthogonally, both for quasi-longitudinal and quasi-shear acoustic modes. The proposed calculation method can be readily used for the optimization of the acousto-optic interaction geometry in crystals with arbitrary symmetry.

Quasi-Collinear AOTF Spectral Transmission Under Temperature Gradients Aroused by Ultrasound Power Absotption.

Quasi-collinear geometry is a special configuration of acousto-optic (AO) diffraction that provides an extremely large AO interaction length for achieving extremely high spectral resolution of AO tunable filters (AOTFs). Large AO interaction length also makes it possible to implement multifrequency diffraction in quasi-collinear AOTFs, which has found multiple applications in modern optoelectronics. The most widespread of them being ultrashort laser pulse shaping when the pulse shape and spectral composition is controlled by the spectral composition of the ultrasound pulse aroused in the AO crystal. The operation of quasi-collinear AOTFs is accompanied by the appearance of the temperature gradients in the AO device mainly due to the acoustic power absorption by the material. We experimentally assessed the influence of these gradients on the AOTF spectral characteristics. A theoretical model based on the Raman-Nath equations was proposed, which allows to consider the influence of ultrasound attenuation and temperature gradients on the AOTF transmission. This model is valid for transmission simulations both in single- and modulated-frequency AOTF operation modes. The study includes the effects of acoustic wave attenuation and AO phase matching shift caused by inhomogeneous crystal temperature along the optical beam path. The compensation strategy based on ultrasound frequency and magnitude adjustment is proposed for minimizing the effect of temperature gradients and acoustic field attenuation on AOTF spectral transmission for broadband operation in ultrashort laser pulse shaping.

Characterization and alignment of acousto-optic devices using digital tailored RF waveforms.

Acousto-optic (AO) devices are used in a variety of light control and processing applications in different environments, including laboratory conditions and the field environment, as well as on air- and space-borne platforms. Accurate alignment and calibration of AO deflectors and tunable filters is crucial for correct operation and to achieve specified performances of those devices. We describe a simple routine to test and align AO devices with a programmable RF waveform generator. Using specially tailored RF waveforms as test signals enables single-shot measurement of an AO device's diffraction efficiency as a function of the applied RF signal frequency and amplitude. MATLAB code is available to implement the testing procedure and application demonstrations for an AO deflector and two types of AO tunable filters.

SUMOylation in Skeletal Development, Homeostasis, and Disease.

The modification of proteins by small ubiquitin-related modifier (SUMO) molecules, SUMOylation, is a key post-translational modification involved in a variety of biological processes, such as chromosome organization, DNA replication and repair, transcription, nuclear transport, and cell signaling transduction. In recent years, emerging evidence has shown that SUMOylation regulates the development and homeostasis of the skeletal system, with its dysregulation causing skeletal diseases, suggesting that SUMOylation pathways may serve as a promising therapeutic target. In this review, we summarize the current understanding of the molecular mechanisms by which SUMOylation pathways regulate skeletal cells in physiological and disease contexts.

High-efficiency KYW acousto-optic Q-switch for a Ho:YAG laser.

A new, to the best of our knowledge, type of acousto-optic Q-switch was developed using slow shear acoustic mode in potassium yttrium tungstate (KYW) crystal. Two Q-switch configurations were created: one for vertical and one for horizontal light polarization, both providing over 50% diffraction efficiency at a wavelength of 2.1 µm and an RF driving power below 8 W. The laser-induced damage threshold of the KYW crystal was found to equal 650 MW/cm2. Operation of a nanosecond periodically pulsed Ho:YAG laser emitting 15 mJ pulses at 2.1 µm with the KYW Q-switch is reported.

Ring-shaped optical trap based on an acousto-optic tunable spatial filter.

We report on a novel, to the best of our knowledge, optical scheme of an annular optical trap based on an acousto-optic tunable spatial filter. Design of the optical trap is proposed and validated. Experimental demonstration with polystyrene microspheres includes controllable arrangement of freely floating particles into a circular pattern, aggregation, and disaggregation of the particles. Dynamical adjustment of the trapping field potential diameter is achieved by programmable frequency-swept controlling of the acousto-optic filter.

Enzymatic Machinery of Ubiquitin and Ubiquitin-Like Modification Systems in Chondrocyte Homeostasis and Osteoarthritis.

PURPOSE OF REVIEW: To date, a vast amount of information regarding ubiquitination (Ub) and ubiquitylation-like (Ubl) modification-related mechanisms has been reported in the context of skeletal cell homeostasis and diseases. In this review, we mainly focus on recent findings regarding the contribution of enzymatic machinery that directly adds or removes Ub and Ubl modifications from protein targets in chondrocyte homeostasis and osteoarthritis (OA) development. RECENT FINDINGS: Mechanisms that promote homeostasis of articular chondrocytes are crucial for maintaining the integrity of articular joints to prevent osteoarthritis development. Articular chondrocytes are postmitotic cells that continuously produce and remodel cartilage matrix. In addition, the long lifespan of chondrocytes makes them susceptible to accumulating cellular damage. Ub and the evolutionarily conserved Ubl modifications, such as SUMOylation, ATGylation, and UFMylation, play important roles in promoting chondrocyte homeostasis, including regulating cell signaling and protein stability, resolving cellular stresses and inflammation, and maintaining differentiation and survival of chondrocytes. Uncovering new components/functions of Ub/Ubl modification machinery may provide novel drug targets to treat OA.

Acousto-Optic Cells with Phased-Array Transducers and Their Application in Systems of Optical Information Processing.

This paper presents the results of theoretical and experimental studies of anisotropic acousto-optic interaction in a spatially periodical acoustic field created by a phased-array transducer with antiphase excitation of adjacent sections. In this case, contrary to the nonsectioned transducer, light diffraction is absent when the optical beam falls on the phased-array cell at the Bragg angle. However, the diffraction takes place at some other angles (called "optimal" here), which are situated on the opposite sides to the Bragg angle. Our calculations show that the diffraction efficiency can reach 100% at these optimal angles in spite of a noticeable acousto-optic phase mismatch. This kind of acousto-optic interaction possesses a number of interesting regularities which can be useful for designing acousto-optic devices of a new type. Our experiments were performed with a paratellurite (TeO2) cell in which a shear acoustic mode was excited at a 9∘ angle to the crystal plane (001). The piezoelectric transducer had to nine antiphase sections. The efficiency of electric to acoustic power conversion was 99% at the maximum frequency response, and the ultrasound excitation band extended from 70 to 160 MHz. The experiments have confirmed basic results of the theoretical analysis.

Optimization of noncollinear AOTF design for laser beam shaping.

Optimization of a wide-angle paratellurite acousto-optic tunable filter (AOTF) is performed for applications in laser beam shaping systems. The AOTF configuration with annular transfer function is analyzed. It is demonstrated that the optimal AOTF design for single-frequency operation as a narrow-band spatial frequency filter is obtained at acoustic propagation angle of 5.6° relative to the [110] axis. The optimal design for maximization of AOTF resolution in multifrequency laser beam shaping operation mode is obtained at acoustic propagation angle of 13.8°.

First insight into the whole-genome sequence variations in Mycobacterium bovis BCG-1 (Russia) vaccine seed lots and their progeny clinical isolates from children with BCG-induced adverse events.

BACKGROUND: The only licensed live Bacille Calmette-Guérin (BCG) vaccine used to prevent severe childhood tuberculosis comprises genetically divergent strains with variable protective efficacy and rates of BCG-induced adverse events. The whole-genome sequencing (WGS) allowed evaluating the genome stability of BCG strains and the impact of spontaneous heterogeneity in seed and commercial lots on the efficacy of BCG-vaccines in different countries. Our study aimed to assess sequence variations and their putative effects on genes and protein functions in the BCG-1 (Russia) seed lots compared to their progeny isolates available from immunocompetent children with BCG-induced disease (mainly, osteitis). RESULTS: Based on the WGS data, we analyzed the links between seed lots 361, 367, and 368 used for vaccine manufacture in Russia in different periods, and their nine progeny isolates recovered from immunocompetent children with BCG-induced disease. The complete catalog of variants in genes relative to the reference genome (GenBank: CP013741) included 4 synonymous and 8 nonsynonymous single nucleotide polymorphisms, and 3 frameshift deletions. Seed lot 361 shared variants with 2 of 6 descendant isolates that had higher proportions of such polymorphisms in several genes, including ppsC, eccD5, and eccA5 involved in metabolism and cell wall processes and reportedly associated with virulence in mycobacteria. One isolate preserved variants of its parent seed lot 361 without gain of further changes in the sequence profile within 14 years. CONCLUSIONS: The background genomic information allowed us for the first time to follow the BCG diversity starting from the freeze-dried seed lots to descendant clinical isolates. Sequence variations in several genes of seed lot 361 did not alter the genomic stability and viability of the vaccine and appeared accumulated in isolates during the survival in the human organism. The impact of the observed variations in the context of association with the development of BCG-induced disease should be evaluated in parallel with the immune status and host genetics. Comparative genomic studies of BCG seed lots and their descendant clinical isolates represent a beneficial approach to better understand the molecular bases of efficacy and adverse events during the long-term survival of BCG in the host organism.

AOTF-based hyperspectral imaging phase microscopy.

Phase imaging microscopy with incoherent object illumination is convenient and affordable for biomedical research and clinics since it provides easy integration with a variety of bright-field optical microscopes. We report the design of a new hyperspectral imaging system based on a combination of a spatial light modulator (SLM) and an acousto-optic tunable filter (AOTF) for phase imaging microscopy. Contrast of phase-only objects originates from matched spectral and spatial filtering performed by the SLM and the AOTF located in Fourier-conjugate optical planes in the back-end of the optical system. The system is designed as an add-on to a standard optical microscope with incoherent diascopic sample illumination.

Linear Phase Design of Piezoelectric Transducers for Acousto-Optic Dispersion Delay Lines Using Differential Evolution for Matching Circuit Optimization.

A numerical method for providing linear phase response of bulk acoustic wave (BAW) piezoelectric transducers (PTs) of acousto-optic devices is developed. Our approach is based on the analytic approximation of the phase response of the PT with the matching electrical circuit and optimization with a differential evolution genetic algorithm. Simulations and experiments were performed for two typical BAW excitation schemes: direct and reflective. Variance of the group delay in the specified frequency range was reduced by an order of magnitude for reflective excitation of BAWs.