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Simple Summary: Glutamic acid decarboxylase (GAD) is an enzyme that catalyses the formation of γ-aminobutyric acid (GABA), the most important inhibitory neurotransmitter, from glutamic acid (Glu), which is the major neuromodulator in the central nervous system and is involved in most processes such as learning and memory, and in the mechanisms underlying aggressive animal behaviour. However, an excess of Glu in the neuronal space has a cytotoxic and neurodegenerative effect on neurons, and numerous studies have shown this negative effect on the proper functioning of the nervous system. GAD is therefore a key enzyme that ensures the balance between the concentration of Glu and GABA necessary for the proper functioning of brain mechanisms, including the stress response mechanism. The aim of this study was to examine if and how stress and Glu and its selected antagonists affect the level of the GAD enzyme in rabbit brain structures and, if so, in which structures these changes take place and whether GAD can be, next to adrenal hormones, an alternative marker to determine the level of stress in animals. In summary, the conducted study showed that selected rabbit brain structures showed variable GAD concentration in different ways under stressful conditions. The results presented in this paper improve our understanding of the rabbit's limbic system and broaden our understanding of the stress response in this animal species under the influence of a stress factor. It is advisable that further studies assess precisely the Glu–GAD–GABA system under stressful conditions in other animal species, including farm animals, in particular those exposed to stress. Glutamic acid decarboxylase (GAD) is an enzyme that catalyses the formation of γ-aminobutyric acid (GABA), the most important inhibitory neurotransmitter, from glutamic acid (Glu), which is considered the most important excitatory transmitter in the central and peripheral nervous systems. GAD is a key enzyme that provides a balance between Glu and GABA concentration. Hence, it can be assumed that if the GAD executes the synthesis of GABA from Glu, it is important in the stress response, and thus also in triggering the emotional states of the body that accompany stress. The aim of the study was to investigate the concentration of the GAD in motivational structures in the brain of the rabbit (Oryctolagus cuniculus) under altered homeostatic conditions caused by stress and variable availability of Glu. Summarising, the experimental results clearly showed variable concentrations of GAD in the motivational structures of the rabbit brain. The highest concentration of GAD was found in the hypothalamus, which suggests a strong effect of Glu and GABA on the activity of this brain structure. The GAD concentrations in individual experimental groups depended to a greater extent on blocking the activity of glutamate receptors than on the effects of a single stress exposure. The results obtained clearly support the possibility that a rapid change in the concentration of GAD could shift bodily responses to quickly achieve homeostasis, especially in this species. Further studies are necessary to reveal the role of the Glu–GAD–GABA system in the modulation of stress situations as well as in body homeostasis. [ABSTRACT FROM AUTHOR]

Objective: Neurodegeneration is thought to be the primary cause of neurological disability in multiple sclerosis (MS). Dysfunctional RNA‐binding proteins (RBPs) including their mislocalization from nucleus to cytoplasm, stress granule formation, and altered RNA metabolism have been found to underlie neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia. Yet, little is known about the role of dysfunctional RBPs in the pathogenesis of neurodegeneration in MS. As a follow‐up to our seminal finding of altered RBP function in a single case of MS, we posited that there would be evidence of RBP dysfunction in cortical neurons in MS. Methods: Cortical neurons from 12 MS and six control cases were analyzed by immunohistochemistry for heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and TAR‐DNA‐binding protein‐43 (TDP‐43). Seven distinct neuronal phenotypes were identified based on the nucleocytoplasmic staining of these RBPs. Statistical analyses were performed by analyzing each phenotype in relation to MS versus controls. Results: Analyses revealed a continuum of hnRNP A1 and TDP‐43 nucleocytoplasmic staining was found in cortical neurons, from neurons with entirely nuclear staining with little cytoplasmic staining in contrast to those with complete nuclear depletion of RBPs concurrent with robust cytoplasmic staining. The neuronal phenotypes that showed the most nucleocytoplasmic mislocalization of hnRNP A1 and TDP‐43 statistically distinguished MS from control cases (P < 0.01, P < 0.001, respectively). Interpretation: The discovery of hnRNP A1 and TDP‐43 nucleocytoplasmic mislocalization in neurons in MS brain demonstrate that dysfunctional RBPs may play a role in neurodegeneration in MS, as they do in other neurological diseases. [ABSTRACT FROM AUTHOR]

Post-earthquake crisis management is a key capability for a country to be able to recover after a major seismic event. Instrumental seismic data transmitted and processed in a very short time can contribute to better management of the emergency and can give insights on the earthquake's impact on a specific area. Romania is a country with a high seismic hazard, mostly due to the Vrancea intermediate-depth earthquakes. The elastic acceleration response spectrum of a seismic motion provides important information on the level of maximum acceleration the buildings were subjected to. Based on new data analysis and knowledge advancements, the acceleration elastic response spectrum for horizontal ground components recommended by the Romanian seismic codes has been evolving over the last six decades. This study aims to propose a framework for post-earthquake warning based on code spectrum exceedances. A comprehensive background analysis was undertaken using strong motion data from previous earthquakes corroborated with observational damage, to prove the method's applicability. Moreover, a case-study for two densely populated Romanian cities (Focsani and Bucharest) is presented, using data from a 5.5 MW earthquake (October 28, 2018) and considering the evolution of the three generations of code-based spectral levels for the two cities. Data recorded in free-field and in buildings were analyzed and has confirmed that no structural damage occurred within the two cities. For future strong seismic events, this tool can provide useful information on the effect of the earthquake on structures in the most exposed areas. [ABSTRACT FROM AUTHOR]

The series of Er 2-x Ho x Fe 14 B (x = 0.5, 1.0, 1.5, 2.0) intermetallic compounds was studied in order to investigate different types of spin arrangements expected in this series. The variety of processes connected with spin reorientation, especially transition through conical spin arrangements was of special interest. The compounds have been measured with 57 Fe Mössbauer spectroscopy over the temperature range 5.2–320 K. Each compound was studied with precise Mössbauer scanning in the vicinity of the transition. A special fitting procedure of Mössbauer spectra, enabling to analyze up to ten spectra simultaneously, was developed to determine the arrangement of spins. The path of spin rotation was proposed. The results were verified and compared by applying computer simulations based on the Yamada-Kato model. The spin arrangement diagram was constructed. Obtained results are convincing enough to conclude that Mössbauer spectroscopy can be very helpful in studies of tilt angle in conical spin arrangements in the studied type compounds. [ABSTRACT FROM AUTHOR]

Computer systems with virtual memory are susceptible to design bugs and runtime faults in their address translation systems. Detecting bugs and faults requires a clear specification of correct behavior. A new framework for address translation aware memory consistency models addresses this need. [ABSTRACT FROM PUBLISHER]

White matter degeneration in the central nervous system (CNS) has been correlated with a decline in cognitive function during aging. Ultrastructural examination of the aging human brain shows a loss of myelin, yet little is known about molecular and biochemical changes that lead to myelin degeneration. In this study, we investigate myelination across the lifespan in C57BL/6 mice using electron microscopy and Fourier transform infrared (FTIR) spectroscopic imaging to better understand the relationship between structural and biochemical changes in CNS white matter tracts. A decrease in the number of myelinated axons was associated with altered lipid profiles in the corpus callosum of aged mice. FTIR spectroscopic imaging revealed alterations in functional groups associated with phospholipids, including the lipid acyl, lipid ester and phosphate vibrations. Biochemical changes in white matter were observed prior to structural changes and most predominant in the anterior regions of the corpus callosum. This was supported by biochemical analysis of fatty acid composition that demonstrated an overall trend towards increased monounsaturated fatty acids and decreased polyunsaturated fatty acids with age. To further explore the molecular mechanisms underlying these biochemical alterations, gene expression profiles of lipid metabolism and oxidative stress pathways were investigated. A decrease in the expression of several genes involved in glutathione metabolism suggests that oxidative damage to lipids may contribute to age-related white matter degeneration. [ABSTRACT FROM AUTHOR]

Objective: Histology reveals that early active multiple sclerosis lesions can be classified into 3 main interindividually heterogeneous but intraindividually stable immunopathological patterns of active demyelination (patterns I–III). In patterns I and II, a T‐cell‐ and macrophage‐associated demyelination is suggested, with pattern II only showing signs of a humoral immune response. Pattern III is characterized by inflammatory lesions with an oligodendrocyte degeneration. Patterns suggest pathogenic heterogeneity, and we postulated that they have distinct magnetic resonance imaging (MRI) correlates that may serve as biomarkers. Methods: We evaluated in an international collaborative retrospective cohort study the MRI lesion characteristics of 789 conventional prebiopsy and follow‐up MRIs in relation to their histopathologically classified immunopathological patterns (n = 161 subjects) and lesion edge features (n = 112). Results: A strong association of a ringlike enhancement and a hypointense T2‐weighted (T2w) rim with patterns I and II, but not pattern III, was observed. Only a fraction of pattern III patients showed a ringlike enhancement, and this was always atypical. Ringlike enhancement and T2w rims colocalized, and ringlike enhancement showed a strong association with macrophage rims as shown by histology. A strong concordance of MRI lesion characteristics, meaning that different lesions showed the same features, was found when comparing biopsied and nonbiopsied lesions at a given time point, indicating lesion homogeneity within individual patients. Interpretation: We provide robust evidence that MRI characteristics reflect specific morphological features of multiple sclerosis immunopatterns and that ringlike enhancement and T2w hypointense rims might serve as a valuable noninvasive biomarker to differentiate pathological patterns of demyelination. ANN NEUROL 2021;90:440–454 [ABSTRACT FROM AUTHOR]

Objective: Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disease. Iron distribution is altered in MS patients' brains, suggesting iron liberation within active lesions amplifies demyelination and neurodegeneration. Whether the amount and distribution of iron are similar or different among different MS immunopatterns is currently unknown. Methods: We used synchrotron X‐ray fluorescence imaging, histology, and immunohistochemistry to compare the iron quantity and distribution between immunopattern II and III early active MS lesions. We analyzed archival autopsy and biopsy tissue from 21 MS patients. Results: Immunopattern II early active lesions contain 64% more iron (95% confidence interval [CI] = 17–127%, p = 0.004) than immunopattern III lesions, and 30% more iron than the surrounding periplaque white matter (95% CI = 3–64%, p = 0.03). Iron in immunopattern III lesions is 28% lower than in the periplaque white matter (95% CI = −40 to −14%, p < 0.001). When normalizing the iron content of early active lesions to that of surrounding periplaque white matter, the ratio is significantly higher in immunopattern II (p < 0.001). Microfocused X‐ray fluorescence imaging shows that iron in immunopattern II lesions localizes to macrophages, whereas macrophages in immunopattern III lesions contain little iron. Interpretation: Iron distribution and content are heterogeneous in early active MS lesions. Iron accumulates in macrophages in immunopattern II, but not immunopattern III lesions. This heterogeneity in the two most common MS immunopatterns may be explained by different macrophage polarization, origin, or different demyelination mechanisms, and paves the way for developing new or using existing iron‐sensitive magnetic resonance imaging techniques to differentiate among immunopatterns in the general nonbiopsied MS patient population. ANN NEUROL 2021;89:498–510 [ABSTRACT FROM AUTHOR]

Cobalt (II) ferrite-chromites CoCr 2-x Fe x O 4 (x = 0.0 ÷ 2.0, step is 0.2) with spinel structure have been synthesized using sol-gel method with citrate metal-polymer precursor. The relations between structural, morphological and catalytic properties of the mixed spinels have been studied. The CoCr 2-x Fe x O 4 powders were analyzed using X-ray diffraction analysis, Mössbauer spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, energy-dispersive analysis and Brunauer–Emmett–Teller (BET) methods. The average crystallite size was calculated using the Williamson-Hall and size-strain plot methods. Increase of Fe content resulted in increase of the crystallite size from 10 nm (CoCr 2 O 4) to 35 nm (CoFe 2 O 4). Chromium ions were located mainly in octahedral sites, whereas the cobalt and ferric ions were distributed between the octahedral and tetrahedral sites. The lattice parameter was dependent mostly on the octahedral site radius. Superparamagnetic properties of the nanoparticles were described by two-level relaxation model. The samples with a high content of chromium (III) have highly porous structure. Porosity of the samples was decreased with increasing the Fe content. IR spectra contain two peaks corresponding to two characteristic sites in the cubic spinel structure. The mixed ferrite-chromite spinels have catalytic activity in decomposition of hydrogen peroxide. Rate of H 2 O 2 decomposition in the presence of cobalt (II) ferrite-chromite NPs corresponds to the first-order kinetic model. Within 25 min, the decomposition degree is 76.6% with the most active CoFe 2 O 4 sample. Catalytic activity of the samples depends on two factors: the specific surface area and the surface active sites. Antistructure modeling revealed that the tetrahedral Fe(III) sites have electron acceptor properties. The formed Fe(II) ions are active centers in the Fenton-like processes. Probably, the red-ox pairs Co2+/Co3+ in the spinel lattice promote catalytic activity due to acceleration of electron transfer. The spinel cobalt (II) ferrite-chromites are promising catalysts for oxidation of toxic organic impurities in wastewaters with using H 2 O 2. [ABSTRACT FROM AUTHOR]

Nanostructured Zn-doped cobalt ferrites (Co1−xZnxFe2O4, where x ranges from 0.0 to 1.0 with a step of 0.1) were studied in order to elucidate the relation between their cationic distribution within the spinel sublattices and catalytic properties. The thermal transformation of the precursors (metal hydroxides) obtained through the hydroxide co-precipitation method was studied by DTA, TGA and FTIR. The thermal behavior of the precursors showed that cobalt ferrite was formed at a lower temperature (376 °C) in comparison to zinc ferrite (478 °C). FTIR analysis revealed vibrational bands around 400 cm−1 and 600 cm−1 related to (MO4)6− and (MO6)9− groups, respectively. The cationic distribution was determined from Mössbauer spectra analysis and the results showed that Zn ions occupy the A-sites, while Co and Fe ions are located in the A- and B-sites. The spectra indicate spinel magnetic ordering in samples with x = 0.0…0.5. The increase in Zn content influences the difference in the Pauling electronegativities, distances between magnetic ions (hopping length) and polaron radius of Co1−xZnxFe2O4 ferrites, inducing changes in the ionic bond strength for the A- and B-sites. Photoelectrochemical measurements demonstrated that the introduction of Zn2+ into the spinel structure modifies the ability of the materials to reduce O2. Whereas photoinduced reduction of dioxygen at CoFe2O4 competes successfully with anodic photocurrent generation (observed as a decrease of photocurrent), for ZnFe2O4 this process is negligible. The relation between the cationic distribution (analyzed in terms of antistructure modeling) and the catalytic activity of spinel ferrites was demonstrated for the example of the soot combustion process. It was shown that the octahedral cobalt centers exhibit a higher catalytic activity than the tetrahedral ones. [ABSTRACT FROM AUTHOR]

Abstract Dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonuclear protein A1 (hnRNP A1) has been shown to contribute to the pathogenesis of neurodegenerative diseases, but its involvement in multiple sclerosis (MS) is largely unknown. In a neuronal cell line, interferon-γ caused hnRNP A1 nucleocytoplasmic mislocalization; colocalization of hnRNP A1 in stress granules (SGs); and inhibition of translation. Neurons in the brain of a MS patient showed pathogenic RBP dysfunction, including nuclear depletion of hnRNP A1, its mislocalization to the cytoplasm, and its colocalization in SGs. These data indicate a role for dysfunctional hnRNP A1 in the pathogenesis of MS. Graphical abstract Unlabelled Image Highlights • The RNA binding protein hnRNP A1 is dysfunctional in MS. • IFNγ contributes to hnRNP A1 dysfunction. • Neurons in MS brain show pathogenic features of hnRNP A1 dysfunction. • The features include hnRNP A1 nuclear depletion & colocalization in cytoplasmic stress granules. [ABSTRACT FROM AUTHOR]

We studied the magnetic properties of ferromagnetic-semiconductor composites based on nickel and porous-GaN, motivated by the effort to couple magnetic and semiconductor functionality. Nickel-infiltrated and nickel-coated (laminated thin-film) porous GaN structures were fabricated by electrodeposition, and their magnetic properties were subsequently examined collectively, by vibrating sample magnetometry and on the nanoscale, by magnetic force microscopy. We successfully demonstrated the ability to realize nickel infiltrated porous GaN, where the magnetic properties were dominated by the infiltrated material without a measurable surface contribution. We found that the structure and magnetization of electrodeposited porous-GaN/Ni composites depended on GaN degree of porosity and the amount of deposited nickel. The magnetization evolves from a nearly isotropic response in the infiltrated structures, to a shape-anisotropy controlled magnetic thin-film behavior. Furthermore, both infiltrated and thin-film nickel electrodeposited on porous GaN were found to have low (< 0.1%) strain and corresponding low coercivity: < 6.4 and < 2.4 kA/m for infiltrated and thin-film, correspondingly. An unconventional trend of increased remanence at room temperature, compared to cryogenic temperature, was observed in the thin film. The most likely cause for these findings is increased compliance of the porous GaN compared to bulk, allowing strain relaxation at room temperature. These results encourage deeper investigation of magnetic nanostructure property tuning and of magnetic property coupling to GaN and similar materials. • Nickel was electrodeposited on nanoporous GaN. • GaN conductivity and pore size determine nickel infiltration and cover. • Nickel was found to have minimal strain, attributed to the soft porous substrate. • The magnetization of nickel infiltrated in porous GaN develops with deposited material from nearly isotropic to the anisotropic response typical of a thin-film. • The remanence of nickel thin-film was found to increase from cryogenic to room temperature, attributed to strain relaxation. [ABSTRACT FROM AUTHOR]

NanoPDF64 is a tool designed for structural analysis of nanocrystals based on examination of powder diffraction data with application of real-space analysis. The program allows for fast building of models of nanocrystals consisting of up to several hundred thousand atoms with either cubic or hexagonal close packed structure. The nanocrystal structure may be modified by introducing stacking faults, density modulation waves ( i.e. the core-shell model) and thermal atomic vibrations. The program calculates diffraction patterns and, by Fourier transform, the reduced pair distribution functions G( r) for the models. Experimental G( r)s may be quantitatively analyzed by least-squares fitting with an analytical formula. [ABSTRACT FROM AUTHOR]

Summary: The identification of pathological processes that could be targeted by therapeutic interventions is a major goal of research into multiple sclerosis (MS). Pathological assessment is the gold standard for such identification, but has intrinsic limitations owing to the limited availability of autopsy and biopsy tissue. MRI has gained a leading role in the assessment of MS because it allows doctors to obtain an ante mortem picture of the degree of CNS involvement. A number of correlative pathological and MRI studies have helped to define in vivo the pathological substrates of MS in focal lesions and normal-appearing white matter, not only in the brain, but also in the spinal cord. These studies have resulted in the identification of aspects of pathophysiology that were previously neglected, including grey matter involvement and vascular pathology. Despite these important achievements, numerous open questions still need to be addressed to resolve controversies about how the pathology of MS results in fixed neurological disability. [ABSTRACT FROM AUTHOR]

Summary As basal cell carcinoma (BCC) is the most frequent form of skin cancer with local malignancy, we focused on assessing the apoptotic/proliferative indexes and lymphocytic inflammatory infiltrate, and attempt to link these data with the low invasivity of the tumor. Twenty-six BCC cases were included in the study, confirmed as either nodular, morpheiform or adenoid type. On serial sections, immunohistochemistry was utilized to visualize markers for the lymphocytic infiltrate (CD20cy and CD3), apoptosis (activated caspase-3) and mitosis (Ki-67). Automated quantification of the signals of each of these markers was next performed by computer-assisted image analysis. In BCC, a high mitotic index is paralleled by a high apoptotic index, this probably explaining directly the benign evolution of the tumors, although morpheiform and adenoid forms are more infiltrative in the surrounding tissue. The stromal lymphocytic infiltrate was composed of mostly T lymphocytes, and did not correlate with the apoptotic/mitotic indexes, but it was increased in the more aggressive forms. In BCC at least, analyzing both mitotic and apoptotic indexes would be a more straightforward evaluation of a tumor's dynamics. Although inflammatory infiltrate gives important clues regarding tumor invasive capacity, this should not be regarded aside from the proliferative/apoptotic indexes. [ABSTRACT FROM AUTHOR]

The magnesium-zinc ferrites Mg 1-x Zn x Fe 2 O 4 (x = 0...1) were studied as magnetic sorbents for environmental applications. Low-temperature Mössbauer spectroscopy was used to determine the distribution of magnesium and ferric ions in the spinel crystal lattice. The influence of Zn content on magnetic parameters was investigated on the basis of VSM data. As the molar ratio of zinc to magnesium increases from 0 to 1, the pH PZC value decreases from 10.5 to 8.9. Langmuir and Freundlich models were used to check whether single-layer or multi-layer adsorption occurs. The adsorption of Cr(VI) and Ni(II) ions is well fitted by the Langmuir equation. To check the physical or chemical nature of the sorption process, the Dubinin-Radushkevich equation was used. It was found that the processes of adsorption of Cr(VI) and Ni(II) ions are of a chemical nature. The best Cr(VI) ion adsorption capacity was found for the Mg 0·2 Zn 0·8 Fe 2 O 4 sample (q e = 30.49 mg/g). The percentage of heavy metal removal by the mixed ferrite samples increases with increasing zinc content. The most effective sorbent for Ni(II) removal is the Mg 0·4 Zn 0·6 Fe 2 O 4 sample (93.2%). Modeling the antistructure provides deeper insight into the mechanism of heavy metal adsorption. The obtained magnesium-zinc ferrites are promising magnetic adsorbents for removing chromate and nickel ions from the environment. Image 1 • Magnesium-zinc ferrites were investigated as adsorbents for the Cr(VI) and Ni(II) removal. • Mg 0·2 Zn 0·8 Fe 2 O 4 sample showed the best adsorption capacity (q e = 30.49 mg/g). • Mg 0·4 Zn 0·6 Fe 2 O 4 sample is the most effective sorbent for Ni(II) removal (93.2%). • Adsorption capacity is influenced by the surface active centers. • The higher the content of octahedral Mg cations, the lower the adsorption capacity. [ABSTRACT FROM AUTHOR]

Mg–Zn ferrites with porous cavity structure were produced by sol-gel auto-combustion method utilizing a new mixture of dl -alanine and urea as an organic fuel-reductant. The influence of non-magnetic Zn ions content on the structural, morphological and adsorption characteristics of Mg–Zn NPs has been investigated. It was found that Zn effects the porosity of Mg–Zn ferrospinels. X-ray diffraction analysis confirmed the formation of cubic spinel phase and the crystallite size was calculated by the SSP method, W-H method and modified Scherrer formula. SEM observations revealed mesh-like microstructure with the presence of 1–2 μm macropores and agglomerated nanoparticles. The EDS spectra confirmed the desired chemical composition of ferrites powders. Mössbauer spectroscopy confirmed the valence state of cations and their distribution over the spinel sublattices. The adsorption characteristics of spinel compounds were studied on Congo Red dye removal. The appropriateness of Langmuir, Freundlich, and Dubinin-Radushkevich adsorption models were investigated and the parameters of all models were determined. The observed data fitted well by Langmuir model, indicating that the Congo Red adsorption occurred on a homogeneous surface and that the active surface centers possessed similar energy values. The Dubinin-Radushkevich isotherm model was utilized to calculate the free energy of Congo Red adsorption, i.e. setting in the range 7.81–22.4 kJ/mol and indicating that the Zn content affects the mechanism of Congo Red adsorption onto ferrite surfaces and the removal efficiency is enhanced with the rise in Zn content. Image 1 • Mg–Zn ferrites with porous cavity microstructure have been synthesized. • Cationic distribution of Mg–Zn ferrites confirmed by both XRD and Mossbauer spectroscopy. • Presence of Zn ions in Mg ferrite enhance its surface morphology. • Mg–Zn ferrites exhibit enhanced adsorption efficiency for the Congo Red dye. [ABSTRACT FROM AUTHOR]

Objective: Despite the advances in treatments for multiple sclerosis (MS), unremitting neurodegeneration continues to drive disability and disease progression. Smoldering/slowly expanding lesions (SELs) and dysfunction of the RNA binding protein (RBP) heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) are pathologic hallmarks of MS cortex and intricately tied to disability and neurodegeneration, respectively. We hypothesized that neuronal hnRNP A1 dysfunction contributes to neurodegeneration and is exacerbated by smoldering/SELs in progressive MS., Methods: Neuronal hnRNP A1 pathology (nucleocytoplasmic mislocalization of hnRNP A1) was examined in healthy control and MS brains using immunohistochemistry. MS cases were stratified by severity of hnRNP A1 pathology to examine the link between RBP dysfunction, demyelination, and neurodegeneration., Results: We found that smoldering/SELs were only present within a subset of MS tissues characterized by elevated neuronal hnRNP A1 pathology (MS-A1 high ) in adjacent cortical gray matter. In contrast to healthy controls and MS with low hnRNP A1 pathology (MS-A1 low ), MS-A1 high showed elevated markers of neurodegeneration, including neuronal loss and injury, brain atrophy, axonal loss, and axon degeneration. Additionally, we discovered a subpopulation of morphologically intact neurons lacking expression of NeuN, a neuron-specific RBP, in cortical projection neurons in MS-A1 high cases., Interpretation: hnRNP A1 dysfunction contributes to neurodegeneration and may be exacerbated by smoldering/SELs in progressive MS. The discovery of NeuN-negative neurons suggests that some cortical neurons may only be injured and not lost. By characterizing RBP pathology in MS cortex, this study has important implications for understanding the pathogenic mechanisms driving neurodegeneration, the substrate of disability and disease progression. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Introduction: During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the management of patients with lower urinary tract symptoms (LUTS) underwent dynamic adjustments in response to an evolving understanding of the virus's impact on different patient populations. Healthcare practitioners reevaluated therapeutic approaches for conditions like benign prostatic hyperplasia (BPH), considering the potential implications of this condition on the severity and progression of coronavirus disease 2019 (COVID-19). This study aims to investigate potential correlations between SARS-CoV-2 infection severity, exacerbation of LUTS, and BPH progression., Material and Methods: This retrospective study includes patients hospitalized in our Urology Department between January 2021 and January 2023, presenting with both SARS-CoV-2 and BPH. Their ages ranged from 57 to 88 years, with a mean age of 65.4 years. The diagnosis of BPH relied on a diagnostic triad consisting of digital rectal examination, biological markers (including prostate-specific antigen (PSA) and free PSA, and ultrasound examination, with both conditions confirmed based on test results. Transurethral resection of the prostate (TURP) procedures utilized monopolar Karl Storz resection equipment, using sorbitol and bipolar Olympus devices for transurethral resection of the prostate in saline (TURPis). Haemostasia was performed using roller balls. Anticoagulation followed a prescribed scheme by cardiologists and infectious disease specialists. Statistical analysis was conducted using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp., Results: Among the 138 hospitalized patients affected by both BPH and COVID-19, 18 required emergency endoscopic procedures (specifically TURP or TURPis) to achieve hemostasis (Figures 1, 2). These individuals presented persistent hematuria despite conservative treatments. The mean duration of surgery was 57.9 minutes. Patients who underwent surgery had a longer average hospital stay compared to those who did not, with durations of 10.5 days versus 7.5 days, respectively. Additionally, urethrovesical catheter insertion was necessary in 29 cases due to acute urinary retention or worsening voiding symptoms during hospitalization. These patients are scheduled for further urological evaluation following the resolution of the COVID-19 episode. In a cohort of 53 patients for whom data were accessible, comparisons were made between the pre-COVID status and the levels of the International Prostate Symptom Score (IPSS), post-voiding residue (PVR), and quality of life (QoL). The findings revealed a mean pre-COVID IPSS value of 11.6 and a COVID-related value of 14.2, with a statistically significant difference noted (p < 0.05). The mean pre-COVID PVR was 42.3 cm 2 , whereas during the COVID-19 period, it measured 62.5 cm 2 , also exhibiting a significant difference (p < 0.05). Additionally, the QoL showed a mean pre-COVID-19 score of 2.4 and a COVID-19-associated score of 2.9, again demonstrating statistical significance (p < 0.05)., Conclusion: The onset of the SARS-CoV-2 pandemic posed novel challenges in the medical realm, impacting the approach to BPH management. A common practice was delaying treatment for chronic BPH until viral infection remission to reduce associated risks. Additionally, our study revealed a worse evolution in LUTS among individuals with severe COVID-19 symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Balacescu et al.)

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that remarkable facilitate the aminoacylation process during translation. With a high fidelity, the mischarged tRNA is prevented through implementing pre- and post-transfer proofreading mechanisms. For instance, Lysine-tRNA synthetase charges the native substrate, lysine, to its cognate tRNA. In spite of the great structural similarity between lysine to the noncognate and toxic ornithine, with the side chain of lysine being only one methylene group longer, LysRS is able to achieve this discrimination with a high efficiency. In this work, the hybrid quantum mechanics/molecular mechanics (QM/MM) investigation was applied to probe the pre-transfer editing mechanism catalyzed by lysyl-tRNA synthetase to reject the noncognte aminoacyl, L-ornityl (Orn), compared to the cognate substrate, L-lysyl. Particularly, the self-cyclization pre-transfer editing mechanism was explored for the two substrates. The substrate-assisted self-cyclization editing of Orn-AMP, where its phosphate moiety acts as the catalytic base, is found to be the rate-determining step with an energy barrier of 101.2 kJ mol -1 . Meanwhile, the corresponding rate-limiting pathway for the native Lys-AMP lies at 140.2 kJ mol -1 . This observation clearly indicated the infeasibility of this catalytic scenario in the presence of the native substrate. Interestingly, a thermodynamically favorable cyclic product of -92.9 kJ mol -1 with respect to the aminoacyl reactant complex demonstrated evidence of a successful pre-transfer editing. This reaction resulted in the discharge of the on-cognate -ornithine derivative from LysU's active site. These valuable mechanistic insights are valuable to enrich our knowledge of this extremely efficient and specific catalytic machinery of LysRS.Communicated by Ramaswamy H. Sarma.

In situ methods are valuable in all fields of research. In toxicology, the importance of dose is well known, elevating the need for in situ techniques to measure levels of toxicants and their byproducts in precise anatomically identifiable locations. More recently, additional emphasis has been placed on the value of techniques which can detect chemical form or speciation, which is equally important in the toxicology of a chemical compound. Many important but conventional methods risk losing valuable information due to extractions, digestions, or the general reliance on mobile phases. Few analytical tools possess the power and diversity of X-ray methods as in-situ methods. Here we present an overview, intended for toxicologists and pathologists, of a variety of synchrotron X-ray methods for determining in situ chemical form and distribution of heavier elements. The versatility and range of these synchrotron techniques, which are both established and emerging, is demonstrated in the context of the study of neurotoxicology of mercury, a global pollutant with the ability to harm both human health and the environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Remyelination and neurodegeneration prevention mitigate disability in Multiple Sclerosis (MS). We have shown acute intermittent hypoxia (AIH) is a novel, non-invasive and effective therapy for peripheral nerve repair, including remyelination. Thus, we posited AIH would improve repair following CNS demyelination and address the paucity of MS repair treatments. AIH's capacity to enhance intrinsic repair, functional recovery and alter disease course in the experimental autoimmune encephalomyelitis (EAE) model of MS was assessed. EAE was induced by MOG 35-55 immunization in C57BL/6 female mice. EAE mice received either AIH (10 cycles-5 min 11% oxygen alternating with 5 min 21% oxygen) or Normoxia (control; 21% oxygen for same duration) once daily for 7d beginning at near peak EAE disease score of 2.5. Mice were followed post-treatment for an additional 7d before assessing histopathology or 14d to examine maintenance of AIH effects. Alterations in histopathological correlates of multiple repair indices were analyzed quantitatively in focally demyelinated ventral lumbar spinal cord areas to assess AIH impacts. AIH begun at near peak disease significantly improved daily clinical scores/functional recovery and associated histopathology relative to Normoxia controls and the former were maintained for at least 14d post-treatment. AIH enhanced correlates of myelination, axon protection and oligodendrocyte precursor cell recruitment to demyelinated areas. AIH also effected a dramatic reduction in inflammation, while polarizing remaining macrophages/microglia toward a pro-repair state. Collectively, this supports a role for AIH as a novel non-invasive therapy to enhance CNS repair and alter disease course following demyelination and holds promise as a neuroregenerative MS strategy., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)