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Myelinating oligodendrocytes arise from the stepwise differentiation of oligodendrocyte progenitor cells (OPCs). Approximately 5% of all adult brain cells are OPCs. Why would a mature brain need such a large number of OPCs? New myelination is possibly required for higher‐order functions such as cognition and learning. Additionally, this pool of OPCs represents a source of new oligodendrocytes to replace those lost during injury, inflammation, or in diseases such as multiple sclerosis (MS). How OPCs are instructed to differentiate into oligodendrocytes is poorly understood, and for reasons presently unclear, resident pools of OPCs are progressively less utilized in MS. The complement component 1, q subcomponent‐like (C1QL) protein family has been studied for their functions at neuron–neuron synapses, but we show that OPCs express C1ql1. We created OPC‐specific conditional knockout mice and show that C1QL1 deficiency reduces the differentiation of OPCs into oligodendrocytes and reduces myelin production during both development and recovery from cuprizone‐induced demyelination. In vivo over‐expression of C1QL1 causes the opposite phenotype: increased oligodendrocyte density and myelination during recovery from demyelination. We further used primary cultured OPCs to show that C1QL1 levels can bidirectionally regulate the extent of OPC differentiation in vitro. Our results suggest that C1QL1 may initiate a previously unrecognized signaling pathway to promote differentiation of OPCs into oligodendrocytes. This study has relevance for possible novel therapies for demyelinating diseases and may illuminate a previously undescribed mechanism to regulate the function of myelination in cognition and learning. [ABSTRACT FROM AUTHOR]

CSF1R-related disorder (CSF1R-RD) is a neurodegenerative condition that predominantly affects white matter due to genetic alterations in the CSF1R gene, which is expressed by microglia. We studied an elderly man with a hereditary, progressive dementing disorder of unclear etiology. Standard genetic testing for leukodystrophy and other neurodegenerative conditions was negative. Brain autopsy revealed classic features of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), including confluent white matter degeneration with axonal spheroids and pigmented glial cells in the affected white matter, consistent with CSF1R-RD. Subsequent long-read sequencing identified a novel deletion in CSF1R that was not detectable with short-read exome sequencing. To gain insight into potential mechanisms underlying white matter degeneration in CSF1R-RD, we studied multiple brain regions exhibiting varying degrees of white matter pathology. We found decreased CSF1R transcript and protein across brain regions, including intact white matter. Single nuclear RNA sequencing (snRNAseq) identified two disease-associated microglial cell states: lipid-laden microglia (expressing GPNMB, ATG7, LGALS1, LGALS3) and inflammatory microglia (expressing IL2RA, ATP2C1, FCGBP, VSIR, SESN3), along with a small population of CD44+ peripheral monocyte-derived macrophages exhibiting migratory and phagocytic signatures. GPNMB+ lipid-laden microglia with ameboid morphology represented the end-stage disease microglia state. Disease-associated oligodendrocytes exhibited cell stress signatures and dysregulated apoptosis-related genes. Disease-associated oligodendrocyte precursor cells (OPCs) displayed a failure in their differentiation into mature myelin-forming oligodendrocytes, as evidenced by upregulated LRP1, PDGFRA, SOX5, NFIA, and downregulated NKX2-2, NKX6.2, SOX4, SOX8, TCF7L2, YY1, ZNF488. Overall, our findings highlight microglia–oligodendroglia crosstalk in demyelination, with CSF1R dysfunction promoting phagocytic and inflammatory microglia states, an arrest in OPC differentiation, and oligodendrocyte depletion. [ABSTRACT FROM AUTHOR]

Background and Purpose: ApTOLL is an aptamer selected to antagonize toll‐like receptor 4 (TLR4), a relevant actor for innate immunity involved in inflammatory responses in multiple sclerosis (MS) and other diseases. The currently available therapeutic arsenal to treat MS is composed of immunomodulators but, to date, there are no (re)myelinating drugs available in clinics. In our present study, we studied the effect of ApTOLL on different animal models of MS. Experimental Approach: The experimental autoimmune encephalomyelitis (EAE) model was used to evaluate the effect of ApTOLL on reducing the inflammatory component. A more direct effect on oligodendroglia was studied with the cuprizone model and purified primary cultures of murine and human oligodendrocyte precursor cells (OPCs) isolated through magnetic‐activated cell sorting (MACS) from samples of brain cortex. Also, we tested these effects in an ex vivo model of organotypic cultures demyelinated with lysolecithin (LPC). Key Results: ApTOLL treatment positively impacted the clinical symptomatology of mice in the EAE and cuprizone models, which was associated with better preservation plus restoration of myelin and oligodendrocytes in the demyelinated lesions of animals. Restoration was corroborated on purified cultures of rodent and human OPCs. Conclusion and Implications: Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti‐inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients. [ABSTRACT FROM AUTHOR]

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS. [ABSTRACT FROM AUTHOR]

For the first time, this paper explores the role of hydration kinetics on microcrack development in cement mortars using the μ-CT technique with a resolution of 2.2 µm. Three binders were tested: fine-grained ordinary Portland cement (OPC) with Blaine fineness of 391 m2/kg, coarse-grained OPC made from the same clinker with Blaine fineness of 273 m2/kg, and H-cement as a representative of the alkali-activated binder. It was found that most microcracks have a width in the range of 5–10 µm, increasing their occurrence with the progress of sealed hydration. While H-cement and coarse-grained OPC showed a comparable number of microcracks, fine-grained OPC exhibited more than twice the number of microcracks. In this sense, high hydration kinetics induce more microcracks, promoting later coalescence into visible cracks and disintegration of concrete at the end. Therefore, durable concrete with minimum microcracks should be derived from slow hydration kinetics or alkali-activation processes. [ABSTRACT FROM AUTHOR]

This Perspectives paper advances understanding of coaching in pediatric rehabilitation. We compare three coaching approaches designed for pediatric rehabilitation: Coping with and Caring for Infants with Special Needs (COPCA), Occupational Performance Coaching (OPC), and Solution-Focused Coaching in Pediatric Rehabilitation (SFC-peds). Our objectives are to contrast the theory underpinning the approaches, discuss the evidence for outcomes and hypothesized mechanisms of change, consider the necessary mindsets of effective coaches, and propose directions for research and practice. The coaching approaches have different theoretical bases and are designed for specific contexts, yet are similar in their mechanisms of change and intended outcomes. There is growing evidence of important effects of coaching on coachees' goal achievement, empowerment, and capacity building. Studies indicate that stakeholders value coaching, and provide a preliminary understanding of the mechanisms, including engagement and self-efficacy, by which coaching approaches support clients' self-directed and sustained change. Open, curious, and client-centered practitioner mindsets are fundamental to effective coaching. Coaching is a distinctive group of relational, goal-oriented, and evidence-based approaches that support goal achievement and empowerment. These approaches reflect and advance an ongoing paradigm shift in pediatric rehabilitation—a movement from therapist-as-expert approaches to those that build empowerment and capacity. Coaching is a distinctive group of theory-based approaches that support clients' goal achievement and empowerment, and build capacity Coaching practitioners are collaborative facilitators who assist clients and families with their own discovery of solutions that fit their everyday contexts The evidence suggests that coaching triggers engagement and self-efficacy, which are the mechanisms by which changes in longer-term outcomes occur Open, curious, and client/family-centered practitioner mindsets are fundamental to effective coaching [ABSTRACT FROM AUTHOR]

HPV16 is responsible for approximately 60% and 90% of global HPV–induced cervical and oropharyngeal cancers, respectively. HPV16 intratype variants have been identified by HPV genome sequencing and classified into four phylogenetic lineages (A–D). Our understanding of HPV16 variants mostly derives from epidemiological studies on cervical cancer (CC) in which HPV16 B, C, and D lineages (previously named "non-European" variants) were mainly associated with high-grade cervical lesions and cancer. Although a predominance of HPV16 lineage A (previously named "European variants") has been observed in head and neck squamous cell carcinoma (HNSCC), epidemiological and in vitro biological studies are still limited for this tumor site. Next Generation Sequencing (NGS) of the entire HPV genome has deepened our knowledge of the prevalence and distribution of HPV variants in CC and HNSCC. Research on cervical cancer has shown that certain HPV16 sublineages, such as D2, D3, A3, and A4, are associated with an increased risk of cervical cancer, and sublineages A4, D2, and D3 are linked to a higher risk of developing adenocarcinomas. Additionally, lineage C and sublineages D2 or D3 of HPV16 show an elevated risk of developing premalignant cervical lesions. However, it is still crucial to conduct large-scale studies on HPV16 variants in different HPV–related tumor sites to deeply evaluate their association with disease development and outcomes. This review discusses the current knowledge and updates on HPV16 phylogenetic variants distribution in HPV–driven anogenital and head and neck cancers. [ABSTRACT FROM AUTHOR]

Aerosols, as well as suspended particulate matter, impact atmospheric pollution, the climate, and human health, directly or indirectly. Particle size, chemical composition, and other aerosol characteristics are determinant factors for atmospheric pollution dynamics and more. In the last decade, low-cost devices have been widely used in instrumentation to measure aerosols. However, they present some issues, such as the problem of discriminating whether the aerosol is composed of liquid particles or solid. This issue could lead to errors in the estimation of mass concentration in monitoring environments where there is fog. In this study, we investigate the use of an optical particle counter (OPC) coupled to a quartz crystal microbalance with an integrated microheater (H-QCM) to enhance measurement performances. The H-QCM was used not only to measure the collected mass on its surface but also, by using the integrated microheater, it was able to heat the collected mass by performing heating cycles. In particular, we tested the developed system with aerosolized saline solutions of sodium chloride (NaCl), with three decreasing concentrations of salt and three electronic cigarette solutions (e-liquid), with different concentrations of propylene glycol and glycerin mixtures. The results showed that the OPC coherently counted the salt dilution effects, and the H-QCM output confirmed the presence of liquid and solid particles in the aerosols. In the case of e-liquid aerosols, the OPC counted the particles, and the HQCM output highlighted that in the aerosol, there were no solid particles but a liquid phase only. These findings contribute to the refinement of aerosol measurement methodologies by low-cost sensors, fostering a more comprehensive understanding. [ABSTRACT FROM AUTHOR]

Oligodendrocyte progenitor cells (OPCs) were regarded for years solely for their regenerative role; however, their immune‐modulatory roles have gained much attention recently, particularly in the context of multiple sclerosis (MS). Despite extensive studies on OPCs, there are limited data elucidating the interactions between their intrinsic regenerative and immune functions, as well as their relationship with the inflamed central nervous system (CNS) environment, a key factor in MS pathology. We examined the effects of pro‐inflammatory cytokines, represented by interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α, as well as anti‐inflammatory cytokines, represented by interleukin (IL)‐4 and IL‐10, on OPC differentiation and immune characteristics. Using primary cultures, enzyme‐linked immunosorbent assay and immunofluorescence stainings, we assessed differentiation capacity, phagocytic activity, major histocompatibility complex (MHC)‐II expression, and cytokine secretion. We observed that the anti‐inflammatory milieu (IL4 and IL10) reduced both OPC differentiation and immune functions. Conversely, exposure to TNF‐α led to intact differentiation, increased phagocytic activity, high levels of MHC‐II expression, and cytokines secretion. Those effects were attributed to signalling via TNF‐receptor‐2 and counteracted the detrimental effects of IFN‐γ on OPC differentiation. Our findings suggest that a pro‐regenerative, permissive inflammatory environment is needed for OPCs to execute both regenerative and immune‐modulatory functions. [ABSTRACT FROM AUTHOR]

Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors. [ABSTRACT FROM AUTHOR]

Background: To retrospectively access outcome, adverse events and prognostic factors in oropharyngeal carcinoma (OPC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: Ninety-eight OPC patients were treated between 2000 and 2015. Thirty-three patients received definitive and 65 adjuvant radiotherapy. Seventy-one percent had simultaneous chemotherapy. Patients were systematically followed up (mean 114 months, range 19-197 months). Statistical analysis used Kaplan-Meier method, Cox regression analysis, and log-rank test. Adverse events were classified according to common toxicity criteria version (CTCAE) 4.03. Results: The 1-, 5-, and 10-year overall survival rates in the adjuvant vs. definitive cohort were 90.8% vs. 66.7%, 67.4% vs. 33.1%, and 57.7% vs. 16.5%. Survival in the adjuvant cohort was significantly longer than in the definitive cohort (P < 0.00005). Patients <65 years had a significantly longer survival than older patients. Locoregional tumor control rates after 1-, 5-, and 10 years in the adjuvant vs. definitive cohort were 90.2% vs. 66.7%, 82.2% vs 45.4%, and 72.1% vs. 30.3%. Locoregional tumor control in the adjuvant cohort was significantly longer than in the definite cohort (P < 0.005). Distant metastases were diagnosed in 20.4% of all patients. Most patients had mild CTCAE grade 1 and 2 adverse events and mild late adverse events including xerostomia, dysphagia, and lymphedema. Conclusion: Intensity-modulated radiotherapy for OPC is an important part of the treatment algorithm alone and in particular after surgery while the additional benefits of chemotherapy might be age dependent. Despite advanced tumor stages, nearly half of our patients were alive in the long term. The majority of patients had relatively mild chronic adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the occupational variation in incidence of oropharyngeal cancer (OPC). Methods: We calculated standardized incidence ratios (SIRs) of OPC in occupational categories in the Nordic countries relative to the entire national populations. The data covered 6155 OPC cases. Results: Among men high risk of OPC was observed, among else, in waiters (SIR 6.28, 95% CI 4.68–8.26), beverage workers (SIR 3.00, 95% CI 1.72–4.88), and artistic workers (SIR 2.97, 95% CI 2.31–3.76). Among women high risk of OPC was observed in waiters (SIR 2.02, 95% CI 1.41–2.81) and packers (SIR 1.73, 95% CI 1.07–2.64). The lowest SIRs were observed in female gardeners (SIR 0.27, 95% CI 0.12–0.51) and male farmers (SIR 0.30, 95% CI 0.25–0.35). Conclusion: The 20-fold variation in incidence of OPC between occupations needs further investigation in studies with detailed information on occupational and non-occupational risk factors. [ABSTRACT FROM AUTHOR]

In the central nervous system, oligodendrocyte precursor cells (OPCs) are recognized as the progenitors responsible for the generation of oligodendrocytes, which play a critical role in myelination. Extensive research has shed light on the mechanisms underlying OPC proliferation and differentiation into mature myelin-forming oligodendrocytes. However, recent advances in the field have revealed that OPCs have multiple functions beyond their role as progenitors, exerting control over neural circuits and brain function through distinct pathways. This review aims to provide a comprehensive understanding of OPCs by first introducing their well-established features. Subsequently, we delve into the emerging roles of OPCs in modulating brain function in both healthy and diseased states. Unraveling the cellular and molecular mechanisms by which OPCs influence brain function holds great promise for identifying novel therapeutic targets for central nervous system diseases. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease is characterised by decreased cerebral blood flow and blood–brain barrier impairments which play a key role in the development of white matter lesions. We hypothesised that cerebral hypoperfusion causes local hypoxia, affecting oligodendrocyte precursor cell—endothelial cell signalling leading to blood–brain barrier dysfunction as an early mechanism for the development of white matter lesions. Bilateral carotid artery stenosis was used as a mouse model for cerebral hypoperfusion. Pimonidazole, a hypoxic cell marker, was injected prior to humane sacrifice at day 7. Myelin content, vascular density, blood–brain barrier leakages, and hypoxic cell density were quantified. Primary mouse oligodendrocyte precursor cells were exposed to hypoxia and RNA sequencing was performed. Vegfa gene expression and protein secretion was examined in an oligodendrocyte precursor cell line exposed to hypoxia. Additionally, human blood plasma VEGFA levels were measured and correlated to blood–brain barrier permeability in normal-appearing white matter and white matter lesions of cerebral small vessel disease patients and controls. Cerebral blood flow was reduced in the stenosis mice, with an increase in hypoxic cell number and blood–brain barrier leakages in the cortical areas but no changes in myelin content or vascular density. Vegfa upregulation was identified in hypoxic oligodendrocyte precursor cells, which was mediated via Hif1α and Epas1. In humans, VEGFA plasma levels were increased in patients versus controls. VEGFA plasma levels were associated with increased blood–brain barrier permeability in normal appearing white matter of patients. Cerebral hypoperfusion mediates hypoxia induced VEGFA expression in oligodendrocyte precursor cells through Hif1α/Epas1 signalling. VEGFA could in turn increase BBB permeability. In humans, increased VEGFA plasma levels in cerebral small vessel disease patients were associated with increased blood–brain barrier permeability in the normal appearing white matter. Our results support a role of VEGFA expression in cerebral hypoperfusion as seen in cerebral small vessel disease. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) play diverse roles in the brain, extending beyond their classically recognized contributions to oligodendrogenesis and myelination. In the developing and adult visual system, OPCs have been shown to remodel axons and to eliminate synapses through phagocytic engulfment. The engulfment of synapses by OPCs is influenced by multiple factors, including neural activity and molecular signals from other brain cells. Future work is needed to define the biological consequences and underlying molecular mechanisms of synapse engulfment by OPCs. Oligodendrocyte precursor cells (OPCs) are non-neuronal brain cells that give rise to oligodendrocytes, glia that myelinate the axons of neurons in the brain. Classically known for their contributions to myelination via oligodendrogenesis, OPCs are increasingly appreciated to play diverse roles in the nervous system, ranging from blood vessel formation to antigen presentation. Here, we review emerging literature suggesting that OPCs may be essential for the establishment and remodeling of neural circuits in the developing and adult brain via mechanisms that are distinct from the production of oligodendrocytes. We discuss the specialized features of OPCs that position these cells to integrate activity-dependent and molecular cues to shape brain wiring. Finally, we place OPCs within the context of a growing field focused on understanding the importance of communication between neurons and glia in the contexts of both health and disease. [ABSTRACT FROM AUTHOR]

aOPCs populate the entire mature CNS throughout the lifespan. The main properties of aOPCs are highly idiosyncratic. They have a complex morphology with motile processes and proliferate well into advanced ages. They receive and form synaptic contacts and many aOPCs are electrically excitable. In various forms of neuropathology, aOPCs undergo multiple and complex transformations. Pathological changes of aOPCs include degeneration and death, changes in reactivity, atrophy with loss of function, and the emergence of aberrant phenotypes which may drive pathological progression. In brain pathologies, aOPCs are the main source of CNS remyelination and are often considered in the context of this role. Emerging evidence, however, indicates that the roles of aOPCs in different diseases, including neurotrauma, multiple sclerosis, psychiatric disorders, and neurodegeneration, extend far beyond their remyelinating capacity. Adult oligodendrocyte precursor cells (aOPCs), transformed from fetal OPCs, are idiosyncratic neuroglia of the central nervous system (CNS) that are distinct in many ways from other glial cells. OPCs have been classically studied in the context of their remyelinating capacity. Recent studies, however, revealed that aOPCs not only contribute to post-lesional remyelination but also play diverse crucial roles in multiple neurological diseases. In this review we briefly present the physiology of aOPCs and summarize current knowledge of the beneficial and detrimental roles of aOPCs in different CNS diseases. We discuss unique features of aOPC death, reactivity, and changes during senescence, as well as aOPC interactions with other glial cells and pathological remodeling during disease. Finally, we outline future perspectives for the study of aOPCs in brain pathologies which may instigate the development of aOPC-targeting therapeutic strategies. [ABSTRACT FROM AUTHOR]

Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13- 18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p ≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes. [ABSTRACT FROM AUTHOR]

Background and Purpose: G‐protein coupled receptor 17 (GPR17) is an orphan receptor involved in the process of myelination, due to its ability to inhibit the maturation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes. Despite multiple claims that the biological ligand has been identified, it remains an orphan receptor. Experimental Approach: Seventy‐seven oxysterols were screened in a cell‐free [35S]GTPγS binding assay using membranes from cells expressing GPR17. The positive hits were characterized using adenosine 3′,5′ cyclic monophosphate (cAMP), inositol monophosphate (IP1) and calcium mobilization assays, with results confirmed in rat primary oligodendrocytes. Rat and pig brain extracts were separated by high‐performance liquid chromatography (HPLC) and endogenous activator(s) were identified in receptor activation assays. Gene expression studies of GPR17, and CYP46A1 (cytochrome P450 family 46 subfamily A member 1) enzymes responsible for the conversion of cholesterol into specific oxysterols, were performed using quantitative real‐time PCR. Key Results: Five oxysterols were able to stimulate GPR17 activity, including the brain cholesterol, 24(S)‐hydroxycholesterol (24S‐HC). A specific brain fraction from rat and pig extracts containing 24S‐HC activates GPR17 in vitro. Expression of Gpr17 during mouse brain development correlates with the expression of Cyp46a1 and the levels of 24S‐HC itself. Other active oxysterols have low brain concentrations below effective ranges. Conclusions and Implications: Oxysterols, including but not limited to 24S‐HC, could be physiological activators for GPR17 and thus potentially regulate OPC differentiation and myelination through activation of the receptor. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) incidence is increasing among men. Biomarkers that can identify oral HPV16/18 infections likely to persist, the obligate precursor for HPV-OPC, are needed. Methods We assessed the association between oral Epstein-Barr virus (EBV) and oral HPV16/18 persistence among 63 men in the HPV Infection in Men Study who tested positive for HPV16/18 at the baseline visit. Control of oral coinfections, including EBV, could serve as a biomarker of immune competence and the ability to control oral HPV. Results Detection of oral EBV was significantly associated with oral HPV16/18 ≥12-month persistence. Conclusions Detection of oral EBV deserves evaluation as a biomarker for oral HPV persistence and HPV-related OPC. [ABSTRACT FROM AUTHOR]

Oligodendrocyte production and myelination continues lifelong in the central nervous system (CNS), and all stages of this process can be adaptively regulated by neuronal activity. While artificial exogenous stimulation of neuronal circuits greatly enhances oligodendrocyte progenitor cell (OPC) production and increases myelination during development, the extent to which physiological stimuli replicates this is unclear, particularly in the adult CNS when the rate of new myelin addition slows. Here, we used environmental enrichment (EE) to physiologically stimulate neuronal activity for 6 weeks in 9‐week‐old C57BL/six male and female mice and found no increase in compact myelin in the corpus callosum or somatosensory cortex. Instead, we observed a global increase in callosal axon diameter with thicker myelin sheaths, elongated paranodes and shortened nodes of Ranvier. These findings indicate that EE induced the dynamic structural remodelling of myelinated axons. Additionally, we observed a global increase in the differentiation of OPCs and pre‐myelinating oligodendroglia in the corpus callosum and somatosensory cortex. Our findings of structural remodelling of myelinated axons in response to physiological neural stimuli during young adulthood provide important insights in understanding experience‐dependent myelin plasticity throughout the lifespan and provide a platform to investigate axon–myelin interactions in a physiologically relevant context. [ABSTRACT FROM AUTHOR]

Thermal energy storage (TES) systems are dependent on materials capable of operating at elevated temperatures for their performance and for prevailing as an integral part of industries. High-temperature TES assists in increasing the dispatchability of present power plants as well as increasing the efficiency in heat industry applications. Ordinary Portland cement (OPC)-based concretes are widely used as a sensible TES material in different applications. However, their performance is limited to operation temperatures below 400 °C due to the thermal degradation processes in its structure. In the present work, the performance and heat storage capacity of geopolymer-based concrete (GEO) have been studied experimentally and a comparison was carried out with OPC-based materials. Two thermal scenarios were examined, and results indicate that GEO withstand high running temperatures, higher than 500 °C, revealing higher thermal storage capacity than OPC-based materials. The high thermal energy storage, along with the high thermal diffusion coefficient at high temperatures, makes GEO a potential material that has good competitive properties compared with OPC-based TES. Experiments show the ability of geopolymer-based concrete for thermal energy storage applications, especially in industries that require feasible material for operation at high temperatures. [ABSTRACT FROM AUTHOR]

Introduction: The oncogenic human papillomaviruses (HPV) types 16 and 18 contribute to more than 73% cases of all HPV-related cancers and commonly affect the anogenital and head and neck region, with rapidly rising incidence rates of HPV-related oropharyngeal squamous cell carcinomas (OPSCC). HPV vaccination has the potential to decrease the burden of HPV-related disease, but vaccination rates remain low in many countries. We investigated the level of awareness of HPV, and HPV-OPSCC in particular, in a representative sample of the German population. Materials and Methods: As part of an online, population-based survey, an electronic questionnaire was administered to a representative sample of 1,095 adult individuals with a specific emphasis on awareness of HPV, transmission, and indicator symptoms of oropharyngeal cancer. Statistical analysis of levels of awareness and relation of these to age, gender, and socioeconomic background were conducted using the IBM SPSS Statistics Version 25.0. Results: 699/1,095 (63.8%) subjects had never heard of HPV. Of the subjects with awareness for HPV, 210 knew that HPV could be transmitted during sex (58.3%) and 138 recognized HPV as a risk factor for OPSCC (14.2%), unrelated to gender (p = 0.357), educational status (p = 0.581), or family status (p = 0.719). 416 subjects knew that a preventive vaccine against HPV existed (44.9%). Women were significantly more aware of HPV (34.2% vs. 22.8%, p < 0.001) and the vaccination (56.4% vs. 32.7%, p < 0.001) as were men. Younger individuals (age group 25–34) were significantly more aware of HPV (p < 0.001), likely as they were offered and/or had received the HPV vaccination. There was no regional variation of HPV awareness within the German state (p = 0.051). Conclusion: Here we demonstrate a significant lack of awareness of HPV and HPV vaccination in a representative sample of the German population. Levels of awareness of the link of HPV and oropharyngeal cancer are particularly low, bearing in mind that this cancer is commonly affecting men and incidence rates are rapidly rising in many European countries and the USA. Awareness programs and further education are required to tackle the low awareness rates and increase the uptake of the vaccination program not only in Germany, but also worldwide. [ABSTRACT FROM AUTHOR]

Aiming at the problem of low precision of high-speed start-stop position of belt drive system controlled by PLC, the text takes the belt drive system driven by the brushless DC servo motor (BLDCM) as the research object, studying the PLC intelligent control system based on OPC communication. Firstly, a mathematical model is established. Then, a fuzzy adaptive PID control algorithm is proposed to perform self-tune the tape speed and its deviation rate. Finally, the simulation comparison is made with the traditional PID control in terms of speed and step response. Compared with the traditional PID, the overshoot of the fuzzy self-adaptive PID algorithm decreases by 20.3%; the response speed is increased by 33.33%. A prototype of the belt drive system is developed, and the result of the algorithm verification experiment shows that the experimental data is basically consistent with the simulation data, the error controlled within 8%. Research provide theoretical and experimental bases for improving the position accuracy and robustness of the belt drive system. [ABSTRACT FROM AUTHOR]

Ischemic preconditioning (IPC) is an approach of protection against cerebral ischemia by inducing endogenous cytoprotective machinery. However, few studies in neurogenesis and oligodendrogenesis after IPC have been reported, especially the latter. The purpose of this study is to test our hypothesis that IPC may also induce cell proliferation and oligodendrogenesis in the subventricular zone and striatum, as well as to investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) on oligodendrogenesis. IPC was induced in mice by 12-min ischemia through the occlusion of the middle cerebral artery. Newly generated cells were labeled with 5-bromo-2′-deoxyuridine. Our findings demonstrated that IPC stimulated the proliferation of neural stem cells in the subventricular zone, promoted the generation of oligodendrocyte precursor cells in the striatum and corpus callosum/external capsule (CC/EC), and stimulated oligodendrocyte precursor cells differentiation into oligodendrocytes in the striatum and the CC/EC. Furthermore, we describe a crucial role for Nrf2 in IPC-induced oligodendrogenesis in the subventricular zone, striatum, and CC/EC and show for the first time that Nrf2 promoted the migration and differentiation of oligodendrocyte precursor cells into oligodendrocytes in the striatum and CC/EC. Our data imply that IPC stimulates the oligodendrogenesis in the brain and that Nrf2 signaling may contribute to the oligodendrogenesis. [ABSTRACT FROM AUTHOR]

Gravimetry-based direct measurements of mass concentration require offline analysis which is not suited for field campaigns. Hence such campaigns rely on the estimation of mass concentration by indirect methods mostly calibrated in controlled laboratory conditions. Optical particle counter (OPC) employs algorithms converting the measured number concentration to mass concentration using appropriate conversion factors. The accuracy of such conversion has not been validated for widely varying atmospheric conditions. This study compares the mass concentration estimated by OPC with those directly obtained from gravimetry-based instruments for outdoor samples collected in Bathinda City, Punjab, India from January 2022 to November 2023. The difference in the gravimetrically measured and OPC predicted values quantified in terms of ratios (gravimetric to optically estimated mass concentration), came out to be 1.42 ± 0.77, 0.99 ± 0.51, and 1.17 ± 0.58 for PM10, PM2.5 and PM1, respectively. This difference when estimated with the back-up filter of OPC itself (C Factor), was 1.37 ± 0.66. More than half of the samples showed ratios outside the 0.8–1.2 range thus indicating under or over-estimation in the OPC predicted values. The probable role of variation in density, shape, and refractive index of atmospheric aerosol particles towards the observed inaccuracy of estimated mass concentration has been highlighted. In the absence of clear guidelines and protocols, the study suggests ways to improve the accuracy via periodic measurement of the C Factor and/or incorporating calibration factors in such measurements. [Display omitted] • Estimation of mass concentration by optical counters has been compared with PM1, PM2.5 and PM10 gravimetric samplers. • Results in terms of difference in different size fractions. • Possible reasons could be variation in ambient aerosol density, refractive index and shape. • Incorporating correction and calibration factor improves OPC data accuracy. [ABSTRACT FROM AUTHOR]

White matter injury (WMI) causes oligodendrocyte precursor cell (OPC) differentiation arrest and functional deficits, with no effective therapies to date. Here, we report increased expression of growth hormone (GH) in the hypoxic neonatal mouse brain, a model of WMI. GH treatment during or post hypoxic exposure rescues hypoxia-induced hypomyelination and promotes functional recovery in adolescent mice. Single-cell sequencing reveals that Ghr mRNA expression is highly enriched in vascular cells. Cell-lineage labeling and tracing identify the GHR-expressing vascular cells as a subpopulation of pericytes. These cells display tip-cell-like morphology with kinetic polarized filopodia revealed by two-photon live imaging and seemingly direct blood vessel branching and bridging. Gain-of-function and loss-of-function experiments indicate that GHR signaling in pericytes is sufficient to modulate angiogenesis in neonatal brains, which enhances OPC differentiation and myelination indirectly. These findings demonstrate that targeting GHR and/or downstream effectors may represent a promising therapeutic strategy for WMI. [Display omitted] • GH treatment promotes myelin repair and functional recovery after hypoxia • GHR is selectively expressed by a subpopulation of pericytes • GHR-positive pericyte-tip cells lead blood vessel bridging and branching • GHR-positive pericytes modulate angiogenesis and govern myelination indirectly Ren et al. report increased growth hormone level in hypoxic brains and identify growth-hormone-receptor-expressing cells as a sub-group of pericytes that mediate angiogenesis in developing brains. Growth hormone treatment promotes myelination and functional recovery after hypoxia, demonstrating growth hormone receptor as a potential therapeutic target against hypoxic insults. [ABSTRACT FROM AUTHOR]

A significant barrier to adoption of de-escalated treatment protocols for human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is that few predictors of poor prognosis exist. We conducted the first large whole-genome sequencing (WGS) study to characterize the genetic variation of the HPV type 16 (HPV16) genome and to evaluate its association with HPV-OPC patient survival. A total of 460 OPC tumor specimens from two large United States medical centers (1980-2017) underwent HPV16 whole-genome sequencing. Site-specific variable positions [single nucleotide polymorphisms (SNPs)] across the HPV16 genome were identified. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival by HPV16 SNPs. Harrell C-index and time-dependent positive predictive value (PPV) curves and areas under the PPV curves were used to evaluate the predictive accuracy of HPV16 SNPs for overall survival. A total of 384 OPC tumor specimens (83.48%) passed quality control filters with sufficient depth and coverage of HPV16 genome sequencing to be analyzed. Some 284 HPV16 SNPs with a minor allele frequency ≥1% were identified. Eight HPV16 SNPs were significantly associated with worse survival after false discovery rate correction (individual prevalence: 1.0%-5.5%; combined prevalence: 15.10%); E1 gene position 1053 [HR for overall survival (HR os): 3.75, 95% CI 1.77-7.95; P fdr = 0.0099]; L2 gene positions 4410 (HR os : 5.32, 95% CI 1.91-14.81; P fdr = 0.0120), 4539 (HR os : 6.54, 95% CI 2.03-21.08; P fdr = 0.0117); 5050 (HR os : 6.53, 95% CI 2.34-18.24; P fdr = 0.0030), and 5254 (HR os : 7.76, 95% CI 2.41–24.98; P fdr = 0.0030); and L1 gene positions 5962 (HR os : 4.40, 95% CI 1.88-10.31; P fdr = 0.0110) and 6025 (HR os : 5.71, 95% CI 2.43-13.41; P fdr = 0.0008) and position 7173 within the upstream regulatory region (HR os : 9.90, 95% CI 3.05-32.12; P fdr = 0.0007). Median survival time for patients with ≥1 high-risk HPV16 SNPs was 3.96 years compared with 18.67 years for patients without a high-risk SNP; log-rank test P < 0.001. HPV16 SNPs significantly improved the predictive accuracy for overall survival above traditional factors (age, smoking, stage, treatment); increase in C-index was 0.069 (95% CI 0.019-0.119, P < 0.001); increase in area under the PPV curve for predicting 5-year survival was 0.068 (95% CI 0.015-0.111, P = 0.008). HPV16 genetic variation is associated with HPV-OPC prognosis and can improve prognostic accuracy. • Few prognostic markers of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) exist. • We conducted the first large HPV16 whole-genome sequencing study of 384 HPV16+OPCs • We found eight HPV16 SNPs to be strongly associated with HPV-OPC prognosis. • Median survival was 4 years for HPV-OPC patients with ≥1 high-risk HPV16 SNPs versus 19 years for patients without. • HPV16 SNPs improved predictive accuracy for HPV-OPC overall survival compared with age, stage, treatment and smoking alone. [ABSTRACT FROM AUTHOR]

Proanthocyanidins (OPC) extracted from natural plants was used as free radical trapping agent and blended with polyvinyl alcohol (PVA). The PVA/OPC composite films were produced by solution casting. The thermodynamic stability of the composite films was measured by using differential scanning calorimetry (DSC) and thermogravimetric analyser (TGA). The properties of UV shielding and light transmission were investigated using double-beam UV-Vis spectrophotometer (UV-Vis). And the crystalline properties were characterized using small angle X-ray scattering (SAXS). The results show that the addition of OPC inhibited the crystallization of PVA, the thermal stability and the melt processing window of the composite films were effectively improved by adding 1.0%-2.0% OPC. And the PVA/OPC composites films exhibited excellent mechanical properties, light transmittance and UV shielding properties. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes which myelinate axons in the central nervous system. Although classically thought to be a homogeneous population, OPCs are reported to have different developmental origins and display regional and temporal diversity in their transcriptome, response to growth factors, and physiological properties. Similarly, evidence is accumulating that myelinating oligodendrocytes display transcriptional heterogeneity. Analyzing this reported heterogeneity suggests that OPCs, and perhaps also myelinating oligodendrocytes, may exist in different functional cell states. Here, we review the evidence indicating that OPCs and oligodendrocytes are diverse, and we discuss the implications of functional OPC states for myelination in the adult brain and for myelin repair. [ABSTRACT FROM AUTHOR]

Demyelination is observed in animal models of intractable epilepsy (IE). Epileptogenesis damages the myelin sheath and dysregulates oligodendrocyte precursor cell (OPC) development. However, the molecular pathways regulating demyelination in epilepsy are unclear. Here, we predicted the molecular mechanisms regulating demyelination in a rat model of lithium-pilocarpine hydrochloride-induced epilepsy. We identified DGKA/Mboat2/Inpp5j and NOS/Keratin 28 as the main target molecules that regulate demyelination via glycerolipid and glycerophospholipid metabolism, phosphatidylinositol signaling, and estrogen signaling in demyelinated forebrain slice cultures (FSCs). In seizure-like FCSs, the actin cytoskeleton was regulated by Cnp and MBP via Pak4/Tmsb4x (also known as Tβ4) and Kif5c/Kntc1. Tβ4 possibly prevented OPC differentiation and maturation and inhibited MBP phosphorylation via the p38MAPK/ERK1/JNK1 pathway. The MAPK signaling pathway was more likely activated in seizure-like FCSs than in demyelinated FCSs. pMBP expression was decreased in the hippocampus of lithium-pilocarpine hydrochloride-induced acute epilepsy rats. The expression of remyelination-related factors was suppressed in the hippocampus and corpus callosum in lithium-pilocarpine hydrochloride-induced epilepsy rats. These findings suggest that the actin cytoskeleton, Tβ4, and MAPK signaling pathways regulate the decrease in pMBP in the hippocampus in a rat model of epilepsy. Our results indicate that regulating the actin cytoskeleton, Tβ4, and MAPK signaling pathways may facilitate the prevention of demyelination in IE. [ABSTRACT FROM AUTHOR]

It has been shown that following demyelination, Oligodendrocyte Progenitor Cells (OPCs) migrate to the lesion site and begin to proliferate, and differentiate. This study aimed to investigate the effects of Hydroxychloroquine (HCQ) on the expression of OLIG-2 and PDGFR-α markers during the myelination process. C57BL/6 mice were fed cuprizone pellets for 5 weeks to induce demyelination and return to a normal diet for 1 week to stimulate remyelination. During the Phase I all of the animals except CPZ and Vehicle groups were exposed to HCQ (2.5, 10, and 100 mg/kg) via drinking water. At the end of the study, animals were euthanized, perfused and the brain samples were assessed for myelination and immunohistochemistry evaluation. What is remarkable is the high rate of Olig2 + cells in the groups treated with 10 and 100 mg/kg HCQ in the demyelination phase and its decreasing trend in the remyelination phase. However, there was no significant difference between groups during phase I and Phase II based on the percentage of olig-2+/total cells in the corpus callosum region. The number of PDGFR-α+ cells in the group treated with 10 mg/kg HCQ was significant in the first phase (p value < 0.05). Considering that the 100 mg/kg HCQ group had the highest level of PDGFR-α as well as the highest level of myelin repair in LFB staining, it could be inferred that it was the most effective dose in inducing proliferation and migration of OPCs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a chronic demyelinating disease with a functional disturbance in the immune system and axonal damages. It was shown that Apamin as a blood–brain barrier shuttle acts as a Ca2+ activated K+ channels (SK channels) blocker. In this study, the effects of Apamin on oligodendrocyte differentiation markers were evaluated on an induced model of MS. Briefly, C57BL/6 male mice (22 ± 5 g) except the control group were fed with 0.2% (w/w) cuprizone pellets for 6 weeks. After cuprizone withdrawal, mice were divided randomly into six groups. Apamin (100 µg/kg/BW) was administered intraperitoneally as a co-treatment during phase I (demyelination) or post-treatment phase II (remyelination) twice a week. Mice were anesthetized, perfused with phosphate-buffered saline, then fixed brains were coronally sectioned and the changes in oligodendrocytes markers such as Olig2, PDGFR-α, and BrdU incorporation were assessed by immunohistochemistry assay. Apamin administration increased Olig2+ cells in phase I as compared to the control group (p < 0.0001). Also, a decreasing trend in PDGFRa+ cells observed after cuprizone withdrawal (p < 0.001). 5-Bromo-2′-deoxyuridine (BrdU) incorporation test was confirmed stimulation of oligodendrocyte progenitor cell proliferation in phase I in the Apamin exposed group (p < 0.0001), especially at the subventricular zone. This study highlights the potential therapeutic effects of Apamin as a bee venom–derived peptide on oligodendrocyte precursor proliferation and elevation in myelin content in an oxidative induced multiple sclerosis model due to cuprizone exposure. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) retain the capacity to remyelinate axons in the corpus callosum (CC) upon demyelination. However, the dynamics of OPC activation, mode of cell division, migration, and differentiation on a single-cell level remain poorly understood due to the lack of longitudinal observations of individual cells within the injured brain. After inducing focal demyelination with lysophosphatidylcholin in the CC of adult mice, we used twophoton microscopy to follow for up to 2 mo OPCs and their differentiating progeny, genetically labeled through conditional recombination driven by the regulatory elements of the gene Achaete-scute homolog 1. OPCs underwent several rounds of symmetric and asymmetric cell divisions, producing a subset of daughter cells that differentiates into myelinating oligodendrocytes. While OPCs continue to proliferate, differentiation into myelinating oligodendrocytes declines with time, and death of OPC-derived daughter cells increases. Thus, chronic in vivo imaging delineates the cellular principles leading to remyelination in the adult brain, providing a framework for the development of strategies to enhance endogenous brain repair in acute and chronic demyelinating disease. [ABSTRACT FROM AUTHOR]

According to a September 2021 report by Positive Technologies, 91% of the world's industrial companies have information systems vulnerable to cyberattacks. The industrial sector is the second most attacked sector in the U.S., and the leading one in developed countries. Ukraine ranks sixth and seventh in the top 20 for the largest industrial attacks. Many scientific publications are devoted to industrial cybersecurity in the world, but, unfortunately, in Ukraine this area of cybersecurity is poorly studied. To develop the topic of increasing the level of cybersecurity of industrial control systems, we focused on the problems of cybersecurity of the lower level of control - the operator control station of the technological plant. Previously, we investigated the problem of cybersecurity of the industrial computer network of the lower level Modbus RTU. Continuing the topic, in this paper we investigate the cybersecurity of important software - the OPC server. This study proposes to pay attention to a vulnerability that has not yet been investigated. This vulnerability is related to the fact that having an extensive network of workstations in the enterprise, an attacker can substitute OPC server on any workstation (usually the most important one in production) with his own OPC server and do it in such a way that on the one hand to bring the technological unit of the selected site to stop or crash, but on the other hand to prevent the operator of technological unit, watching the SCADA-system on the computer screen, from noticing anything. A special diagnostic system has been developed to detect a cyber attack. Appropriate software has been developed and, with its help, all solutions have been simulated in real time using components of real industrial software and Modbus network model. The developed solutions and software can be used in industry. [ABSTRACT FROM AUTHOR]

White matter (WM) is a highly prominent feature in the human cerebrum and is comprised of bundles of myelinated axons that form the connectome of the brain. Myelin is formed by oligodendrocytes and is essential for rapid neuronal electrical communication that underlies the massive computing power of the human brain. Oligodendrocytes are generated throughout life by oligodendrocyte precursor cells (OPCs), which are identified by expression of the chondroitin sulphate proteoglycan NG2 (Cspg4), and are often termed NG2-glia. Adult NG2+ OPCs are slowly proliferating cells that have the stem cell–like property of self-renewal and differentiation into a pool of 'late OPCs' or 'differentiation committed' OPCs(COPs) identified by specific expression of the G-protein-coupled receptor GPR17, which are capable of differentiation into myelinating oligodendrocytes. In the adult brain, these reservoirs of OPCs and COPs ensure rapid myelination of new neuronal connections formed in response to neuronal signalling, which underpins learning and cognitive function. However, there is an age-related decline in myelination that is associated with a loss of neuronal function and cognitive decline. The underlying causes of myelin loss in ageing are manifold, but a key factor is the decay in OPC 'stemness' and a decline in their replenishment of COPs, which results in the ultimate failure of myelin regeneration. These changes in ageing OPCs are underpinned by dysregulation of neuronal signalling and OPC metabolic function. Here, we highlight the role of purine signalling in regulating OPC self-renewal and the potential importance of GPR17 and the P2X7 receptor subtype in age-related changes in OPC metabolism. Moreover, age is the main factor in the failure of myelination in chronic multiple sclerosis and myelin loss in Alzheimer's disease, hence understanding the importance of purine signalling in OPC regeneration and myelination is critical for developing new strategies for promoting repair in age-dependent neuropathology. [ABSTRACT FROM AUTHOR]

The oval paracentral nucleus (OPC) was initially isolated from the paracentral nucleus (PC) within the intralaminar thalamic nuclei in rats. We have recently shown that the rat OPC receives proprioceptive inputs from jaw-closing muscle spindles (JCMSs). However, it remains unknown which cortical areas receive thalamic inputs from the OPC, and whether the cortical areas receiving the OPC inputs are distinct from those receiving inputs from the other intralaminar nuclei and sensory thalamic nuclei. To address this issue, we injected an anterograde tracer, biotinylated dextranamine (BDA), into the OPC, which was electrophysiologically identified by recording of proprioceptive inputs from the JCMSs. Many BDA-labeled axonal fibers and terminals from the OPC were ipsilaterally observed in the rostral and rostroventral regions of the primary somatosensory cortex (S1), the rostral region of the secondary somatosensory cortex (S2), and the most rostrocaudal levels of the granular insular cortex (GI). In contrast, a BDA injection into the caudal PC, which was located slightly rostral to the OPC, resulted in ipsilateral labeling of axonal fibers and terminals in the rostrolateral region of the medial agranular cortex and the rostromedial region of the lateral agranular cortex. Furthermore, injections of a retrograde tracer, Fluorogold, into these S1, S2, and GI regions, resulted in preferential labeling of neurons in the ipsilateral OPC among the intralaminar and sensory thalamic nuclei. These findings reveal that the rat OPC has widespread, but strong corticopetal projections, indicating that there exist divergent corticopetal pathways from the intralaminar thalamic nucleus, which process JCMS proprioceptive sensation. [ABSTRACT FROM AUTHOR]

VLSI mask optimization is one of the most critical stages in manufacturability aware design, which is costly due to the complicated mask optimization and lithography simulation. Recent researches have shown prominent advantages of machine learning techniques dealing with complicated and big data problems, which bring potential of dedicated machine learning solution for DFM problems and facilitate the VLSI design cycle. However, uncertainty nature of state-of-the-art machine learning models have posed great challenges when developing alternative solutions. In this paper, we focus on a heterogeneous OPC framework that assists mask layout optimization. Instead of fitting neural networks for mask optimization tasks directly, a multi-class classification model is developed to capture design characteristics and hence determine the most suitable OPC engines. Experimental results have shown the efficiency and effectiveness of proposed frameworks that have the potential to be alternatives to existing EDA solutions. • Survey on machine learning models assisting printability estimation and direct-printable mask synthesis. • Heterogeneous OPC flow to use a machine learning model select OPC engine for a given pattern. • Bottleneck-attention layer to capture design characteristics and achieve our objectives. [ABSTRACT FROM AUTHOR]

This paper presents a modification in conventional asymmetrically clipped optical OFDM (ACO-OFDM) frame for direct detection intensity modulation (DD-IM) system. The conventional ACO-OFDM for DD-IM utilizes only one-fourth of available subcarriers for information symbols and therefore the bandwidth efficiency is very low. Authors propose to retain the othwerwise discarded negative polarity symbols to increase the bandwidth efficiency and transmission power for given number of subcarriers in ACO-OFDM. Proposed dual frame OFDM consists of two similar subframes and one of them is transmitted with optical phase conjugation for dispersion and non-linearity mitigation in multimode optical fiber. Proposed system is compared with another scheme-phase conjugated sub-carrier coding (PCSC) in OFDM. At − 15 dBm received optical power, proposed dual frame shows bit error rate (BER) 1.974 ∗ 10 - 3 when compared to PCSC that shows BER value of 1.13 ∗ 10 - 1 . BER Performance for the proposed dual frame OFDM with QPSK and QAM-16 modulation schemes is also compared in this research work. [ABSTRACT FROM AUTHOR]

• Optic nerves present an increased density of OPC during regeneration. • Optic nerves present an increased density of oligodendrocytes during regeneration. • Optic nerves present an increased density of myelin regulatory factor during regeneration. • The stimulatory protocol employed in this study promotes myelination of regenerating RGC axons. Recently, regeneration of CNS tracts has been partially accomplished by strategies of intrinsic neuronal growth stimulation. However, restoration of function is dependent on proper myelination of regenerating axons. Previous work from our group (Goulart et al., 2018) has shown an increase in oligodendrocyte staining in the regenerating optic nerve, 2 weeks after crush, in animals that were submitted to conditional deletion of pten gene in retinal ganglion cells and intravitreal injection of zymosan + cAMP. Thus, in the present study we aimed to investigate the maturation of the oligodendroglial lineage and myelination during the regeneration of the optic nerve under the same conditions of our previous work. We showed that the combined treatment promoted an increase of myelinated fibers within the optic nerve, 12 weeks after lesion, as well as an increase in Sox10 positive cells. Early-OPCs, positive to A2B5, were also increased at 12 weeks, whereas O4 positive, late-OPCs, were increased from 2 until 12 weeks after crush. At 12 weeks after crush, the optic nerve of Regenerating group presented more CC1 positive oligodendrocytes and increased MRF positive myelinating oligodendrocytes, culminating in CTB traced regenerating axons superimposed to MBP staining, suggestive of myelination. Thus, our work showed that conditional deletion of pten gene in retinal ganglion cells and intravitreal inflammatory stimuli + cAMP stimulate full maturation of the olidodendroglial lineage, from OPC proliferation and differentiation to myelination of regenerating CNS axons. [ABSTRACT FROM AUTHOR]

• First born ventral vOPCs block expansion of later born dorsal dOPCs in the spinal cord. • vOPCs enwrap injured motor neurons and aid in removing glutamatergic vGlut1 synapses. • After compensatory expansion, dOPCs change morphology and fail to remove vGlut1 synapses. • Morphology of OPC in SOD1 mice resembles that of dOPC after compensatory expansion. Oligodendrocyte precursor cells (OPCs) arise sequentially first from a ventral and then from a dorsal precursor domain at the end of neurogenesis during spinal cord development. Whether the sequential production of OPCs is of physiological significance has not been examined. Here we show that ablating Shh signaling from nascent ventricular zone derivatives and partially from the floor plate results in a severe diminishment of ventral derived OPCs but normal numbers of motor neurons in the postnatal spinal cord. In the absence of ventral vOPCs, dorsal dOPCs populate the entire spinal cord resulting in an increased OPC density in the ventral horns. These OPCs take on an altered morphology, do not participate in the removal of excitatory vGlut1 synapses from injured motor neurons, and exhibit morphological features similar to those found in the vicinity of motor neurons in the SOD1 mouse model of Amyotrophic Lateral Sclerosis (ALS). Our data indicate that vOPCs prevent dOPCs from invading ventral spinal cord laminae and suggest that vOPCs have a unique ability to communicate with injured motor neurons. [ABSTRACT FROM AUTHOR]

There is increasing evidence that myelin disruption is related to cognitive decline in Alzheimer's disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by adult oligodendrocyte progenitor cells (OPCs), also known as NG2-glia. To address whether alterations in myelination are related to age-dependent changes in OPCs, we analyzed NG2 and myelin basic protein (MBP) immunolabelling in the hippocampus of 3×Tg-AD mice at 6 and 24 months of age, compared with non-Tg age-matched controls. There was an age-related decrease in MBP immunostaining and OPC density, together with a decline in the number of OPC sister cells, a measure of OPC replication. Notably, the loss of myelin and OPC sister cells occurred earlier at 6 months in 3xTg-AD, suggesting accelerated aging, although there was not a concomitant decline in OPC numbers at this age, suggesting the observed changes in myelin were not a consequence of replicative exhaustion, but possibly of OPC disruption or senescence. In line with this, a key finding is that compared to age-match controls, OPC displayed marked morphological atrophy at 6 months in 3xTg-AD followed by morphological hypertrophy at 24 months, as deduced from significant changes in total cell surface area, total cell volume, somata volume and branching of main processes. Moreover, we show that hypertrophic OPCs surround and infiltrate amyloid-β (Aβ) plaques, a key pathological hallmark of AD. The results indicate that OPCs undergo complex age-related remodeling in the hippocampus of the 3xTg-AD mouse model. We conclude that OPC disruption is an early pathological sign in AD and is a potential factor in accelerated myelin loss and cognitive decline. • Life-long generation of myelin is the function of adult oligodendrocyte progenitor cells (OPCs). • Age-related loss of myelin is accelerated in the 3xTg-AD mouse model of Alzheimer's disease (AD). • OPCs are disrupted at an early stage of 3xTg-AD. • Dysregulation of OPC and myelin loss are important biomarkers for AD-like pathology. [ABSTRACT FROM AUTHOR]

CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord graymatter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3-/- mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo. [ABSTRACT FROM AUTHOR]

Remyelination is common under physiological conditions and usually occurs as a response to a pathological demyelinating event. Its potentiation is an important goal for the development of therapies against pathologies such as multiple sclerosis and white matter injury. Visualization and quantification in vivo of demyelination and remyelination processes are essential for longitudinal studies that will allow the testing and development of pro-myelinating strategies. In this study, ethidium bromide (EB) was stereotaxically injected into the caudal cerebellar peduncle (c.c.p.) in rats to produce demyelination; the resulting lesion was characterized (i) transversally through histology using Black-Gold II (BGII) staining, and (ii) longitudinally through diffusion-weighted magnetic resonance imaging (dMRI), by computing fractional anisotropy (FA) and diffusivity parameters to detect microstructural changes. Using this characterization, we evaluated, in the lesioned c.c.p., the effect of N-butyl-β-carboline-3-carboxylate (β-CCB), a potentiator of GABAergic signaling in oligodendrocytes. The dMRI analysis revealed significant changes in the anisotropic and diffusivity properties of the c.c.p. A decreased FA and increased radial diffusivity (λ ⊥) were evident following c.c.p. lesioning. These changes correlated strongly with an apparent decrease in myelin content as evidenced by BGII. Daily systemic β-CCB administration for 2 weeks in lesioned animals increased FA and decreased λ ⊥ , suggesting an improvement in myelination, which was supported by histological analysis. This study shows that structural changes in the demyelination–remyelination of the caudal cerebellar peduncle (DRCCP) model can be monitored longitudinally by MRI, and it suggests that remyelination is enhanced by β-CCB treatment. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries. • MRI was used to study de- and re-myelination in rat lesioned cerebellar peduncle. • Demyelination and remyelination were assessed in vivo by DTI analysis (FA and λ metrics). • FA and λ changes implied a myelination decrease at the lesioned cerebellar peduncle. • GABAergic signaling potentiation by β-CCB promoted DTI metrics recovery. • DTI and histological evaluation suggested that β-CCB improved re-myelination. [ABSTRACT FROM AUTHOR]

A set of comprehensive test patterns is important for a number of lithography applications. Pattern diversity is, however, hard to achieve either from parametric patterns or from actual patterns even though they are carefully extracted and classified. Automatic layout pattern synthesis is proposed in this paper. A generative adversarial network (GAN) is employed to generate a new set of discrete cosine transform (DCT) signals. It is converted to an image format through inverse DCT (IDCT). The image is blurred since output DCT signals from GAN correspond to lower frequency region. Another GAN, this time a conditional GAN (cGAN), is introduced to get sharpened layout pattern. A key in this process is to train the two GANs in such a way that generated patterns are different from existing actual patterns while they are still valid layouts. Experiments indicate that synthetic patterns are less redundant and cover 76% more space in image parameter set space than actual patterns. We choose a machine-learning guided OPC as an example application: when synthetic patterns are included to train OPC model, edge proximity error decreases by 21%. Resist model calibration is chosen as a second example: when synthetic patterns are combined with parametric- and real-patterns, CD RMSE decreases by 10.3%. [ABSTRACT FROM AUTHOR]

The formation of myelin around axons by oligodendrocytes (OL) poses an enormous synthetic and energy challenge for the glial cell. Local translation of transcripts, including the mRNA for the essential myelin protein Myelin Basic Protein (MBP) at the site of myelin deposition has been recognised as an efficient mechanism to assure proper myelin sheath assembly. Oligodendroglial precursor cells (OPCs) form synapses with neurons and may localise many additional mRNAs in a similar fashion to synapses between neurons. In some diseases in which demyelination occurs, an abundance of OPCs is present but there is a failure to efficiently remyelinate and to synthesise MBP. This compromises axonal survival and function. OPCs are especially sensitive to cellular stress as occurring in neurodegenerative diseases, which can impinge on their ability to translate mRNAs into protein. Stress causes the build up of cytoplasmic stress granules (SG) in which many RNAs are sequestered and translationally stalled until the stress ceases. Chronic stress in particular could convert this initially protective reaction of the cell into damage, as persistence of SG may lead to pathological aggregate formation or long-term translation block of SG-associated RNAs. The recent recognition that many neurodegenerative diseases often exhibit an early white matter pathology with a proliferation of surviving OPCs, renders a study of the stress-associated processes in oligodendrocytes and OPCs especially relevant. Here, we discuss a potential dysfunction of RNA regulation in myelin diseases such as Multiple Sclerosis (MS) and Vanishing white matter disease (VWM) and potential contributions of OL dysfunction to neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Fragile X syndrome (FXS). [ABSTRACT FROM AUTHOR]

Deterioration of concrete structures made with ordinary portland cement (OPC) as a binder is inevitable, and this requires repair or rehabilitation using appropriate repair materials. A strong and highly adhesive repair material is very important in order to ascertain the safety of damaged concrete structures. The existing repair materials, especially those that utilized conventional OPC-based materials, appear to require a certain curing condition, which prior studies have revealed to result in a weak link between the repair material and the repaired structures. Hence, an alternative material which is geopolymer mortar was utilized in this study as a repair material, and the impact of geopolymer mortars with various binder-to-sand ratios was evaluated. The physical and mechanical properties of the geopolymer mortars were assessed in addition to their performance as a repair material in terms of their bonding characteristics to conventional concrete. Findings from this study revealed that geopolymer mortar with a binder-to-sand ratio of 1:2 exhibited the highest bonding strength. In addition, geopolymer mortars with a binder-to-sand ratio of 1:3 to 4:1 exhibited better bonding strength compared to when geopolymer paste was used. • The bonding performance of damaged concrete repaired with FA-based geopolymer mortar is still limited. • Binder to sand ratio has been identified to have significant effects on the repaired concrete. • The bonding mechanism of geopolymer repair mortar for damaged concrete is rarely discussed, despite its importance in concrete repair. [ABSTRACT FROM AUTHOR]

The majority of oligodendrocytes in the neocortex originate from neural progenitors that reside in the dorsal forebrain. We recently showed that Sonic Hedgehog (Shh) signaling in these dorsal progenitors is required to produce normal numbers of neocortical oligodendrocytes during embryonic development. Conditional deletion of the Shh signaling effector, Smo, in dorsal progenitors caused a dramatic reduction in oligodendrocyte numbers in the embryonic neocortex. In the current study, we show that the depleted oligodendrocyte lineage in Smo conditional mutants is able to recover to control numbers over time. This eventual recovery is achieved in part by expansion of the ventrally-derived wild-type lineage that normally makes up a minority of the total oligodendrocyte population. However, we find that the remaining dorsally-derived mutant cells also increase in numbers over time to contribute equally to the recovery of the total population. Additionally, we found that the ways in which the dorsal and ventral sources cooperate to achieve recovery is different for distinct populations of oligodendrocyte-lineage cells. Oligodendrocyte precursor cells (OPCs) in the neocortical white matter recover completely by expansion of the remaining dorsally-derived Smo mutant cells. On the other hand, mature oligodendrocytes in the white and gray matter recover through an equal contribution from dorsal mutant and ventral wild-type lineages. Interestingly, the only population that did not make a full recovery was OPCs in the gray matter. We find that gray matter OPCs are less proliferative in Smo cKO mutants compared to controls, which may explain their inability to fully recover. Our data indicate that certain populations of the dorsal oligodendrocyte lineage are more affected by loss of Shh signaling than others. Furthermore, these studies shed new light on the complex relationship between dorsal and ventral sources of oligodendrocytes in the developing neocortex. • Depleted oligodendrocytes in Smo mutant brains eventually recover to normal levels. • Recovery occurs by expansion of both dorsal mutant and ventral wild type cells. • Total oligodendrocytes and OPCs reach normal numbers by early postnatal ages. • Oligodendrocytes and OPCs in white and gray matter recover by different means. • Gray matter OPCs never fully recover due to a defect in proliferation. [ABSTRACT FROM AUTHOR]

Introduction. Current advances in assisted medical procreation (AMP) allow couples with fertility disorders to conceive in most cases. However, implantation disorders of the embryo remain a source of failure of these techniques for which modern medicine does not yet have a clear therapeutic response. Acupuncture has been used for over 25 years in support of PMA and its effects on some causes of implantation disorders have been demonstrated. However, its clinical efficacy in increasing pregnancy and viable birth rates remains questionable, given the contradictory results reported by recent meta-analyzes. One of the explanations suggests that in addition to the heterogeneity of the acupuncture protocols, these are too often too limited and that the dose-effect is therefore insufficient to be significant. Methods. This is why in this clinical trial without control population and using the concept of objective performance criteria (OPC), we tested the hypothesis that an electro-acupuncture treatment protocol spread over 3 months and ending during the transfer of embryos into the mother's uterus increases the rate of pregnancy and birth when integrated into the PMA. Results. We report here the results of this protocol in a population of patients suffering from implantation disorders and that we compare retrospectively with the results published every year in Belgium by all accredited centers of AMP. Discussion. Finally, we review the evidence from the literature that explain the mechanisms of action of electro-acupuncture in this population of patients. Conclusion. This preliminary OPC-type clinical trial is to our knowledge the first evaluating the effects of a long EA protocol in these particular patients having experienced many unsuccessful AMP trials due to implantation failures. In the future these positive results have to be confirmed by a multicentric randomized controlled trial. [ABSTRACT FROM AUTHOR]