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Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

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Neural Regeneration Research 2024年第11期19卷 2377-2386页

作者： charles h.Nelson Udai B.Pandey Department of Pediatrics Division of Child NeurologyChildren’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA Children’s Neuroscience Institute Children’s Hospital of PittsburghUniversity of Pittsburgh Medical CenterPittsburghPAUSA

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding *** the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent *** many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its *** this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder ***,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of *** review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

关键词： cerebellar atrophy GEMIN5 neurodevelopmental disorder neurological disease SMN complex

Recent development and challenges in enhancing fire performance on wood and wood-based composites:A 10-year review from 2012 to 2021

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Journal of Bioresources and Bioproducts 2024年第1期9卷 27-42页

作者： charles Michael Albert Kang Chiang Liew Faculty of Tropical Forestry Universiti Malaysia SabahKota Kinabalu 88400Kota KinabaluSabah 88400Malaysia

Due to their durability,versatility,and aesthetic value,wood and wood-based composites are widely used as building *** fact that these materials are flammable,however,raises a major worry since they might cause fire hazards and significant loss of life and *** article investigates the variables that affect fire performance as well as the various fire-retardant treatments and their *** current developments and challenges in improving the fire performance of wood and wood-based composites treated with fire-retardant materials are summarized in this ***,organic chemicals,and densification are some recent developments in fire-retardant treatments that are also *** points from the review are summarized,along with potential areas for further research and development.

关键词： Fire performance Fire-retardant materials Wood Wood-based composite Nanoparticles coating Surface charring Bio-based fire retardant Densification

historic,pre-stock enhancement,demographic conditions of exploited populations of dusky flathead,Platycephalus fuscus,in eastern Australia

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Aquaculture and Fisheries 2024年第2期9卷 314-323页

作者： charles A.Gray WildFish Research Grays PointSydney2232Australia

Responsible stock enhancement initiatives require baseline data of wild population demographic conditions that can be used in testing management *** study provides the first fishery-independent assessment of length-and age-based biological characteristics of exploited populations of Platycephalus fuscus in eastern Australia prior to stock *** was conducted over seven estuaries spanning seven degrees of latitude and the geographical range of proposed stock *** in all estuaries showed evidence of length and age truncation,especially those subject to commercial fisheries where young individuals of both sexes dominated *** longevities were 12 and 11 years for females and males respectively,but few females>5 years and males>3 years were generally *** dominated populations,and on average,the mean lengths and ages of females were greater than males within each estuary and across all age *** dimorphic variation in growth was evident across all estuaries,with females attaining greater maximum lengths than ***-specific differences in individual growth were not *** average,over 50%of females sampled in each estuary were>the minimum legal length(MLL),but the opposite was evident for *** contrast,over 25%of males in each estuary were>the mean length at maturity(L50),whereas in all but one estuaryhe females were>the *** male and female *** should recruit to the fishery in 2 and 3 years,and contribute to the spawning stock in 1.5 and 4.5 years,*** study provides important historical baseline data that can contribute to testing stock enhancement outcomes on populations.

关键词： Baseline data Fishery enhancement Management evaluation Platycephalidae Recreational fishing Restocking Stock assessment

Extinction of Light in the Galactic halo: First Observational Evidence of the Interaction of Light and Dark Matter

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Journal of Modern Physics 2024年第8期15卷 1144-1198页

作者： charles h. McGruder III Department of Physics and Astronomy Western Kentucky University Bowling Green USA

We study the distribution of quasars on the celestial sphere according to ground-based SDSS and space-based WISE and Gaia observations. All distributions as a function of galactic latitude, b, exhibit a decrease in quasar frequency well outside the dust in and near the galactic plane. We prove that the observed decrease in quasar frequency at high galactic latitudes is not accompanied by reddening, meaning that it can not be caused by dust. The scattering of light by the circumgalactic gas is negligible because the Thomson scattering cross section is very small. We conclude the observed scattering of light must be caused by dark matter in the galactic halo. We determine the mass and charge of dark matter particles. If the dark matter particle is a fermion its mass, mDMand charge eDM=δe, where e is the elementary charge are: mDM=3.2×10−2eV and δ=3.856×10−5. If however the dark matter particle is spinless then: mDM=0.511eV and δ=2.132×10−4. These values for the charge of a dark matter particle are orders of magnitude higher than the upper limit of the neutrino charge according to laboratory experiments. Consequently, dark matter particles are not charged neutrinos. Since dark matter particles are charged, they must emit and absorb electromagnetic radiation. however, PDM~δ2, or: PDM~1.487×10−9Pe, where Peis the power output of a single electron.

关键词： Milky Way Dark Matter halo (1049)

Cosmology without the Cosmological Principle and without Violating the Copernican Principle: Taub-NUT Universe

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Journal of Modern Physics 2024年第8期15卷 1069-1096页

作者： charles h. McGruder III Department of Physics and Astronomy Western Kentucky University Bowling Green Kentucky USA

We develop a theory of cosmology, which is not based on the cosmological principle. We achieve this without violating the Copernican principle. It is well known that the gravitational redshift associated with the Schwarzschild solution applied to the distant supernova does not lead to the observed redsift-distance relationship. We show, however, that generalizations of the Schwarzschild metric, the Taub-NUT metrics, do indeed lead to the observed redshift-distance relationship and to the observed time dilation. These universes are not expanding rather the observed cosmological redshift is due to the gravitational redshift associated with these solutions. Time dilation in these stationary universes has the same dependency on redshift that generally has been seen as proof that space is expanding. Our theory resolves the hubble tension.

关键词： Cosmology General Relativity

NRF2 signaling cascade in amyotrophic lateral sclerosis:bridging the gap between promise and reality

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Neural Regeneration Research 2024年第5期19卷 1006-1012页

作者： Pauline Tarot Christelle Lasbleiz Jean-charles Liévens MMDN Univ MontpellierEPHEINSERMMontpellierFrance CNRS ParisFranceEPHEINSERMMontpellierFrance

Amyotrophic lateral sclerosis is a very disabling disease due to the degeneration of motor *** include muscle weakness and atrophy,spasticity,and progressive ***,there is no treatment to reverse damage to motor neurons and cure amyotrophic lateral *** only two treatments actually approved,riluzole and edaravone,have shown mitigated beneficial *** difficulty to find a cure lies in the complexity and multifaceted pattern of amyotrophic lateral sclerosis *** mechanisms,abnormal RNA metabolism,nucleocytoplasmic transport defects,accumulation of unfolded protein,and mitochondrial dysfunction would in fine induce oxidative damage and vice versa.A potent therapeutic strategy will be to find molecules that break this vicious *** the nuclear factor erythroid-2 related factor 2 signaling may fulfill this objective since nuclear factor erythroid-2 related factor 2 has a multitarget profile controlling antioxidant defense,mitochondrial functioning,and *** here discuss the interest of developing nuclear factor erythroid-2 related factor 2-based therapy in regard to the pathophysiological mechanisms and we provide a general overview of the attempted clinical assays in amyotrophic lateral sclerosis.

关键词： amyotrophic lateral sclerosis C9orf72 NRF2 oxidative defense oxidative stress sulforaphane superoxide dismutase 1 TDP43

Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii charles F.Zorumski Yukitoshi Izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

Metabolic reprogramming of the inflammatory response in the nervous system:the crossover between inflammation and metabolism

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Neural Regeneration Research 2024年第10期19卷 2189-2201页

作者： Jesus Amo-Aparicio charles A.Dinarello Ruben Lopez-Vales Department of Medicine University of ColoradoAuroraCOUSA Institute of Neurosciences and Department Cell BiologyPhysiology and ImmunologyUniversitat Autònoma de BarcelonaBellaterraSpain Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos ⅢSpain

Metabolism is a fundamental process by which biochemicals are broken down to produce energy(catabolism) or used to build macromolecules(anabolism). Metabolism has received renewed attention as a mechanism that generates molecules that modulate multiple cellular responses. This was first identified in cancer cells as the Warburg effect, but it is also present in immunocompetent cells. Studies have revealed a bidirectional influence of cellular metabolism and immune cell function, highlighting the significance of metabolic reprogramming in immune cell activation and effector functions. Metabolic processes such as glycolysis, oxidative phosphorylation, and fatty acid oxidation have been shown to undergo dynamic changes during immune cell response, facilitating the energetic and biosynthetic demands. This review aims to provide a better understanding of the metabolic reprogramming that occurs in different immune cells upon activation, with a special focus on central nervous system disorders. Understanding the metabolic changes of the immune response not only provides insights into the fundamental mechanisms that regulate immune cell function but also opens new approaches for therapeutic strategies aimed at manipulating the immune system.

关键词： central nervous system fatty acid oxidation glycolysis inflammation macrophage metabolism microglia neurodegeneration oxidative phosphorylation

New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao charles K.F.Chan Institute for Stem Cell Biology and Regenerative Medicine Stanford University School of MedicineStanford CA 94305USA Department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA Department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain