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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is en

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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A simple method for pulse contrast enhancement via self-focusing

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High Power Laser Science and Engineering 2024年第2期12卷 51-61页

作者： Zaharit Refaeli Gilad Marcus Yariv Shamir applied Physics division Soreq NRCYavneIsrael applied Physics Institute The Hebrew UniversityThe Edmond J.Safra Campus-Givat RamJerusalemIsrael

Here we report on a simple-to-implement and cost-effective approach for laser pulse contrast enhancement,based on the χ(3)nonlinear self-focusing *** intentionally induced and gently controlled self-focusing in a thin glass transforms the time-dependent intensity into variation in beam *** by a spatial discriminating filter,only the strongly focused fraction traverses the setup,at the expense of efficiency.A numerical model,accounting for the pulse and material parameters via a Gaussian ABCD matrix,provides an estimate for the instantaneous beam waist and transmission efficiency,which enables us to evaluate the resulting contrast *** estimated contrast enhancement spans between 0.5 and 2.5 orders of magnitude,in conjunction with approximately 25%–90%estimated efficiency,depending on the pulse *** a preliminary experiment we demonstrated the effect with 10s-μJ sub GW regime with approximately 40%efficiency and a contrast improvement of more than or equal to 20 dB.

关键词： nonlinear optics pulse contrast self-focusing ultrafast laser

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Unveiling the distinctive traits of functional rye centromeres:minisatellites, retrotransposons, and R-loop formation

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Science China Life Sciences 2024年第9期67卷 1989-2002页

作者： Chang Liu Shulan Fu Congyang Yi Yang Liu Yuhong Huang Xianrui Guo Kaibiao Zhang Qian Liu James A.Birchler Fangpu Han State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Plant genetics and Breeding Sichuan Agricultural University division of Biological Science University of Missouri

Centromeres play a vital role in cellular division by facilitating kinetochore assembly and spindle attachments. Despite their conserved functionality, centromeric DNA sequences exhibit rapid evolution, presenting diverse sizes and compositions across species. The functional significance of rye centromeric DNA sequences, particularly in centromere identity, remains unclear. In this study, we comprehensively characterized the sequence composition and organization of rye centromeres. Our findings revealed that these centromeres are primarily composed of long terminal repeat retrotransposons(LTR-RTs) and interspersed minisatellites. We systematically classified LTR-RTs into five categories, highlighting the prevalence of younger CRS1, CRS2, and CRS3 of CRSs(centromeric retrotransposons of Secale cereale) were primarily located in the core centromeres and exhibited a higher association with CENH3 nucleosomes. The minisatellites, mainly derived from retrotransposons, along with CRSs, played a pivotal role in establishing functional centromeres in rye. Additionally, we observed the formation of R-loops at specific regions of CRS1, CRS2, and CRS3, with both rye pericentromeres and centromeres exhibiting enrichment in R-loops. Notably, these R-loops selectively formed at binding regions of the CENH3 nucleosome in rye centromeres, suggesting a potential role in mediating the precise loading of CENH3 to centromeres and contributing to centromere specification. Our work provides insights into the DNA sequence composition, distribution, and potential function of R-loops in rye centromeres. This knowledge contributes valuable information to understanding the genetics and epigenetics of rye centromeres, offering implications for the development of synthetic centromeres in future plant modifications and beyond.

关键词： centromere LTR-RTs minisatellite rye R-loop

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings division of genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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Lax-Oleinik-Type Formulas and Efficient Algorithms for Certain High-Dimensional Optimal Control Problems

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Communications on applied Mathematics and Computation 2024年第2期6卷 1428-1471页

作者： Paula Chen Jerome Darbon Tingwei Meng division of applied Mathematics Brown UniversityProvidenceRIUSA Department of Mathematics UCLALos AngelesCAUSA

Two of the main challenges in optimal control are solving problems with state-dependent running costs and developing efficient numerical solvers that are computationally tractable in high *** this paper,we provide analytical solutions to certain optimal control problems whose running cost depends on the state variable and with constraints on the *** also provide Lax-Oleinik-type representation formulas for the corresponding Hamilton-Jacobi partial differential equations with state-dependent ***,we present an efficient,grid-free numerical solver based on our representation formulas,which is shown to scale linearly with the state dimension,and thus,to overcome the curse of *** existing optimization methods and the min-plus technique,we extend our numerical solvers to address more general classes of convex and nonconvex initial *** demonstrate the capabilities of our numerical solvers using implementations on a central processing unit(CPU)and a field-programmable gate array(FPGA).In several cases,our FPGA implementation obtains over a 10 times speedup compared to the CPU,which demonstrates the promising performance boosts FPGAs can *** numerical results show that our solvers have the potential to serve as a building block for solving broader classes of high-dimensional optimal control problems in real-time.

关键词： Optimal control Hamilton-Jacobi partial differential equations Grid-free numerical methods High dimensions Field-programmable gate arrays(FPGAs)

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Phylogenetic, phylogeographic and divergence time analysis of Anopheles subpictus species complex using ITS2 and COI sequences

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 214-225,I0004-I0038页

作者： Lihini Sandaleka Muthukumarana Methsala Madurangi Wedage Samanthika Rathnayake Nissanka Kolitha De Silva Department of Zoology Faculty of Applied SciencesUniversity of Sri JayewardenepuraGangodawilaNugegodaSri Lanka genetics and Molecular Biology Unit Faculty of Applied SciencesUniversity of Sri JayewardenepuraGangodawilaNugegodaSri Lanka Sri Lanka Institute of Biotechnology PitipanaHomagamaSri Lanka

Objective:To address the phylogenetic and phylogeographic relationship between different lineages of Anopheles(An.)subpictus species complex in most parts of the Asian continent by maximum utilization of Internal Transcriber Spacer 2(ITS2)and cytochrome C oxidase I(COI)sequences deposited at the ***:Seventy-five ITS2,210 COI and 26 concatenated sequences available in the NCBI database were *** analysis was performed using Bayesian likelihood trees,whereas median-joining haplotype networks and time-scale divergence trees were generated for phylogeographic *** diversity indices and genetic differentiation were also ***:Two genetically divergent molecular forms of *** species complex corresponding to sibling species A and B are *** A evolved around 37-82 million years ago in Sri Lanka,India,and the Netherlands,and species B evolved around 22-79 million years ago in Sri Lanka,India,and ***,Thailand,and Cambodia have two molecular forms:one is phylogenetically similar to species *** forms differ from species A and B and evolved recently in the above mentioned countries,Indonesia and the *** subdivision among Sri Lanka,India,and the Netherlands is almost absent.A substantial genetic differentiation was obtained for some populations due to isolation by large geographical *** diversity indices reveal the presence of a long-established stable mosquito population,at mutation-drift equilibrium,regardless of population ***:*** species complex consists of more than two genetically divergent molecular *** A is highly divergent from the *** Lanka and India contain only species A and B.

关键词： Molecular systematics ITS2 COI DNA sequences Phylogeny Phylogeography

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Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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Journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas Eduardo E.Rodriguez Laura M.Jensen Raluca G.Mateescu Peter J.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PEBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

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The immune system: uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan José Lasarte Immunology and Immunotherapy Program Centre for Applied Medical Research (CIMA) University of NavarraIDISNA division of Gene Therapy for Neurological Disorders Centre for Applied Medical Research (CIMA) University of NavarraIDISNA Pathology Anatomy and Physiology Department School of Medicine University of NavarraIDISNA

Humans and animals use the classic five senses-sight, hearing, touch, smell, and taste-to detect and monitor their environment, with the sense of position and movement often referred to as the sixth sense. The perception of external signals through the senses is essential to an organism’s survival, transmitting signals to the central nervous system(CNS) and prompting physiological changes in other biological systems. In addition to the direct effects of sense-induced mediators in the brain,

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Poly(A)-specific RNase(PARN)generates and regulates miR-125a-5p 3’-isoforms,displaying an altered expression in breast cancer

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1805-1807页

作者： Luisa Tomasello Shoshanah M.Holub Giovanni Nigita Rosario Distefano Carlo M.Croce Department of Cancer Biology and genetics The Ohio State UniversityColumbusOHUSA Department of Internal Medicine Division of HematologyThe Ohio State UniversityColumbusOHUSA

Dear Editor,MicroRNAs(miRNAs)are small non-coding RNAs crucial for post-transcriptional gene regulation,processed from primary miRNA transcripts by Drosha and Dicer.1 Latest advancements in Next Generation Sequencing highlighted the existence of miRNA isoforms(isomiRs)resulting from alternative processing,RNA editing,or post-transcriptional modifications.

关键词： breast cancer advancement

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Modified DS np Chart Using Generalized Multiple Dependent State Sampling under Time Truncated Life Test

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Computer Modeling in Engineering & Sciences 2024年第3期138卷 2471-2495页

作者： Wimonmas Bamrungsetthapong Pramote Charongrattanasakul division of applied Statistics Department of Mathematics and Computer ScienceFaculty of Science and TechnologyRajamangala University of Technology ThanyaburiPathum Thani12110Thailand division of Mathematics Department of Mathematics and Computer ScienceFaculty of Science and TechnologyRajamangala University of Technology KrungthepBangkok10120Thailand

This study presents the design of a modified attributed control chart based on a double sampling(DS)np chart applied in combination with generalized multiple dependent state(GMDS)sampling to monitor the mean life of the product based on the time truncated life test employing theWeibull *** control chart developed supports the examination of the mean lifespan variation for a particular product in the process of *** control limit levels are used:the warning control limit,inner control limit,and outer control ***,they enhance the capability for variation detection.A genetic algorithm can be used for optimization during the in-control process,whereby the optimal parameters can be established for the proposed control *** control chart performance is assessed using the average run length,while the influence of the model parameters upon the control chart solution is assessed via sensitivity analysis based on an orthogonal experimental design withmultiple linear regression.A comparative study was conducted based on the out-of-control average run length,in which the developed control chart offered greater sensitivity in the detection of process shifts while making use of smaller samples on average than is the case for existing control ***,to exhibit the utility of the developed control chart,this paper presents its application using simulated data with parameters drawn from the real set of data.

关键词： Modified DS np chart generalizedmultiple dependent state sampling time truncated life test Weibull distribution average run length average sample size

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