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Promoting axon regeneration in the central nervous system by increasing PI3-kinase signaling

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Neural Regeneration Research 2022年第6期17卷 1172-1182页

作者： Bart Nieuwenhuis Richard eva John van Geest Center for Brain Repair Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK

Much research has focused on the PI3-kinase and PTEN signaling pathway with the aim to stimulate repair of the injured central nervous *** in the central nervous system fail to regenerate,meaning that injuries or diseases that cause loss of axonal connectivity have life-changing *** 2008,genetic deletion of PTEN was identified as a means of stimulating robust regeneration in the optic *** is a phosphatase that opposes the actions of PI3-kinase,a family of enzymes that function to generate the membrane phospholipid PIP_(3) from PIP_(2)(phosphatidylinositol(3,4,5)-trisphosphate from phosphatidylinositol(4,5)-bisphosphate).Deletion of PTEN therefore allows elevated signaling downstream of PI3-kinase,and was initially demonstrated to promote axon regeneration by signaling through *** recently,additional mechanisms have been identified that contribute to the neuron-intrinsic control of regenerative *** review describes neuronal signaling pathways downstream of PI3-kinase and PIP3,and considers them in relation to both developmental and regenerative axon *** briefly discuss the key neuron-intrinsic mechanisms that govern regenerative ability,and describe how these are affected by signaling through *** highlight the recent finding of a developmental decline in the generation of PIP_(3) as a key reason for regenerative failure,and summarize the studies that target an increase in signaling downstream of PI3-kinase to facilitate regeneration in the adult central nervous ***,we discuss obstacles that remain to be overcome in order to generate a robust strategy for repairing the injured central nervous system through manipulation of PI3-kinase signaling.

关键词： axon cytoskeleton axon regeneration axon transport cell signaling central nervous system growth cone neuroprotection PI3-kinase PI3K PTEN trafficking transcription translation

Aquaporin 5 in Alzheimer’s disease:a link between oral and brain pathology?

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Neural Regeneration Research 2023年第7期18卷 1491-1492页

作者： Cristina Municio eva Carro Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpain Network Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED) Instituto de Salud Carlos IIIMadridSpain Neurobiology of Alzheimer’s Disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpain

The involvement of aquaporins(AQPs)in the development of diseases has been widely described(Azad et al.,2021).AQP5 has been described in astrocytes changing after traumatic brain injuries(Chai et al.,2013),but the precise role of AQP5 in Alzheimer’s disease(AD)pathology is yet to be *** have recently reported that AQP5 expression changes during the development of AD(Antequera et al.,2022).The AQP5 expression in salivary glands is decreased in 6-month-old APP/PS1 mice and AD *** decrease in AQP5 expression could be involved in the mechanism of salivary gland dysfunction described in a previous study(Antequera et al.,2021).Now,we propose a new indirect role of AQP5 in the connection between infection-induced oral dysbiosis and AD(Sureda et al.,2020).Here,we suggest that the proinflammatory response induced by oral pathogen infection results in the downregulation of AQP5 contributing to the salivary gland secretory *** these alterations destabilize the peripheral immune-inflammatory balance and exacerbate neuroinflammation and neurodegeneration leading to AD pathology.

关键词： salivary pathology Alzheimer

Predicting the output error of the suboptimal state estimator to improve the performance of the MPC-based artificial pancreas

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Control Theory and Technology 2023年第4期21卷 541-554页

作者： Martin Dodek eva Miklovičová Institute of Robotics and Cybernetics Faculty of Electrical Engineering and Information TechnologySlovak University of Technology in BratislavaIlkovičova 3Bratislava81219Slovakia

The error of single step-ahead output prediction is the information traditionally used to correct the state estimate while exploiting the new measurement of the system ***,its dynamics and statistical properties can be further studied and exploited in other *** is known that in the case of suboptimal state estimation,this output prediction error forms a correlated sequence,hence it can be effectively predicted in real *** a suboptimal scenario is typical in applications where the process noise model is not known or it is ***,the paper deals with the problems of analytical and empirical modeling,identification,and prediction of the output error of the suboptimal state estimator for the sake of improving the output prediction accuracy and ultimately the performance of the model predictive *** improvements are validated on an empirical model of type 1 diabetes within an in-silico experiment focused on glycemia prediction and implementation of the MPC-based artificial pancreas.

关键词： Suboptimal state estimation Prediction Autoregressive model Moving average model Model predictive control Diabetes mellitus Artificial pancreas

Influence of temperature and pressure during thermoforming of softwood pulp

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Journal of Bioresources and Bioproducts 2023年第4期8卷 408-420页

作者： eva Pasquier Robert Skunde Jost Ruwoldt RISE PFI AS Høgskoleringen 6BTrondheim 7491Norway TU-Berlin Institute for Polymer Technology and Polymer PhysicsErnst Reuter Platz 1Berlin 10587Germany

In this study,the influence of thermoforming conditions on the resulting material properties was investigated,which aimed at developing advanced wood-fiber-based materials for the replacement of fossil *** bleached softwood pulps were studied,i.e.,northern bleached softwood Kraft pulp(NBSK)and chemi-thermomechanical softwood pulp(CTMP).The thermoforming conditions were varied between 2–100 MPa and 150–200℃,while pressing sheets of 500 g/m^(2)for 10 min to represent thin-walled packaging more *** our results showed,the temperature had a more pronounced effect on the CTMP substrates than on the Kraft *** was explained by the greater abundance of lignin and hemicelluloses,while fibrillar dimensions and the fines content may play a role in ***,the CTMP exhibited an optimum in terms of tensile strength at intermediate thermoforming *** effect was attributed to two counteracting effects:1)Improved fiber adhesion due to enhanced densification,and 2)embrittlement caused by the loss of *** temperatures likely softened the lignin,enabling fiber collapse and a tighter *** the Kraft substrates,the tensile strength increased linearly with *** pulps showed reduced wetting at elevated thermoforming temperature and pressure,which was attributed to hornification and densification ***,the effect of temperature was again more pronounced for CTMP than for the Kraft *** was concluded that the thermoforming temperature and pressure strongly affected the properties of the final *** chemical composition of the pulps will distinctly affect their response to thermoforming,which could be useful for tailoring cellulose-based replacements for packaging products.

关键词： Thermoforming Molded pulp Fiber-based materials Softwood pulp CTMP NBSK

Control of the Hedgehog pathway by compartmentalized PKA in the primary cilium

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Science China(Life Sciences) 2022年第3期65卷 500-514页

作者： eva Cai Jingyi Zhang Xuecai Ge Department of Molecular and Cell Biology School of Natural SciencesUniversity of CaliforniaMerced CA 95340USA

The Hedgehog(Hh)signaling is one of the essential signaling pathways during embryogenesis and in *** signal transduction relies on primary cilium,a specialized cell surface organelle viewed as the hub of cell *** kinase A(PKA)has been recognized as a potent negative regulator of the Hh pathway,raising the question of how such a ubiquitous kinase specifically regulates one signaling *** reviewed recent genetic,molecular and biochemical studies that have advanced our mechanistic understanding of PKA’s role in Hh signaling in vertebrates,focusing on the compartmentalized PKA at the centrosome and in the primary *** outlined the recently developed genetic and optical tools that can be harvested to study PKA activities during the course of Hh signal transduction.

关键词： Hedgehog signaling protein kinase A(PKA) primary cilium centrosome compartmentalized cell signaling

Purinergic signaling systems across comparative models of spinal cord injury

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Neural Regeneration Research 2022年第3期17卷 2391-2398页

作者： eva E.Stefanova Angela L.Scott Department of Pathology and Molecular Medicine McMaster UniversityHamiltonONCanada

Within the last several decades,the scientific community has made substantial progress in elucidating the complex pathophysiology underlying spinal cord ***,despite the many advances using conventional mammalian models,both cellular and axonal regeneration following spinal cord injury have remained out of *** this sense,turning to non-mammalian,regenerative species presents a unique opportunity to identify pro-regenerative cues and chara cterize a spinal cord microenvironment permissive to *** the signaling pathways hypothesized to be dysregulated during spinal cord injury is the purinergic signaling *** addition to its well-known role as energy currency in cells,ATP and its metabolites are small molecule neurotransmitte rs that mediate many diverse cellular processes within the central nervous *** our unde rstanding of the roles of the purinergic system following spinal cord injury is limited,this signaling pathway has been implicated in all injury-induced secondary processes,including cellular death,inflammation,reactive gliosis,and neural *** that the purinergic system is also evolutionarily conserved between mammalian and non-mammalian species,comparisons of these roles may provide important insights into conditions responsible for recovery ***,we compare the secondary processes between key model species and the influence of purinergic signaling in each *** our understanding of this signaling system and pro-regenerative conditions continues to evolve,so does the potential for the development of novel therapeutic interventions for spinal cord injury.

关键词： cell death differenriation glia inflammation neurogenesis proliferation purinergic signaling reactive gliosis regeneration spinal cord injury teleost

Implication of salivary lactoferrin and periodontal-mediated infections in Alzheimer's disease

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Neural Regeneration Research 2023年第12期18卷 2691-2692页

作者： Cristina Municio eva Carro Group of Neurodegenerative Diseases Hospital Universitario 12 de Octubre Research Institute(imas12)MadridSpainNetwork Center for Biomedical Research in Neurodegenerative Diseases(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neurobiology of Alzheimer’s disease Unit Functional Unit for Research into Chronic DiseasesInstituto de Salud Carlos IIIMadridSpainNetwork Centre for Biomedical Research in Neurodegenerative Diseases(CIBERNED)Instituto de Salud Carlos IIIMadridSpain

Lactoferrin is an antimicrobial prote in characterized by the exertion of many protective functions,including antibacterial,antifungal,antiviral,and antiparasitic properties,as well as anti-inflammatory and immunomodulatory activities(Kruzel et al.,2017).Lactoferrin is one of the major proteins present in exocrine secretions,including saliva,and is therefore associated with host defense against oral pathogens and control of the oral *** recent years,it has become clear that alterations in the oral microbiome may contribute to opportunistic pathogen infections in the brains of Alzheimer’s disease(AD)patients and thus participate in or contribute to the development of this neurodegenerative disease(Sureda et al.,2020).Pathogenic oral microbes can affect neurological processes by entering brain tissue through various pathways and directly damaging the central nervous *** the central nervous system,oral microbes may trigger an immune response that increases amyloidβ(Aβ)production and may even trigger the Aβcascade to promote the onset of AD,as we discuss in our previous study supporting the“infectious hypothesis”in AD(González-Sánchez et al.,2020).

关键词： Alzheimer infections protective

SPINOPHILIN: A multiplayer tumor suppressor

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Genes & Diseases 2023年第1期10卷 187-198页

作者： eva M.Verdugo-Sivianes Amancio Carnero Instituto de Biomedicina de Sevilla IBISHospital Universitario Virgen del RocioConsejo Superior de Investigaciones CientificasUniversidad de SevillaSeville 41013Spain CIBERONC Instituto de Salud Carlos IlMadrid 28029Spain

SPINOPHILIN(SPN,PPP1R9B or NEURABIN-2)is a multifunctional protein that regulates protein-protein interactions in different cell signaling *** is also one of the regulatory subunits of protein phosphatase 1(PP1),implicated in the dephosphorylation of retinoblastoma protein(pRB)during cell *** SPN gene has been described as a tumor suppressor in different human tumor contexts,in which low levels of SPN are correlated with a higher grade and worse *** addition,mutations of the SPN protein have been reported in human ***,an oncogenic mutation of sPN,A566V,was described,which affects both the SPN-PP1 interaction and the phosphatase activity of the holoenzyme,and promotes p53-dependent tumorigenesis by increasing the cancer stem cell(CsC)pool in breast ***,the loss or mutation of SPN could be late events that promotes tumor progression by increasing the CSC pool and,eventually,the malignant behavior of the tumor.

关键词： Cancer therapy Phosphatase PP1 SPINOPHILIN Tumor suppressor Tumorigenesis

Unexpected bonds:ubiquitin-like conjugation of cGAS/CDNTases supports their enzymatic activity and antiphage defense

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3899-3901页

作者： Katarzyna Andryka-Cegielski Sofía Soler eva Bartok Institute of Experimental Haematology and Transfusion Medicine University HospitalUniversity of BonnBonnGermany Institute of Clinical Chemistry and Clinical Pharmacology University HospitalUniversity of BonnBonnGermany

In their recently published study in Nature,Jenson et al.1 provide compelling,unexpected evidence that bacterial cGAMP synthase(cGAS)and other cGAS/DncV-like Nucleotidyltransferases(CD-NTase)undergo ubiquitin-like conjugation(ULC)in type-II cyclic-oligonucleotide-based anti-phage signaling systems(CBASS).cGAS conjugation promotes cyclic-nucleotide(CN)formation and thus antiphage ***,the authors also reveal a new class of phage-encoded CBASS inhibitor,T4 Vs.4,a CN-sponge which limits CBASS effector function and promotes phage replication,revealing another weapon in the“arms race”between phages and their bacterial hosts.

关键词： bonds enzymatic sponge