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Ubiquitin homeostasis disruption, a common cause of proteostasis collapse in amyotrophic lateral sclerosis?

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Neural Regeneration Research 2022年第10期17卷 2218-2220页

作者： Christen G.Chisholm jeremy s.Lum natalie E.Farrawell justin j.Yerbury Illawarra Health and Medical Research Institute/Molecular Horizons and school of Chemistry and Molecular Bioscience Science Medicine and Health FacultyUniversity of WollongongNorthfields AveWollongongNSWAustralia

Amyotrophic lateral sclerosis(ALs)is associated with proteostasis collapse:ALs is an unrelenting neurodegenerative disease that is characterized by the loss of motor neurons in the brain and spinal cord,resulting in the progressive atrophy,and eventual paralysis,of skeletal *** due to respiratory failure usually occurs within 2-5 years from symptom *** 90%of ALs cases are of unknown etiology and are termed sporadic ALs(sALs).The remaining 10%of ALs cases present with a family history(familial ALs;fALs)and are associated with genetic mutations in a range of over 20 functionally heterogeneous *** of disease origin,the pathological hallmark of ALs is the accumulation of ubiquitylated protein inclusions in motor neurons and surrounding glial *** presence of these inclusions,compromised largely of misfolded and aggregated proteins,implies a collapse in *** refers to the maintenance of the proteome in a state of balance or equilibrium so that a cell can perform its proper function.

关键词： stasis homeostasis collapse

Associations of self-reported and device-assessed physical activity with fatigue,quality of life,and sleep quality in adults living with and beyond cancer

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journal of sport and Health science 2023年第6期12卷 664-673,F0003页

作者： Phillippa Lally natalie Ella Miller Claire Lawrence Rebecca j Beeken Abigail Fisher Department of Behavioural science and Health University College LondonLondon WC1E 6BTUK Department of Psychology University of SurreyGuildford GU27XHUK Leeds Institute of Health sciences Leeds LS29NLUK

Background Greater physical activity is associated with improved outcomes in people living with and beyond ***,most studies in exercise oncology use self-reported measures of physical *** have explored agreement between self-reported and device-based measures of physical activity in people living with and beyond *** study aimed to describe physical activity in adults affected by cancer across self-reported and device-assessed activity,to explore levels of agreement between these measures in terms of their utility for categorizing participants as meeting/not meeting physical activity guidelines,and to explore whether meeting guidelines is associated with fatigue,quality of life,and sleep *** A total of 1348 adults living with and beyond cancer from the Advancing survivorship Cancer Outcomes Trial completed a survey assessing fatigue,quality of life,sleep quality,and physical *** Godin-shephard Leisure-Time Physical Activity Questionnaire was used to calculate a Leisure score Index(LsI)and an estimate of moderate-to-vigorous physical activity(MVPA).Average daily steps and weekly aerobic steps were derived from pedometers worn by *** The percentage of individuals meeting physical activity guidelines was 44.3%using LsI,49.5%using MVPA,10.8%using average daily steps,and 28.5%using weekly aerobic ***(Cohen'sκ)between self-reported and pedometer measures ranged from 0.13(LsI *** daily steps)to 0.60(LsI ***).After adjusting for sociodemographic and health-related covariates,meeting activity guidelines using all measures was associated with not experiencing severe fatigue(odds ratios(ORs):1.43–1.97).Meeting guidelines using MVPA was associated with no quality-of-life issues(OR=1.53).Meeting guidelines using both self-reported measures were associated with good sleep quality(ORs:1.33–1.40).Conclusion Less than half of all adults affected by cancer are meeting physical activity guidelines,

关键词： Cancer survivorship Fatigue Physical activity Quality of life sleepTagedAPTARAEnd

Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

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World journal of stem Cells 2015年第2期7卷 281-299页

作者： john D West natalie j Dorà j Martin Collinson Genes and Development Group Centre for Integrative PhysiologyCollege of Medicine and Veterinary MedicineUniversity of Edinburgh Institute of Medical sciences School of Medical SciencesCollege of Life Sciences and MedicineForesterhillUniversity of Aberdeen

In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LEsC)hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient(or transit) amplifying cells(TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LEsCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. second, the corneal epithelial stem cell(CEsC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LEsCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LEsC and CEsC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LEsC and CEsC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LEsC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CEsC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the

关键词： Eye Cornea Corneal epithelium Limbalepithelium stem cell Lineage tracing

CO2 activation on bimetallic CuNi nanoparticles

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Progress in Natural science:Materials International 2016年第5期26卷 487-492页

作者： natalie Austin Brandon Butina Giannis Mpourmpakis Department of Chemical Engineering University of Pittsburgh

Density functional theory calculations have been performed to investigate the structural, electronic, and CO2adsorption properties of 55-atom bimetallic Cu Ni nanoparticles（NPs） in core-shell and decorated architectures,as well as of their monometallic counterparts. Our results revealed that with respect to the monometallic Cu55and Ni55parents, the formation of decorated Cu12Ni43and core-shell Cu42Ni13are energetically favorable. We found that CO2chemisorbs on monometallic Ni55, core-shell Cu13Ni42, and decorated Cu12Ni43and Cu43Ni12,whereas, it physisorbs on monometallic Cu55and core-shell Cu42Ni13. The presence of surface Ni on the NPs is key in strongly adsorbing and activating the CO2molecule（linear to bent transition and elongation of C=O bonds）. This activation occurs through a charge transfer from the NPs to the CO2molecule, where the local metal d-orbital density localization on surface Ni plays a pivotal role. This work identifies insightful structureproperty relationships for CO2activation and highlights the importance of keeping a balance between NP stability and CO2adsorption behavior in designing catalytic bimetallic NPs that activate CO2.

关键词： Density functional theory Alloys CO2adsorption Catalysis stability

Galvanically induced potentials to enable minimal tribochemical wear of stainless steel lubricated with sodium chloride and ionic liquid aqueous solution

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Friction 2018年第2期6卷 230-242页

作者： Tobias AMANN Felix GATTI natalie OBERLE Andreas KAILER jürgen RüHE Fraunhofer Institute for Mechanics of Materials IWM Institute for Macromolecular Chemistry University of Freiburg IMTEK-Department of Microsystems Engineering University of Freiburg

The effect of galvanically induced potentials on the friction and wear behavior of a 1 RK91 stainless steel regarding to tribocorrosion was investigated using an oscillating ball-on-disk tribometer equipped with an electrochemical cell. The aim of this investigation is to develop a water-based lubricant. Therefore 1 molar sodium chloride(NaCl) and 1% 1-ethyl-3-methylimidazolium chloride [C_2 mim][Cl] water solutions were used. Tribological performance at two galvanically induced potentials was compared with the non-polarized state: cathodic potential-coupling with pure aluminum- and anodic potential-coupling with pure copper. Frictional and electrochemical response was recorded during the tests. In addition, wear morphology and chemical composition of the steel were analyzed using scanning electron microscopy(sEM) and X-ray photoelectron spectroscopy(XPs), respectively. The galvanically induced cathodic polarization of the stainless steel surface results in electrochemical corrosion protection and the formation of a tribolayer. Cations from the electrolyte(sodium Na^+ and 1-ethyl- 3-methylimidazolium [C_2 mim]^+) interact and adhere on the surface. These chemical interactions lead to considerably reduced wear using 1 NaC l(86%) and 1% 1-ethyl-3-methylimidazolium chloride [C_2 mim][Cl](74%) compared to the nonpolarized system. In addition, mechanical and corrosive part of wear was identified using this electrochemical technique. Therefore this method describes a promising method to develop water-based lubricants for technical applications.

关键词： sliding wear tribochemistry potential controlled friction and wear galvanic coupling ionic liquids tribolayer formation

Intriguing Origins of Protein Lysine Methylation:Influencing Cell Function Through Dynamic Methylation

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Genomics, Proteomics & Bioinformatics 2019年第6期17卷 551-557页

作者： natalie Mezey William C.s.Cho Kyle K.Biggar Institute of Biochemistry and Department of Biology Carleton UniversityOttawaON K1S 5B6Canada Department of Clinical Oncology Queen Elizabeth HospitalKowloonHong Kong Special Administrative RegionChina

Introduction“There is a kink(shoulder)on[the]Lys peak...”These words scribed in Richard ***’s laboratory notebook marked the discovery of protein methylation and a segue into a new field of scientific research[1].Initially,through ion-exchange chromatography and two-dimensional paper chromatography of the hydrolysate of salmonella typhimurium flagellin,this“kink”was interpreted as a“new amino acid”,the e-Nmethyl-lysine(NML).This discovery,bolstered by a subsequent examination of purified NML,was the first glimpse of protein methylation in living cells[1].

关键词： Lys Intriguing Origins of Protein Lysine Methylation:Influencing Cell Function Through Dynamic Methylation

Association between dairy intake,lipids and vascular structure and function in diabetes

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World journal of Diabetes 2017年第5期8卷 202-212页

作者： Kristina s Petersen jennifer B Keogh natalie Lister jacquelyn M Weir Peter j Meikle Peter M Clifton school of Pharmacy and Medical sciences and sansom Institute for Health Research University of South Australia Baker IDI Heart and Diabetes Institute

AIM To determine lipid species that change in response to a change in dairy consumption. In addition, to investigate whether dairy associated lipid species are correlated with changes in measures of vascular structure and *** A 12-mo randomised controlled trial was conducted to determine the effect of increased consumption of fruit, vegetables and dairy, compared to usual diet, on measures of vascular structure and function in adults with type 1 and type 2 diabetes(n = 108). Thispaper comprises post-hoc analyses investigating the relationship between dairy intake, serum lipid species and vascular health. Central and peripheral blood pressure, carotid femoral pulse wave velocity, augmentation index, serum lipid species and dietary intake were measured at baseline and 3-mo. Common carotid artery intima media thickness was measured at baseline and *** serum lipid species [lysophosphatidylcholine(LPC) 14:0, LPC 15:0, LPC 16:1, phosphatidylcholine(PC) 29:0 PC 30:0, PC 31:0 and cholesterol ester(CE) 14:0] were associated with the change in full fat dairy consumption(rho 0.19-0.25; P some lipids was positively associated with the 3-mo change in central systolic [LPC 14:0(rho 0.30; P = 0.007), PC 30:0(rho 0.28; P = 0.010)] and diastolic blood pressure [LPC 14:0(rho 0.32; P = 0.004), LPC 15:0(rho 0.23; P = 0.04), LPC 16:1(rho 0.23; P = 0.035), PC 29:0(rho 0.28; P = 0.01), PC 30:0(rho 0.36; P = 0.001), PC 31:0(rho 0.30; P = 0.007)] and 12-mo change in common carotid artery intimal medial thickness [CE 14:0(rho 0.22; P = 0.02)]. Pulse wave velocity and augmentation index were unrelated to dairy and lipid *** An increase in dairy associated lipids appears to be associated with an increase in blood pressure and common carotid intimal medial thickness.

关键词： Lipids Phospholipids Atherosclerosis Dairy Lysophosphatidylcholine Lipidomics Carotid intima media thickness Pulse wave velocity Diabetes

Endosomal trafficking defects in patient cells with KIAA1109 biallelic variants

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Genes & Diseases 2019年第1期6卷 56-67页

作者： Megan s.Kane Callie j.Diamonstein natalie Hauser john F.Deeken john E.Niederhuber Thierry Vilboux Inova Translational Medicine Institute Inova Health SystemFairfaxVAUnited States Department of Medicine Virginia Commonwealth UniversityRichmondVAUnited States Department of Public Health sciences University of Virginia School of MedicineCharlottesvilleVAUnited States Department of Oncology and surgery Johns Hopkins University School of MedicineBaltimoreMDUnited States

The uncharacterized gene KIAA1109 has recently been associated with a congenital neurological malformation disorder that variably presents with arthrogryposis,craniofacial and/or cardiac *** have identified two additional patients with compound heterozygous KIAA1109 variants presenting with the same neurological *** mechanism whereby KIAA1109 loss of function causes this spectrum of disorders was the primary focus of our *** hypothesized that KIAA1109 function could be conserved relative to the fly gene tweek and examined endocytosis and endosome recycling in patient ***,we examined the structure of the cytoskeleton and cilia based on functional overlap with endocytosis and several known etiologies for neuronal migration *** primary dermal fibroblasts from one patient and a healthy donor,we performed immunofluorescence and endocytosis assays to examine the endosomal,cytoskeletal,and ciliary cellular *** found notable abnormalities in endosomal trafficking and endosome recycling *** also observed changes in the actin cytoskeleton and cilia structural *** conclude that the function of KIAA1109 in humans may indeed overlap with the function of the Drosophila ortholog,resulting in perturbations to endosomal trafficking and the actin *** alterations have ripple effects,altering many pathways that are critical for proper neuronal migration and embryonic development.

关键词： Cilia Endocytosis KIAA1109 Neurological malformation Vesicular trafficking

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

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Genomics, Proteomics & Bioinformatics 2016年第3期14卷 155-165页

作者： natalie Kaminsky Ofer Bihari sivan Kanner Ari Barzilai Department of Neurobiology George S.WiseFaculty of Life SciencesTel Aviv University sagol school of Neuroscience Tel Aviv University

The DNA damage response（DDR） is a complex biological system activated by different types of DNA *** in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration,premature aging,and various types of ***,malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson＇s,Alzheimer＇s,and Huntington＇s *** many years,brain degenerative disorders were thought to result from aberrant neural *** we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells（astrocytes,microglia,and oligodendrocytes）.Impairment in the functionality of glial cells results in pathological neuro-glial interactions that,in turn,generate a ‘‘hostile＂ environment that impairs the functionality of neuronal *** events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

关键词： DNA damage response Genomic instability Brain degenerative diseases Glial cells Astrocytes Microglia