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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

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Nano Research 2024年第10期17卷 9052-9064页

作者： savannah E.Est-Witte sydney R.shannon Dennis H.Gong Kaitlyn G.Calabresi jawaun j.Harris Kaitlyn storm Edwin j.Yoo Ariel Isser Vivek P.jani natalie K.Livingston Mary O.Omotoso Kelly Rhodes Elana Ben-Akiva Randall A.Meyer Zoe T.Hsieh simone sidoli stephany Y.Tzeng jonathan P.schneck jordan j.Green Translational Tissue Engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell Engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

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

The impact of vitamin D deficiency on neurogenesis in the adult brain

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Neural Regeneration Research 2017年第3期12卷 393-394页

作者： natalie j.Groves Thomas H.j.Burne Queensland Brain Institute The University of QueenslandSt.LuciaAustralia Queensland Centre for Mental Health Research The Park Centrefor Mental HealthWacolAustralia

There is increasing evidence from epidemiological studies indicating that vitamin D deficiency during adulthood is associated with adverse brain outcomes in humans（Ginde et al.,2009）and rodents（Groves et al.,2014）... 详细信息

关键词： The impact of vitamin D deficiency on neurogenesis in the adult brain GAD

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

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

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

Distribution,structure and biosynthetic gene families of(1,3;1,4)-β-glucan in sorghum bicolor

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journal of Integrative Plant Biology 2015年第4期57卷 429-445页

作者： Riksfardini A.Ermawar Helen M.Collins Caitlin s.Byrt natalie s.Betts Marilyn Henderson Neil j.shirley julian schwerdt jelle Lahnstein Geoffrey B.Fincher Rachel A.Burton Australian Research Council Centre of Excellence in Plant Cell Walls University of Adelaide

In cereals, the presence of soluble polysaccharides including（1,3;1,4）-b-glucan has downstream implications for human health, animal feed and biofuel applications. sorghum bicolor（L.） Moench is a versatile crop, but there are limited reports regarding the content of such soluble ***, the amount of（1,3;1,4）-b-glucan present in sorghum tissues was measured using a Megazyme assay. Very low amounts were present in the grain, ranging from 0.16%–0.27%（w/w）, while there was a greater quantity in vegetative tissues at 0.12–1.71%（w/w）. The fine structure of（1,3;1,4）-b-glucan, as denoted by the ratio of cellotriosyl and cellotetraosyl residues,was assessed by high performance liquid chromatography（HPLC） and ranged from 2.6–3：1 in the grain, while ratios in vegetative tissues were lower at 2.1–2.6：1. The distribution of（1,3;1,4）-b-glucan was examined using a specific antibody and observed with fl uorescence and transmission electron microscopy. Micrographs showed a variable distribution of（1,3;1,4）-b-glucan in fl uenced by temporal and spatial factors. The sorghum orthologs of genes implicated in the synthesis of（1,3;1,4）-b-glucan in other cereals, such as the Cellulose synthase-like（Csl） F and H gene families were de *** pro filing of these genes across sorghum tissues was carried out using real-time quantitative polymerase chain reaction, indicating that, as in other cereals, Csl F6 transcripts dominated.

关键词： Cellulose synthase-like genes cell wall composition mixed-linkage glucan grain sorghum

Ultraviolet light exposure and its penetrance through the eye in a porcine model

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International journal of Ophthalmology(English edition) 2023年第2期16卷 172-177页

作者： Hideki Fukuoka Helena E.Gali jennifer j.Bu Ruti sella natalie A.Afshari shiley Eye Institute Viterbi Family Department of OphthalmologyUniversity of California San DiegoLa JollaCA 92093USA

AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact ***:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye *** light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye *** the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the ***,UVprotective contact lenses were placed over the structures,and UV light penetrance was *** of UV light exposure were taken outdoors at various locations and ***:Cornea absorbed 63.56%of UV light that reached the *** and lens absorbed 99.34%of UV *** eye absorbed 99.77%of UV *** UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,*** light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a ***:Cornea absorbs the majority of UV light that reaches the eye in this ***-protective contact lenses reduce UV exposure to the *** with high albedo expose the eye to higher levels of UV light.

关键词： ultraviolet light penetrance contact lens cornea lens