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Lipid nanoparticles deliver mRNA to the blood-brain barrier

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Nano Research 2024年第10期17卷 9126-9134页

作者： Yanina Kuzminich Avraham Shakked Randi Calkins Sebastian Rudden Camille Jones Jessie Doan Bora Jang Elisa Schrader Echeverri Ryan Zenhausern Liming Lian David Loughrey Hannah E.Peck rachelle Wiese Dorothy Koveal Philip J.Santangelo James E.Dahlman George C.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Parker H.Petit Institute for Bioengineering and Biosciences Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Emory University School of Medicine and Georgia Institute of TechnologyAtlantaGA 30332USA

Lipid nanoparticles(LNPs)have delivered RNA to hepatocytes in patients after intravenous *** clinical data support efforts to design LNPs that transfect cells in the central nervous system(CNS).However,delivery to the CNS has been difficult,in large part because quantifying on-target delivery alongside common off-target cell types in adult mice remains *** we report methods to isolate different cell types from the CNS,and subsequently present mRNA delivery readouts using a liver-detargeted *** data suggest that LNPs without targeting ligands can transfect cerebral endothelial cells in mice after intravenous *** the difficulty of crossing the blood-brain barrier,they also underscore the value of quantifying delivery in the CNS with cell-type resolution instead of whole-tissue resolution.

关键词： lipid nanoparticle mRNA nanomedicine central nervous system blood-brain barrier

The blood-brain barrier models to study apolipoprotein E genotypes in Alzheimer’s disease

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Neural Regeneration Research 2022年第9期17卷 1973-1974页

作者： Irundika HK Dias rachelle Taiwo Dan Ma Aston Medical School College of Health and Life SciencesAston UniversityBirminghamUK

Alzheimer’s disease(AD)is a neurodegenerative disease that is characterized by an age-dependent progressive decline of memory,impairment of cognitive functions and changes in personality and *** the improvement in understanding of the mechanisms underlying the disease,AD remains an incurable complex disorder with multifaceted pathophysiology to *** E(ApoE)is the main cholesterol carrier in the brain that supports lipid transport between brain *** individuals carrying the APOE4 allele are known to be at increased risk of developing AD compared with those carrying the more common APOE3 allele.

关键词： Alzheimer cholesterol impairment

Variation Patterns of NLR Clusters in Arabidopsis thaliana Genomes

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Plant Communications 2020年第4期1卷 129-143页

作者： rachelle R.Q.Lee Eunyoung Chae Department of Biological Sciences National University of SingaporeSingapore 117558Singapore

The nucleotide-binding domain and leucine-rich repeat(NLR)gene family is highly expanded in the plant lineage with extensive sequence and structure *** survey the landscape of NLR expansion,we mined the published long-read data generated by the resistance gene enrichment sequencing of 64 diverse Arabidopsis thaliana *** found that the hot spots of massive multi-gene NLR cluster expansion did not typically span the whole cluster;instead,they were restricted to a handful of,or only one,dominant radiation(s).All sequences in such a radiation were distinct from other genes in the cluster but not from each other in the clade,making it difficult to assign trustworthy reference-based orthologies when multiple reference genes were present in the ***,NLR genes can be broadly divided into two types:radiating or high-fidelity,where high-fidelity genes are well conserved and well separated from other clades.A similar distinction could be made for NLR clusters,depending on whether cluster size was determined primarily by extensive radiation or the presence of numerous high-fidelity *** also identified groups of well-conserved NLR clades that were missing from the Columbia-0 reference *** suggests that the classification of NLRs using gene IDs from a single reference accession can rarely capture all major paralogs in a cluster accurately and representatively and that a referenceagnostic perspective is required to properly characterize these additional ***,we present a quantitative visualization method for differentiating these situations in a given clade of interest.

关键词： NLR cluster evolution phylogenetics disease resistance plant immunity

Erectile dysfunction after transurethral prostatectomy for lower urinary tract symptoms:results from a center with over 500 patients

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Asian Journal of Andrology 2006年第1期8卷 69-74页

作者： Vassilis Poulakis Nikolaos Ferakis Ulrich Witzsch rachelle de Vries Eduard Becht Department of Urology and Pediatric Urology Northwest HospitalFrankfurt am Main D-60488Germany

Aim： To identify possible risk factors for erectile dysfunction （ED） after transurethral resection of prostate （TURP） for benign prostatic hyperplasia （BPH）. Methods： Between March 1999 and March 2004, 629 patients underwent TURP in our department for the treatment of symptomatic BPH. All patients underwent transrectal ultrasound examination. In addition, the flow rate, urine residue, International Prostate Symptom Score （IPSS） and quality of life （QOL） were recorded for those who presented without a catheter. Finally, the erectile function of the patient was evaluated according to the International Index of Erectile Function Instrument （IIEF-5） questionnaire. It was determined that ED existed where there was a total score of less than 21. The flow rate, IPSS and QOL assessment were performed at 3 and 6 months post-treatment. The IIEF-5 assessment was repeated at a 6-month follow-up. A logistic regression analysis was used to identify potential risk factors for ED. Results： At baseline, 522 （83 %） patients answered the IIEF-5 questionnaire. The mean patient age was （63.7 ± 9.7） years. The ED rate was 65%. After 6 months, 459 （88%） out of the 522 patients returned the IIEF questionnaire. The rest of the group was excluded from the statistical analysis. Six months after TURP, the rate of patients reporting ED increased to 77 %. Statistical analysis revealed that the only important factors associated with newly reported ED after TURP were diabetes mellitus （P = 0.003, r = 3.67） and observed intraoperative capsular perforation （P = 0.02, r = 1.12）. Conclusion： The incidence of postoperative, newly reported ED after TURP was 12%. Risk factors for its occurrence were diabetes mellitus and intraoperative capsular perforation. （Asian J Androl 2006 Jan; 8： 69-74）

关键词： benign prostatic hyperplasia transurethral resection of prostate erectile dysfunction

Neurotropic effects of aspartame, stevia and sucralose on memory retention and on the histology of the hippocampus of the ICR mice(Mus musculus)

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Asian Pacific Journal of Tropical Biomedicine 2016年第2期6卷 114-118页

作者： Lejan Miguel Alabastro Villareal rachelle Anne Montes Cruz Michael Bagui Ples Rodel Jonathan Santos Vitor Ⅱ Biology Department College of Science De La Salle University

Objective: To identify the effects of the consumption of non-nutritive sweeteners on memory retention and on the histology of the ***: In this study, 20 mice were used to determine if there is an effect of consuming the maximum allowable dose of the non-nutritive sweeteners on the memory retention and on the histology of the hippocampus. The mice were distributed into four groups and the treatments were given via oral gavage: Group 1(water), Group 2(aspartame: 1 000 mg/kg), Group 3(stevia: 1 000 mg/kg) and Group 4(sucralose:16 000 mg/kg). Treatments were administered to the different experimental groups for 32 days, after which memory retention was tested using the two-day water maze *** the tests, the mice were sacrificed and the brain was analyzed histologically for neurotrophic ***: Based on the results of the two-day water maze protocol, there were no differences between the non-nutritive sweeteners and the control group. However, stevia showed high cellular apoptosis followed by aspartame, sucralose and control ***: There was no significant effect on the memory of the mice. It showed histologically however, that stevia had a significant neurotropic effect compared to the other sweeteners.

关键词： Aspartame Hippocampus Learning Memory Mus musculus Stevia Sucralose

How Do Family Structure and Family Process Matter?A Comparative Study on the Impacts of Military Deployment and Single Parenthood on Children’s Psychological Well-Being

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Sociology Study 2021年第1期11卷 1-16页

作者： Ruoqing rachelle Wang-Cendejas University of Southern California Los AngelesCAUSA

Children from two-parent families have better outcomes,on average,than children from single-parent *** the mechanisms associated with family structure and family process that produce divergent outcomes are less well *** on data from the 2011-2015 National Health Interview Survey(N=26,783),I leverage the case of military families with deployment and examine the impacts of parenting quality,economic capital,and social capital on children’s psychological *** regression results show that single parenthood produced by divorce,separation,and birth out of wedlock leads to worse child outcomes than single parenthood produced by military deployment,and family process partially explains the variation in children’s well-being beyond family *** families,military or civilian,deployed or not,enjoy advantages that translate into positive child ***,therefore,emerges as the primary axis of inequality,and maintaining a healthy marriage better promotes children’s well-being.

关键词： family structure family process military deployment single parenthood children’s well-being

The Fatherhood Premium： Mirage or Reality？ How Do Occupational Characteristics Matter

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Sociology Study 2018年第4期8卷 157-170页

作者： Ruoqing rachelle Wang-Cendejas Ling Bai University of Southern California USA CITIC Technology Co. Ltd. China

A differential fatherhood premium exists among selected groups of fathers of various socio-economic backgrounds. Besides marital status, residential arrangement, biological paternity, and other demographic dimensions, the mechanisms associated with fathers＇ structural characteristics of work that produce divergent labor market outcomes are less well understood. The authors leveraged the cases of productivity and specialization, family and responsibility, and compensating differentials and examined the impacts of work context and occupational characteristics on the pay gap between fathers and non-fathers Based on joint data from the 1997-2015 National Longitudinal Survey of Youth （NLSY97） and Occupational Information Network （O＇NET）（n -- 37,138）, the authors used fixed-effects models to estimate the associations between job features and the fatherhood premium. The regression results showed that occupations entailing competition and requiring on-the-job training are associated with more wage bonus; occupations offering inflexible schedule are associated with less wage gain These work-related characteristics further emphasize fathers＇ work structure and context, human capital accumulation, and work-family conflict. Overall, these findings are consistent with the theoretical perspectives of productivity and specialization and compensating differentials, adding new evidences to the structural explanations of the fatherhood premium.

关键词： Fatherhood premium occupational characteristics work-family conflict

Effect of vaccination,border testing,and quarantine requirements on the risk of COVID-19 in New Zealand:A modelling study

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Infectious Disease Modelling 2022年第1期7卷 184-198页

作者： Nicholas Steyn Audrey Lustig Shaun C.Hendy rachelle N.Binny Michael J.Plank Department of Physics University of AucklandNew Zealand School of Mathematics and Statistics University of CanterburyNew Zealand Te Punaha Matatini Centre of Research Excellence in Complex SystemsNew Zealand Manaaki Whenua LincolnNew Zealand

We couple a simple model of quarantine and testing strategies for international travellers with a model for transmission of SARS-CoV-2 in a partly vaccinated *** use this model to estimate the risk of an infectious traveller causing a community outbreak under various border control strategies and different levels of vaccine coverage in the *** are calculated from N¼100,000 independent realisations of the stochastic *** find that strategies that rely on home isolation are significantly higher risk than the current mandatory 14-day stay in government-managed ***,combinations of testing and home isolation can still reduce the risk of a community outbreak to around one outbreak per 100 infected *** also find that,under some circumstances,using daily lateral flow tests or a combination of lateral flow tests and polymerase chain reaction(PCR)tests can reduce risk to a comparable or lower level than using PCR tests *** with controls on the number of travellers from countries with high prevalence of COVID-19,our results allow different options for managing the risk of COVID-19 at the border to be *** can be used to inform strategies for relaxing border controls in a phased way,while limiting the risk of community outbreaks as vaccine coverage increases.

关键词： vaccine testing border

An assessment of the potential impact of the Omicron variant of SARS-CoV-2 in Aotearoa New Zealand

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Infectious Disease Modelling 2022年第2期7卷 94-105页

作者： Giorgia Vattiato Oliver Maclaren Audrey Lustig rachelle N.Binny Shaun C.Hendy Michael J.Plank School of Mathematics and Statistics University of CanterburyChristchurchNew Zealand Department of Physics University of AucklandAucklandNew Zealand Manaaki Whenua LincolnNew Zealand Department of Engineering Science University of AucklandAucklandNew Zealand

New Zealand delayed the introduction of the Omicron variant of SARS-CoV-2 into the community by the continued use of strict border controls through to January *** allowed time for vaccination rates to increase and the roll out of third doses of the vaccine(boosters)to *** also meant more data on the characteristics of Omicron became available prior to the first cases of community *** we present a mathematical model of an Omicron epidemic,incorporating the effects of the booster roll out and waning of vaccine-induced immunity,and based on estimates of vaccine effectiveness and disease severity from international *** model considers differing levels of immunity against infection,severe illness and death,and ignores waning of infection-induced *** model was used to provide an assessment of the potential impact of an Omicron wave in the New Zealand population,which helped inform government preparedness and *** the time the modelling was carried out,the date of introduction of Omicron into the New Zealand community was *** therefore simulated outbreaks with different start dates,as well as investigating different levels of booster *** found that an outbreak starting on 1 February or 1 March led to a lower health burden than an outbreak starting on 1 January because of increased booster coverage,particularly in older age *** also found that outbreaks starting later in the year led to worse health outcomes than an outbreak starting on 1 *** is because waning immunity in older groups started to outweigh the increased protection from higher booster coverage in younger *** an outbreak starting on 1 February and with high booster uptake,the number of occupied hospital beds in the model peaked between 800 and 3,300 depending on assumed transmission *** conclude that combining an accelerated booster programme with public health measures to flatten the curve are key to avoid overwhelming the hea

关键词： COVID-19 Epidemiological modelling Immunity Infectious diseases Public health Vaccination