Beta Amyloid Peptide:Research Paper: Environment-Sensitive Probes for Illuminating Amyloid Aggregation In Vitro and in Zebrafish

Environment-Sensitive Probes for Illuminating Amyloid Aggregation In Vitro and in Zebrafish

Abstract

The aberrant aggregation of certain peptides and proteins, forming extracellular plaques of fibrillar material, is one of the hallmarks of amyloid diseases, such as Alzheimer's and Parkinson's. Herein, we have designed a new family of solvatochromic dyes based on the 9-amino-quinolimide moiety capable of reporting during the early stages of amyloid fibrillization. We have rationally improved the photophysical properties of quinolimides by placing diverse amino groups at the 9-position of the quinolimide core, leading to higher solvatochromic and fluorogenic character and higher lifetime dependence on the hydrophobicity of the environment, which represent excellent properties for the sensitive detection of prefibrillar aggregates. Among the different probes prepared, the 9-azetidinyl-quinolimide derivative showed striking performance in the following β-amyloid peptide (Aβ) aggregation in solution in real time and identifying the formation of different types of early oligomers of Aβ, the most important species linked to cytotoxicity, using novel, multidimensional fluorescence microscopy, with one- or two-photon excitation. Interestingly, the new dye allowed the visualization of proteinaceous inclusion bodies in a zebrafish model with neuronal damage induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Our results support the potential of the novel fluorophores as powerful tools to follow amyloid aggregation using fluorescence microscopy in vivo, revealing heterogeneous populations of different types of aggregates and, more broadly, to study protein interactions.

Keywords: amyloid aggregation; environment-sensitive probes; fluorescent probes; quinolimide derivatives; ratiometric fluorescence lifetime imaging microscopy; two-photon excitation imaging; zebrafish imaging; β-amyloid peptide aggregation sensing.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32551591/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide:Research Paper: Alzheimer Gene BIN1 may Simultaneously Influence Dementia Risk and Androgen Deprivation Therapy Dosage in Prostate Cancer

Alzheimer Gene BIN1 may Simultaneously Influence Dementia Risk and Androgen Deprivation Therapy Dosage in Prostate Cancer

Abstract

Background: Androgen deprivation therapy (ADT) is extensively used in prostate cancer. Yet the risk of impaired cognition or Alzheimer disease (AD) in men with prostate cancer receiving ADT is uncertain. Some studies of prostate cancer and ADT suggest that the risk of AD is not increased. But other studies have found an increased risk of AD and cognitive impairment.

Objectives: As the uncertainty about ADT and dementia might relate to the genetics of prostate cancer and AD, the authors used the Cancer Genome Atlas (TCGA) to examine the relationship in men with prostate cancer between genes implicated in AD and genes implicated in prostate cancer.

Methods: The authors examined the genomics of 492 prostate cancer cases in the Genomic Data Commons (GDC) TCGA Prostate Cancer (PRAD) data set. To access and analyze the data, 2 web-based interfaces were used: (1) the UCSC Xena browser, a web-based visual integration and exploration tool for TCGA data, including clinical and phenotypic annotations; and (2) cBioportal, a web-based interface that enables integrative analysis of complex cancer genomics and clinical profiles.

Results: Co-occurrence analysis indicates that alterations in the prostate cancer gene Speckle-type POZ protein (SPOP) significantly co-occur with alterations in the AD gene BIN1 (P<0.001). The presence of somatic mutations (deleterious and missense/in frame) in SPOP deranges BIN1 gene expression. SPOP/BIN1 RNA gene expression in 492 prostate cancer specimens is significantly correlated (P<0.001). Increased expression of SPOP in 492 prostate cancers is associated with reduced survival (P=0.00275). Men receiving pharmacologic therapy had a tumor with a significantly higher Gleason score (P=0.023). Gleason score and BIN1 RNA gene expression, unit log2 (fragments per kilobase of transcript per million mapped reads upper quartile [FPKM-UQ]+1), in 499 prostate cancer specimens were significantly inversely correlated (P<0.001).

Conclusions: BIN1 forms part of a network that interacts with the MYC oncogene, activated at the earliest phases of prostate cancer and in its position on chr8q24 linked to disease aggressiveness. Dynamic regulation of the BIN1-Tau interaction is involved in AD. BIN1 loss in AD allows phosphorylated tau to be mis-sorted to synapses, which likely alters the integrity of the postsynapse, alongside reducing the functionally important release of physiological forms of tau. Alzheimer symptoms are usually preceded by a preclinical phase that may be 16 years long. The authors suggest that the ADT dosage reflects the severity of a process that is already underway. The severity is determined by the genetics of the tumor itself, at least in part by BIN1. ADT is not causing new cases of AD. The oncologist treats higher-grade prostate cancer with more ADT, which serves as a surrogate marker for disease severity. Our analysis of TCGA data does not support the idea that ADT causes AD or dementia.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32568785/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide:Research Paper: Gait Change in Dual Task as a Behavioral Marker to Detect Mild Cognitive Impairment in Elderly Persons: A Systematic Review and Meta-analysis

Gait Change in Dual Task as a Behavioral Marker to Detect Mild Cognitive Impairment in Elderly Persons: A Systematic Review and Meta-analysis

Abstract

Objectives: To systematically summarize the evidence of gait tests as screening tools for mild cognitive impairment (MCI).

Data sources: Electronic database searches were conducted in PubMed, EBSCO, Cochrane, Web of Science, Ovid, China National Knowledge Infrastructure, WanFang, and SinoMed, and studies published before November 30, 2018, were included.

Study selection: Synonyms of MCI, gait, and cognitive-motor interference (CMI) were searched. Studies that analyzed gait change of people with MCI in single- or dual-task gait tests were included.

Data extraction: The quality of the included studies was assessed with Downs and Black methodological quality appraisal tools. Study characteristics, participants' characteristics, test descriptions, and results were extracted from the included studies.

Data synthesis: Twenty-two studies involving 1928 participants were included. Meta-analysis showed that gait velocity difference in dual task (effect size [ES]=-0.89) were more obvious than in single task (ES=-0.74) between older adults with and without MCI, and the ES increased with the complexity of cognitive load (countdown by 1s, ES=-0.83; verbal fluency, ES=-0.96; serial reduction by 7s, ES=-1.26). The dual-task cost of gait velocity showed high sensitivity (ES=0.90) in detecting MCI. Meta-regression analysis demonstrated strong criterion-related validity between the CMI of gait velocity and the Montreal Cognitive Assessment score.

Conclusions: In comparison with the single-task gait test, gait change under cognitive load is more pronounced in older adults with MCI. CMI of gait velocity can be a potential screening tool for MCI in elderly persons.

Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/32553899/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: CONFERENCE CALENDAR: ISTAART Webinar Series: Ask the Editors — A&D, TRCI and DADM

ISTAART Webinar Series: Ask the Editors — A&D, TRCI and DADM

21 October 2020 DOWNLOAD TO YOUR CALENDAR
Online Meeting
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Speakers: Zaven S. Khachaturian, PhD (Alzheimer's and Dementia and Translational Research and Clinical Interventions), Ara S. Khachaturian, PhD (Alzheimer's and Dementia), Peter J. Snyder, PhD (Diagnosis, Assessment and Disease Monitoring), and Kathleen M. Hayden, PhD, Wake Forest School of Medicine, Winston-Salem, North Carolina

Time: 10 am EDT 

This article originally appeared in the "https://www.alzforum.org/conference-calendar/1469796" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: CONFERENCE CALENDAR: ISTAART Webinar Series - Meet HABS (Harvard Aging Brain Study)

ISTAART Webinar Series - Meet HABS (Harvard Aging Brain Study)

20 October 2020 DOWNLOAD TO YOUR CALENDAR
Online Meeting
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Moderator: Yakeel Quiroz, PhD, Massachusetts General Hospital/Harvard Medical School

Co-PIs: Keith Johnson, MD, and Reisa Sperling, MD, Harvard Medical School

Time: 2 pm EDT 

This article originally appeared in the "https://www.alzforum.org/conference-calendar/1469751" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: CONFERENCE CALENDAR: ISTAART Journal Club: Meet the Author

ISTAART Journal Club: Meet the Author

14 October 2020 DOWNLOAD TO YOUR CALENDAR
Online Meeting
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Moderator: Mariana Luciano de Almeida, MA, University of California, San Francisco

Authors: Anna Marseglia, PhD and Weili Xu, PhD, Karolinska Institutet and Stockholm University

Paper: Can Active Life Mitigate the Impact of Diabetes on Dementia and Brain Aging? - Alzheimer's Disease and Dementia, 2020

 

Moderator: Naiara Demnitz, PhD, University of Oxford 

Authors: Gill Livingston, MBChB, MD and Naaheed Mukadam, PhD, University College London

Paper: Dementia Prevention, Intervention and Care: 2020 Report of the Lancet Commission, Lancet, 2020

Time: 11 am EDT 

This article originally appeared in the "https://www.alzforum.org/conference-calendar/1469781" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: CONFERENCE CALENDAR: "Proteostasis Consortium" Seminars: Effects of Early-life ROS on Aging and Age-related Diseases

"Proteostasis Consortium" Seminars: Effects of Early-life ROS on Aging and Age-related Diseases

30 September 2020 DOWNLOAD TO YOUR CALENDAR
Online Meeting
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Organizers: The Proteostasis Consortium led by Richard Morimoto, Ph.D., Northwestern University
Speaker: Ursula Jakob, PhD, University of Michigan, Ann Arbor
Meeting time: 12 PM EDT

Zoom link: https://stanford.zoom.us/j/94026057431 

This article originally appeared in the "https://www.alzforum.org/conference-calendar/1469751" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Jobs: Postdoctoral Fellow

Postdoctoral Fellow

Employer

Alzheimer's Clinical & Translational Research Unit (ACTRU) and Massachusetts Alzheimer's Disease Research Center (MADRC)

Location

Charlestown, Massachusetts

Principal Investigator

Steven Arnold

Principal Investigator

Becky Carlyle

Contact

BCARLYLE@mgh.harvard.edu

Description

The Alzheimer's Clinical & Translational Research Unit (ACTRU) and Massachusetts Alzheimer's Disease Research Center (MADRC) seek to hire a highly motivated and organized self-starter to work with its rapidly expanding biomarkers operation. This role will be to develop novel, mechanism-associated protein biomarkers for use in innovative clinical trials. Work will focus on biofluid and brain tissue biomarkers, including the development of novel methods for quantifying endogeneous peptide proteoforms, tissue fractionation protocols, and developing mass-spectrometry methods, both targeted and non-targeted, for robust and high-throughput biomarker quantification in collaboration with mass-spectrometry core facilities. Work will be performed under the supervision of the co-director of the MADRC Biomarker Core and the director of the Alzheimer's Clinical & Translational Research unit. Applications for this position are encouraged from under-represented minorities.

https://partners.taleo.net/careersection/ghc/jobdetail.ftl?job=3128131&tz=GMT-04%3A00&tzname=America%2FNew_York

WORKING CONDITIONS:

Incumbent will have a desk and bench in the laboratory in Building 114 in the Charlestown Navy Yard that is equipped with a networked computer. Incumbent will spend some time in the Mass-Spectrometry Facility in Building 149 in the Charlestown Navy Yard.

Primary Location: USA-MA-Charlestown Work Locations: 114 16th Street, Charlestown 02129

Secondary Location: USA-MA-Charlestown Work Locations: 149 13th Street, Charlestown 02129

EEO Statement

Massachusetts General Hospital is an Equal Opportunity Employer. By embracing diverse skills, perspectives and ideas, it chooses to lead.

Applications from protected veterans and individuals with disabilities are strongly encouraged.

Requirements

PRINCIPAL DUTIES AND RESPONSIBILITIES:

Biofluid sample preparation, including the development of new and high-throughput methods for rapid and accurate quantification of mechanism-associated biomarkers and endogenously cleaved neuropeptides.

The development of methods for analysis of cellular compartmentalization in frozen human brain tissue and iPSC cell lines, for accurate quantification of mechanism-associated biomarkers.

Development of mass-spectrometry methods for both targeted and untargeted assessment of biofluids, brain tissue, and iPSCs derived from individuals with Alzheimer's disease and related dementias.

In collaboration with the ACTRU data analysis team, perform assessment of data quality control metrics, analyze data and perform statistical testing, and prepare reports and figures for publication.

Present data through publication of manuscripts and attendance at national and international conferences.

Participate in weekly lab meetings and present data.

All other duties, as assigned.

SKILLS & COMPETENCIES REQUIRED:

Must be highly organized, detail-oriented, and have a strong motivation to learn. Strong technical expertise in biochemistry or molecular/cell biology. Experience with mass spectrometry-based proteomics. Experience with protein purification techniques is preferred (LC, MS sample prep for example). Experience with analyzing large datasets is preferred. Must have excellent interpersonal, speaking, and writing abilities. Ability to work both independently and collaboratively as a member of a team. On own initiative, ability to identify potential problems and troubleshoot problems as necessary. Must be able to prioritize and perform multiple tasks independently.

EDUCATION:

Ph.D. in cell biology, biochemistry, chemistry, systems biology or a related field is required.

Equivalent Experience –– please document if educational requirements can be met through equivalent experience. Candidates who can demonstrate equivalent experience to a Ph.D. through work in a Proteomics Core, for example, will be considered.

EXPERIENCE:

Required: Ph.D. training or three-plus years of relevant work in a mass-spectrometry facility.

FISCAL RESPONSIBILITY:

Will assist PI with ordering using the electronic ordering system. Will record spending to assist in monitoring budgets.

This article originally appeared in the "https://www.alzforum.org/jobs/postdoctoral-fellow-8" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Jobs: Postdoctoral Research Associate

Postdoctoral Research Associate

Employer

Washington University School of Medicine - Neurogenomics and Informatics Center

Location

St. Louis, Missouri

Principal Investigator

Laura Ibanez

Contact

Interested candidates should send their cover letter and CV to Dr. Ibanez (ibanezl@wustl.edu).

Description

The NeuroGenetics and Informatics (NGI) center at Washington University School of Medicine is recruiting a postdoctoral research scientist. The NGI generates and analyzes high-throughput multidimensional omic data to study neurodegeneration and diseases of the central nervous system with emphasis on Alzheimer's disease, Parkinson's disease, and other dementias. The ultimate goal of the NGI is to understand the biology of these diseases, to define novel biomarkers, and to identify novel therapeutic targets.

Washington University School of Medicine is renowned for its research cohorts of neurodegenerative disorders, which include clinical, neuroimaging, and fluid biomarker phenotypes.

WashU has recently received several awards from the NIH, Department of Defense, and private foundations to generate new molecular tools to predict and monitor neurodegenerative disease. The final goal is to create a highly specific and minimally invasive tool that can be translated to a clinical setting. WashU is seeking highly motivated researchers with strong analytical skills, especially in RNAseq analyses and machine learning to lead the analyses for these projects. The new postdoc will join a large and highly motivated multi-disciplinary team.

For further details, please see our website: https://neurogenomics.wustl.edu/

Benefits

This position is eligible for full-time benefits.  Please click the following link to view a summary of benefits: https://hr.wustl.edu/benefits/.

EOE Statement

Washington University is an Equal Opportunity Employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, age, sex, sexual orientation, gender identity or expression, national origin, genetic information, disability, or protected veteran status.

Requirements

• The successful applicant will hold, or expect to shortly obtain, a Ph.D. qualification in genetics, bioinformatics, computer science, data science, statistical genomics or a related discipline involving the interrogation of "omics" datasets.
• Hands-on experience with large-scale human datasets with special emphasis on transcriptomic data and machine-learning algorithms is expected.
• Solid skills in at least one programming language (R, python or perl) and experience working in Linux and/or high-performance cluster environments.
• A strong ability to perform analytical reasoning to extract biological insights from data-driven approaches will be critical.
• Writing and presentation skills will be critical to share the results with the scientific community.
• Familiarity to interrogate publicly available resources will be highly beneficial.
• Basic molecular biology lab skills (nucleic acid extraction, PCR, library preparation) will be highly beneficial.

This article originally appeared in the "https://www.alzforum.org/jobs/postdoctoral-research-associate" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.  

Beta Amyloid Peptide: Jobs: Bioinformatics Research Analyst

Bioinformatics Research Analyst

Employer

Washington University School of Medicine - Neurogenomics and Informatics Center

Location

St. Louis, Missouri

Principal Investigator

Laura Ibanez

Contact

ibanezl@wustl.edu

Candidates can apply by navigating to https://jobs.wustl.edu/ and searching for the job opening number (49023)

Description

The NeuroGenetics and Informatics (NGI) center at Washington University School of Medicine is recruiting a bioinformatics research analyst to work in Dr. Ibanez's group at the Washington University School of Medicine. The NGI generates and analyzes high-throughput multidimensional omic data to study neurodegeneration and diseases of the central nervous system, with emphasis on Alzheimer's disease, Parkinson's disease, and other dementias. The goal of Dr. Ibanez's research is to use omic approaches to generate biomarkers for Alzheimer's Disease, Parkinson Disease and other neurodegenerative disease.

Her lab is focused on the generation of minimally invasive tools to predict neurodegenerative diseases and monitor progression and response to treatment using RNA-Seq data and machine-learning algorithms.

The center is looking for a bioinformatics research analyst with expertise in RNA-Seq data analyses and machine learning to work in different projects that focus on the identification of genes dysregulated in Alzheimer's and Parkinson's disease that can be used as biomarkers.

She/he will join a multidisciplinary team of computational and statistical researchers working in bioinformatics, statistical genomics, and genetics. The team comprises more than 20 people dedicated to understanding the architecture of neurodegenerative diseases.

PRINCIPLE DUTIES & RESPONSIBILITIES:

Essential Functions:

1. To write and optimize analyses pipelines (scripts) for RNA-Seq.

2. Analyze data including QC, and organize the data properly.

3. Perform statistical analyses.

4. Create reports of the analyses.

Requirements

The candidate will hold a master in statistics, bioinformatics, computational biology, biostatistics, statistical genetics, medical statistics, mathematics or similar. The candidate should have a strong background in RNA-Seq analyses (STAR, SALMON, DESEQ2) and machine learning. Working knowledge of UNIX, Perl/Python, R and Docker are also required.

This article originally appeared in the "https://www.alzforum.org/jobs/bioinformatics-research-analyst" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.