Imaging/Microscopy

Aging (Aging-US)

Aging-US published this trending research paper on April 18, 2023, in Volume 15, Issue 9, entitled, “Exogenous exposures shape genetic predisposition to lipids, Alzheimer’s, and coronary heart disease in the MLXIPL gene locus" by researchers from the Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA; Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, MO.

DOI - https://doi.org/10.18632/aging.204665

Corresponding authors - Yury Loika - yury.loika@duke.edu, and Alexander M. Kulminski - alexander.kulminski@duke.edu

Abstract

Associations of single nucleotide polymorphisms (SNPs) of the MLXIPL lipid gene with Alzheimer’s (AD) and coronary heart disease (CHD) and potentially causal mediation effects of their risk factors, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), were examined in two samples of European ancestry from the US (22,712 individuals 587/2,608 AD/CHD cases) and the UK Biobank (UKB) (232,341 individuals; 809/15,269 AD/CHD cases). Our results suggest that these associations can be regulated by several biological mechanisms and shaped by exogenous exposures. Two patterns of associations (represented by rs17145750 and rs6967028) were identified. Minor alleles of rs17145750 and rs6967028 demonstrated primary (secondary) association with high TG (lower HDL-C) and high HDL-C (lower TG) levels, respectively. The primary association explained ~50% of the secondary one suggesting partly independent mechanisms of TG and HDL-C regulation. The magnitude of the association of rs17145750 with HDL-C was significantly higher in the US vs. UKB sample and likely related to differences in exogenous exposures in the two countries. rs17145750 demonstrated a significant detrimental indirect effect through TG on AD risk in the UKB only (βIE = 0.015, pIE = 1.9 × 10−3), which suggests protective effects of high TG levels against AD, likely shaped by exogenous exposures. Also, rs17145750 demonstrated significant protective indirect effects through TG and HDL-C in the associations with CHD in both samples. In contrast, rs6967028 demonstrated an adverse mediation effect through HDL-C on CHD risk in the US sample only (βIE = 0.019, pIE = 8.6 × 10−4). This trade-off suggests different roles of triglyceride mediated mechanisms in the pathogenesis of AD and CHD.

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Keywords - aging, MLXIPL, lipids, triglycerides, coronary heart disease, Alzheimer’s disease

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

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External Factors Shape Genetic Predisposition to Lipids, Alzheimer’s and Heart Disease in MLXIPL Gene

Shimadzu Analytical & Measuring

With unparalleled speed, sensitivity and spatial resolution, Shimadzu’s iMScope QT imaging mass microscope clears the
way to next-generation mass spectrometry imaging. It enables fast acquisition of high-mass, high-resolution images at the optical and molecular level, can simultaneously visualize and analyze samples, and offers full fusion with morphology studies. Integration with the Q-TOF LCMS-9030 enables obtaining distribution information and quantitative data for comprehensive analysis and it's easy to switch between MS imaging configuration and LCMS.

High-End Imaging with an Unequalled Combination of Speed, Sensitivity, and Resolution 

TotalLab

In this video, I'll show you how you can obtain quantifiable data from lateral flow tests (LFT/LFA) in a 21 CFR Part 11/GxP/EU Annex 11 compliant manner using Phoretix 1D, which allows you to produce a full audit trail for every single lateral flow test you analyse to ensure regulatory compliance.

00:00 - Intro
00:20 - Explanation of TotalLab GxP Compliance Module
00:50 - How to log in to the software
01:40 - Username entry
01:50 - Password entry
02:17 - 21 CFR Sign in
02:23 - Project screen overview
02:32 - Creating a new compliant project
02:46 - Attaching notes to the audit trail of a project
03:10 - Adding files to your project
03:42 - Audit trail explanation
04:20 - Checking out a project for analysis
04:32 - Software integrations with the TotalLab GxP module
04:39 - Opening Phoretix 1D analysis software
04:50 - Analysing lateral flow tests
10:27 - Saving your analysis
10:32 - Audit trail build-up explanation
10:48 - Extended notes within the audit trail
11:40 - Checking a project back in to the secure folder
12:05 - Adding notes to a project check-in
12:23 - Checking the revision number of a project
12:54 - Viewing previous revisions of a project
13:08 - Viewing changes in data between revisions
13:41 - Exporting a 21 CFR compliant project report in .pdf
14:00 - Overview of report
15:20 - Sending a project for sign-off
15:50 - Adding notes for project sign-off to the audit trail
17:22 - Signing off a project
17:36 - Identifying projects awaiting sign-off
17:50 - Audit trail for project awaiting sign-off
18:36- Checking out a read-only copy of a project for inspection
19:20 - Password-protected sign-off
19:35 - Adding notes to project sign-off
21:05 - Project signed-off and closed

Quantifying the bands allows accurate comparison of the reactivity of different antibodies to positive samples and the definition of the limits of detection of those antibodies to positive samples (to determine the minimum testing sample volume).

A previous version of our 1D analysis software, CLIQS, has already been used for this purpose with the research published here: https://www.mdpi.com/2079-6374/11/12/510/htm

Another of our products, CLIQS 1D Pro, allows the building of a database of lateral flow tests that can be searched or allow tests to be compared to the entire database for similarities and differences.

For a free trial of Phoretix 1D to see how well it works with your lateral flow test images, please fill in the form here: https://totallab.com/products/phoretix-1d-free-trial/

For a free trial of CLIQS 1D Pro to see how well it works creating a database of your lateral flow test images, please fill in the form here: https://totallab.com/products/cliqs-1d-pro-free-trial/

For a free trial of our Phoretix 1D GxP software, to see how well it operates within a 21 CFR Part 11/GxP/Annex 11 compliant format, please fill in the form here:
https://totallab.com/products/gxp-module-demo/

#21CFR #GxP #lateralflowtest #LFA #analysis #GxP #database #software #LFT  #1D #imageanalysis #automatic #howto #antibody #testing

How to Analyse Lateral Flow Tests (LFT/LFA) in compliance with 21 CFR Part 11 Using Phoretix 1D

In this video, I'll show you how you can get free access to advanced Western blot/1D image quantification software.

00:00 - Intro
00:25 - Full free trial
00:40 - Free academic use licensing
01:10 - How to access free licensing mode
01:30 - Opening tutorial images
01:47 - Single-channel image analysis
03:03 - Image setup and contrast edits
03:45 - Automatic lane detection/manual lane detection
04:00 - Background removal
04:34 - Molecular weight marker import
05:10 - Multichannel image analysis

For a free trial of Phoretix 1D to see how well it works with your images, please fill in the form here:
https://totallab.com/products/phoretix-1d-free-trial/

Phoretix 1D can provide quantitative analysis of blot and gel images, lateral flow test images, TLC (thin layer chromotography) images and more.
 
See our other image analysis-based products here: https://totallab.com/products/

And if you want to get in touch with us here at TotalLab:

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LinkedIn: https://www.linkedin.com/company/totallab-ltd/

#westernblot #electrophoresis #SDS-PAGE #tlc #quantification #immunoblot #software #imageanalysis #cliqs #totallab1d #imagej #21cfr #FDA #science #lifescience

Free 1D Gel or Blot Quantification Software Phoretix 1D - LINK IN DESCRIPTION

Oncotarget

Oncotarget published this research paper in Volume 14, entitled, “Novel inflammation-combined prognostic index to predict survival outcomes in patients with gastric cancer" by researchers from the Department of Digestive and General Surgery, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan; Department of Surgery, Matsue Red Cross Hospital, Matsue, Shimane 690-0886, Japan; Department of Surgery, Masuda Red Cross Hospital, Masuda, Shimane 698-8501, Japan.

DOI - https://doi.org/10.18632/oncotarget.28353

Correspondence to - Noriyuki Hirahara - norinorihirahara@yahoo.co.jp

Abstract

Background: We focused on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and devised an inflammation-combined prognostic index (ICPI) as a prognostic marker of cancer-specific survival (CSS).

Methods: We reviewed the clinicopathological data of 480 patients with gastric cancer undergoing curative laparoscopic gastrectomy between 2009 and 2019. This study examined the significance of LMR, NLR, PLR, and ICPI as cancer-specific prognostic markers.

Results: In univariate analysis, tumor diameter, histological differentiation, pathological tumor-node-metastasis (pTNM) stage, LMR, NLR, PLR, C-reactive protein (CRP) level, carcinoembryonic antigen (CEA), and postoperative chemotherapy were significantly associated with CSS. In multivariate analysis, pTNM stage and CEA were the independent risk factors for CSS, although LMR, NLR, and PLR were not the independent risk factors for CSS.

The ICPI formula was constructed using hazard ratios for three inflammation-based biomarkers with worse prognosis identified in the univariate analysis: LMR <4.315, NLR ≥2.344, and PLR ≥212.01, which were each scored as 1, with all remaining values pointed at 0. ICPI was calculated as follows: ICPI = 2.9 × LMR + 2.8 × NLR + 2.8 × PLR. The optimal cutoff value of ICPII was 2.9. On multivariate analysis, pTNM stage, CEA, and ICPI were independent prognostic factors for CSS. In the Kaplan–Meier survival analysis, CSS in the high ICPI group was significantly worse than that in the low ICPI group.

Conclusion: ICPI was devised as a novel predictive index for prognosis, and its usefulness was clarified.

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Keywords - gastric cancer, laparoscopic gastrectomy, novel predictive index, inflammation-combined prognostic index, cancer-specific survival

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Gastric Cancer Survival Outcome Prediction With Novel Inflammation Index

Technology Networks

In this episode, we will be speaking with *Paul Andrews, Director of Operations at the National Phenotypic Screening Centre, who will be talking to us about drug screening strategies and preclinical drug development. This series is kindly brought to you by CN Bio, click here to find out more: https://bit.ly/2xFrpC1 *(speaker and sponsor are not affiliated)

TSE Explores Drug Discovery - Testing a Drug Compound: Preclinical Screening S05E03

Aging-US published this research paper as the cover for Volume 15, Issue 2, entitled, "Clearance of p16Ink4a-positive cells in a mouse transgenic model does not change β-cell mass and has limited effects on their proliferative capacity" by researchers from the Joslin Diabetes Center, Harvard Medical School, Boston, MA.

DOI - https://doi.org/10.18632/aging.204483

Corresponding author - Cristina Aguayo-Mazzucato - cristina.aguayo-mazzucato@joslin.harvard.edu

Abstract

Type 2 diabetes is partly characterized by decreased β-cell mass and function which have been linked to cellular senescence. Despite a low basal proliferative rate of adult β-cells, they can respond to growth stimuli, but this proliferative capacity decreases with age and correlates with increased expression of senescence effector, p16Ink4a. We hypothesized that selective deletion of p16Ink4a-positive cells would enhance the proliferative capacity of the remaining β-cells due to the elimination of the local senescence-associated secretory phenotype (SASP). We aimed to investigate the effects of p16Ink4a-positive cell removal on the mass and proliferative capacity of remaining β-cells using INK-ATTAC mice as a transgenic model of senolysis. Clearance of p16Ink4a positive subpopulation was tested in mice of different ages, males and females, and with two different insulin resistance models: high-fat diet (HFD) and insulin receptor antagonist (S961). Clearance of p16Ink4a-positive cells did not affect the overall β-cell mass. β-cell proliferative capacity negatively correlated with cellular senescence load and clearance of p16Ink4a positive cells in 1-year-old HFD mice improved β-cell function and increased proliferative capacity in a subset of animals. Single-cell sequencing revealed that the targeted p16Ink4a subpopulation of β-cells is non-proliferative and non-SASP producing whereas additional senescent subpopulations remained contributing to continued local SASP secretion. In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes.

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Keywords - aging, beta cells, mass, proliferation, senolysis, senescence

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://youtube.com/Aging-US
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Media Contact
18009220957
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Clearance of p16Ink4a-positive Cells in Mice: Effects on β-cell Mass and Proliferation

Aging-US published this research paper as the cover for Volume 15, Issue 1, entitled, "Single-cell transcriptomics of peripheral blood in the aging mouse" by researchers from the Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI; Center for Computational Molecular Biology, Brown University, Providence, RI; Center on the Biology of Aging, Brown University, Providence, RI.

DOI - https://doi.org/10.18632/aging.204471

Corresponding author - Nicola Neretti - nicola_neretti@brown.edu

Abstract

Compositional and transcriptional changes in the hematopoietic system have been used as biomarkers of immunosenescence and aging. Here, we use single-cell RNA-sequencing to study the aging peripheral blood in mice and characterize the changes in cell-type composition and transcriptional profiles associated with age. We identified 17 clusters from a total of 14,588 single cells. We detected a general upregulation of antigen processing and presentation and chemokine signaling pathways and a downregulation of genes involved in ribosome pathways with age. In old peripheral blood, we also observed an increased percentage of cells expressing senescence markers (Cdkn1a, and Cdkn2a). In addition, we detected a cluster of activated T cells exclusively found in old blood, with lower expression of Cd28 and higher expression of Bcl2 and Cdkn2a, suggesting that the cells are senescent and resistant to apoptosis.

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Keywords - aging, single-cell transcriptomics, senescence, peripheral blood

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

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18009220957
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Single-cell Transcriptomics of Peripheral Blood in the Aging Mouse

Aging-US published this trending research paper in Volume 14, Issue 24, entitled, "Transcriptomic analysis of human ALS skeletal muscle reveals a disease-specific pattern of dysregulated circRNAs" by researchers from Laboratory of Genetics and Genomics, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, MD; Department of Neurology, The University of Alabama at Birmingham, Birmingham, AL; Birmingham Veterans Affairs Medical Center, Birmingham, AL; Center for Neural Science and Medicine, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA; Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA; Center for Neurodegeneration and Experimental Therapeutics, The University of Alabama at Birmingham, Birmingham, AL; Cell, Developmental, and Integrative Biology, The University of Alabama at Birmingham, Birmingham, AL.

DOI - https://doi.org/10.18632/aging.204450

Corresponding authors - Myriam Gorospe - GorospeM@grc.nia.nih.gov, Dimitrios Tsitsipatis - dimitrios.tsitsipatis@nih.gov, Peter H. King - phking@uabmc.edu 

Abstract

Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. Here, we set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, we first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS compared to normal individuals. By RT-qPCR analysis, we confirmed that 8 circRNAs were significantly elevated and 10 were significantly reduced in ALS, while the linear mRNA counterparts, arising from shared precursor RNAs, generally did not change. Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, a subset of the circRNAs significantly elevated in ALS muscle biopsies were significantly reduced in the spinal cord samples from ALS patients and ALS (SOD1G93A) mice. In sum, we have identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies.

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Keywords - aging, amyotrophic lateral sclerosis, circular RNAs, neurodegenerative disease, human skeletal muscle, human spinal cord tissue

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

Please visit our website at https://www.Aging-US.com​​ and connect with us:

SoundCloud - https://soundcloud.com/Aging-Us
Facebook - https://www.facebook.com/AgingUS/
Twitter - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/agingus​
LinkedIn - https://www.linkedin.com/company/aging/
Pinterest - https://www.pinterest.com/AgingUS/

Media Contact
18009220957
MEDIA@IMPACTJOURNALS.COM

Imaging/Microscopy

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