Bringing Order out of Chaos: Establishing an Epistatic Relationship between CD33 and TREM2.
Ontology highlight
ABSTRACT:
SUBMITTER: Huang TY
PROVIDER: S-EPMC7224407 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Bringing Order out of Chaos: Establishing an Epistatic Relationship between CD33 and TREM2.
Neuron 20190901 5
TREM2 and CD33 are microglial receptors associated with Alzheimer's disease (AD) risk. In this issue of Neuron, Griciuc et al. (2019) demonstrate opposing effects of CD33 and TREM2 on AD phenotypes, where CD33 deletion promotes neuroprotection in a manner dependent on TREM2. ...[more]
Similar Datasets
Project description:The increasing number of drugs targeting specific proteins implicated in tumourigenesis and the commercial promotion of relatively affordable genome-wide analyses has led to an increasing expectation among patients with cancer that they can now receive effective personalised treatment based on the often complex genomic signature of their tumour. For such approaches to work in routine practice, the development of correspondingly complex biomarker assays through an appropriate and rigorous regulatory framework will be required. It is becoming increasingly evident that a re-engineering of clinical research is necessary so that regulatory considerations and procedures facilitate the efficient translation of these required biomarker assays from the discovery setting through to clinical application. This article discusses the practical requirements and challenges of developing such new precision medicine strategies, based on leveraging complex genomic profiles, as discussed at the Innovation and Biomarkers in Cancer Drug Development meeting (8th-9th September 2016, Brussels, Belgium).
| S-EPMC7888555 | biostudies-literature
Project description:We used a protein quantitative trait analysis in monocytes from 226 individuals to evaluate cross-talk between Alzheimer loci. The NME8 locus influenced PTK2B and the CD33 risk allele led to greater TREM2 expression. There was also a decreased TREM1/TREM2 ratio with a TREM1 risk allele, decreased TREM2 expression with CD33 suppression and elevated cortical TREM2 mRNA expression with amyloid pathology.
| S-EPMC4682915 | biostudies-literature
Project description:The mechanisms for chaos terrain formation on Europa have long been a source of debate in the scientific community. There exist numerous theoretical and numerical models for chaos formation, but to date there has been a lack of quantifiable observations that can be used to constrain models and permit comparison to the outputs of these chaos models. Here, we use mapping and statistical analysis to develop a quantitative description of chaos terrain and their observed morphologies. For nine chaos features, we map every block, or region of pre-existing terrain within disrupted matrix. We demonstrate that chaos terrains follow a continuous spectrum of morphologies between two endmembers, platy and knobby. We find that any given chaos terrain's morphology can be quantified by means of the linearized exponential slope of its cumulative block area distribution. This quantitative metric provides a new diagnostic parameter in future studies of chaos terrain formation and comparison.
| S-EPMC9287068 | biostudies-literature
Project description:The microglial receptors CD33 and TREM2 have been associated with risk for Alzheimer's disease (AD). Here, we investigated crosstalk between CD33 and TREM2. We showed that knockout of CD33 attenuated amyloid beta (A?) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated A? pathology and neurodegeneration but reduced Iba1+ cell numbers, all of which could not be rescued by additional CD33 knockout. RNA-seq profiling of microglia revealed that genes related to phagocytosis and signaling (IL-6, IL-8, acute phase response) are upregulated in 5xFAD;CD33-/- and downregulated in 5xFAD;TREM2-/- mice. Differential gene expression in 5xFAD;CD33-/- microglia depended on the presence of TREM2, suggesting TREM2 acts downstream of CD33. Crosstalk between CD33 and TREM2 includes regulation of the IL-1?/IL-1RN axis and a gene set in the "receptor activity chemokine" cluster. Our results should facilitate AD therapeutics targeting these receptors.
| S-EPMC6728215 | biostudies-literature
Project description:The study of the foraging behavior of group animals (especially ants) is of practical ecological importance, but it also contributes to the development of widely applicable optimization problem-solving techniques. Biologists have discovered that single ants exhibit low-dimensional deterministic-chaotic activities. However, the influences of the nest, ants' physical abilities, and ants' knowledge (or experience) on foraging behavior have received relatively little attention in studies of the collective behavior of ants. This paper provides new insights into basic mechanisms of effective foraging for social insects or group animals that have a home. We propose that the whole foraging process of ants is controlled by three successive strategies: hunting, homing, and path building. A mathematical model is developed to study this complex scheme. We show that the transition from chaotic to periodic regimes observed in our model results from an optimization scheme for group animals with a home. According to our investigation, the behavior of such insects is not represented by random but rather deterministic walks (as generated by deterministic dynamical systems, e.g., by maps) in a random environment: the animals use their intelligence and experience to guide them. The more knowledge an ant has, the higher its foraging efficiency is. When young insects join the collective to forage with old and middle-aged ants, it benefits the whole colony in the long run. The resulting strategy can even be optimal.
| S-EPMC4060675 | biostudies-literature
Project description: Not available
| S-EPMC6355486 | biostudies-literature
Project description:Introduction: Alzheimer's disease (AD), which is a progressive neurodegenerative disorder, causes structural and functional brain disruption. MS4A6A, TREM2, and CD33 gene polymorphisms loci have been found to be associated with the pathobiology of late-onset AD (LOAD). In the present study, we tested the hypothesis of association of LOAD with rs983392, rs75932628, and rs3865444 polymorphisms in MS4A6A, TREM2, CD33 genes, respectively. Methods: In the present study, 113 LOAD patients and 100 healthy unrelated age- and gender-matched controls were selected. DNA was extracted from blood samples by the salting-out method and the genotyping was performed by RFLP-PCR. Electrophoresis was carried out on agarose gel. Sequencing was thereafter utilized for the confirmation of the results. Results: Only CD33 rs3865444 polymorphism revealed a significant difference in the genotypic frequencies of GG (P = 0.001) and GT (P = 0.001), and allelic frequencies of G (P = 0.033) and T (P = 0.03) between LOAD patients and controls. Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population.
| S-EPMC6879710 | biostudies-literature
Project description:Multidimensional solid-state NMR spectroscopy is used to refine the identification and abundance determination of functional groups in insoluble organic matter (IOM) isolated from a carbonaceous chondrite (Murchison, CM2). It is shown that IOM is composed primarily of highly substituted single ring aromatics, substituted furan/pyran moieties, highly branched oxygenated aliphatics, and carbonyl groups. A pathway for producing an IOM-like molecular structure through formaldehyde polymerization is proposed and tested experimentally. Solid-state (13)C NMR analysis of aqueously altered formaldehyde polymer reveals considerable similarity with chondritic IOM. Carbon X-ray absorption near edge structure spectroscopy of formaldehyde polymer reveals the presence of similar functional groups across certain Comet 81P/Wild 2 organic solids, interplanetary dust particles, and primitive IOM. Variation in functional group concentration amongst these extraterrestrial materials is understood to be a result of various degrees of processing in the parent bodies, in space, during atmospheric entry, etc. These results support the hypothesis that chondritic IOM and cometary refractory organic solids are related chemically and likely were derived from formaldehyde polymer. The fine-scale morphology of formaldehyde polymer produced in the experiment reveals abundant nanospherules that are similar in size and shape to organic nanoglobules that are ubiquitous in primitive chondrites.
| S-EPMC3228457 | biostudies-literature
Project description:RAD51 recombinase polymerizes at the site of double-strand breaks (DSBs) where it performs DSB repair. The loss of RAD51 causes extensive chromosomal breaks, leading to apoptosis. The polymerization of RAD51 is regulated by a number of RAD51 mediators, such as BRCA1, BRCA2, RAD52, SFR1, SWS1, and the five RAD51 paralogs, including XRCC3. We here show that brca2-null mutant cells were able to proliferate, indicating that RAD51 can perform DSB repair in the absence of BRCA2. We disrupted the BRCA1, RAD52, SFR1, SWS1, and XRCC3 genes in the brca2-null cells. All the resulting double-mutant cells displayed a phenotype that was very similar to that of the brca2-null cells. We suggest that BRCA2 might thus serve as a platform to recruit various RAD51 mediators at the appropriate position at the DNA-damage site.
| S-EPMC3136442 | biostudies-literature
Project description:A majority of American adults report having used sex toys, which, by design, interact with intimate and permeable body parts yet have not been subject to sufficient risk assessment or management. Physical and chemical data are presented examining potential risks associated with four types of currently available sex toys: anal toy, beads, dual vibrator, and external vibrator. A standardized abrasion machine made real-time breakdown of products into microplastics and nanoplastics. The microplastics from the sex toys were then solvent extracted and analyzed using GC-MS. Rates of microplastics and nanoplastics released during abrasion testing from most microplastic release to least was the anal toy, beads, dual vibrator, external vibrator. Both micro- and nanoplastics particles were generated following the abrasion test, with the 50 percentile diameters (D50) ranging from the anal beads at 658.5 μm, dual vibrator at 887.83 μm, anal toy at 950 μm, and external vibrator at 1673.33 μm. The material matrix of each product was analyzed using ATR-FTIR, with results identifying the anal toy as polyethylene terephthalate (PET), the anal beads as polyvinyl chloride (PVC), the external vibrator as a silicone blend (polydimethylsiloxane [PDMS]), and the dual vibrator as a rubber mixture (polyisoprene). After extraction, phthalates known to be endocrine disruptors were present in all tested sex toys at levels exceeding hazard warnings. Analogous findings have been reported for similar materials that, when incorporated into other product categories, are subject to regulatory scrutiny in both the US and EU. This data set is not intended to be representative of sex toys as an entire class of products, nor are the abrasion experiments claiming to simulate exact use conditions. However, these exploratory data frame potential concerns, highlighting research questions and the need for prompt prioritization of protective action. Therefore, future studies and multi-stakeholder action are needed to understand and reduce risk for this class of products.Supplementary informationThe online version contains supplementary material available at 10.1186/s43591-023-00054-6.
| S-EPMC10034881 | biostudies-literature