Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: genetics

Cellular and molecular mechanisms of astrocyte plasticity in learning and memory

Astrocyte plasticity in learning and memory.

Neuronal hallmark features of learning and memory, such as activity dependent plasticity, circuit-level modulation, and gene regulatory mechanisms, are also observed in astrocytes.

Astrocytic calcium displays plastic, activity-dependent recruitment and refinement (akin to neuronal activity) across neuronal subtypes, brain regions, and behavioral paradigms, and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)-mediated manipulations highlight astrocytic recruitment of circuit-specific neurons.

Astrocyte peripheral processes display activity-dependent plasticity and are able to discriminate between neuronal subtypes, circuits, and even individual synapses.

Single-cell RNA sequencing reveals molecularly defined subtypes of astrocytes that display unique transcriptional responses to learning and memory and implicates potential ‘ensemble’-like networks of astrocytes. sciencenewshighlights ScienceMission https://sciencemission.com/astrocyte-plasticity

Learning and memory arise from coordinated activity-dependent plasticity across neural circuits and brain regions. Astrocytes are increasingly recognized as active contributors to learning and memory via their roles in sensing, integrating, and responding to contextual information. Astrocytes modulate synaptic transmission, engage in circuit-specific signaling, and display context-dependent calcium dynamics that influence behavior. In this review, we focus on astrocyte functions across rodent models that display plasticity traditionally ascribed to neurons, including activity-dependent molecular and structural plasticity, circuit-level modulation, ensemble-like networks, and transcriptional, translational, proteomic, and epigenetic plasticity.

Continue reading “Cellular and molecular mechanisms of astrocyte plasticity in learning and memory” | >

New genetic risk score better predicts diabetes, obesity and downstream complications

Type 2 diabetes (T2D) and obesity are metabolic conditions with many causes, including overlapping and distinct genetic features. A polygenic risk score (PRS) can capture multiple genetic risk factors to provide an estimate for whether a person may develop a complex medical condition and how they might fare long-term.

Building stronger genetic risk scores By integrating genetic findings from several of the world’s largest biobanks, investigators from Mass General Brigham built metabolic PRSs for predicting obesity and T2D, which outperformed existing disease-prediction models and predicted downstream morbidity and clinical interventions. Findings are published in Cell Metabolism.

“Our intention was to not only capture the risk of being diagnosed with obesity or diabetes, but also to better predict health consequences across the life course by integrating many aspects of metabolic function,” said co-first author Min Seo Kim, MD, MSc.

Designed to remember

In a new Science study, researchers report that specific regions dense in cytosine and guanosine dinucleotides are epigenetically modified during inflammation to enable gene expression and that these changes persist during the animal’s lifetime.

The finding has implications for understanding how the genome determines the longevity of memory, which affects tissue fitness.

Learn more in a new Science Perspective.

Specific DNA sequence features encode the persistence of epigenetic memory of inflammation.

Guillaume Blot and Przemyslaw Sapieha Authors Info & Affiliations

Science

Continue reading “Designed to remember” | >

Advancements in organoid models emulating metastatic niches

Metastatic niche in organoid models.

The mortality rate of cancer patients remains high, mainly due to the lack of metastasis-tailored treatments, highlighting the need for alternative experimental approaches that capture metastatic development in a human context.

Human-induced pluripotent stem cell derived organoids cocultured with cancer cells (‘chimeroids’) have the potential to emulate aspects of colonized organ specific microenvironments and offer an alternative platform for target identification and drug discovery, as these models are amenable to scalable genetic and chemical perturbation screens.

Conceptually, organoid models have progressed from epithelial-only organoids to multilineage, niche enriched systems incorporating stromal, vascular, and tissue-resident immune components, thereby bringing in vitro models closer to organ-specific metastatic microenvironments.

Yet no single organoid model fully recapitulates the entire complexity of an organ in vivo; thus, model selection must be driven by the specific scientific question, ensuring that the relevant stage of metastatic development and organ microenvironment are appropriately represented. ScienceMission sciencenewshighlights https://sciencemission.com/organoid-models-emulating-metastatic-niches

Metastases cause most cancer-related deaths, underscoring the need for therapies targeting metastatic stages, including the tumor microenvironment. Yet translating biological insights into treatments remains difficult. Preclinical metastasis research largely relies on rodent models, which have species-specific limitations and are incompatible with large-scale perturbation screens in a human context. Human organoids aim to emulate organ microenvironments in vitro and, when cocultured with cancer cells, can provide complementary models. These ‘chimeroids’ may enable scalable studies of cancer–microenvironment interactions and support genetic and pharmacological screens to discover new targets, offering insights into the final, often lethal step of metastasis—tissue colonization.

Continue reading “Advancements in organoid models emulating metastatic niches” | >

A new era in childhood obesity

Childhood obesity!

Obesity associated with the melanocortin system can be diagnosed in childhood, including both monogenic and syndromic forms.

Genetic obesity is characterized by early onset and extreme hyperphagia, although there is no precise definition for these features.

Numerous polymalformative syndromes include obesity among their main phenotypic traits. Among these are ciliopathies, in which alterations in the neuronal ciliary system can disrupt hypothalamic proopiomelanocortin neuron signaling, helping to explain the hyperphagia and obesity frequently observed in some of these disorders.

Pharmacological treatment of patients with impairment of the leptin– melanocortin pathway can be classified into specific and nonspecific treatments.

The use of these therapies is expanding to new indications, and additional treatments are under clinical investigation for both monogenic and polygenic obesity sciencenewshighlights ScienceMission https://sciencemission.com/childhood-obesity-19506

Continue reading “A new era in childhood obesity” | >

Consistently Higher HRV, Lower RHR Since 2018

Join us on Patreon! / michaellustgartenphd.

Discount Links/Affiliates:
Blood testing (where I get the majority of my labs): https://www.ultalabtests.com/partners… Metabolomics: https://www.iollo.com?ref=michael-lus… Use Code: CONQUERAGING At Checkout Clearly Filtered Water Filter: https://get.aspr.app/SHoPY Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=… Use Code: CONQUERAGING NAD+ Quantification: https://www.jinfiniti.com/intracellul… Use Code: ConquerAging At Checkout Oral Microbiome: https://www.bristlehealth.com/?ref=mi… Enter Code: ConquerAging SiphoxHealth Blood Testing (ApoB, GrimAge): https://siphoxhealth.com/mlustgarten Green Tea: https://www.ochaandco.com/?ref=fqbtflod Use Code: ML10OFF Diet Tracking: https://shareasale.com/r.cfm?b=139013… If you’d like to support the channel, you can do that with the website, Buy Me A Coffee: https://www.buymeacoffee.com/mlhnrca Conquer Aging Or Die Trying Merch! https://my-store-d4e7df.creator-sprin…

Blood Testing Essentials (Biological Age, CVD-Risk, Kidney Health and Function):
PhenoAge (Biological Age): https://www.ultalabtests.com/partners…

Risk-weighted ApoB (a better CVD predictor than LDL, non-HDL cholesterol, and ApoB): https://www.ultalabtests.com/partners…

Kidney health and function: https://www.ultalabtests.com/partners…

At-Home Metabolomics: https://www.iollo.com?ref=michael-lus…

Continue reading “Consistently Higher HRV, Lower RHR Since 2018” | >

New genetic toolkit enables genome-wide analysis

Researchers at Cornell University have developed a powerful new genetic toolkit that allows scientists to study how genes function at the level of individual cells, an advance that could accelerate discoveries in development, neuroscience and disease.

The system builds on MAGIC (Mosaic Analysis by gRNA-Induced Crossing-over), a method originally created by the labs of Chun Han, associate professor in the Department of Molecular Biology and Genetics in the College of Agriculture and Life Sciences (CALS) and the Weill Institute for Cell and Molecular Biology. MAGIC uses CRISPR gene editing to generate individual mutant cells within otherwise normal tissue, enabling precise comparisons within a living organism.

In the new study, graduate researcher Yifan Shen expanded the approach into a genome-wide toolkit for Drosophila melanogaster, creating resources that work across all chromosomes and allow researchers to study genes that were previously difficult, or impossible, to analyze at single-cell resolution.

Endogenous aldehydes: A driver of clonal hematopoiesis from within?

Detoxification of endogenous aldehydes is critical for preserving genomic integrity in hematopoietic stem cells. In this issue, Kamimae-Lanning et al. show that excess formaldehyde can drive clonal hematopoiesis through attrition of blood-forming progenitors, accelerating neutral drift in the absence of known genetic drivers of positive selection.

Seed banks may complicate gene drives aimed at controlling weeds

Gene drives—a genetic engineering approach that quickly spreads specific genetic changes throughout a population, whether to kill it off or add a new trait—may have potential for controlling weeds. But so far, gene drives have primarily been studied in mosquitoes, and have yet to be deployed in the real world.

In a first-of-its-kind study, researchers modeled how a gene drive would proceed in plants. Their simulations suggest that a gene drive’s success may hinge on seed banks—underground reservoirs of seeds that can germinate years or even decades later. Without proper consideration, they found, these stored seeds can slow down or even doom the gene drive, because they continually reintroduce plants without the gene drive into the population.

Modeling studies like this one can help scientists design successful gene drives in plants and discover and mitigate potential problems before deployment in the wild, the researchers said.

/* */