Valerie Bressler-Hill on LinkedIn: Mass Spectrometry–Based Proteomics Analysis of Human Substantia Nigra From… (2024)

Dysfunction in fast-spiking parvalbumin interneurons (PV-INs) may represent an early pathophysiological perturbation in Alzheimer’s Disease (AD). Defining early proteomic alterations in PV-INs can provide key biological and translationally-relevant insights. The scientists used cell-type-specific in-vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state PV-IN proteomes. PV-IN proteomic signatures include high metabolic and translational activity, with over-representation of AD-risk and cognitive resilience-related proteins p/b Yale School of Medicine, Emory University School of Medicine, Emory University, Georgia Institute of Technology, Yale University, Annie M Goettemoeller,Claudia Espinosa-Garcia,Ali Tfaily,Ruth Nelson,Aditya Natu,Eric Dammer, Juliet Santiago, PhD,Sneha Malepati,Hailian Xiao,Nicholas Seyfried,Levi Wood,Srikant Rangaraju #alzheimers #proteomics #translationalresearchhttps://bit.ly/4aNz0vu

15

📓 New Research: Extracellular Vesicles and Cryo-EM 🔬 In the article “Relevance of multilamellar and multicompartmental vesicles in biological fluids: understanding the significance of proportional variations and disease correlation”, Saadeldin et al. summarize the role of #extracellularvesicles (EVs) in #cellsignaling and their biogenesis. The authors highlight the potential of #cryoEM in characterizing the morphological features of EVs, including the presence of multicompartmental vesicles. Cryo-EM imaging allows for the preservation of native conformation and eliminates the need for staining, making it an ideal technique for studying EVs.👨🔬 The authors discuss the diverse morphologies of EVs observed in different biological samples, such as unilamellar, multilamellar, and multicompartmental vesicles. They emphasize the importance of studying multicompartmental vesicles due to their potential correlation with human diseases. For example, the proportion of multicompartmental vesicles has been found to be higher in the cerebrospinal fluid of patients with Parkinson’s disease compared to other neurological disorders.📓 Read about the significance of studying structural aspects of EVs and the potential of cryo-EM in characterizing them:https://lnkd.in/gjEV_GsG✍ To speak to our scientists about harnessing the power of cryo-EM for your EV project or #nanoparticlecharacterization, email us atinfo@nanoimagingservices.comor contact us athttps://lnkd.in/gTnWGWhp

15

2 Comments

Pharmacological inhibitor protects nerve cells in ALS rare disease A groundbreaking development in the world of medical science! Researchers have discovered a new pharmacological inhibitor with the potential to revolutionize ALS treatment. This game-changer can take control of a central cell death mechanism, effectively stemming the unfortunate motor neuron demise associated with this rare disease. Not only does this discovery open up new avenues for ALS treatment, but it also advances our understanding of the intricate workings of motor neurons. By deciphering these complex relationships, we're inching closer to a cure. This is a real beacon of hope in our unceasing quest to conquer ALS. Discover more about this remarkable research in the link below. https://lnkd.in/epf383AP

6

Multi-omics analysis of blood-brain barrierIn this study, researchers employed integrated multi-omics analyses to comprehensively profile the transcriptome, proteome, and chromatin accessibility of adult brain ECs, using abbreviated experimental methods for brevity. They validated identified brain EC-enriched proteins and transcription factors in normal mouse and human brain tissue and assessed their expression changes in mice with Alzheimer's disease. The researchers identified TCF/LEF, SOX, and ETS families as the top transcription factors regulating the BBB, providing a theoretical foundation for further epigenetic research on BBB mechanisms. Through comprehensive screening, eight proteins and three transcription factors with high expression in adult mouse brain capillary ECs were identified, showcasing molecular similarities between mouse and human BBB. Finally, to uncover disease-related molecular signatures of BBB, researchers examined the expression levels of brain EC-enriched proteins and transcription factors in a mouse model of Alzheimer's disease. Significant downregulations of LEF1 and EC enriched proteins were observed, revealing potential molecular alterations in the BBB in Alzheimer's disease, warranting further investigations.#ScienceMission #sciencenewshighlights https://lnkd.in/gw5j5csg

16

Is it possible to isolate enteric nervous system cells previously linked to #IBD, #colorectalcancer, and #neurodegeneration?🔬With the help of #flowcytometry, researchers at Erasmus MC say yes.Until now, protocols for the isolation of ENS cells have involved culturing, which can alter the transcriptome and mask disease-induced changes. However, this research team demonstrated that human ENS neuronal and glial cells can be selectively isolated by flow cytometry using the co-expression profiles of CD56, CD90, and CD24. This innovative approach has great implications for downstream analyses, including #microsocpy, #masscytometry, #rnaseq, and imaging flow cytometry. As researchers continue to push the boundaries of flow cytometry, powerful tools of panel design become more critical than ever. FluoroFinder's Panel Builder provides a streamlined solution for panel design with reagents from all suppliers, empowering researchers to maximize the potential of their fluorescent experiments.https://lnkd.in/gtUKeNki

7

The Institute is pleased to host Takanori Takebe, M.D., Ph.D., on Wednesday, June 7, 5-6 PM, at the Learning Theater, MMEC3-200 for a talk on "Hepatobility Development and Disease." Takebe works to develop and apply novel approaches and tools to recapitulate, probe and manipulate human #liver development and to understand the personalized molecular mechanisms that lead to disease. To that end, he is building experimental organogenesis approaches to engineer hepato-pancreato-biliary systems using pluripotent stem cells in vitro and in animals to construct and deconstruct previously inaccessible phases of human liver health and disease. #organoids #stemcellresearch

3

Another article from my group at Symbiosis School of Biological Sciences , wherein we relook at the existing neurodegenerative models for Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington’s Disease (HD). – both in vivo and in vitro – and review their usability and scope of improvement using emerging technologies.Here, we emphasize recent improvements in 3D cultures, underscoring the importance of microfluidics techniques and biomaterials for studying neurodegenerative disorders (NDs), highlighting their advantages and the scope of prospective developments. Our contention is that corroboration of these advanced in vitro techniques in a precise manner would catapult our understanding of the pathophysiology and underlying mechanisms of human NDs.Kudos 👍👏 to Prajakta Teli for the extensive literature review and the time she spent preparing the intricate figures that do justice to the article! #neurodegeneration #neurodegenerativediseases #animalresearch #alzheimersdisease #parkinsonsdisease #huntingtonsdisease #biomedicalresearch #biomaterials #microfluidics https://lnkd.in/d9qpB_xn

80

6 Comments

https://lnkd.in/eFrmGWEWThis article discusses the discovery of a novel mechanism by which neurons repair DNA damage by researchers at Harvard Medical School. My research in Dr. Porter’s Lab focuses on investigating the role of cell cycle proteins in the DNA damage response; I found this article particularly relevant as the findings offer insight and future directions applicable to my project.In the study, a new DNA repair mechanism was identified in mice; namely, the NPAS4-NuA4 protein complex which induces a DNA repair pathway exclusive to neurons. The researchers conducted biochemical experiments to identify the complex, its activity at different sites, and the effect on the lifespan of the mice studied. I found it particularly interesting that this may provide a explanation as to how neurons can maintain their longevity, despite the inability to replicate or regenerate – an intriguing question surrounding neuronal development. Furthermore, researchers are currently working on replicating results in human neurons which may provide insight into how the brain changes as we age and the cause behind neurogenerative diseases such as Alzheimer’s. I am intrigued to see what findings this research will continue to yield and how it will shape our understanding of DNA repair and brain development.

The Institute is pleased to host Takanori Takebe, M.D., Ph.D., on Wednesday, June 7, 5-6 PM, at the Learning Theater, MMEC3-200 for a talk on "Hepatobility Development and Disease." Takebe works to develop and apply novel approaches and tools to recapitulate, probe and manipulate human #liver development and to understand the personalized molecular mechanisms that lead to disease. To that end, he is building experimental organogenesis approaches to engineer hepato-pancreato-biliary systems using pluripotent stem cells in vitro and in animals to construct and deconstruct previously inaccessible phases of human liver health and disease. #organoids #stemcellresearch

3

Spatial RNA sequencing is one of the disruptive technologies that can help us better understanding and refining the molecular and cellular functions in complex tissues and organs. Excited to share this study from @Jonas Brorson, Lin Lin , Jakob Wang , Niels Jessen , Jean Farup and the rest of the MUSCLE team. It is an excellent biomedical and clinical matching, coherently deciphering expression changes of all human #proteincodinggenes at spatially resolved levels during the repair process of human skeletal muscles. One in-depth and important biological finding is that the complement system plays a vital role in muscle regeneration by orchestrating the interaction between muscle-residue mesenchymal stromal cells, also known as fibro-adipogenic progenitors (FAPs), and macrophages.

37

3 Comments