1. In Memory of Steve Zelditch - American Mathematical Society
Steve Zelditch, our beloved and admired colleague and a major figure in spectral theory, semiclassical analysis, quantum chaos, and Kähler geometry, ...
2. Shaking up the silence: consequences of HMGN1 ...
3 dec 2022 · In fact, HMGN proteins are the only non-histone proteins capable of binding between the DNA and the histone octamer core, basically within the ...
Intellectual disability is a well-known hallmark of Down Syndrome (DS) that results from the triplication of the critical region of human chromosome 21 (HSA21). Major studies were conducted in recent years to gain an understanding about the contribution of individual triplicated genes to DS-related brain pathology. Global transcriptomic alterations and widespread changes in the establishment of neural lineages, as well as their differentiation and functional maturity, suggest genome-wide chromatin organization alterations in trisomy. High Mobility Group Nucleosome Binding Domain 1 (HMGN1), expressed from HSA21, is a chromatin remodeling protein that facilitates chromatin decompaction and is associated with acetylated lysine 27 on histone H3 (H3K27ac), a mark correlated with active transcription. Recent studies causatively linked overexpression of HMGN1 in trisomy and the development of DS-associated B cell acute lymphoblastic leukemia (B-ALL). HMGN1 has been shown to antagonize the activity of the Polycomb Repressive Complex 2 (PRC2) and prevent the deposition of histone H3 lysine 27 trimethylation mark (H3K27me3), which is associated with transcriptional repression and gene silencing. However, the possible ramifications of the increased levels of HMGN1 through the derepression of PRC2 target genes on brain cell pathology have not gained attention. In this review, we discuss the functional significance of HMGN1 in brain development and summarize accumulating reports about the...
3. [PDF] KL-VS heterozygosity is associated with lower amyloid-dependent tau ...
Zeldich, E. et al. The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. J. Biol. Chem. 289, 24700–24715. (2014) ...
4. Extracellular Vesicle Treatment Alleviates Neurodevelopmental and ...
9 feb 2023 · Extracellular vesicles (EVs) (or exosomes) are membrane-bound vesicles released from cells into the extracellular matrix as a form of ...
Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer’s disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS.
5. Klotho overexpression improves amyloid‐β clearance and cognition ...
21 sep 2020 · Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer's disease-like pathology and cognitive deficits in mice.
Alzheimer's disease (AD) is the most prevalent type of dementia, characterized by the presence of amyloid‐β (Aβ) plaques. We previously reported that Klotho lowered Aβ levels in the brain and protected against cognitive deficits in amyloid precursor ...
6. [PDF] Quantum ergodicity and mixing of eigenfunctions
Quantum ergodicity and mixing belong to the field of Quantum Chaos, which studies quantizations of 'chaotic' classical Hamiltonian systems.
7. [PDF] Upregulation of Epac-1 in Hepatic Stellate Cells by Prostaglandin E2 ...
bound to the albumin drug carrier. Mice were sacrificed at week 8. Two ... Yu JL, Deng R, Chung SK, and Chan GC (2016) Epac activation regulates human.
8. Com. v. Zeldich, L. (memorandum)
MEMORANDUM BY FITZGERALD, J.:FILED DECEMBER 07, 2015Appellant, Leonid Zeldich, appeals from the order entered in theBucks County Court of Common Pleas denying ...
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9. Shedding of Klotho: Functional Implications in Chronic Kidney ...
28 jan 2021 · α-Klotho (Klotho) exists in two different forms, a membrane-bound and soluble form, which are highly expressed in the kidney.
α-Klotho (Klotho) exists in two different forms, a membrane-bound and soluble form, which are highly expressed in the kidney. Both forms play an important role in various physiological and pathophysiological processes. Recently, it has been ...
10. [PDF] Mineral Handling in Kidney Disease - Radboud Repository
Lee, S. L., Yu, A. S., and Lyton, J. (1994) Tissue-specific expression ... bound ɑklotho as its obligate co-receptor (12,13). ɑklotho is predominantly ...
11. [PDF] 5th T21RS
Yu E1, Xing Z1, Cortes-Gomez E1, Jiang X1, Liu C1, Douglas A1, Pao A1, Gao ... Zeldich E1,5, Herrema K2, Kharitonova E1, Baker Campbell N1, Wilson M3 ...
12. DEIJ | Anatomy & Neurobiology
If you are interested in joining or learning more, please email ancamed@bu.edu. The Department of Anatomy & Neurobiology (A&N) is committed to diversity, equity ...
The emphasis of A&N’s Community Engagement Subcommittee is to help department students, staff, and faculty engage with the local community, particularly with students from under-resourced neighborhoods. Department members have joined both national and local organizations in outreach efforts including, among others: Dana Foundation’s Brain Awareness Week, Upward Bound, Hugo Mentors, Framingham Heart Study’s U19 Mentorship Program, and Anatomy Academy. By engaging in these partnerships, the subcommittee seeks to cultivate mutually advantageous connections between the department and community members, nurturing positive outcomes for both entities.
13. c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI ...
15 jul 2024 · Many of these enzymes, which can exist as either membrane-bound or ... Zeldich D, et al. (2019) Small molecule amyloid-β protein ...
Treatments for Alzheimer’s disease have primarily focused on removing brain amyloid plaques to improve cognitive outcomes in patients. We developed small compounds, known as BK40143 and BK40197, and we hypothesize that these drugs alleviate microglial-mediated neuroinflammation and induce autophagic clearance of neurotoxic proteins to improve behavior in models of neurodegeneration. Specificity binding assays of BK40143 and BK40197 showed primary binding to c-KIT/Platelet Derived Growth Factor Receptors (PDGFR)α/β, whereas BK40197 also differentially binds to FYVE finger-containing phosphoinositide kinase (PIKFYVE). Both compounds penetrate the CNS, and treatment with these drugs inhibited the maturation of peripheral mast cells in transgenic mice, correlating with cognitive improvements on measures of memory and anxiety. In the brain, microglial activation was profoundly attenuated and amyloid-beta and tau were reduced via autophagy. Multi-kinase inhibition, including c-KIT, exerts multifunctional effects to reduce neurodegenerative pathology via autophagy and microglial activity and may represent a potential therapeutic option for neurodegeneration. The data supporting the current study are available from the corresponding author on request.
14. [PDF] Semaphorins in Adult Nervous System Plasticity and Disease
11 mei 2021 · secreted and membrane-bound Semaphorins as well as Npn ... Yu, H. H., and Kolodkin, A. L.. (2002). MICALs, a family of conserved ...