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1.
J Phys Chem Lett ; 15(11): 2951-2956, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38452374

ABSTRACT

The influence of gold nanocluster-solvent interactions on nanostructure optical properties was determined. Using [Au11(BINAP)4X2]+, where X = Cl or Br, as a model system, the dramatic influence of halogen-solvent hydrogen bonding on nanocluster optical properties was resolved. The creation of a nanocluster-solvent hydrogen-bond network yielded intense photoluminescence (PL) and an accompanying 2-fold reduction in vibration-mediated nonradiative decay rates. PL was quenched for systems that did not support hydrogen bonding. As reflected by absorption line widths, Raman scattering, and transient absorption spectroscopy measurements, the hydrogen-bond network increased nanocluster structural rigidity and reduced nonradiative carrier decay rates. The results highlight the significant role of the nanocluster-solvent interface in determining the properties of structurally precise materials.

2.
NPJ Parkinsons Dis ; 10(1): 7, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172128

ABSTRACT

Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson's disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.

3.
Curr Opin Anaesthesiol ; 32(5): 585-591, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31145199

ABSTRACT

PURPOSE OF REVIEW: Stroke is the second leading cause of death and the third leading cause of disability worldwide. Treatment is time limited and delays cost lives. This review discusses modern stroke management, during a time when treatments and guidelines are rapidly evolving. RECENT FINDINGS: Stroke thrombectomy has become the therapy of choice for large vessel occlusion (LVO) strokes. Perfusion imaging techniques, both computed tomography (CT) and MRI, now allow treatment beyond a set time window in specific patients. Both general anaesthesia and conscious sedation are options for patients undergoing stroke thrombectomy. SUMMARY: An individualized approach to the patient's anaesthetic management is optimal, and depends on close communication with the neurointerventionalist regarding patient and procedure-specific variables. No specific anaesthetic agent is preferred. Guiding principles are minimization of time delay, and maintenance of cerebral perfusion pressure.


Subject(s)
Anesthesia, General/methods , Conscious Sedation/methods , Endovascular Procedures/adverse effects , Intracranial Thrombosis/complications , Stroke/surgery , Thrombectomy/adverse effects , Anesthesia, General/adverse effects , Anesthetics/adverse effects , Brain/blood supply , Brain/diagnostic imaging , Brain/surgery , Cerebrovascular Circulation/drug effects , Conscious Sedation/adverse effects , Endovascular Procedures/methods , Evidence-Based Medicine/methods , Humans , Intracranial Thrombosis/diagnostic imaging , Intracranial Thrombosis/surgery , Magnetic Resonance Imaging , Stroke/etiology , Thrombectomy/methods , Time Factors , Time-to-Treatment , Tomography, X-Ray Computed , Treatment Outcome
4.
J Ophthalmol ; 2015: 746150, 2015.
Article in English | MEDLINE | ID: mdl-26351574

ABSTRACT

Spectral-domain OCT is an established tool to assist clinicians in detecting glaucoma and monitor disease progression. The widespread use of this imaging modality is due, at least in part, to continuous hardware and software advancements. However, recent evidence indicates that OCT scan artifacts are frequently encountered in clinical practice. Poor image quality invariably challenges the interpretation of test results, with potential implications for the care of glaucoma patients. Therefore, adequate knowledge of various imaging artifacts is necessary. In this work, we describe several factors affecting Cirrus HD-OCT optic disc scan quality and their effects on measurement variability.

5.
J Biol Chem ; 284(5): 2598-2602, 2009 Jan 30.
Article in English | MEDLINE | ID: mdl-19004816

ABSTRACT

Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129). The kinase or kinases responsible for this phosphorylation have been the subject of intense investigation. Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons. PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay. Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo. Finally, specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels. These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.


Subject(s)
Central Nervous System/metabolism , Protein Kinases/metabolism , Serine/metabolism , alpha-Synuclein/metabolism , Animals , Base Sequence , Cell Line , Central Nervous System/enzymology , DNA Primers , Enzyme-Linked Immunosorbent Assay , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , Protein Serine-Threonine Kinases , RNA Interference , alpha-Synuclein/chemistry
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