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result(s) for
"West, Nicole"
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Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer’s Disease
by
West, Nicole R.
,
Bhattacharyya, Anita
,
Christian, Bradley T.
in
Aging
,
Alzheimer's disease
,
Amygdala
2021
Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer’s disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.
Journal Article
Single‐nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth
by
Arachchilage, Kalpana Hanthanan
,
MacGregor, Shawn
,
Martinez, Jose L.
in
Basal Forebrain - metabolism
,
Basal Forebrain - pathology
,
basal forebrain cholinergic neurons (BFCNs)
2025
INTRODUCTION Basal forebrain cholinergic neurons (BFCNs) are integral to learning, attention, and memory, and are prone to degeneration in Down syndrome (DS), Alzheimer's disease, and other neurodegenerative diseases. However, the mechanisms that lead to the degeneration of these neurons are not known. METHODS Single‐nucleus gene expression and Assay for Transposase‐Accessible Chromatin (ATAC) sequencing were performed on postmortem human basal forebrain from unaffected control and DS tissue samples at 0–2 years of age (n = 4 each). RESULTS Sequencing analysis of postmortem human basal forebrain identifies gene expression differences in DS early in life. Genes encoding proteins associated with energy metabolism pathways, specifically oxidative phosphorylation and glycolysis, and genes encoding antioxidant enzymes are upregulated in DS BFCNs. DISCUSSION Multiomic analyses reveal that energy metabolism may be disrupted in DS BFCNs by birth. Increased oxidative phosphorylation and the accumulation of reactive oxygen species byproducts may be early contributors to DS BFCN neurodegeneration. Highlights First multiomic gene expression and ATAC analysis of human basal forebrain. Basal forebrain pathology in DS begins by birth. Cell type proportions are altered in early postnatal DS basal forebrain. Gene expression suggests dysregulated energy metabolism in DS BFCNs. Genes encoding oxidative phosphorylation subunits and glycolysis enzymes are dysregulated in DS BFCNs.
Journal Article
By Us, For Us: The Impact of a Professional Counterspace on African American Women in Student Affairs
2019
This study investigated outcomes associated with consistently participating in a professional counterspace developed by and for African American women higher education administrators. Data were obtained from semi-structured interviews with seven African American women student affairs professionals employed at predominantly White institutions, who consistently attended the African American Women’s Summit (AAWS) between 2006-2011. Participants noted the Summit’s impact on their physical, spiritual and interpersonal wellness; opportunities created by the AAWS for mentoring and networking; and the encouragement they received to advance their careers through professional development. Included is a discussion of the concept of professional counterspaces situated in Black feminist thought and critical race theory, which are the theoretical frameworks that grounded this inquiry. Implications for practice, theory, and further research are also presented.
Journal Article
Applying infectious disease forecasting to public health: a path forward using influenza forecasting examples
by
Lutz, Chelsea S.
,
Mgbere, Osaro
,
West, Nicole
in
BASIC BIOLOGICAL SCIENCES
,
Best practices
,
Biostatistics
2019
Background
Infectious disease forecasting aims to predict characteristics of both seasonal epidemics and future pandemics. Accurate and timely infectious disease forecasts could aid public health responses by informing key preparation and mitigation efforts.
Main body
For forecasts to be fully integrated into public health decision-making, federal, state, and local officials must understand how forecasts were made, how to interpret forecasts, and how well the forecasts have performed in the past. Since the 2013–14 influenza season, the Influenza Division at the Centers for Disease Control and Prevention (CDC) has hosted collaborative challenges to forecast the timing, intensity, and short-term trajectory of influenza-like illness in the United States. Additional efforts to advance forecasting science have included influenza initiatives focused on state-level and hospitalization forecasts, as well as other infectious diseases. Using CDC influenza forecasting challenges as an example, this paper provides an overview of infectious disease forecasting; applications of forecasting to public health; and current work to develop best practices for forecast methodology, applications, and communication.
Conclusions
These efforts, along with other infectious disease forecasting initiatives, can foster the continued advancement of forecasting science.
Journal Article
The (Re)Construction of Black Womanhood Among Black College Women at PWIs: A Hip Hop Feminism Model of Multiple Identities
2022
The purpose of this study was to explore how Hip Hop informed the construction of gendered racial and sexual identities among Black women at predominately white institutions (PWIs). Ten Black women undergraduates at a PWI in the midwestern region of the US engaged in individual and focus group interviews, which included participating in an activity called the Soundtrack of My Life. The research team performed a constant comparative thematic analysis and identified three themes: (a) using Hip Hop to explore the multiplicity of Black womanhood, (b) unpacking the hypersexualization of Black women in Hip Hop, and (c) leveraging Hip Hop to navigate respectability politics. These findings explicate the specific ways Black women in college rely on Hip Hop to reconstruct Black womanhood via multiple intersecting identities. This study adds to previous identity frameworks by discussing the complex nature of Hip Hop culture's influence on the construction of Black womanhood among college women and proposes the Hip Hop feminism model of multiple identities.
Journal Article
The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation
by
Sternbach, Sarah
,
Singhal, Naveen K.
,
McDonough, Jennifer
in
5-Methyltetrahydrofolate-homocysteine S-methyltransferase
,
Abbreviations
,
Adenosylmethionine
2021
Research into the epigenome is of growing importance as a loss of epigenetic control has been implicated in the development of neurodegenerative diseases. Previous studies have implicated aberrant DNA and histone methylation in multiple sclerosis (MS) disease pathogenesis. We have previously reported that the methyl donor betaine is depleted in MS and is linked to changes in histone H3 trimethylation (H3K4me3) in neurons. We have also shown that betaine increases histone methyltransferase activity by activating chromatin bound betaine homocysteine S-methyltransferase (BHMT). Here, we investigated the role of the BHMT-betaine methylation pathway in oligodendrocytes. Immunocytochemistry in the human MO3.13 cell line, primary rat oligodendrocytes, and tissue from MS postmortem brain confirmed the presence of the BHMT enzyme in the nucleus in oligodendrocytes. BHMT expression is increased 2-fold following oxidative insult, and qRT-PCR demonstrated that betaine can promote an increase in expression of oligodendrocyte maturation genes SOX10 and NKX-2.2 under oxidative conditions. Chromatin fractionation provided evidence of a direct interaction of BHMT on chromatin and co-IP analysis indicates an interaction between BHMT and DNMT3a. Our data show that both histone and DNA methyltransferase activity are increased following betaine administration. Betaine effects were shown to be dependent on BHMT expression following siRNA knockdown of BHMT. This is the first report of BHMT expression in oligodendrocytes and suggests that betaine acts through BHMT to modulate histone and DNA methyltransferase activity on chromatin. These data suggest that methyl donor availability can impact epigenetic changes and maturation in oligodendrocytes.
Journal Article
Pose-gait analysis for cetacean biologging tag data
2022
Biologging tags are a key enabling tool for investigating cetacean behavior and locomotion in their natural habitat. Identifying and then parameterizing gait from movement sensor data is critical for these investigations, but how best to characterize gait from tag data remains an open question. Further, the location and orientation of a tag on an animal in the field are variable and can change multiple times during a deployment. As a result, the relative orientation of the tag with respect to (wrt) the animal must be determined for analysis. Currently, custom scripts that involve species-specific heuristics tend to be used in the literature. These methods require a level of knowledge and experience that can affect the reliability and repeatability of the analysis. Swimming gait is composed of a sequence of body poses that have a specific spatial pattern, and tag-based measurements of this pattern can be utilized to determine the relative orientation of the tag. This work presents an automated data processing pipeline (and software) that takes advantage of these patterns to 1) Identify relative motion between the tag and animal; 2) Estimate the relative orientation of the tag wrt the animal using a data-driven approach; and 3) Calculate gait parameters that are stable and invariant to animal pose. Validation results from bottlenose dolphin tag data show that the average relative orientation error (tag wrt the body) after processing was within 11 degrees in roll, pitch, and yaw directions. The average precision and recall for detecting instances of relative motion in the dolphin data were 0.87 and 0.89, respectively. Tag data from humpback and beluga whales were then used to demonstrate how the gait analysis can be used to enhance tag-based investigations of movement and behavior. The MATLAB source code and data presented in the paper are publicly available ( https://github.com/ding-z/cetacean-pose-gait-analysis.git ), along with suggested best practices.
Journal Article
Corrigendum: Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer's Disease
by
West, Nicole R.
,
Bhattacharyya, Anita
,
Christian, Bradley T.
in
Alzheimer's disease
,
basal forebrain cholinergic neurons
,
down syndrome
2021
[This corrects the article DOI: 10.3389/fnagi.2021.703876.].[This corrects the article DOI: 10.3389/fnagi.2021.703876.].
Journal Article
The African American Women's Summit: A Student Affairs Professional Development Program
2017
The African American Women's Summit (AAWS) is a professional development program in the United States created by and for African American women in student affairs. This article reviews the evolution and structure of the AAWS. A discussion, grounded in Black feminist thought, is included relative to the impact of the AAWS on African American women student affairs professionals.
Journal Article
A Decade of a Student Affairs Preconference Program: Perceptions and Characteristics of African American Women's Summit Participants
2017
Research related to professional development in student affairs has found that few attendees benefit from participating in preconference programs. The African American Women's Summit (AAWS) is a preconference program created by and for African American women in student affairs and serves as a professional counterspace for this significantly underrepresented population of higher education administrators. This article presents 10 years of data (2005-2015) related to participants' perceptions of the quality and relevance of the AAWS. An in-depth demographic profile of participants is included to describe the personal, professional, and educational characteristics of the African American women student affairs professionals who participated in the study. The majority of participants were 26-30 years old, employed at the director/dean level and below, had earned master's degrees, responded positively about the value of this preconference program, and noted that the AAWS represented a safe space where they were encouraged personally and professionally. These findings suggest that preconference programs, like the AAWS, developed as professional counterspaces are especially valued by minority student affairs professionals who are employed in paraprofessional, and entry- and mid-level positions.
Journal Article