University at Albany, State University of New York
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The Transdiagnostic Role and Measurement of Cognitive Inflexibility Across Understudied Eating Disorder Groups: A Multi-Method Investigation
Get PDFCognitive inflexibility is an established transdiagnostic executive function deficit that maintains a wide array of psychiatric conditions. Eating disorders (ED) are serious, life-threatening conditions that remain underdiagnosed and understudied across diverse demographic groups. There is growing evidence for a role of cognitive inflexibility in driving hallmark ED symptoms, particularly in anorexia nervosa. Treatments targeting cognitive inflexibility may improve the currently poor outcomes of these conditions. To date, the role of cognitive inflexibility remains to be examined across demographically and diagnostically diverse ED groups. The first two studies presented here examine associations between cognitive inflexibility and symptom presentation in two relatively understudied ED diagnostic groups, namely avoidant/restrictive food intake disorder (Study 1), and orthorexia nervosa (Study 2). The following two studies then evaluate associations between cognitive inflexibility and symptom presentation in two relatively understudied demographic groups at risk for disordered eating, namely men with drive for muscularity (Study 3), and pregnant women (Study 4). The last two studies address the current lack of valid, reliable, and easily administered assessments of cognitive flexibility suitable for use in diverse populations. Study 5 evaluates the psychometric properties of the Eating Disorder Flexibility Index (EDFLIX), the only current self-report measure of both general and ED-specific flexibility in the published literature. Study 6 is a preliminary investigation of the utility of salivary oxytocin and heart rate variability as novel biomarkers of cognitive inflexibility
Examining Downshear Reformation in Tropical Cyclones
Get PDFThe development of a new low-level circulation center in tropical cyclones, known as downshear reformation, can lead to sudden changes in storm structure and intensity, representing a challenge in forecasting tropical cyclones. This phenomenon is commonly observed in weak tropical cyclones (e.g., tropical depressions, tropical storms) experiencing moderate to strong vertical wind shear (\u3e 5 m s-1), when the vertical wind shear organizes convection in the downshear region of the tropical cyclone, and lower-tropospheric vorticity is generated within the intense convection. Downshear reformation has been proposed as a mechanism for intensification, sometimes rapidly, in tropical cyclones under unfavorable environmental wind shear. Some of the processes involved in the reformation that aid the intensification of the storm include the increase of diabatic heating near the center, vortex tilt and misalignment reduction, and the repositioning of the center in a more favorable environment. However, not all sheared tropical cyclones undergo downshear reformation, and the factors associated with this process still need to be clarified. This research aims to identify the factors and mechanisms that favor downshear reformation in tropical cyclones, using an analog approach.
Tropical cyclones that reformed in the North Atlantic Basin from 1998-2020 were compared to analog tropical cyclones with similar intensity, vertical wind shear, and maximum potential intensity but did not undergo downshear reformation using ERA5 reanalysis and GridSat-B1 data. The comparison between composites showed that reformed storms have greater low-level and mid-tropospheric relative humidity downshear, more significant surface latent heat fluxes downshear, and larger low-level equivalent potential temperatures. These factors increase thermodynamic favorability and sustained convection downshear, favoring a new center\u27s development
Pdgfra and b Copositive Fibroblasts Drive Fibrosis in Mouse Salivary Glands Through TGFβ Signaling
Get PDFFibrosis is of significant concern to the medical community as numerous disease processes are characterized by progressive fibrosis leading to organ damage. We begin the process of examining the mechanism of fibrosis to salivary gland hypofunction and briefly consider Sjögren’s Disease (SjD). Method: We employed single-cell RNA sequencing data from a reversible mouse salivary gland injury model and from NOD/ShiLtJ mice, a model of secondary SjD. We performed treatment comparisons with the help of Seurat dotplots and UMAPS. Using differential gene expression analysis and the publicly available R packages: clusterProfiler, WikiPathways and Cytoscape, we identified the processes and pathways increased in the fibroblast population and the Pdgfra/b copositive population and visualized the hits from our dataset in a published fibrosis pathway network. Results: We determined that fibrosis of mouse salivary glands is orchestrated by a subtype of fibroblasts identified as Pdgfra/b copositive fibroblasts. This subtype expands in response to ligation injury likely through TGFB signaling. We highlight that fibrosis is a characteristic process of the fibroblasts in a Sjögren’s Disease mouse model. We show the molecules involved in the fibrosis process in the Pdgfra/b copositive fibroblasts. The reversible fibrosis mouse model is a relevant model showing concordance with the human ductal obstructive injury. Conclusions: Pdgfra/b copositive fibroblasts are a disease subtype that rise upon injury and are proliferative and fibrotic. Bioinformatics revealed five processes are increased in fibroblasts in response to injury: blood circulation, leukocyte migration, cell chemotaxis and extracellular matrix organization. G-coupled protein receptor signaling is the most significant pathway increased through Wnt signaling which give rise to the TGFB mediated fibrosis. This work paves the way for further targeted in-vivo and in-vitro analyses for the contribution of TGFB to this fibroblast disease sub-type
What we don\u27t know about why nearly one in five IT workers leave NYS government employment: a systematic literature review
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Assessing the Inclusion of Organizational Response Information in Wireless Emergency Alerts
No full textLifespan of Greater Rochester: Findings from Participant Interviews after “Scams 101” Presentation
Get PDFTo assess whether the “Scams 101” presentation impacted participants’ ability to protect themselves against fraud and scams, the Center for Human Services Research (CHSR) interviewed 20 participants. Interviews were conducted between January and May of 2024; participants had attended the presentation between two and five months prior to being interviewed
Understanding Attitudes Among Professionals Who Interact With Youth Who Exhibit Problematic Sexual Behavior
Get PDFProblematic sexual behaviors (PSB) among youth have been a prominent public health and social concern. Although these behaviors have previously been considered to comprise a “curiosity” or an “experimentation”, PSB is now recognized as causing harm and suffering for victims and family members while also having a considerable economic influence in medical, behavioral health, social services, and criminal justice systems. Much research has examined how perceptions and attitudes impact our behaviors towards PSB among adults, but none examines how perceptions and attitudes impact our behaviors towards youth. Knowing there are several gaps in literature, the current study was conducted to explore attitudes among professionals (social workers, probation officers, and police) that may potentially interact with youth who exhibit PSB. An embedded mixed-methods design was carried out with social workers, probation officers, and police. Quantitative data were collected from professionals who interact with youth who exhibit PSB (N = 51), and qualitative data were collected from social workers, probation, and police officers (N = 12). Rigorous data analyses techniques were employed, including an inductive and deductive thematic analysis and focused coding schemas to analyze qualitative data and mixed-effects regression models to analyze quantitative data. Qualitative results revealed that experiences such as employment, prevailing language and biases influence one’s response to PSB. Quantitative results revealed that social workers, probation officers, and police respond more punitively towards more serious PSB such as rape. The models also demonstrated that although probation officers initially react more punitively to PSB compared to social workers, police officers respond even more punitively. Inherent implications suggest that there is a need for professional development and training that focuses on trauma-informed practices and current research on evidence-based practices for PSB, funding for more organizations to provide specialized PSB services, a need for solution-focused approaches and interprofessional collaboration, and a need for consistent policies across different systems. Future research should focus on delving deeper into what aspects of trauma-informed practices are more important than others. It should also explore other professional’s and paraprofessional’s attitudes and the supports needed to effectively respond to PSB among youth
Development Of Selective Rna Aptamers For Kainate Receptors
Get PDFIonotropic glutamate receptors (iGluRs) play a major role in mediating the excitatoryfunctions in the central nervous system (CNS). iGluRs are ligand-gated ion channels that are activated when glutamate binds to the extracellular ligand binding domain, thereby leading to the opening of the ion channels. Three subtypes of iGluRs include kainate receptors, α-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, and N-methyl-D-aspartate (NMDA) receptors. Abnormal and dysregulation of these receptors have cytotoxic effects for neurons and have been implicated in various neurological diseases. For instance, elevated expression of a key AMPA receptor subunit has been linked to conditions such as ALS, where cytotoxic levels of Ca2+ ions enter the motor neurons, triggering cell death. Downregulations of iGluR surface expression has been linked to learning and mood disorders. Auxiliary proteins, such as transmembrane AMPAR regulatory proteins (TARPs) for AMPA receptors and neuropilin and tolloid-like (Neto) proteins for kainate receptors respectively, also play an important role in regulating receptor surface expression and modulating receptor activities. Developing a set of regulatory options that could control these abnormal receptor activities would be therapeutically beneficial. Small molecule compounds have been developed over the past decades to modulate iGluR activity. These compounds, however, generally have low water solubility and low selectivity to differentiate subtypes, let alone subunits. In clinical settings, the use of these compounds has shown significant sides effects but no or low therapeutic efficacy. In particular, the development of modulators for kainate receptors lags far behind in the iGluR field, as compared with the development of modulators for either AMPA or NMDA receptors. For 2 example, virtually all compounds that have developed to date have higher selectivity towards the GluK1 kainate receptor subunit. In other words, no selective modulators have been developed towards the GluK2 subunit. Yet, the GluK2 kainate receptor subunit is the most prevalent kainate receptor subunit found throughout the brain. My doctoral thesis work concerns the development of RNA-based modulators of kainate receptors. Below, I will discuss how I used two different methods in developing RNA aptamers with higher potency and higher selectivity for kainate receptors, as compared with traditional, small molecule compounds. In Chapter 1, I will describe the classic use of systematic evolution of ligands by exponential enrichment (SELEX) in developing RNA aptamers for kainate receptors. Two separate SELEX runs were performed: one with homomeric GluK2 channels and the other with heteromeric GluK2/K5 channels (kainate receptors have 5 subunits, and GluK2/K5 is a major kainate receptor complex found in vivo). Both SELEX runs included the addition of both Neto1 and Neto2 proteins to increase the chance of finding selective RNA aptamers. To further increase the chance of finding useful aptamers that may have low copy numbers, the DNA libraries from individual rounds of SELEX operation were analyzed using Next-Generation Sequencing (NGS) approach, instead of traditional Sanger sequencing technique, which limits the number of DNA clones that could be detected and analyzed. In particular, I will describe that among all the new RNA aptamers I have isolated, S-A94, a 94 nucleotide (nt)-long RNA aptamer, is a kainate receptor aptamer: whole-cell current recording showed that S-A94 selectively potentiates the closed-channel GluK1 without affecting GluK2. Through mutational analysis, I found that the minimal, but fully functional, length of this aptamer is a 52 nt RNA. 3 In Chapter 2, I will describe a new method in developing highly selective RNA aptamers, including a GluK2 subunit-selective aptamer. This work was based on a previously identified RNA aptamer by our group, termed AB9s-b, which was the first molecular agent capable of inhibiting GluK1 and GluK2 equally potently. In the sequence of AB9s-b, it was discovered that a segment of RNA sequence is responsible for kainate receptor inhibition. This provided a unique platform to mutate this known sequence so that hopefully a mutated AB9s-b would exhibit an improved selectivity such that the newly developed RNA aptamer would become GluK2-selective without any cross activity towards any other subunits of iGluRs. Two sets of AB9s-b mutants were created. The first set consisted of sequence mutants in which three-base sequence segments were changed while maintaining the original secondary structure of AB9s-b. The second set were structural mutants where the sequence was maintained while the secondary structure was changed. The function of all the mutants were determined through whole-cell current recording using HEK-293 cells that express individual iGluRs. Between these two groups of mutants, a wide variety of aptamers with varying selectivity between GluK1 and GluK2 have been created. Of note is 3sb-U9 aptamer. 3sb-U9 was one of the sequence mutants with the loop of the hairpin motif mutated from the original AB9s-b mutant. 3sb-U9 was the first modulator with single subunit selectivity in that it uniquely potentiates GluK2 without any other cross activity for any other kainate subunits or any other AMPA or NMDA receptors. No molecular modulator with such a subunit selectivity has ever been reported in the field. Furthermore, with the help from molecular docking simulations, we have gained some understanding of how the interaction of 3sb-U9 with the GluK2 vs other kainate and AMPA receptors may have endowed this aptamer to be uniquely selective. In summary, my research has been able to develop new 4 methodology and identify new RNA aptamers for regulating kainate receptors. My work has shown that developing RNA aptamers is a promising approach to address the challenge of developing subunit-selective kainate receptor modulators, which has thus far defied the field