Biology subjects

Rasheed, M.

Publications and source records attributed to Rasheed, M..

5 recordsLinked to original sources

bioRxiv2025

Associations between amygdala connectivity and experienced discrimination in children

Discrimination is a chronic stressor linked to adverse health outcomes, particularly in racial and ethnic minorities. Understanding associations between early discrimination and the brain in childhood may help identify mechanisms through which discrimination impacts future health. Data from 4512 children (ages 9-11) and a subsample of Black, Indigenous, and People of Color (BIPOC; N = 1567) from the Adolescent Brain and Cognitive Development (ABCD) Study(R) was used to create linear mixed-effects models that evaluated associations between Perceived Discrimination (PD) and amygdala resting-state fMRI connectivity (AC) to the salience network (SN), default mode network (DMN), and thalamus. PD was measured using the youth self-reported PD Scale. Results indicated that greater PD significantly predicted greater AC to the right thalamus in our full sample. In secondary analyses, environmental and behavioral factors were evaluated as potential moderators for associations significant at least at a trend level in both our full sample and BIPOC subsample. In our BIPOC subsample, traumatic events experienced moderated the relationship between PD and AC to the anterior cingulate cortex (ACC; SN), such that greater traumatic experiences predicted stronger positive associations between PD and this connection. Results suggest PD impacts neural connections in early life, highlighting the need to consider the impact of discrimination on risk for psychopathology.

neuroscience↗

bioRxiv2024

Systemic and targeted activation of Nrf2 reverses doxorubicin-induced cognitive impairments and sensorimotor deficits in mice

While cancer survivorship has increased due to advances in treatments, chemotherapy often carries long-lived neurotoxic side effects which reduce quality of life. Commonly affected domains include memory, executive function, attention, processing speed and sensorimotor function, colloquially known as chemotherapy-induced cognitive impairment (CICI) or "chemobrain". Oxidative stress and neuroimmune signaling in the brain have been mechanistically linked to the deleterious effects of chemotherapy on cognition and sensorimotor function. With this in mind, we tested if activation of the master regulator of antioxidant response nuclear factor E2-related factor 2 (Nrf2) alleviates cognitive and sensorimotor impairments induced by doxorubicin. The FDA-approved systemic Nrf2 activator, diroximel fumarate (DRF) was used, along with our recently developed prodrug 1c which has the advantage of specifically releasing monomethyl fumarate at sites of oxidative stress. DRF and 1c both reversed doxorubicin-induced deficits in executive function, spatial and working memory, as well as decrements in fine motor coordination and grip strength, across both male and female mice. Both treatments reversed doxorubicin-induced loss of synaptic proteins and microglia phenotypic transition in the hippocampus. Doxorubicin-induced myelin damage in the corpus callosum was reversed by both Nrf2 activators. These results demonstrate the therapeutic potential of Nrf2 activators to reverse doxorubicin-induced cognitive impairments, motor incoordination, and associated structural and phenotypic changes in the brain. The localized release of monomethyl fumarate by 1c has the potential to diminish unwanted effects of fumarates while retaining efficacy.

neuroscience↗

bioRxiv2023

Modelling complex growth profiles of Bacteroides fragilis and Escherichia coli on various carbohydrates in an anaerobic environment

Previously published models for microbial growth focus only on either death or growth and are unable to account for differently shaped growth curves. Currently, there is no model capable of incorporating combinations of microbial growth trends. This study creates a bacterial growth model that incorporates growth, death, lag, and tail phases as well as applies this model to the growth trends of Bacteroides fragilis and Escherichia coli on 13 different carbohydrate substances. Growth trends were collected by measuring the optical densities over 72 hours for either B. fragilis or E. coli in a chemically defined media supplemented by a mono- or disaccharide. The Digital Environment to Enable Data-driven Science (DEEDS) platform was utilized to parse data and apply the developed model to obtain parameter values. E. coli was found to grow on the chemically defined media alone while B. fragilis was unable to grow on it alone. E. coli growth was led by 10 mM concentration of substrates while B. fragilis growth was substrate dependent. Bacterial death only occurred for B. fragilis but was found to be dependent on concentration for the two most significant substrates. A singular model was developed that does not require prior knowledge of metabolomics and is capable of incorporating a combination of growth and death trends.

microbiology↗

bioRxiv2019

Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11 allogeneic and 4 autologous HCT). Ascorbate levels declined post conditioning to 27.3 ({+/-}14.1) by day 0 (p <0.05 compared with baseline), reaching a nadir level of 21.5 ({+/-}13.8) on day 14 (p <0.05) post-transplant. Patients undergoing allogeneic HCT continued to have low AA levels to day 60 post transplant, whereas recipients of autologous HCT recovered plasma AA levels to normal. The role of AA in maintaining endothelial function and hematopoietic as well as T cell recovery is provided, developing the rationale for repletion of vitamin C following HCT.

physiology↗

bioRxiv2018

Antibody responses to the Zika virus polyprotein in pregnant and non-pregnant macaques

The specificity of the antibody response against Zika virus (ZIKV) is not well-characterized. This is due, in part, to the antigenic similarity between ZIKV and closely related dengue virus (DENV) serotypes. Since these and other similar viruses co-circulate, are spread by the same mosquito species, and can cause similar acute clinical syndromes, it is difficult to disentangle ZIKV-specific antibody responses from responses to closely-related arboviruses in humans. Here we use high-density peptide microarrays to profile anti-ZIKV antibody reactivity in pregnant and non-pregnant macaque monkeys with known exposure histories and compare these results to reactivity following DENV infection. We also compare cross-reactive binding of ZIKV-immune sera to the full proteomes of 28 arboviruses. We independently confirm a purported ZIKV-specific IgG antibody response targeting ZIKV nonstructural protein 2B (NS2B) that was recently reported in ZIKV-infected people and we show that antibody reactivity in pregnant animals can be detected as late as 127 days post-infection (dpi). However, we also show that these responses wane over time, sometimes rapidly, and in one case the response was elicited following DENV infection in a previously ZIKV-exposed animal. These results suggest epidemiologic studies assessing seroprevalence of ZIKV immunity using linear epitope-based strategies will remain challenging to interpret due to susceptibility to false positive results. However, the method used here demonstrates the potential for rapid profiling of proteome-wide antibody responses to a myriad of neglected diseases simultaneously and may be especially useful for distinguishing antibody reactivity among closely related pathogens.\n\nAuthor summaryZIKV has emerged as a vector-borne pathogen capable of causing serious illness in infected adults and congenital birth defects. The vulnerability of communities to future ZIKV outbreaks will depend, in part, on the prevalence and longevity of protective immunity, thought to be mediated principally by antibodies. We currently lack diagnostic assays able to differentiate ZIKV-specific antibodies from antibodies produced following infection with closely related DENV, and we do not know how long anti-ZIKV responses are detectable. Here we profile antibodies recognizing linear epitopes throughout the entire ZIKV polyprotein, and we profile cross-reactivity with the proteomes of other co-endemic arboviruses. We show that while ZIKV-specific antibody binding can be detected, these responses are generally weak and ephemeral, and false positives may arise through DENV infection. This may complicate efforts to discern ZIKV infection and to determine ZIKV seroprevalence using linear epitope-based assays. The method used in this study, however, has promise as a tool for profiling antibody responses for a broad array of neglected tropical diseases and other pathogens and in distinguishing serology of closely-related viruses.

microbiology↗