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Martinez, Bridget

Publications and source records attributed to Martinez, Bridget.

6 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of miRNAs had altered levels of expression in the brain and spinal cord, motor neurons of spinal cord and brainstem, and hypoglossal, facial, and red motor nuclei and were mostly upregulated. Among the miRNAs found to be upregulated in two of the studies were miR-21, miR-155, miR-125b, miR-146a, miR-124, miR-9, and miR-19b, while those downregulated in two of the studies included miR-146a, miR-29, miR-9, and miR-125b. A change of direction in miRNA expression occurred in some tissues when compared (e.g., miR-29b-3p in cerebellum and spinal cord of wobbler mice at 40 days), or at different disease stages (e.g., miR-200a in spinal cord of SOD1(G93A) mice at 95 days vs. 108 and 112 days). In the animal models, suppression of miR-129-5p resulted in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and tended to improve motor neuron survival in the SOD1(G93A) mouse model. Suppression of miR-155 was also associated with increased lifespan, while lowering of miR-29a tended to improve lifespan in males and increase muscle strength in SOD1(G93A) mice. Overexpression of members of miR-17~92 cluster improved motor neuron survival in SOD1(G93A) mice. Treatment with an artificial miRNA designed to target hSOD1 increased lifespan and improved muscle strength in SOD1(G93A) animals. Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific miRNAs whose suppression or directed against hSOD1 results in increased lifespan, improved muscle strength, reduced neuromuscular junction degeneration, and improved motor neuron survival in SOD1(G93A) animals.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex, and which were mostly downregulated. Among the altered microRNAs were miR-9/9*, miR-29b, miR-124a, miR-132, miR-128, miR-139, miR-122, miR-138, miR-23b, miR-135b, miR-181 (all downregulated) and miR-448 (upregulated), and similar changes had been previously found in Huntington’s disease patients. In the animal cell studies, the altered microRNAs included miR-9, miR-9*, miR-135b, miR-222 (all downregulated) and miR-214 (upregulated). In the animal models, overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level, lowered the mutant huntingtin aggregates in striatum and cortex, and improved performance in behavioral tests. Improved performance in behavioral tests also occurred with overexpression of miR-132 and miR-124. In the animal cell models, overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin -enriched foci of ≥ 2 µm. Also, overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic acid. Exogenous expression of miR-214, miR-146a, miR-150, and miR-125b decreased endogenous expression of huntingtin mRNA and protein in Hdh Q111 /Hdh Q111 cells. Further studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

MicroRNAs in laser-induced choroidal neovascularization in mice and rats: their expression and potential therapeutic targets

Choroidal neovascularization characterizes wet age-related macular degeneration. Choroidal neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis. A primary cause of choroidal neovascularization pathogenesis is alterations in pro- and anti-angiogenic factors derived from the retinal pigment epithelium, with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal neovascularization. MicroRNAs (miRNAs) which are short, non-coding, endogenous RNA molecules have a major role in regulating various pathological processes, including inflammation and angiogenesis. A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular degeneration. Upregulation of miR-505 (days 1 and 3 post-laser), miR-155 (day 14) occurred in retina; miR-342-5p (days 3 and 7), miR-126-3p (day 14) in choroid; miR-23a, miR-24, miR-27a (day 7) in retina/choroid; miR-505 (days 1 and 3) in retinal pigment epithelium/choroid; downregulation of miR-155 (days 1 and 3), miR-29a, miR-29b, miR-29c (day 5), miR-93 (day 14), miR-126 (day 14) occurred in retinal pigment epithelium/choroid. Therapies using miRNA mimics or inhibitors were found to decrease choroidal neovascularization lesions. Choroidal neovascularization development was reduced by overexpression of miR-155, miR-188-5p, miR-(5,B,7), miR-126-3p, miR-342-5p, miR-93, miR-126, miR-195a-3p, miR24, miR-21, miR-31, miR-150, and miR-184, or suppression of miR-505, miR-126-3p, miR155, and miR-23/27. Further studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported findings. Important experimental variables need to be standardized; these include the strain and age of animals, gender, number and position of laser burns to the eye, laser parameters to induce choroidal neovascularization lesions including wavelength, power, spot size, and duration.

therapeutic targets↗
DOE OSTI2020

MicroRNAs as diagnostic and prognostic biomarkers of age-related macular degeneration: advances and limitations

A main cause of vision loss in the elderly is age-related macular degeneration (AMD). Among the cellular, biochemical, and molecular changes linked to this disease, inflammation and angiogenesis appear as being crucial in AMD pathogenesis and progression. There are two forms of the disease: dry AMD, accounting for 80–90% of cases, and wet AMD. The disease usually begins as dry AMD associated with retinal pigment epithelium and photoreceptor degeneration, whereas wet AMD is associated with choroidal neovascularization resulting in severe vision impairment. The new vessels are largely malformed, leading to blood and fluid leakage within the disrupted tissue, which provokes inflammation and scar formation and results in retinal damage and detachment. MicroRNAs are dysregulated in AMD and may facilitate the early detection of the disease and monitoring disease progression. Two recent reviews of microRNAs in AMD had indicated weaknesses or limitations in four earlier investigations. Studies in the last three years have shown considerable progress in overcoming some of these concerns and identifying specific microRNAs as biomarkers for AMD. Further large-scale studies are warranted using appropriate statistical methods to take into account gender and age disparity in the study populations and confounding factors such as smoking status.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

A holistic cyber-physical security protocol for authenticating the provenance and integrity of structural health monitoring imagery data

Modern infrastructure systems, such as bridges, dams, power generation stations, and buildings increasingly have an intrinsic cyber-physical nature to them. Infrastructure now commonly, includes actuators, network connections, sensors, control systems, and computational resources. It is of increasing concern that modern infrastructure is vulnerable to cyber-attacks that can damage both the cyber and physical nature of the infrastructure. To date, the physical and cyber health of infrastructure has been considered separately. However, the increasing concerns associated with the cyber-physical security of infrastructure coupled with the emergence of 5G networks made using components that are not universally considered trustworthy, and the emergence of techniques for creating deepfakes and adversarial examples suggests the time has come to begin considering cyber health and structural health with a more holistic approach. In this work, a protocol is developed for ensuring the imagery data captured by a structural health monitoring system can be unambiguously attributed to legitimate sensors associated with the structural health monitoring system. A computer vision approach based on the idea of mutual information is then presented to detect damage in an image. This work presents the protocol for authenticating the provenance of imager data and demonstrates that this protocol does not have overly adverse effects when used with the mutual information-based technique for detecting damage in the resulting imagery data.

Jung, HweeKwon↗