Effects of Apolipoprotein E, Sex, and Estrogen on the Neuroplasticity of Olfactory Receptor Neurons in Mice Following Olfactory Bulbectomy

Apolipoprotein E (apoE) is well studied for its role in cholesterol transportation and metabolizing lipoproteins. ApoE is found in the olfactory system especially in the olfactory nerve and glomeruli of the olfactory bulb. Studies from our laboratory indicate that apoE is a required component for timely regeneration and olfactory receptor neuron maturation. The mechanism for which apoE contributes to neuron function and developing late onset Alzheimer\u27s disease is still being studied. A mutant form of apoE (apoE 4) is believed to be a prominent genetic risk factor for this neurodegenerative disease. Over sixty percent of Alzheimer\u27s disease patients in the United Sates are women. This revelation has concentrated more focus on the loss of estrogen as a potential risk factor. To better understand how apoE and estrogen may contribute to Alzheimer\u27s disease, this study utilizes apoE knockout mice and estradiol treatment. Using the olfactory system as a model, the right olfactory bulb was removed from all treatments of wild type (WT) and apoE knockout (KO) mice. Retrograde olfactory receptor neuron death and regeneration was observed between males and females of both genotypes in the olfactory epithelium. The results show massive olfactory receptor neuron death within days of olfactory bulb ablation in male mice compared to their female counter part. When estrogen was given at above the physiological dose, the duration of neuroprotection increased. However, when no estrogen was present olfactory receptor neurons died faster. Overall, mice treated with estrogen exhibited a more rapid rate of regeneration regardless of the presence of apoE. Animals without apoE illustrated similar results to those with apoE but the average data values were slightly lower for apoE knockout mice than WTmice, illustrating that apoE is required for proper olfactory epithelium maintenance. These results were fairly consistent 4 throughout the data; however data for estradiol treated animals varied among genotypes. To measure the rate of olfactory receptor neuron death olfactory epithelium thickness was measured at 3, 7 and 21 days following olfactory bulbectomy. To observe the rate of death of mature olfactory receptor neurons olfactory marker protein (OMP) immunohistochemistry was performed. To gauge the rate of globose basal (stem) cell division bromodeoxyuridine (BrdU) immunohistochemistry was performed. By removing the olfactory bulb, the target for olfactory receptor neuron which served as the signal transduction, the olfactory epithelium fails to return to its original thickness suggesting olfactory receptor neuron maturity is dependent on proper target connectivity

Effects of Apolipoprotein E, Sex, and Estrogen on the Neuroplasticity of Olfactory Receptor Neurons in Mice Following Olfactory Bulbectomy

Apolipoprotein E (apoE) is well studied for its role in cholesterol transportation and metabolizing lipoproteins. ApoE is found in the olfactory system especially in the olfactory nerve and glomeruli of the olfactory bulb. Studies from our laboratory indicate that apoE is a required component for timely regeneration and olfactory receptor neuron maturation. The mechanism for which apoE contributes to neuron function and developing late onset Alzheimer\u27s disease is still being studied. A mutant form of apoE (apoE 4) is believed to be a prominent genetic risk factor for this neurodegenerative disease. Over sixty percent of Alzheimer\u27s disease patients in the United Sates are women. This revelation has concentrated more focus on the loss of estrogen as a potential risk factor. To better understand how apoE and estrogen may contribute to Alzheimer\u27s disease, this study utilizes apoE knockout mice and estradiol treatment. Using the olfactory system as a model, the right olfactory bulb was removed from all treatments of wild type (WT) and apoE knockout (KO) mice. Retrograde olfactory receptor neuron death and regeneration was observed between males and females of both genotypes in the olfactory epithelium. The results show massive olfactory receptor neuron death within days of olfactory bulb ablation in male mice compared to their female counter part. When estrogen was given at above the physiological dose, the duration of neuroprotection increased. However, when no estrogen was present olfactory receptor neurons died faster. Overall, mice treated with estrogen exhibited a more rapid rate of regeneration regardless of the presence of apoE. Animals without apoE illustrated similar results to those with apoE but the average data values were slightly lower for apoE knockout mice than WTmice, illustrating that apoE is required for proper olfactory epithelium maintenance. These results were fairly consistent 4 throughout the data; however data for estradiol treated animals varied among genotypes. To measure the rate of olfactory receptor neuron death olfactory epithelium thickness was measured at 3, 7 and 21 days following olfactory bulbectomy. To observe the rate of death of mature olfactory receptor neurons olfactory marker protein (OMP) immunohistochemistry was performed. To gauge the rate of globose basal (stem) cell division bromodeoxyuridine (BrdU) immunohistochemistry was performed. By removing the olfactory bulb, the target for olfactory receptor neuron which served as the signal transduction, the olfactory epithelium fails to return to its original thickness suggesting olfactory receptor neuron maturity is dependent on proper target connectivity

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Microstructure-based approach for predicting crack initiation and early growth in metals.

Fatigue cracking in metals has been and is an area of great importance to the science and technology of structural materials for quite some time. The earliest stages of fatigue crack nucleation and growth are dominated by the microstructure and yet few models are able to predict the fatigue behavior during these stages because of a lack of microstructural physics in the models. This program has developed several new simulation tools to increase the microstructural physics available for fatigue prediction. In addition, this program has extended and developed microscale experimental methods to allow the validation of new microstructural models for deformation in metals. We have applied these developments to fatigue experiments in metals where the microstructure has been intentionally varied

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit