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Full-Text Articles in Life Sciences
Genetic Effects Mediated Through Epistatic Networks Onto Metabolic Traits, Juan Francisco Macias-Velasco
Genetic Effects Mediated Through Epistatic Networks Onto Metabolic Traits, Juan Francisco Macias-Velasco
Arts & Sciences Electronic Theses and Dissertations
Predicting variation in complex traits from DNA sequence is a major public health goal, but our understanding of the genotype-to-phenotype relationship is incomplete. It will remain so unless we can adequately integrate genetic, epigenetic, and environmental information into a systems level framework. In a step towards that goal, quantitative trait mapping studies have attempted to account for environmental factors such as sex and diet, and epigenetic factors such as allelic parent-of-origin effects. Several studies used an advanced intercross of the LG/J and SM/J inbred mouse strains to unravel the genetic architecture of multiple metabolic traits. These studies found that parent-of-origin …
A Study On The Hormonal Regulation And Novel Role Of Na+ Leak Channel, Non-Selective (Nalcn) In Human Myometrial Smooth Muscle Cells, Chinwendu Amazu
A Study On The Hormonal Regulation And Novel Role Of Na+ Leak Channel, Non-Selective (Nalcn) In Human Myometrial Smooth Muscle Cells, Chinwendu Amazu
Arts & Sciences Electronic Theses and Dissertations
During pregnancy, the uterus transitions from a quiescent state to an excitable, highly contractile state to deliver the fetus. Two important contributors essential for this transition are progesterone (P4) and estrogen (E2), which promote quiescence or contraction, respectively, by acting on the myometrial smooth muscle cells (MSMCs). While these hormones regulate uterine contractions, it is unclear how they affect electrical activity of MSMCs, which underlies uterine contractile activity. Our lab recently identified Na+ leak channel, non-selective (NALCN) as a component of the leak current in human MSMCs and showed that mice lacking NALCN in the uterus have dysfunctional labor. In …
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
The Role Of Neuronal Atp-Sensitive Potassium Channels In Learning And Memory, Shaul Vladimir Yahil
Arts & Sciences Electronic Theses and Dissertations
ATP-sensitive potassium (KATP) channels link cellular metabolism and membrane excitability in many tissues, including brain and pancreas. Gain-of-function (GOF) mutations to KATP channels cause neonatal diabetes, with some patients exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Diabetic symptoms have been attributed to loss of membrane excitability and insulin secretion in pancreatic β-cells, though the origin of neurological deficits and the effects of neuronal KATP-GOF mutations more generally remain elusive. In this dissertation, I will present evidence that mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited predominantly learning and memory deficits. …
Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda
Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda
Arts & Sciences Electronic Theses and Dissertations
Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Retinal Ganglion Cells Underlying Visual Perception And Predation In Mice, Keith Patrick Johnson
Arts & Sciences Electronic Theses and Dissertations
The spike trains of retinal ganglion cells (RGCs) are the sole source of visual information to the brain. In mice, more than 40 RGC types send signals to more than 50 brain areas. RGCs that perform nonlinear operations to extract specific visual features (e.g., the motion of an object against a background) are called feature detectors. Those that linearly integrate local changes in light inten-sity are known as pixel encoders. Most mouse RGC types are feature detectors. In the first part of my dissertation, I discovered a pixel encoder RGC type in mice, the PixON-RGC. I revealed how the unique …