Understanding the development of teaching and learning resources: A review

This paper is a literature review of research concerned with the production of learning resources in higher education (HE). It forms part of a larger research project in progress

The Effects of in Vitro Fish Oil and Dietary Fish Meal Supplementation on Microdomains Within Bovine Luteal Cells

Lipid microdomains are regions of plasma membrane rich in cholesterol and sphingolipids, ranging in size from 10–200 nm in diameter. These structures serve as platforms to facilitate co-localization of intracellular signaling proteins during agonistinduced signal transduction. The omega-3 polyunsaturated fatty acids are a distinct class of fatty acids that have been shown to incorporate into lipid microdomains, disrupting the structural integrity of domains, and possibly attenuation of cell signaling. Fish byproducts, such as fish oil or meal, are a rich source of omega-3 polyunsaturated fatty acids that can be supplemented into cell cultures and diets of breeding females as a means for incorporating fatty acids into reproductive tissues. In chapter 2, we report that 0.03% (v/v) fish oils disrupt the spatial distribution of lipid microdomain and increases the lateral mobility of the prostaglandin (PG) F2α (FP) receptor, which was unaffected by PGF2α treatment. In charter 3, we report that fish oil inhibited PGF2α-induced mitogenactivated protein kinase (MAPK) signaling and disrupt PGF2α-induced receptor internalization and endosomal trafficking of the FP receptor in bovine luteal cells. In chapter 4, we examined the effect of individual omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on disruption of lipid microdomains and lateral mobility of the FP receptor. We found that 10 and 100 μM EPA and DHA equally disrupts lipid microdomains and increase the lateral mobility of the FP receptor. Additionally, this disruption was equivalent to media supplementation of fish oil. Taken together, we found that supplementing cultured bovine luteal cells with fish oil leads to disruption of lipid microdomains, localization, and increases lateral mobility of the FP receptor, while attenuating PGF2α-induced MAPK signaling and receptor internalization. The effect of dietary fish meal supplementation on structural integrity of lipid microdomains, lateral mobility of the FP receptor, and luteal sensitivity to intrauterine infusions of PGF2α are reported in Chapters 5 through 7. In Chapter 5, We report that fish oil and meal disrupted both lipid-lipid and lipid-protein interactions within lipid microdomains, translocating ganglioside, GM1, and critical structural proteins (flotillin and caveolin) from lipid microdomain regions of plasma membrane into bulk lipid fractions. Additionally, we show that omega-3 polyunsaturated fatty acids, EPA and DHA, incorporated into bulk lipid fractions forming EPA- and DHA-rich domains. These EPA- and DHA-rich domains have a poor affinity for cholesterol, which resulted in translocation of cholesterol from bulk lipid into lipid microdomains. Next, we examined the effect of dietary supplementation on spatial distribution of lipid microdomains and the lateral mobility of the FP receptor. In Chapter 6, it was demonstrated that dietary supplementation of fish meal effected the fatty acid composition in luteal cells which lead to disruption in spatial distribution of lipid microdomains, and increased the lateral mobility of the FP receptor. Lastly, the final experiment investigated the effects of supplementation of fish meal on the structural and functional regression of the corpus luteum following intrauterine infusion of low doses of PGF2α. In chapter 7, we report that dietary supplementation of fish meal decreases luteal sensitivity to intrauterine infusions of PGF2α that prevented 54% of CL from functional regression and maintained progesterone production (progesterone per CL volume) from 0 to 48 h. Taken together, manipulation of lipid microdomains, FP receptor dynamics, and decreased luteal sensitivity to PGF2α may lead to the development of methods for increasing reproductive efficiency in breeding cattle

Mitochondrial Fusion Promotes Steroidogenesis in MA10 Leydig Cells

Infertility affects 1 out of every 6 couples, worldwide, with male infertility playing a primary factor in a third of all cases. Dysregulation of sex hormones is a major cause of infertility. Male hypogonadism is a condition in which the testis does not produce adequate concentrations of testosterone. Males suffering from hypogonadism can be born with the condition or develop it later in life, often from acute injury or infection. Male hypogonadism is treated with testosterone replacement to return testosterone levels to normal. However, one side effect of testosterone treatment is infertility. Understanding mechanisms that regulate the synthesis of sex steroids holds great potential to positively impact reproductive health and overall quality of life. Mitochondria play a key role in the synthesis of all steroid hormones. The first and rate-limiting step in the production of all steroid hormones is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane. In the current study, we examined the hypothesis that mitochondrial fusion promotes acute steroid synthesis in LH-responsive Leydig cells.https://digitalcommons.unmc.edu/surp2022/1005/thumbnail.jp

Cost, health impacts and cost effectiveness of iceless refrigeration in India's last-mile vaccine cold chain delivery

Background: Compared with ice-based vaccine carriers (IBVCs), iceless vaccine carrier (ILVC) last-mile delivery could optimize vaccine effectiveness by reducing spoilage. We estimated ILVC-associated spoilage costs averted and cost effectiveness. Methods: IBVC vaccine spoilage costs were estimated for six vaccines. ILVC incremental costs were based on yearly ILVC cost over total doses. Cost effectiveness was estimated via Markov modeling of rotavirus vaccine. Results: The spoilage cost using IBVCs was USD9 603 294. Using ILVCs, the incremental cost per vaccine dose was USD0.026, the cost-benefit ratio was 0.28, the number of averted disability-adjusted life years was 0.03 per child and there was a saving of USD0.80 per child vaccinated. Conclusions: ILVCs may bring cost savings and health gains compared with IBVCs

Some Aspects of Liquefaction Assessment of Duncan Dam

A comprehensive program of field, laboratory and analytical investigations was carried out to assess the potential for liquefaction of the foundation soils and seismic stability of Duncan Dam. Duncan Oam is located on Duncan River in southeastern British Columbia, Canada. The 39 m high zoned earthfill dam is founded on a thick sequence of sands, silts and gravels. The liquefaction studies were carried out in two phases between 1988 and 1992 to characterize in detail the engineering properties of the foundation soils; and to assess its potential for triggering liquefaction, and the post liquefaction stability and deformation of the dam using parameters based on two approaches; one a site specific laboratory based direct method (Lab.method) and the other an indirect method (Seed\u27s method) which is based on field penetration data and field experience during past earthquakes. This paper describes some advanced aspects of the field and laboratory investigations including laboratory testing of undisturbed soil samples obtained after freezing the ground insitu. The influence of confining stress (K0) and initial static shear stress (K0) on liquefaction were investigated and site specific correlations for K0 and K. are presented. The laboratory investigations indicate that the residual strengths of the liquefied sand is a function of initial consolidation stress

Ground Improvement by Dynamic Compaction at a Tailings Disposal Facility

This paper presents two case histories of ground improvement by dynamic compaction (DC) at the Myra Falls mine in Vancouver Island, British Columbia, Canada. Dynamic compaction was employed to densify soils at two sites within the operating mine: a waste rock dump beneath a new processing plant to reduce settlements beneath the structure foundations (Site A); and coarse fluvial and colluvial soils at the toe of an existing tailings embankment to improve seismic resistance against liquefaction (Site B). At Site A, the variable plant loadings required variable compaction energy to achieve uniform foundation performance. At Site B, the foundation soils contained some fine grained soils that dictated a time-controlled sequential DC approach to allow excess pore pressures to dissipate between passes. Because of large uncertainties in the expected performance of DC at both sites, a fair and cost effective DC contract based on unit price per energy was adopted, instead of the traditional performance-based lump sum price contract. This paper describes the ground conditions at the two sites, DC methodologies employed, and ground improvement performance based on measurements of crater volumes and pre- and post-densification in-situ testing by Becker Penetration Tests

Protein Kinase A and 59 AMP-Activated Protein Kinase Signaling Pathways Exert Opposite Effects on Induction of Autophagy in Luteal Cells

In the absence of pregnancy the ovarian corpus luteum undergoes regression, a process characterized by decreased production of progesterone and structural luteolysis involving apoptosis. Autophagy has been observed in the corpus luteum during luteal regression. Autophagy is a self-degradative process important for balancing sources of cellular energy at critical times in development and in response to nutrient stress, but it can also lead to apoptosis. Mechanistic target of rapamycin (MTOR) and 5′ AMP-activated protein kinase (AMPK), key players in autophagy, are known to inhibit or activate autophagy, respectively. Here, we analyzed the signaling pathways regulating the initiation of autophagy in bovine luteal cells. In vivo studies showed increased activating phosphorylation of AMPKα (Thr172) and elevated content of LC3B, a known marker of autophagy, in luteal tissue during PGF2α-induced luteolysis. In vitro, AMPK activators 1) stimulated phosphorylation of regulatory associated protein of MTOR (RPTOR) leading to decreased activity of MTOR, 2) increased phosphorylation of Unc-51-Like Kinase 1 (ULK1) and Beclin 1 (BECN1), at sites specific for AMPK and required for autophagy initiation, 3) increased levels of LC3B, and 4) enhanced colocalization of autophagosomes with lysosomes indicating elevated autophagy. In contrast, LH/PKA signaling in luteal cells 1) reduced activation of AMPKα and phosphorylation of RPTOR, 2) elevated MTOR activity, 3) stimulated phosphorylation of ULK1 at site required for ULK1 inactivation, and 4) inhibited autophagosome formation as reflected by reduced content of LC3B-II. Pretreatment with AICAR, a pharmacological activator of AMPK, inhibited LH-mediated effects on RPTOR, ULK1 and BECN1. Our results indicate that luteotrophic signaling via LH/PKA/MTOR inhibits, while luteolytic signaling via PGF2α/Ca2+/AMPK activates key signaling pathways involved in luteal cell autophagy

Yes-associated protein 1 is required for proliferation and function of bovine granulosa cells in vitro

Yes-associated protein 1 (YAP1) is a major component of the Hippo signaling pathway. Although the exact extracellular signals that control the Hippo pathway are currently unknown, increasing evidence supports a critical role for the Hippo pathway in embryonic development, regulation of organ size, and carcinogenesis. Granulosa cells (GCs) within the ovarian follicle proliferate and produce steroids and growth factors, which facilitate the growth of follicle and maturation of the oocyte.We hypothesize that YAP1 plays a role in proliferation and estrogen secretion of GCs. In the current study, we examined the expression of the Hippo signaling pathway in bovine ovaries and determined whether it was important for GC proliferation and estrogen production. Mammalian STE20-like protein kinase 1 (MST1) and large tumor suppressor kinase 2 (LATS2) were identified as prominent upstream components of the Hippo pathway expressed in granulosa and theca cells of the follicle and large and small cells of the corpus luteum. Immunohistochemistry revealed that YAP1 was localized to the nucleus of growing follicles. In vitro, nuclear localization of the downstream Hippo signaling effector proteins YAP1 and transcriptional co-activator with PDZbinding motif (TAZ) was inversely correlated with GC density, with greater nuclear localization under conditions of low cell density. Treatment with verteporfin and siRNA targeting YAP1 or TAZ revealed a critical role for these transcriptional co-activators in GC proliferation. Furthermore, knockdown of YAP1 in GCs inhibited follicle-stimulating hormone (FSH)-induced estradiol biosynthesis. The data indicate that Hippo pathway transcription co-activators YAP1/TAZ play an important role in GC proliferation and estradiol synthesis, two processes necessary for maintaining normal follicle development

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptormediated activation of PINK–Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility

Flow pumping system for physiological waveforms

A pulsatile flow pumping system is developed to replicate flow waveforms with reasonable accuracy for experiments simulating physiological blood flows at numerous points in the body. The system divides the task of flow waveform generation between two pumps: a gear pump generates the mean component and a piston pump generates the oscillatory component. The system is driven by two programmable servo controllers. The frequency response of the system is used to characterize its operation. The system has been successfully tested in vascular flow experiments where sinusoidal, carotid, and coronary flow waveforms are replicated