Frequency of Genetic Variants at the MC1R Locus in a Student Population

The Melanocortin-1 Receptor gene (MC1R) encodes a protein that is associated with pigmentation in vertebrate animals. An extraordinary number of variations in this gene have arisen over time due to the importance of pigmentation in camouflage, photosensitivity, vitamin D production, and other evolutionary factors. Variations in the MC1R gene sequence became important to survival as humans migrated out of Africa and into cooler climates with less sun exposure, where lighter skin pigmentation (and therefore more vitamin D production) was key to survival. These genetic variations (alleles) continue to exist in modern humans. Recent research into the MC1R gene variations shows that variants occur at different frequencies in different human populations. For example, a variant named R151C occurs in about 9% of humans of European descent but is not detected in humans of Asian descent.https://scholarworks.moreheadstate.edu/celebration_posters_2022/1012/thumbnail.jp

Formation of viable cell fragments by treatment with colchicine

Time-lapse cinematography of human fibroblasts revealed that mitotic cells separated into numerous cell fragments containing varying amounts of chromatin and cytoplasm when treated with colchicine. As cell fragments were very loosely attached to the surface of the culture vessel during their formation, they could be easily detached like mitotic cells by gently shaking the vessel and thus separated from normal interphase cells. Fragments obtained by this procedure were able to exclude trypan blue indicating, therefore, an intact cell membrane. When placed into Petri dishes many of them attached to and even spread out on the surface. Five hours later the majority of the attached fragments incorporated [3H]leucine. Time-lapse films showed that fragments were able to extend and retract pseudopodia at least for several hours after their formation. Although the fragments degenerated within a few days, in the present experiments the possibility was not excluded that fragments which had lost only a very small amount of chromatin and cytoplasm survived for longer periods of time. The observations clearly indicate viability of many newly formed fragments

Denying renal transplantation to an adolescent medical cannabis user: An ethical case study

Medical cannabis is now legal in over half of the United States. As more patients adopt this unconventional therapy, it is inevitable that potential transplant recipients will disclose their cannabis use during transplant evaluation. Transplant teams are tasked with the decision to utilize a pressure resource, often with little guidance from international and national professional organizations. Many healthcare providers remain uniformed or misinformed about the risks of cannabis use and organ transplantation. In order to illustrate the multifaceted and complex evaluation of transplant patients using medical cannabis, this article presents the case of a 20‐year‐old woman recommended for renal transplant who was originally denied active listing due to her medical cannabis use. A review of the literature explores the perceived and actual risks of cannabis use in the immunocompromised patient. Furthermore, a discussion of the ethics of medical cannabis use and organ transplantation is included with recommendations for multidisciplinary transplant teams.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150568/1/petr13467.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150568/2/petr13467_am.pd

The association of polymorphism rs3736228 within the LRP5 gene with Bone Mineral Density in a Cohort of Caucasian Young Adults

INTRODUCTION: Osteoporosis is a significant burden for our aging population. Developing a better understanding of the genetic underpinnings of poor bone quality may assist in the future development of prevention strategies. Correa-Rodriguez et al. have identified a group of single nucleotide polymorphisms (SNPs) that were associated with bone mineral density (BMD) in a population of Spanish Caucasians. In particular, they found that SNP rs3736228 in the low-density lipoprotein receptor related protein 5 (LRP5) gene had an influence on BMD. While the role of LRP5 in the Wnt canonical pathway has been fairly well characterized, its association with phenotypic BMD and osteoporosis has only been explored in a limited fashion. The aim of this study is to expand on this, and to replicate the findings of previous studies in a cohort of healthy young adults. METHODS: Cohort: The University of Calgary cohort from the Assessing Inherited Metabolic Syndrome Markers in the Young (UC AIMMY) study. Participants included consist of 168 healthy, predominantly Caucasian young adults. Phenotypes: height, weight, BMI, and total BMD. Genotyping: Allelic discrimination was determined. Statistical Analysis: After being tested for Hardy-Weinberg equilibrium (HWE), the data was run through analysis of covariance (ANCOVA). RESULTS: Using a dominant model, we found that females with one or more copies of the risk T allele of SNP rs3736228 had a significant negative association with total BMD (p = 0.0347). However, a similar association was not seen in males in this cohort. We did not find a significant association for this polymorphism and height, weight, or BMI. DISCUSSION: Polymorphisms in rs3736228 alter the codon in position 1330, downregulating the LRP5 cell surface receptor function. The LRP5 gene has now been shown in multiple studies to be associated with bone quality measures like calcaneal Qualitative Ultrasound (QUS) and BMD. Our study suggests that SNP rs3736228 also influences BMD in healthy young females. This supports the work of Correa-Rodriguez et al that found that when stratifying by sex, females only showed a trend towards significance (p = 0.092) in QUS measures. SIGNIFICANCE: This study expands our understanding of the importance of LRP5 rs3736228 polymorphisms in BMD by extending its relationship to a cohort of predominantly Caucasian college students. While the development of BMD is polygenic, this work broadened the role of SNP rs3736228 across the age span, and the sexual dimorphism seen in musculoskeletal traits

CONSIDERATIONS FOR GROUT FORMULATIONS FOR FACILITY CLOSURES USING IN SITU STRATEGIES

The U.S. Department of Energy (DOE) is conducting in situ closures (entombment) at a large number of facilities throughout the complex. Among the largest closure actions currently underway are the closures of the P and R Reactors at the Savannah River Site (SRS), near Aiken, South Carolina. In these facilities, subgrade open spaces are being stabilized with grout; this ensures the long term structural integrity of the facilities and permanently immobilizes and isolates residual contamination. The large size and structural complexity of these facilities present a wide variety of challenges for the identification and selection of appropriate fill materials. Considerations for grout formulations must account for flowability, long term stability, set times, heat generation and interactions with materials within the structure. The large size and configuration of the facility necessitates that grout must be pumped from the exterior to the spaces to be filled, which requires that the material must retain a high degree of flowability to move through piping without clogging while achieving the required leveling properties at the pour site. Set times and curing properties must be controlled to meet operations schedules, while not generating sufficient heat to compromise the properties of the fill material. The properties of residual materials can result in additional requirements for grout formulations. If significant quantities of aluminum are present in the facility, common formulations of highly alkaline grouts may not be appropriate because of the potential for hydrogen generation with the resultant risks. SRS is developing specialized inorganic grout formulations that are designed to address this issue. One circum-neutral chemical grout formulation identified for initial consideration did not possess the proper chemical characteristics, having exceptionally short set times and high heat of hydration. Research efforts are directed toward developing grout formulations that can meet operational requirements for chemical compatibility, extended set times and reduced heat generation

Sustaining knowledge in the neutron generator community and benchmarking study.

In 2004, the Responsive Neutron Generator Product Deployment department embarked upon a partnership with the Systems Engineering and Analysis knowledge management (KM) team to develop knowledge management systems for the neutron generator (NG) community. This partnership continues today. The most recent challenge was to improve the current KM system (KMS) development approach by identifying a process that will allow staff members to capture knowledge as they learn it. This 'as-you-go' approach will lead to a sustainable KM process for the NG community. This paper presents a historical overview of NG KMSs, as well as research conducted to move toward sustainable KM

Translating Research on Myoelectric Control into Clinics-Are the Performance Assessment Methods Adequate?

Missing an upper limb dramatically impairs daily-life activities. Significant efforts in overcoming the issues arising from this disability have been made in both academia and industry, although their clinical outcome is still limited. Translation of prosthetic research into clinics has been challenging because of the difficulties in meeting the necessary requirements of the market. In this perspective, we focus on myocontrol algorithms for upper limb prostheses and we emphasize that one relevant factor determining the relatively small clinical impact of these methods is the limit of commonly used laboratory performance metrics. The laboratory conditions, in which the majority of the solutions are being evaluated, fail to sufficiently replicate real-life challenges. We qualitatively substantiate this argument with data from seven transradial amputees. Their ability to control a myoelectric prosthesis was tested by measuring the accuracy of offline EMG signal classification, as a typical laboratory performance metrics, as well as by clinical scores when performing standard tests of daily living. Despite all subjects reached relatively high classification accuracy offline, their clinical scores were largely different and were not strongly predicted by classification accuracy. As argued in previous reports, we reinforce the suggestion to test myocontrol systems using clinical tests on amputees, fully fitted with sockets and prostheses highly resembling the systems they would use in daily living, as evaluation benchmark. Agreement on this level of testing for systems developed in research laboratories would facilitate clinically relevant progresses in this field.<br

Astrocyte-mediated short-term synaptic depression in the rat hippocampal CA1 area: two modes of decreasing release probability

<p>Abstract</p> <p>Background</p> <p>Synaptic burst activation feeds back as a short-term depression of release probability at hippocampal CA3-CA1 synapses. This short-term synaptic plasticity requires functional astrocytes and it affects both the recently active (< 1 s) synapses (post-burst depression) as well as inactive neighboring synapses (transient heterosynaptic depression). The aim of this study was to investigate and compare the components contributing to the depression of release probability in these two different scenarios.</p> <p>Results</p> <p>When tested using paired-pulses, following a period of inactivity, the transient heterosynaptic depression was expressed as a reduction in the response to only the first pulse, whereas the response to the second pulse was unaffected. This selective depression of only the first response in a high-frequency burst was shared by the homosynaptic post-burst depression, but it was partially counteracted by augmentation at these recently active synapses. In addition, the expression of the homosynaptic post-burst depression included an astrocyte-mediated reduction of the pool of release-ready primed vesicles.</p> <p>Conclusions</p> <p>Our results suggest that activated astrocytes depress the release probability via two different mechanisms; by depression of vesicular release probability only at inactive synapses and by imposing a delay in the recovery of the primed pool of vesicles following depletion. These mechanisms restrict the expression of the astrocyte-mediated depression to temporal windows that are typical for synaptic burst activity.</p