The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.

Although the spliceogenic nature of the BRCA2 c.68-7T>A variant has been demonstrated, its association with cancer risk remains ontroversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T>A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 x 10-115. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T>A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants

Understanding evolutionary processes during past Quaternary climatic cycles: Can it be applied to the future?

Climate change affected ecological community make-up during the Quaternary which was probably both the cause of, and was caused by, evolutionary processes such as species evolution, adaptation and extinction of species and populations

URB597 Administration decreases neuroinflammation and promotes autophagy in Alzheimer's disease models

In recent years, much attention has been focused on the endocannabinoid system as a therapeutic target for neurodegenerative diseases, including Alzheimer's disease (AD). The first endocannabinoid to be characterized was anandamide (N -arachidonoyl ethanolamine, AEA), which is hydrolyzed in postsynaptic neurons by the fatty acid amide hydrolase (FAAH). Notably, the post-mortem examination of brains from AD patients has revealed several alterations of the endocannabinoid system reporting a decrease in cortical AEA levels and a parallel increase in FAAH activity. On this ground, by using both cellular and a transgenic mouse model of AD, we aimed at determining whether pharmacological inhibition of FAAH via URB597 administration may affect microglia polarization and provide beneficial effects in restoring autophagic process and reducing amyloid-β (Aβ) aggregates, which are all neuropathological features of AD. The evaluation of morphological and major markers of microglial activation (iNOS and ARG-1) showed the ability of URB597 to revert microglial activation towards an anti-inflammatory condition, which was associated with the decrease of pro-inflammatory cytokines and an increase of anti-inflammatory cytokines together with the restoration of key factors involved in autophagic processes. These data were confirmed in vivo in the Tg2576 mice where the broad-spectrum action of endocannabinoids ranging from the anti-inflammatory action to the restoration of autophagic flux was demonstrated by the increase of proteins such as ATG7, Beclin1, LC3 and activation of ULK1 signaling following mTOR decrease after URB597 treatment. Moreover, treatment with URB597 decreases the expression of BACE1 through the modulation of CB2 receptors, leading to the reduction of amyloid plaques. Taken together, these data suggest that inhibition of FAAH can drive the polarization of microglia towards an anti-inflammatory phenotype and demonstrate that the modulation of the endocannabinoid system in AD, via URB597 administration, could be a potential and effective therapy not only to fight neuroinflammation but also to regulate the autophagic machinery

Classification Models for Plant Diseases Diagnosis: A Review

Plants are important source of our life. Crop production in a good figure and good quality is important to us. The diagnosis of a disease in a plant can be manual or automatic. But manual detection of disease in a plant is not always correct as sometimes it can be not be seen by naked eyes so an automatic method of detection of plant diseases should be there. It can make use of various artificial intelligence based or machine learning based methods. It is a tedious task as it needs to be identified in earlier stage so that it will not affect the entire crop. Disease affects all species of plant, both cultivated and wild. Plant disease occurrence and infection severity vary seasonally, regarding the environmental circumstances, the kinds of crops cultivated, and the existence of the pathogen. This review attempts to provide an exhaustive review of various plant diseases and its types, various methods to diagnose plant diseases and various classification models used so as to help researchers to identify the areas of scope where plant pathology can be improved

Clemson Catalog, 2007-2008, Volume 82

https://tigerprints.clemson.edu/clemson_catalog/1157/thumbnail.jp

The Best of All Breathing: Hunting and Environmental Change in Mississippi 1900-1980

This thesis examines hunting in Mississippi with regard to the changing relationship between humans and their environment. Hunting is the basic human interaction with nature. It is timeless activity, yet at the same time an activity deeply impacted by the human relation to the land. In approaching the change in hunting this thesis examined human population change by reviewing the demographic consequences of the rural exodus in addition to the response of animal populations to the human exodus and to the restocking efforts of wildlife biologists. At the same time that people were leaving the farms, organized game conservation was working to replace such wildlife as deer and turkeys that had declined in the face of the agrarian population. A regrowth in large game populations and a decline in small game populations was at once a product and accompanying process of the changing (rural to urban) lifestyle. Hunting existed through either extreme of the relationship to land, from the early diffuse agrarian lifestyle to the later urban non-agricultural mode. During the early relationship to the land, hunting was characterized by an intensive harvest of mostly small game according to the available leisure and subsistence requirements of the agricultural cycle. Property rights were less prevalent than the concept of a communal right to game. After the rural exodus people hunted larger game according to seasons determined more by scientific precepts of wildlife conservation and during times dictated by non- agricultural work regimens. Property rights likewise became more important than the idea of communal ownership of game. As the character of hunting took on more modern aspects, the ethical systems professed by hunters became more concerned with the preservation of the game and thus the experience of hunting. Earlier ethical systems among non-subsistence hunters usually emphasized fair play in the taking of animals. Later, hunters became more concerned with the continued survival of game and therefore absorbed the ideals of conservation into the sporting ethos. For later hunters ethical hunting must not only maintain the legitimating circumstances of possible death and possible escape for the animal, it must not endanger the overall health of the game population

Determination of Time Dependent Stress Distribution on Potato Tubers at Mechanical Collision

This study focuses on determining internal stress progression and the realistic representation of time dependent deformation behaviour of potato tubers under a sample mechanical collision case. A reverse engineering approach, physical material tests and finite element method (FEM)-based explicit dynamics simulations were utilised to investigate the collision based deformation characteristics of the potato tubers. Useful numerical data and deformation visuals were obtained from the simulation results. The numerical results are presented in a format that can be used for the determination of bruise susceptibility magnitude on solid-like agricultural products. The modulus of elasticity was calculated from experimental data as 3.12 [MPa] and simulation results showed that the maximum equivalent stress was 1.40 [MPa] and 3.13 [MPa] on the impacting and impacted tubers respectively. These stress values indicate that bruising is likely on the tubers. This study contributes to further research on the usage of numerical-methods-based nonlinear explicit dynamics simulation techniques in complicated deformation and bruising investigations and industrial applications related to solid-like agricultural products

Clemson Catalog, 2010-2011, Volume 85

https://tigerprints.clemson.edu/clemson_catalog/1160/thumbnail.jp