Assessing the pathogenicity of a disease-associated genetic variant in animals accurately is vital, both on a population and individual scale. At the population level, breeding decisions based on invalid DNA tests can lead to the incorrect inclusion or exclusion of animals and compromise the long-term health of a population, and at the level of the individual animal, lead to incorrect treatment and even life-ending decisions. Criteria to determine pathogenicity are not standardized, i.
View Article and Find Full Text PDFRecent paleobotanical discoveries have renewed interest in the distinctively recurved, seed-bearing cupules of Mesozoic plants, which are important for understanding seed plant phylogeny and the origin of the second integument of the angiosperm ovule. Reanalysis of the enigmatic seed-bearing organ Dordrechtites elongatus from the Triassic of South Africa, the type species of the genus, combined with information from similar material from Antarctica, Argentina and Australia, indicates that Dordrechtites is a highly modified lateral branch of a seed cone. Short lateral projections from a primary cone axis each bear several Dordrechtites units.
View Article and Find Full Text PDFPrevailing theories about animal foraging behaviours and the food webs they occupy offer divergent predictions about whether seasonally limited food availability promotes dietary diversification or specialization. Emphasis on how animals compete for food predominates in work on the foraging ecology of large mammalian herbivores, whereas emphasis on how the diversity of available foods generally constrains dietary opportunity predominates work on entire food webs. Reconciling predictions about what promotes dietary diversification is challenging because species' different body sizes and mobilities modulate how they seek and compete for resources-the mechanistic bases of common predictions may not pertain to all species equally.
View Article and Find Full Text PDFThe mitochondria-ER-cortex anchor (MECA) forms a tripartite membrane contact site between mitochondria, the endoplasmic reticulum (ER), and the plasma membrane (PM). The core component of MECA, Num1, interacts with the PM and mitochondria via two distinct lipid-binding domains; however, the molecular mechanism by which Num1 interacts with the ER is unclear. Here, we demonstrate that Num1 contains a FFAT motif in its C-terminus that interacts with the integral ER membrane protein Scs2.
View Article and Find Full Text PDFCats with a distinctive white hair pattern of unknown molecular cause have been discovered in the Finnish domestic cat population. Based on the unique appearance of these cats, we have named this phenotype salmiak ("salty licorice"). The use of a commercially available panel test to genotype four salmiak-colored cats revealed the absence of all known variants associated with white-haired phenotypic loci: full White (W), Spotting (W) and the Birman white Gloves associated (w) allele of the KIT proto-oncogene (KIT) gene.
View Article and Find Full Text PDFIntroduction: The correct labeling of a genetic variant as pathogenic is important as breeding decisions based on incorrect DNA tests can lead to the unwarranted exclusion of animals, potentially compromising the long-term health of a population. In human medicine, the American college of Medical Genetics (ACMG) guidelines provide a framework for variant classification. This study aims to apply these guidelines to six genetic variants associated with hypertrophic cardiomyopathy (HCM) in certain cat breeds and to propose a modified criterion for variant classification.
View Article and Find Full Text PDFHypertension control remains poor. Multiple barriers at the level of patients, providers, and health systems interfere with implementation of hypertension guidelines and effective lowering of BP. Some strategies such as self-measured blood pressure (SMBP) and remote management by pharmacists are safe and effectively lower BP but have not been effectively implemented.
View Article and Find Full Text PDFThe coat color phenotype 'sable' occurs in the English Cocker Spaniel dog breed. It closely resembles other canine color patterns known as domino/grizzle/pied (e allele) and grizzle/domino (e allele) determined by variants in the melanocortin 1 receptor gene (MC1R; 'extension' or E locus), a key multi-allele regulator of coat color. We examined genetic variation in MC1R, and found one new non-synonymous variant, c.
View Article and Find Full Text PDFGlucose metabolism is critical for the African trypanosome, , serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against ENO (ENO) and found the compounds to be potent enzyme inhibitors and trypanocides.
View Article and Find Full Text PDFHundreds of genetic variants associated with canine traits and disorders have been identified, with commercial tests offered. However, the geographic distributions and changes in allele and genotype frequencies over prolonged, continuous periods of time are lacking. This study utilized a large set of genotypes from dogs tested for the progressive rod-cone degeneration-progressive retinal atrophy (prcd-PRA) G>A missense variant ( = 86,667) and the collie eye anomaly (CEA)-associated deletion ( = 33,834) provided by the commercial genetic testing company (Optigen/Wisdom Panel, Mars Petcare Science & Diagnostics).
View Article and Find Full Text PDFHundreds of genetic variants implicated in Mendelian disease have been characterized in dogs and commercial screening is being offered for most of them worldwide. There is typically limited information available regarding the broader population frequency of variants and uncertainty regarding their functional and clinical impact in ancestry backgrounds beyond the discovery breed. Genetic panel screening of disease-associated variants, commercially offered directly to the consumer or via a veterinary clinician, provides an opportunity to establish large-scale cohorts with phenotype data available to address open questions related to variant prevalence and relevance.
View Article and Find Full Text PDFIntroduction: Implementing a health system-based hypertension programme may lower blood pressure (BP).
Methods: We performed a randomized, controlled pilot study to assess feasibility, acceptability, and safety of a home-based virtual hypertension programme integrating evidence-based strategies to overcome current barriers to BP control. Trained clinical pharmacists staffed the virtual collaborative care clinic (vCCC) to remotely manage hypertension using a BP dashboard and phone "visits" to monitor BP, adherence, side effects of medications, and prescribe anti-hypertensives.
In the largest DNA-based study of domestic cats to date, 11,036 individuals (10,419 pedigreed cats and 617 non-pedigreed cats) were genotyped via commercial panel testing elucidating the distribution and frequency of known disease, blood type, and physical trait associated genetic variants across cat breeds. This study provides allele frequencies for many disease-associated variants for the first time and provides updates on previously reported information with evidence suggesting that DNA testing has been effectively used to reduce disease associated variants within certain pedigreed cat populations over time. We identified 13 disease-associated variants in 47 breeds or breed types in which the variant had not previously been documented, highlighting the relevance of comprehensive genetic screening across breeds.
View Article and Find Full Text PDFPositioning organelles at the right place and time is critical for their function and inheritance. In budding yeast, mitochondrial and nuclear positioning require the anchoring of mitochondria and dynein to the cell cortex by clusters of Num1. We have previously shown that mitochondria drive the assembly of cortical Num1 clusters, which then serve as anchoring sites for mitochondria and dynein.
View Article and Find Full Text PDFBackground: Dog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.
View Article and Find Full Text PDFWe examined the impact of an APOE ε4 genotype on Alzheimer's disease (AD) subject platelet and lymphocyte metabolism. Mean platelet mitochondrial cytochrome oxidase Vmax activity was lower in APOE ε4 carriers and lymphocyte Annexin V, a marker of apoptosis, was significantly higher. Proteins that mediate mitophagy and energy sensing were higher in APOE ε4 lymphocytes which could represent compensatory changes and recapitulate phenomena observed in post-mortem AD brains.
View Article and Find Full Text PDFLeishmaniasis is a vector-borne parasitic disease caused by protozoa of the genus Leishmania. Twenty different species are known to cause disease in humans with varying degrees of pathology. These diseases are transmitted throughout the geographic range of phlebotomine sandflies, found between the latitudes 50°N and 40°S.
View Article and Find Full Text PDFBackground: The Melanocortin 1 Receptor (MC1R) plays a central role in regulation of coat color determination in various species and is commonly referred to as the "E (extension) Locus". Allelic variation of the MC1R gene is associated with coat color phenotypes E (melanistic mask), E (grizzle/domino) and e (recessive red) in dogs. In addition, a previous study of archeological dog specimens over 10,000 years of age identified a variant p.
View Article and Find Full Text PDFGiven unprecedented rates of biodiversity loss, there is an urgency to better understand the ecological consequences of interactions among organisms that may lost or altered. Positive interactions among organisms of the same or different species that directly or indirectly improve performance of at least one participant can structure populations and communities and control ecosystem process. However, we are still in need of synthetic approaches to better understand how positive interactions scale spatio-temporally across a range of taxa and ecosystems.
View Article and Find Full Text PDFBackground: Discrete breed ideals are not restricted to delimiting dog breeds from another, but also are key drivers of subpopulation differentiation. As genetic differentiation due to population fragmentation results in increased rates of inbreeding and loss of genetic diversity, detecting and alleviating the reasons of population fragmentation can provide effective tools for the maintenance of healthy dog breeds.
Results: Using a genome-wide SNP array, we detected genetic differentiation to subpopulations in six breeds, Belgian Shepherd, English Greyhound, Finnish Lapphund, Italian Greyhound, Labrador Retriever and Shetland Sheepdog, either due to geographical isolation or as a result of differential breeding strategies.
Introduction: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking.
Methods: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability.
Enzymes play important roles in many biological processes. Amino acid residues in the active site pocket of an enzyme, which are in direct contact with the substrate(s), are generally believed to be critical for substrate recognition and catalysis. Identifying and understanding how these "catalytic" residues help enzymes achieve enormous rate enhancement has been the focus of many structural and biochemical studies over the past several decades.
View Article and Find Full Text PDFCanine coat color is a readily observed phenotype of great interest to dog enthusiasts; it is also an excellent avenue to explore the mechanisms of genetics and inheritance. As such, multiple commercial testing laboratories include basic color alleles in their popular screening panels, allowing for the creation of genotyped datasets at a scale not before appreciated in canine genetic research. These vast datasets have revealed rare genotype anomalies that encourage further exploration of color and pattern inheritance.
View Article and Find Full Text PDFDirect-to-consumer canine genetic testing is becoming increasingly popular among dog owners. The data collected therein provides intriguing insight into the current status of morphological variation present within purebred populations. Mars WISDOM PANELTM data from 11,790 anonymized dogs, representing 212 breeds and 4 wild canine species, were evaluated at genes associated with 7 coat color traits and 5 physical characteristics.
View Article and Find Full Text PDF