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Probiotics are one of the management tools to improve the host's healthy microbiota. The positive effects of probiotics on host health are speciesspecific, so probiotics isolated from host's own gut may be most beneficial. Many of the metabolites (e.g., short-chain fatty acids, bacteriocins, and hydrogen peroxide) produced by Lactobacillus johnsonii have specific inhibitory profiles against invading pathogens. In this study, we isolated L. johnsonii GJ231 from the intestinal tract of healthy female beagles. The genome size of 1.763 M encoded a total of 1,691 predicted genes. Many carbohydrate-active enzymes responsible for carbohydrate degradation and the production of short-chain fatty acids were also predicted. The metabolic profile of short-chain fatty acids in L. johnsonii GJ231 was determined using LC-MS/MS. The bacteriocinproducing gene bacteriocin (lactacin F) in L. johnsonii GJ231 was also predicted. In vitro, experiments demonstrated that GJ231 can thrive in weak acids, 0.3% bile salts, and artificial gastrointestinal fluid models. It was tolerant of to high temperatures up to 70℃, was non-hemolytic, inhibited pathogenic bacteria, and had a high antioxidant capacity. In vivo safety experiments conducted in mice revealed that oral administration of GJ231 not only had no toxic side effect but also increased their antioxidant capacity. In conclusion, combining the above test results, which collectively demonstrate that canine-derived L. johnsonii GJ231 was a non-pathogenic, acid-tolerant and bile-salt-tolerant probiotic strain that inhibits pathogenic bacteria and improves host antioxidant function. This may make it a promising candidate for the development of innovative functional foods for pets. [ABSTRACT FROM AUTHOR]

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy. [ABSTRACT FROM AUTHOR]

There is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 108 CFU/day/dog), MG group (2 × 109 CFU/day/dog), and HG group (2 × 1010 CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups (p < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group (p < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups (p < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups (p < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The a diversity and the relative abundances of beneficial bacteria (Faecalibacterium, Lachnospiraceae_NK4A1316, and Ruminococcaceae_UCG-005) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups (p < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group (p < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals. [ABSTRACT FROM AUTHOR]

This report presents the first case of nodular dermatofibrosis with renal cysts (NDRC) in a beagle. In this atypical case, the gene mutation associated with the disease was not present, the renal cysts showed dynamic changes in size and number, and the patient has greatly surpassed the NDRC life expectation. [ABSTRACT FROM AUTHOR]

Phylogenies are central to many research areas in biology and commonly estimated using likelihood-based methods. Unfortunately, any likelihood-based method, including Bayesian inference, can be restrictively slow for large datasets—with many taxa and/or many sites in the sequence alignment—or complex substitutions models. The primary limiting factor when using large datasets and/or complex models in probabilistic phylogenetic analyses is the likelihood calculation, which dominates the total computation time. To address this bottleneck, we incorporated the high-performance phylogenetic library BEAGLE into RevBayes , which enables multi-threading on multi-core CPUs and GPUs, as well as hardware specific vectorized instructions for faster likelihood calculations. Our new implementation of RevBayes+BEAGLE retains the flexibility and dynamic nature that users expect from vanilla RevBayes. In addition, we implemented native parallelization within RevBayes without an external library using the message passing interface (MPI); RevBayes+MPI. We evaluated our new implementation of RevBayes+BEAGLE using multi-threading on CPUs and 2 different powerful GPUs (NVidia Titan V and NVIDIA A100) against our native implementation of RevBayes+MPI. We found good improvements in speedup when multiple cores were used, with up to 20-fold speedup when using multiple CPU cores and over 90-fold speedup when using multiple GPU cores. The improvement depended on the data type used, DNA or amino acids, and the size of the alignment, but less on the size of the tree. We additionally investigated the cost of rescaling partial likelihoods to avoid numerical underflow and showed that unnecessarily frequent and inefficient rescaling can increase runtimes up to 4-fold. Finally, we presented and compared a new approach to store partial likelihoods on branches instead of nodes that can speed up computations up to 1.7 times but comes at twice the memory requirements. [ABSTRACT FROM AUTHOR]

Using existing software technologies for imputing missing genetic data (GD), such as Beagle, HPImpute, Impute, MACH, AlphaPlantImpute, MissForest, and LinkImputeR, has its advantages and disadvantages. The wide range of input parameters and their nonlinear dependence on the target results require a lot of time and effort to find optimal values in each specific case. Thus, optimizing resources for GD imputation and improving its quality is an important current issue for the quality analysis of digitized deoxyribonucleic acid (DNA) samples. This work provides a critical analysis of existing methods and approaches for obtaining high-quality imputed GD. We observed that most of them do not investigate the problem of time and resource costs, which play a significant role in a mass approach. It is also worth noting that the considered articles are often characterized by high development complexity and, at times, unclear (or missing) descriptions of the input parameters for the methods, algorithms, or models under consideration. As a result, two algorithms were developed in this work. The first one aims to optimize the imputation time, allowing for real-time solutions, while the second one aims to improve imputation accuracy by selecting the best results at each iteration. The success of the first algorithm in improving imputation speed ranges from 47% (for small files) to 87% of the time (for medium and larger files), depending on the available resources. For the second algorithm, the accuracy has been improved by about 0.1%. This, in turn, encourages continued research on the latest version of Beagle software, particularly in the selection of optimal input parameters and possibly other models with similar or higher imputation accuracy. [ABSTRACT FROM AUTHOR]

Abstract This report presents the first case of nodular dermatofibrosis with renal cysts (NDRC) in a beagle. In this atypical case, the gene mutation associated with the disease was not present, the renal cysts showed dynamic changes in size and number, and the patient has greatly surpassed the NDRC life expectation.

Con la vuelta de la democracia y la llegada de Alfonsín al gobierno comenzó un nuevo tiempo en la Argentina. Su administración implementó todas las herramientas que estuvieron al alcance para que se lleven a la práctica mecanismos democráticos. Una de ellas fue la consulta popular que se llevó a cabo en el marco de las negociaciones para firmar el Tratado de Paz y Amistad con Chile, país con el que estaba en litigio hacía más de 100 años por el Canal de Beagle. El presente trabajo se propone recordar ese momento a partir de la memoria de los colaboradores directos de Alfonsín, al cumplirse 40 años de democracia en nuestro país.

Osteoarthritis (OA) affects >500 million people globally, and this number is expected to increase. OA management primarily focuses on symptom alleviation, using non-steroidal anti-inflammatory drugs, including Celecoxib. However, such medication has serious side effects, emphasizing the need for disease-specific treatment. The meniscectomy and cranial cruciate ligament transection (CCLx)-treated beagle dog was used to investigate the efficacy of a modified-release formulation of SKI306X (SKCPT) from Clematis mandshurica, Prunella vulgaris, and Trichosanthes kirilowii in managing arthritis. SKCPT's anti-inflammatory and analgesic properties have been assessed via stifle circumference, gait, incapacitance, histopathology, and ELISA tests. The different SKCPT concentrations and formulations also affected the outcome. SKCPT improved the gait, histopathological, and ELISA OA assessment parameters compared to the control group. Pro-inflammatory cytokines and matrix metalloproteinases were significantly lower in the SKCPT-treated groups than in the control group. This study found that SKCPT reduces arthritic lesions and improves abnormal gait. The 300 mg modified-release formulation was more efficacious than others, suggesting a promising approach for managing OA symptoms and addressing disease pathogenesis. A high active ingredient level and a release pattern make this formulation effective for twice-daily arthritis treatment. [ABSTRACT FROM AUTHOR]

Markov models of character substitution on phylogenies form the foundation of phylogenetic inference frameworks. Early models made the simplifying assumption that the substitution process is homogeneous over time and across sites in the molecular sequence alignment. While standard practice adopts extensions that accommodate heterogeneity of substitution rates across sites, heterogeneity in the process over time in a site-specific manner remains frequently overlooked. This is problematic, as evolutionary processes that act at the molecular level are highly variable, subjecting different sites to different selective constraints over time, impacting their substitution behavior. We propose incorporating time variability through Markov-modulated models (MMMs), which extend covarion-like models and allow the substitution process (including relative character exchange rates as well as the overall substitution rate) at individual sites to vary across lineages. We implement a general MMM framework in BEAST, a popular Bayesian phylogenetic inference software package, allowing researchers to compose a wide range of MMMs through flexible XML specification. Using examples from bacterial, viral, and plastid genome evolution, we show that MMMs impact phylogenetic tree estimation and can substantially improve model fit compared to standard substitution models. Through simulations, we show that marginal likelihood estimation accurately identifies the generative model and does not systematically prefer the more parameter-rich MMMs. To mitigate the increased computational demands associated with MMMs, our implementation exploits recent developments in BEAGLE, a high-performance computational library for phylogenetic inference. [Bayesian inference; BEAGLE; BEAST; covarion, heterotachy; Markov-modulated models; phylogenetics.].

This brief communication describes a rare spontaneous background lesion in the lower urinary tract of two male laboratory beagles. Proliferative lesions comprising a constellation of histological features consistent with polypoid cystitis were observed in the bladder of two adolescent dogs from a routine preclinical toxicology study. Both animals were clinically asymptomatic and had only minor alterations in urinalysis parameters. While chronic polypoid cystitis is well-recognized in adult pet dogs, this is the first reported case in purpose-bred laboratory beagles. An awareness of this uncommon background finding is important for toxicological pathologists to distinguish it from potential test article-related findings. [ABSTRACT FROM AUTHOR]

Infections with HIV-1 group M subtype B viruses account for the majority of the HIV epidemic in the Western world. Phylogeographic studies have placed the introduction of subtype B in the United States in New York around 1970, where it grew into a major source of spread. Currently, it is estimated that over one million people are living with HIV in the US and that most are infected with subtype B variants. Here, we aim to identify the drivers of HIV-1 subtype B dispersal in the United States by analyzing a collection of 23,588 pol sequences, collected for drug resistance testing from 45 states during 2004-2011. To this end, we introduce a workflow to reduce this large collection of data to more computationally-manageable sample sizes and apply the BEAST framework to test which covariates associate with the spread of HIV-1 across state borders. Our results show that we are able to consistently identify certain predictors of spread under reasonable run times across datasets of up to 10,000 sequences. However, the general lack of phylogenetic structure and the high uncertainty associated with HIV trees make it difficult to interpret the epidemiological relevance of the drivers of spread we are able to identify. While the workflow we present here could be applied to other virus datasets of a similar scale, the characteristic star-like shape of HIV-1 phylogenies poses a serious obstacle to reconstructing a detailed evolutionary and spatial history for HIV-1 subtype B in the US.

Nonparametric coalescent-based models are often employed to infer past population dynamics over time. Several of these models, such as the skyride and skygrid models, are equipped with a block-updating Markov chain Monte Carlo sampling scheme to efficiently estimate model parameters. The advent of powerful computational hardware along with the use of high-performance libraries for statistical phylogenetics has, however, made the development of alternative estimation methods feasible. We here present the implementation and performance assessment of a Hamiltonian Monte Carlo gradient-based sampler to infer the parameters of the skygrid model. The skygrid is a popular and flexible coalescent-based model for estimating population dynamics over time and is available in BEAST 1.10.5, a widely-used software package for Bayesian pylogenetic and phylodynamic analysis. Taking into account the increased computational cost of gradient evaluation, we report substantial increases in effective sample size per time unit compared to the established block-updating sampler. We expect gradient-based samplers to assume an increasingly important role for different classes of parameters typically estimated in Bayesian phylogenetic and phylodynamic analyses.

IntroductionWhile oxidative stress has been studied in pathologic conditions in dogs, data in presumably healthy dogs and standardized protocols are lacking. This work purposed to bridge the gap by presenting provisional physiological ranges for oxidative stress biomarkers in a group of Beagle dogs.MethodsBased on our long-standing clinical expertise in the field of oxidative stress, nine plasma biomarkers of oxidative stress were evaluated for their concentrations (mean ± SD) in 14 healthy adult Beagle dogs.ResultsSelected biomarkers were: vitamins C (7.90 ± 1.36 μg/mL) and E (34.1 ± 6.63 μg/mL), zinc (0.80 ± 0.17 mg/L), copper (0.54 ± 0.048 mg/L), selenium (256 ± 25.7 μg/L), total and oxidized glutathione (822 ± 108 μM and 3.56 ± 1.76 μM), myeloperoxidase (67.4 ± 56.2 ng/mL), and isoprostanes (340 ± 95.3 ng/mL). Glutathione peroxidase activity and superoxide anion production in whole blood were also measured. Glutathione peroxidase activity was 473 ± 34.0 IU/g of hemoglobin and superoxide anion production in whole blood was 18,930 ± 12,742 counts per 30 min. Reduced glutathione/oxidized glutathione and copper/zinc ratios were, respectively, 280 ± 139 and 0.70 ± 0.15. Sex-related differences were recorded for zinc (p = 0.0081), copper/zinc ratio (p = 0.0036) and plasma isoprostanes (p = 0.0045).ConclusionProvisional physiological norms covering 95% of our group were proposed for each biomarker and should be of interest for future studies of canine oxidative stress.

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Extraintestinal pathogenic Escherichia coli expressing cytotoxic necrotizing factor (CNF) 1 and 2 virulence factors is a rarely reported cause of acute, fatal necrohemorrhagic pneumonia in canines. A review of cases of necrohemorrhagic pneumonia in beagles at our facility between 2013 and 2021 revealed 21 dogs that died or were euthanized after acute onset lethargy, dyspnea, and hemorrhage. Some affected animals had recently been transported to the facility. In all dogs, lung lobes were discolored dark red and consolidated. Histologic lesions in 17 of these included alveolar necrosis, hemorrhage, edema, fibrin, acute inflammation, and intralesional colonies of bacilli. Lung was cultured for 10 dogs with E. coli isolated and CNF1 identified by virulence factor PCR in 7 of those. Based on these findings, extraintestinal E. coli should be considered an important cause of acute fatal necrohemorrhagic pneumonia in purpose-bred beagle research dogs and may be associated with a recent history of transport. [ABSTRACT FROM AUTHOR]

Using existing software technologies for imputing missing genetic data (GD), such as Beagle, HPImpute, Impute, MACH, AlphaPlantImpute, MissForest, and LinkImputeR, has its advantages and disadvantages. The wide range of input parameters and their nonlinear dependence on the target results require a lot of time and effort to find optimal values in each specific case. Thus, optimizing resources for GD imputation and improving its quality is an important current issue for the quality analysis of digitized deoxyribonucleic acid (DNA) samples. This work provides a critical analysis of existing methods and approaches for obtaining high-quality imputed GD. We observed that most of them do not investigate the problem of time and resource costs, which play a significant role in a mass approach. It is also worth noting that the considered articles are often characterized by high development complexity and, at times, unclear (or missing) descriptions of the input parameters for the methods, algorithms, or models under consideration. As a result, two algorithms were developed in this work. The first one aims to optimize the imputation time, allowing for real-time solutions, while the second one aims to improve imputation accuracy by selecting the best results at each iteration. The success of the first algorithm in improving imputation speed ranges from 47% (for small files) to 87% of the time (for medium and larger files), depending on the available resources. For the second algorithm, the accuracy has been improved by about 0.1%. This, in turn, encourages continued research on the latest version of Beagle software, particularly in the selection of optimal input parameters and possibly other models with similar or higher imputation accuracy.

Osteoarthritis (OA) affects >500 million people globally, and this number is expected to increase. OA management primarily focuses on symptom alleviation, using non-steroidal anti-inflammatory drugs, including Celecoxib. However, such medication has serious side effects, emphasizing the need for disease-specific treatment. The meniscectomy and cranial cruciate ligament transection (CCLx)-treated beagle dog was used to investigate the efficacy of a modified-release formulation of SKI306X (SKCPT) from Clematis mandshurica, Prunella vulgaris, and Trichosanthes kirilowii in managing arthritis. SKCPT’s anti-inflammatory and analgesic properties have been assessed via stifle circumference, gait, incapacitance, histopathology, and ELISA tests. The different SKCPT concentrations and formulations also affected the outcome. SKCPT improved the gait, histopathological, and ELISA OA assessment parameters compared to the control group. Pro-inflammatory cytokines and matrix metalloproteinases were significantly lower in the SKCPT-treated groups than in the control group. This study found that SKCPT reduces arthritic lesions and improves abnormal gait. The 300 mg modified-release formulation was more efficacious than others, suggesting a promising approach for managing OA symptoms and addressing disease pathogenesis. A high active ingredient level and a release pattern make this formulation effective for twice-daily arthritis treatment.

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern of cognitive maintenance and duration of their effect, there was improvement in spatial learning, as well as maintenance of memory, attention, and working memory relative to placebo dogs. CN/NFAT inhibition is a promising target for prevention of cognitive decline that may be rapidly implemented in human clinical trials., Competing Interests: Declaration of Competing Interest Personal financial interest as LGP is the main shareholder of one of Aperus Pharma Co. Ltd’s company shares., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Probiotics are one of the management tools to improve the host's healthy microbiota. The positive effects of probiotics on host health are species-specific, so probiotics isolated from host's own gut may be most beneficial. Many of the metabolites (e.g., short-chain fatty acids, bacteriocins, and hydrogen peroxide) produced by Lactobacillus johnsonii have specific inhibitory profiles against invading pathogens. In this study, we isolated L. johnsonii GJ231 from the intestinal tract of healthy female beagles. The genome size of 1.763 M encoded a total of 1,691 predicted genes. Many carbohydrate-active enzymes responsible for carbohydrate degradation and the production of short-chain fatty acids were also predicted. The metabolic profile of short-chain fatty acids in L. johnsonii GJ231 was determined using LC-MS/MS. The bacteriocin-producing gene bacteriocin (lactacin F) in L. johnsonii GJ231 was also predicted. In vitro , experiments demonstrated that GJ231 can thrive in weak acids, 0.3% bile salts, and artificial gastrointestinal fluid models. It was tolerant of to high temperatures up to 70°C, was non- hemolytic, inhibited pathogenic bacteria, and had a high antioxidant capacity. In vivo safety experiments conducted in mice revealed that oral administration of GJ231 not only had no toxic side effect but also increased their antioxidant capacity. In conclusion, combining the above test results, which collectively demonstrate that canine-derived L. johnsonii GJ231 was a non-pathogenic, acid-tolerant and bile-salt-tolerant probiotic strain that inhibits pathogenic bacteria and improves host antioxidant function. This may make it a promising candidate for the development of innovative functional foods for pets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Li, Zhang and Li.)

A simple, rapid, efficient and reproducible method based on High Performance Liquid Chromatography (HPLC) for simultaneous determination of prodrug of voriconazole (POV) and voriconazole in beagle plasma has been established and validated. Omeprazole was utilized as the sole internal standard. Analytes and internal standards were extracted through protein precipitation and separated on a Venusil XBP C18 chromatography column (4.6 × 250 mm, 5 μm). The mobile phase was methanol and 20 mmol/L potassium dihydrogen phosphate. Chromatographic separation was achieved by using an isocratic elution procedure that used 65% methanol and a flow rate of 1 mL/min. The ultraviolet (UV) detection wavelength was 256 nm and the total running time was 15 min. This method showed good linear ranges of 100-75,000 ng/mL for voriconazole prodrug and 200-100,000 ng/mL for voriconazole respectively. The precision and accuracy were acceptable. Analytes in plasma samples are stable under different temperatures and storage conditions. The developed HPLC method has been successfully applied to the studies of toxicokinetics of POV after intravenous drip in beagle and provided important information for the further development and application. [ABSTRACT FROM AUTHOR]

Imputation may be used to rescue genomic data from animals that would otherwise be eliminated due to a lower than desired call rate. The aim of this study was to compare the accuracy of genotype imputation for Afrikaner, Brahman, and Brangus cattle of South Africa using within- and multiple-breed reference populations. A total of 373, 309, and 101 Afrikaner, Brahman, and Brangus cattle, respectively, were genotyped using the GeneSeek Genomic Profiler 150 K panel that contained 141,746 markers. Markers with MAF ≤ 0.02 and call rates ≤ 0.95 or that deviated from Hardy Weinberg Equilibrium frequency with a probability of ≤ 0.0001 were excluded from the data as were animals with a call rate ≤ 0.90. The remaining data included 99,086 SNPs and 360 Afrikaner, 75,291 SNPs and 288 animals Brahman, and 97,897 SNPs and 99 Brangus animals. A total of 7986, 7002, and 7000 SNP from 50 Afrikaner and Brahman and 30 Brangus cattle, respectively, were masked and then imputed using BEAGLE v3 and FImpute v2. The within-breed imputation yielded accuracies ranging from 89.9 to 96.6% for the three breeds. The multiple-breed imputation yielded corresponding accuracies from 69.21 to 88.35%. The results showed that population homogeneity and numerical representation for within and across breed strategies, respectively, are crucial components for improving imputation accuracies. [ABSTRACT FROM AUTHOR]

In vitro models of animals vulnerable to SARS-CoV-2 infection can support the characterization of effective antiviral drugs, such as synthetic inhibitors of the transmembrane protease serine 2 (TMPRSS2). Changes in cytochrome P450 (CYP) 1A2 activities in the presence of the potential TMPRSS2/matriptase inhibitors (MI) were measured using fluorometric and luminescent assays. Furthermore, the cytotoxicity of these inhibitors was evaluated using the MTS method. In addition, 60 min-long microsomal stability assays were performed using an UPLC-MS/MS procedure to elucidate depletion rates of the inhibitors. CYP1A2 was influenced significantly by MI-463 and MI-1900 in rat microsomes, by MI-432 and MI-482 in beagle microsomes, and by MI-432, MI-463, MI-482, and MI-1900 in cynomolgus monkey microsomes. The IC50 values in monkey microsomes were 1.30 ± 0.14 µM, 2.4 ± 1.4 µM, 0.21 ± 0.09 µM, and 1.1 ± 0.8 µM for inhibitors MI-432, MI-463, MI-482, and MI-1900, respectively. The depletion rates of the parent compounds were lower than 50%, independently of the investigated animal species. The host cell factor TMPRSS2 is of key importance for the cross-species spread of SARS-CoV-2. Studies of the in vitro biotransformation of TMPRSS2 inhibitors provide additional information for the development of new antiviral drugs. [ABSTRACT FROM AUTHOR]

Genomic applications such as genomic selection and genome-wide association have become increasingly common since the advent of genome sequencing. The cost of sequencing has decreased in the past two decades; however, genotyping costs are still prohibitive to gathering large datasets for these genomic applications, especially in nonmodel species where resources are less abundant. Genotype imputation makes it possible to infer whole-genome information from limited input data, making large sampling for genomic applications more feasible. Imputation becomes increasingly difficult in heterozygous species where haplotypes must be phased. The practical haplotype graph (PHG) is a recently developed tool that can accurately impute genotypes, using a reference panel of haplotypes. We showcase the ability of the PHG to impute genomic information in the highly heterozygous crop cassava (Manihot esculenta). Accurately phased haplotypes were sampled from runs of homozygosity across a diverse panel of individuals to populate PHG, which proved more accurate than relying on computational phasing methods. The PHG achieved high imputation accuracy, using sparse skim-sequencing input, which translated to substantial genomic prediction accuracy in cross-validation testing. The PHG showed improved imputation accuracy, compared to a standard imputation tool Beagle, especially in predicting rare alleles. [ABSTRACT FROM AUTHOR]

Abstract Background The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel.

Imputation is one of the key steps in the preprocessing and quality control protocol of any genetic study. Most imputation algorithms were originally developed for the use in human genetics and thus are optimized for a high level of genetic diversity. Different versions of BEAGLE were evaluated on genetic datasets of doubled haploids of two European maize landraces, a commercial breeding line and a diversity panel in chicken, respectively, with different levels of genetic diversity and structure which can be taken into account in BEAGLE by parameter tuning. Especially for phasing BEAGLE 5.0 outperformed the newest version (5.1) which in turn also lead to improved imputation. Earlier versions were far more dependent on the adaption of parameters in all our tests. For all versions, the parameter ne (effective population size) had a major effect on the error rate for imputation of ungenotyped markers, reducing error rates by up to 98.5%. Further improvement was obtained by tuning of the parameters affecting the structure of the haplotype cluster that is used to initialize the underlying Hidden Markov Model of BEAGLE. The number of markers with extremely high error rates for the maize datasets were more than halved by the use of a flint reference genome (F7, PE0075 etc.) instead of the commonly used B73. On average, error rates for imputation of ungenotyped markers were reduced by 8.5% by excluding genetically distant individuals from the reference panel for the chicken diversity panel. To optimize imputation accuracy one has to find a balance between representing as much of the genetic diversity as possible while avoiding the introduction of noise by including genetically distant individuals.

Application of Genomic Selection among other selection methods mainly depends upon the cost of genotyping, as cheaper the cost more animals can be genotyped to increase reference population size. Imputation approaches have been useful in reducing the cost. Imputation strategies and GS have been comprehensively studied in several taurine dairy cattle populations but very limited information is available on Bos Indicus populations. Factors that affect the efficiency of imputation are population structure, linkage disequilibrium between markers, and marker density in target and reference SPN panels. For present study, INDUSCHIP-1, a customized Illumina bovine microarray chip for indigenous cattle breeds, designed by NDDB, Anand was used for genotyping Gir cattle in India. The objective of the study is to evaluate the performance of INDUSCHIP-1 for imputation to Illumina BovineHD and also to select an LD SNP panel useful to impute at INDUSCHIP-1 level in Gir cattle. A fivefold cross validation by masking genotypes of animals to keep either INDUSCHIP-1 SNPs or LD SNPs and imputing to either HD level or at INDUSCHIP-1 level respectively, was performed. Population-based imputation algorithm BEAGLE was used without including pedigree information. Imputation accuracies evaluated as concordance level (allele correct rate expressed in percentage). All imputation accuracy, represented as % concordance between actual genotypes and imputed genotypes were showed as an average of five replicates for each chromosome. Mean concordance of 92.33% was observed when INDUSCHIP-1 genotypes were imputed at Illumina HD 777K level. The use of INDUSCHIP-1 as a HD Panel resulted in the accuracy of 88.42%. SNP selection criteria used for LD panel in the present study was very simple and seems effective. Distribution of polymorphic SNPs along the length of chromosomes and across all the chromosomes showed that this custom selected panel is a promising option for developing LD genotyping chip for Gir cattle.

Background: Simulated nucleotide or amino acid sequences are frequently used to assess the performance of phylogenetic reconstruction methods. BEAST, a Bayesian statistical framework that focuses on reconstructing time-calibrated molecular evolutionary processes, supports a wide array of evolutionary models, but lacked matching machinery for simulation of character evolution along phylogenies.Results: We present a flexible Monte Carlo simulation tool, called πBUSS, that employs the BEAGLE high performance library for phylogenetic computations to rapidly generate large sequence alignments under complex evolutionary models. πBUSS sports a user-friendly graphical user interface (GUI) that allows combining a rich array of models across an arbitrary number of partitions. A command-line interface mirrors the options available through the GUI and facilitates scripting in large-scale simulation studies. πBUSS may serve as an easy-to-use, standard sequence simulation tool, but the available models and data types are particularly useful to assess the performance of complex BEAST inferences. The connection with BEAST is further strengthened through the use of a common extensible markup language (XML), allowing to specify also more advanced evolutionary models. To support simulation under the latter, as well as to support simulation and analysis in a single run, we also add the πBUSS core simulation routine to the list of BEAST XML parsers.Conclusions: πBUSS offers a unique combination of flexibility and ease-of-use for sequence simulation under realistic evolutionary scenarios. Through different interfaces, πBUSS supports simulation studies ranging from modest endeavors for illustrative purposes to complex and large-scale assessments of evolutionary inference procedures. Applications are not restricted to the BEAST framework, or even time-measured evolutionary histories, and πBUSS can be connected to various other programs using standard input and output format. © 2014 Bielejec et al.; licensee BioMed Central Ltd.

A correspondência de Charles Darwin com John Henslow ao longo da viagem do Beagle (1831-1836), parcialmente publicada antes de seu retorno à Inglaterra, possibilitou o acesso do jovem naturalista ao centro da comunidade científica britânica. Ademais, a análise dessas cartas revela aspectos da atuação do Beagle em assuntos de interesse da Grã-Bretanha, nos campos científico, econômico, político e religioso. Defendemos nesse artigo que o Beagle compunha uma rede de atores humanos e não-humanos, fomentada pela diplomacia britânica e mobilizada pelas embarcações, que faziam circular informações entre Londres, as colônias britânicas e os países da América do Sul. Assim, conclui-se que o Beagle era um agente do imperialismo que colaborava nas pretensões britânicas de consolidar seu domínio sobre o hemisfério sul.

Yong-liang Zhu, Shuang-long Li, Ke-li Chen, Kun-peng Ma, De-qian Wu, Xiang-jun Qiu Medical College of Henan University of Science and Technology, Luoyang 471023, People’s Republic of ChinaCorrespondence: Xiang-jun QiuMedical College of Henan University of Science and Technology, Luoyang 471023, People’s Republic of ChinaEmail lyxiangjun@126.comObjective: To investigate the effects of Chinese herb Danzhi Xiaoyao pills on the pharmacokinetics of venlafaxine and its metabolites O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) in beagles by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).Methods: Six beagles (half male, half female) were chosen to test, being fasted before the experiment but having free access to drinking water 1 day before being fed drugs. After oral administration of venlafaxine hydrochloride tablets (10.28 mg/kg), the blood samples were collected in succession at different points in time. After 1-week washout period, Danzhi Xiaoyao pills (0.6g/kg) were given through oral administration to the six beagles every morning until the 7th day, venlafaxine hydrochloride tablets (10.28 mg/kg) were given after feeding Danzhi Xiaoyao pills (0.6g/kg) half an hour and blood samples were collected continuously at different points. All samples were analyzed by UPLC-MS/MS, and the main pharmacokinetic parameters of venlafaxine, ODV and NDV were computed by DAS 2.0.Results: The Cmax of the venlafaxine group (control group) and the combination group (experimental group) were (2267.26±252.89) ng/mL and (1542.64±190.73) ng/mL, respectively. The AUC(0-∞) of the two groups were (13,934.79±3609.23) ng·h/mL and (8001.91±2167.58) ng·h/mL, respectively. The ODV Cmax of the two groups were (2253.80±215.81) ng/mL and (2721.37±118.20) ng/mL, and AUC(0-∞) were (13,974.99±2784.04) ng·h/mL and (17,539.44±1894.29) ng·h/mL, respectively. The NDV Cmax of the two groups were (50.98±5.76) ng/mL and (58.74±12.33) ng/mL, and AUC(0-∞) were (179.26±34.94) ng·h/mL and (220.68±51.41) ng·h/mL, respectively. After administration of Danzhi Xiaoyao pills, the Cmax and AUC(0-∞) of venlafaxine decreased significantly, indicating that the plasma exposure of venlafaxine decreased. The increase of Cmax and AUC(0-∞) of ODV and NDV indicated a rise in plasma exposure.Conclusion: Danzhi Xiaoyao pills can accelerate the metabolism of venlafaxine in beagles. In clinical, when venlafaxine was co-administrated with Danzhi Xiaoyao pills, dose adjustment of venlafaxine should be taken into account.Keywords: beagle, UPLC-MS/MS, Danzhi Xiaoyao pills, venlafaxine, ODV, NDV, drug–drug interaction

Abstract Background Haplotype data contains more information than genotype data and provides possibilities such as imputing low frequency variants, inferring points of recombination, detecting recurrent mutations, mapping linkage disequilibrium (LD), studying selection signatures, estimating IBD probabilities, etc. In addition, haplotype structure is used to assess genetic diversity and expected accuracy in genomic selection programs. Nevertheless, the quality and efficiency of phasing has rarely been a subject of thorough study but was assessed mainly as a by-product in imputation quality studies. Moreover, phasing studies based on data of a poultry population are non-existent. The aim of this study was to evaluate the phasing quality of FImpute and Beagle, two of the most used phasing software. Results We simulated ten replicated samples of a layer population comprising 888 individuals from a real SNP dataset of 580 k and a pedigree of 12 generations. Chromosomes analyzed were 1, 7 and 20. We measured the percentage of SNPs that were phased equally between true and phased haplotypes (Eqp), proportion of individuals completely correctly phased, number of incorrectly phased SNPs or Breakpoints (Bkp) and the length of inverted haplotype segments. Results were obtained for three different groups of individuals, with no parents or offspring genotyped in the dataset, with only one parent, and with both parents, respectively. The phasing was performed with Beagle (v3.3 and v4.1) and FImpute v2.2 (with and without pedigree). Eqp values ranged from 88 to 100%, with the best results from haplotypes phased with Beagle v4.1 and FImpute with pedigree information and at least one parent genotyped. FImpute haplotypes showed a higher number of Bkp than Beagle. As a consequence, switched haplotype segments were longer for Beagle than for FImpute. Conclusion We concluded that for the dataset applied in this study Beagle v4.1 or FImpute with pedigree information and at least one parent genotyped in the data set were the best alternatives for obtaining high quality phased haplotypes.

Abstract Background Open angle glaucoma is the only type of primary glaucoma reported in Beagles. This case report describes a primary angle-closure glaucoma in a Beagle and its diagnostic and prognostic relevance. Case presentation A 12-year-old, neutered male Beagle presented to the Michigan State University (MSU) Comparative Ophthalmology Service for evaluation of suspected visual impairment. Complete ophthalmic examination of the left eye (OS) revealed: blepharospasm, absent menace response, moderate episcleral congestion, mild diffuse corneal edema, mydriasis, asteroid hyalosis, decreased myelination and cupping of the optic nerve head, and mild retinal vascular attenuation. Examinations of the right eye (OD) were within normal limits. Intraocular Pressure (IOP) were 24 mmHg OD and 49 mmHg OS. Gonioscopy OD revealed a narrow iridocorneal angle with moderate pectinate ligament dysplasia characterized by broad-based pectinate ligament strands (fibrae latae) and solid sheets (laminae) throughout all 4 quadrants. DNA testing revealed that the dog did not carry the Gly661Arg ADAMTS10 mutation responsible for primary open angle glaucoma (POAG) in Beagles. The OS was medically managed with latanoprost 0.005% and dorzolamide HCl 2% /timolol malate 0.5% ophthalmic solutions for 7 months and then enucleated due to uncontrolled IOP. Histopathologic evaluation was consistent with goniodysgenesis with a broad, non-perforate, sheet-like band of uveal stroma bridging from the base of the iris to the terminal arborization of Descemet’s membrane. Approximately 14 months from the initial diagnosis of glaucoma OS, OD also developed glaucoma and was enucleated. Histopathologic findings were consistent with goniodysgenesis OD. Conclusions To our knowledge, this is the first reported case of PACG with goniodysgenesis in a Beagle supported by clinical, genetic, and histopathologic data. It highlights the importance of gonioscopy in Beagles with glaucoma. Further studies with a larger number of dogs are warranted to characterize clinical manifestations and inheritance of PACG in this breed.

Understanding the role of Quantum Chromodynamics in generating nuclear forces is important for uncovering the mechanism of short-ranged nuclear interactions and their manifestation in short range correlations (SRC). The future Electron-Ion-Collider (EIC) at Brookhaven National Laboratory in the US will provide an unprecedented opportunity to systematically investigate the underlying physics of SRC for energies and kinematic regions that are otherwise impossible to reach. We study SRCs in electron-deuteron scattering events using the Monte Carlo event generator BeAGLE. Specifically, we investigate the sensitivity of observables to high internal nucleon momentum in incoherent diffractive J/ψ vector meson production. In a plane wave impulse approximation, the initial state deuteron wave function can be accessed directly from the four-momentum of the spectator nucleon. We use realistic physics estimates and a conceptual far-forward detector simulations of the EIC to fully reveal the potential of this exclusive process. In particular, we provide the luminosity and detector requirements necessary to study SRCs in the deuteron at an EIC.

In vitro models of animals vulnerable to SARS-CoV-2 infection can support the characterization of effective antiviral drugs, such as synthetic inhibitors of the transmembrane protease serine 2 (TMPRSS2). Changes in cytochrome P450 (CYP) 1A2 activities in the presence of the potential TMPRSS2/matriptase inhibitors (MI) were measured using fluorometric and luminescent assays. Furthermore, the cytotoxicity of these inhibitors was evaluated using the MTS method. In addition, 60 min-long microsomal stability assays were performed using an UPLC-MS/MS procedure to elucidate depletion rates of the inhibitors. CYP1A2 was influenced significantly by MI-463 and MI-1900 in rat microsomes, by MI-432 and MI-482 in beagle microsomes, and by MI-432, MI-463, MI-482, and MI-1900 in cynomolgus monkey microsomes. The IC50 values in monkey microsomes were 1.30 ± 0.14 µM, 2.4 ± 1.4 µM, 0.21 ± 0.09 µM, and 1.1 ± 0.8 µM for inhibitors MI-432, MI-463, MI-482, and MI-1900, respectively. The depletion rates of the parent compounds were lower than 50%, independently of the investigated animal species. The host cell factor TMPRSS2 is of key importance for the cross-species spread of SARS-CoV-2. Studies of the in vitro biotransformation of TMPRSS2 inhibitors provide additional information for the development of new antiviral drugs.

There is growing interest in the potential health benefits of probiotics for both humans and animals. The study aimed to investigate the effects of feeding the canine-derived probiotic Pediococcus acidilactici GLP06 to adult beagles by analysing the microbiome and metabolome. Twenty-four healthy adult beagles were randomly assigned to four groups. The CK group received a standard diet, while the three probiotic groups, the LG group (2 × 10 8  CFU/day/dog), MG group (2 × 10 9  CFU/day/dog), and HG group (2 × 10 10  CFU/day/dog), received the standard diet supplemented with varying amounts of probiotics. The results show that, compared to the CK group, total antioxidant capacity was significantly increased in the MG and HG groups ( p  < 0.05), and superoxide dismutase and catalase were significantly increased in the HG group ( p  < 0.05). Compared to the CK group, malondialdehyde and blood urea nitrogen content were significantly decreased in the MG and HG groups ( p  < 0.05). Additionally, secretory immunoglobulin A activity was significantly increased in the HG group compared to the CK and LG groups ( p  < 0.05), and immunoglobulin G activity was significantly increased in the HG group compared to the CK, LG, and MG groups ( p  < 0.05). In addition, compared with the CK group, the abundance of Faecalitalea and Collinsella increased in the LG group, and the relative abundance of Tyzzerella and Parasutterella increased in the MG group. The α diversity and the relative abundances of beneficial bacteria ( Faecalibacterium , Lachnospiraceae&#95;NK4A1316 , and Ruminococcaceae&#95;UCG-005 ) were higher in the HG group than in the CK group. Furthermore, acetic acid content was significantly increased in the HG group compared to the CK, LG, and MG groups ( p  < 0.05). Butyric acid, isobutyric acid, and the total SCFA content were significantly increased in the HG group compared to the CK group ( p  < 0.05). Moreover, metabolome analysis revealed 111 upregulated and 171 downregulated metabolites in the HG group. In conclusion, this study presents evidence that supplementing with P. acidilactici GLP06 can have a positive impact on antioxidant activity, immunoproteins, SCFAs, and gut microbiota in adult beagles. These findings highlight the potential of probiotics as a dietary intervention to enhance gut health and overall wellbeing in companion animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Zhang, Li, Liu, Bao and Li.)

The present report describes a novel approach to and presents the surgical results for laparoscopic hepatectomy of the left lobes in small dogs. A purely laparoscopic four-port approach was used in seven beagles. The left triangular ligament was cut first, then the base of the left medial lobe (LMB) was ligated with silk thread using a needle, and the liver parenchyma of the LMB approximately 0.5 cm above the ligation site was removed with LigaSure. The left lateral lobe (LLB) was removed in the same manner. Blood was collected on postoperative days 1, 3, 7, and 14 for laboratory testing. Left hepatic lobe resection was successfully completed in all dogs, with an average operation time of 102.53 ± 9.07 min and an average blood loss of 32.10 ± 6.43 ml. Serious postoperative complications were not observed. The white blood cell (WBC) count and alkaline phosphatase (ALP) level were significantly increased in experimental dogs 1 day after surgery (P < 0.05); aspartate transferase (AST) and alanine transaminase (ALT) were significantly different before and after surgery (P < 0.01); and all the indicators were basically normal seven days after the operation. Exploratory laparoscopy at 28 days revealed adhesion of the surface of the liver section to the omentum or the gastric wall, but there were no other abnormal findings. The combined application of liver pedicle ligation and LigaSure for liver lobectomy provides a simple and effective method for generating liver lobectomy models for research on liver disease and regeneration and a feasible laparoscopic liver lobectomy operation scheme for small dogs (10-15 kg). [ABSTRACT FROM AUTHOR]

Lafora Disease (LD) is a rare, fatal, late-onset, progressive form of myoclonic epilepsy, occurring in humans and dogs. Clinical manifestations of LD usually include seizures, spontaneous and reflex myoclonus with contractions of the neck and limb muscles. We studied the electroencephalogram (EEG) patterns of two beagles in whom LD was subsequently confirmed by genetic testing. In both cases, the EEG recordings, accompanied by electromyography (EMG), have shown similar uncommon patterns. The hypovoltaged background rhythm was interrupted by waxing “crescendo” polyspikes-slow wave complexes appearing 80–250 ms after the start of intermittent photic stimulation, followed by myoclonic jerks after 80–150 ms. This study highlights the value of EEG in establishing a presumptive diagnosis of LD in dogs.

The canine influenza virus (CIV) outbreaks have raised concerns as they pose a threat to the health of dogs. The successful construction of a canine influenza (CI) infection model is essential to study the CIV. Here we investigated the pathogenicity of different infectious doses of H3N2 CIV in Beagle dogs. Thirty-seven healthy Beagle dogs were used in the experiment and were infected with 103, 104, 105, and 106 50% egg-infectious doses (EID50). Compared to the dogs in the other three groups, those in the 106 EID50 group presented with obvious clinical symptoms, high virus titer, and typical pathological changes. Considering the ensemble of clinical scores, body temperature, virus shedding, lung lesions, pathological section scores, and visceral virus titers, we determined that 106 EID50 is the minimum infectious dose for the Beagle infection model. The other three infectious doses had almost no clinical symptoms. These results indicate that 106 EID50 is the minimum infectious dose of H3N2 CIV that can cause obvious clinical manifestations and pathological changes associated with CI in Beagle dogs. The theoretical framework developed in this research will guide the establishment of an infection model of CIV for future research.

Background: The trading of individual animal genotype information often involves only the exchange of the called genotypes and not necessarily the additional information required to effectively call structural variants. The main aim here was to determine if it is possible to impute copy number variants (CNVs) using the flanking single nucleotide polymorphism (SNP) haplotype structure in cattle. While this objective was achieved using high-density genotype panels (i.e., 713,162 SNPs), a secondary objective investigated the concordance of CNVs called with this high-density genotype panel compared to CNVs called from a medium-density panel (i.e., 45,677 SNPs in the present study). This is the first study to compare CNVs called from high-density and medium-density SNP genotypes from the same animals. High (and medium-density) genotypes were available on 991 Holstein-Friesian, 1015 Charolais, and 1394 Limousin bulls. The concordance between CNVs called from the medium-density and high-density genotypes were calculated separately for each animal. A subset of CNVs which were called from the high-density genotypes was selected for imputation. Imputation was carried out separately for each breed using a set of high-density SNPs flanking the midpoint of each CNV. A CNV was deemed to be imputed correctly when the called copy number matched the imputed copy number. Results: For 97.0% of CNVs called from the high-density genotypes, the corresponding genomic position on the medium-density of the animal did not contain a called CNV. The average accuracy of imputation for CNV deletions was 0.281, with a standard deviation of 0.286. The average accuracy of imputation of the CNV normal state, i.e. the absence of a CNV, was 0.982 with a standard deviation of 0.022. Two CNV duplications were imputed in the Charolais, a single CNV duplication in the Limousins, and a single CNV duplication in the Holstein-Friesians; in all cases the CNV duplications were incorrectly imputed. Conclusion: The vast majority of CNVs called from the high-density genotypes were not detected using the medium-density genotypes. Furthermore, CNVs cannot be accurately predicted from flanking SNP haplotypes, at least based on the imputation algorithms routinely used in cattle, and using the SNPs currently available on the high-density genotype panel. [ABSTRACT FROM AUTHOR]

Imputation is one of the key steps in the preprocessing and quality control protocol of any genetic study. Most imputation algorithms were originally developed for the use in human genetics and thus are optimized for a high level of genetic diversity. Different versions of BEAGLE were evaluated on genetic datasets of doubled haploids of two European maize landraces, a commercial breeding line and a diversity panel in chicken, respectively, with different levels of genetic diversity and structure which can be taken into account in BEAGLE by parameter tuning. Especially for phasing BEAGLE 5.0 outperformed the newest version (5.1) which in turn also lead to improved imputation. Earlier versions were far more dependent on the adaption of parameters in all our tests. For all versions, the parameter ne (effective population size) had a major effect on the error rate for imputation of ungenotyped markers, reducing error rates by up to 98.5%. Further improvement was obtained by tuning of the parameters affecting the structure of the haplotype cluster that is used to initialize the underlying Hidden Markov Model of BEAGLE. The number of markers with extremely high error rates for the maize datasets were more than halved by the use of a flint reference genome (F7, PE0075 etc.) instead of the commonly used B73. On average, error rates for imputation of ungenotyped markers were reduced by 8.5% by excluding genetically distant individuals from the reference panel for the chicken diversity panel. To optimize imputation accuracy one has to find a balance between representing as much of the genetic diversity as possible while avoiding the introduction of noise by including genetically distant individuals. [ABSTRACT FROM AUTHOR]

Psychologists have made substantial progress at developing empirically validated formal expressions of how people perceive, learn, remember, think, and know. In this article, we present an academic search engine for cognitive psychology that leverages computational expressions of human cognition (vector-space models of semantics) to represent and find articles in the psychological record. The method shows how psychological theory can be used to inform and aid the design of psychologically intuitive computer interfaces. [ABSTRACT FROM AUTHOR]

Application of magnetic resonance imaging (MRI) techniques reveals that human brain aging varies across cortical regions. One area particularly sensitive to normal aging is the frontal lobes. In vitro neuropathological studies and behavioral measures in a canine model of aging previously suggested that the frontal lobes of the dog might be sensitive to aging. In the present study, MRI scans were acquired to compare age-related changes in frontal lobe volume with changes in executive functions and beta-amyloid pathology in the frontal cortex of beagle dogs aged 3 months to 15 years. Decreases in total brain volume appeared only in senior dogs ( aged 12 years and older), whereas frontal lobe atrophy developed earlier, appearing in the old dogs ( aged 8 - 11 years). Hippocampal volume also declined with age, but not occipital lobe volume past maturity. Reduced frontal lobe volume correlated with impaired performance on measures of executive function, including inhibitory control and complex working memory, and with increased beta-amyloid accumulation in the frontal cortex. Age-related hippocampal atrophy also correlated with complex working memory but not inhibitory control, whereas occipital lobe volume did not correlate with any cognitive measure. These findings are consistent with the frontal lobe theory of aging in humans, which suggests that the frontal lobes and functions subserved by this region are compromised early in aging.

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application. [ABSTRACT FROM AUTHOR]

Weissella (W.) cibaria strain Chonnam Medical University (CMU) has shown oral colonizing ability and inhibitory effects on the formation of volatile sulfur compounds (VSCs) in vitro studies. The present study was conducted to analyze the effects of the W. cibaria CMU on canine oral health. Halitosis, calculus, plaque, gingivitis, and intraoral microbiota were assessed in 3 groups: control (maltodextrin), W. cibaria CMU low concentration (CMU-L, 2 × 107 colony forming unit [CFU]), and high-concentration (CMU-H, 2 × 109 CFU). Halitosis was analyzed using both organoleptic evaluation and measurement of VSCs. Intraoral microbiota were analyzed by real-time polymerase chain reaction. From week 4, the total VSC level in the CMU-H group (4.0 ± 1.30 ng/10 mL) was significantly lower than in the control group (6.3 ± 2.28 ng/10 mL). Significant reduction in methyl mercaptan in the CMU-treated groups was also observed. In addition, the plaque index in the CMU-treated groups was significantly decreased. The CMU-treated groups showed significant decreases in Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia and demonstrated the colonizing ability of W. cibaria CMU in the oral cavity. We demonstrated that W. cibaria CMU suppresses halitosis, colonizes the oral cavity, and inhibits the proliferation of malodor-causing oral bacteria in beagles. According to these results, we expect that W. cibaria CMU could be a new oral hygiene solution by reducing VSC production and inhibiting the growth of oral harmful bacteria in companion animals. [ABSTRACT FROM AUTHOR]