SummaryDirect conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs) into mature induced neuronal (iN) cells by forced expression of three transcription factors: ASCL1, MYT1L, and BRN2. Here, we show that ASCL1 alone is sufficient to generate functional iN cells from mouse and human fibroblasts and embryonic stem cells, indicating that ASCL1 is the key driver of iN cell reprogramming in different cell contexts and that the role of MYT1L and BRN2 is primarily to enhance the neuronal maturation process. ASCL1-induced single-factor neurons (1F-iN) expressed mature neuronal markers, exhibited typical passive and active intrinsic membrane properties, and formed functional pre- and postsynaptic structures. Surprisingly, ASCL1-induced iN cells were predominantly excitatory, demonstrating that ASCL1 is permissive but alone not deterministic for the inhibitory neuronal lineage.

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BackgroundHypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved.Hypothesis/ObjectivesObservational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH).AnimalsOne thousand seven hundred and thirty client‐owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH).MethodsRetrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long‐term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death.ResultsDuring the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9‐15 years.Conclusions and Clinical ImportancePreclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

In this paper, we implement the intelligent neural network controller hardware with a field programmable gate array (FPGA)-based general purpose chip and a digital signal processing (DSP) board to solve nonlinear system control problems. The designed intelligent control hardware can perform real-time control of the backpropagation learning algorithm of a neural network. The basic proportional-integral-derivative (PID) control algorithms are implemented in an FPGA chip and a neural network controller is implemented in a DSP board. By using a high capacity of an FPGA chip, the additional hardware such as an encoder counter and a pulsewidth modulation (PWM) generator is implemented in a single FPGA chip. As a result, the controller becomes cost effective. It was tested for controlling nonlinear systems such as a robot finger and an inverted pendulum on a moving cart to show performance of the controller.Index Terms-Digital signal processing (DSP), field programmable gate array (FPGA), inverted pendulum, neural network controller, proportional-integral-derivative (PID) controller, robot finger.

BackgroundThe prevalence and prognostic importance of atrial fibrillation (AF) on survival in nonsmall breed dogs with myxomatous mitral valvular disease (MMVD) and congestive heart failure (CHF) remain unknown.AimTo identify the prevalence of AF in nonsmall breed dogs with CHF because of MMVD and to characterize the impact of AF on survival outcome.AnimalSixty‐four client‐owned dogs (>15 kg) with MMVD and CHF.MethodsRetrospective review of medical records for dogs weighing >15 kg with MMVD treated for CHF.ResultsThirty‐three dogs presented with AF or developed AF during follow‐up examinations, and 31 dogs were free of AF until cardiac‐related death. For dogs with AF, median survival time (MST) was 142 days (range: 9–478) while dogs without AF lived 234 days (range: 13–879 days). AF increased risk of cardiac‐related death (HR = 2.544; 95% CI = 1.41–4.59; P = .0019) when compared to dogs without AF. MST was significantly prolonged for dogs with AF whose rates were adequately controlled (<160 bpm; 171 days; n = 13) when compared to dogs that failed to respond to negative chronotropic agents (61 days; n = 20; P = .032). The administration of combination treatment (diltiazem and digoxin) significantly decreased median HR to 144 bpm (range: 84–218 bpm) in dogs with AF and significantly prolonged MST (diltiazem+digoxin: 130 days versus diltiazem: 35 days, P = .0241) when compared to diltiazem alone.Conclusions and Clinical ImportanceInadequately controlled AF is associated with a higher rate of mortality. Optimization of therapeutic strategies for the rate control of AF remains determined.

Many studies have been carried out with respect to packaging methods and temperature conditions of beef. However, the effects of packaging methods and temperature conditions on the quality characteristics have not been extensively studied in low-grade beef. Low-grade beef samples were divided into 3 groups (C: ziplock bag packaging, T1: vacuum packaging, and T2: modified atmosphere packaging (MAP), CO2/N2 = 3:7) and samples were stored at 4°C for 21 days. The water-holding capacity (WHC) was significantly lower in T1 than in the other samples up to 14 days of storage. The thiobarbituric acid reactive substances and volatile basic nitrogen values were significantly lower in T1 and T2 than in C after 7 to 14 days of storage. The total bacterial counts were significantly lower in T1 and T2 than in C after 14 days of storage. In a sensory evaluation, tenderness and overall acceptability were significantly higher in T1 and T2 than in C at the end of the storage period (21 days). We propose that the MAP method can improve beef quality characteristics of low-grade beef during cold storage. However, the beneficial effects did not outweigh the cost increase to implement MAP.

Hip dysplasia is a common inherited trait of dogs that results in secondary osteoarthritis. In this article the methods used to uncover the mutations contributing to this condition are reviewed, beginning with hip phenotyping. Coarse, genome-wide, microsatellite-based screens of pedigrees of greyhounds and dysplastic Labrador retrievers were used to identify linked quantitative trait loci (QTL). Fine-mapping across two chromosomes (CFA11 and 29) was employed using single nucleotide polymorphism (SNP) genotyping. Power analyses and preferential selection of dogs for ongoing SNP-based genotyping is described with the aim of refining the QTL intervals to 1-2 megabases on these and several additional chromosomes prior to candidate gene screening. The review considers how a mutation or a genetic marker such as a SNP or haplotype of SNPs might be combined with pedigree and phenotype information to create a 'breeding value' that could improve the accuracy of predicting a dog's hip conformation.

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