Suppression of aging in mice by the hormone Klotho

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.     

Time-dependent central compensatory mechanisms of finger dexterity after spinal cord injury

Transection of the direct cortico-motoneuronal pathway at the mid-cervical segment of the spinal cord in the macaque monkey results in a transient impairment of finger movements. Finger dexterity recovers within a few months. Combined brain imaging and reversible pharmacological inactivation of motor cortical regions suggest that the recovery involves the bilateral primary motor cortex during the early recovery stage and more extensive regions of the contralesional primary motor cortex and bilateral premotor cortex during the late recovery stage. These changes in the activation pattern of frontal motor-related areas represent an adaptive strategy for functional compensation after spinal cord injury.     

Involvement of a phosphorylation-mediated pathway to regulate the function of NSPL1 in exercise

Skeletal-type neuroendocrine-specific protein like 1 (sk-NSPL1) has been demonstrated to be physiologically important in regulating the membrane translocation of glucose transporter 4 (GLUT4) in skeletal muscles. We investigated the levels of phosphorylation in proteins that are thought to be involved in exercise in wild-type and sk-NSPL1-deficient muscles with specific antibodies and phosphate-metal affinity chromatography resin (p-resin). In both normal skeletal muscle and sk-NSPL1-deficient muscle, adenosine monophosphate (AMP)-dependent kinase (AMPK) and acetyl-CoA carboxylase (ACC) were phosphorylated and adsorbed onto p-resin at high levels after exercise. On the other hand, the effect of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), which is an activator of AMPK, in blood glucose was greatly diminished in mutant mice. P-resin adsorbed sk-NSPL1 in the membrane fraction from wild-type muscle after exercise and AICAR administration. Isolated sk-NSPL1 from wild-type also had increased adsorption onto p-resin after treatment with Ca(2+) and adenosine triphosphate (ATP). After long-term incubation of sk-NSPL1-containing membrane without ATP, sk-NSPL1 adsorption onto anion-exchange resin was drastically reduced. These results suggest that the function of sk-NSPL1 is regulated by a [Ca(2+)](i)- and AMPK-mediated pathway under exercise, and support the hypothesis that sk-NSPL1 is an important factor in the downstream of the exercise-dependent pathway in GLUT4 translocation.     

Epidemiological and morphological studies of double-chambered right ventricle in dogs

The double-chambered right ventricle (DCRV) is a rare congenital cardiac disease in dogs, and its detailed epidemiological and morphological features are not clearly understood. By investigating the profile, clinical signs, and characteristics of examination findings of eleven dogs with DCRV by means of a retrospective study, we attempted to clarify the epidemiology and morphology of the condition. The study group consisted of nine males and two females. Breeds included Pug (n=3), Miniature Dachshund (n=1), French Bull-dog (n=1), Shiba (n=1), and Retrievers (n=5). The attachment site of the anomalous muscular bundle was continuous with the cardiac apex in nine dogs, and it was attached to the right ventricle free wall in the other two dogs. In dogs with DCRV, at least one of the following conditions was present concurrently: congenital or acquired tricuspid valve regurgitation (TR), ventricular septal defect, and atrial septal defect. Also, the pressure difference between the two chambers increased over time, and progressive right-sided heart failure was observed. In summary, DCRV occurs in small breeds of dog as well as in large breeds of dog and it may be more prevalent in males. The existence of two types of DCRV in dogs was established. Dog with DCRVs will have a high incidence of concurrent cardiac abnormalities. Concurrent TR may be either congenital or acquired. DCRV is a congenital disorder, but the clinical condition progresses as the dog develops.     

Directed evolution of yeast ferric reductase to produce plants with tolerance to iron deficiency in alkaline soils

One of the most serious problems in agriculture worldwide is low iron (Fe) availability, due to high soil pH. About 30% of arable land is too alkaline for optimal crop production. Non-graminaceous and dicot plants, which use a reduction strategy to uptake Fe, suffer from Fe deficiency under these conditions, because the ferric chalets reductase in the root plasma membrane functions inefficiently at high pH. The refrel (reconstructed yeast ferric reductase) gene was subjected to random mutagenesis to obtain variants with high activity under high pH conditions. A mutant library was screened using a yeast in vivo assay system, and screens at pH 8.0 and 8.5 produced 10 candidates. In vivo ferric reductase activity was analyzed quantitatively. Yeast cells carrying the variant with the highest ferric reductase activity showed 6.0, 8.7, and 38 times greater activity at pH 8.0, 8.5, and 9.0, respectively, than did cells containing the original refrel gene. An amino acid substitution at position 312 was common to most of the high-activity variants. This substitution is believed to play an important role in the increased reductase activity at high pH. Interestingly, this mutation is near a hams-coordinating histidine co on, and the corresponding residue is probably located in the intramembranous region close to the cytoplasm. The variant gene with the highest reductase activity was introduced into tobacco, and transgenic tobacco carrying the gene showed enhanced tolerance to low Fe availability. This result should be useful in the engineering of non-graminaceous and dicot plants tolerant to Fe deficiency in alkaline soils.     

Equine keratomycosis in Japan

Objective To describe the incidence, clinical progress, visual outcome, and laboratory findings of equine keratomycosis in Japan. Procedure Retrospective study of the medical records of horses clinically and mycologically diagnosed with keratomycosis at the Equine Hospitals of the Japan Racing Association from 2005 to 2011. Results The diagnosis of keratomycosis was confirmed in eight horses (40.0% of the 20 horses with infectious keratitis from which fungi and/or bacteria were isolated). Fungi recovered from corneal swabs were identified as Aspergillus flavus (4), Aspergillus niger (1), Fusarium solani (1), and Mortierella wolfii (2). All horses were treated medically with topical antifungals, and one horse was also treated surgically. The median of treatment period was 40 days. Two horses were rendered blind in the affected eye and the others retained vision. Conclusions Equine keratomycosis comprises a considerable portion of infectious keratitis in Japan, and the causative fungi that we isolated had been isolated previously from horses with keratomycosis in other regions with the exception of M. wolfii. Culture and cytological examination of corneal lesions should be immediately performed on eyes with signs of keratitis, particularly on those not improving with antibacterial medication, as early initiation of aggressive antifungal treatment tended to result in better outcome and shorter treatment period.     

Influence of heart rate on myocardial function using two-dimensional speckle-tracking echocardiography in healthy dogs

ObjectiveThe objective of this study was to evaluate the influence of heart rate (HR) on myocardial function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) in healthy dogs.AnimalsThirteen healthy beagle dogs.MethodsAnimals were anesthetized and HR was controlled with right atrial pacing. Myocardial function of each dog was assessed using 2D-STE at pacing rates of 120, 140, 160, and 180 bpm.ResultsAll strain and strain rate variables in the longitudinal, circumferential, and radial directions were not significantly different between pacing rates. Peak early diastolic torsion rate at 180 bpm was significantly increased compared with that at 120 bpm (P = 0.003).ConclusionTorsion rate in early diastole was elevated at 180 bpm, which may reflect improved myocardial relaxation with higher HR. Changes in left ventricular torsion during tachycardia may play an important role in preserving stroke volume in the presence of shortened ejection and filling times.     

Statistical Analysis of Metal Concentrations in a Sediment Core to Reveal Influences of Human Activities on Atmospheric Environment for 200 Years

Metal concentrations in a sediment core from a moat outside Osaka Castle in Japan were measured by ICP-MS following a microwave extraction method. Concentrations of metals in the sediment core samples peaked around 1945 when the World War II ended. This is in part due to great air raids on Osaka. In cluster analysis using metal concentrations, the fractions of sediment core samples were classified into two groups, representing natural sources (1795–1915) and anthropogenic sources (1922–1976), respectively. Results of lead isotope ratios also showed the anthropogenic influences from 1915 by changing the ratio values compared to those of natural sources. In addition, several components contributing to metal concentrations were identified by principal component analysis. The main component was controlled by natural sources and a decrease of the component score corresponded to an increased influence from anthropogenic sources. The largest impact of anthropogenic sources was shown around 1945.     

The pathogenicity of canine parvovirus type-2b, FP84 strain isolated from a domestic cat, in domestic cats

Canine parvovirus type-2a (CPV-2a) and type-2b (CPV-2b) have recently been isolated from domestic cats. The pathogenicity of CPV-2b in domestic cats is still unclear. In this study, we performed infection tests to examine the pathogenicity of CPV-2b, FP84 strain, isolated from a domestic cat. The results demonstrated that the CPV strain FP84 is able to infect and replicate well in domestic cats. Two of the 3 cats used in the test died. They showed loss of appetite, diarrhea, leukopenia and dehydration. Since FP84 was found to be virulent to domestic cats, it is necessary to examine the efficacy of inactivated feline panleukopenia virus vaccines against CPV infection in domestic cats.