Deficits in social memory, cognition, and aberrant responses to stimulants are common among persons affected by schizophrenia and other conditions with a presumed developmental etiology. We ...previously found that expression changes in the adenosine metabolizing enzyme adenosine kinase (ADK) in the adult brain are associated with deficits in various cognitive domains. To distinguish between developmental and adult functions of ADK, we used two transgenic mouse lines with widespread disruption of ADK expression in the adult brain, but differences in the onset of ADK deletion. Specifically, we compared Nestin-Cre+/-:ADK-floxfl/fl (ADKΔBrain) mice with global loss of ADK in the whole brain, beginning in mid-gestation and persisting for life, with Gfa2-Cre+/-:ADK-floxfl/fl (ADKΔAstro) mice that have normal ADK expression throughout development, but lose astrocyte-specific ADK-expression in young adulthood. Because ADK-expression in adulthood is generally confined to astrocytes, adult ADKΔAstro mice show a similar expression profile of ADK in key areas of the brain related to neuropsychiatric behavior, compared to adult ADKΔBrain mice. We sought to determine a neurodevelopmental role of ADK on the expression of psychiatric behaviors in adult male and female mice. Adult ADKΔBrain mice showed significant deficits in social memory in males, significant contextual learning impairments in both sexes, and a hyper-responsiveness to amphetamine in males. In contrast, ADKΔAstro mice showed normal social memory and contextual learning but hypo-responsiveness to amphetamine in males. Our results demonstrate a key developmental role of ADK in mediating behaviors in adulthood related to neuropsychiatric disease and support the greater prevalence of these disorders among males.
•Perturbation of adenosine kinase expression during development results in behavioral deficits, predominately in male mice.•There were prominent sex differences in behavior, in line with clinical populations, in adenosine kinase deficient mice.•Adenosine homeostasis may play a role during development in determining susceptibility to later neuropsychiatric disease.
Triptolide, the primary active component of a traditional Chinese medicine Tripterygium wilfordii Hook F, has a wide range of pharmacological activities. In the present study, the metabolism of ...triptolide by cytochrome P450s was investigated in human and rat liver microsomes. Triptolide was converted to four metabolites (M-1, M-2, M-3, and M-4) in rat liver microsomes and three (M-2, M-3, and M-4) in human liver microsomes. All the products were identified as mono-hydroxylated triptolides by liquid chromatography-mass spectrometry (LC-MS). The studies with chemical selective inhibitors, complementary DNA-expressed human cytochrome P450s, correlation analysis, and enzyme kinetics were also conducted. The results demonstrate that CYP3A4 and CYP2C19 could be involved in the metabolism of triptolide in human liver, and that CYP3A4 was the primary isoform responsible for its hydroxylation.
CaTiO₃nanoparticles of 30-40 nm in size were synthesized via a polyacrylamide gel route. Ag nanoparticles with size of 8-16 nm were deposited onto CaTiO₃particles by a photochemical reduction method ...to yield CaTiO₃@Ag composites. The photocatalytic activity of prepared samples was evaluated by degrading methyl orange under ultraviolet irradiation. It is demonstrated that Ag-decorated CaTiO₃ particles exhibit an enhanced photocatalytic activity compared to bare CaTiO₃ particles. After 60 min of photocatalysis, the degradation percentage of MO increases from 54% for bare CaTiO₃particles to 72% for CaTiO₃@Ag composites. This can be explained by the fact that photogenerated electrons are captured by Ag nanoparticles and photogenerated holes are therefore increasingly available to react with OH⁻/H₂O to generate hydroxyl (·OH) radicals. ·OH radicals were detected by fluorimetry using terephthalic acid as a probe molecule, revealing an enhanced yield on the irradiated CaTiO₃@Ag composites. In addition, it is found that the addition of ethanol, which acts as an ·OH scavenger, leads to a quenching of ·OH radicals and simultaneous decrease in the photocatalytic efficiency. This suggests that ·OH radicals are the dominant active species responsible for the dye degradation.
We report on the first measurement of charm-strange meson $D_s^{\pm}$ production at midrapidity in Au+Au collisions at $\sqrt{s_{_{\rm NN}}}$ = 200 GeV from the STAR experiment. The yield ratio ...between strange ($D_{s}^{\pm}$) and non-strange ($D^{0}$) open-charm mesons is presented and compared to model calculations. A significant enhancement, relative to a PYTHIA simulation of $p$+$p$ collisions, is observed in the $D_{s}^{\pm}/D^0$ yield ratio in Au+Au collisions over a large range of collision centralities. Model calculations incorporating abundant strange-quark production in the quark-gluon plasma (QGP) and coalescence hadronization qualitatively reproduce the data. The transverse-momentum integrated yield ratio of $D_{s}^{\pm}/D^0$ at midrapidity is consistent with a prediction from a statistical hadronization model with the parameters constrained by the yields of light and strange hadrons measured at the same collision energy. These results suggest that the coalescence of charm quarks with strange quarks in the QGP plays an important role in $D_{s}^{\pm}$ meson production in heavy-ion collisions.
The objective of the present study was to evaluate the effects of isovalerate supplementation on growth performance and ruminal fermentation in pre- and post-weaning dairy calves. Forty-eight Chinese ...Holstein male calves at 15 days of age and 45·1 ± 0·36 kg body weight (BW) were assigned randomly to four groups. The treatments were: control, low-isovalerate, moderate-isovalerate (MIV) and high-isovalerate (HIV) with 0, 3, 6 and 9 g isovalerate per calf per day, respectively. Isovalerate was hand-mixed into milk in pre-weaning calves and the concentrate portion in post-weaning calves. The study lasted 75 days, including a 15-day adaptation period followed by a 60-day sampling period. Weaning was conducted when calves were 60 days old. Six calves were chosen from each treatment at random and slaughtered at 30 and 90 days of age. Average daily weight gain increased linearly whether during pre-weaning or post-weaning period with increasing isovalerate supplementation. Dry matter intake linearly increased at 90 days of age with increasing isovalerate supplementation. During weaning, ruminal pH and ammonia nitrogen (N) decreased linearly, whereas total ruminal volatile fatty acid concentration increased linearly with increasing isovalerate supplementation. The ratio of acetate to propionate increased linearly with increasing isovalerate supplementation due to increased acetate concentration and the unchanged propionate concentration. Activities of caboxymethyl-cellulase, cellobiase, xylanase and pectinase linearly increased at 90 days of age, α-amylase and β-amylase activities linearly increased at 30 and 90 days of age. Relative quantities of Butyrivibrio fibrisolvens, Ruminococcus albus, Fibrobacter succinogenes and Ruminococcus flavefaciens increased linearly with increasing isovalerate supplementation. Ruminal fermentation, enzyme activities and cellulolytic bacteria were higher for HIV and MIV than for the control. The present results indicate that isovalerate accelerated growth of calves by improving ruminal fermentation, microbial enzyme activities and cellulolytic bacteria growth during weaning. In the experimental conditions of the current trial, the optimum isovalerate dose was about 6·0 g isovalerate per calf per day.
The current experiment was conducted to evaluate the effects of different dietary protein levels and rumen-protected folic acid (RPFA) supplementation on ruminal fermentation, microbial enzyme ...activity, bacterial populations and urinary excretion of purine derivatives (PD) in growing beef steers. Low-protein (LP) or high-protein (HP) diets were fed to eight ruminally cannulated first-generation cross-bred (Blonde d'Aquitaine × Simmental) beef steers with or without RPFA supplementation. Steers were fed a total mixed ration, and dietary concentrate to maize silage ratio was 50 : 50 (dry matter (DM) basis). No interaction between dietary crude protein (CP) levels and RPFA supplementation was observed during the experiment. Ruminal pH was unaffected by RPFA supplementation, but decreased with increasing dietary CP levels. Ruminal total volatile fatty acid concentration increased with increasing dietary CP levels or RPFA supplementation. Molar proportion of acetate increased with RPFA supplementation, but tended to decrease with increasing dietary CP levels. The proportion of propionate decreased with RPFA supplementation, but was unaffected by dietary CP levels. As a result, the acetate to propionate ratio increased with RPFA supplementation, but tended to be lower for the HP diets than the LP diets. Ammonia-nitrogen content decreased with RPFA supplementation, but increased with increasing dietary CP levels. In situ ruminal degradability of maize straw and concentrate increased with increasing dietary CP levels or RPFA supplementation. Microbial enzyme (carboxymethyl-cellulase, cellobiase, xylanase, pectinase, α-amylase and protease) activity, bacterial populations (Ruminococcus albus, Ruminococcus flavefaciens, Butyrivibrio fibrisolvens, Prevotella ruminicola, Fibrobacter succinogenes and Ruminobacter amylophilus) and urinary PD excretion increased with increasing dietary CP levels or RPFA supplementation. The current study showed that increasing dietary CP levels from 109·1 to 130·7 g/kg DM or supplementing 75 mg RPFA improved ruminal fermentation and microbial protein synthesis by increasing bacterial population and microbial enzyme activity.
Abstract
The effects of pantothenic acid (PA) and folic acid (FA) addition on digestibility coefficient, ruminal fermentation and urinary purine derivative (PD) excretion in dairy bulls were ...evaluated. Eight rumen-cannulated Holstein dairy bulls were allocated to a replicated 4 × 4 Latin square design according to a 2 × 2 factorial arrangement. Diets were supplemented with two levels of FA (0 or 8.0 mg/kg dietary dry matter DM) and two of PA (0 or 60 mg/kg DM). The PA × FA interaction was not significant for all variables. Both supplements increased DM intake and average daily gain, but decreased a feed conversion ratio. Digestibility of DM, organic matter, crude protein and neutral detergent fibre increased, but ether extract digestibility was unchanged for both supplements. Digestibility of acid detergent fibre only increased with FA supplementation. For both supplements, ruminal pH and ammonia nitrogen (N) decreased, but total volatile fatty acid (VFA) concentration increased. Acetate proportion only increased with FA supplementation. Propionate proportion decreased for both supplements. Consequently, the acetate to propionate ratio increased. For both supplements, activity of xylanase and pectinase, population of
Ruminococcus albus
,
R. flavefaciens
,
Fibrobacter succinogenes
and
Ruminobacter amylophilus
and total PD excretion increased. Additionally, activity of carboxymethylcellulase, cellobiase,
α
-amylase and protease, and population of total bacteria, fungi, protozoa, methanogens,
Butyrivibrio fibrisolvens
and
Prevotella ruminicola
increased with FA addition. The results suggested that PA and FA supplementation stimulated ruminal microbial growth and enzyme activity, resulting in an increased digestibility coefficient and ruminal total VFA concentration in dairy bulls.
•Guanidinoacetic acid (GAA) or betaine (BT) increased growth performance and rumen microbial populations in bulls.•Supplementing BT changed rumen fermentation pattern with greater acetate ...production.•Supplementing GAA at 0.6 g/kg DM did not affect blood concentrations of folate, homocysteine and methionine.•No additional effect on performance was found with both GAA and BT compared to GAA or BT alone.
This study evaluated the influences of guanidinoacetic acid (GAA) and betaine (BT) on growth performance, nutrient digestion and ruminal fermentation in bulls. Forty-four Angus bulls were blocked by live body weight and then randomly divided into four groups in a 2 × 2 factorial design. Betaine of 0 or 0.6 g/kg dry matter (DM) was added to diets containing 0 or 0.6 g/kg DM GAA, respectively. The experiment included a 20 day period for adaptation and a 60 day period for data collection. Average daily gain and feed efficiency were increased by GAA or BT but no further increase was observed for supplementing BT and GAA together than for addition with BT or GAA alone. Supplementary GAA or BT did not influence DM intake but increased apparent digestibility of DM, organic matter (OM), crude protein (CP) and acid detergent fibre (ADF). Digestibility of neutral detergent fibre (NDF) was increased by GAA inclusion but was unaltered with BT provision. Ruminal pH reduced but total volatile fatty acids and ammonia nitrogen elevated with dietary inclusion of GAA or BT. Rumen short chain fatty acids percentages and fermentation pattern were not influenced by GAA. Dietary inclusion of BT increased molar proportions of acetate, valerate, isobutyrate and isovalerate as well as the ratio of acetate to propionate. Rumen populations of Ruminococcus flavefaciens and Fibrobacter succinogenes increased with addition of GAA or BT and the increase was greater when BT was added in diets with GAA compared to diets without GAA. Addition of GAA or BT increased activities of cellobiase, xylanase, α-amylase and protease and populations of total bacteria, cellulolytic bacteria and Ruminobacter amylophilus but did not affect Prevotella ruminicola. Addition of BT increased carboxymethyl-cellulase and pectinase activities and total fungi population. Blood creatine content was increased by GAA or BT and was greater for addition of GAA and BT together than for GAA or BT addition alone. Serum contents of glucose, folate, arginine and methionine were unchanged but total protein increased with GAA or BT provision. Blood homocysteine content was unaffected by GAA but decreased with BT supplementation. The data showed that GAA or BT addition improved growth performance and feed efficiency but supplementing GAA and BT together did not further increase the performance of bulls when compared with GAA or BT inclusion alone.
Multiple familial trichoepithelioma (MFT) (OMIM: 601606) is an autosomal dominantly inherited disorder characterized by numerous, skin-colored papules and nodules with pilar differentiation. ...Recently, several mutations in the cylindromatosis (
CYLD
) gene have been reported in MFT. In this study, a mutation analysis of the
CYLD
was conducted in a Chinese pedigree of typical MFT. Affected individuals were identified through probands from Shanxi Province, China. Lesional skin biopsy of the proband revealed the typical histopathological characteristics of trichoepithelioma. Individuals belonging to five consecutive generations were similarly affected, which indicated an autosomal dominant inheritance pattern. Genomic DNA was extracted from peripheral blood lymphocytes using standard phenol/chloroform extraction method. All the coding exons (4–20) and exon–intron boundaries of the
CYLD
gene were amplified by polymerase chain reaction (PCR). Direct sequencing of all PCR products amplified from the complete coding regions of the
CYLD
gene was performed to identify mutations. Sequencing of the
CYLD
gene was performed in a further 100 unrelated, unaffected control individuals to exclude the possibility of polymorphism. A novel heterozygous frameshift mutation c.1169_1170delCA (p.Thr390Argfs) was identified in exon 10 of the
CYLD
gene in the affected family members. This mutation was also detected in unaffected family members, but not in the unrelated, healthy individuals who were also analyzed. Our study expands the database on the
CYLD
gene mutations in MFT and should be useful in providing genetic counseling and prenatal diagnosis for families affected by MFT.
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