This study used priming exercise in young boys to investigate (i) how muscle oxygen delivery and oxygen utilization, and muscle activity modulate oxygen uptake kinetics during exercise; and (ii) ...whether the accelerated oxygen uptake kinetics following priming exercise can improve exercise tolerance. Seven boys that were aged 11.3 ± 1.6 years completed either a single bout (bout 1) or repeated bouts with 6 min of recovery (bout 2) of very heavy-intensity cycling exercise. During the tests oxygen uptake, muscle oxygenation, muscle electrical activity and exercise tolerance were measured. Priming exercise most likely shortened the oxygen uptake mean response time (change, ±90% confidence limits; –8.0 s, ±3.0), possibly increased the phase II oxygen uptake amplitude (0.11 L·min
−1
, ±0.09) and very likely reduced the oxygen uptake slow component amplitude (–0.08 L·min
−1
, ±0.07). Priming resulted in a likely reduction in integrated electromyography (–24% baseline, ±21% and –25% baseline, ±19) and a very likely reduction in Δ deoxyhaemoglobin/Δoxygen uptake (–0.16, ±0.11 and –0.09, ±0.05) over the phase II and slow component portions of the oxygen uptake response, respectively. A correlation was present between the change in tissue oxygenation index during bout 2 and the change in the phase II (r = –0.72, likely negative) and slow component (r = 0.72, likely positive) oxygen uptake amplitudes following priming exercise, but not for muscle activity. Exercise tolerance was likely reduced (change –177 s, ±180) following priming exercise. The altered phase II and slow component oxygen uptake amplitudes in boys following priming exercise are linked to an improved localised matching of muscle oxygen delivery to oxygen uptake and not muscle electrical activity. Despite more rapid oxygen uptake kinetics following priming exercise, exercise tolerance was not enhanced.
Gliomatosis peritonei is a rare pathologic finding that is associated with ovarian teratomas and malignant mixed germ cell tumors. The occurrence of gliomatosis as a mature glial implant can impart ...an improved prognosis to patients with immature ovarian teratoma, making prompt and accurate diagnosis important. We describe a case of recurrent immature teratoma in a 10-yr-old female patient, in which comparative analysis of the RNA sequencing gene expression data from the patient's tumor was used effectively to aid in the diagnosis of gliomatosis peritonei.
Mast cells generated from Rac2-deficient (−/−) mice demonstrated defective actin-based functions, including adhesion, migration, and degranulation. Rac2
−/− mast cells generated lower numbers and ...less mast cell colonies in response to growth factors and were deficient in vivo. Rac2
−/− mast cells demonstrated a significant reduction in growth factor–induced survival, which correlated with the lack of activation of Akt and significant changes in the expression of the Bcl-2 family members BAD and Bcl-X
L, in spite of a 3-fold induction of Rac1 protein. These results suggest that Rac2 plays a unique role in multiple cellular functions and describe an essential role for Rac2 in growth factor–dependent survival and expression of BAD/Bcl-X
L.
Background:
The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor pro‐opiomelanocortin. A growing body of literature suggests that the MC system ...modulates neurobiological responses to drugs of abuse. Because ethanol has direct effects on central pro‐opiomelanocortin activity, it is possible that MC neuropeptides participate in the control of voluntary ethanol consumption. Here we assessed the possibility that MC receptor (MCR) agonists modulate ethanol intake via the MC3 receptor (MC3R) and/or the MC4 receptor (MC4R) and whether the MCR antagonist AgRP‐(83‐132) controls ethanol consumption.
Methods:
Mc3r‐deficient (Mc3r−/−) and wild‐type (Mc3r+/+) littermate mice were given intraperitoneal (10 mg/kg) and intracerebroventricular (1.0 μg ICV) doses of melanotan II (MTII), a nonselective MCR agonist. To assess the role of MC4R, C57BL/6J mice were given an ICV infusion of the highly selective MC4R agonist cyclo(NH‐CH2‐CH2‐CO‐His‐d‐Phe‐Arg‐Trp‐Glu)‐NH2 (1.0 or 3.0 μg). Finally, naïve C57BL/6J mice were given an ICV infusion of AgRP‐(83‐132) (0.05 and 1.0 μg).
Results:
MTII was similarly effective at reducing ethanol drinking in Mc3r‐deficient (Mc3r−/−) and wild‐type (Mc3r+/+) littermate mice. Furthermore, ICV infusion of the MC4R agonist significantly reduced ethanol drinking, whereas ICV infusion of AgRP‐(83‐132) significantly increased ethanol drinking in C57BL/6J mice. Neither MTII nor AgRP‐(83‐132) altered blood ethanol levels at doses that modulated ethanol drinking.
Conclusions:
The present results suggest that MC4R, and not MC3R, modulates MCR agonist–induced reduction of ethanol consumption and that ethanol intake is increased by the antagonistic actions of AgRP‐(83‐132). These findings strengthen the argument that MCR signaling controls ethanol consumption and that compounds directed at MCR may represent promising targets for treating alcohol abuse disorders in addition to obesity.
Research on the actions of ethanol at the GABAergic synapse has traditionally focused on postsynaptic mechanisms, but recent data demonstrate that ethanol also increases both evoked and spontaneous ...GABA release in many brain regions. Using whole-cell voltage-clamp recordings, we previously showed that ethanol increases spontaneous GABA release at the rat interneuron–Purkinje cell synapse. This presynaptic ethanol effect is dependent on calcium release from internal stores, possibly through activation of inositol 1,4,5-trisphosphate receptors (IP3Rs). After confirming that ethanol targets vesicular GABA release, in the present study we used electron microscopic immunohistochemistry to demonstrate that IP3Rs are located in presynaptic terminals of cerebellar interneurons. Activation of IP3Rs requires binding of IP3, generated through activation of phospholipase C (PLC). We find that the PLC antagonist edelfosine prevents ethanol from increasing spontaneous GABA release. Diacylglycerol generated by PLC and calcium released by activation of the IP3R activate protein kinase C (PKC). Ethanol-enhanced GABA release was blocked by two PKC antagonists, chelerythrine and calphostin C. When a membrane impermeable PKC antagonist, PKC (19–36), was delivered intracellularly to the postsynaptic neuron, ethanol continued to increase spontaneous GABA release. Overall, these results suggest that activation of the PLC/IP3R/PKC pathway is necessary for ethanol to increase spontaneous GABA release from presynaptic terminals onto Purkinje cells.
This study used priming exercise in young boys to investigate (i) how muscle oxygen delivery and oxygen utilization, and muscle activity modulate oxygen uptake kinetics during exercise; and (ii) ...whether the accelerated oxygen uptake kinetics following priming exercise can improve exercise tolerance. Seven boys that were aged 11.3 ± 1.6 years completed either a single bout (bout 1) or repeated bouts with 6 min of recovery (bout 2) of very heavy-intensity cycling exercise. During the tests oxygen uptake, muscle oxygenation, muscle electrical activity and exercise tolerance were measured. Priming exercise most likely shortened the oxygen uptake mean response time (change, ±90% confidence limits; –8.0 s, ±3.0), possibly increased the phase II oxygen uptake amplitude (0.11 L·min
−1
, ±0.09) and very likely reduced the oxygen uptake slow component amplitude (–0.08 L·min
−1
, ±0.07). Priming resulted in a likely reduction in integrated electromyography (–24% baseline, ±21% and –25% baseline, ±19) and a very likely reduction in Δ deoxyhaemoglobin/Δoxygen uptake (–0.16, ±0.11 and –0.09, ±0.05) over the phase II and slow component portions of the oxygen uptake response, respectively. A correlation was present between the change in tissue oxygenation index during bout 2 and the change in the phase II (r = –0.72, likely negative) and slow component (r = 0.72, likely positive) oxygen uptake amplitudes following priming exercise, but not for muscle activity. Exercise tolerance was likely reduced (change –177 s, ±180) following priming exercise. The altered phase II and slow component oxygen uptake amplitudes in boys following priming exercise are linked to an improved localised matching of muscle oxygen delivery to oxygen uptake and not muscle electrical activity. Despite more rapid oxygen uptake kinetics following priming exercise, exercise tolerance was not enhanced.
Cement-bonded particleboard (CBPB) as a composite of wood chips and reacted Portland cement is dimensionally unstable in service in the presence of changes in relative humidity (RH). One solution to ...this deficiency is the application of surface coatings to reduce its magnitude. The work reported here first evaluated the compatibility of various sealers to the highly alkaline surface of CBPB using small coupons of material. Three proprietary sealers were then applied to large-sized samples, and the most promising sealer was then subjected to long-term exposure. The test results indicated the following: (1) The ranking in effectiveness of sealers was proprietary system>model systems, and solvent-borne sealers>water-borne sealers. (2) The behaviour of coated CBPB reflected the change of RH, although the amplitude of the change was much reduced. CBPB coated with the most effective sealer showed 70–90% reduction in both mass and dimensions over the whole range of RH exposure, with the exception of the samples on moving from 65% to 90% RH compared with uncoated CBPB. (3) For the most effective sealer, doubling of the number of coats reduced mass change to about 60% that of a single coat during cyclic exposure and 20% to 70% for dimensions, but the level of reduction decreased as the number of coats increased. (4) All coatings showed a strong resistance to carbonation. Coated CBPB did not exhibit a consistent increase in mass and decrease in dimensions with cycles. (5) Under long-term exposure, there was a slight deterioration of the coatings. (6) The hysteresis loops for both mass and dimensional changes of coated CBPB moved upwards as the number of cycles increased; this is in contrast to that for dimensional change of uncoated CBPB.
Little is known of the persistence and pathogenicity of human herpesvirus 6 (HHV-6) after primary infection, including the role of strain variant. Over 2 to 5 years, 2,716 children and 149 families ...were studied. Peripheral blood mononuclear cell (PBMC), saliva, and cerebrospinal fluid (CSF) specimens were examined for HHV-6 DNA and variant. Ninety-nine percent of isolates causing primary infection were HHV-6 variant B (HHV-6B), which predominated in 95%–98% of the variants persisting in PBMC and saliva specimens from children and adults. Of 668 CSF samples, 13% contained HHV-6 DNA; of 77 children examined after primary infection, 61% had HHV-6 DNA detected only in their CSF and 39% had HHV-6 DNA in both CSF and PBMCs. HHV-6 variant A (HHV-6A) was detected significantly (P = .0001) more frequently in CSF than in PBMCs or saliva. In children for whom HHV-6 was identified in both CSF and PBMCs, PBMCs contained only HHV-6B, while CSF contained HHV-6A or HHV-6B, not both. Thus, in patients with dual infection, only HHV-6A persisted in CSF, which suggests that HHV-6A has greater neurotropism. Findings for adults indicate that dual infection occurs; variant persistence is similar to that for children. The frequency of HHV-6A infection increased little with age, thereby indicating that HHV- 6A infection remains uncommon into adulthood. This study suggests that HHV-6 variants have different immunobiologic courses and neurotropism.
The human α7 neuronal nicotinic acetylcholine receptor gene (HGMW-approved symbol CHRNA7) has been characterized from genomic clones. The gene is similar in structure to the chick α7 gene with 10 ...exons and conserved splice junction positions. The size of the human gene is estimated to be larger than 75 kb. A putative promoter 5′ of the translation start in exon 1 has been cloned and sequenced. The promoter region lacks a TATA box and has a high GC content (77%). Consensus Sp1, AP-2, Egr-1, and CREB transcription factor binding sites appear to be conserved between bovine and human genes. The α7 nAChR gene was found to be partially duplicated, with both loci mapping to the chromosome 15q13 region. A yeast artificial chromosome contig was constructed over a genetic distance of 5 cM that includes both α7 loci and the region between them. Four novel exons are described, located in genomic clones containing the partially duplicated gene. The duplicated sequences, including the novel exons, are expressed in human brain.
Expression of a D1 dopamine receptor was examined in the rat brain by using a combination of in situ hybridization and in vitro receptor autoradiography. Cells expressing D1 receptor mRNA were ...localized to many, but not all, brain regions receiving dopaminergic innervation. The highest levels of hybridization were detected in the caudate-putamen, nucleus accumbens, and olfactory tubercle. Cells expressing D1 receptor mRNA were also detected throughout the cerebral cortex, limbic system, hypothalamus, and thalamus. D1 receptor mRNA was differentially expressed in distinct regions of the hippocampal formation. Dentate granule cells were labeled in dorsal but not ventral regions, whereas the subicular complex was prominently labeled in ventral but not dorsal regions. Intermediate to high levels of D1 binding sites, but no hybridizing D1 receptor mRNA, were detected in the substantia nigra pars reticulata, globus pallidus, entopeduncular nucleus, and subthalamic nucleus. In these brain regions, which are involved in the efferent flow of information from the basal ganglia, D1 receptors may be localized on afferent nerve terminals originating in other brain regions. These results indicate that in addition to a role in control of motor function, the D1 receptor may also participate in the cognitive, affective, and neuroendocrine effects of dopaminergic neurotransmission.
PDF
