Implementation of a movement paradigm using the Commodore 64 microcomputer

Implementation of an alternating movement paradigm for monkeys was achieved using an inexpensive but versatile microcomputer, the Commodore 64. During task performance, the computer monitors one of three user selectable input signals (e.g. joint position) and continuously displays this signal as a moving cursor on a video monitor along with a user positioned target box. Other user defined parameters include in-target holding time and reinforcement ratio. The system also provides two sound cues to signal entry of the cursor into the target box and successful completion of a trial. Extensive use is made of the computer's intrinsic hardware features for implementation of movement paradigm functions. Use of external components is limited to digitizing and interface hardware. A two part software package consisting of a BASIC and a machine language program performs all task and hardware related functions. Acquisition and display of analog input signals, display of target positions, and delivery of auditory cues and applesauce rewards are all controlled by the machine language program. All user defined parameters are specified from the BASIC menu program. The specific programs described in this paper should be applicable to the control of tasks requiring alternation of a behavioral parameter between two target zones.     

Nodal and Cripto-1: Embryonic Pattern Formation Genes Involved in Mammary Gland Development and Tumorigenesis

Members of the TGFbeta superfamily and EGF-CFC family, such as Nodal and Cripto, are important mediators of anterior-posterior and left-right axis specification during embryogenesis. In this paper, we review the role of Nodal and Cripto as critical morphogen-like molecules, with an emphasis on Nodal and EGF-CFC signaling during embryonic pattern formation. New evidence from gene expression and transgenic mouse studies have shown that both Nodal and Cripto-1 are expressed within the mammary duct and that modulation of these genes can disrupt normal branching morphogenesis resulting in epithelial disorganization and defective ductal architecture. We describe these new findings and propose that Cripto and Nodal are candidate mammary morphogens. Finally, the data linking overexpression of Cripto and perturbations of Cripto signaling to cell transformation and tumor formation are discussed. The fact that Cripto can modulate multiple pathways suggests it may act to deregulate growth inhibitors/homeostasis factors early in the cell transformation process and then activate prosurvival pathways dependent on MAPK and PI3K/Akt later in fully transformed phenotypes.     

Trace and major elements in whole blood,serum, cerebrospinal fluid and urine of patients with Parkinson’s disease

Summary. Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine, serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinsons disease (PD) and 13 age-matched controls to ascertain the potential role of biological fluids as markers for this pathology. Analyses were performed by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field Inductively Coupled Plasma Mass Spectrometry. The serum oxidant status (SOS) and anti-oxidant capacity (SAC) were also determined. Results showed a decreasing trend for Al in all the fluids of PD patients, with the strongest evidence in serum. Calcium levels in urine, serum and blood of PD patients were significantly higher than in controls. Copper and Mg concentrations were significantly lower in serum of PD patients. Levels of Fe in urine, blood and CSF of patients and controls were dissimilar, with an increase in the first two matrices and a decrease in CSF. No significant difference was found in levels of Mn between patients and controls. Urinary excretion of Si was significantly higher in PD subjects than in controls. No clear difference between Zn levels in the two groups was found for serum, urine or CSF, but an increase in Zn levels in the blood of PD patients was observed. The SOS level in PD was significantly higher while the corresponding SAC was found to be lower in patients than in controls, in line with the hypothesis that oxidative damage is a key factor in the pathogenesis of PD. The results on the whole indicate the involvement of Fe and Zn (increased concentration in blood) as well as of Cu (decreased serum level) in PD. The augmented levels of Ca and Mg in the fluids and of Si in urine of patients may suggest an involuntary intake of these elements during therapy.     

Role of mitogen-activated protein kinase pathways in the production of tumor necrosis factor-alpha,interleukin-10, and monocyte chemotactic protein-1 by Mycobacterium tuberculosis H37Rv-infected human monocytes

The role of mitogen-activated protein kinase (MAPK) pathways in the secretion of tumor necrosis factor (TNF)-, interleukin (IL)-10, IL-8, and monocyte chemotactic protein-1 (MCP-1) was investigated in human monocytes that were infected with Mycobacterium tuberculosis H37Rv. Analysis of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase showed rapid phosphorylation of both subfamilies in response to M. tuberculosis H37Rv. Using highly specific inhibitors of p38 (SB203580) and of MAPK kinase-1 (U0126 and PD98059), we found that both p38 and ERK were essential for M. tuberculosis H37Rv-induced TNF- production, whereas activation of the p38 pathway, but not that of ERK, was essential for M. tuberculosis H37Rv-induced IL-10 production. Interestingly, the ERK pathway, but not that of p38, was critical for MCP-1 secretion from human monocytes that were infected with M. tuberculosis H37Rv. However, IL-8 secretion was not regulated by ERK1/2 or p38 MAPK. Collectively, these results suggest that induction of the MAPK pathway is required for the expression of TNF-, IL-10, and MCP-1 by human monocytes during M. tuberculosis H37Rv infection.     

Chronic ethanol consumption impairs receptor-mediated endocytosis of MAA-modified albumin by liver endothelial cells

Alcoholic liver disease has been associated with abnormalities in receptor-mediated endocytosis (RME) which results in abnormal degradation of metabolically altered proteins. Model systems using formaldehyde-modified albumin (f-Alb) have shown an impairment in RME following chronic alcohol consumption utilizing both in situ perfused rat livers and isolated rat liver endothelial cells (LECs). The discovery that alcohol metabolite derived aldehydes can modify proteins prompted a study to determine if malondialdehyde-acetaldehyde-modified albumin (MAA-Alb) would be degraded similar to that reported for f-Alb, and whether ethanol-fed rats would demonstrate an impaired RME with respect to this ligand which occurs as a consequence of chronic ethanol consumption. MAA-Alb was degraded slightly more than f-Alb in both in situ perfused livers and at the single cell level. This degradation was completely inhibited with 100x unlabeled f-Alb, which suggests the use of a similar receptor. Following alcohol consumption there was a 50-60% decrease in MAA-Alb degradation in whole livers and isolated LECs. Utilizing isolated LECs it was determined that impairment in internalization was the most likely mechanism for the decrease in the amount of MAA-Alb that was degraded. These data show that chronic alcohol consumption by rats does in fact impair RME of alcohol metabolite-derived adducted proteins, and this impairment is due to a defect in the post-internalization step rather than the binding or degradation of the modified protein.     

利用CT扫描及CAD技术建立肺三维有限元模型

目的探讨建立肺有限元模型的方法,以期应用于临床实验研究。方法通过CT扫描、Unigraph-icsV18.0进行影像边界记录、定标等方法,按照点、线、面、体的顺序重建三维结构,采用CAD数据处理技术,输入相关的材料特性,构建肺三维有限元模型。并通过有限元分析验证重建模型的有效性。结果采用Uni-graphicsV18.0建立肺的实体模型并划分单元,分析在生理载荷下肺不同组成部分的应力分布。结论该研究为肺有限元模型的建立提供了一种简便、准确的方法,为分析和研究各种情况下肺生物力学表现和为建立肺癌的运动模型创造了条件。     

NMR Studies of Retinoid-Protein Interactions: The Conformation of [13C]-β-Ionones Bound to β-Lactoglobulin B

Purpose. Vitamin A (retinol) and its metabolites comprise the natural retinoids. While the biological action of these molecules are thought to be primarily mediated by ca. 55 kDa nuclear retinoic acid receptors, a number of structurally similar 15-20 kDa proteins are involved in the transport, and possibly metabolism, of these compounds. The milk protein -lactoglobulin B (-LG) is an 18 kDa protein which binds retinol and may be involved in oral delivery of retinol to neonates. -LG also binds drugs and other natural products and is of potential interest as a protective delivery vehicle. Methods. To examine the conformation of the model retinoid -ionone both in solution and when bound to -LG, NMR and computational methods have been employed. Results. Taken together, NMR studies of -ionone in solution measuring scalar and dipolar coupling, as well as CHARMm calculations, suggest -ionone prefers a slightly twisted 6-s-cis conformation. Isotope-edited NMR studies of ^l3C-labeled -ionones bound to -LG, primarily employing the HMQC-NOE experiment, suggest -ionone also binds to -LG in its 6-s-cis conformation. Conclusions. The methods employed here allow estimates of protein-bound ligand conformation. However, additional sites of ligand labeling will be necessary to aid in binding site localization.     

Comparison of the MGIT TBc immunochromatographic assay with the Accuprobe Gen-Probe TB assay for identification of Mycobacterium tuberculosis complex: results from a low-burden tuberculosis setting

We compared the BD MPT64 TBc Antigen assay with the Gen-Probe TB assay for identifying Mycobacterium tuberculosis (MTB) from liquid culture vials. The BD TBc Antigen assay was more sensitive than and as specific as the Gen-Probe TB assay, making it a useful alternative for the rapid detection of MTB.     

Insulin Resistance and Type 2 Diabetes Mellitus: Its Relationship with the β3-Adrenergic Receptor

The β₃ subtype of adrenaline and noradrenaline receptors has been extensively characterized at structural and functional levels. Ligand binding and adenyl cyclase activation studies have helped to define their unique β-adrenergic profile. Humans, other larger mammals, and rodents share most of the characteristic β₃-adrenergic receptor properties, although obvious species-specific differences have been identified. Most studies in animal models have shown a distinct β₃-adrenergic receptor activity that results in an increase in energy expenditure, decrease of fat mass (especially of intra-abdominal fat), and increased glucose disposal efficiency. It is of interest that mild weight increase was shown to develop in female but not male mice, in whom the β₃-adrenergic receptor gene was disrupted. Recently, the incidence of a naturally occurring variant of the human β₃-adrenergic receptor was shown to correlate with hereditary obesity in Pima Indians and Japanese individuals. In Western obese patients, this phenotype increased the capacity to gain weight and develop type 2 diabetes mellitus. Studies of humans with the Trp⁶⁴Arg variant have shown controversial results. Many studies have failed to show any effect in heterozygous male subjects, and only modest effects in homozygous male subjects. In women, several studies have shown modest-to-significant effects regarding weight gain, intra-abdominal fat, and decreased insulin sensitivity in heterozygous and homozygous women. Other studies have failed to show any effect in heterozygous females.Disruptions in the activity of the β₃-adrenergic receptor in the homozygous male and the heterozygous or homozygous female appear to have a profound effect in animal models, but a limited consequence in human physiology. Association with obesity or diabetes in humans is still controversial. This difference between animal and human models may be explained by the different quantity and distribution of metabolically active brown adipose tissue in the two.