Multiple L1 progenitors in prosimian primates: phylogenetic evidence from ORF1 sequences

One of the uncertainties regarding the evolution of L1 elements is whether there are numerous progenitor genes. We present phylogenetic evidence from ORF1 sequences of slow loris (Nycticebus coucang) and galago (Galago crassicaudatus) that there were at least two distinct progenitors, active at the same time, in the ancestor of this family of prosimian primates. A maximum parsimony analysis that included representative L1s from human, rabbit, and rodents, along with the prosimian sequences, revealed that one of the galago L1s (Gc11) grouped very strongly with the slow loris sequences. The remaining galago elements formed their own unique and strongly supported clade. An analysis of replacement and silent site changes for each link of the most parsimonious tree indicated that during the descent of the Gc11 sequence approximately two times more synonymous than nonsynonymous substitutions had occurred, implying that the Gc11 founder was functional for some time after the split of galago and slow loris. Strong purifying selection was also evident on the galago branch of the tree. These data indicate that there were two distinct and contemporaneous L1 progenitors in the lorisoid ancestor, evolving under purifying selection, that were retained as functional L1s in the galago lineage (and presumably also in the slow loris). The prosimian ORF1 sequences could be further subdivided into subfamilies. ORF1 sequences from both the galago and slow loris have a premature termination codon near the 3' end, not shared by the other mammalian sequences, that shortens the open reading frame by 288 bp. An analysis of synonymous and nonsynonymous substitutions for the 5' and 3' portions, that included intra- and inter-subfamily comparisons, as well as comparisons among the other mammalian sequences, suggested that this premature stop codon is a prosimian acquisition that has rendered the 3' portion of ORF1 in these primates noncoding.     

Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies

BACKGROUND: Neurobehavioral studies have identified multiple cognitive and motor system disturbances in depressed patients. Neuroimaging studies have identified abnormalities in neocortex, striatum, and cerebellar vermis that are probable causes of these impairments. METHODS: To further clarify the origins of motor and cognitive disturbances in major depression, unmedicated depressed inpatients (n = 29) and an age- and gendermatched healthy comparison group (n = 19) were tested with a battery of oculomotor tasks selected to assess the functional integrity of frontostriatal circuitry and the cerebellar vermis. RESULTS: Depressed patients demonstrated increased rates of response suppression errors on an antisaccade task, less accurate memory for spatial location information in a spatial delayed response task, dysmetric visually guided saccades, and increased rates of saccadic intrusions during visual fixation. CONCLUSIONS: These results provide quantitative documentation of significant disturbances in neurophysiological processes subserved by prefrontal cortex and the cerebellar vermis during episodes of major depression.     

Cortical end-stopped perceptive fields: evidence from dichoptic and amblyopic studies

Psychophysical length and width spatial interactions associated with a line target were measured in normal observers dichoptically and in observers with naturally acquired amblyopia to investigate the neural locus of end-stopped perceptive fields. Results show (1) interocular transfer of psychophysical end-stopping, flank-inhibition, and length and width summation; and (2) severe, but significantly different, loss of end-stopping and flank-inhibition in the central visual fields of amblyopic eyes. Together, these results suggest a cortical basis for end-stopped perceptive fields, and that psychophysical end-stopping and flank-inhibition are a consequence of distinct cortical inhibition. The damaging effects of amblyopia on end-stopping and flank-inhibition are weaker and less different from each other under transient conditions. Our results provide further evidence supporting the suggestion that end-stopped perceptive fields are the psychophysical analogs of cortical end-stopped receptive fields.     

Mechanisms of normal and abnormal neurulation: evidence from embryo culture studies

In this paper we estimate the size of several categories of "Israeli" immigrants in the United States. According to the 1990 U.S. census, there were about 95,000 Israeli-born immigrants in the United States in that year. Using the language and ancestry information available in the Public Use Microdata Sample (PUMS) of the 1990 census, we estimate that of this total, about 80,000 are Jews and 15,000 are Palestinian Arabs born in Israel. In addition to the Israeli-born, we present a range for the number of Jewish immigrants from Israel who are not Israeli-born (about 30,000-56,000). Thus our estimate for the total number of Jewish immigrants from Israel in the United States in 1990 is between 110,000 and 135,000. Fertility information available in the PUMS, also enable us to provide estimates for the number of second-generation Israelis in the United States in the 1990 (about 42,000). Finally, using both the 1980 and 1990 PUMS, we provide estimates for the rate of return migration among Israeli-born Jewish immigrants in the United States.     

Prevention of colon cancer by pre- and probiotics: evidence from laboratory studies

Oligofructose and inulin, selective fermentable chicory fructans, have been shown to stimulate the growth of bifidobacteria which are regarded as beneficial strains in the colon. Studies were designed to evaluate inulin (Raftiline) and oligofructose (Raftilose), for their potential inhibitory properties against aberrant crypt foci (ACF) formation in the colon of rats. ACF are putative preneoplastic lesions from which adenomas and carcinomas may develop. The results of this study demonstrate that dietary administration of oligofructose and inulin inhibits the formation of preneoplastic lesions in the colon suggesting the potential colon tumour inhibitory properties of chicory fructans. Since these prebiotics selectively stimulate the growth of bifidobacteria, tumour inhibitory activity of lyophilized cultures of Bifidobacterium longum (BL) against azoxymethane (AOM)-induced colon carcinogenesis in rats and modulating effect of these cultures on colonic tumour cell proliferation, ornithine decarboxylase (ODC) activity, and ras-p21 oncoprotein expression were investigated. Dietary administration of lyophilized cultures of BL strongly suppressed AOM-induced colon tumour development. Inhibition of colon carcinogenesis was associated with a decrease in colonic mucosal cell proliferation and colonic mucosal and tumour ODC and ras-p21 activities.     

Pulse radiolysis studies on cytochrome cd1 nitrite reductase from Thiosphaera pantotropha: evidence for a fast intramolecular electron transfer from c-heme to d1-heme

Electron transfer within cytochrome cd1 from Thiosphaera pantotropha was investigated by the technique of pulse radiolysis. The reduction of the heme centers in this nitrite reductase occurred in two phases as judged from kinetic difference spectra. In the faster phase, radiolytically generated N-methylnicotinamide (NMA) radicals selectively reduced the c-heme of the enzyme. From the absorbance increase at 420 nm, a characteristic of formation of the ferrousc-heme, the second-order rate constant for this electron transfer process was estimated to be 3.8 x 10(9) M-1 s-1 at pH 7.0. In the slower phase, a decrease of absorption around 420 and 550 nm, corresponding to a reoxidation of the c-heme, was accompanied by an increase of absorption around 460 and 640 nm, characteristic of formation of the reduced d1-heme. This indicated that an intramolecular electron transfer from the c-heme to the d1-heme occurred. The first-order rate constant of this process was calculated to be 1.4 x 10(3) s-1 at pH 7.0 and was independent of the enzyme concentration. In the presence of nitrite the interheme electron transfer rate was not affected, but on a time scale of seconds a new species associated with the d1-heme, having an absorption maximum at 640 nm, was detected and is proposed to reflect ligand binding to this heme. These results suggest the role of the c-heme as the electron acceptor site in cytochrome cd1 and in mediating the electron transfer to the catalytic site of the enzyme. Moreover, the fast interheme electron transfer rate argues against this process being the rate determining step in catalysis.     

Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals

The microsomal enzyme acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) catalyzes the esterification of cellular cholesterol with fatty acids to form cholesterol esters. ACAT activity is found in many tissues, including macrophages, the adrenal glands, and the liver. In macrophages, ACAT is thought to participate in foam cell formation and thereby to contribute to atherosclerotic lesion development. Disruption of the gene for ACAT (Acact) in mice resulted in decreased cholesterol esterification in ACAT-deficient fibroblasts and adrenal membranes, and markedly reduced cholesterol ester levels in adrenal glands and peritoneal macrophages; the latter finding will be useful in testing the role of ACAT and macrophage foam cell formation in atherosclerosis. In contrast, the livers of ACAT-deficient mice contained substantial amounts of cholesterol esters and exhibited no reduction in cholesterol esterification activity. These tissue-specific reductions in cholesterol esterification provide evidence that in mammals this process involves more than one form of esterification enzyme.     

Short- and long-term effects of training phonological awareness in kindergarten: evidence from two German studies

Two training studies replicated and extended a Scandinavian study by Lundberg, Frost, and Petersen (1988). In Study 1, a 6-month metalinguistic training program was given to kindergartners (mean age: 5 years 7 months) who were later compared to a control group in the regular kindergarten program. Tests of phonological awareness and other metalinguistic and cognitive variables were given before and after training; a metalinguistic transfer test was given after training. Reading and spelling skills were assessed at the end of Grades 1 and 2, respectively. The training program was improved and monitored more closely in Study 2. Both studies revealed short- and long-term effects, consistent with Lundberg et al. (1988) and extending findings from Anglo-American and Scandinavian populations to German children.     

Decision making and reward in frontal cortex: Complementary evidence from neurophysiological and neuropsychological studies.

Patients with damage to the prefrontal cortex (PFC)—especially the ventral and medial parts of PFC—often show a marked inability to make choices that meet their needs and goals. These decision-making impairments often reflect both a deficit in learning concerning the consequences of a choice, as well as deficits in the ability to adapt future choices based on experienced value of the current choice. Thus, areas of PFC must support some value computations that are necessary for optimal choice. However, recent frameworks of decision making have highlighted that optimal and adaptive decision making does not simply rest on a single computation, but a number of different value computations may be necessary. Using this framework as a guide, we summarize evidence from both lesion studies and single-neuron physiology for the representation of different value computations across PFC areas. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Retinotopic organisation of cortical mechanisms responsive to colour: evidence from patient studies

This paper deals with the visual responses of three patients who have impaired colour vision consequent on cortical dysfunction which, in two of them, is associated with demonstrable neuronal damage. The studies to be described are concerned particularly with the spatial attributes of their chromatic response mechanisms. Data are presented which establish that a hemianope GY has coarse chromatic discrimination for large stimuli located within his 'blind' hemifield. GY responds to stimuli containing differently coloured equiluminant components as if the coloured components were averaged over the whole field and it is speculated that such spatial averaging may correspond to the process which, in normal vision, provides compensation for change of illuminant in order to achieve colour constancy. Colour constancy is impaired in a second patient, BL, who has cortical lesions involving the lingual and fusiform gyri, areas which are partially spared in GY. It is shown that movement, but not colour, presented to GY's normal hemifield generates a response localised in his blind hemifield and disinhibitory interaction between movement and colour is illustrated for a patient MW, in whom colour chromatic stimuli generate spreading inhibition of visual responses. This inhibitory interaction is propagated between widely separated stimuli, including those which are located on opposite sides of the vertical meridian. We discuss these experimental results in relation to anatomical and physiological mechanisms of the primate visual cortex.     

Distribution of heterochromatin on the mitotic chromosomes of Musca domestica L. in relation to the activity of male-determining factors

Nitric oxide (NO) is a pluripotent regulatory molecule, yet the molecular mechanisms by which it exerts its effects are largely unknown. Few physiologic target molecules of NO have been identified, and even for these, the modifications caused by NO remain uncharacterized. Human glutathione reductase (hGR), a central enzyme of cellular antioxidant defense, is inhibited by S-nitrosoglutathione (GSNO) and by diglutathionyl-dinitroso-iron (DNIC-[GSH]2), two in vivo transport forms of NO. Here, crystal structures of hGR inactivated by GSNO and DNIC-[GSH]2 at 1.7 A resolution provide the first picture of enzyme inactivation by NO-carriers: in GSNO-modified hGR, the active site residue Cys 63 is oxidized to an unusually stable cysteine sulfenic acid (R-SOH), whereas modification with DNIC-[GSH]2 oxidizes Cys 63 to a cysteine sulfinic acid (R-SO2H). Our results illustrate that various forms of NO can mediate distinct chemistry, and that sulfhydryl oxidation must be considered as a major mechanism of NO action.     

基于L1基础自动化系统的铁区MES的实现

针对宝钢不锈钢有限公司铁区没有完善的L2系统但需要实现铁区MES应用的情况,提出了基于L1基础自动化系统的铁区MES解决方案。铁区MES直接从L1系统获取实时生产数据并进行相关处理,完成部分原来由L2系统承担的任务,从而实现了铁区MES的主要功能和MES对铁区所有工序的全覆盖。该方案投入生产后运行正常,对于铁区没有完善L2系统但需要实现MES应用的企业,有一定的推广借鉴价值。     

The moderating effect of self-esteem in reaction to voice: Converging evidence from five studies.

It has been posited that high self-esteem persons (high SEs) are more confident than low self-esteem persons (low SEs) of their capability to provide meaningful input in a decision process. If this is so, then high SEs should be more influenced by their perceived level of voice, relative to low SEs. Survey data from 4 field studies showed that voice was more positively related to various dependent variables among high SEs than low SEs. In Study 5, the authors experimentally manipulated voice as well as participants' beliefs about their capability to provide meaningful input. As expected, voice had a greater impact on the reactions of participants who were led to believe that they were more capable of providing meaningful input. Theoretical implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D2 receptors may modulate the function of the striatal transporter for dopamine: kinetic evidence from studies in vitro and in vivo

Recently it was hypothesized by others that the D2 dopamine receptor can regulate the uptake of dopamine. However, the evidence in support of this hypothesis, although compelling, was not based on observations related to direct measures of the kinetic activity of the transporter itself. Here kinetic evidence in support of this hypothesis is shown. The apparent time-resolved initial velocity of the transport of 1.0 microM dopamine into striatal suspensions, measured using rotating disk electrode voltammetry, was found to increase in the presence of the D2 receptor agonist, quinpirole, at 100 nM. This effect was reversed by sulpiride. In separate studies it was shown that acute and chronic treatments with haloperidol at 0.5 mg/kg, i.p., reduced the reuptake transport of dopamine in vivo following intrastriatal stimulation of its release by K+. Thus, it appears that D2 receptors may influence the functioning of the striatal transporter for dopamine. These results are consistent with a model in which presynaptically released dopamine may feed back onto the function of its transporter to increase the velocity of the clearance of synaptic dopamine following an action potential, suggesting the existence of a mechanism, in addition to release and synthesis modulation, for fine-tuning dopaminergic chemical signaling.     

Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies

We have studied cerebral autoregulation and vasoreactivity to carbon dioxide in 10 patients with the sepsis syndrome receiving intensive therapy. All patients were sedated with infusions of midazolam and fentanyl, and their lungs were ventilated mechanically with oxygen-air to maintain normoxia and normocapnia. Inotropic support and antibiotics were administered as necessary. During a period of constant level of sedation and stable haemodynamics, cerebral autoregulation was tested by increasing mean arterial pressure (MAP) by 23 (SD 2) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler ultrasonography. Carbon dioxide reactivity was tested by varying PaCO2 between 3.0 and 7.0 kPa and simultaneously recording vmca. There was no significant change in vmca (57 (22) and 59 (23) cm s-1) during the increase in MAP (75 (11) to 98 (10) mm Hg). The mean index of autoregulation (IOR) was 0.92 (SEM 0.03), which was not significantly different from 1, indicating near perfect autoregulation. Although absolute carbon dioxide reactivity was lower than reported previously in awake subjects, relative carbon dioxide reactivity was within normal limits for all patients (11.6 (SEM 0.8) cm s-1 and 20.3 (3) % kPa-1, respectively). We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remained intact in patients with the sepsis syndrome, providing indirect evidence that at least in the early stages of the syndrome, the widespread sepsis-induced vasoparalysis does not involve the cerebral vasculature.     

The existence of a precursor of cathepsin D: evidence from autolysis, denaturation and activation studies

This report evidences that the single polypeptide chain of cathepsin D undergoes in vitro autolysis resulting in heavy (Mr about 30000) and light (Mr about 15000) polypeptide chains. These two chains are held together through non-covalent interaction, thus constituting a stable active conformation. Fluorescence and circular dichroism measurements demonstrate the irreversible denaturation of cathepsin D. The existence of cathepsin D precursor, cathepsinogen D, of about 50000 molecular weight was proved. Cathepsinogen D is converted to the active enzyme by intramolecular activation, releasing activation-inhibitory peptide(s).     

Portacaval anastomosis results in altered neuron--astrocytic metabolic trafficking of amino acids: evidence from 13C-NMR studies

13C-NMR spectroscopy was used to evaluate the dynamic consequences of portacaval anastomosis on neuronal and astrocytic metabolism and metabolic trafficking between neurons and astrocytes. Glutamate is predominantly labeled from [1-13C]glucose, whereas [2-13C]acetate is more efficient in labeling glutamine, in accordance with its primary metabolism in astrocytes. Alanine and succinate labeling was only observed with [1-13C]glucose as precursor. Brain [1-13C]glucose metabolism in portacaval-shunted rats was similar to that in sham-operated controls with the exception of labeled glutamine and succinate formation, which was increased in shunted rats. The 13C enrichment was, however, decreased owing to an increase in total glutamine and succinate. Using [2-13C]acetate, on the other hand, flux of astrocytic label to neurons was severely decreased because label incorporation into glutamate, aspartate, and GABA was decreased following portacaval shunting. The latter amino acids are predominantly localized in neurons. These findings demonstrate that metabolic trafficking of amino acids from astrocytes to neurons is impaired in portacaval-shunted rats.     

Expression of two alpha 2-adrenergic receptor subtypes in human placenta: evidence from direct binding studies

Adrenergic receptors may play an important role for mediating a variety of metabolic and haemodynamic effects of catecholamines including placental blood flow. The alpha-adrenergic receptors of the human placenta were characterized in vitro by the use of [3H]rauwolscine and [3H]prazosin as radioligands. Saturation experiments would suggest that the alpha-adrenoceptors in the human placenta are alpha 2. Comparative binding studies were performed, using recently synthesized compounds (Beecham Pharmaceuticals, UK) selective for alpha 2A (BRL-44408) and alpha 2B (BRL-41992) subtypes. The results indicate that human placenta contains at least two pharmacologically distinct alpha 2-adrenoceptor subtypes with approximately 60 per cent alpha 2A and 40 per cent alpha 2B receptors. In contrast with the pattern of increasing beta-adrenoceptor density, the concentration of alpha 2-adrenoceptors in term placentae is significantly lower than in placentae from the first trimester.