面孔社会信息对注视提示效应的调制及其神经机制

眼睛注视是一种独特的非言语社会线索,能够诱发对生存和进化至关重要的注意效应。近年来,研究者采用中央线索提示范式及其变式,关注了面孔社会信息尤其是表情对这一注意效应的调节。面孔表情的调节作用与具体的表情类型有关,同时会受到任务因素和个体因素的影响。这一调节作用会随个体发展而逐渐成熟,与负责对面孔表情和注视方向各自及整合加工的机制相关,涉及到杏仁核和颞上沟脑区。除了面孔表情,其他面孔社会信息(如熟悉性和可信任度、优势度和社会地位、群体属性)也可以调节注视提示效应。这一调节可能涉及额叶视区、额顶注意网络。对面孔表情及其他社会信息调制注视提示效应的行为学证据及其神经机制进行系统综述,能够深化当前对面孔加工和注视提示效应间关系的理解,为社会认知障碍的临床诊断和干预提供参考。     

What We Observe Is Biased by What Other People Tell Us: Beliefs about the Reliability of Gaze Behavior Modulate Attentional Orienting to Gaze Cues

For effective social interactions with other people, information about the physical environment must be integrated with information about the interaction partner. In order to achieve this, processing of social information is guided by two components: a bottom-up mechanism reflexively triggered by stimulus-related information in the social scene and a top-down mechanism activated by task-related context information. In the present study, we investigated whether these components interact during attentional orienting to gaze direction. In particular, we examined whether the spatial specificity of gaze cueing is modulated by expectations about the reliability of gaze behavior. Expectations were either induced by instruction or could be derived from experience with displayed gaze behavior. Spatially specific cueing effects were observed with highly predictive gaze cues, but also when participants merely believed that actually non-predictive cues were highly predictive. Conversely, cueing effects for the whole gazed-at hemifield were observed with non-predictive gaze cues, and spatially specific cueing effects were attenuated when actually predictive gaze cues were believed to be non-predictive. This pattern indicates that (i) information about cue predictivity gained from sampling gaze behavior across social episodes can be incorporated in the attentional orienting to social cues, and that (ii) beliefs about gaze behavior modulate attentional orienting to gaze direction even when they contradict information available from social episodes.     

Stabilization of Gaze during Early Xenopus Development by Swimming-Related Utricular Signals

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Spatial and Temporal Attention Modulate the Early Stages of Face Processing: Behavioural Evidence from a Reaching Paradigm

A presently unresolved question within the face perception literature is whether attending to the location of a face modulates face processing (i.e. spatial attention). Opinions on this matter diverge along methodological lines – where neuroimaging studies have observed that the allocation of spatial attention serves to enhance the neural response to a face, findings from behavioural paradigms suggest face processing is carried out independently of spatial attention. In the present study, we reconcile this divide by using a continuous behavioural response measure that indexes face processing at a temporal resolution not available in discrete behavioural measures (e.g. button press). Using reaching trajectories as our response measure, we observed that although participants were able to process faces both when attended and unattended (as others have found), face processing was not impervious to attentional modulation. Attending to the face conferred clear benefits on sex-classification processes at less than 350ms of stimulus processing time. These findings constitute the first reliable demonstration of the modulatory effects of both spatial and temporal attention on face processing within a behavioural paradigm.     

Pharmacological Evidence for the Modulation of Monoamine Release by Adenosine in the Invertebrate Nervous System

An in vitro preparation from the pedal ganglia of the marine bivalve, Mytilus edulis, was used to examine the modulation of transmitter release by adenosine and its analogs from invertebrate nervous tissue. The ganglia of this organism contain the monoamines dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and the presynaptic release of these substances is known to be calcium-dependent. This organism also contains a DA-sensitive adenylate cyclase system which resembles that seen in mammals. Neural tissue from the pedal ganglia was incubated with labeled monoamines, and release studies were then conducted in superfusion chambers; release of monoamines was evoked by the addition of 50 mM KCl. Addition to the superfusion medium of the adenosine analog, 5'-N-ethylcarboxamidoadenosine (NECA; 10 nM), inhibited the release of 5-HT and DA, and to a lesser extent NE, whereas 100-fold higher concentrations of adenosine itself and the adenosine analog, R-N6-phenylisopropyladenosine, were required to achieve comparable levels of inhibition. The inhibitory effects of NECA on neurotransmitter release were blocked by the adenosine receptor antagonist, theophylline (IC50 = 10-14 microM). The results from this study indicate for the first time the possible role of adenosine as a modulator of neurotransmitter release in the invertebrate nervous system.     

Molecular Evidence for the Early History of Living Amphibians

The evolutionary relationships of the three orders of living amphibians (lissamphibians) has been difficult to resolve, partly because of their specialized morphologies. Traditionally, frogs and salamanders are considered to be closest relatives, and all three orders are thought to have arisen in the Paleozoic (>250 myr). Here, we present evidence from the DNA sequences of four mitochondrial genes (2.7 kilobases) that challenges the conventional hypothesis and supports a salamander–caecilian relationship. This, in light of the fossil record and distribution of the families, suggests a more recent (Mesozoic) origin for salamanders and caecilians directly linked to the initial breakup of the supercontinent Pangaea. We propose that this single geologic event isolated salamanders and archaeobatrachian frogs on the northern continents (Laurasia) and the caecilians and neobatrachian frogs on the southern continents (Gondwana). Among the neobatrachian frog families, molecular evidence supports a South American clade and an African clade, inferred here to be the result of mid-Cretaceous vicariance.     

Evidence of Slow Motions by Cross-Correlated Chemical Shift Modulation in Deuterated and Protonated Proteins

Cross-correlated fluctuations of isotropic chemical shifts can provide evidence for slow motions in biomolecules. Slow side-chain dynamics have been investigated in (15)N and (13)C enriched ubiquitin by monitoring the relaxation of C(alpha)-C(beta) two-spin coherences (Frueh et al., 2001). This method, which had hitherto been demonstrated only for protonated ubiquitin, has now been applied to both protonated and deuterated proteins. Deuteration reduces the dipole-dipole contributions to the DD/DD cross-correlation, thus facilitating the observation of subtle effects due to cross-correlation of the fluctuations of the isotropic (13)C chemical shifts. The decays of double- and zero-quantum coherences are significantly slower in the deuterated protein than in the protonated sample. Slow motions are found both in loops and in secondary structure elements.     

Infection with Eimeria tenella: Modulation of Lymphocyte Blastogenesis by Specific Antigen,and Evidence for Immunodepression1

ABSTRACT. The blastogenic effects of specific parasite antigen and of mitogens on the lymphocytes of chickens infected with Eimeria tenella were examined. Lymphocytes from infected chickens were stimulated to divide when cultured with parasite antigen, but their responses to the T-cell mitogen, phytohemagglutinin (PHA), were depressed throughout the period of infection. Responses to the B-cell mitogen, lipopolysaccharide (LPS), were depressed during the first week of infection but enhanced in the second week. The inclusion of plasma samples from infected chickens in the culture medium depressed the responses of normal spleen lymphocytes to PHA, suggesting that soluble suppressor factors are generated during infection.     

Why Most Biomedical Findings Echoed by Newspapers Turn Out to be False: The Case of Attention Deficit Hyperactivity Disorder

Context

Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies.

Objective

To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies.

Methods

We focused on attention deficit hyperactivity disorder (ADHD). Using Factiva and PubMed databases, we identified 47 scientific publications on ADHD published in the 1990s and soon echoed by 347 newspapers articles. We selected the ten most echoed publications and collected all their relevant subsequent studies until 2011. We checked whether findings reported in each “top 10” publication were consistent with previous and subsequent observations. We also compared the newspaper coverage of the “top 10” publications to that of their related scientific studies.

Results

Seven of the “top 10” publications were initial studies and the conclusions in six of them were either refuted or strongly attenuated subsequently. The seventh was not confirmed or refuted, but its main conclusion appears unlikely. Among the three “top 10” that were not initial studies, two were confirmed subsequently and the third was attenuated. The newspaper coverage of the “top 10” publications (223 articles) was much larger than that of the 67 related studies (57 articles). Moreover, only one of the latter newspaper articles reported that the corresponding “top 10” finding had been attenuated. The average impact factor of the scientific journals publishing studies echoed by newspapers (17.1 n = 56) was higher (p<0.0001) than that corresponding to related publications that were not echoed (6.4 n = 56).

Conclusion

Because newspapers preferentially echo initial ADHD findings appearing in prominent journals, they report on uncertain findings that are often refuted or attenuated by subsequent studies. If this media reporting bias generalizes to health sciences, it represents a major cause of distortion in health science communication.     

Modulation of thrombin-stimulated lipid responses in cultured fibroblasts. Evidence for two coupling mechanisms

Treatment of cultured fibroblasts with thrombin results in the stimulation of cell division and lipid metabolism. Proteolytically active alpha-thrombin rapidly stimulates (a) release of arachidonic acid, (b) generation of inositol phosphates, and (c) increase in cellular diacylglycerol levels. Pretreatment of the fibroblasts with chymotrypsin before alpha-thrombin prevented the first two responses, (a) and (b), and reduced response c. Treatment of fibroblasts with gamma-thrombin, a proteolytic derivative of alpha-thrombin, produced a response indistinguishable from the alpha-thrombin treatment when preceded by chymotrypsin. These data support a model, similar to one for platelets [McGowan, E. B., & Detwiler, T. C. (1986) J. Biol. Chem. 261, 739-746], that fibroblasts possess two coupling mechanisms for the stimulation of lipid metabolism by thrombin. Similar to platelets, one mechanism, R1, mediates the stimulated release of arachidonic acid and is capable of activating Ni, a GTP-binding protein. R1 is inactivated by chymotrypsin and does not respond to gamma-thrombin. The other mechanism, R2, responds to gamma-thrombin and is not activated by chymotrypsin. In contrast to the mechanisms proposed for platelets, we demonstrate that the phospholipase C responsible for the hydrolysis of phosphoinositides is not activated by R2 but is activated via R1. Importantly, stimulation of either mechanism results in the elevation of cellular diacylglycerol. This indicates that the stimulated elevation of diacylglycerol, or those events dependent upon the elevation of diacylglycerol, is not a reliable indicator for establishing the hydrolysis of phosphoinositides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurochemical Evidence for Agmatine Modulation of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Neurotoxicity

Agmatine treatment is known to exert neuroprotective effects in several models of neurotoxic and ischemic brain and spinal cord injuries. Here we sought to find out whether agmatine treatment would also prove to be neuroprotective in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson’s disease. Concomitant daily treatment (intraperitoneal injections) with agmatine (100 mg/kg for 5 days) and MPTP (40 mg/kg for 2 days) exacerbated MPTP-related toxicity as evidenced by a larger reduction in dopamine uptake into striatal synaptosomes (42.4% as compared to 58.3% of control, respectively). In contrast, agmatine treatment commencing after MPTP, produced partial protection (31%) against MPTP dopaminergic toxicity. The findings implicate agmatine in mechanisms regulating MPTP neurotoxicity, but underscore the characteristic neuroprotective efficacy of agmatine when applied after the insult.     

Out of Asia: Mitochondrial DNA Evidence for an Oriental Origin of Tiger Frogs, Genus Hoplobatrachus

Most examples of intercontinental dispersal events after the Miocene contact between Africa and Asia involve mammal lineages. Among amphibians, a number of probably related groups are known from both continents, but their phylogenies are so far largely unresolved. To test the hypothesis of Miocene dispersal against a Mesozoic vicariance scenario in the context of Gondwana fragmentation, we analyzed fragments of the mitochondrial 16S rRNA gene (572 bp) in 40 specimens of 34 species of the anuran family Ranidae. Results corroborated the monophyly of tiger frogs (genus Hoplobatrachus), a genus with representatives in Africa and Asia. The African H. occipitalis was the sister group of the Asian H. crassus, H. chinensis, and H. tigerinus. Hoplobatrachus was placed in a clade also containing the Asian genera Euphlyctis and Nannophrys. Combined analysis of sequences of 16S and 12S rRNA genes (total 903 bp) in a reduced set of taxa corroborated the monophyly of the lineage containing these three genera and identified the Asian genus Fejervarya as its possible sister group. The fact that the African H. occipitalis is nested within an otherwise exclusively Asian clade indicates its probable Oriental origin. Rough molecular clock estimates did not contradict the assumption that the dispersal event took place in the Miocene. Our data further identified a similar molecular divergence between closely related Asian and African species of Rana (belonging to the section Hylarana), indicating that Neogene intercontinental dispersal also may have taken place in this group and possibly in rhacophorid treefrogs.     

Neuro-Anatomical Evidence Indicating Indirect Modulation of Macrophages by Vagal Efferents in the Intestine but Not in the Spleen

Background

Electrical stimulation of the vagus nerve suppresses intestinal inflammation and normalizes gut motility in a mouse model of postoperative ileus. The exact anatomical interaction between the vagus nerve and the intestinal immune system remains however a matter of debate. In the present study, we provide additional evidence on the direct and indirect vagal innervation of the spleen and analyzed the anatomical evidence for neuroimmune modulation of macrophages by vagal preganglionic and enteric postganglionic nerve fibers within the intestine.

Methods

Dextran conjugates were used to label vagal preganglionic (motor) fibers projecting to the small intestine and spleen. Moreover, identification of the neurochemical phenotype of the vagal efferent fibers and enteric neurons was performed by immunofluorescent labeling. F4/80 antibody was used to label resident macrophages.

Results

Our anterograde tracing experiments did not reveal dextran-labeled vagal fibers or terminals in the mesenteric ganglion or spleen. Vagal efferent fibers were confined within the myenteric plexus region of the small intestine and mainly endings around nNOS, VIP and ChAT positive enteric neurons. nNOS, VIP and ChAT positive fibers were found in close proximity of intestinal resident macrophages carrying α7 nicotinic receptors. Of note, VIP receptors were found on resident macrophages located in close proximity of VIP positive nerve fibers.

Conclusion

In the present study, we show that the vagus nerve does not directly interact with resident macrophages in the gut or spleen. Instead, the vagus nerve preferentially interacts with nNOS, VIP and ChAT enteric neurons located within the gut muscularis with nerve endings in close proximity of the resident macrophages.     

Evidence of High Out of Pocket Spending for HIV Care Leading to Catastrophic Expenditure for Affected Patients in Lao People's Democratic Republic

Background

The scaling up of antiviral treatment (ART) coverage in the past decade has increased access to care for numerous people living with HIV/AIDS (PLWHA) in low-resource settings. Out-of-pocket payments (OOPs) represent a barrier for healthcare access, adherence and ART effectiveness, and can be economically catastrophic for PLWHA and their family. We evaluated OOPs of PLWHA attending outpatient and inpatient care units and estimated the financial burden for their households in the Lao People''s Democratic Republic. We assumed that such OOPs may result in catastrophic health expenses in this context with fragile economical balance and low health insurance coverage.

Methods

We conducted a cross-sectional survey of a randomized sample of routine outpatients and a prospective survey of consecutive new inpatients at two referral hospitals (Setthathirat in the capital city, Savannaket in the province). After obtaining informed consent, PLWHA were interviewed using a standardized 82-item questionnaire including information on socio-economic characteristics, disease history and coping strategies. All OOPs occurring during a routine visit or a hospital stay were recorded. Household capacity-to-pay (overall income minus essential expenses), direct and indirect OOPs, OOPs per outpatient visit and per inpatient stay as well as catastrophic spending (greater than or equal to 40% of the capacity-to-pay) were calculated. A multivariate analysis of factors associated with catastrophic spending was conducted.

Results

A total of 320 PLWHA [280 inpatients and 40 outpatients; 132 (41.2%) defined as poor, and 269 (84.1%) on ART] were enrolled. Monthly median household income, essential expenses and capacity-to-pay were US$147.0 (IQR: 86–242), $126 (IQR: 82–192) and $14 (IQR: 19–80), respectively. At the provincial hospital OOPs were higher during routine visits, but three fold lower during hospitalization than in the central hospital ($21.0 versus $18.5 and $110.8 versus $329.8 respectively (p<0.01). The most notable OOPs were related to transportation and to loss of income. A total of 150 patients (46.8%; 95%CI: 41.3–52.5) were affected by catastrophic health expenses; 36 outpatients (90.0%; 95%CI: 76.3–97.2) and 114 inpatients (40.7%; 95%CI: 34.9–46.7). A total of 141 (44.0%) patients had contracted loans, and 127 (39.6%) had to sell some of their assets. In the multivariate analysis, being of Lao Loum ethnic group (Coef.-1.4; p = 0.04); being poor (Coef. -1.0; p = 0.01) and living more than 100 km away from the hospital (Coef.-1.0; p = 0.002) were positively associated with catastrophic spending. Conversely being in the highest wealth quartile (Coef. 1.6; p<0.001), living alone (Coef. 1.1; p = 0.04), attending the provincial hospital (Coef. 1.0; p = 0.002), and being on ART (Coef.1.2; p = 0.003), were negatively associated with catastrophic spending.

Conclusion

PLWHA’s households face catastrophic OOPs that are not directly attributable to the cost of ART or to follow-up tests, particularly during a hospitalization period. Transportation, distance to healthcare and time spent at the health facility are the major contributors for OOPs and for indirect opportunity costs. Being on ART and attending the provincial hospital were associated with a lower risk of catastrophic spending. Decentralization of care, access to ART and alleviation of OOPs are crucial factors to successfully decrease the household burden of HIV-AIDS expenses.     

Modulation of the estrogen receptor's affinity for DNA by estradiol

The binding constant for estrogen receptor-DNA interaction when measured in the presence and absence of estradiol revealed a distinct difference dependent upon whether the receptor was hormone-bound or hormone-free. The binding constant of estrogen receptor-DNA interaction was determined by analysis of the exponential elution profile of the estrogen receptor from DNA-Sepharose columns using Tris buffer at a constant salt concentration. The binding constant of the hormone-bound estrogen receptor for DNA in Tris buffer, pH 7.4, containing 0.2 M KCl was 10.1 +/- 0.8 X 10(6) M-1, 5-fold higher than the value for the hormone-free estrogen receptor. Analysis of the number of ionic bonds between the estrogen receptor and DNA indicates that the hormone-free receptor establishes eight salt bridges, while the hormone-bound estrogen receptor establishes 10-13. The affinity of the hormone-bound estrogen receptor for DNA in Tris buffer at pH 7.4 in 0.2 M KCl is 10-fold greater than at pH 8.0, suggesting that ionic bonding between the receptor and DNA may involve histidine residues of the receptor. The concentration-dependence of the hormone-bound receptor's affinity for DNA emphasizes the receptor's associative state as an influence on the receptor's DNA binding characteristics. Our results demonstrate that estradiol modifies the conformation of the estrogen receptor to a state having an increased affinity for DNA.     

Modulation of steroid affinity for the androgen receptor by sucrose

The effects of sucrose on androgen binding to its receptor were investigated. Sucrose decreased the rate of thermal inactivation of unoccupied and occupied androgen receptor (AR) and the rates of [3H]5 alpha-dihydrotestosterone [( 3H]DHT) dissociation from both activated and nonactivated AR complexes. Binding of [3H]DHT to AR in vivo, or in intact cells at 37 degrees C, caused reduction of [3H]DHT dissociation from cytosolic and nuclear complexes, as compared to in vitro labeled receptor complexes. Further, exposure of these complexes to sucrose at 0 degrees C caused an additional reduction of dissociation rates. Thus, the decrease of [3H]DHT dissociation induced by sucrose is independent of the reaction that reduces DHT dissociation from activated and transformed AR. Sucrose also reduced the ability of mersalyl acid to inactivate AR complexes. This effect of sucrose was markedly diminished in the presence of 2M urea. Sucrose did not significantly affect the association rate, sedimentation properties, or nuclear binding ability of AR complexes, but it did decrease the equilibrium dissociation constant. Other monosaccharides and disaccharides also stabilized AR. These data suggest that sucrose induces conformational changes in the steroid binding domain of androgen receptor, thereby reducing the rates of inactivation, steroid dissociation, and the accessibility of sulfhydryl groups to mersalyl.     

Modulation of Early Inflammatory Response by Different Balanced and Non-Balanced Colloids and Crystalloids in a Rodent Model of Endotoxemia

The use of hydroxyethyl starch (HES) in sepsis has been shown to increase mortality and acute kidney injury. However, the knowledge of the exact mechanism by which several fluids, especially starch preparations may impair end-organ function particularly in the kidney, is still missing. The aim of this study was to measure the influence of different crystalloid and colloid fluid compositions on the inflammatory response in the kidney, the liver and the lung using a rodent model of acute endotoxemia. Rats were anesthetized and mechanically ventilated. Lipopolysaccharide (5 mg/kg) was administered intravenously. After one hour crystalloids [lactate-buffered (RLac) or acetate-buffered (RAc)] were infused i.v. (30 ml/kg) in all groups. At 2 hours rats either received different crystalloids (75 ml/kg of RLac or RAc) or colloids (25 ml/kg of HES in saline or HES in RAc or gelatin in saline). Expression of messenger RNA for cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemotactic protein-1 (MCP-1), necrosis factor α (TNFα) and intercellular adhesion molecule 1 (ICAM-1) was assessed in kidney, liver and lung tissue by real-time PCR after 4 hours. The use of acetate-buffered solutions was associated with a significantly higher expression of CINC-1 and TNFα mRNA in the liver, in the kidney and in the lung. Only marginal effects of gelatin and hydroxyethyl starch on mRNA expression of inflammatory mediators were observed. The study provides evidence that the type of buffering agent of different colloidal and crystalloid solutions might be a crucial factor determining the extent of early end-organ inflammatory response in sepsis.     

Structural Modulation of Brain Development by Oxygen: Evidence on Adolescents Migrating from High Altitude to Sea Level Environment

The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15–18 years), who were born and raised in Qinghai-Tibetan Plateau (2900–4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.