Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a]pyrimidin-4-imines as potent 5-HT6 antagonists

Comprehensive structure activity relationship (SAR) studies were conducted on a focused screening hit, 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine (1, IC₅₀: 4.0 nM), as 5-HT₆ selective antagonists. Activity was improved some 2–4 fold when small, electron-donating groups were added to the central core as observed in 19, 20 and 26. Molecular docking of key compounds in a homology model of the human 5-HT₆ receptor was used to rationalize our structure–activity relationship (SAR) findings. In pharmacokinetic experiments, compound 1 displayed good brain uptake in rats following intra-peritoneal administration, but limited oral bioavailability.     

The evolutionary origins and ecological context of tool use in New Caledonian crows

New Caledonian (NC) crows Corvus moneduloides are the most prolific avian tool users. In the wild, they use at least three distinct tool types to extract invertebrate prey from deadwood and vegetation, with some of their tools requiring complex manufacture, modification and/or deployment. Experiments with captive-bred, hand-raised NC crows have demonstrated that the species has a strong genetic predisposition for basic tool use and manufacture, suggesting that this behaviour is an evolved adaptation. This view is supported by recent stable-isotope analyses of the diets of wild crows, which revealed that tool use provides access to highly profitable hidden prey, with preliminary data indicating that parents preferentially feed their offspring with tool-derived food. Building on this work, our review examines the possible evolutionary origins of these birds’ remarkable tool-use behaviour. Whilst robust comparative analyses are impossible, given the phylogenetic rarity of animal tool use, our examination of a wide range of circumstantial evidence enables a first attempt at reconstructing a plausible evolutionary scenario. We suggest that a common ancestor of NC crows, originating from a (probably) non-tool-using South-East Asian or Australasian crow population, colonised New Caledonia after its last emersion several million years ago. The presence of profitable but out-of-reach food, in combination with a lack of direct competition for these resources, resulted in a vacant woodpecker-like niche. Crows may have possessed certain behavioural and/or morphological features upon their arrival that predisposed them to express tool-use rather than specialised prey-excavation behaviour, although it is possible that woodpecker-like foraging preceded tool use. Low levels of predation risk may have further facilitated tool-use behaviour, by allowing greater expenditure of time and energy on object interaction and exploration, as well as the evolution of a ‘slow’ life-history, in which prolonged juvenile development enables acquisition of complex behaviours. Intriguingly, humans may well have influenced the evolution of at least some of the species’ tool-oriented behaviours, via their possible introduction of candlenut trees together with the beetle larvae that infest them. Research on NC crows’ tool-use behaviour in its full ecological context is still in its infancy, and we expect that, as more evidence accumulates, some of our assumptions and predictions will be proved wrong. However, it is clear from our analysis of existing work, and the development of some original ideas, that the unusual evolutionary trajectory of NC crows is probably the consequence of an intricate constellation of interplaying factors.     

Enhancement of performances in a learning task in suckler calves after weaning and relocation: Motivational versus cognitive control?: A pilot study

Weaning in suckler calves influences performance in a learning task. The aim of the present study was to investigate whether the improved performance after weaning, including relocation, is due to differences in motivation for the reward or in learning abilities. Forty Aubrac calves were used; half of them were weaned from their dams at around eight months, the other half were weaned one month later. After weaning, calves were housed in groups of four in a new setting. From the day after weaning of the last group of calves, the animals were subjected to two tests: (1) an arena test, (2) a T-maze test where one arm led to either a social or a food reward. The T-maze test consisted of three sessions: in Session 1, trials were conducted until the animal acquired the task (i.e. did not take the unrewarded arm on three consecutive trials); in Session 2, the motivation for the reward was assessed via the walking time of the animal to reach the reward; in Session 3, the place of reward was reversed and the animals were trained until they acquired the new task.

Calves weaned for one day explored more (P < 0.05) and had lower heart rates during the arena test (P < 0.05) compared to the ones weaned for one month. During the T-maze test, calves weaned for one month versus one day did not differ in their capacities to learn the initial route (Session 1) or in their motivation for either the social or food reward (Session 2). Calves weaned for one day learned significantly faster (P < 0.05) the reversed route (Session 3) than calves weaned for one month. Hence, the better performances at reversal in the T-maze by calves that have just been weaned cannot be accounted for by a higher motivation for the reward. A better cognitive control of their behaviour due to a lower stress state is suggested by our results.     

Neuropsychological Aspects of Liver Disease and its Treatment

Liver disease can lead to serious impairment in cognitive functioning, through the development of a condition known as hepatic encephalopathy (HE). While gross impairment is clinically obvious, milder variants of the condition may escape detection at bedside examination and yet may have a significant impact on day-to-day activities. In this brief review article, the neuropsychology of liver disease is examined, focusing on nature, aetiology and significance. The possible contributory role of endogenous benzodiazepines in HE is described, as is the evidence regarding the effect of benzodiazepine antagonism on cognitive functioning in HE. The functional localisation of HE is briefly reviewed, as is the use of neuropsychological measures to evaluate treatment efficacy, e.g. following shunt procedures or liver transplantation. Finally, living donor liver transplantation is described, and the case is made for rigorous longitudinal neuropsychological evaluation of potential donors and recipients. Special issue article in honor of George Fink.     

Neuroelectric measurement of cognition during aerobic exercise

The application of neuroimaging techniques to assess changes in brain and cognition during exercise has received little attention due to issues related to artifact associated with gross motor movement inherent in physical activity behaviors. Although many neuroimaging techniques have not yet progressed to a point where movement artifact may be controlled, event-related brain potentials (ERPs), which measure neuroelectric responses to specific events, can account for such issues in controlled environments. This paper discusses the deviations from standard neuroelectric recording procedures and signal processing that are necessary for the collection and analysis of ERPs during gross motor movement. Considerations include the properties of the exercise behavior, task instructions, and the position of materials in the stimulus environment, as well as issues related to electrode impedance, additional reduction techniques, and the plotting of single trials to identify movement artifacts. These techniques provide a means for collecting clean data from the neuroelectric system to provide further understanding of changes in brain and cognition that occur online during exercise behavior, and serves as a novel application of neuroimaging to the kinesiological sciences.     

The autonomy of biological individuals and artificial models

This paper aims to offer an overview of the meaning of autonomy for biological individuals and artificial models rooted in a specific perspective that pays attention to the historical and structural aspects of its origins and evolution. Taking autopoiesis and the recursivity characteristic of its circular logic as a starting point, we depart from some of its consequences to claim that the theory of autonomy should also take into account historical and structural features. Autonomy should not be considered only in internal or constitutive terms, the largely neglected interactive aspects stemming from it should be equally addressed. Artificial models contribute to get a better understanding of the role of autonomy for life and the varieties of its organization and phenomenological diversity.     

The research of constructing dynamic cognition model based on brain network

Estimating the functional interactions and connections between brain regions to corresponding process in cognitive, behavioral and psychiatric domains is a central pursuit for understanding the human connectome. Few studies have examined the effects of dynamic evolution on cognitive processing and brain activation using brain network model in scalp electroencephalography (EEG) data. Aim of this study was to investigate the brain functional connectivity and construct dynamic programing model from EEG data and to evaluate a possible correlation between topological characteristics of the brain connectivity and cognitive evolution processing. Here, functional connectivity between brain regions is defined as the statistical dependence between EEG signals in different brain areas and is typically determined by calculating the relationship between regional time series using wavelet coherence. We present an accelerated dynamic programing algorithm to construct dynamic cognitive model that we found that spatially distributed regions coherence connection difference, the topologic characteristics with which they can transfer information, producing temporary network states. Our findings suggest that brain dynamics give rise to variations in complex network properties over time after variation audio stimulation, dynamic programing model gives the dynamic evolution processing at different time and frequency. In this paper, by applying a new construct approach to understand whole brain network dynamics, firstly, brain network is constructed by wavelet coherence, secondly, different time active brain regions are selected by network topological characteristics and minimum spanning tree. Finally, dynamic evolution model is constructed to understand cognitive process by dynamic programing algorithm, this model is applied to the auditory experiment, results showed that, quantitatively, more correlation was observed after variation audio stimulation, the EEG function connection dynamic evolution model on cognitive processing is feasible with wavelet coherence EEG recording.     

不同性别冠心病患者对于急性心肌梗死相关症状的认识现况调查

目的:了解不同性别冠心病(CAD)患者对于急性心肌梗死(AMI)相关症状的认知情况,为有效缩短AMI院前延误(PHD)提供依据。方法:于2015年10月至2016年3月在同济大学附属同济医院和上海市闸北区中心医院心内科门诊及病房,对确诊为CAD的受访者进行调查,收集受访者的一般资料,要求受访者区分胸痛、呼吸困难、出汗、恶心呕吐、晕厥是否为AMI相关症状。使用多元回归分析的方法,分析不同性别患者对上述症状的认知情况。结果:共680例CAD患者自愿接受调查,男性受访者对多数AMI相关症状的知晓率普遍高于女性。性别组间比较的多因素Logistic回归分析显示,相比较于女性,男性CAD患者对AMI相关症状出汗,恶心呕吐、晕厥认知度的OR值分别为1.41(1.04-2.41)、1.79(1.09-2.95)、1.96(1.42-2.72)。结论:不同性别患者对AMI相关症状认识水平存在差异,女性在出汗,恶心呕吐,晕厥不典型AMI相关症状认识程度较男性差。应加强对该人群的健康教育,以最大可能的缩短决策延误时间。     

Investigating the Effects of Antipsychotics and Schizotypy on the N400 Using Event-Related Potentials and Semantic Categorization

Within the field of cognitive neuroscience, functional magnetic resonance imaging (fMRI) is a popular method of visualizing brain function. This is in part because of its excellent spatial resolution, which allows researchers to identify brain areas associated with specific cognitive processes. However, in the quest to localize brain functions, it is relevant to note that many cognitive, sensory, and motor processes have temporal distinctions that are imperative to capture, an aspect that is left unfulfilled by fMRI’s suboptimal temporal resolution. To better understand cognitive processes, it is thus advantageous to utilize event-related potential (ERP) recording as a method of gathering information about the brain. Some of its advantages include its fantastic temporal resolution, which gives researchers the ability to follow the activity of the brain down to the millisecond. It also directly indexes both excitatory and inhibitory post-synaptic potentials by which most brain computations are performed. This sits in contrast to fMRI, which captures an index of metabolic activity. Further, the non-invasive ERP method does not require a contrast condition: raw ERPs can be examined for just one experimental condition, a distinction from fMRI where control conditions must be subtracted from the experimental condition, leading to uncertainty in associating observations with experimental or contrast conditions. While it is limited by its poor spatial and subcortical activity resolution, ERP recordings’ utility, relative cost-effectiveness, and associated advantages offer strong rationale for its use in cognitive neuroscience to track rapid temporal changes in neural activity. In an effort to foster increase in its use as a research imaging method, and to ensure proper and accurate data collection, the present article will outline – in the framework of a paradigm using semantic categorization to examine the effects of antipsychotics and schizotypy on the N400 – the procedure and key aspects associated with ERP data acquisition.     

The Indonesian Homo erectus brain endocasts revisited

New brain endocast reconstructions of Homo erectus discoveries from Indonesia since 1963 (H. erectus VI, 1963; VII, 1965; VIII, 1969) have been made and their volumes determined. In addition, older discoveries (H. erectus I, 1891; II, 1937; IV, 1937–38) have been reendocast and reconstructed, and have yielded volumes considerably different from those previously published. This is particularly so in the case of Dubois's original discovery, which yields a volume of 940 ml rather than the widely quoted volume of 750 ml. In addition, a number of morphological observations regarding hemispheric asymmetries (petalias) are provided, which suggest a condition similar to modern Homo sapiens.