The neural bases of social intention understanding: the role of interaction goals

Decoding others' intentions is a crucial aspect of social cognition. Neuroimaging studies suggest that inferring immediate goals engages the neural system for action understanding (i.e. mirror system), while the decoding of long-term intentions requires the system subserving the attribution of mental states (i.e. mentalizing). A controversial issue, stimulated by recent inconsistent results, concerns whether the two systems are concurrently vs. exclusively involved in intention understanding. This issue is particularly relevant in the case of social interactions, whose processing has been mostly, but not uncontroversially, associated with the mentalizing system. We tested the alternative hypothesis that the relative contribution of the two systems in intention understanding may also depend on the shared goal of interacting agents. To this purpose, 27 participants observed social interactions differing in their cooperative vs. affective shared goal during functional-Magnetic-Resonance-Imaging. The processing of both types of interactions activated the right temporo-parietal junction involved in mentalizing on action goals. Additionally, whole-brain and regions-of-interest analyses showed that the action understanding system (inferior prefrontal-parietal cortex) was more strongly activated by cooperative interactions, while the mentalizing-proper system (medial prefrontal cortex) was more strongly engaged by affective interactions. These differences were modulated by individual differences in empathizing. Both systems can thus be involved in understanding social intentions, with a relative weighting depending on the specific shared goal of the interaction.     

The AutoDock suite at 30

The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug design and development. The suite builds on 30 years of methods development, including empirical free energy force fields, docking engines, methods for site prediction, and interactive tools for visualization and analysis. Specialized tools are available for challenging systems, including covalent inhibitors, peptides, compounds with macrocycles, systems where ordered hydration plays a key role, and systems with substantial receptor flexibility. All methods in the AutoDock suite are freely available for use and reuse, which has engendered the continued growth of a diverse community of primary users and third‐party developers.     

Mechanisms of interleukin-6 protection against ischemia-reperfusion injury in rat liver

Numerous animal studies simulating liver injury have demonstrated that interleukin-6 (IL-6) exerts a protective effect. This study was designed to further analyze the molecular mechanisms underlying the protective role of IL-6 in a rat model of liver ischemia/reperfusion injury. We show that IL-6: (i) at high doses reduces cell damage which occurs in ischemic-reperfused liver, while at low doses displays only a limited protective capacity, (ii) anticipates and enhances hepatocyte compensatory proliferation seen in ischemic-reperfused liver also at a low, more pharmacologically acceptable dose, (iii) sustains the acute phase response which is dampened in ischemic-reperfused liver, (iv) strengthens the heat shock-stress response shown by ischemic-reperfused liver and (v) overcomes the dysfunctions of the unfolding protein response found in ischemic-reperfused liver. We also show that IL-6-enhanced STAT3 activation probably plays a crucial role in the potentiation of the different protective pathways activated in ischemic-reperfused liver. Our data confirm that IL-6 is a potential therapeutic in liver injury of different etiologies and reveal novel mechanisms by which IL-6 sustains liver function after ischemia/reperfusion injury.     

Molecular Identification of Bacteria by Total Sequence Screening: Determining the Cause of Death in Ancient Human Subjects

Research of ancient pathogens in ancient human skeletons has been mainly carried out on the basis of one essential historical or archaeological observation, permitting specific pathogens to be targeted. Detection of ancient human pathogens without such evidence is more difficult, since the quantity and quality of ancient DNA, as well as the environmental bacteria potentially present in the sample, limit the analyses possible. Using human lung tissue and/or teeth samples from burials in eastern Siberia, dating from the end of 17^th to the 19^th century, we propose a methodology that includes the: 1) amplification of all 16S rDNA gene sequences present in each sample; 2) identification of all bacterial DNA sequences with a degree of identity ≥95%, according to quality criteria; 3) identification and confirmation of bacterial pathogens by the amplification of the rpoB gene; and 4) establishment of authenticity criteria for ancient DNA. This study demonstrates that from teeth samples originating from ancient human subjects, we can realise: 1) the correct identification of bacterial molecular sequence signatures by quality criteria; 2) the separation of environmental and pathogenic bacterial 16S rDNA sequences; 3) the distribution of bacterial species for each subject and for each burial; and 4) the characterisation of bacteria specific to the permafrost. Moreover, we identified three pathogens in different teeth samples by 16S rDNA sequence amplification: Bordetella sp., Streptococcus pneumoniae and Shigella dysenteriae. We tested for the presence of these pathogens by amplifying the rpoB gene. For the first time, we confirmed sequences from Bordetella pertussis in the lungs of an ancient male Siberian subject, whose grave dated from the end of the 17^th century to the early 18^th century.     

Differential regulation of the postsynaptic clustering of γ-aminobutyric acid type A (GABAA) receptors by collybistin isoforms

Collybistin promotes submembrane clustering of gephyrin and is essential for the postsynaptic localization of gephyrin and γ-aminobutyric acid type A (GABA(A)) receptors at GABAergic synapses in hippocampus and amygdala. Four collybistin isoforms are expressed in brain neurons; CB2 and CB3 differ in the C terminus and occur with and without the Src homology 3 (SH3) domain. We have found that in transfected hippocampal neurons, all collybistin isoforms (CB2(SH3+), CB2(SH3-), CB3(SH3+), and CB3(SH3-)) target to and concentrate at GABAergic postsynapses. Moreover, in non-transfected neurons, collybistin concentrates at GABAergic synapses. Hippocampal neurons co-transfected with CB2(SH3-) and gephyrin developed very large postsynaptic gephyrin and GABA(A) receptor clusters (superclusters). This effect was accompanied by a significant increase in the amplitude of miniature inhibitory postsynaptic currents. Co-transfection with CB2(SH3+) and gephyrin induced the formation of many (supernumerary) non-synaptic clusters. Transfection with gephyrin alone did not affect cluster number or size, but gephyrin potentiated the clustering effect of CB2(SH3-) or CB2(SH3+). Co-transfection with CB2(SH3-) or CB2(SH3+) and gephyrin did not affect the density of presynaptic GABAergic terminals contacting the transfected cells, indicating that collybistin is not synaptogenic. Nevertheless, the synaptic superclusters induced by CB2(SH3-) and gephyrin were accompanied by enlarged presynaptic GABAergic terminals. The enhanced clustering of gephyrin and GABA(A) receptors induced by collybistin isoforms was not accompanied by enhanced clustering of neuroligin 2. Moreover, during the development of GABAergic synapses, the clustering of gephyrin and GABA(A) receptors preceded the clustering of neuroligin 2. We propose a model in which the SH3- isoforms play a major role in the postsynaptic accumulation of GABA(A) receptors and in GABAergic synaptic strength.     

Effects of Ambient Temperature on Sleep and Cardiovascular Regulation in Mice: The Role of Hypocretin/Orexin Neurons

The central neural pathways underlying the physiological coordination between thermoregulation and the controls of the wake-sleep behavior and cardiovascular function remain insufficiently understood. Growing evidence supports the involvement of hypocretin (orexin) peptides in behavioral, cardiovascular, and thermoregulatory functions. We investigated whether the effects of ambient temperature on wake-sleep behavior and cardiovascular control depend on the hypothalamic neurons that release hypocretin peptides. Orexin-ataxin3 transgenic mice with genetic ablation of hypocretin neurons (n = 11) and wild-type controls (n = 12) were instrumented with electrodes for sleep scoring and a telemetric blood pressure transducer. Simultaneous sleep and blood pressure recordings were performed on freely-behaving mice at ambient temperatures ranging between mild cold (20°C) and the thermoneutral zone (30°C). In both mouse groups, the time spent awake and blood pressure were higher at 20°C than at 30°C. The cold-related increase in blood pressure was significantly smaller in rapid-eye-movement sleep (REMS) than either in non-rapid-eye-movement sleep (NREMS) or wakefulness. Blood pressure was higher in wakefulness than either in NREMS or REMS at both ambient temperatures. This effect was significantly blunted in orexin-ataxin3 mice irrespective of ambient temperature and particularly during REMS. These data demonstrate that hypocretin neurons are not a necessary part of the central pathways that coordinate thermoregulation with wake-sleep behavior and cardiovascular control. Data also support the hypothesis that hypocretin neurons modulate changes in blood pressure between wakefulness and the sleep states. These concepts may have clinical implications in patients with narcolepsy with cataplexy, who lack hypocretin neurons.     

Correlation between interaction strengths drives stability in large ecological networks

Food webs have markedly non‐random network structure. Ecologists maintain that this non‐random structure is key for stability, since large random ecological networks would invariably be unstable and thus should not be observed empirically. Here we show that a simple yet overlooked feature of natural food webs, the correlation between the effects of consumers on resources and those of resources on consumers, substantially accounts for their stability. Remarkably, random food webs built by preserving just the distribution and correlation of interaction strengths have stability properties similar to those of the corresponding empirical systems. Surprisingly, we find that the effect of topological network structure on stability, which has been the focus of countless studies, is small compared to that of correlation. Hence, any study of the effects of network structure on stability must first take into account the distribution and correlation of interaction strengths.     

Unconventional method based on circular dichroism to detect peanut DNA in food by means of a PNA probe and a cyanine dye

In this paper we report an innovative and unconventional method based on circular dichroism for the identification of peanut DNA in food, which can be detected after PCR amplification at the nanomolar level by using an achiral PNA probe complementary to a tract of the peanut Ara h 2 gene and an achiral 3,3'-diethylthiadicarbocyanine dye [DiSC(2)(5)]. Peanuts are one of the most common causes of severe allergic reactions to foods and are particularly dangerous when they are "hidden" (undeclared) in food. For better protection of consumers, detection methods are required to specifically detect the presence of hidden allergens in a wide variety of food items. Alternative to the detection of the proteins is the determination of species-specific DNA, which is more resistant to technological treatments. PNAs are very specific probes able to recognize DNA sequences with high affinity and evidence for the binding can be obtained by using the DiSC(2)(5) dye, which aggregates onto the PNA-DNA duplex giving rise to a characteristic visibile band at 540 nm. Because the PNA-DNA duplex is in a right-handed helical conformation, the aggregation of the dye to the duplex gives also rise to a strong CD signal in the 500-600 nm region with a strong exciton coupling due to the formation of multimeric species, since the handedness of the helix is transferred to the dye aggregate. The dye does not interact with the free single-stranded DNA and although aggregating on the achiral PNA, this interaction is obviously not detectable by circular dichroism. Thus, only the formation of the PNA-DNA duplex, which takes place only upon specific Watson-Crick hydrogen binding between the PNA and the DNA bases, is detected, ensuring a very high specificity and sensitivity. The method has been optimized in a model system by using a synthetic oligonucleotide complementary to the PNA probe, showing that the intensity of the signal is linearly related to the amount of the DNA. The optimized method has been applied to the identification and quantitation of DNA extracted and amplified by PCR from peanuts and from peanut-containing foods, allowing for a very sensitive detection at a very low level (few pmol).     

Improving the spatial orientation of human teeth using a virtual 3D approach

Since teeth are resistant to decomposition processes, they provide important and at times unique sources of information about fossil humans. Fortunately, dental remains reflect significant evolutionary changes. These changes make a very important and often exclusive contribution to the definition of new taxa or the attribution of fossil specimens to existing taxa.The traditional approach to dental morphometric analyses usually focuses on the recording of several measures of the tooth with calipers, especially the two basic crown diameters (buccolingual and mesiodistal). However, since these measures do not adequately represent the complex morphology of the tooth, 2D images and 3D digital models of dental morphology have been used. For both types of analysis, the possibility of correctly comparing homologous teeth depends on the adoption of a common orientation system. The lack of such a system makes it difficult to compare the results of different studies.Here we describe a new method for orienting teeth specifically devised for the upper and lower first molar (M1). Samples of unworn maxillary (n = 15) and mandibular (n = 15) first molars of modern humans were scanned with a Roland Picza 3D digitizer. The 3D virtual models were used to compare our new orientation method with those proposed in the literature. The new orientation system, which meets a geometric criterion, is based on three points identified on the cervical line and ensures acceptable repeatability of the spatial positioning and orientation independent of the shape and wear of the first molar under investigation. This orientation system is a first step toward the creation of a virtual set of hominid and fossil human first molars, which will allow us to make comparisons via a sophisticated and noninvasive approach. This pilot study also provides guidelines to extend the new methodology to the other types of teeth.     

Learning flexible sensori-motor mappings in a complex network

Given the complex structure of the brain, how can synaptic plasticity explain the learning and forgetting of associations when these are continuously changing? We address this question by studying different reinforcement learning rules in a multilayer network in order to reproduce monkey behavior in a visuomotor association task. Our model can only reproduce the learning performance of the monkey if the synaptic modifications depend on the pre- and postsynaptic activity, and if the intrinsic level of stochasticity is low. This favored learning rule is based on reward modulated Hebbian synaptic plasticity and shows the interesting feature that the learning performance does not substantially degrade when adding layers to the network, even for a complex problem.