An fMRI study of joint action–varying levels of cooperation correlates with activity in control networks

As social agents, humans continually interact with the people around them. Here, motor cooperation was investigated using a paradigm in which pairs of participants, one being scanned with fMRI, jointly controlled a visually presented object with joystick movements. The object oscillated dynamically along two dimensions, color and width of gratings, corresponding to the two cardinal directions of joystick movements. While the overall control of each participant on the object was kept constant, the amount of cooperation along the two dimensions varied along four levels, from no (each participant controlled one dimension exclusively) to full (each participant controlled half of each dimension) cooperation. Increasing cooperation correlated with BOLD signal in the left parietal operculum and anterior cingulate cortex (ACC), while decreasing cooperation correlated with activity in the right inferior frontal and superior temporal gyri, the intraparietal sulci and inferior temporal gyri bilaterally, and the dorsomedial prefrontal cortex. As joint performance improved with the level of cooperation, we assessed the brain responses correlating with behavior, and found that activity in most of the areas associated with levels of cooperation also correlated with the joint performance. The only brain area found exclusively in the negative correlation with cooperation was in the dorso medial frontal cortex, involved in monitoring action outcome. Given the cluster location and condition-related signal change, we propose that this region monitored actions to extract the level of cooperation in order to optimize the joint response. Our results, therefore, indicate that, in the current experimental paradigm involving joint control of a visually presented object with joystick movements, the level of cooperation affected brain networks involved in action control, but not mentalizing

What if I Get Busted? Deception, Choice, and Decision-Making in Social Interaction

Deception is an essentially social act, yet little is known about how social consequences affect the decision to deceive. In this study, participants played a computerized game of deception without constraints on whether or when to attempt to deceive their opponent. Participants were questioned by an opponent outside the scanner about their knowledge of the content of a display. Importantly, questions were posed so that, in some conditions, it was possible to be deceptive, while in other conditions it was not. To simulate a realistic interaction, participants could be confronted about their claims by the opponent. This design, therefore, creates a context in which a deceptive participant runs the risk of being punished if their deception is detected. Our results show that participants were slower to give honest than to give deceptive responses when they knew more about the display and could use this knowledge for their own benefit. The condition in which confrontation was not possible was associated with increased activity in subgenual anterior cingulate cortex. The processing of a question which allows a deceptive response was associated with activation in right caudate and inferior frontal gyrus. Our findings suggest the decision to deceive is affected by the potential risk of social confrontation rather than the claim itself

When Pinocchio's nose does not grow:belief regarding lie-detectability modulates production of deception

Does the brain activity underlying the production of deception differ depending on whether or not one believes their deception can be detected? To address this question, we had participants commit a mock theft in a laboratory setting, and then interrogated them while they underwent functional MRI (fMRI) scanning. Crucially, during some parts of the interrogation participants believed a lie detector was activated, whereas in other parts they were told it was switched off. We were thus able to examine the neural activity associated with the contrast between producing true versus false claims, as well as the independent contrast between believing that deception could and could not be detected. We found increased activation in the right amygdala and inferior frontal gyrus (IFG), as well as the left posterior cingulate cortex (PCC), during the production of false (compared to true) claims. Importantly, there was a significant interaction between the effects of deception and belief in the left temporal pole and right hippocampus/parahippocampal gyrus, where activity increased during the production of deception when participants believed their false claims could be detected, but not when they believed the lie detector was switched off. As these regions are associated with binding socially complex perceptual input and memory retrieval, we conclude that producing deceptive behavior in a context in which one believes this deception can be detected is associated with a cognitively taxing effort to reconcile contradictions between one’s actions and recollections

Ingestion of marine debris by Wedge-tailed Shearwaters ( Ardenna pacifica ) on Lord Howe Island, Australia during 2005–2018

publisher: Elsevier articletitle: Ingestion of marine debris by Wedge-tailed Shearwaters (Ardenna pacifica) on Lord Howe Island, Australia during 2005–2018 journaltitle: Marine Pollution Bulletin articlelink: https://doi.org/10.1016/j.marpolbul.2018.06.023 content_type: article copyright: © 2018 Elsevier Ltd. All rights reserved.The attached document is the authors’ submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Relationship between Activity in Human Primary Motor Cortex during Action Observation and the Mirror Neuron System

The attenuation of the beta cortical oscillations during action observation has been interpreted as evidence of a mirror neuron system (MNS) in humans. Here we investigated the modulation of beta cortical oscillations with the viewpoint of an observed action. We asked subjects to observe videos of an actor making a variety of arm movements. We show that when subjects were observing arm movements there was a significant modulation of beta oscillations overlying left and right sensorimotor cortices. This pattern of attenuation was driven by the side of the screen on which the observed movement occurred and not by the hand that was observed moving. These results are discussed in terms of the firing patterns of mirror neurons in F5 which have been reported to have similar properties

A rapid systematic review and evidence synthesis of effective coverage measures and cascades for childbirth, newborn and child health in low- and middle-income countries.

BACKGROUND: Effective coverage measures aim to estimate the proportion of a population in need of a service that received a positive health outcome. In 2020, the Effective Coverage Think Tank Group recommended using a 'coverage cascade' for maternal, newborn, child and adolescent health and nutrition (MNCAHN), which organises components of effective coverage in a stepwise fashion, with each step accounting for different aspects of quality of care (QoC), applied at the population level. The cascade outlines six steps that increase the likelihood that the population in need experience the intended health benefit: 1) the population in need (target population) who contact a health service; 2) that has the inputs available to deliver the service; 3) who receive the health service; 4) according to quality standards; 5) and adhere to prescribed medication(s) or health workers instructions; and 6) experience the expected health outcome. We examined how effective coverage of life-saving interventions from childbirth to children aged nine has been defined and assessed which steps of the cascade are captured by existing measures. METHODS: We undertook a rapid systematic review. Seven scientific literature databases were searched covering the period from May 1, 2017 to July, 8 2021. Reference lists from reviews published in 2018 and 2019 were examined to identify studies published prior to May 2017. Eligible studies reported population-level contact coverage measures adjusted for at least one dimension of QoC. RESULTS: Based on these two search approaches this review includes literature published from 2010 to 2021. From 16 662 records reviewed, 33 studies were included, reporting 64 effective coverage measures. The most frequently examined measures were for childbirth and immediate newborn care (n = 24). No studies examined measures among children aged five to nine years. Definitions of effective coverage varied across studies. Key sources of variability included (i) whether a single effective coverage measure was reported for a package of interventions or separate measures were calculated for each intervention; (ii) the number and type of coverage cascade steps applied to adjust for QoC; and (iii) the individual items included in the effective coverage definition and the methods used to generate a composite quality measure. CONCLUSION: In the MNCAHN literature there is substantial heterogeneity in both definitions and construction of effective coverage, limiting the comparability of measures over time and place. Current measurement approaches are not closely aligned with the proposed cascade. For widespread adoption, there is a need for greater standardisation of indicator definitions and transparency in reporting, so governments can use these measures to improve investments in MNACHN and implement life-saving health policies and programs

Enhanced Food Anticipatory Activity Associated with Enhanced Activation of Extrahypothalamic Neural Pathways in Serotonin2C Receptor Null Mutant Mice

The ability to entrain circadian rhythms to food availability is important for survival. Food-entrained circadian rhythms are characterized by increased locomotor activity in anticipation of food availability (food anticipatory activity). However, the molecular components and neural circuitry underlying the regulation of food anticipatory activity remain unclear. Here we show that serotonin2C receptor (5-HT2CR) null mutant mice subjected to a daytime restricted feeding schedule exhibit enhanced food anticipatory activity compared to wild-type littermates, without phenotypic differences in the impact of restricted feeding on food consumption, body weight loss, or blood glucose levels. Moreover, we show that the enhanced food anticipatory activity in 5-HT2CR null mutant mice develops independent of external light cues and persists during two days of total food deprivation, indicating that food anticipatory activity in 5-HT2CR null mutant mice reflects the locomotor output of a food-entrainable oscillator. Whereas restricted feeding induces c-fos expression to a similar extent in hypothalamic nuclei of wild-type and null mutant animals, it produces enhanced expression in the nucleus accumbens and other extrahypothalamic regions of null mutant mice relative to wild-type subjects. These data suggest that 5-HT2CRs gate food anticipatory activity through mechanisms involving extrahypothalamic neural pathways

Neonatal CD8 T-cell Hierarchy Is Distinct from Adults and Is Influenced by Intrinsic T cell Properties in Respiratory Syncytial Virus Infected Mice

Following respiratory syncytial virus infection of adult CB6F1 hybrid mice, a predictable CD8+ T cell epitope hierarchy is established with a strongly dominant response to a Kd-restricted peptide (SYIGSINNI) from the M2 protein. The response to KdM282-90 is ∼5-fold higher than the response to a subdominant epitope from the M protein (NAITNAKII, DbM187-195). After infection of neonatal mice, a distinctly different epitope hierarchy emerges with codominant responses to KdM282-90 and DbM187-195. Adoptive transfer of naïve CD8+ T cells from adults into congenic neonates prior to infection indicates that intrinsic CD8+ T cell factors contribute to age-related differences in hierarchy. Epitope-specific precursor frequency differs between adults and neonates and influences, but does not predict the hierarchy following infection. Additionally, dominance of KdM282-90 –specific cells does not correlate with TdT activity. Epitope-specific Vβ repertoire usage is more restricted and functional avidity is lower in neonatal mice. The neonatal pattern of codominance changes after infection at 10 days of age, and rapidly shifts to the adult pattern of extreme KdM282- 90 -dominance. Thus, the functional properties of T cells are selectively modified by developmental factors in an epitope-specific and age-dependent manner

Countdown to 2030 : tracking progress towards universal coverage for reproductive, maternal, newborn, and child health

Building upon the successes of Countdown to 2015, Countdown to 2030 aims to support the monitoring and measurement of women's, children's, and adolescents' health in the 81 countries that account for 95% of maternal and 90% of all child deaths worldwide. To achieve the Sustainable Development Goals by 2030, the rate of decline in prevalence of maternal and child mortality, stillbirths, and stunting among children younger than 5 years of age needs to accelerate considerably compared with progress since 2000. Such accelerations are only possible with a rapid scale-up of effective interventions to all population groups within countries (particularly in countries with the highest mortality and in those affected by conflict), supported by improvements in underlying socioeconomic conditions, including women's empowerment. Three main conclusions emerge from our analysis of intervention coverage, equity, and drivers of reproductive, maternal, newborn, and child health (RMNCH) in the 81 Countdown countries. First, even though strong progress was made in the coverage of many essential RMNCH interventions during the past decade, many countries are still a long way from universal coverage for most essential interventions. Furthermore, a growing body of evidence suggests that available services in many countries are of poor quality, limiting the potential effect on RMNCH outcomes. Second, within-country inequalities in intervention coverage are reducing in most countries (and are now almost non-existent in a few countries), but the pace is too slow. Third, health-sector (eg, weak country health systems) and non-health-sector drivers (eg, conflict settings) are major impediments to delivering high-quality services to all populations. Although more data for RMNCH interventions are available now, major data gaps still preclude the use of evidence to drive decision making and accountability. Countdown to 2030 is investing in improvements in measurement in several areas, such as quality of care and effective coverage, nutrition programmes, adolescent health, early childhood development, and evidence for conflict settings, and is prioritising its regional networks to enhance local analytic capacity and evidence for RMNCH

Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses

Secreted and membrane tethered matrix metalloproteinases (MMPs) are key homeostatic proteases regulating the extracellular signaling and structural matrix environment of cells and tissues. For drug targeting of proteases, selectivity for individual molecules is highly desired and can be met by high yield active site specificity profiling. Using the high throughput Proteomic Identification of protease Cleavage Sites (PICS) method to simultaneously profile both the prime and non-prime sides of the cleavage sites of nine human MMPs, we identified more than 4300 cleavages from P6 to P6′ in biologically diverse human peptide libraries. MMP specificity and kinetic efficiency were mainly guided by aliphatic and aromatic residues in P1′ (with a ~ 32–93% preference for leucine depending on the MMP), and basic and small residues in P2′ and P3′, respectively. A wide differential preference for the hallmark P3 proline was found between MMPs ranging from 15 to 46%, yet when combined in the same peptide with the universally preferred P1′ leucine, an unexpected negative cooperativity emerged. This was not observed in previous studies, probably due to the paucity of approaches that profile both the prime and non-prime sides together, and the masking of subsite cooperativity effects by global heat maps and iceLogos. These caveats make it critical to check for these biologically highly important effects by fixing all 20 amino acids one-by-one in the respective subsites and thorough assessing of the inferred specificity logo changes. Indeed an analysis of bona fide MEROPS physiological substrate cleavage data revealed that of the 37 natural substrates with either a P3-Pro or a P1′-Leu only 5 shared both features, confirming the PICS data. Upon probing with several new quenched-fluorescent peptides, rationally designed on our specificity data, the negative cooperativity was explained by reduced non-prime side flexibility constraining accommodation of the rigidifying P3 proline with leucine locked in S1′. Similar negative cooperativity between P3 proline and the novel preference for asparagine in P1 cements our conclusion that non-prime side flexibility greatly impacts MMP binding affinity and cleavage efficiency. Thus, unexpected sequence cooperativity consequences were revealed by PICS that uniquely encompasses both the non-prime and prime sides flanking the proteomic-pinpointed scissile bond