Testosterone and cortisol figure prominently in the research literature having to do with human competition. In this review, we track the history of this literature, concentrating particularly on ...major theoretical and empirical contributions, and provide commentary on what we see as important unresolved issues. In men and women, athletic competition is typically associated with an increase in testosterone (T) and cortisol (C). Hormone changes in response to non-athletic competition are less predictable. Person (e.g., power motivation, mood, aggressiveness, social anxiety, sex, and baseline levels of T and C) and context (e.g., whether a competition is won or lost, the closeness of the competition, whether the outcome is perceived as being influenced by ability vs. chance, provocations) factors can influence hormone responses to competition. From early on, studies pointed to a positive relationship between T and dominance motivation/status striving. Recent research, however, suggests that this relationship only holds for individuals with low levels of C – this is the core idea of the dual-hormone hypothesis, and it is certain that the broadest applications of the hypothesis have not yet been realized. Individuals differ with respect to the extent to which they embrace competition, but the hormonal correlates of competitiveness remain largely unexplored. Although rapid increases in both T and C associated with competition are likely adaptive, we still know very little about the psychological benefits of these hormonal changes. Administration studies have and will continue to contribute to this inquiry. We close with a discussion of what, we think, are important methodological and mechanistic issues for future research.
•A review of the history and research surrounding the testosterone and cortisol response to social competition in humans•Theoretical and empirical contributions from studies of athletic and non-athletic/laboratory competition are included•Person and context factors that impact the hormonal response to competition are considered•Methodological and mechanistic issues within the literature are discussed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This follow-up study of children who were enrolled in a randomized trial of hypothermia for perinatal asphyxial encephalopathy showed that at the age of 6 to 7 years, the hypothermia group had a ...higher rate of survival with an IQ score of 85 or more than the control group.
Perinatal asphyxial encephalopathy is associated with a high risk of death or early neurodevelopmental impairment. Among survivors, cerebral palsy, functional disability, and cognitive impairment often develop later in childhood. The cost of this condition to patients, their families, and society is high.
In several randomized, controlled trials involving infants with clear evidence of asphyxial encephalopathy, moderate hypothermia (33 to 34°C) for 72 hours, initiated within 6 hours after delivery, has been shown to reduce the risk of death or disability at 18 to 24 months of age and to increase the rate of survival free of disability.
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The observation that . . .
The fatty acyl composition of phospholipids determines the biophysical character of membranes and impacts the function of membrane proteins. Here, we define a nuclear receptor pathway for the dynamic ...modulation of membrane composition in response to changes in cellular lipid metabolism. Ligand activation of liver X receptors (LXRs) preferentially drives the incorporation of polyunsaturated fatty acids into phospholipids through induction of the remodeling enzyme Lpcat3. Promotion of Lpcat3 activity ameliorates endoplasmic reticulum (ER) stress induced by saturated free fatty acids in vitro or by hepatic lipid accumulation in vivo. Conversely, Lpcat3 knockdown in liver exacerbates ER stress and inflammation. Mechanistically, Lpcat3 modulates inflammation both by regulating inflammatory kinase activation through changes in membrane composition and by affecting substrate availability for inflammatory mediator production. These results outline an endogenous mechanism for the preservation of membrane homeostasis during lipid stress and identify Lpcat3 as an important mediator of LXR effects on metabolism.
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•Induction of Lpcat3 expression by LXRs promotes phospholipid remodeling•LXR-Lpcat3 activation drives unsaturated fatty acid incorporation into phospholipids•Lpcat3 activity in liver modulates lipid-induced ER stress and inflammation•Lpcat3 affects inflammation through regulation of membrane c-Src activity
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
There has been a recent proliferation in neuroimaging research focusing on brain development in the prenatal, neonatal and very early childhood brain. Early brain injury and preterm birth ...are associated with increased risk of neurodevelopmental disorders, indicating the importance of this early period for later outcome.
Scope and methodology
Although using a wide range of different methodologies and investigating diverse samples, the common aim of many of these studies has been to both track normative development and investigate deviations in this development to predict behavioural, cognitive and neurological function in childhood. Here we review structural and functional neuroimaging studies investigating the developing brain. We focus on practical and technical complexities of studying this early age range and discuss how neuroimaging techniques have been successfully applied to investigate later neurodevelopmental outcome.
Conclusions
Neuroimaging markers of later outcome still have surprisingly low predictive power and their specificity to individual neurodevelopmental disorders is still under question. However, the field is still young, and substantial challenges to both acquiring and modeling neonatal data are being met.
Read the Commentary on this article at doi: 10.1111/jcpp.12890
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Regulatory T (Treg) cells induce an immunosuppressive microenvironment that is a major obstacle for successful tumor immunotherapy. Dissecting the regulatory mechanisms between energy metabolism and ...functionality in Treg cells will provide insight toward developing novel immunotherapies against cancer. Here we report that human naturally occurring and tumor-associated Treg cells exhibit distinct metabolic profiles with selectivity for glucose metabolism compared with effector T cells. Treg-mediated accelerated glucose consumption induces cellular senescence and suppression of responder T cells through cross-talk. TLR8 signaling selectively inhibits glucose uptake and glycolysis in human Treg cells, resulting in reversal of Treg suppression. Importantly, TLR8 signaling-mediated reprogramming of glucose metabolism and function in human Treg cells can enhance anti-tumor immunity in vivo in a melanoma adoptive transfer T cell therapy model. Our studies identify mechanistic links between innate signaling and metabolic regulation of human Treg suppression, which may be used as a strategy to advance tumor immunotherapy.
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•Human Tregs exhibit distinct metabolic profiles compared with effector T cells•Activated Tregs uniquely accelerate glucose consumption for their suppression•TLR8 signaling selectively inhibits glucose uptake and glycolysis in human Tregs•TLR8-mediated reprogramming of Treg glucose metabolism enhances anti-tumor immunity
Treg-mediated immunosuppression is a significant obstacle for tumor immunotherapy. Li et al. show that human Treg cells heighten glucose consumption and subsequently trigger cellular senescence and suppression of effector T cells. With TLR8 signaling, they selectively inhibit glucose uptake and glycolysis in human Treg cells, resulting in Treg function reversal and enhanced anti-tumor immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sinking particles are a critical conduit for the export of organic material from surface waters to the deep ocean. Despite their importance in oceanic carbon cycling and export, little is known about ...the biotic composition, origins, and variability of sinking particles reaching abyssal depths. Here, we analyzed particle-associated nucleic acids captured and preserved in sediment traps at 4,000-m depth in the North Pacific Subtropical Gyre. Over the 9-month time-series, Bacteria dominated both the rRNA-gene and rRNA pools, followed by eukaryotes (protists and animals) and trace amounts of Archaea. Deep-sea piezophile-like Gammaproteobacteria, along with Epsilonproteobacteria, comprised >80% of the bacterial inventory. Protists (mostly Rhizaria, Syndinales, and ciliates) and metazoa (predominantly pelagic mollusks and cnidarians) were the most common sinking particle-associated eukaryotes. Some near-surface water-derived eukaryotes, especially Foraminifera, Radiolaria, and pteropods, varied greatly in their abundance patterns, presumably due to sporadic export events. The dominance of piezophile-like Gammaproteobacteria and Epsilonproteobacteria, along with the prevalence of their nitrogen cycling-associated gene transcripts, suggested a central role for these bacteria in the mineralization and biogeochemical transformation of sinking particulate organic matter in the deep ocean. Our data also reflected several different modes of particle export dynamics, including summer export, more stochastic inputs from the upper water column by protists and pteropods, and contributions from sinking mid- and deep-water organisms. In total, our observations revealed the variable and heterogeneous biological origins and microbial activities of sinking particles that connect their downward transport, transformation, and degradation to deep-sea biogeochemical processes.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Injectable biomaterials are increasingly being explored to minimize risks and complications associated with surgical implantation. We describe a strategy for delivery via conventional needle–syringe ...injection of large preformed macroporous scaffolds with well-defined properties. Injectable 3D scaffolds, in the form of elastic sponge-like matrices, were prepared by environmentally friendly cryotropic gelation of a naturally sourced polymer. Cryogels with shape-memory properties may be molded to a variety of shapes and sizes, and may be optionally loaded with therapeutic agents or cells. These scaffolds have the capability to withstand reversible deformations at over 90% strain level, and a rapid volumetric recovery allows the structurally defined scaffolds to be injected through a small-bore needle with nearly complete geometric restoration once delivered. These gels demonstrated long-term release of biomolecules in vivo. Furthermore, cryogels impregnated with bioluminescent reporter cells provided enhanced survival, higher local retention, and extended engraftment of transplanted cells at the injection site compared with a standard injection technique. These injectable scaffolds show great promise for various biomedical applications, including cell therapies.
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Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether ...the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00934700 , and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. Interpretation Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. Funding UK Medical Research Council.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Patients undergoing Magnetic Resonance Imaging (MRI) often experience anxiety and sometimes distress prior to and during scanning. Here a full MRI compatible virtual reality (VR) system is described ...and tested with the aim of creating a radically different experience. Potential benefits could accrue from the strong sense of immersion that can be created with VR, which could create sense experiences designed to avoid the perception of being enclosed and could also provide new modes of diversion and interaction that could make even lengthy MRI examinations much less challenging. Most current VR systems rely on head mounted displays combined with head motion tracking to achieve and maintain a visceral sense of a tangible virtual world, but this technology and approach encourages physical motion, which would be unacceptable and could be physically incompatible for MRI. The proposed VR system uses gaze tracking to control and interact with a virtual world. MRI compatible cameras are used to allow real time eye tracking and robust gaze tracking is achieved through an adaptive calibration strategy in which each successive VR interaction initiated by the subject updates the gaze estimation model. A dedicated VR framework has been developed including a rich virtual world and gaze-controlled game content. To aid in achieving immersive experiences physical sensations, including noise, vibration and proprioception associated with patient table movements, have been made congruent with the presented virtual scene. A live video link allows subject-carer interaction, projecting a supportive presence into the virtual world.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Rich-club organization of the newborn human brain Ball, Gareth; Aljabar, Paul; Zebari, Sally ...
Proceedings of the National Academy of Sciences - PNAS,
05/2014, Volume:
111, Issue:
20
Journal Article
Peer reviewed
Open access
Combining diffusion magnetic resonance imaging and network analysis in the adult human brain has identified a set of highly connected cortical hubs that form a “rich club”—a high-cost, high-capacity ...backbone thought to enable efficient network communication. Rich-club architecture appears to be a persistent feature of the mature mammalian brain, but it is not known when this structure emerges during human development. In this longitudinal study we chart the emergence of structural organization in mid to late gestation. We demonstrate that a rich club of interconnected cortical hubs is already present by 30 wk gestation. Subsequently, until the time of normal birth, the principal development is a proliferation of connections between core hubs and the rest of the brain. We also consider the impact of environmental factors on early network development, and compare term-born neonates to preterm infants at term-equivalent age. Though rich-club organization remains intact following premature birth, we reveal significant disruptions in both in cortical–subcortical connectivity and short-distance corticocortical connections. Rich club organization is present well before the normal time of birth and may provide the fundamental structural architecture for the subsequent emergence of complex neurological functions. Premature exposure to the extrauterine environment is associated with altered network architecture and reduced network capacity, which may in part account for the high prevalence of cognitive problems in preterm infants.
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