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1,828 result(s) for "Wilson, Stuart"
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Eastern Europe
Lonely Planet's Eastern Europe is your passport to the most relevant, up-to-date advice on what to see and skip, and what hidden discoveries await you. Hop from thermal baths to coffee houses to 'ruin bars' in Budapest, glide from island to island in Croatia and meander through 14th-century alleyways in Prague - all with your trusted travel companion. Get to the heart of Eastern Europe and begin your journey now!
Increased vapor pressure deficit due to higher temperature leads to greater transpiration and faster mortality during drought for tree seedlings common to the forest–grassland ecotone
Tree species growing along the forest–grassland ecotone are near the moisture limit of their range. Small increases in temperature can increase vapor pressure deficit (VPD) which may increase tree water use and potentially hasten mortality during severe drought. We tested a 40% increase in VPD due to an increase in growing temperature from 30 to 33°C (constant dewpoint 21°C) on seedlings of 10 tree species common to the forest–grassland ecotone in the southern Great Plains, USA. Measurement at 33 vs 30°C during reciprocal leaf gas exchange measurements, that is, measurement of all seedlings at both growing temperatures, increased transpiration for seedlings grown at 30°C by 40% and 20% for seedlings grown at 33°C. Higher initial transpiration of seedlings in the 33°C growing temperature treatment resulted in more negative xylem water potentials and fewer days until transpiration decreased after watering was withheld. The seedlings grown at 33°C died 13% (average 2 d) sooner than seedlings grown at 30°C during terminal drought. If temperature and severity of droughts increase in the future, the forest–grassland ecotone could shift because low seedling survival rate may not sufficiently support forest regeneration and migration.
The m6A-methylase complex recruits TREX and regulates mRNA export
N 6 -methyladenosine (m 6 A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Recruitment of the TREX mRNA export complex to mRNA is driven by transcription, 5′ capping and pre-mRNA splicing. Here we identify a fourth mechanism in human cells driving the association of TREX with mRNA involving the m 6 A methylase complex. We show that the m 6 A complex recruits TREX to m 6 A modified mRNAs and this process is essential for their efficient export. TREX also stimulates recruitment of the m 6 A reader protein YTHDC1 to the mRNA and the m 6 A complex influences the interaction of TREX with YTHDC1. Together our studies reveal a key role for TREX in the export of m 6 A modified mRNAs.
Failure to demonstrate short-cutting in a replication and extension of Tolman et al.’s spatial learning experiment with humans
Successful demonstrations of novel short-cut taking by animals, including humans, are open to interpretation in terms of learning that is not necessarily spatial. A classic example is that of Tolman, Ritchie, and Kalish (1946) who allowed rats to repeat a sequence of turns through the corridors of a maze to locate a food reward. When the entrance to the corridors was subsequently blocked and alternative corridors were made available, rats successfully selected the corridor leading most directly to the food location. However, the presence of a distinctive light above the goal, in both the training and testing phases, means that approach to the light as a beacon could have been the source of successful short-cutting. We report a replication of the experimental design of Tolman et al. with human participants who explored geometrically equivalent virtual environments. An experimental group, who followed the original procedure in the absence of any distinctive cues proximal to the goal, did not select the corridor which led most directly to the goal. A control group, who experienced a light above the goal during training and testing, were more likely to select a corridor which led in the direction of the goal. A second control group experienced the light above the goal during training, but in the test the location of this cue was shifted by 90° with respect to the start point of exploration. This latter group responded unsystematically in the test, neither selecting a corridor leading to the original goal location, nor one leading directly to the relocated light cue. The results do not support the hypothesis that travelling a multi-path route automatically leads to an integrated cognitive representation of that route. The data offer support for the importance of local cues which can serve as beacons to indicate the location of a goal.
The Tudor SND1 protein is an m6A RNA reader essential for replication of Kaposi’s sarcoma-associated herpesvirus
N6-methyladenosine (m6A) is the most abundant internal RNA modification of cellular mRNAs. m6A is recognised by YTH domain-containing proteins, which selectively bind to m6A-decorated RNAs regulating their turnover and translation. Using an m6A-modified hairpin present in the Kaposi’s sarcoma associated herpesvirus (KSHV) ORF50 RNA, we identified seven members from the ‘Royal family’ as putative m6A readers, including SND1. RIP-seq and eCLIP analysis characterised the SND1 binding profile transcriptome-wide, revealing SND1 as an m6A reader. We further demonstrate that the m6A modification of the ORF50 RNA is critical for SND1 binding, which in turn stabilises the ORF50 transcript. Importantly, SND1 depletion leads to inhibition of KSHV early gene expression showing that SND1 is essential for KSHV lytic replication. This work demonstrates that members of the ‘Royal family’ have m6A-reading ability, greatly increasing their epigenetic functions beyond protein methylation. When a cell needs to make a protein, it reads from the master copy of the gene in the DNA and prints out temporary duplicates called mRNA. These duplicates then act as templates for protein production. Both DNA and mRNA can be further modified by adding on chemical tags that recruit specific proteins. While chemical modifications in DNA are known to control the activity of genes, their role in mRNA is only just being uncovered. One of the most common chemical modifications in mRNA is the addition of a methyl group called m6A. This methyl group has also been found in the mRNA of certain viruses, including the Kaposi’s sarcoma-associated herpesvirus (KSHV) which causes cancer. Recent work has shown that a family of proteins, known as the YTH family, can recognise and bind to this specific methyl group and regulate the rate at which mRNA degrades. To investigate whether other proteins can recognise m6A, Baquero-Pérez et al. mapped the m6A residues of mRNAs encoded by KSHV genes and looked at which proteins the methyl mark interacts with. The experiments revealed that a family of proteins – nicknamed the ‘Royal family’ – that recognise methyl groups in proteins, can also bind to mRNA that contains m6A. Baquero-Pérez et al. showed that a member of this family, SND1, can read the m6A methyl mark on mRNAs from both the virus and the host cell. Further experiments showed that SND1 binds to and stabilises a viral mRNA which provides the template for a protein that the virus needs to replicate. When SND1 was removed from human immune cells infected with KSHV, this caused the virus to replicate less efficiently. The discovery that the Royal family of proteins can recognise methylated mRNA as well as methylated proteins suggests that there may be a common feature that allows proteins to read methylation. Understanding the shape of this feature could lead to new treatments that block viruses from making the proteins they need to replicate.
Biological action at a distance: Correlated pattern formation in adjacent tessellation domains without communication
Tessellations emerge in many natural systems, and the constituent domains often contain regular patterns, raising the intriguing possibility that pattern formation within adjacent domains might be correlated by the geometry, without the direct exchange of information between parts comprising either domain. We confirm this paradoxical effect, by simulating pattern formation via reaction-diffusion in domains whose boundary shapes tessellate, and showing that correlations between adjacent patterns are strong compared to controls that self-organize in domains with equivalent sizes but unrelated shapes. The effect holds in systems with linear and non-linear diffusive terms, and for boundary shapes derived from regular and irregular tessellations. Based on the prediction that correlations between adjacent patterns should be bimodally distributed, we develop methods for testing whether a given set of domain boundaries constrained pattern formation within those domains. We then confirm such a prediction by analysing the development of ‘subbarrel’ patterns, which are thought to emerge via reaction-diffusion, and whose enclosing borders form a Voronoi tessellation on the surface of the rodent somatosensory cortex. In more general terms, this result demonstrates how causal links can be established between the dynamical processes through which biological patterns emerge and the constraints that shape them.
Familiarization: A theory of repetition suppression predicts interference between overlapping cortical representations
Repetition suppression refers to a reduction in the cortical response to a novel stimulus that results from repeated presentation of the stimulus. We demonstrate repetition suppression in a well established computational model of cortical plasticity, according to which the relative strengths of lateral inhibitory interactions are modified by Hebbian learning. We present the model as an extension to the traditional account of repetition suppression offered by sharpening theory, which emphasises the contribution of afferent plasticity, by instead attributing the effect primarily to plasticity of intra-cortical circuitry. In support, repetition suppression is shown to emerge in simulations with plasticity enabled only in intra-cortical connections. We show in simulation how an extended 'inhibitory sharpening theory' can explain the disruption of repetition suppression reported in studies that include an intermediate phase of exposure to additional novel stimuli composed of features similar to those of the original stimulus. The model suggests a re-interpretation of repetition suppression as a manifestation of the process by which an initially distributed representation of a novel object becomes a more localist representation. Thus, inhibitory sharpening may constitute a more general process by which representation emerges from cortical re-organisation.
Self-organised criticality in the evolution of a thermodynamic model of rodent thermoregulatory huddling
A thermodynamic model of thermoregulatory huddling interactions between endotherms is developed. The model is presented as a Monte Carlo algorithm in which animals are iteratively exchanged between groups, with a probability of exchanging groups defined in terms of the temperature of the environment and the body temperatures of the animals. The temperature-dependent exchange of animals between groups is shown to reproduce a second-order critical phase transition, i.e., a smooth switch to huddling when the environment gets colder, as measured in recent experiments. A peak in the rate at which group sizes change, referred to as pup flow, is predicted at the critical temperature of the phase transition, consistent with a thermodynamic description of huddling, and with a description of the huddle as a self-organising system. The model was subjected to a simple evolutionary procedure, by iteratively substituting the physiologies of individuals that fail to balance the costs of thermoregulation (by huddling in groups) with the costs of thermogenesis (by contributing heat). The resulting tension between cooperative and competitive interactions was found to generate a phenomenon called self-organised criticality, as evidenced by the emergence of avalanches in fitness that propagate across many generations. The emergence of avalanches reveals how huddling can introduce correlations in fitness between individuals and thereby constrain evolutionary dynamics. Finally, a full agent-based model of huddling interactions is also shown to generate criticality when subjected to the same evolutionary pressures. The agent-based model is related to the Monte Carlo model in the way that a Vicsek model is related to an Ising model in statistical physics. Huddling therefore presents an opportunity to use thermodynamic theory to study an emergent adaptive animal behaviour. In more general terms, huddling is proposed as an ideal system for investigating the interaction between self-organisation and natural selection empirically.
What stops hospital clinical staff from following protocols? An analysis of the incidence and factors behind the failure of bedside clinical staff to activate the rapid response system in a multi-campus Australian metropolitan healthcare service
ObjectiveTo explore the causes of failure to activate the rapid response system (RRS). The organisation has a recognised incidence of staff failing to act when confronted with a deteriorating patient and leading to adverse outcomes.DesignA multi-method study using the following: a point prevalence survey to determine the incidence of abnormal simple bedside observations and activation of the rapid response team by clinical staff; a prospective audit of all patients experiencing a cardiac arrest, unplanned intensive care unit admission or death over an 8-week period; structured interviews of staff to explore cognitive and sociocultural barriers to activating the RRS.SettingSouthern Health is a comprehensive healthcare network with 570 adult in-patient beds across four metropolitan teaching hospitals in the south-eastern sector of Melbourne.MeasurementsFrequency of physiological instability and outcomes within the in-patient hospital population. Qualitative data from staff interviews were thematically coded.ResultsThe incidence of physiological instability in the acute adult population was 4.04%. Nearly half of these patients (42%) did not receive an appropriate clinical response from the staff, despite most (69.2%) recognising their patient met physiological criteria for activating the RRS, and being ‘quite’, or ‘very’ concerned about their patient (75.8%). Structured interviews with 91 staff members identified predominantly sociocultural reasons for failure to activate the RRS.ConclusionsDespite an organisational commitment to the RRS, clinical staff act on local cultural rules within the clinical environment that are usually not explicit. Better understanding of these informal rules may lead to more appropriate activation of the RRS.