Mechanism for synchronized motion between two humans in mutual tapping experiments: Transition from alternative mode to synchronization mode

We performed mutual tapping experiments between two humans to investigate the conditions required for synchronized motion. A transition from an alternative mode to a synchronization mode was discovered under the same conditions when a subject changed from a reactive mode to an anticipation mode in single tapping experiments. Experimental results suggest that the cycle time for each tapping motion is tuned by a proportional control that is based on synchronization errors and cycle time errors. As the tapping frequency increases, the mathematical model based on the feedback control in the sensory-motor closed loop predicts a discrete mode transition as the gain factors of the proportional control decease. The conditions of the synchronization were shown as a consequence of the coupled dynamics based on the subsequent feedback loop in the sensory-motor system.

Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

An alternative approach to investigating lead-lag relationships between stock and stock index futures markets

In the absence of market frictions, the cost-of-carry model of stock index futures pricing predicts that returns on the underlying stock index and the associated stock index futures contract will be perfectly contemporaneously correlated. Evidence suggests, however, that this prediction is violated with clear evidence that the stock index futures market leads the stock market. It is argued that traditional tests, which assume that the underlying data generating process is constant, might be prone to overstate the lead-lag relationship. Using a new test for lead-lag relationships based on cross correlations and cross bicorrelations it is found that, contrary to results from using the traditional methodology, periods where the futures market leads the cash market are few and far between and when any lead-lag relationship is detected, it does not last long. Overall, the results are consistent with the prediction of the standard cost-of-carry model and market efficiency.

Portmanteau model diagnostics and tests for nonlinearity: a comparative Monte Carlo study of two alternative methods

This paper employs an extensive Monte Carlo study to test the size and power of the BDS and close return methods of testing for departures from independent and identical distribution. It is found that the finite sample properties of the BDS test are far superior and that the close return method cannot be recommended as a model diagnostic. Neither test can be reliably used for very small samples, while the close return test has low power even at large sample sizes

Sea surface temperature climate change initiative: alternative image classification algorithms for sea-ice affected oceans

We present a Bayesian image classification scheme for discriminating cloud, clear and sea-ice observations at high latitudes to improve identification of areas of clear-sky over ice-free ocean for SST retrieval. We validate the image classification against a manually classified dataset using Advanced Along Track Scanning Radiometer (AATSR) data. A three way classification scheme using a near-infrared textural feature improves classifier accuracy by 9.9 % over the nadir only version of the cloud clearing used in the ATSR Reprocessing for Climate (ARC) project in high latitude regions. The three way classification gives similar numbers of cloud and ice scenes misclassified as clear but significantly more clear-sky cases are correctly identified (89.9 % compared with 65 % for ARC). We also demonstrate the poetential of a Bayesian image classifier including information from the 0.6 micron channel to be used in sea-ice extent and ice surface temperature retrieval with 77.7 % of ice scenes correctly identified and an overall classifier accuracy of 96 %.

Using an individual-based model to select among alternative foraging strategies of woodpigeons: data support a memory-based model with a flocking mechanism

Population modelling is increasingly recognised as a useful tool for pesticide risk assessment. For vertebrates that may ingest pesticides with their food, such as woodpigeon (Columba palumbus), population models that simulate foraging behaviour explicitly can help predicting both exposure and population-level impact. Optimal foraging theory is often assumed to explain the individual-level decisions driving distributions of individuals in the field, but it may not adequately predict spatial and temporal characteristics of woodpigeon foraging because of the woodpigeons’ excellent memory, ability to fly long distances, and distinctive flocking behaviour. Here we present an individual-based model (IBM) of the woodpigeon. We used the model to predict distributions of foraging woodpigeons that use one of six alternative foraging strategies: optimal foraging, memory-based foraging and random foraging, each with or without flocking mechanisms. We used pattern-oriented modelling to determine which of the foraging strategies is best able to reproduce observed data patterns. Data used for model evaluation were gathered during a long-term woodpigeon study conducted between 1961 and 2004 and a radiotracking study conducted in 2003 and 2004, both in the UK, and are summarised here as three complex patterns: the distributions of foraging birds between vegetation types during the year, the number of fields visited daily by individuals, and the proportion of fields revisited by them on subsequent days. The model with a memory-based foraging strategy and a flocking mechanism was the only one to reproduce these three data patterns, and the optimal foraging model produced poor matches to all of them. The random foraging strategy reproduced two of the three patterns but was not able to guarantee population persistence. We conclude that with the memory-based foraging strategy including a flocking mechanism our model is realistic enough to estimate the potential exposure of woodpigeons to pesticides. We discuss how exposure can be linked to our model, and how the model could be used for risk assessment of pesticides, for example predicting exposure and effects in heterogeneous landscapes planted seasonally with a variety of crops, while accounting for differences in land use between landscapes.

Computerised therapies for anxiety and depression in children and young people: a systematic review and meta-anaylsis

One quarter of children and young people (CYP) experience anxiety and/or depression before adulthood, but treatment is sometimes unavailable or inadequate. Self-help interventions may have a role in augmenting treatment and this work aimed to systematically review the evidence for computerised anxiety and depression interventions in CYP aged 5–25 years old. Databases were searched for randomised controlled trials and 27 studies were identified. For young people (12–25 years) with risk of diagnosed anxiety disorders or depression, computerised CBT (cCBT) had positive effects for symptoms of anxiety (SMD −0.77, 95% CI −1.45 to −0.09, k = 6, N = 220) and depression (SMD −0.62, 95% CI −1.13 to −0.11, k = 7, N = 279). In a general population study of young people, there were small positive effects for anxiety (SMD −0.15, 95% CI −0.26 to −0.03; N = 1273) and depression (SMD −0.15, 95% CI −0.26 to −0.03; N = 1280). There was uncertainty around the effectiveness of cCBT in children (5–11 years). Evidence for other computerised interventions was sparse and inconclusive. Computerised CBT has potential for treating and preventing anxiety and depression in clinical and general populations of young people. Further program development and research is required to extend its use and establish its benefit in children.

Efficient animal-serum free 3D cultivation method for adult human neural crest-derived stem cell therapeutics

Due to their broad differentiation potential and their persistence into adulthood, human neural crest-derived stem cells (NCSCs) harbour great potential for autologous cellular therapies, which include the treatment of neurodegenerative diseases and replacement of complex tissues containing various cell types, as in the case of musculoskeletal injuries. The use of serum-free approaches often results in insufficient proliferation of stem cells and foetal calf serum implicates the use of xenogenic medium components. Thus, there is much need for alternative cultivation strategies. In this study we describe for the first time a novel, human blood plasma based semi-solid medium for cultivation of human NCSCs. We cultivated human neural crest-derived inferior turbinate stem cells (ITSCs) within a blood plasma matrix, where they revealed higher proliferation rates compared to a standard serum-free approach. Three-dimensionality of the matrix was investigated using helium ion microscopy. ITSCs grew within the matrix as revealed by laser scanning microscopy. Genetic stability and maintenance of stemness characteristics were assured in 3D cultivated ITSCs, as demonstrated by unchanged expression profile and the capability for self-renewal. ITSCs pre-cultivated in the 3D matrix differentiated efficiently into ectodermal and mesodermal cell types, particularly including osteogenic cell types. Furthermore, ITSCs cultivated as described here could be easily infected with lentiviruses directly in substrate for potential tracing or gene therapeutic approaches. Taken together, the use of human blood plasma as an additive for a completely defined medium points towards a personalisable and autologous cultivation of human neural crest-derived stem cells under clinical grade conditions.

Alternative generation of CNS neural stem cells and PNS derivatives from neural crest-derived peripheral stem cells

Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central nervous system (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate that rNCSCs completely lose their previous PNS characteristics and acquire the identity of neural stem cells derived from embryonic spinal cord. Reprogramming proceeds rapidly and results in a homogenous population of Olig2-, Sox3-, and Lex-positive CNS stem cells. Low-level expression of pluripotency inducing genes Oct4, Nanog, and Klf4 argues against a transient pluripotent state during reprogramming. The acquisition of CNS properties is prevented in the presence of BMP4 (BMP NCSCs) as shown by marker gene expression and the potential to produce PNS neurons and glia. In addition, genes characteristic for mesenchymal and perivascular progenitors are expressed, which suggests that BMP NCSCs are directed toward a pericyte progenitor/mesenchymal stem cell (MSC) fate. Adult NCSCs from mouse palate, an easily accessible source of adult NCSCs, display strikingly similar properties. They do not generate cells with CNS characteristics but lose the neural crest markers Sox10 and p75 and produce MSC-like cells. These findings show that embryonic NCSCs acquire a full CNS identity in NS culture. In contrast, MSC-like cells are generated from BMP NCSCs and pNCSCs, which reveals that postmigratory NCSCs are a source for MSC-like cells up to the adult stage.

The neurogenic potential of astrocytes is regulated by inflammatory signals

Although the adult brain contains neural stem cells (NSCs) that generate new neurons throughout life, these astrocyte-like populations are restricted to two discrete niches. Despite their terminally differentiated phenotype, adult parenchymal astrocytes can re-acquire NSC-like characteristics following injury, and as such, these 'reactive' astrocytes offer an alternative source of cells for central nervous system (CNS) repair following injury or disease. At present, the mechanisms that regulate the potential of different types of astrocytes are poorly understood. We used in vitro and ex vivo astrocytes to identify candidate pathways important for regulation of astrocyte potential. Using in vitro neural progenitor cell (NPC)-derived astrocytes, we found that exposure of more lineage-restricted astrocytes to either tumor necrosis factor alpha (TNF-α) (via nuclear factor-κB (NFκB)) or the bone morphogenetic protein (BMP) inhibitor, noggin, led to re-acquisition of NPC properties accompanied by transcriptomic and epigenetic changes consistent with a more neurogenic, NPC-like state. Comparative analyses of microarray data from in vitro-derived and ex vivo postnatal parenchymal astrocytes identified several common pathways and upstream regulators associated with inflammation (including transforming growth factor (TGF)-β1 and peroxisome proliferator-activated receptor gamma (PPARγ)) and cell cycle control (including TP53) as candidate regulators of astrocyte phenotype and potential. We propose that inflammatory signalling may control the normal, progressive restriction in potential of differentiating astrocytes as well as under reactive conditions and represent future targets for therapies to harness the latent neurogenic capacity of parenchymal astrocytes.

Proteomic analysis of Artemisia annua – towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin

Background: MS-based proteomics was applied to the analysis of the medicinal plant Artemisia annua, exploiting a recently published contig sequence database (Graham et al. (2010) Science 327, 328–331) and other genomic and proteomic sequence databases for comparison. A. annua is the predominant natural source of artemisinin, the precursor for artemisinin-based combination therapies (ACTs), which are the WHO-recommended treatment for P. falciparum malaria. Results: The comparison of various databases containing A. annua sequences (NCBInr/viridiplantae, UniProt/ viridiplantae, UniProt/A. annua, an A. annua trichome Trinity contig database, the above contig database and another A. annua EST database) revealed significant differences in respect of their suitability for proteomic analysis, showing that an organism-specific database that has undergone extensive curation, leading to longer contig sequences, can greatly increase the number of true positive protein identifications, while reducing the number of false positives. Compared to previously published data an order-of-magnitude more proteins have been identified from trichome-enriched A. annua samples, including proteins which are known to be involved in the biosynthesis of artemisinin, as well as other highly abundant proteins, which suggest additional enzymatic processes occurring within the trichomes that are important for the biosynthesis of artemisinin. Conclusions: The newly gained information allows for the possibility of an enzymatic pathway, utilizing peroxidases, for the less well understood final stages of artemisinin’s biosynthesis, as an alternative to the known non-enzymatic in vitro conversion of dihydroartemisinic acid to artemisinin. Data are available via ProteomeXchange with identifier PXD000703.