Structure of d(TGCGCA)(2) and a comparison with other DNA Hexamers

The X-ray crystal structure of d(TGCGCA)(2) has been determined at 120 K to a resolution of 1.3 Angstrom. Hexamer duplexes, in the Z-DNA conformation, pack in an arrangement similar to the 'pure spermine form' [Egli et al. (1991). Biochemistry, 30, 11388-11402] but with significantly different cell dimensions. The phosphate backbone exists in two equally populated discrete conformations at one nucleotide step, around phosphate 11. The structure contains two ordered cobalt hexammine molecules which have roles in stabilization of both the Z-DNA conformation of the duplex and in crystal packing. A comparison of d(TGCGCA)(2) with other Z-DNA hexamer structures available in the Nucleic Acid Database illustrates the elusive nature of crystal packing. A review of the interactions with the metal cations Na+, Mg2+ and Co3+ reveals a relatively small proportion of phosphate binding and that close contacts between metal ions are common. A prediction of the water structure is compared with the observed pattern in the reported structure

Feasibility of undertaking off-site infant eye-tracking assessments of neuro-cognitive functioning in early-intervention centres

Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to persuade low-SES parents to come to a university setting. One solution is to recruit infants through early intervention children’s centres (CCs). These are often located in areas of high relative deprivation to support young children. Given the increasing portability of eye-tracking equipment, assessment of large clusters of infants could be undertaken in centres by suitably trained early intervention staff. Here we report on a study involving 174 infants and their parents, carried out in partnership with CCs, exploring the feasibility of this approach, We report the processes of setting up the project and participant recruitment. We report the diversity of sample obtained on the engagement of CC staff in training and the process of assessment itself. We report the quality of the data obtained, and the levels of engagement of parents, and infants. We conclude that this approach has great potential for recruiting large and diverse samples worldwide, provides sufficiently reliable data, and is engaging to staff, parents and infants

Input-output theory for fermions in an atom cavity

We generalize the quantum optical input-output theory developed for optical cavities to ultracold fermionic atoms confined in a trapping potential, which forms an "atom cavity". In order to account for the Pauli exclusion principle, quantum Langevin equations for all cavity modes are derived. The dissipative part of these multi-mode Langevin equations includes a coupling between cavity modes. We also derive a set of boundary conditions for the Fermi field that relate the output fields to the input fields and the field radiated by the cavity. Starting from a constant uniform current of fermions incident on one side of the cavity, we use the boundary conditions to calculate the occupation numbers and current density for the fermions that are reflected and transmitted by the cavity

M-CSF instructs myeloid lineage fate in single haematopoietic stem cells

Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors, but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors, leaving cytokines to ensure survival and proliferation of the progeny cells. Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified HSCs with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1(+) cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs and induced a PU.1-dependent myeloid differentiation preference. Our data demonstrate that lineage-specific cytokines can act directly on HSCs in vitro and in vivo to instruct a change of cell identity. This fundamentally changes the current view of how HSCs respond to environmental challenge and implicates stress-induced cytokines as direct instructors of HSC fate

Higher-order mutual coherence of optical and matter waves

We use an operational approach to discuss ways to measure the higher-order cross-correlations between optical and matter-wave fields. We pay particular attention to the fact that atomic fields actually consist of composite particles that can easily be separated into their basic constituents by a detection process such as photoionization. In the case of bosonic fields, that we specifically consider here, this leads to the appearance in the detection signal of exchange contributions due to both the composite bosonic field and its individual fermionic constituents. We also show how time-gated counting schemes allow to isolate specific contributions to the signal, in particular involving different orderings of the Schr\"odinger and Maxwell fields.Comment: 11 pages, 2 figure

Efficiency of scanning and attention to faces in infancy independently predict language development in a multiethnic and bilingual sample of 2-year-olds

Efficient visual exploration in infancy is essential for cognitive and language development. It allows infants to participate in social interactions by attending to faces and learning about objects of interest. Visual scanning of scenes depends on a number of factors and early differences in efficiency are likely contributing to differences in learning and language development during subsequent years. Predicting language development in diverse samples is particularly challenging, as additional multiple sources of variability affect infant performance. In this study we tested how the complexity of visual scanning in the presence or absence of a face at 6-7 months of age is related to language development at 2 years of age in a multi-ethnic and predominantly bilingual sample from diverse socio-economic backgrounds. We used Recurrence Quantification Analysis to measure the temporal and spatial distribution of fixations recurring in the same area of a visual scene. We found that in the absence of a face the temporal distribution of re-fixations on selected objects of interest (but not all) significantly predicted both receptive and expressive language scores, explaining 16 - 20% of the variance. Also, lower rate of re-fixations recurring in the presence of a face predicted higher receptive language scores, suggesting larger vocabulary in infants that effectively disengage from faces. Altogether, our results suggest that dynamic measures, which quantify the complexity of visual scanning can reliably and robustly predict language development in highly diverse samples. They suggest that selective attending to objects predicts language independently of attention to faces. As eye-tracking and language assessments were carried out in early intervention centres, our study demonstrates the utility of mobile eye-tracking setups for early detection of risk in attention and language development

A Pinned Polymer Model of Posture Control

A phenomenological model of human posture control is posited. The dynamics are modelled as an elastically pinned polymer under the influence of noise. The model accurately reproduces the two-point correlation functions of experimental posture data and makes predictions for the response function of the postural control system. The physiological and clinical significance of the model is discussed.Comment: uuencoded post script file, 17 pages with 3 figure

Beyond fixation durations: Recurrence quantification analysis reveals spatiotemporal dynamics of infant visual scanning

Standard looking-duration measures in eye-tracking data provide only general quantitative indices, while details of the spatiotemporal structuring of fixation sequences are lost. To overcome this, various tools have been developed to measure the dynamics of fixations. However, these analyses are only useful when stimuli have high perceptual similarity and they require the previous definition of areas of interest (AOIs). Although these methods have been widely applied in adult studies, relatively little is known about the temporal structuring of infant gaze-foraging behaviors such as variability of scanning over time or individual scanning patterns. Thus, to shed more light on the spatiotemporal characteristics of infant fixation sequences we apply for the first time a new methodology for nonlinear time-series analysis—the recurrence quantification analysis (RQA). We present how the dynamics of infant scanning varies depending on the scene content during a "pop-out" search task. Moreover, we show how the normalization of RQA measures with average fixation durations provides a more detailed account of the dynamics of fixation sequences. Finally, we link the RQA measures of temporal dynamics of scanning with the spatial information about the stimuli using heat maps of recurrences without the need for defining a priori AOIs and present how infants’ foraging strategies are driven by the image content. We conclude from our findings that the RQA methodology has potential applications in the analysis of the temporal dynamics of infant visual foraging offering advantages over existing methods

Multiple locus VNTR analysis highlights that geographical clustering and distribution of Dichelobacter nodosus, the causal agent of footrot in sheep, correlates with inter-country movements

Dichelobacter nodosus is a Gram-negative, anaerobic bacterium and the causal agent of footrot in sheep. Multiple locus variable number tandem repeat (VNTR) analysis (MLVA) is a portable technique that involves the identification and enumeration of polymorphic tandem repeats across the genome. The aims of this study were to develop an MLVA scheme for D. nodosus suitable for use as a molecular typing tool, and to apply it to a global collection of isolates. Seventy-seven isolates selected from regions with a long history of footrot (GB, Australia) and regions where footrot has recently been reported (India, Scandinavia), were characterised. From an initial 61 potential VNTR regions, four loci were identified as usable and in combination had the attributes required of a typing method for use in bacterial epidemiology: high discriminatory power (D > 0.95), typeability and reproducibility. Results from the analysis indicate that D. nodosus appears to have evolved via recombinational exchanges and clonal diversification. This has resulted in some clonal complexes that contain isolates from multiple countries and continents; and others that contain isolates from a single geographic location (country or region). The distribution of alleles between countries matches historical accounts of sheep movements, suggesting that the MLVA technique is sufficiently specific and sensitive for an epidemiological investigation of the global distribution of D. nodosus