A new design for a traveling-wave Zeeman decelerator: II. Experiment

A novel traveling-wave Zeeman decelerator based on a double-helix coil geometry capable of decelerating paramagnetic molecules with high efficiency is presented. Moving magnetic traps are generated by applying time-dependent currents through the decelerator coils. Paramagnetic molecules in low-field-seeking Zeeman states are confined inside the moving traps which are decelerated to lower forward velocities. As a prototypical example, we demonstrate the deceleration of OH radicals from an initial velocity of 445 m s(-1) down to various final velocities. The experimental results are analyzed and numerically reproduced with the help of trajectory simulations confirming the phase-space stability and efficiency of the deceleration of the molecules in the new device

From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes

Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users. Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling). Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources

p75NTR regulates brain mononuclear cell function and neuronal structure in Toxoplasma infection-induced neuroinflammation.

Neurotrophins mediate neuronal growth, differentiation, and survival via tropomyosin receptor kinase (Trk) or p75 neurotrophin receptor (p75NTR ) signaling. The p75NTR is not exclusively expressed by neurons but also by certain immune cells, implying a role for neurotrophin signaling in the immune system. In this study, we investigated the effect of p75NTR on innate immune cell behavior and on neuronal morphology upon chronic Toxoplasma gondii (T. gondii) infection-induced neuroinflammation. Characterization of the immune cells in the periphery and central nervous system (CNS) revealed that innate immune cell subsets in the brain upregulated p75NTR upon infection in wild-type mice. Although cell recruitment and phagocytic capacity of p75NTRexonIV knockout (p75-/- ) mice were not impaired, the activation status of resident microglia and recruited myeloid cell subsets was altered. Importantly, recruited mononuclear cells in brains of infected p75-/- mice upregulated the production of the cytokines interleukin (IL)-10, IL-6 as well as IL-1α. Protein levels of proBDNF, known to negatively influence neuronal morphology by binding p75NTR , were highly increased upon chronic infection in the brain of wild-type and p75-/- mice. Moreover, upon infection the activated immune cells contributed to the proBDNF release. Notably, the neuroinflammation-induced changes in spine density were rescued in the p75-/- mice. In conclusion, these findings indicate that neurotrophin signaling via the p75NTR affects innate immune cell behavior, thus, influencing the structural plasticity of neurons under inflammatory conditions

How to Intervene in the Caries Process in Older Adults: A Joint ORCA and EFCD Expert Delphi Consensus Statement

Aim: To provide recommendations for dental clinicians for the management of dental caries in older adults with special emphasis on root caries lesions. Methods: A consensus workshop followed by a Delphi consensus process were conducted with an expert panel nominated by ORCA, EFCD, and DGZ boards. Based on a systematic review of the literature, as well as non-systematic literature search, recommendations for clinicians were developed and consented in a two-stage Delphi process. Results: Demographic and epidemiologic changes will significantly increase the need of management of older adults and root caries in the future. Ageing is associated with a decline of intrinsic capacities and an increased risk of general diseases. As oral and systemic health are linked, bidirectional consequences of diseases and interventions need to be considered. Caries prevention and treatment in older adults must respond to the patient’s individual abilities for self-care and cooperation and often involves the support of caregivers. Systemic interventions may involve dietary counselling, oral hygiene instruction, the use of fluoridated toothpastes, and the stimulation of salivary flow. Local interventions to manage root lesions may comprise local biofilm control, application of highly fluoridated toothpastes or varnishes as well as antimicrobial agents. Restorative treatment is often compromised by the accessibility of such root caries lesions as well as the ability of the senior patient to cooperate. If optimum restorative treatment is impossible or inappropriate, longterm stabilization, e.g., by using glass-ionomer cements, and palliative treatments that aim to maintain oral function as long and as well as possible may be the treatment of choice for the individual

How to Intervene in the Caries Process in Older Adults: A Joint ORCA and EFCD Expert Delphi Consensus Statement

Aim: To provide recommendations for dental clinicians for the management of dental caries in older adults with special emphasis on root caries lesions. Methods: A consensus workshop followed by a Delphi consensus process were conducted with an expert panel nominated by ORCA, EFCD, and DGZ boards. Based on a systematic review of the literature, as well as non-systematic literature search, recommendations for clinicians were developed and consented in a two-stage Delphi process. Results: Demographic and epidemiologic changes will significantly increase the need of management of older adults and root caries in the future. Ageing is associated with a decline of intrinsic capacities and an increased risk of general diseases. As oral and systemic health are linked, bidirectional consequences of diseases and interventions need to be considered. Caries prevention and treatment in older adults must respond to the patient's individual abilities for self-care and cooperation and often involves the support of caregivers. Systemic interventions may involve dietary counselling, oral hygiene instruction, the use of fluoridated toothpastes, and the stimulation of salivary flow. Local interventions to manage root lesions may comprise local biofilm control, application of highly fluoridated toothpastes or varnishes as well as antimicrobial agents. Restorative treatment is often compromised by the accessibility of such root caries lesions as well as the ability of the senior patient to cooperate. If optimum restorative treatment is impossible or inappropriate, long-term stabilization, e.g., by using glass-ionomer cements, and palliative treatments that aim to maintain oral function as long and as well as possible may be the treatment of choice for the individual

How to Intervene in the Caries Process in Children: A Joint ORCA and EFCD Expert Delphi Consensus Statement

This paper provides recommendations for dentists for the treatment of dental caries in children, with an emphasis on early childhood caries (ECC), primary teeth, and occlusal surfaces in permanent teeth. A consensus workshop followed by an e-Delphi consensus process was conducted with an expert panel nominated by the European Organization for Caries Research (ORCA) and European Federation of Conservative Dentistry (EFCD)/German Association of Conservative Dentistry (DGZ) boards. Based on 3 systematic reviews and a nonsystematic literature search, recommendations were developed. The caries decline has led to a more polarized disease distribution in children and adolescents along social gradients which should be taken into account when managing the caries process at all levels, such as the individual, the group, or a population. The control or reduction of caries activity is the basis for successful caries management. In children, caries management requires adequate daily oral hygiene and fluoride application via toothpaste, ensured by caregivers, and especially for ECC prevention an emphasis on sugar intake reduction is needed. These noninvasive interventions are also suitable to arrest or control initial or even cavitated dentine caries lesions in the absence of irreversible pulpitis. Fluoride varnish or silver diammine fluoride can be added as supplementary agents. In pits and fissures, composite resin materials can be used as preventive sealants and for defect-oriented minimally invasive restorations. In primary molars, preformed metal crowns are more successful than multisurface fillings, especially in caries-active patients. With persisting high caries activity, multiple lesions, and limited cooperation, caries control should consist of robust measures with high success rates, even including extraction in selected cases. This applies especially to treatments performed under general anesthesia

Epigenetic dynamics of monocyte-to-macrophage differentiation

Background Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete transcriptome and epigenome of human monocytes that were differentiated in vitro by addition of colony-stimulating factor 1 in serum-free medium. Results Numerous mRNAs and miRNAs were significantly up- or down-regulated. More than 100 discrete DNA regions, most often far away from transcription start sites, were rapidly demethylated by the ten eleven translocation enzymes, became nucleosome-free and gained histone marks indicative of active enhancers. These regions were unique for macrophages and associated with genes involved in the regulation of the actin cytoskeleton, phagocytosis and innate immune response. Conclusions In summary, we have discovered a phagocytic gene network that is repressed by DNA methylation in monocytes and rapidly de-repressed after the onset of macrophage differentiation

IL-12 protects from psoriasiform skin inflammation

Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has led to a breakthrough in the management of moderate to severe disease. Aside from neutralizing IL-23, which is thought to be responsible for the curative effect, anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here we dissect the individual contribution of these two cytokines to the formation of psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12 and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation we show that IL-12, in contrast to IL-23, has a regulatory function by restraining the invasion of an IL-17-committed γδT (γδT17) cell subset. We discover that IL-12 receptor signalling in keratinocytes initiates a protective transcriptional programme that limits skin inflammation, suggesting that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is counterproductive in the therapy of psoriasis

Aesthetics by Numbers: Links between Perceived Texture Qualities and Computed Visual Texture Properties.

Our world is filled with texture. For the human visual system, this is an important source of information for assessing environmental and material properties. Indeed-and presumably for this reason-the human visual system has regions dedicated to processing textures. Despite their abundance and apparent relevance, only recently the relationships between texture features and high-level judgments have captured the interest of mainstream science, despite long-standing indications for such relationships. In this study, we explore such relationships, as these might be used to predict perceived texture qualities. This is relevant, not only from a psychological/neuroscience perspective, but also for more applied fields such as design, architecture, and the visual arts. In two separate experiments, observers judged various qualities of visual textures such as beauty, roughness, naturalness, elegance, and complexity. Based on factor analysis, we find that in both experiments, ~75% of the variability in the judgments could be explained by a two-dimensional space, with axes that are closely aligned to the beauty and roughness judgments. That a two-dimensional judgment space suffices to capture most of the variability in the perceived texture qualities suggests that observers use a relatively limited set of internal scales on which to base various judgments, including aesthetic ones. Finally, for both of these judgments, we determined the relationship with a large number of texture features computed for each of the texture stimuli. We find that the presence of lower spatial frequencies, oblique orientations, higher intensity variation, higher saturation, and redness correlates with higher beauty ratings. Features that captured image intensity and uniformity correlated with roughness ratings. Therefore, a number of computational texture features are predictive of these judgments. This suggests that perceived texture qualities-including the aesthetic appreciation-are sufficiently universal to be predicted-with reasonable accuracy-based on the computed feature content of the textures