Comparative genomics and mutagenesis analyses of choline metabolism in the marine Roseobacter clade

Choline is ubiquitous in marine eukaryotes and appears to be widely distributed in surface marine waters; however, its metabolism by marine bacteria is poorly understood. Here, using comparative genomics and molecular genetic approaches, we reveal that the capacity for choline catabolism is widespread in marine heterotrophs of the marine Roseobacter clade (MRC). Using the model bacterium Ruegeria pomeroyi, we confirm that the betA, betB and betC genes, encoding choline dehydrogenase, betaine aldehyde dehydrogenase and choline sulfatase, respectively, are involved in choline metabolism. The betT gene, encoding an organic solute transporter, was essential for the rapid uptake of choline but not glycine betaine (GBT). Growth of choline and GBT as a sole carbon source resulted in the re-mineralization of these nitrogen-rich compounds into ammonium. Oxidation of the methyl groups from choline requires formyltetrahydrofolate synthetase encoded by fhs in R.pomeroyi, deletion of which resulted in incomplete degradation of GBT. We demonstrate that this was due to an imbalance in the supply of reducing equivalents required for choline catabolism, which can be alleviated by the addition of formate. Together, our results demonstrate that choline metabolism is ubiquitous in the MRC and reveal the role of Fhs in methyl group oxidation in R.pomeroyi

Total energy calculation of high pressure selenium: The origin of incommensurate modulations in Se-IV and the instability of proposed Se-II

We present calculation of the high pressure crystal structures in selenium, including rational approximants to the recently reported incommensurate phases. We show how the incommensurate phases can be intuitively explained in terms of imaginary phonon frequencies arising from Kohn anomalies in the putative undistorted phase. We also find inconsistencies between the calculated and experimental Se-II phase - the calculations show it to be a metastable metal while the experiment finds a stable semiconductor. We propose that the experimentally reported structure is probably in error.Comment: 4 pages 4 figure

Design of a five-axis ultra-precision micro-milling machine—UltraMill. Part 1: Holistic design approach, design considerations and specifications

High-accuracy three-dimensional miniature components and microstructures are increasingly in demand in the sector of electro-optics, automotive, biotechnology, aerospace and information-technology industries. A rational approach to mechanical micro machining is to develop ultra-precision machines with small footprints. In part 1 of this two-part paper, the-state-of-the-art of ultra-precision machines with micro-machining capability is critically reviewed. The design considerations and specifications of a five-axis ultra-precision micro-milling machine—UltraMill—are discussed. Three prioritised design issues: motion accuracy, dynamic stiffness and thermal stability, formulate the holistic design approach for UltraMill. This approach has been applied to the development of key machine components and their integration so as to achieve high accuracy and nanometer surface finish

Characterization of Developmental Pathway of Natural Killer Cells from Embryonic Stem Cells In Vitro

In vitro differentiation of embryonic stem (ES) cells is often used to study hematopoiesis. However, the differentiation pathway of lymphocytes, in particular natural killer (NK) cells, from ES cells is still unclear. Here, we used a multi-step in vitro ES cell differentiation system to study lymphocyte development from ES cells, and to characterize NK developmental intermediates. We generated embryoid bodies (EBs) from ES cells, isolated CD34(+) EB cells and cultured them on OP9 stroma with a cocktail of cytokines to generate cells we termed ES-derived hematopoietic progenitors (ES-HPs). EB cell subsets, as well as ES-HPs derived from EBs, were tested for NK, T, B and myeloid lineage potentials using lineage specific cultures. ES-HPs derived from CD34(+) EBs differentiated into NK cells when cultured on OP9 stroma with IL-2 and IL-15, and into T cells on Delta-like 1-transduced OP9 (OP9-DL1) with IL-7 and Flt3-L. Among CD34(+) EB cells, NK and T cell potentials were detected in a CD45(−) subset, whereas CD45(+) EB cells had myeloid but not lymphoid potentials. Limiting dilution analysis of ES-HPs generated from CD34(+)CD45(−) EB cells showed that CD45(+)Mac-1(−)Ter119(−) ES-HPs are highly enriched for NK progenitors, but they also have T, B and myeloid potentials. We concluded that CD45(−)CD34(+) EB cells have lymphoid potential, and they differentiate into more mature CD45(+)Lin(−) hematopoietic progenitors that have lymphoid and myeloid potential. NK progenitors among ES-HPs are CD122(−) and they rapidly acquire CD122 as they differentiate along the NK lineage

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse

Extensive central nervous system involvement in Merkel cell carcinoma: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Merkel cell carcinoma is a rare malignant cutaneous neoplasm that is locally invasive and frequently metastasizes to lymph nodes, liver, lungs, bone and brain. The incidence of Merkel cell carcinoma has increased in the past three decades.</p> <p>Case presentation</p> <p>A 65-year-old Caucasian man presented with a sudden onset of severe headache and a three-month history of balance disturbance. Magnetic resonance imaging revealed a large meningeal metastasis. The radiologic workup showed retroperitoneal and inguinal lymph node metastases. Biopsy of the inguinal lymph nodes showed metastases of Merkel cell carcinoma. Biopsy from three different suspected skin lesions revealed no Merkel cell carcinoma, and the primary site of Merkel cell carcinoma remained unknown. Leptomeningeal metastases, new axillary lymph node metastases, and intraspinal (epidural and intradural) metastases were detected within six, seven and eight months, respectively, from the start of symptoms despite treating the intracranial metastasis with gamma knife and the abdominal metastases with surgical dissection and external radiotherapy. This indicates the aggressive nature of the disease.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report in the literature of an intracranial meningeal metastasis of Merkel cell carcinoma treated with gamma knife and of intraspinal intradural metastases of Merkel cell carcinoma. Despite good initial response to radiotherapy, recurrence and occurrence of new metastases are common in Merkel cell carcinoma.</p

Referrals to a facial pain service

AIM: To assess the quality of referral letters to a facial pain service and highlight the key requirements of such letters. METHOD: The source of all referral letters to the service for five years was established. For one year the information provided in 94 referrals was assessed. Using a predetermined checklist of essential information the referral letters were compared to these set criteria. RESULTS: The service received 7,001 referrals and, on average, general dental practitioners (GDPs) referred 303 more patients per year than general medical practitioners (GMPs). Seventy-one percent of all referrals were from primary care practitioners, the rest were from specialists. Over 70% of GMP and 52% of GDP letters included a past medical history, with GMPs more likely to suggest a possible diagnosis and include previous secondary care referrals. The mean score for GMP referrals compared to the standard proforma (maximum of 12) was 5.6 and for GDP referrals 5.0. A relevant drug history was included by 75.6% GMP compared to 38.7% of GDPs. GMPs were more likely to include any relevant mental health history. CONCLUSIONS: The overall quality of referral letters is low which makes it difficult for the specialists to provide robust treatment plans

ZrTiO4 materials obtained by Spark Plasma Reaction Sintering

Zirconium titanate (ZrTiO4), have many attractive properties such as high resistivity, high dielectric constant, high permittivity at microwave frequencies and excellent temperature stability for microwave properties. Zirconium titanate dense materials are proposed for many structural applications, but fully reacted and completely dense pieces are difficult to obtain by conventional routes. In this work, fully dense zirconium titanate materials ( 98%) were obtained at lower temperatures (1300 1400 C) and short processing time by non-conventional technique; spark plasma-reaction sintering (SPRS). Homogeneous and stable starting powders mixture with the adequate composition was prepared from the raw materials: m-ZrO2 ( 0.3 lm) and anatase-TiO2 ( 40 nm). Dense materials were mechanically and microstructural characterised. The fracture strength was measured by biaxial testing, giving values of about 200 MPa.This study has been supported by the Spanish Ministry of Science and Innovation MAT2009-14144-C03-02, MAT2012-38364-C03-02 and MAT2012-31090. A. Borrell, acknowledges the Spanish Ministry of Science and Innovation for her Juan de la Cierva contract (JCI-2011-10498) and the Generalitat Valenciana for the BEST/2012/302 grant and the financial support for ACOMP/2012/166.Borrell Tomás, MA.; Salvador Moya, MD.; García-Rocha, V.; Fernández, A.; Gómez, A.; López-López, E.; Moreno, R. (2014). ZrTiO4 materials obtained by Spark Plasma Reaction Sintering. Composites Part B: Engineering. 56:330-335. https://doi.org/10.1016/j.compositesb.2013.08.046S3303355