The journey of Zika to the developing brain

Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments

The Private Provision of Public Goods: An Analysis of Homes on Golf Courses

This paper examines the joint production of golf and real estate development. The empirical results of this analysis show that, over time, golf courses are being constructed less for recreational golf and more for contractual assurance of green open space for homes. We believe that this fundamentally provides some evidence that the demand for environmental quality is growing and that markets are increasingly able to find creative contracting mechanisms to satisfy demands for public goods

Catatonic Episodes Related to Substance Use: A Cross-Sectional Study Using Electronic Healthcare Records

OBJECTIVE: Substance use has increasingly been linked to the onset of catatonic episodes; however, no large observational studies have examined this association. This study aimed to identify catatonic episodes temporally associated with acute intoxication, withdrawal or chronic substance use, investigate which substances were involved, and compare clinical characteristics of substance-related and non-substance-related catatonic episodes. METHODS: This study retrospectively identified all catatonic episodes recorded in an electronic case register hosted at a large secondary mental health trust in London, UK. Episodes were categorized as substance-related if the clinical record reported either a positive urine drug screen, an ICD-10 diagnosis of a mental or behavioral disorder due to substance use, or documented substance use between two weeks prior to the catatonic episode and the date of the catatonic episode. RESULTS: 108 of 2130 catatonic episodes (5.1%) were deemed substance-related. The number of contemporaneously reported substance-related episodes increased between 2007 and 2016 [r = 0.72, p = 0.02]. Episodes in the context of acute intoxication (n = 54) were most frequently related to cannabis (n = 31) or cocaine (n = 5) use, whilst those in the context of drug withdrawal (n = 8) were most commonly related to alcohol, opioids and benzodiazepines. There were 50 episodes of catatonia associated with chronic substance use without intoxication or withdrawal, of which the majority were related to cannabis use (n = 37). 21 episodes had overlapping intoxication, withdrawal and chronic use of different substances within an episode. Compared to catatonic episodes not related to substance use, episodes of substance-related catatonia occurred in individuals who were younger (mean age 31.3 years [SD 12.2] vs 35.7 years [SD 16.3], p = 0.01) and more likely to be men (74.0% vs 54.3%, p < 0.001). The clinical features of catatonia were similar between the two groups. CONCLUSIONS: A relatively small proportion of catatonic episodes were temporally associated with reported substance use within their electronic records. Substance-related catatonic episodes were mostly related to cannabis use, but other substances including cocaine, alcohol, opioids and benzodiazepines were sometimes implicated. This is likely an underestimate of substance-related catatonia use due to issues with documentation and appropriate investigation

Comparative SNP diversity among four Eucalyptus species for genes from secondary metabolite biosynthetic pathways

<p>Abstract</p> <p>Background</p> <p>There is little information about the DNA sequence variation within and between closely related plant species. The combination of re-sequencing technologies, large-scale DNA pools and availability of reference gene sequences allowed the extensive characterisation of single nucleotide polymorphisms (SNPs) in genes of four biosynthetic pathways leading to the formation of ecologically relevant secondary metabolites in <it>Eucalyptus</it>. With this approach the occurrence and patterns of SNP variation for a set of genes can be compared across different species from the same genus.</p> <p>Results</p> <p>In a single GS-FLX run, we sequenced over 103 Mbp and assembled them to approximately 50 kbp of reference sequences. An average sequencing depth of 315 reads per nucleotide site was achieved for all four eucalypt species, <it>Eucalyptus globulus</it>, <it>E. nitens</it>, <it>E. camaldulensis </it>and <it>E. loxophleba</it>. We sequenced 23 genes from 1,764 individuals and discovered 8,631 SNPs across the species, with about 1.5 times as many SNPs per kbp in the introns compared to exons. The exons of the two closely related species (<it>E. globulus </it>and <it>E. nitens</it>) had similar numbers of SNPs at synonymous and non-synonymous sites. These species also had similar levels of SNP diversity, whereas <it>E. camaldulensis </it>and <it>E. loxophleba </it>had much higher SNP diversity. Neither the pathway nor the position in the pathway influenced gene diversity. The four species share between 20 and 43% of the SNPs in these genes.</p> <p>Conclusion</p> <p>By using conservative statistical detection methods, we were confident about the validity of each SNP. With numerous individuals sampled over the geographical range of each species, we discovered one SNP in every 33 bp for <it>E. nitens </it>and one in every 31 bp in <it>E. globulus</it>. In contrast, the more distantly related species contained more SNPs: one in every 16 bp for <it>E. camaldulensis </it>and one in 17 bp for <it>E. loxophleba</it>, which is, to the best of our knowledge, the highest frequency of SNPs described in woody plant species.</p

Correlated enhancement of Hc2 and Jc in carbon nanotube-doped MgB2

The use of MgB2 in superconducting applications still awaits for the development of a MgB2-based material where both current-carrying performance and critical magnetic field are optimized simultaneously. We achieved this by doping MgB2 with double-wall carbon nanotubes (DWCNT) as a source of carbon in polycrystalline samples. The optimum nominal DWCNT content for increasing the critical current density, Jc is in the range 2.5-10%at depending on field and temperature. Record values of the upper critical field, Hc2(4K) = 41.9 T (with extrapolated Hc2(0) ~ 44.4 T) are reached in a bulk sample with 10%at DWCNT content. The measured Hc2 vs T in all samples are successfully described using a theoretical model for a two-gap superconductor in the dirty limit first proposed by Gurevich et al.Comment: 12 pages, 3 figure

Transdifferentiation of pancreatic progenitor cells to hepatocyte-like cells is not serum-dependent when facilitated by extracellular matrix proteins

The rising prevalence of chronic liver disease, coupled with a permanent shortage of organs for liver transplantation, has sparked enormous interest in alternative treatment strategies. Previous protocols to generate hepatocyte-like cells (HLCs) via pancreas-to-liver transdifferentiation have utilised fetal bovine serum, introducing unknown variables and severely limiting study reproducibility. Therefore, the main goal of this study was to develop a protocol for transdifferentiation of pancreatic progenitor cells to HLCs in a chemically defined, serum-free culture medium. The clonal pancreatic progenitor cell line AR42J-B13 was cultured in basal growth medium on uncoated plastic culture dishes in the absence or presence of Dexamethasone on uncoated, laminin-or fibronectin-coated culture substrata, with or without serum supplementation. The hepatocytic differentiation potential was evaluated: (i) morphologically through bright-field and scanning electron microscopy, (ii) by assessing pancreatic and hepatic marker expression and (iii) by determining the function of HLCs through their ability to synthesise glycogen or take up and release indocyanine green. Here we demonstrate for the first time that transdifferentiation of pancreatic cells to HLCs is not dependent on serum. These results will assist in converting current differentiation protocols into procedures that are compliant with clinical use in future cell-based therapies to treat liver-related metabolic disorders

Evaluation of Glucosidase Inhibitory and Cytotoxic Potential of Five Selected Edible and Medicinal Ferns

Purpose: To evaluate the glucosidase inhibitory and cytotoxic activities of five selected edible and medicinal ferns, namely, Blechnum orientale, Davallia denticulata, Diplazium esculentum, Nephrolepis biserrata, and Pteris vittata.Methods: The aqueous extracts of the five ferns were prepared by water extraction at 90 ºC for 1 h. Antiglucosidase assay was used to determine the effect of each extract on yeast alpha-glucosidase activity in vitro. Cytotoxicity was evaluated using methylthiazol tetrazolium assay on chronic myelogenous leukaemia cell line (K562). The phenolic, hydroxycinnamic acid, flavonoid and proanthocyanidin contents of the extracts were also determined.Results: The α-glucosidase inhibitory activity of D. esculentum (half maximal effective concentration, EC50 = 6.85 μg/ml) was considerably stronger than that of myricetin (EC50 = 53.21 μg/ml). B. orientale, D. esculentum, N. biserrata, and P. vittata were cytotoxic to K562 cells. P. vittata had the strongest cytotoxicity, although it was less potent than 5-fluorouracil. D. denticulata had the highest phenolic, hydroxycinnamic acid and flavonoid contents of all the extracts while B. orientale had the highest proanthocyanidin content.Conclusion: Among the five ferns evaluated, D. esculentum is a potential source of an antidiabetic agent and is recommended for further investigation in this regard. All the fern extracts, except D. denticulata, exhibited dose-dependent cytotoxicity against K562 cells.Keywords: Medicinal fern, α-Glucosidase inhibition, Cytotoxicity, Blechnum orientale, Davallia denticulata, Diplazium esculentum, Nephrolepis biserrata, Pteris vittat

Mindfulness-Based Interventions in Recurrent Ovarian Cancer: A Mixed-Methods Feasibility Study.

A recurrence of cancer is a traumatic and stressful experience, and a number of approaches have been proposed to manage or treat the associated psychological distress. Meditative techniques such as mindfulness may be able to improve an individual's ability to cope with stressful life events such as cancer diagnosis or treatment. This single-arm mixed-methods study primarily aimed to determine the feasibility of using a mindfulness-based intervention in managing psychosocial distress in recurrent ovarian cancer. Twenty-eight participants took part in a mindfulness-based program, involving six group sessions, each lasting 1.5 hours and delivered at weekly intervals. The study found that the mindfulness-based intervention was acceptable to women with recurrent ovarian cancer and feasible to deliver within a standard cancer care pathway in a UK hospital setting. The results suggested a positive impact on symptoms of depression and anxiety, but further study is needed to explore the effectiveness of the intervention

Blind source separation aided characterization of the γ′ strengthening phase in an advanced nickel-based superalloy by spectroscopic 4D electron microscopy

The γ’ strengthening phase in an advanced nickel-based superalloy, ATI 718Plus, was characterized using a blind source separation applied to a four dimensional X-ray microanalysis dataset obtained by scanning transmission electron microscopy. Selected patterns in the X-ray spectra identified by independent component analysis were found to be spatially and chemically representative of the matrix (γ) and precipitate phases (γ’) present in the superalloy, enabling their size, shape and distribution to be determined. The three dimensional chemical reconstruction of the microstructure may provide insight into the role of the various alloying elements in the evolution of the microstructure at the nano-scale.The research leading to these results has received funding from the European Union Seventh Framework Programme under Grant Agreement 312483 - ESTEEM2 (Integrated Infrastructure Initiative-I3), as well as from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC grant agreement 291522 - 3DIMAGE. D.R. acknowledges support from the Royal Society’s Newton International Fellowship scheme. RKL acknowledges a Junior Research Fellowship at Clare College. RK acknowledges financial support from Rolls-Royce, EPSRC and the BMWi under EP/H022309/1, EP/H500375/1 and grant number 20T0813. F.d.l.P. and C.D. acknowledge 26 funding from the ERC under grant no. 259619 PHOTO EM. Special thanks to Giorgio Divitini and Lech Staniewicz for preparation of the FIB needle specimen and to Stephen A Croxall for SEM/FIB imaging.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.actamat.2016.01.04

Adapting to Change: The State of Singapore Private Enterprise in China

Academy of International Business. Southeast Asia Regional Conference 2013, December 5-7, Bali, Indonesia</h3