Adaptive response of neonatal sepsis-derived Group B Streptococcus to bilirubin

This work was funded by the Neonatal Unit Endowment Fund, Aberdeen Maternity Hospital. RH is funded by a career researcher fellowship from NHS Research Scotland. SG was funded by the MRC Flagship PhD programme. We are grateful for the support of Dr Phil Cash and Aberdeen Proteomics, at University of Aberdeen, in completing this project. Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-018-24811-3.Peer reviewedPublisher PD

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Acid functionalized conjugated microporous polymers as a reusable catalyst for biodiesel production

A series of conjugated microporous polymers (CMPs) based on bromophenol blue (BB) and bromocresol green (BG) have been synthesized via Sonogashira-Hagihara cross coupling reaction with surface areas up to 747 m2/g. The CMPs can be post functionalized with chlorosulfonic acid to yield corresponding sulfonated polymers with high acidity up to 7.67 mmol/g. The sulfonated CMPs showed excellent catalytic activity for the esterification of free fatty acids and transesterification of various vegetable oils and waste cooking oil as well as excellent reusability up to 4 consecutive runs without significant activity loss. These sulfonated CMPs have potential applications as recyclable acid catalysts for environmentally friendly biodiesel production from waste cooking oil

Fine mapping of genes determining extrafusal fiber properties in murine soleus muscle

Peer reviewedPostprin

Shear-driven magnetic buoyancy in the solar tachocline: dependence of the mean electromotive force on diffusivity and latitude

The details of the dynamo process that is responsible for driving the solar magnetic activity cycle are still not fully understood. In particular, while differential rotation provides a plausible mechanism for the regeneration of the toroidal (azimuthal) component of the large-scale magnetic field, there is ongoing debate regarding the process that is responsible for regenerating the Sun’s large-scale poloidal field. Our aim is to demonstrate that magnetic buoyancy, in the presence of rotation, is capable of producing the necessary regenerative effect. Building upon our previous work, we carry out numerical simulations of a local Cartesian model of the tachocline, consisting of a rotating, fully compressible, electrically conducting fluid with a forced shear flow. An initially weak, vertical magnetic field is sheared into a strong, horizontal magnetic layer that becomes subject to magnetic buoyancy instability. By increasing the Prandtl number we lessen the back reaction of the Lorentz force on to the shear flow, maintaining stronger shear and a more intense magnetic layer. This in turn leads to a more vigorous instability and a much stronger mean electromotive force, which has the potential to significantly influence the evolution of the mean magnetic field. These results are only weakly dependent upon the inclination of the rotation vector, i.e. the latitude of the local Cartesian model. Although further work is needed to confirm this, these results suggest that magnetic buoyancy in the tachocline is a viable poloidal field regeneration mechanism for the solar dynamo

Thinking through illusion

Perception of a property (e.g. a colour, a shape, a size) can enable thought about the property, while at the same time misleading the subject as to what the property is like. This long-overlooked claim parallels a more familiar observation concerning perception-based thought about objects, namely that perception can enable a subject to think about an object while at the same time misleading her as to what the object is like. I defend the overlooked claim, and then use it to generate a challenge for a standard way of thinking about the relationship between visual experience and rational belief formation. Put informally, that view holds that just as we can mislead others by saying something false, illusory experience misleads by misrepresenting how things stand in the world. I argue that we ought to abandon this view in favour of some radical alternative account of the relationship between visual experience and rational belief formation

Novel associations in disorders of sex development: findings from the I-DSD registry

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.<p></p> Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.<p></p> Design, Setting, and Patients: Anonymized data were extracted from the I-DSD Registry for diagnosis, karyotype, sex of rearing, genetic investigations, and associated anomalies. If necessary, clarification was sought from the reporting clinician.<p></p> Results: Of 649 accessible cases, associated conditions occurred in 168 (26%); 103 (61%) cases had one condition, 31 (18%) had two conditions, 20 (12%) had three conditions, and 14 (8%) had four or more conditions. Karyotypes with most frequently reported associations included 45,X with 6 of 8 affected cases (75%), 45,X/46,XY with 19 of 42 cases (45%), 46,XY with 112 of 460 cases (24%), and 46,XX with 27 of 121 cases (22%). In the 112 cases of 46,XY DSD, the commonest conditions included small for gestational age in 26 (23%), cardiac anomalies in 22 (20%), and central nervous system disorders in 22 (20%), whereas in the 27 cases of 46,XX DSD, skeletal and renal anomalies were commonest at 12 (44%) and 8 (30%), respectively. Of 170 cases of suspected androgen insensitivity syndrome, 19 (11%) had reported anomalies and 9 of these had confirmed androgen receptor mutations.<p></p> Conclusions: Over a quarter of the cases in the I-DSD Registry have an additional condition. These associations can direct investigators toward novel genetic etiology and also highlight the need for more holistic care of the affected person.<p></p&gt

APRIL is a novel clinical chemo-resistance biomarker in colorectal adenocarcinoma identified by gene expression profiling

<p>Abstract</p> <p>Background</p> <p>5-Fluorouracil(5FU) and oral analogues, such as capecitabine, remain one of the most useful agents for the treatment of colorectal adenocarcinoma. Low toxicity and convenience of administration facilitate use, however clinical resistance is a major limitation. Investigation has failed to fully explain the molecular mechanisms of resistance and no clinically useful predictive biomarkers for 5FU resistance have been identified. We investigated the molecular mechanisms of clinical 5FU resistance in colorectal adenocarcinoma patients in a prospective biomarker discovery project utilising gene expression profiling. The aim was to identify novel 5FU resistance mechanisms and qualify these as candidate biomarkers and therapeutic targets.</p> <p>Methods</p> <p>Putative treatment specific gene expression changes were identified in a transcriptomics study of rectal adenocarcinomas, biopsied and profiled before and after pre-operative short-course radiotherapy or 5FU based chemo-radiotherapy, using microarrays. Tumour from untreated controls at diagnosis and resection identified treatment-independent gene expression changes. Candidate 5FU chemo-resistant genes were identified by comparison of gene expression data sets from these clinical specimens with gene expression signatures from our previous studies of colorectal cancer cell lines, where parental and daughter lines resistant to 5FU were compared. A colorectal adenocarcinoma tissue microarray (n = 234, resected tumours) was used as an independent set to qualify candidates thus identified.</p> <p>Results</p> <p>APRIL/TNFSF13 mRNA was significantly upregulated following 5FU based concurrent chemo-radiotherapy and in 5FU resistant colorectal adenocarcinoma cell lines but not in radiotherapy alone treated colorectal adenocarcinomas. Consistent withAPRIL's known function as an autocrine or paracrine secreted molecule, stromal but not tumour cell protein expression by immunohistochemistry was correlated with poor prognosis (p = 0.019) in the independent set. Stratified analysis revealed that protein expression of APRIL in the tumour stroma is associated with survival in adjuvant 5FU treated patients only (n = 103, p < 0.001), and is independently predictive of lack of clinical benefit from adjuvant 5FU [HR 6.25 (95%CI 1.48-26.32), p = 0.013].</p> <p>Conclusions</p> <p>A combined investigative model, analysing the transcriptional response in clinical tumour specimens and cancers cell lines, has identified APRIL, a novel chemo-resistance biomarker with independent predictive impact in 5FU-treated CRC patients, that may represent a target for novel therapeutics.</p