Thermochemistry of Microhydration of Sodiated and Potassiated Monosaccharides

The thermochemical properties ΔHon , ΔSon, and ΔGon for the hydration of sodiated and potassiated monosaccharides (Ara = arabinose, Xyl = xylose, Rib = ribose, Glc = glucose, and Gal = galactose) have been experimentally studied in the gas phase at 10 mbar by equilibria measurements using an electrospray high-pressure mass spectrometer equipped with a pulsed ion beam reaction chamber. The hydration enthalpies for sodiated complexes were found to be between −46.4 and −57.7 kJ/mol for the first, and −42.7 and −52.3 kJ/mol for the second water molecule. For potassiated complexes, the water binding enthalpies were similar for all studied systems and varied between −48.5 and −52.7 kJ/mol. The thermochemical values for each system correspond to a mixture of the α and β anomeric forms of monosaccharide structures involved in their cationized complexes

The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

Recent studies have demonstrated that the CD3-ζ subunit of the T cell antigen receptor (TCR) complex is involved in signal transduction. However, the function of the remaining invariant subunits, CD3-γ, -δ, and , is still poorly understood. To examine their role in TCR function, we have constructed TCR/CD3 complexes devoid of functional ζ subunit and showed that they are still able to trigger the production of interleukin-2 in response to antigen or superantigen. These data, together with previous results, indicate that the TCR/CD3 complex is composed of at least two parallel transducing units, made of the γδ and ζ chains, respectively, Furthermore, the analysis of partially truncated ζ chains has led us to individualize a functional domain that may have constituted the building block of most of the transducing subunits associated with antigen receptors and some Fc receptors

A newborn with Cornelia de Lange syndrome: a case report

Cornelia de Lange syndrome (CdLS) is a rarely seen multisystem developmental disorder syndrome characterized by facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, and gastrointestinal abnormalities. The features of this disorder vary widely among affected individuals and range from relatively mild to severe. Early in life, the distinctive craniofacial features in mild de Lange syndrome may be indistinguishable from the severe (classical) phenotype. We present here a case of newborn with CdLs

The present and future of serum diagnostic tests for testicular germ cell tumours.

Testicular germ cell tumours (GCTs) are the most common malignancy occurring in young adult men and the incidence of these tumours is increasing. Current research priorities in this field include improving overall survival for patients classified as being 'poor-risk' and reducing late effects of treatment for patients classified as 'good-risk'. Testicular GCTs are broadly classified into seminomas and nonseminomatous GCTs (NSGCTs). The conventional serum protein tumour markers α-fetoprotein (AFP), human chorionic gonadotrophin (hCG) and lactate dehydrogenase (LDH) show some utility in the management of testicular malignant GCT. However, AFP and hCG display limited sensitivity and specificity, being indicative of yolk sac tumour (AFP) and choriocarcinoma or syncytiotrophoblast (hCG) subtypes. Furthermore, LDH is a very nonspecific biomarker. Consequently, seminomas and NSGCTs comprising a pure embryonal carcinoma subtype are generally negative for these conventional markers. As a result, novel universal biomarkers for testicular malignant GCTs are required. MicroRNAs are short, non-protein-coding RNAs that show much general promise as biomarkers. MicroRNAs from two 'clusters', miR-371-373 and miR-302-367, are overexpressed in all malignant GCTs, regardless of age (adult or paediatric), site (gonadal or extragonadal) and subtype (seminomas, yolk sac tumours or embryonal carcinomas). A panel of four circulating microRNAs from these two clusters (miR-371a-3p, miR-372-3p, miR-373-3p and miR-367-3p) is highly sensitive and specific for the diagnosis of malignant GCT, including seminoma and embryonal carcinoma. In the future, circulating microRNAs might be useful in diagnosis, disease monitoring and prognostication of malignant testicular GCTs, which might also reduce reliance on serial CT scanning. For translation into clinical practice, important practical considerations now need addressing.The authors would like to acknowledge grant funding from CwCUK/GOSHCC (M.J.M. N.C. grant W1058), SPARKS (M.J.M. N.C. grant 11CAM01), CRUK (N.C. grant A13080) MRC (M.J.M. grant MC_EX_G0800464) and National Health Service funding to the Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre for Cancer (R.A.H.). The authors also thank the Max Williamson Fund, the Josh Carrick Foundation and The Perse Preparatory School, Cambridge for support.This is the author accepted manuscript. The final version is available fromNature Publishing Group via https://doi.org/10.1038/nrurol.2016.17

Methods for genetic manipulation of Burkholderia gladioli pathovar cocovenenans

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia gladioli </it>pathovar <it>cocovenenans </it>(BGC) is responsible for sporadic food-poisoning outbreaks with high morbidity and mortality in Asian countries. Little is known about the regulation of virulence factor and toxin production in BGC, and studies in this bacterium have been hampered by lack of genetic tools.</p> <p>Findings</p> <p>Establishment of a comprehensive antibiotic susceptibility profile showed that BGC strain ATCC33664 is susceptible to a number of antibiotics including aminoglycosides, carbapenems, fluoroquinolones, tetracyclines and trimethoprim. In this study, we established that gentamicin, kanamycin and trimethoprim are good selection markers for use in BGC. Using a 10 min method for preparation of electrocompetent cells, the bacterium could be transformed by electroporation at high frequencies with replicative plasmids containing the pRO1600-derived origin of replication. These plasmids exhibited a copy number of > 100 in BGC. When co-conjugated with a transposase expressing helper plasmid, mini-Tn<it>7 </it>vectors inserted site- and orientation-specifically at a single <it>glmS</it>-associated insertion site in the BGC genome. Lastly, a <it>Himar1 </it>transposon was used for random transposon mutagenesis of BGC.</p> <p>Conclusions</p> <p>A series of genetic tools previously developed for other Gram-negative bacteria was adapted for use in BGC. These tools now facilitate genetic studies of this pathogen and allow establishment of toxin biosynthetic pathways and their genetic regulation.</p

Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: Confirmation of OCT3/4 specificity for germ cell tumours

Background: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem-and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms-OCT4A, OCT4B and OCT4B1-only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues. Methods: This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts. Results: Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4