M-mode echovenography: a new technique for the evaluation of venous wall and valve motion

The M-mode technique which is widely used in echocardiography allows continuous recording of spontaneous venous wall movements. Compliance of the vein can be quantified. The diameter of the normal vein changes with respiration, while only minor changes are induced by cardiac function. Distensibility and compressibility of the common femoral vein (CFV) were documented. During Valsalva manoeuvre the mean diameter of the CFV increased from 1.05(SD 0.18) cm to 1.52(0.25) cm (p<0.01) in the recumbent position and from 1.50(0.20) cm to 1.63(0.17) cm (NS) in the upright position. A patent vein can be completely compressed by the scan head, a thrombosed vein is incompressible. The valve of the normal subclavian vein describes a characteristic M-shaped tracing. The waveform is modulated by cardiac and respiratory function. The study of venous wall movement and venous valve motion provides new insights into venous physiolog

Identification of tumor antigens as potential target antigens for immunotherapy by serological expression cloning

The presence of tumor infiltrating T cells has been shown to be associated with a favorable prognosis in different tumor types. Several strategies have been developed to identify relevant tumor antigens which can be used for active immunotherapy strategies. The SEREX technique (serological analysis of cDNA expression libraries) identifies tumor antigens based on a spontaneous humoral immune response in cancer patients. This technique is not limited to tumor types that can be grown in cell culture or depends on established T cell clones recognizing the autologous tumor. Several steps of analysis are mandatory to evaluate SEREX-defined antigens before they become new target antigens for active immunotherapy: expression analysis; serological analysis with sera from tumor patients and normal individuals; identification of potential peptide epitopes for CD8 T cells and evaluation in T cell assays. This article summarizes our approach of antigen identification and evaluation giving the example of the recently cloned breast cancer antigen NY-BR-

Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients

The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restriction

Brain structure and function: a multidisciplinary pipeline to study hominoid brain evolution

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

A Corynebacterium glutamicum gene conferring multidrug resistance in the heterologous host Escherichia coli

Jäger W, Kalinowski J, Pühler A. A Corynebacterium glutamicum gene conferring multidrug resistance in the heterologous host Escherichia coli. J Bacteriol. 1997;179(7):2449-2451.A chromosomal DNA fragment from the erythromycin-sensitive bacterium Corynebacterium glutamicum ATCC 13032 was shown to mediate resistance against erythromycin, tetracycline, puromycin, and bleomycin in Escherichia coli. Multicopy cloning of the fragment did not cause a resistance phenotype in C. glutamicum. The corresponding gene encodes a hydrophobic protein with 12 potential transmembrane-spanning cy-helical segments showing similarity to drug-H+ antiporters

Isolation of insertion elements from gram-positive Brevibacterium, Corynebacterium and Rhodococcus strains using the Bacillus subtilis sacB gene as a positive selection marker

Jäger W, Schäfer A, Kalinowski J, Pühler A. Isolation of insertion elements from gram-positive Brevibacterium, Corynebacterium and Rhodococcus strains using the Bacillus subtilis sacB gene as a positive selection marker. FEMS MICROBIOLOGY LETTERS. 1995;126(1):1-6.The sacB gene of Bacillus subtilis was successfully applied in various Arthrobacter, Brevibacterium, Corynebacterium and Rhodococcus strains for the isolation of transposable elements. Three different insertion sequence (IS) elements entrapped in sacB were isolated. The IS elements IS-BI and IS-Cg isolated from Brevibacterium lactofermentum and Corynebacterium glutamicum, respectively, were found to be similar in size (1.45 kb) and generated target duplications of 8 bp. Their inverted repeats showed homology. In contrast, the IS element IS-Rf isolated from Rhodococcus fascians was only 1.3 kb long and generated a 3-bp target duplication. IS-Cg and IS-Rf were not restricted to their original host strains, and we also found strains harbouring more than one element

New gentamicin-resistance and lacZ promoter-probe cassettes suitable for insertion mutagenesis and generation of transcriptional fusions

Becker A, Schmidt M, Jäger W, Pühler A. New gentamicin-resistance and lacZ promoter-probe cassettes suitable for insertion mutagenesis and generation of transcriptional fusions. GENE. 1995;162(1):37-39.A set of antibiotic-resistance and promoter-probe cassettes suitable for insertion mutagenesis and generation of transcriptional fusions was constructed. The cassettes contain the aacC1 gene of transposon Tn1696 conferring resistance to gentamicin in a large variety of Gram(-) and Gram(+) bacteria. In addition to the antibiotic-resistance gene, a promoterless Escherichia coli lacZ gene was included in the cassettes, allowing the determination of the transcriptional activity at the insertion site. The cassettes can be excised from a plasmid mediating ampicillin resistance by many commonly used restriction enzymes. The new constructs have been successfully used for mutagenesis and studies of gene transcription in Rhizobium meliloti