The Breathing Mode in Extended Skyrme Model

We study an extended Skyrme model which includes fourth and sixth-order terms. We explore some static properties like the $\Delta$-nucleon mass splitting and investigate the Skyrmion breathing mode in the framework of the linear response theory. We find that the monopole response function has a pronounced peak located at $\sim$ 400 MeV, which we identify to the Roper resonance $N(1440)$. As compared to the standard one, the extended Skyrme model provides a more accurate description of baryon properties.Comment: 12 pages of plain Latex and 3 figures (available from the authors), preprint IPNO/TH 93-0

Renormalization of Hamiltonian Field Theory; a non-perturbative and non-unitarity approach

Renormalization of Hamiltonian field theory is usually a rather painful algebraic or numerical exercise. By combining a method based on the coupled cluster method, analysed in detail by Suzuki and Okamoto, with a Wilsonian approach to renormalization, we show that a powerful and elegant method exist to solve such problems. The method is in principle non-perturbative, and is not necessarily unitary.Comment: 16 pages, version shortened and improved, references added. To appear in JHE

Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in biallelic state

BACKGROUND: Developmental and epileptic encephalopathies (DEEs) represent a group of severe neurological disorders characterised by an onset of refractory seizures during infancy or early childhood accompanied by psychomotor developmental delay or regression. DEEs are genetically heterogeneous with, to date, more than 80 different genetic subtypes including DEE31 caused by heterozygous missense variants in DNM1. METHODS: We performed a detailed clinical characterisation of two unrelated patients with DEE and used whole-exome sequencing to identify causative variants in these individuals. The identified variants were tested for cosegregation in the respective families. RESULTS: We excluded pathogenic variants in known, DEE-associated genes. We identified homozygous nonsense variants, c.97C>T; p.(Gln33*) in family 1 and c.850C>T; p.(Gln284*) in family 2, in the DNM1 gene, indicating that biallelic, loss-of-function pathogenic variants in DNM1 cause DEE. CONCLUSION: Our finding that homozygous, loss-of-function variants in DNM1 cause DEE expands the spectrum of pathogenic variants in DNM1. All parents who were heterozygous carriers of the identified loss-of-function variants were healthy and did not show any clinical symptoms, indicating that the type of mutation in DNM1 determines the pattern of inheritance

Long-term evolution of an Oligocene/Miocene maar lake from Otago, New Zealand

Foulden Maar is a highly resolved maar lake deposit from the South Island of New Zealand comprising laminated diatomite punctuated by numerous diatomaceous turbidites. Basaltic clasts found in debris flow deposits near the base of the cored sedimentary sequence yielded two new ⁴⁰Ar/³⁹Ar dates of 24.51 ± 0.24 and 23.38 ± 0.24 Ma (2σ). The younger date agrees within error with a previously published ⁴⁰Ar/³⁹Ar date of 23.17 ± 0.19 Ma from a basaltic dyke adjacent to the maar crater. The diatomite is inferred to have been deposited over several tens of thousands of years in the latest Oligocene/earliest Miocene, and may have been coeval with the period of rapid glaciation and subsequent deglaciation of Antarctica known as the Mi-1 event. Sediment magnetic properties and SEM measurements indicate that the magnetic signal is dominated by pseudo-single domain pyrrhotite. The most likely source of detrital pyrrhotite is schist country rock fragments from the inferred tephra ring created by the phreatomagmatic eruption that formed the maar. Variations in magnetic mineral concentration indicate a decrease in erosional input throughout the depositional period, suggesting long-term (tens of thousands of years) environmental change in New Zealand in the latest Oligocene/earliest Miocene

The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

<p>Abstract</p> <p>Background</p> <p>To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome.</p> <p>Methods</p> <p>DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information.</p> <p>Results</p> <p>The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance.</p> <p>Conclusions</p> <p>Analysis from our <it>in vitro </it>and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including <it>IGF2BP2</it>, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear; however, the numbers that have been detected by the disease-specific microarray would suggest that they may be important regulatory transcripts. This study has demonstrated the power of a disease-specific transcriptome-based approach and highlighted the potential novel biologically and clinically relevant information that is gained when using such a methodology.</p

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression

Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of beta-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of beta-catenin, whereas strong nuclear accumulation of beta-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the beta-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future. Oncogene (2009) 28, 3971-3982; doi:10.1038/onc.2009.254; published online 24 August 200