Cold-induced urticaria with a familial transmission: a case report and review of the literature

Abstract Introduction Cryopyrin-associated periodic syndrome is a rare genetic disorder causing cold-induced urticaria, severe arthralgias, and (potentially) renal failure and hearing loss. Therapies that effectively control the symptoms and prevent the complications of this debilitating disorder are now available, making recognition of this disease important. Case presentation A 60-year-old Caucasian woman presented with complaints of rash and joint pains to a general medicine clinic. Her history showed that her symptoms were linked to cold exposure, but the results of a cold stimulation time test were negative. Several generations of her family had similar symptoms. Conclusions This case highlights the importance of considering cryopyrin-associated periodic syndrome in the differential diagnosis of cold-induced urticaria. Several medications targeting interleukin-1-beta are available, providing significant relief from symptoms and improvement in quality of life in affected patients.</p

Causes of the regional variability in observed sea level, sea surface temperature and ocean colour over the period 1993-2011

We analyse the regional variability in observed sea surface height (SSH), sea surface temperature (SST) and ocean colour (OC) from the ESA Climate Change Initiative (CCI) datasets over the period 1993-2011. The analysis focuses on the signature of the ocean large-scale climate fluctuations driven by the atmospheric forcing and do not address the mesoscale variability. We use the ECCO version 4 ocean reanalysis to unravel the role of ocean transport and surface buoyancy fluxes in the observed SSH, SST and OC variability. We show that the SSH regional variability is dominated by the steric effect (except at high latitude) and is mainly shaped by ocean heat transport divergences with some contributions from the surface heat fluxes forcing that can be significant regionally (confirming earlier results). This is in contrast with the SST regional variability, which is the result of the compensation of surface heat fluxes by ocean heat transport in the mixed layer and arises from small departures around this background balance. Bringing together the results of SSH and SST analyses, we show that SSH and SST bear some common variability. This is because both SSH and SST variability show significant contributions from the surface heat fluxes forcing. It is evidenced by the high correlation between SST and buoyancy forced SSH almost everywhere in the ocean except at high latitude. OC, which is determined by phytoplankton biomass, is governed by the availability of light and nutrients that essentially depend on climate fluctuations. For this reason OC show significant correlation with SST and SSH. We show that the correlation with SST display the same pattern as the correlation with SSH with a negative correlation in the tropics and subtropics and a positive correlation at high latitude. We discuss the reasons for this pattern

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells

Background The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein. Methods To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns. Results Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein. Most of the genes that showed altered expression in the HMGA2-overexpressing cells fell into the group of NF-κB-target genes, suggesting a central role for HMGA2 in this pathway. Of particular interest was the pronounced up-regulation of SSX1, already implicated in mesenchymal oncogenesis and stem cell functions, only in cells expressing the truncated protein. Furthermore, over-expression of both HMGA2 forms was associated with a strong repression of the epithelial marker CD24, consistent with the reported low level of CD24 in cancer stem cells. Conclusions We conclude that the c-terminal part of HMGA2 has important functions at least in mesenchymal cells, and the changes in gene expression resulting from overexpressing a protein lacking this domain may add to the malignant potential of sarcomas

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Molecular marks for epigenetic identification of developmental and cancer stem cells

Epigenetic regulations of genes by reversible methylation of DNA (at the carbon-5 of cytosine) and numerous reversible modifications of histones play important roles in normal physiology and development, and epigenetic deregulations are associated with developmental disorders and various disease states, including cancer. Stem cells have the capacity to self-renew indefinitely. Similar to stem cells, some malignant cells have the capacity to divide indefinitely and are referred to as cancer stem cells. In recent times, direct correlation between epigenetic modifications and reprogramming of stem cell and cancer stem cell is emerging. Major discoveries were made with investigations on reprogramming gene products, also known as master regulators of totipotency and inducer of pluoripotency, namely, OCT4, NANOG, cMYC, SOX2, Klf4, and LIN28. The challenge to induce pluripotency is the insertion of four reprogramming genes (Oct4, Sox2, Klf4, and c-Myc) into the genome. There are always risks of silencing of these genes by epigenetic modifications in the host cells, particularly, when introduced through retroviral techniques. In this contribution, we will discuss some of the major discoveries on epigenetic modifications within the chromatin of various genes associated with cancer progression and cancer stem cells in comparison to normal development of stem cell. These modifications may be considered as molecular signatures for predicting disorders of development and for identifying disease states

Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward