Human Resource Development as a possibility for developing the most underdeveloped micro-regions of Hungary

One of the problems in regional development policy having been present for a long time – and presumably to remain for a long while – is developing the most underdeveloped regions. Unfortunately the difference between the developed and the underdeveloped has increased in Hungary during the last two decades – despite the strengthening regional politics. These regions are usually afflicted with multiple disadvantages, therefore it is not enough to explore and change only one cause leading to underdevelopment. It is of complex origin; the effect of several correlated factor-layers can be observed. It is an elemental thesis in case of local improvements that investing into human resources (to put it in an ordinary way, into people) and improving the conditions of the population (qualification, healthcare, standards of living, etc.) is one of the most efficient and less costly means to eliminate underdevelopment. Despite its cost-efficiency only long-term results can be expected; in many cases it takes generations to benefit from the investment. In this work we will review the conclusions and suggestions of the educational aspects of a complex Hungarian development programme

Equilibrium Low Temperature Heat Capacity of the Spin Density Wave compound (TMTTF)2 Br: effect of a Magnetic Field

We have investigated the effect of the magnetic field (B) on the very low-temperature equilibrium heat capacity ceq of the quasi-1 D organic compound (TMTTF)2Br, characterized by a commensurate Spin Density Wave (SDW) ground state. Below 1K, ceq is dominated by a Schottky-like contribution, very sensitive to the experimental time scale, a property that we have previously measured in numerous DW compounds. Under applied field (in the range 0.2- 7 T), the equilibrium dynamics, and hence ceq extracted from the time constant, increases enormously. For B = 2-3 T, ceq varies like B2, in agreement with a magnetic Zeeman coupling. Another specific property, common to other Charge/Spin density wave (DW) compounds, is the occurrence of metastable branches in ceq, induced at very low temperature by the field exceeding a critical value. These effects are discussed within a generalization to SDWs in a magnetic field of the available Larkin-Ovchinnikov local model of strong pinning. A limitation of the model when compared to experiments is pointed out.Comment: 10 pages, 11 figure

Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1

Mitogen-activated protein kinases (MAPKs) are highly conserved protein kinase modules, and they control fundamental cellular processes. While the activation of MAPKs has been well studied, little is known on the mechanisms driving their inactivation. Here we uncover a role for ubiquitination in the inactivation of a MAPK module. Extracellular-signal-regulated kinase 5 (ERK5) is a unique, conserved member of the MAPK family and is activated in response to various stimuli through a three-tier cascade constituting MEK5 and MEKK2/3. We reveal an unexpected role for Inhibitors of Apoptosis Proteins (IAPs) in the inactivation of ERK5 pathway in a bimodal manner involving direct interaction and ubiquitination. XIAP directly interacts with MEKK2/3 and competes with PB1 domain-mediated binding to MEK5. XIAP and cIAP1 conjugate predominantly K63-linked ubiquitin chains to MEKK2 and MEKK3 which directly impede MEK5-ERK5 interaction in a trimeric complex leading to ERK5 inactivation. Consistently, loss of XIAP or cIAP1 by various strategies leads to hyperactivation of ERK5 in normal and tumorigenic cells. Loss of XIAP promotes differentiation of human primary skeletal myoblasts to myocytes in a MEKK2/3-ERK5-dependent manner. Our results reveal a novel, obligatory role for IAPs and ubiquitination in the physical and functional disassembly of ERK5-MAPK module and human muscle cell differentiation

Komplex molekuláris genetikai vizsgálati algoritmus myeloproliferativ neoplasiák diagnosztikájában

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, "classic" myeloproliferative neoplasms. Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients. Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied. Results: All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative. Conclusions: The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases. Orv. Hetil., 2014, 155(52), 2074-2081

Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors : A retrospective study by the chronic malignancies working party of the EBMT

Peer reviewe

Complications of Autologous Stem Cell Transplantation in Multiple Myeloma : Results from the CALM Study

Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent >= 1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0-100 days, 101 days-1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4-108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, andPeer reviewe

Low-complexity regions within protein sequences have position-dependent roles

<p>Abstract</p> <p>Background</p> <p>Regions of protein sequences with biased amino acid composition (so-called Low-Complexity Regions (LCRs)) are abundant in the protein universe. A number of studies have revealed that i) these regions show significant divergence across protein families; ii) the genetic mechanisms from which they arise lends them remarkable degrees of compositional plasticity. They have therefore proved difficult to compare using conventional sequence analysis techniques, and functions remain to be elucidated for most of them. Here we undertake a systematic investigation of LCRs in order to explore their possible functional significance, placed in the particular context of Protein-Protein Interaction (PPI) networks and Gene Ontology (GO)-term analysis.</p> <p>Results</p> <p>In keeping with previous results, we found that LCR-containing proteins tend to have more binding partners across different PPI networks than proteins that have no LCRs. More specifically, our study suggests i) that LCRs are preferentially positioned towards the protein sequence extremities and, in contrast with centrally-located LCRs, such terminal LCRs show a correlation between their lengths and degrees of connectivity, and ii) that centrally-located LCRs are enriched with transcription-related GO terms, while terminal LCRs are enriched with translation and stress response-related terms.</p> <p>Conclusions</p> <p>Our results suggest not only that LCRs may be involved in flexible binding associated with specific functions, but also that their positions within a sequence may be important in determining both their binding properties and their biological roles.</p

Modeling Stem Cell Induction Processes

Technology for converting human cells to pluripotent stem cell using induction processes has the potential to revolutionize regenerative medicine. However, the production of these so called iPS cells is still quite inefficient and may be dominated by stochastic effects. In this work we build mass-action models of the core regulatory elements controlling stem cell induction and maintenance. The models include not only the network of transcription factors NANOG, OCT4, SOX2, but also important epigenetic regulatory features of DNA methylation and histone modification. We show that the network topology reported in the literature is consistent with the observed experimental behavior of bistability and inducibility. Based on simulations of stem cell generation protocols, and in particular focusing on changes in epigenetic cellular states, we show that cooperative and independent reaction mechanisms have experimentally identifiable differences in the dynamics of reprogramming, and we analyze such differences and their biological basis. It had been argued that stochastic and elite models of stem cell generation represent distinct fundamental mechanisms. Work presented here suggests an alternative possibility that they represent differences in the amount of information we have about the distribution of cellular states before and during reprogramming protocols. We show further that unpredictability and variation in reprogramming decreases as the cell progresses along the induction process, and that identifiable groups of cells with elite-seeming behavior can come about by a stochastic process. Finally we show how different mechanisms and kinetic properties impact the prospects of improving the efficiency of iPS cell generation protocols.Fundação para a Ciência e a Tecnologia (BD 42942)MIT-Portugal ProgramNational Institutes of Health (U.S.) (CA112967)Singapore–MIT Alliance for Research and TechnologyIntel Corporatio

Discovering Sequence Motifs with Arbitrary Insertions and Deletions

Biology is encoded in molecular sequences: deciphering this encoding remains a grand scientific challenge. Functional regions of DNA, RNA, and protein sequences often exhibit characteristic but subtle motifs; thus, computational discovery of motifs in sequences is a fundamental and much-studied problem. However, most current algorithms do not allow for insertions or deletions (indels) within motifs, and the few that do have other limitations. We present a method, GLAM2 (Gapped Local Alignment of Motifs), for discovering motifs allowing indels in a fully general manner, and a companion method GLAM2SCAN for searching sequence databases using such motifs. glam2 is a generalization of the gapless Gibbs sampling algorithm. It re-discovers variable-width protein motifs from the PROSITE database significantly more accurately than the alternative methods PRATT and SAM-T2K. Furthermore, it usefully refines protein motifs from the ELM database: in some cases, the refined motifs make orders of magnitude fewer overpredictions than the original ELM regular expressions. GLAM2 performs respectably on the BAliBASE multiple alignment benchmark, and may be superior to leading multiple alignment methods for “motif-like” alignments with N- and C-terminal extensions. Finally, we demonstrate the use of GLAM2 to discover protein kinase substrate motifs and a gapped DNA motif for the LIM-only transcriptional regulatory complex: using GLAM2SCAN, we identify promising targets for the latter. GLAM2 is especially promising for short protein motifs, and it should improve our ability to identify the protein cleavage sites, interaction sites, post-translational modification attachment sites, etc., that underlie much of biology. It may be equally useful for arbitrarily gapped motifs in DNA and RNA, although fewer examples of such motifs are known at present. GLAM2 is public domain software, available for download at http://bioinformatics.org.au/glam2