Nkrp1 family, from lectins to protein interacting molecules.

The C-type lectin-like receptors include the Nkrp1 protein family that regulates the activity of natural killer (NK) cells. Rat Nkrp1a was reported to bind monosaccharide moieties in a Ca2+-dependent manner in preference order of GalNac > GlcNAc >> Fuc >> Gal > Man. These findings established for rat Nkrp1a have been extrapolated to all additional Nkrp1 receptors and have been supported by numerous studies over the past two decades.

Gambling in the Czech Republic.

Aim: To provide an overview of gambling and associated problems in the Czech Republic, including an overview of the historical context, legislation, prevalence, treatment and research base and agenda.

Methods: A review of literature and relevant sources.

Results: The trajectory of gambling patterns in the territory of the Czech Republic in the 20th century reflected broad socio-political changes.

[Overview of primary sternal closure techniques].

The aim of the overview study is to describe the currently used methods of primary median sternotomy closure in adult cardiac surgery. In the review of published literature, we draw on the data and focus on the methodology, indications, advantages, limitations, biomechanical and clinical results of the different methods in relation to the incidence of deep sternal wound complications after median sternotomy in adult cardiac surgery.Key words: sternum sternotomy adult cardiac surgery surgical procedures.

Cytotoxic Lipopeptide Muscotoxin A, Isolated from Soil Cyanobacterium Desmonostoc muscorum, Permeabilizes Phospholipid Membranes by Reducing Their Fluidity.

There is mounting evidence that cyanobacterial lipopeptides can kill mammalian cells, presenting a hazard to human health. Unfortunately, their mechanism of toxicity is poorly understood. We have isolated new cyclic undecalipopeptides muscotoxin A and B containing unique lipophilicresidue 3-amino-2,5-dihydroxydecanoic acid (5-OH Ahdoa).

Automated red blood cell exchange for acute drug removal in a patient with sirolimus toxicity.

Sirolimus is an immunosuppressant used to prevent graft versus host disease in allogeneic hematopoietic stem cell transplant recipients. It has a large volume of distribution (12 ± 7.5 l/kg) and within the intravascular space ∼95% of it is bound to red blood cells.

Streamlining variability in hospital charges for standard thyroidectomy: Developing a strategy to decrease waste.

Background: We assessed the efficiency, consistency, and appropriateness of perioperative processes for standard (total) thyroidectomy and devised a valuable strategy to decrease variability and waste.

Methods: Our multidisciplinary team evaluated <23-hour stay standard thyroidectomy performed by 3 surgical endocrinologists. We used the nominal group technique, process flowcharts, and root cause analysis to evaluate 6 perioperative processes.

Membrane activity of the pentaene macrolide didehydroroflamycoin in model lipid bilayers.

Didehydroroflamycoin (DDHR), a recently isolated member of the polyene macrolide family, was shown to have antibacterial and antifungal activity. However, its mechanism of action has not been investigated. Antibiotics from this family are amphiphilic; thus, they have membrane activity, their biological action is localized in the membrane, and the membrane composition and physical properties facilitate the recognition of a particular compound by the target organism.

A highly diverse spectrum of naphthoquinone derivatives produced by the endophytic fungus Biatriospora sp. CCF 4378.

A strain of Biatriospora sp. CCF 4378 was tested for the production of secondary metabolites under submerged fermentation conditions. Eleven compounds were isolated from the culture broth, and the structures of these compounds were determined using HRMS, NMR and X-ray analysis.

Retro operation on the Trp-cage miniprotein sequence produces an unstructured molecule capable of folding similar to the original only upon 2,2,2-trifluoroethanol addition.

Amino acid sequence and environment are the most important factors determining the structure, stability and dynamics of proteins. To evaluate their roles in the process of folding, we studied a retroversion of the well-described Trp-cage miniprotein in water and 2,2,2-trifluoroethanol (TFE) solution. We show, by circular dichroism spectroscopy and nuclear magnetic resonance (NMR) measurement, that the molecule has no stable structure under conditions in which the Trp-cage is folded.

Full genome sequences and molecular characterization of tick-borne encephalitis virus strains isolated from human patients.

Tick-borne encephalitis virus (TBEV) causes tick-borne encephalitis (TBE), one of the most important human neuroinfections across Eurasia. Up to date, only three full genome sequences of human European TBEV isolates are available, mostly due to difficulties with isolation of the virus from human patients. Here we present full genome characterization of an additional five low-passage TBEV strains isolated from human patients with severe forms of TBE.

Pseudogymnoascus destructans: evidence of virulent skin invasion for bats under natural conditions, Europe.

While Pseudogymnoascus destructans has been responsible for mass bat mortalities from white-nose syndrome (WNS) in North America, its virulence in Europe has been questioned. To shed the light on the issue of host-pathogen interaction between European bats and P. destructans, we examined seventeen bats emerging from the fungus-positive underground hibernacula in the Czech Republic during early spring 2013.

Local dynamics of proteins and DNA evaluated from crystallographic B factors.

The dynamics of protein and nucleic acid structures is as important as their average static picture. The local molecular dynamics concealed in diffraction images is expressed as so-called B factors. To find out how the crystal-derived B factors represent the dynamic behaviour of atoms and residues of proteins and DNA in their complexes, the distributions of scaled B factors from a carefully curated data set of over 700 protein-DNA crystal structures were analyzed [Schneider et al.

A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.

Resistance to the BCR-ABL inhibitor imatinib mesylate (IM) poses a major problem for the treatment of chronic myeloid leukemia (CML). IM resistance often results from a secondary mutation in BCR-ABL that interferes with drug binding. However, in many instances, there is no mutation in BCR-ABL, and the basis of such BCR-ABL-independent IM resistance remains to be elucidated.

Early relapse of Burkitt lymphoma heralded by a bone marrow necrosis and numb chin syndrome successfully treated with allogeneic stem cell transplantation.

The optimal salvage therapy for patients with relapsed Burkitt lymphoma is unknown. Bone marrow necrosis is an underreported (<1% of bone marrow failures). Numb chin syndrome is another rare syndrome associated with aggressive malignancies.

Evaluation of antibacterial properties of novel phthalocyanines against Escherichia coli--comparison of analytical methods.

We analyzed antibacterial effects of several novel phthalocyanines against Escherichia coli and evaluated the suitability of flow cytometry for the detection of antibacterial effects of phthalocyanines in comparison with routinely used cultivation. After 3h of exposure under cool white light eight cationic phthalocyanines showed very high antibacterial activity in the concentration of 2.00 mg L(-1) and four of them were even efficient in the concentration of 0.

Roles of octabutoxy substitution and J-aggregation in stabilization of the excited state in nickel phthalocyanine.

Nickel phthalocyanine (NiPc) complexes are known to show a rapid nonradiative deactivation of the photoexcited state through the internal conversion. This could be exploited in practical applications, such as photoprotection and photodynamic therapy. The butoxy substitution of NiPc plays an important role for drug delivery but also greatly influences its photophysics.

Hemophagocytic lymphohistiocytosis secondary to T-cell/histiocyte-rich large B-cell lymphoma.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by dysregulation of the immune system. Impaired function of cytotoxic T cells and natural killer cells is often seen, and T-cell malignancies represent most cases of lymphoma-associated HLH. HLH associated with B-cell lymphoma is rare.

Evolution of tertiary structure of viral RNA dependent polymerases.

Viral RNA dependent polymerases (vRdPs) are present in all RNA viruses; unfortunately, their sequence similarity is too low for phylogenetic studies. Nevertheless, vRdP protein structures are remarkably conserved. In this study, we used the structural similarity of vRdPs to reconstruct their evolutionary history.

Structural characterization of P1'-diversified urea-based inhibitors of glutamate carboxypeptidase II.

Urea-based inhibitors of human glutamate carboxypeptidase II (GCPII) have advanced into clinical trials for imaging metastatic prostate cancer. In parallel efforts, agents with increased lipophilicity have been designed and evaluated for targeting GCPII residing within the neuraxis. Here we report the structural and computational characterization of six complexes between GCPII and P1'-diversified urea-based inhibitors that have the C-terminal glutamate replaced by more hydrophobic moieties.

MYC protein expression is detected in plasma cell myeloma but not in monoclonal gammopathy of undetermined significance (MGUS).

It has been recognized that monoclonal gammopathy of undetermined significance (MGUS) precedes a diagnosis of plasma cell myeloma in most patients. Recent gene expression array analysis has revealed that an MYC activation signature is detected in plasma cell myeloma but not in MGUS. In this study, we performed immunohistochemical studies using membrane CD138 and nuclear MYC double staining on bone marrow biopsies from patients who met the diagnostic criteria of plasma cell myeloma or MGUS.

Structure, function, and pharmacology of NMDA receptor channels.

NMDA receptors have received much attention over the last few decades, due to their role in many types of neural plasticity on the one hand, and their involvement in excitotoxicity on the other hand. There is great interest in developing clinically relevant NMDA receptor antagonists that would block excitotoxic NMDA receptor activation, without interfering with NMDA receptor function needed for normal synaptic transmission and plasticity. This review summarizes current understanding of the structure of NMDA receptors and the mechanisms of NMDA receptor activation and modulation, with special attention given to data describing the properties of various types of NMDA receptor inhibition.

Identification, characterization, synthesis and HPLC quantification of new process-related impurities and degradation products in retigabine.

Two new impurities were described and determined using gradient HPLC method with UV detection in retigabine (RET). Using LC-HRMS, NMR and IR analysis the impurities were identified as RET-dimer I: diethyl {4,4'-diamino-6,6'-bis[(4-fluorobenzyl)amino]biphenyl-3,3'-diyl}biscarbamate and RET-dimer II: ethyl {2-amino-5-[{2-amino-4-[(4-fluorobenzyl) amino] phenyl} (ethoxycarbonyl) amino]-4-[(4-fluorobenzyl)amino] phenyl}carbamate. Reference standards of these impurities were synthesized followed by semipreparative HPLC purification.

Human interleukin-23 receptor antagonists derived from an albumin-binding domain scaffold inhibit IL-23-dependent ex vivo expansion of IL-17-producing T-cells.

Engineered combinatorial libraries derived from small protein scaffolds represent a powerful tool for generating novel binders with high affinity, required specificity and designed inhibitory function. This work was aimed to generate a collection of recombinant binders of human interleukin-23 receptor (IL-23R), which is a key element of proinflammatory IL-23-mediated signaling. A library of variants derived from the three-helix bundle scaffold of the albumin-binding domain (ABD) of streptococcal protein G and ribosome display were used to select for high-affinity binders of recombinant extracellular IL-23R.

Bioinformatic analysis of the protein/DNA interface.

To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots.

Increasing affinity of interferon-γ receptor 1 to interferon-γ by computer-aided design.

We describe a computer-based protocol to design protein mutations increasing binding affinity between ligand and its receptor. The method was applied to mutate interferon-γ receptor 1 (IFN-γ-Rx) to increase its affinity to natural ligand IFN-γ, protein important for innate immunity. We analyzed all four available crystal structures of the IFN-γ-Rx/IFN-γ complex to identify 40 receptor residues forming the interface with IFN-γ.