The postmortem diagnosis of hypothermia remains problematic even in the era of molecular and digital diagnostic advances. Gross hemorrhages in iliopsoas muscles have been regarded as a helpful diagnostic sign in hypothermia fatalities; nevertheless, they have received marginal attention since their original description. The present study attempts to fill that void by examining occurrence, localization, and diagnostic significance of the bleeding into the core muscles as evidence of death due to hypothermia in a series comprising 51 consecutive hypothermia autopsy cases. Hemorrhages into the core muscles were identified in 33 cases of fatal hypothermia (65%). Hemorrhages were present in iliopsoas muscles (19 cases; 37%), deep back muscles (18 cases; 35%), and in other core muscular groups such as the diaphragm, cervical, pectoral, and intercostal muscles (11 cases; 22%). The results of the study offer an attractive diagnostic opportunity and reaffirm the potential of the careful core muscle dissection for the clarification of hypothermic deaths. Centers lacking high-end imaging technologies and molecular postmortem programs may especially benefit, which may have implications in broader autopsy practice.

• MeSH
• Adult MeSH
• Epithelial Cells metabolism   MeSH
• Erythema pathology   MeSH
• Hypothermia pathology   MeSH
• Muscle, Skeletal pathology   MeSH
• Hemorrhage pathology   MeSH
• Kidney Tubules pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipid Metabolism MeSH
• Prospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Forensic Pathology MeSH
• Case-Control Studies MeSH
• Synovial Membrane pathology   MeSH
• Synovial Fluid MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Carbohydrates form one of the major groups of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation. Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer. Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored. We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies. Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment. In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans. Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.

• MeSH
• Biomarkers metabolism   MeSH
• Chromatography, Liquid methods   MeSH
• Fucose metabolism   MeSH
• Glycopeptides metabolism   MeSH
• Glycoside Hydrolases * MeSH
• Glycosylation MeSH
• Liver Cirrhosis diagnosis   metabolism   MeSH
• Humans MeSH
• Polysaccharides metabolism   MeSH
• Tandem Mass Spectrometry methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH

In spite of ongoing globalisation in many fields, the ethics of radiological protection have long been discussed almost exclusively in terms of 'Western' moral philosophy concepts such as utilitarianism or deontology. A cross-cultural discourse in this field is only just beginning. In 'Principles of Biomedical Ethics', Beauchamp and Childress suggested that there exists a 'common morality' which is 'not relative to cultures or individuals, because it transcends both'. They proposed four cross-culturally valid principles for decision making in medicine: respect for autonomy, non-maleficence, beneficence, and justice. A similar approach is being developed by the International Commission on Radiological Protection Task Group 94 on the ethics of radiological protection. Here, the core values are: human dignity, beneficence/non-maleficence, prudence, and justice. Other values could be added, such as consideration for the interests of society as a whole or the interests of future generations, or procedural values such as transparency and accountability; this paper will include a brief discussion on how they relate to the four basic principles. The main question to be addressed here, however, is whether the proposed core values are indeed part of a 'common morality'. This, as it will be argued, cannot be decided by a global opinion poll, but has to be based on an analysis of the written and oral traditions that have provided ethical orientation throughout history, and are still considered seminal by the majority of people. It turns out that there are indeed many commonalities across cultures, and that the concept of globally shared core values for the radiological protection system is not hopelessly idealistic.

• MeSH
• Beneficence MeSH
• Personhood MeSH
• Humans MeSH
• Radiation Protection methods   MeSH
• Social Values * MeSH
• Social Justice MeSH
• Cross-Cultural Comparison * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.

• MeSH
• Adaptor Proteins, Signal Transducing metabolism   MeSH
• Amino Acid Motifs MeSH
• Fusion Proteins, bcr-abl chemistry   genetics   metabolism   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism   pathology   MeSH
• Protein Array Analysis MeSH
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases metabolism   MeSH
• Phosphorylation MeSH
• HEK293 Cells MeSH
• Protein Kinase Inhibitors pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Pyrimidines pharmacology   MeSH
• Signal Transduction * drug effects   MeSH
• src Homology Domains MeSH
• Src Homology 2 Domain-Containing, Transforming Protein 1 metabolism   MeSH
• Protein Binding drug effects   MeSH
• Binding Sites MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Many patients with chronic myeloid leukemia in deep remission experience return of clinical disease after withdrawal of tyrosine kinase inhibitors (TKIs). This suggests signaling of inactive BCR-ABL, which allows the survival of cancer cells, and relapse. We show that TKI treatment inhibits catalytic activity of BCR-ABL, but does not dissolve BCR-ABL core signaling complex, consisting of CRKL, SHC1, GRB2, SOS1, cCBL, p85a-PI3K, STS1 and SHIP2. Peptide microarray and co-immunoprecipitation results demonstrate that CRKL binds to proline-rich regions located in C-terminal, intrinsically disordered region of BCR-ABL, that SHC1 requires pleckstrin homology, src homology and tyrosine kinase domains of BCR-ABL for binding, and that BCR-ABL sequence motif located in disordered region around phosphorylated tyrosine 177 mediates binding of three core complex members, i.e., GRB2, SOS1, and cCBL. Further, SHIP2 binds to the src homology and tyrosine kinase domains of BCR-ABL and its inositol phosphatase activity contributes to BCR-ABL-mediated phosphorylation of SHC1. Together, this study characterizes protein-protein interactions within the BCR-ABL core complex and determines the contribution of particular BCR-ABL domains to downstream signaling. Understanding the structure and dynamics of BCR-ABL interactome is critical for the development of drugs targeting integrity of the BCR-ABL core complex.

• MeSH
• Adaptor Proteins, Signal Transducing metabolism   MeSH
• Amino Acid Motifs MeSH
• Fusion Proteins, bcr-abl chemistry   genetics   metabolism   MeSH
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism   pathology   MeSH
• Protein Array Analysis MeSH
• Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases metabolism   MeSH
• Phosphorylation MeSH
• HEK293 Cells MeSH
• Protein Kinase Inhibitors pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Pyrimidines pharmacology   MeSH
• Signal Transduction drug effects   MeSH
• Protein Binding drug effects   MeSH
• Binding Sites MeSH
• Check Tag
• Humans MeSH

Článek se zabývá dvěma tématy v oblasti augmentativní a alternativní komunikace (AAK), která jsou důležitá pro zavádění aktivní komunikace uživatelů - jádrovou slovní zásobou a modelováním. Využití jádrové slovní zásoby umožňuje uživateli komplexnější vyjadřování v řadě komunikačních situací, rozšíření komunikace i o jiné nástroje, než je jen žádost. Zavádí užívání vět a zapojuje více slovních druhů, a to vše jak v manuálních znacích, tak v komunikaci pomocí symbolů. Modelování pak představuje nejpřirozenější metodu "nácviku" dorozumívání pomocí AAK, kdy komunikaci pomocí metod AAK uživateli předvádí a ukazuje jeho okolí v každodenních situacích.

The article deals with two topics of augmentative and alternative communication (AAC), which are important for the implementation of active user communication - core vocabulary and modelling. Use of the core vocabulary allows an AAC user to express him-/herself more comprehensively in many communication opportunities and to extend communication to situations other than mere requests. It introduces the use of sentences and expands the vocabulary in both manual signs and symbol communication. Modelling represents the most natural method of "training" communication using AAC, during which ACC methods are demonstrated to the user by his/her communication partners in everyday situations.

• Keywords
• jádrová slovní zásoba,
• MeSH
• Communication MeSH
• Humans MeSH
• Communication Devices for People with Disabilities * MeSH
• Vocabulary MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

The changes in the necrotic core and the penumbra following induction of focal ischemia have been the focus of attention for some time. However, evidence shows, that ischemic injury is not confined to the primarily affected structures and may influence the remote areas as well. Yet many studies fail to probe into the structures beyond the penumbra, and possibly do not even find any significant results due to their short-term design, as secondary damage occurs later. This slower reaction can be perceived as a therapeutic opportunity, in contrast to the ischemic core defined as irreversibly damaged tissue, where the window for salvation is comparatively short. The pathologies in remote structures occur relatively frequently and are clearly linked to the post-stroke neurological outcome. In order to develop efficient therapies, a deeper understanding of what exactly happens in the exo-focal regions is necessary. The mechanisms of glia contribution to the ischemic damage in core/penumbra are relatively well described and include impaired ion homeostasis, excessive cell swelling, glutamate excitotoxic mechanism, release of pro-inflammatory cytokines and phagocytosis or damage propagation via astrocytic syncytia. However, little is known about glia involvement in post-ischemic processes in remote areas. In this literature review, we discuss the definitions of the terms "ischemic core", "penumbra" and "remote areas." Furthermore, we present evidence showing the array of structural and functional changes in the more remote regions from the primary site of focal ischemia, with a special focus on glia and the extracellular matrix. The collected information is compared with the processes commonly occurring in the ischemic core or in the penumbra. Moreover, the possible causes of this phenomenon and the approaches for investigation are described, and finally, we evaluate the efficacy of therapies, which have been studied for their anti-ischemic effect in remote areas in recent years.

• Publication type
• Journal Article MeSH
• Review MeSH

The eukaryotic endomembrane system (ES) is served by hundreds of dedicated proteins. Experimental characterization of the ES-associated molecular machinery in several model eukaryotes complemented by a recent progress in phylogenomics and comparative genomics have revealed a conserved complex core of the machinery that appears to have been established before the last eukaryotic common ancestor (LECA). At the same time, modern eukaryotes exhibit a huge variation in the ES resulting from a multitude of evolutionary processes operating along the ever-branching paths from the LECA to its descendants. The most important source of evolutionary novelty in the ES functioning has undoubtedly been gene duplication followed by divergence of the gene copies, responsible not only for the pre-LECA establishment of many multi-paralog families of proteins in the very core of the ES-associated machinery, but also for post-LECA lineage-specific elaborations via family expansions and the origin of novel components. Extreme sequence divergence has obscured actual homologous relationships between potentially many components of the machinery, even between orthologous proteins, as illustrated by the yeast Vps51 subunit of the vesicle tethering complex GARP hypothesized here to be a highly modified ortholog of a conserved eukaryotic family typified by the zebrafish Fat-free (Ffr) protein. A dynamic evolution of many ES-associated proteins, especially those centred around RAB and ARF GTPases, seems to take place at the level of their domain architectures. Finally, reductive evolution and recurrent gene loss are emerging as pervasive factors shaping the ES in all phylogenetic lineages.

• MeSH
• Gene Duplication MeSH
• Eukaryotic Cells metabolism   physiology   MeSH
• Humans MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Evolution, Molecular MeSH
• Amino Acid Sequence MeSH
• Sequence Alignment MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

The temporal and spatial trends in sediment of 22 poly- and perfluorinated (PFAS) compounds were investigated in the southern Great Lakes Erie and Ontario as well as Lake St. Clair. Surface concentrations measured by Ponar grab samples indicated a trend for greater concentrations near to urban sites. Mean concentrations ∑22PFAS were 15.6, 18.2 and 19 ng g-1 dm for Lakes St. Clair, Erie and Ontario, respectively. Perfluoro-n-butanoic acid (PFBA) and Perfluoro-n-hexanoic acid (PFHxA) were frequently determined in surface sediment and upper core samples indicating a shift in use patterns. Where PFBA was identified it was at relatively great concentrations typically >10 ng g-1 dm. However as PFBA and PFHxA are less likely to bind to sediment they may be indicative of pore water concentrations Sedimentation rates between Lake Erie and Lake Ontario differ greatly with greater rates observed in Lake Erie. In Lake Ontario, in general concentrations of PFAS observed in core samples closely follow the increase in use along with an observable change due to regulation implementation in the 1970s for water protection. However some of the more water soluble PFAS were observed in deeper core layers than the time of production could account for, indicating potential diffusion within the sediment. Given the greater sedimentation rates in Lake Erie, it was hoped to observe in greater resolution changes since the mid-1990s. However, though some decrease was observed at some locations the results are not clear. Many cores in Lake Erie had clearly observable gas voids, indicative of gas ebullition activity due to biogenic production, there were also observable mussel beds that could indicate mixing by bioturbation of core layers.

• MeSH
• Water Pollutants, Chemical analysis   MeSH
• Water Pollution, Chemical statistics & numerical data   MeSH
• Fluorocarbons analysis   MeSH
• Lakes MeSH
• Environmental Monitoring * MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Great Lakes Region MeSH
• Ontario MeSH

Endoskopická ultrasonografia patrí k najdynamickejšie sa vyvíjajúcim diagnostickým a terapeutickým metódam v gastrointestinálnej a pankreatobiliárnej endoskopii. Jej veľkou výhodou je bezprostredná blízkosť so stenou tráviacej trubice a s priľahlými orgánmi bez rušivých elementov, ako je vzduch alebo tukové tkanivo. Kým pôvodne bola určená len na diagnostiku ochorení pankreasu, v súčasnosti sa jej indikácie výrazne rozšírili a rozširujú sa ďalej. Pomocou FNA alebo core-biopsy dokáže významne zvýšiť svoju presnosť v diferenciálnej diagnostike mnohých ochorení. Svoje uplatnenie nachádza čoraz viac aj ako terapeutická metóda. Blokáda alebo neurolýza celiakálneho plexu, ako aj transgastrická alebo transduodenálna drenáž pankreatických pseudocýst sú už súčasťou rutinnej endoskopickej praxe na mnohých pracoviskách.

Endoscopic sonography belongs to the most dynamically developing diagnostic and therapeutical methods in gastrointestinal and pancreatobiliary endoscopy. Its big advantage is the nearness to the wall of digestive tube and closed organs without disturbing elements as air or adipose tissue. Whereas originally it was designed for diagnostics of pancreas diseases, at present its indications have widened significantly and they are widening further. With help of FNA or core-biopsy it is able to increase its accuracy significantly in differential diagnostics of many diseases. Increasingly it finds its application also as a therapeutical method. Blockage or neurolysis of coeliac plexus as well as transgastric or transduodenal drainage of pancreatic pseudocysts are already part of routine endoscopic practice at many workplaces.