Berberine bridge enzyme-like (BBE-like) proteins form a multigene family (pfam 08031), which is present in plants, fungi and bacteria. They adopt the vanillyl alcohol-oxidase fold and predominantly show bi-covalent tethering of the FAD cofactor to a cysteine and histidine residue, respectively. The Arabidopsis thaliana genome was recently shown to contain genes coding for 28 BBE-like proteins, while featuring four distinct active site compositions. We determined the structure of a member of the AtBBE-like protein family (termed AtBBE-like 28), which has an active site composition that has not been structurally and biochemically characterized thus far. The most salient and distinguishing features of the active site found in AtBBE-like 28 are a mono-covalent linkage of a histidine to the 8α-position of the flavin-isoalloxazine ring and the lack of a second covalent linkage to the 6-position, owing to the replacement of a cysteine with a histidine. In addition, the structure reveals the interaction of a glutamic acid (Glu426) with an aspartic acid (Asp369) at the active site, which appear to share a proton. This arrangement leads to the delocalization of a negative charge at the active site that may be exploited for catalysis. The structure also indicates a shift of the position of the isoalloxazine ring in comparison to other members of the BBE-like family. The dioxygen surrogate chloride was found near the C(4a) position of the isoalloxazine ring in the oxygen pocket, pointing to a rapid reoxidation of reduced enzyme by dioxygen. A T-DNA insertional mutant line for AtBBE-like 28 results in a phenotype, that is characterized by reduced biomass and lower salt stress tolerance. Multiple sequence analysis showed that the active site composition found in AtBBE-like 28 is only present in the Brassicaceae, suggesting that it plays a specific role in the metabolism of this plant family.

• MeSH
• Arabidopsis enzymologie   genetika   MeSH
• druhová specificita MeSH
• katalytická doména MeSH
• kyselina asparagová chemie   genetika   MeSH
• kyselina glutamová chemie   genetika   MeSH
• mutageneze MeSH
• N-demethylasy chemie   genetika   MeSH
• proteiny huseníčku chemie   genetika   MeSH
• sekundární struktura proteinů MeSH
• tolerance k soli fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH

Microbial biodegradation and biotransformation reactions are essential to most bioremediation processes, yet the specific organisms, genes, and mechanisms involved are often not well understood. Stable isotope probing (SIP) enables researchers to directly link microbial metabolic capability to phylogenetic and metagenomic information within a community context by tracking isotopically labeled substances into phylogenetically and functionally informative biomarkers. SIP is thus applicable as a tool for the identification of active members of the microbial community and associated genes integral to the community functional potential, such as biodegradative processes. The rapid evolution of SIP over the last decade and integration with metagenomics provide researchers with a much deeper insight into potential biodegradative genes, processes, and applications, thereby enabling an improved mechanistic understanding that can facilitate advances in the field of bioremediation.

• MeSH
• biodegradace * MeSH
• fylogeneze MeSH
• izotopové značení metody   MeSH
• látky znečišťující životní prostředí metabolismus   MeSH
• metagenomika metody   trendy   MeSH
• uhlík metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH

The pregnane X receptor (PXR, encoded by the NR1I2 gene) is a ligand-regulated transcription factor originally described as a master regulator of xenobiotic detoxification. Later, however, PXR was also shown to interact with endogenous metabolism and to be further associated with various pathological states. This review focuses predominantly on such aspects, currently less covered in literature, as the control of PXR expression per se in the context of inter-individual differences in drug metabolism. There is growing evidence that non-coding RNAs post-transcriptionally regulate PXR. Effects on PXR have especially been reported for microRNAs (miRNAs), which include miR-148a, miR-18a-5p, miR-140-3p, miR-30c-1-3p and miR-877-5p. Likewise, miRNAs control the expression of both transcription factors involved in PXR expression and regulators of PXR function. The impact of NR1I2 genetic polymorphisms on miRNA-mediated PXR regulation is also discussed. As revealed recently, long non-coding RNAs (lncRNAs) appear to interfere with PXR expression. Reciprocally, PXR activation regulates non-coding RNA expression, thus comprising another level of PXR action in addition to the direct transactivation of protein-coding genes. PXR expression is further controlled by several transcription factors (cross-regulation) giving rise to different PXR transcript variants. Controversies remain regarding the suggested role of feedback regulation (auto-regulation) of PXR expression. In this review, we comprehensively summarize the miRNA-mediated, lncRNA-mediated and transcriptional regulation of PXR expression, and we propose that deciphering the precise mechanisms of PXR expression may bridge our knowledge gap in inter-individual differences in drug metabolism and toxicity.

• MeSH
• biologická variabilita populace * MeSH
• biotransformace MeSH
• farmakogenetika MeSH
• farmakogenomické varianty * MeSH
• fenotyp MeSH
• genetická transkripce * MeSH
• genotyp MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• posttranskripční úpravy RNA * MeSH
• pregnanový X receptor genetika   metabolismus   MeSH
• RNA dlouhá nekódující genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Having the administrative and clinical information concerning the patient presented in a comprehensible format, language, and terminology is valuable for any healthcare provider. In Europe, this type of information is represented by the Patient Summary Guideline and on the other side of the Atlantic by the Continuity of Care Document (CCD). Trillium Bridge is a project co-funded by the European Commission that “compares specifications of EU and US patient summaries with the aim of developing and testing common and consistent specifications and systems enabling interoperability of electronic health records across the Atlantic.” The objective of this article is to summarize the findings of the comparison between these two Patient Summaries. Both documents are using the same syntax, namely Clinical Document Architecture (CDA), making the comparison easier. The documents were compared from a clinical, syntactic, and terminological point of view focusing on semantic interoperability. A common denominator was found in terms of sections, data elements, and value sets. Comparing the value sets led the project team to assess available official maps such as the SNOMED CT and ICD-10 and determine their applicability. In some cases, such as the National Cancer Institute Thesaurus and the EDQM standard terms, no maps were found and the team proposed associations. The common denominator thus identified allows for significant parts of the data to be exchanged, setting the baseline for the transatlantic exchange of a meaningful set of patient summary data and establishing a springboard for an international patient summary standard.

• MeSH
• chorobopisy - počítačové systémy MeSH
• chorobopisy - spojování * MeSH
• chorobopisy normy   MeSH
• elektronické zdravotní záznamy * normy   MeSH
• Evropská unie MeSH
• klinické kódování MeSH
• kontinuita péče o pacienty MeSH
• lidé MeSH
• programy národního zdraví MeSH
• řízený slovník MeSH
• terminologie jako téma * MeSH
• záznamy jako téma normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přednášky MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

Authors Wagner et al. in your journal demonstrated effectiveness of mechanical chest compressions in the coronary catheterization laboratory to facilitate coronary intervention and survival in patients requiring prolonged resuscitation efforts. We dare to comment on this article and advocate to use mechanical chest compressions only as a bridge to extracorporeal membrane oxygenation to completely substitute failed circulation and enable percutaneous coronary intervention or other procedures to treat the cause of cardiac arrest.

• MeSH
• hrudník MeSH
• kardiopulmonální resuscitace metody   MeSH
• koronární angioplastika * MeSH
• lidé MeSH
• masáž srdce metody   MeSH
• srdeční zástava terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Introduction: Simulation training offers an authentic team-based learning opportunity without risk to real patients. The Educational Corner at the annual congress of the European Branch of Extracorporeal Life Support Organisation (EuroELSO) provided an opportunity for multiple simulation training sessions facilitated by experts from all over the world.Aim: We aimed to review the educational impact of EuroELSO Educational Corner and whether it provides a quality ECLS training to a wide spectrum of multidisciplinary international attendees utilising high and low fidelity simulation, workshops and hands on sessions.Methods: During the congress, 43 sessions were conducted dedicated to ECLS education with identified educational objectives. The sessions focused on management of adults and children on V-V or V-A ECMO. Adult sessions covered emergencies on mechanical circulatory support with management of LVAD and Impella, managing refractory hypoxemia on V-V ECMO, emergencies on ECMO, renal replacement therapy on ECMO, V-V ECMO, ECPR cannulation and performing perfect simulation. Paediatric sessions covered ECPR neck and central cannulation, renal replacement on ECMO, troubleshooting, cannulation workshop, V-V recirculation, ECMO for single ventricle, PIMS-TS and CDH, ECMO transport and neurological injury.Results: The Educational Corner was attended by more than 400 participants over the two congress days. Majority of responders (88%) reported that training sessions met the set educational goals and objectives and that this would change their current practice. Almost all (94%) reported that they received useful information and 95% would recommend the session to their colleagues.Conclusion: The Educational Corner, as an integral component of the annual EuroELSO congress, achieved the set educational goals and provided quality education based on the recipient survey. Structured multidisciplinary ECLS education with standardised curriculum and feedback is an important key step in delivering quality training to an international audience. Standardisation of European ECLS education remains an important focus of the EuroELSO.

• MeSH
• dítě MeSH
• dospělí MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• mimotělní membránová oxygenace * výchova   MeSH
• náhlé příhody MeSH
• tréninková simulace * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Londýn MeSH

Lower plant species including some green algae, non-vascular plants (bryophytes) as well as the oldest vascular plants (lycopods) and ferns (monilophytes) possess a unique aldehyde dehydrogenase (ALDH) gene named ALDH21, which is upregulated during dehydration. However, the gene is absent in flowering plants. Here, we show that ALDH21 from the moss Physcomitrella patens codes for a tetrameric NADP+ -dependent succinic semialdehyde dehydrogenase (SSALDH), which converts succinic semialdehyde, an intermediate of the γ-aminobutyric acid (GABA) shunt pathway, into succinate in the cytosol. NAD+ is a very poor coenzyme for ALDH21 unlike for mitochondrial SSALDHs (ALDH5), which are the closest related ALDH members. Structural comparison between the apoform and the coenzyme complex reveal that NADP+ binding induces a conformational change of the loop carrying Arg-228, which seals the NADP+ in the coenzyme cavity via its 2'-phosphate and α-phosphate groups. The crystal structure with the bound product succinate shows that its carboxylate group establishes salt bridges with both Arg-121 and Arg-457, and a hydrogen bond with Tyr-296. While both arginine residues are pre-formed for substrate/product binding, Tyr-296 moves by more than 1 Å. Both R121A and R457A variants are almost inactive, demonstrating a key role of each arginine in catalysis. Our study implies that bryophytes but presumably also some green algae, lycopods and ferns, which carry both ALDH21 and ALDH5 genes, can oxidize SSAL to succinate in both cytosol and mitochondria, indicating a more diverse GABA shunt pathway compared with higher plants carrying only the mitochondrial ALDH5.

• MeSH
• Bryophyta enzymologie   genetika   MeSH
• fylogeneze MeSH
• GABA analogy a deriváty   metabolismus   MeSH
• kapradiny enzymologie   genetika   MeSH
• konformace proteinů MeSH
• kyselina jantarová metabolismus   MeSH
• rostlinné geny genetika   fyziologie   MeSH
• substrátová specifita MeSH
• sukcinátsemialdehyddehydrogenasa genetika   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH

Several subunits of the multifunctional eukaryotic translation initiation factor 3 (eIF3) contain well-defined domains. Among them is the conserved bipartite PCI domain, typically serving as the principal scaffold for multisubunit 26S proteasome lid, CSN and eIF3 complexes, which constitutes most of the C-terminal region of the c/NIP1 subunit. Interestingly, the c/NIP1-PCI domain is exceptional in that its deletion, despite being lethal, does not affect eIF3 integrity. Here, we show that a short C-terminal truncation and two clustered mutations directly disturbing the PCI domain produce lethal or slow growth phenotypes and significantly reduce amounts of 40S-bound eIF3 and eIF5 in vivo. The extreme C-terminus directly interacts with blades 1-3 of the small ribosomal protein RACK1/ASC1, which is a part of the 40S head, and, consistently, deletion of the ASC1 coding region likewise affects eIF3 association with ribosomes. The PCI domain per se shows strong but unspecific binding to RNA, for the first time implicating this typical protein-protein binding domain in mediating protein-RNA interactions also. Importantly, as our clustered mutations severely reduce RNA binding, we conclude that the c/NIP1 C-terminal region forms an important intermolecular bridge between eIF3 and the 40S head region by contacting RACK1/ASC1 and most probably 18S rRNA.

• MeSH
• adaptorové proteiny signální transdukční chemie   genetika   metabolismus   MeSH
• delece genu MeSH
• eukaryotický iniciační faktor 3 chemie   genetika   metabolismus   MeSH
• iniciace translace peptidového řetězce MeSH
• interakční proteinové domény a motivy MeSH
• malé podjednotky ribozomu eukaryotické chemie   metabolismus   MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• podjednotky proteinů chemie   metabolismus   MeSH
• proteiny vázající GTP chemie   genetika   metabolismus   MeSH
• RNA ribozomální 18S metabolismus   MeSH
• Saccharomyces cerevisiae - proteiny biosyntéza   chemie   genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• transkripční faktory bZIP biosyntéza   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Srdeční zástava je závažný stav s vysokou mortalitou, závažnou morbiditou, představovanou především neurologickým postižením s nutností dlouhodobé nemocniční péče. Projekt je navržen jako prospektivní, randomizovaná studie role přednemocničního použití mechanizované srdeční masáže v kombinaci s léčbou mírnou hypotermií systémem intranazálního evaporativního chlazení , které budou sloužit k překlenutí k nemocniční emergentní implantaci mimotělní mechanické podpory (ECLS - extracorporal life support) následované neodkladnou invazívní diagnostikou a léčbou u pacientů s refrakterní mimonemocniční srdeční zástavou před svědky převážně kardiálního původu ve srovnání se standardní léčbou. Bude zhodnocena proveditelnost, bezpečnost, užitečnost, nákladová efektivita a vliv na kvalitu života tohoto kombinovaného hyperinvazívního přístupu. Studie je rovněž navržena tak, aby zhodnotila, zda kombinace uvedených metod má příznivý vliv na šestiměsíční přežití s dobrým neurologickým výsledkem (primární cíl).; Cardiac arrest is a serious condition with high mortality and significant morbidity represented predominantly by neurological damage with the need for prolonged hospital care. The project is designed as a prospective, randomized study on prehospital use of a chest compression device combined with intraarrest evaporative cooling as a bridge to in hospital emergency ECLS (extracorporeal life support) implantation followed by immediate invasive diagnostics and treatment in cases of witnessed out-of-hospital refractory cardiac arrest (OHCA) of predominantly cardiac origin to assess the feasibility, safety, usefulness, cost-effectiveness and impact on quality of life of this combined hyperinvasive approach. The study is also intended to asseess whether the combination of above methods might have a beneficial effect on 6 monts survival with favourable neurological recovery (primary outcome).

• MeSH
• kardiopulmonální resuscitace MeSH
• koronární angioplastika MeSH
• masáž srdce MeSH
• mimotělní oběh MeSH
• urgentní zdravotnické služby MeSH
• zástava srdce mimo nemocnici MeSH
• Publikační typ
• randomizované kontrolované studie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• kardiologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

PURPOSE OF REVIEW: European Resuscitation Council Guidelines for Cardiopulmonary Resuscitation prioritize treatments like chest compression and defibrillation, known to be highly effective for cardiac arrest from cardiac origin. This review highlights the need to modify this approach in special circumstances. RECENT FINDINGS: Potentially reversible causes of cardiac arrest are clustered into four Hs and four Ts (Hypoxia, Hypovolaemia, Hyperkalaemia/other electrolyte disorders, Hypothermia, Thrombosis, Tamponade, Tension pneumothorax, Toxic agents). Point-of-care ultrasound has its role in identification of the cause and targeting treatment. Time-critical interventions may even prevent cardiac arrest if applied early. The extracorporeal CPR (eCPR) or mechanical CPR should be considered for bridging the period needed to reverse the precipitating cause(s). There is low quality of evidence available to guide the treatment in the majority of situations. Some topics (pulmonary embolism, eCPR, drowning, pregnancy and opioid toxicity) were included in recent ILCOR reviews and evidence updates but majority of recommendations is based on individual systematic reviews, scoping reviews, evidence updates and expert consensus. SUMMARY: Cardiac arrests from reversible causes happen with lower incidence. Return of spontaneous circulation and neurologically intact survival can hardly be achieved without a modified approach focusing on immediate treatment of the underlying cause(s) of cardiac arrest.

• MeSH
• hypotermie * MeSH
• kardiopulmonální resuscitace * MeSH
• lidé MeSH
• srdeční zástava * terapie   MeSH
• těhotenství MeSH
• vodní a elektrolytová nerovnováha * MeSH
• zástava srdce mimo nemocnici * terapie   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH