UNLABELLED: This study investigates the underlying mechanisms driving the formation of the largest known burial site of the Northern European Mesolithic, Yuzhniy Oleniy Ostrov (YOO). Radiogenic strontium isotope analysis (87Sr/86Sr) was used to identify group dynamics within the cemetery and examine the site's place within local and supra-regional networks. The analysis of 57 humans and 31 animals was supported by the creation of an environmental baseline which identified four key geological zones and defines the strontium characteristics of Lake Onega. Only two individuals had strontium values indicating time spent outside of Lake Onega's northern shores, where the majority of the burial population is likely to have resided. These results suggest that the YOO cemetery predominantly served as a burial place for those with semi-permanent residence in this area, with no significant evidence for gender-based relocation patterns indicative of patri- or matrilocal residency. However, materials seem to have travelled towards Lake Onega even over great distances and the presence of the two outlier individuals suggests these exchanges also involved long-distance travel of people. Our results align with an increasing number of studies that suggest a high degree of residential stability for Late Mesolithic foraging groups relying primarily on aquatic resources, yet simultaneously places the Lake Onega community within a wider Mesolithic communication network. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12520-024-02129-8.

• Klíčová slova
• Bioarchaeology, Geology, Hunter-gatherer-fishers, Mesolithic, Mobility, Strontium,
• Publikační typ
• časopisecké články MeSH

UNLABELLED: Cyanobacteria are ubiquitous aquatic organisms with a remarkable evolutionary history reaching as far as 1.9 Ga. They play a vital role in ecosystems yet also raise concerns due to their association with harmful algal blooms. Understanding the historical patterns and drivers behind these blooms is crucial for effective ecosystem management. Lake-sediment cores are valuable natural environmental archives, recording the histories of such blooms. Among others, phycocyanin, a pigment specific to cyanobacteria, emerges as a promising biomarker for reconstructing past cyanobacterial bloom events. However, due to the physicochemical properties of phycocyanin, there is no validated method available to extract and measure this pigment from complex sediment matrix. This study explores the applicability of hyperspectral imaging (HSI), a non-destructive technique, as a novel approach for high resolution in-situ detection and quantification of phycocyanin in lake sediments. Our experiments show that phycocyanin can be detected by HSI with an absorption trough at 620 nm (relative absorption band depth, RABD620). We established a semi-quantitative calibration of the spectral index RABD620 by conducting spiking experiments with phycocyanin standard (known phycocyanin mass) on organic-rich and mineral-rich sediments of varying water contents. We also assessed potential interference from chlorophyll a, another photosynthetic pigment, ensuring the reliability of hyperspectral phycocyanin measurements. Our findings demonstrate a significant correlation (R2 ranging from 0.37 to 0.997) between the RABD620 index and associated phycocyanin amounts in organic-rich and minerogenic sediments. This indicates the potential of the spectral index to directly measure in-situ biomarker concentrations on split sediment cores. Although confounding factors such as water and chlorophyll a content can influence the spectral signal, this method offers a rapid and non-destructive approach for studying historical cyanobacterial blooms in sedimentary records. This opens promising grounds for various applications, including ecosystem-health assessment and environmental change monitoring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10933-024-00350-y.

• Klíčová slova
• Algal blooms, Cyanobacteria, Environmental change, Paleolimnology, Pigments,
• Publikační typ
• časopisecké články MeSH

Plasma flows with enhanced dynamic pressure, known as magnetosheath jets, are often found downstream of collisionless shocks. As they propagate through the magnetosheath, they interact with the surrounding plasma, shaping its properties, and potentially becoming geoeffective upon reaching the magnetopause. In recent years (since 2016), new research has produced vital results that have significantly enhanced our understanding on many aspects of jets. In this review, we summarise and discuss these findings. Spacecraft and ground-based observations, as well as global and local simulations, have contributed greatly to our understanding of the causes and effects of magnetosheath jets. First, we discuss recent findings on jet occurrence and formation, including in other planetary environments. New insights into jet properties and evolution are then examined using observations and simulations. Finally, we review the impact of jets upon interaction with the magnetopause and subsequent consequences for the magnetosphere-ionosphere system. We conclude with an outlook and assessment on future challenges. This includes an overview on future space missions that may prove crucial in tackling the outstanding open questions on jets in the terrestrial magnetosheath as well as other planetary and shock environments.

• Klíčová slova
• Bow shock, Foreshock, Magnetopause, Magnetosheath, Magnetosheath jets, Solar wind,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Reversed-phase ultrahigh-performance liquid chromatography-mass spectrometry (RP-UHPLC/MS) method is optimized for the quantitation of a large number of lipid species in biological samples, primarily in human plasma and serum. The method uses a C18 bridged ethylene hybrid (BEH) column (150 × 2.1 mm; 1.7 μm) for the separation of lipids from 23 subclasses with a total run time of 25 min. Lipid species separation allows the resolution of isobaric and isomeric lipid forms. A triple quadrupole mass spectrometer is used for targeted lipidomic analysis using multiple reaction monitoring (MRM) in the positive ion mode. Data are evaluated by Skyline software, and the concentrations of analytes are determined using internal standards per each individual lipid class.

• Klíčová slova
• High-throughput lipidomics, Mass spectrometry, Plasma, Quantitation, Reversed-phase, Serum, Ultrahigh-performance liquid chromatography,
• MeSH
• chromatografie s reverzní fází * metody   MeSH
• hmotnostní spektrometrie metody   MeSH
• kapalinová chromatografie-hmotnostní spektrometrie MeSH
• lidé MeSH
• lipidomika * metody   MeSH
• lipidy * analýza   MeSH
• rychlé screeningové testy metody   MeSH
• software MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• lipidy * MeSH

In esophageal squamous cell carcinoma, genetic activation of NRF2 increases resistance to chemotherapy and radiotherapy, which results in a significantly worse prognosis for patients. Therefore NRF2-activated cancers create an urgent clinical need to identify new therapeutic options. In this context, we previously identified the geldanamycin family of HSP90 inhibitors, which includes 17DMAG, to be synthetic lethal with NRF2 activity. As the first-generation of geldanamycin-derivative drugs were withdrawn from clinical trials due to hepatotoxicity, we designed second-generation compounds with C19-substituted structures in order to inhibit glutathione conjugation-mediated hepatotoxicity. In this study, using a variety of in vitro and in vivo cancer models, we found that C19-substituted 17DMAG compounds maintain their enhanced toxicity profile and synthetic lethal interaction with NRF2-NQO1-activated cancer cells. Importantly, using a xenograft mouse tumor model, we found that C19-substituted 17DMAG displayed significant anticancer efficacy against NRF2-NQO1-activated cancer cells without causing hepatotoxicity. These results clearly demonstrate the improved clinical potential for this new class of HSP90 inhibitor anticancer drugs, and suggest that patients with NRF2-NQO1-activated esophageal carcinoma may benefit from this novel therapeutic approach.

• Klíčová slova
• C19-position substituted geldanamycin derivatives, ESCC, HSP90, NQO1, NRF2-NQO1-activated cancer,
• MeSH
• antitumorózní látky farmakologie   chemie   MeSH
• benzochinony * farmakologie   chemie   MeSH
• faktor 2 související s NF-E2 * metabolismus   genetika   MeSH
• lidé MeSH
• makrocyklické laktamy * farmakologie   chemie   terapeutické užití   MeSH
• myši nahé MeSH
• myši MeSH
• NAD(P)H dehydrogenasa (chinon) * metabolismus   genetika   MeSH
• nádorové buněčné linie MeSH
• nádory jícnu * farmakoterapie   metabolismus   genetika   MeSH
• proteiny tepelného šoku HSP90 antagonisté a inhibitory   metabolismus   MeSH
• skvamózní karcinom jícnu * farmakoterapie   genetika   metabolismus   MeSH
• xenogenní modely - testy antitumorózní aktivity * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• benzochinony * MeSH
• faktor 2 související s NF-E2 * MeSH
• geldanamycin MeSH Prohlížeč
• makrocyklické laktamy * MeSH
• NAD(P)H dehydrogenasa (chinon) * MeSH
• NFE2L2 protein, human MeSH Prohlížeč
• NQO1 protein, human MeSH Prohlížeč
• proteiny tepelného šoku HSP90 MeSH

PURPOSE: To evaluate treatment outcomes and toxicity in patients with stage T1-3N0M0 oral cancer treated with surgery followed by high-dose-rate brachytherapy (HDR-BT). METHODS AND MATERIALS: Retrospective study of 50 patients with stage T1-T3N0 tongue and floor-of-mouth cancer who underwent tumour excision (+ elective neck dissection) followed by postoperative HDR-BT due to the presence of negative prognostic factors (close or positive resection margins, lymphovascular and/or perineural invasion, deep invasion). The plastic tube technique (dose: 18 x 3 Gy b.i.d.) was used. Survival outcomes, toxicity, and prognostic factors were evaluated. RESULTS: At a median follow-up of 81 months (range, 4-121), actuarial 5-year local control (LC), nodal control (NC) and progression-free survival (PFS) rates were 79%, 69%, and 64%. After salvage treatment (surgery + external beam radiotherapy), LC, NC, and PFS increased to 87%, 77%, and 72.3%, respectively. Five-year overall survival and cancer-specific survival (CSS) rates were 73% and 77%. Treatmentrelated toxicity included two cases of mandibular osteoradionecrosis and five cases of small soft tissue necrosis. T stage was significantly correlated with nodal control (p=0.02) and CSS (p=0.04). Tumour grade correlated with DFS (p=0.01). CONCLUSION: Postoperative HDR-BT 18 x 3 Gy b.i.d. seems to be an effective method in patients with T1-3N0M0 oral cancer with negative prognostic factors after tumour resection.

• Klíčová slova
• Brachytherapy, Early oral cancer, Postoperative treatment,
• MeSH
• brachyterapie * metody   MeSH
• celková dávka radioterapie * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory úst * radioterapie   patologie   chirurgie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• aortální stenóza * chirurgie   komplikace   MeSH
• chirurgická náhrada chlopně metody   MeSH
• frakční průtoková rezerva myokardu * MeSH
• koronární angioplastika * metody   MeSH
• koronární bypass * metody   MeSH
• lidé MeSH
• nemoci koronárních tepen * chirurgie   komplikace   terapie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

Over the last decade, considerable progress has been made in unraveling RNA virus diversity. This has contributed to our understanding of the evolution of these viruses, which include emerging zoonotic human pathogens. Current success has been greatly facilitated by the development of next-generation sequencing platforms instrumental for meta-transcriptomic studies. However, due to the rapid evolution of RNA viruses, there are numerous "blind spots" waiting to be explored; one of those is the RNA virome of unicellular eukaryotes. Here, we present the pipeline, which has been successfully used to characterize various types of RNA viruses, including Leishbuviridae (Bunyaviricetes, Hareavirales) in the parasitic flagellates of the family Trypanosomatidae. The pipeline relies on axenic in vitro cell culture and double-stranded RNA enrichment, followed by direct RNA-sequencing. A detailed procedure description starting from the initial total RNA preparation to the final assembly of the viral segments is provided.

• Klíčová slova
• Leishbuviridae, NGS, Protists, RNA isolation, Trypanosomatidae, Virus Discovery, dsRNA,
• MeSH
• dvouvláknová RNA genetika   MeSH
• genom virový MeSH
• RNA virová genetika   MeSH
• RNA-viry genetika   klasifikace   MeSH
• sekvenční analýza RNA metody   MeSH
• Trypanosomatina * genetika   MeSH
• vysoce účinné nukleotidové sekvenování * metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dvouvláknová RNA MeSH
• RNA virová MeSH

Sexual compatibility in the Basidiomycota is governed by genetic identity at one or two loci, resulting in compatibility systems called bipolar and tetrapolar. The loci are known as HD and P/R, encoding homeodomain transcription factors and pheromone precursors and receptors, respectively. Bipolarity is known to evolve either by linkage of the two loci or by loss of mating-type determination of either the HD or the P/R locus. The ancestor to basidiomycete fungi is thought to have been tetrapolar, and many transitions to bipolarity have been described in different lineages. In the diverse genus Marasmius (Agaricales), both compatibility systems are found, and the system has been shown to follow the infrageneric sections of the genus, suggesting a single origin of bipolarity. Here, we tested this hypothesis using a comprehensive phylogenetic framework and investigated the mode by which bipolarity has evolved in this group. We utilized available genomic data and marker sequences to investigate evolution of sexual compatibility in Marasmius and allied genera. By generating a concatenated multilocus phylogeny, we found support for a single transition to known bipolarity within Marasmius. Furthermore, utilizing genomic data of the bipolar species Marasmius oreades, we found that the HD and P/R loci likely have remained unlinked through this transition. By comparing nucleotide diversity at the HD and P/R loci in Ma. oreades, we show that the HD locus has retained high diversity, and thus likely the function of determining sexual identity, as similarly in other bipolar mushroom-forming fungi. Finally, we describe the genomic architecture of the MAT loci of species of both sexual compatibility systems in Marasmiaceae and related families.

• Klíčová slova
• Homeodomain, MAT, mating system, mating type, mushroom, pheromone receptor,
• MeSH
• Agaricales genetika   klasifikace   MeSH
• biologická evoluce MeSH
• fungální geny pro párovací typ * genetika   MeSH
• fylogeneze * MeSH
• molekulární evoluce MeSH
• receptory pro feromony genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptory pro feromony MeSH

INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.

• Klíčová slova
• cortical bone trajectory, midline lumbar fusion, multifidus muscles, spinal fusion, spinal instability, spinal stabilisation,
• MeSH
• bederní obratle * chirurgie   diagnostické zobrazování   MeSH
• fúze páteře * metody   MeSH
• hluboké zádové svaly * diagnostické zobrazování   patologie   MeSH
• kortikální kost chirurgie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• pedikulární šrouby MeSH
• pooperační komplikace diagnostické zobrazování   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• spondylolistéza * chirurgie   diagnostické zobrazování   MeSH
• svalová atrofie * etiologie   diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH