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Grey Rhino is a metaphor for security threat, which is unkept irrational for large extent also high probability of harmful effect on a subject of risk owner. Business continuity management system is assessed in a diagram as controlling instrument aimed at operational hazard mitigation of continuity disturbance of affected subject. A ´from Operations´ Value Added – O´VA is established as qualitative dynamic information about productivity of activities. The measures are designed in crisis scenario for quality improvement of subject´s crisis readiness. An indicator of business risk continuity slip is defined. In a connection with war conflict on Ukraine is assessed if it is Grey Rhino manifestation.

Abstract Conditional addition of photons represents a crucial tool for optical quantum state engineering and it forms a fundamental building block of advanced quantum photonic devices. Here we report on experimental implementation of the conditional addition of several photons. We demonstrate the addition of one, two, and three photons to input coherent states with various amplitudes. The resulting highly nonclassical photon-added states are completely characterized with time-domain homodyne tomography, and the nonclassicality of the prepared states is witnessed by the negativity of their Wigner functions. We experimentally demonstrate that the conditional addition of photons realizes approximate noiseless quantum amplification of coherent states with sufficiently large amplitude. We also investigate certification of the stellar rank of the generated multiphoton-added coherent states, which quantifies the non-Gaussian resources required for their preparation. Our results pave the way towards the experimental realization of complex optical quantum operations based on combination of multiple photon additions and subtractions.

Abstract The developmental plasticity of the root system plays an essential role in the adaptation of plants to the environment. Among many other signals, auxin and its directional, intercellular transport are critical in regulating root growth and development. In particular, the PIN-FORMED2 (PIN2) auxin exporter acts as a key regulator of root gravitropic growth. Multiple regulators have been reported to be involved in PIN2-mediated root growth; however, our information remains incomplete. Here, we identified ROWY Bro1-domain proteins as important regulators of PIN2 sorting control. Genetic analysis revealed that Arabidopsis rowy1 single mutants and higher-order rowy1 rowy2 rowy3 triple mutants presented a wavy root growth phenotype. Cell biological experiments revealed that ROWY1 and PIN2 colocalized to the apical side of the plasma membrane in the root epidermis and that ROWYs are required for correct PM targeting of PIN2. In addition, ROWYs also affected PIN3 protein abundance in the stele, suggesting the potential involvement of additional PIN transporters as well as other proteins. A global transcriptome analysis revealed that ROWY genes are involved in the Fe2+ availability perception pathway. This work establishes ROWYs as important novel regulators of root gravitropic growth by connecting micronutrient availability to the proper subcellular targeting of PIN auxin transporters.

RNA capping is a prominent RNA modification that influences RNA stability, metabolism, and function. While it was long limited to the study of the most abundant eukaryotic canonical m7G cap, the field recently went through a large paradigm shift with the discovery of non-canonical RNA capping in bacteria and ultimately all domains of life. The repertoire of non-canonical caps has expanded to encompass metabolite caps, including NAD, FAD, CoA, UDP-Glucose, and ADP-ribose, alongside alarmone dinucleoside polyphosphate caps, and methylated phosphate cap-like structures. This review offers an introduction into the field, presenting a summary of the current knowledge about non-canonical RNA caps. We highlight the often still enigmatic biological roles of the caps together with their processing enzymes, focusing on the most recent discoveries. Furthermore, we present the methods used for the detection and analysis of these non-canonical RNA caps and thus provide an introduction into this dynamic new field.

Abstract This article presents a proposal for a new solution of tangential-rotary picks intended for mining, especially hard rocks with roadheaders. The design of these picks is characterized by many innovative solutions aimed at significantly increasing their service life. The method to achieve this goal is to provide effective central spraying of the ring tip picks, crown picks, or similar types of picks while using the spray water to cause the picks to rotate as they contact the rock being mined. An important element of the work is to conduct extensive simulation studies using FEM to determine the stress distribution in the pick shank subjected to external load from cutting. The new design of the tangential-rotary pick is equipped with a reinforcing sleeve, in which a state of compressive stress is induced. This enables a significant improvement in the fatigue strength of the pick shanks. The conducted FEM comparative tests confirm the accuracy of the adopted design assumptions. They also determine the beneficial value of the tension nut torque, which tightens the reinforcing sleeve located on the pick shank.

Abstract A key mechanism employed by plants to adapt to salinity stress involves maintaining ion homeostasis via the actions of ion transporters. While the function of cation transporters in maintaining ion homeostasis in plants has been extensively studied, little is known about the roles of their anion counterparts in this process. Here, we describe a mechanism of salt adaptation in plants. We characterized the chloride channel (CLC) gene AtCLCf, whose expression is regulated by WRKY transcription factor under salt stress in Arabidopsis thaliana. Loss-of-function atclcf seedlings show increased sensitivity to salt, whereas AtCLCf overexpression confers enhanced resistance to salt stress. Salt stress induces the translocation of GFP-AtCLCf fusion protein to the plasma membrane (PM). Blocking AtCLCf translocation using the exocytosis inhibitor brefeldin-A or mutating the small GTPase gene AtRABA1b/BEX5 (RAS GENES FROM RAT BRAINA1b homolog) increases salt sensitivity in plants. Electrophysiology and liposome-based assays confirm the Cl−/H+ antiport function of AtCLCf. Therefore, we have uncovered a mechanism of plant adaptation to salt stress involving the NaCl-induced translocation of AtCLCf to the PM, thus facilitating Cl− removal at the roots, and increasing the plant’s salinity tolerance.

Background & Aims: Tacrolimus has been associated with recurrence of primary biliary cholangitis (PBC) after liver transplantation (LT), which in turn may reduce survival. This study aimed to assess the association between the type of calcineurin inhibitor used and long-term outcomes following LT in patients with PBC. Methods: Survival analyses were used to assess the association between immunosuppressive drugs and graft or patient survival among adult patients with PBC in the European Liver Transplant Registry. Patients who received a donation after brain death graft between 1990 and 2021 with at least 1 year of event-free follow-up were included. Results: In total, 3,175 patients with PBC were followed for a median duration of 11.4 years (IQR 5.9–17.9) after LT. Tacrolimus (Tac) was registered in 2,056 (64.8%) and cyclosporin in 819 (25.8%) patients. Following adjustment for recipient age, recipient sex, donor age, and year of LT, Tac was not associated with higher risk of graft loss (adjusted hazard ratio [aHR] 1.07, 95% CI 0.92-1.25, p = 0.402) or death (aHR 1.06, 95% CI 0.90-1.24, p = 0.473) over cyclosporin. In this model, maintenance mycophenolate mofetil (MMF) was associated with a lower risk of graft loss (aHR 0.72, 95% CI 0.60-0.87, p

Abstract Phytoalexin sakuranetin functions in resistance against rice blast. However, the mechanisms underlying the effects of sakuranetin remains elusive. Here, we report that rice lines expressing resistance (R) genes were found to contain high levels of sakuranetin, which correlates with attenuated endocytic trafficking of plasma membrane (PM) proteins. Exogenous and endogenous sakuranetin attenuates the endocytosis of various PM proteins and the fungal effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, resulting from uptake into rice cells by Magnaporthe oryzae, was reduced following treatment with sakuranetin. Pharmacological manipulation of clathrin-mediated endocytic (CME) suggests that this pathway is targeted by sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey resistance against rice blast. Our data reveals a mechanism of rice against M. oryzae by increasing sakuranetin levels and repressing the CME of pathogen effectors, which is distinct from the action of many R genes that mainly function by modulating transcription.

Abstract Correlative light and electron microscopy (CLEM) is an important tool for the localisation of target molecule(s) and their spatial correlation with the ultrastructural map of subcellular features at the nanometre scale. Adoption of these advanced imaging methods has been limited in plant biology, due to challenges with plant tissue permeability, fluorescence labelling efficiency, indexing of features of interest throughout the complex 3D volume and their re-localization on micrographs of ultrathin cross-sections. Here, we demonstrate an imaging approach based on tissue processing and embedding into methacrylate resin followed by imaging of sections by both, single-molecule localization microscopy and transmission electron microscopy using consecutive CLEM and same-section CLEM correlative workflow. Importantly, we demonstrate that the use of a particular type of embedding resin is not only compatible with single-molecule localization microscopy but shows improvements in the fluorophore blinking behavior relative to the whole-mount approaches. Here, we use a commercially available Click-iT ethynyl-deoxyuridine cell proliferation kit to visualize the DNA replication sites of wild-type Arabidopsis thaliana seedlings, as well as fasciata1 and nucleolin1 plants and apply our in-section CLEM imaging workflow for the analysis of S-phase progression and nucleolar organization in mutant plants with aberrant nucleolar phenotypes.

The pandemic has had a significant impact on many aspects of students’ lives, including their lifestyles. This article presents findings from a quantitative survey conducted among 381 university students which aimed to evaluate the effects of COVID-19 lockdowns on the students’ lifestyle choices and examine the relationships between age, gender and related lifestyle characteristics. The results indicated notable changes in university students’ daily routines during the pandemic with heightened engagement in digital activities such as social networking, movie and series watching, and gaming. Their appetites and alcohol consumption increased. Some students experienced physical and psychological exhaustion, loneliness, depression and sleep problems. The research results showed relationships between age and regular engagement in sports, social media usage, movie and series watching, gaming, weight loss, and feelings of loneliness and depression. Despite students’ concerns about being socially isolated, support from their families helped them cope with the challenges brought about by the pandemic. A crucial finding is that most students reported being satisfied with the shift to distance learning, confirming that it could be a viable alternative for education. Enhanced understanding of these relationships is vital for higher education institutions to be able to improve students’ learning satisfaction, well-being and academic performance.

Introduction Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.Methods and analysis The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age

The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in gn knockouts. The functional GN mutant variant GNfewerroots, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.

Abstract Background Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after the original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia, and activation of T cells with elevated IFN-γ. Observing the production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II, and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. Results We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the pre-IVIG presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. Conclusions Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF. Graphical Abstract

Abstract Obesity adversely affects bone and fat metabolism in mice and humans. Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have been shown to improve glucose metabolism and bone homeostasis in obesity. However, the impact of omega-3 PUFAs on bone marrow adipose tissue (BMAT) and bone marrow stromal cell (BMSC) metabolism has not been intensively studied yet. In the present study we demonstrated that omega-3 PUFA supplementation in high fat diet (HFD + F) improved bone parameters, mechanical properties along with decreased BMAT in obese mice when compared to the HFD group. Primary BMSCs isolated from HFD + F mice showed decreased adipocyte and higher osteoblast differentiation with lower senescent phenotype along with decreased osteoclast formation suggesting improved bone marrow microenvironment promoting bone formation in mice. Thus, our study highlights the beneficial effects of omega-3 PUFA-enriched diet on bone and cellular metabolism and its potential use in the treatment of metabolic bone diseases.

Background: Autologous vein grafts are widely used for bypass procedures in cardiovascular surgery. However, these grafts are susceptible to failure due to vein graft disease. Our study aimed to evaluate the impact of the latest-generation FRAME external support on vein graft remodeling in a preclinical model. Methods: We performed autologous internal jugular vein interposition grafting in porcine carotid arteries for one month. Four grafts were supported with a FRAME mesh, while seven unsupported grafts served as controls. The conduits were examined through flowmetry, angiography, macroscopy, and microscopy. Results: The one-month patency rate of FRAME-supported grafts was 100% (4/4), whereas that of unsupported controls was 43% (3/7, Log-rank p = 0.071). On explant angiography, FRAME grafts exhibited significantly more areas with no or mild stenosis (9/12) compared to control grafts (3/21, p = 0.0009). Blood flow at explantation was higher in the FRAME grafts (145 ± 51 mL/min) than in the controls (46 ± 85 mL/min, p = 0.066). Area and thickness of neo-intimal hyperplasia (NIH) at proximal anastomoses were similar for the FRAME and the control groups: 5.79 ± 1.38 versus 6.94 ± 1.10 mm2, respectively (p = 0.558) and 480 ± 95 vs. 587 ± 52 μm2/μm, respectively (p = 0.401). However, in the midgraft portions, the NIH area and thickness were significantly lower in the FRAME group than in the control group: 3.73 ± 0.64 vs. 6.27 ± 0.64 mm2, respectively (p = 0.022) and 258 ± 49 vs. 518 ± 36 μm2/μm, respectively (p = 0.0002). Conclusions: In our porcine model, the external mesh FRAME improved the patency of vein-to-carotid artery grafts and protected them from stenosis, particularly in the mid regions. The midgraft neo-intimal hyperplasia was two-fold thinner in the meshed grafts than in the controls.

Abstract Dermanyssus gallinae is a blood-feeding mite that parasitises wild birds and farmed poultry. Its remarkably swift processing of blood, together with the capacity to blood-feed during most developmental stages, makes this mite a highly debilitating pest. To identify specific adaptations to digestion of a haemoglobin-rich diet, we constructed and compared transcriptomes from starved and blood-fed stages of the parasite and identified midgut-enriched transcripts. We noted that midgut transcripts encoding cysteine proteases were upregulated with a blood meal. Mapping the full proteolytic apparatus, we noted a reduction in the suite of cysteine proteases, missing homologues for Cathepsin B and C. We have further identified and phylogenetically analysed three distinct transcripts encoding vitellogenins that facilitate the reproductive capacity of the mites. We also fully mapped transcripts for haem biosynthesis and the ferritin-based system of iron storage and inter-tissue trafficking. Additionally, we identified transcripts encoding proteins implicated in immune signalling (Toll and IMD pathways) and activity (defensins and thioester-containing proteins), RNAi, and ion channelling (with targets for commercial acaricides such as Fluralaner, Fipronil, and Ivermectin). Viral sequences were filtered from the Illumina reads and we described, in part, the RNA-virome of D. gallinae with identification of a novel virus, Red mite quaranjavirus 1.

Introduction The English Diabetic Eye Screening Programme (DESP) offers people living with diabetes (PLD) annual eye screening. We examined incidence and determinants of sight-threatening diabetic retinopathy (STDR) in a sociodemographically diverse multi-ethnic population.Research design and methods North East London DESP cohort data (January 2012 to December 2021) with 137 591 PLD with no retinopathy, or non-STDR at baseline in one/both eyes, were used to calculate STDR incidence rates by sociodemographic factors, diabetes type, and duration. HR from Cox models examined associations with STDR.Results There were 16 388 incident STDR cases over a median of 5.4 years (IQR 2.8–8.2; STDR rate 2.214, 95% CI 2.214 to 2.215 per 100 person-years). People with no retinopathy at baseline had a lower risk of sight-threatening diabetic retinopathy (STDR) compared with those with non-STDR in one eye (HR 3.03, 95% CI 2.91 to 3.15, p

Introduction The English National Health Service (NHS) Diabetic Eye Screening Programme (DESP) performs around 2.3 million eye screening appointments annually, generating approximately 13 million retinal images that are graded by humans for the presence or severity of diabetic retinopathy. Previous research has shown that automated retinal image analysis systems, including artificial intelligence (AI), can identify images with no disease from those with diabetic retinopathy as safely and effectively as human graders, and could significantly reduce the workload for human graders. Some algorithms can also determine the level of severity of the retinopathy with similar performance to humans. There is a need to examine perceptions and concerns surrounding AI-assisted eye-screening among people living with diabetes and NHS staff, if AI was to be introduced into the DESP, to identify factors that may influence acceptance of this technology.Methods and analysis People living with diabetes and staff from the North East London (NEL) NHS DESP were invited to participate in two respective focus groups to codesign two online surveys exploring their perceptions and concerns around the potential introduction of AI-assisted screening.Focus group participants were representative of the local population in terms of ages and ethnicity. Participants’ feedback was taken into consideration to update surveys which were circulated for further feedback. Surveys will be piloted at the NEL DESP and followed by semistructured interviews to assess accessibility, usability and to validate the surveys.Validated surveys will be distributed by other NHS DESP sites, and also via patient groups on social media, relevant charities and the British Association of Retinal Screeners. Post-survey evaluative interviews will be undertaken among those who consent to participate in further research.Ethics and dissemination Ethical approval has been obtained by the NHS Research Ethics Committee (IRAS ID: 316631). Survey results will be shared and discussed with focus groups to facilitate preparation of findings for publication and to inform codesign of outreach activities to address concerns and perceptions identified.

Abstract Soft tissue sample thickness measurement is one of the major sources of differences between mechanical responses published by different groups. New method for the estimation of unloaded sample thickness of soft tissues is proposed in this study. Ten 30 × 30 mm and ten 20 × 20 mm samples of porcine anterior thoracic aortas were loaded by gradually increased radial force. Their deformed thickness was then recorded in order to generate a pressure-thickness response. Next, the limit pressure to which the response can be considered linear was estimated. Line was fitted to the linear part of the curve and extrapolated towards zero pressure to estimate unloaded thickness (7 kPa fit). For comparison, data near zero pressure were fitted separately and extrapolated towards zero (Near Zero fit). The limit pressure for the linearity of the response was around 7 kPa. The Unloaded thickness for 30 × 30 mm samples was 2.68 ± 0.31 mm and 2.68 ± 0.3 mm for Near Zero fit and 7 kPa fit, respectively. The Unloaded thickness for 20 × 20 mm samples was 2.60 ± 0.35 mm and 2.59 ± 0.35 mm for Near Zero fit and 7 kPa fit, respectively. The median of thickness difference between smaller and larger samples was not found statistically different. Proposed method can estimate unloaded undeformed sample thickness quickly and reliably.

In mining machines with friction discs, but also in multi-rope traction elevators, it is necessary to distribute the applied tensile load, generated by the weight of the cage and counterweight, evenly in all cross-sections of the load-bearing ropes. Hydraulic devices used for this purpose can operate on the principle of Pascal’s law. This article presents a structural design, a 3D model and an implemented solution of a laboratory device capable of simulating a practical method of evenly distributing the total weight of the load into partial tensile forces of the same size acting on a selected number of load-bearing ropes. The laboratory equipment uses two pairs of three steel cables of finite length for the simulations. During the experimental measurements, tensile forces derived from the tractive force of the piston rods, pushed into the bodies of the hydraulic cylinders by the pressure of the hydraulic oil supplied through the pipeline under the pistons of the hydraulic cylinders, were detected. The resulting amount of hydraulic oil pressure in the hydraulic circuit influenced by different values of the hydraulic oil pressures in the hydraulic cylinders and by the pressure in the supply pipe was experimentally studied on the laboratory equipment. Simulations were also carried out in order to detect the hydraulic oil pressure in the hydraulic circuit caused by the change in the different magnitudes of the tensile forces in the ropes. From the experiments carried out, it follows that with the appropriate choice of hydraulic elements and the design of the hydraulic circuit, the weight of the load, acting as the total pulling force in the ropes, can be evenly distributed (with a deviation of up to 5%) to all cross-sections of the load-bearing ropes. If the exact values of the hydraulic oil volumes under the pistons of all hydraulic cylinders are not known, it is not possible to calculate the pressure values in the hydraulic circuit when the valves of the hydraulic pipes are gradually opened.

The current repertoire of methods available for studying RNA-protein interactions in plants is somewhat limited. Employing an RNA-centric approach, particularly with less abundant RNAs, presents various challenges. Many of the existing methods were initially designed for different model systems, with their application in plants receiving limited attention thus far. The Comprehensive Identification of RNA-Binding Proteins by Mass Spectrometry (ChIRP-MS) technique, initially developed for mammalian cells, has been adapted in this study for application in Arabidopsis thaliana. The procedures have been meticulously modified and optimized for telomerase RNA, a notable example of a low-abundance RNA recently identified. Following these optimization steps, ChIRP-MS can serve as an effective screening method for identifying candidate proteins interacting with any target RNA of interest.

This paper describes dispersed cryptospores and trilete spores from tropical, temperate and cool climate belts within Přídolí and compares them with the land plant megafossil record. The palynology of earlier intervals in the Silurian are also reviewed. A common feature of the cryptospore and trilete spore records is that their number is surprisingly lowest in the tropical climatic belt and much higher in the temperate and especially in the cool latitude, and the highest number of cryptospore taxa occurring only in one belt is found in the cool belt while the highest number of trilete spore taxa that occurred only in one belt is recorded in the temperate belt. In general, based on the dispersed spore record, we can estimate that the plant assemblages of the tropical belt were dominated by rhyniophytes; trimerophytes probably prevailed over rhyniophytes in the temperate belt, and rhyniophytes again dominated within the cool belt.

An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration. Patient summary: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps.

Summary: While the pivotal role of linker histone H1 in shaping nucleosome organization is well established, its functional interplays with chromatin factors along the epigenome are just starting to emerge. Here we show that, in Arabidopsis, as in mammals, H1 occupies Polycomb Repressive Complex 2 (PRC2) target genes where it favors chromatin condensation and H3K27me3 deposition. We further show that, contrasting with its conserved function in PRC2 activation at genes, H1 selectively prevents H3K27me3 accumulation at telomeres and large pericentromeric interstitial telomeric repeat (ITR) domains by restricting DNA accessibility to Telomere Repeat Binding (TRB) proteins, a group of H1-related Myb factors mediating PRC2 cis recruitment. This study provides a mechanistic framework by which H1 avoids the formation of gigantic H3K27me3-rich domains at telomeric sequences and contributes to safeguard nucleus architecture.

The article focuses on the relationship between the use of employee training and development and the competency-based approach. The objective of this article is to evaluate the use of the competency-based approach in employee training and development in organisations in the Czech Republic based on long-term research (n = 1,360) since the year 2013. The results showed that the competency-based approach in the management of organisations is utilized by only 21.8% of the organisations. An important finding is that 93.2% of organisations using the competency-based approach support employee training and development. The results confirmed that there is the relationship between the use of the competency-based approach and training and development in the organisation (p < 0.001, Cramer’s V = 0.178) and also between the use of the competency-based approach and evaluation of training and development efficiency in the organisation (p < 0.001, Cramer’s V = 0.299).

In most flowering plants, a single megaspore mother cell (MMC) is formed in each ovule. Here the authors show that miR160 and the auxin response factor ARF17 act to promote MMC fate via SPL/NZZ and control auxin signaling to prevent somatic cells from acquiring MMC fate.

Directionality of auxin transport is determined by polar localization of PIN-FORMED (PIN) proteins. Here the authors show that Arabidopsis WAV3 E3 ubiquitin ligases contribute to PIN polarity by selectively antagonizing ectopic deposition of de novo synthesized PIN proteins following cell division.

Abstract Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th–April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017–2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017–2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Kernel Tuning Toolkit (KTT) is an autotuning framework for CUDA, OpenCL and Vulkan kernels. KTT provides advanced autotuning features such as support for both dynamic (online) and offline tuning, and an ability to tune multiple kernels together with shared tuning parameters. Furthermore, it offers customization features that make integration into larger software suites possible. The framework handles all major steps required for autotuning implementation, including configuration space creation and exploration, kernel code execution and output validation. The public API is available natively in C++ and via bindings in Python.

The ability for plant regeneration from dedifferentiated cells opens up the possibility for molecular bioengineering to produce crops with desirable traits. Developmental and environmental signals that control cell totipotency are regulated by gene expression via dynamic chromatin remodeling. Using a mass spectrometry-based approach, we investigated epigenetic changes to the histone proteins during callus formation from roots and shoots of Arabidopsis thaliana seedlings. Increased levels of the histone H3.3 variant were found to be the major and most prominent feature of 20-day calli, associated with chromatin relaxation. The methylation status in root- and shoot-derived calli reached the same level during long-term propagation, whereas differences in acetylation levels provided a long-lasting imprint of root and shoot origin. On the other hand, epigenetic signs of origin completely disappeared during 20 days of calli propagation in the presence of histone deacetylase inhibitors (HDACi), sodium butyrate, and trichostatin A. Each HDACi affected the state of post-translational histone modifications in a specific manner; NaB-treated calli were epigenetically more similar to root-derived calli, and TSA-treated calli resembled shoot-derived calli.

Objective: Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy. Methods: We used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity. Results: Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly. Conclusions: Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.

Abstract Electrical discharge machining (EDM) is an unconventional machining technology. It allows machining of at least at least electrically conductive materials. The trend of miniaturization of industrial products is obvious. However, the required quality and accuracy must be maintained, which can be achieved with micro-EDM. One of the industrial products is also optical devices used for testing cars. These contain miniaturized parts, which are, however, necessary for their proper functioning. For this reason, this study was performed, which focused on the production of a precise slot measuring 5000 × 170 µm in a copper foil with a thickness of 125 µm. The same copper foil was used as a tool, which represents an advance in the production of micro-parts.The use of the same semi-product for the production of the slit as well as the tool itself has not yet been presented in any similar study. A design of experiment Box and Behnken Response Surface Design was performed for a total of 15 rounds, monitoring the effect of machine setting parameters (Pulse current, Pulse on time and Voltage) on responses in the form of Erosion rate, corner radius, slot length and width. Using multi-criteria optimization, the optimal setting of the machine parameters for the production of a given slit was determined, which is Pulse current = 2.1 A, Pulse on time = 40 µs and Voltage = 238.8 V. Micro-EDM technology has been found to be suitable for the production of miniaturized slits.

BackgroundCastleman´s disease is an extremely rare heterogenous lymphoproliferative pathology with a mostly benign behavior. It is a localized or generalized lymph node enlargement of an unknown aetiology. Unicentric form is typically a slow-growing solitary mass occurring mostly in the mediastinum, abdominal cavity, retroperitoneum, pelvis and neck. Aetiology and pathogenesis of CD is probably diverse, varying in different types of this heterogeneous disease.Materials and MethodsAuthors present a review of this issue based on their extensive experience. The aim is to summarize the crucial factors in the management of diagnostics and a surgical treatment of the unicentric form of Castleman´s disease. One of the key issues in the unicentric form is precise preoperative diagnostics and thus choosing the right surgical treatment strategy. Authors highlight pitfalls of the diagnosis and surgical treatment.ResultsAll histological types such as a hyaline vascular type, plasmacytic type and a mixed type are presented as well as options of surgical and conservative treatment. Differential diagnosis and malignant potential is discussed.ConclusionPatients with Castleman´s disease should be treated in the high- volume centers, with a great experience in major surgical procedures as well as with preoperative imaging diagnostic techniques. Specialized pathologists and oncologists focusing on this issue are also absolutely necessary to avoid misdiagnosis. Only this complex approach can lead to excellent outcomes in patients with UCD.

Aim. To non-invasively identify the hemodynamic changes in critically ill children during the first 48 h following initiation of mechanical ventilation by the ultrasound cardiac output monitor (USCOM) method and compare the data in children with pulmonary and non-pulmonary pathology. Materials and Methods. This was a prospective observational study to evaluate the influence of mechanical ventilation on hemodynamic changes and to describe hemodynamic profiles of mechanically ventilated children. A total of 56 children with respiratory failure were included in the present study. Ventilated patients are divided into two groups. Group A (n=36) includes patients with pulmonary pathology. Group B (n=20) consists of patients with extra pulmonary etiology of respiratory failure. Hemodynamic parameters (cardiac index and systemic vascular resistance index) were evaluated using ultrasound cardiac output monitoring (USCOM 1A) immediately following initiation of mechanical ventilation and again at 6, 12, and 48 h. Pharmacological circulatory support (inotropes, vasopressors, levosimendan and phosphodiesterase III inhibitors) was individually and continuously modified based on real-time hemodynamic parameters and optimal fluid balance. Results. No significant differences in hemodynamic profiles were found between Group A and Group B. Conclusion. The protective strategy of mechanical ventilation was not associated with significant differences in hemodynamic profiles between children ventilated for pulmonary and non-pulmonary pathologies. Clinical Significance. Hemodynamically unstable children ventilated for pulmonary pathology with the protective strategy of mechanical ventilation had a greater requirement for inotropic and combined inotropic and vasoactive circulatory support than children ventilated for non-pulmonary causes of respiratory failure.

Structural biology has evolved greatly due to the advances introduced in fields like electron microscopy. This image-capturing technique, combined with improved algorithms and current data processing software, allows the recovery of different conformational states of a macromolecule, opening new possibilities for the study of its flexibility and dynamic events. However, the ensemble analysis of these different conformations, and in particular their placement into a common variable space in which the differences and similarities can be easily recognized, is not an easy matter. To simplify the analysis of continuous heterogeneity data, this work proposes a new automatic algorithm that relies on a mathematical basis defined over the sphere to estimate the deformation fields describing conformational transitions among different structures. Thanks to the approximation of these deformation fields, it is possible to describe the forces acting on the molecules due to the presence of different motions. It is also possible to represent and compare several structures in a low-dimensional mapping, which summarizes the structural characteristics of different states. All these analyses are integrated into a common framework, providing the user with the ability to combine them seamlessly. In addition, this new approach is a significant step forward compared with principal component analysis and normal mode analysis of cryo-electron microscopy maps, avoiding the need to select components or modes and producing localized analysis.

Objective: The use of thiazolidinediones (TZDs) as insulin sensitizers has been shown to have side effects including increased accumulation of bone marrow adipocytes (BMAds) associated with a higher fracture risk and bone loss. A novel TZD analog MSDC-0602K with low affinity to PPARγ has been developed to reduce adverse effects of TZD therapy. However, the effect of MSDC-0602K on bone phenotype and bone marrow mesenchymal stem cells (BM-MSCs) in relation to obesity has not been intensively studied yet. Methods: Here, we investigated whether 8-week treatment with MSDC-0602K has a less detrimental effect on bone loss and BM-MSC properties in obese mice in comparison to first generation of TZDs, pioglitazone. Bone parameters (bone microstructure, bone marrow adiposity, bone strength) were examined by μCT and 3-point bending test. Primary BM-MSCs were isolated and measured for osteoblast and adipocyte differentiation. Cellular senescence, bioenergetic profiling, nutrient consumption and insulin signaling were also determined. Results: The findings demonstrate that MSDC-0602K improved bone parameters along with increased proportion of smaller BMAds in tibia of obese mice when compared to pioglitazone. Further, primary BM-MSCs isolated from treated mice and human BM-MSCs revealed decreased adipocyte and higher osteoblast differentiation accompanied with less inflammatory and senescent phenotype induced by MSDC-0602K vs. pioglitazone. These changes were further reflected by increased glycolytic activity differently affecting glutamine and glucose cellular metabolism in MSDC-0602K-treated cells compared to pioglitazone, associated with higher osteogenesis. Conclusion: Our study provides novel insights into the action of MSDC-0602K in obese mice, characterized by the absence of detrimental effects on bone quality and BM-MSC metabolism when compared to classical TZDs and thus suggesting a potential therapeutical use of MSDC-0602K in both metabolic and bone diseases.

The article discusses the interaction of metabolic products of a wood-destroying fungus of the dry rot species (Serpula lacrymans (Wulfen) P. Karst.) with a commonly used lime mortar. Mortar samples used in the presented experiment were made mostly in laboratory conditions so as to make it possible to set input conditions and to determine initial properties of the examined samples. Matured lime mortar samples were placed in cultivation boxes with a growth of Serpula lacrymans and exposed to its action for a predetermined period of time. For a comparison, mortar samples taken “in situ” from real structures were also subjected to the experiment. The examined samples were subjected to a thermal analysis and a comparative measurement by infrared spectroscopy (FTIR). The results of the measurement of infected samples were compared with the results obtained in the reference (control) samples. The experiment carried out was focused on assessing the presence of calcium oxalate, which is secreted into the surroundings of the mycelium during the active growing of Serpula lacrymans.

The paper presents the measured values of tensile forces acting on transmission idlers in the upper and lower run of a conveyor belt placed on a laboratory machine designed at the Department of Machine and Industrial Design, Faculty of Mechanical Engineering, VSB-Technical University of Ostrava. The tensile forces detected by two strain gauge load cells and recorded using DEWESoft software were used to calculate the friction coefficient, which acts on the surface of the driving drum casing and the conveyor belt. The friction coefficient at the slip point, or during the slippage of the conveyor belt on the rubber or steel casing of the driving drum, was determined for two states of the surfaces that are in contact. Experimental measurements on a laboratory machine determined four values of friction coefficients for two types of drum surfaces and for two states of contact surfaces, which were compared with the recommended standard values. The measured values reached higher values in comparison with the values given by the CSN standards. The highest deviation of 273.3% is achieved using a steel wet surface, and the lowest deviation of 106.3% is achieved when using a rubber dry lining for the driving drum casing. On the presented laboratory machine, it is possible to measure tensile forces for different speeds of movement, different belt angles on the driving drum, various types of belt surfaces, different types of drum casing linings, and different sizes of tension forces for the endless loop of the conveyor belt. For these characteristics of the conveyor belt, the magnitude of the friction coefficient acting between the belt and the drum surfaces can be determined.

Abstract Altered copy number of certain highly repetitive regions of the genome, such as satellite DNA within heterochromatin and ribosomal RNA loci (rDNA), is hypothesized to help safeguard the genome against damage derived from external stressors. We quantified copy number of the 18S rDNA and a pericentromeric satellite DNA (Msat‐160) in bank voles (Myodes glareolus) inhabiting the Chernobyl Exclusion Zone (CEZ), an area that is contaminated by radionuclides and where organisms are exposed to elevated levels of ionizing radiation. We found a significant increase in 18S rDNA and Msat‐160 content in the genomes of bank voles from contaminated locations within the CEZ compared with animals from uncontaminated locations. Moreover, 18S rDNA and Msat‐160 copy number were positively correlated in the genomes of bank voles from uncontaminated, but not in the genomes of animals inhabiting contaminated, areas. These results show the capacity for local‐scale geographic variation in genome architecture and are consistent with the genomic safeguard hypothesis. Disruption of cellular processes related to genomic stability appears to be a hallmark effect in bank voles inhabiting areas contaminated by radionuclides.

Abstract Telomerase RNA (TR) carries the template for synthesis of telomere DNA and provides a scaffold for telomerase assembly. Fungal TRs are long and have been compared to higher eukaryotes, where they show considerable diversity within phylogenetically close groups. TRs of several Saccharomycetaceae were recently identified, however, many of these remained uncharacterised in the template region. Here we show that this is mainly due to high variability in telomere sequence. We predicted the telomere sequences using Tandem Repeats Finder and then we identified corresponding putative template regions in TR candidates. Remarkably long telomere units and the corresponding putative TRs were found in Tetrapisispora species. Notably, variable lengths of the annealing sequence of the template region (1–10 nt) were found. Consequently, species with the same telomere sequence may not harbour identical TR templates. Thus, TR sequence alone can be used to predict a template region and telomere sequence, but not to determine these exactly. A conserved feature of telomere sequences, tracts of adjacent Gs, led us to test the propensity of individual telomere sequences to form G4. The results show highly diverse values of G4-propensity, indicating the lack of ubiquitous conservation of this feature across Saccharomycetaceae.

Objective: Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing. Methods: In this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference. Results: ATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below. Conclusion: Our results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure.

Při archeologickém výzkumu hradu vBrandýse nad Orlicí byla objevena polovina skládacích slunečních hodin archeologizovaná někdy v první polovině 16. století. Hodiny byly vyrobeny v Norimberku rodinou Tucherů.