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Abstract Deposition of monosodium urate and calcium pyrophosphate (MSU and CPP) micro-crystals is responsible for painful and recurrent inflammation flares in gout and chondrocalcinosis. In these pathologies, the inflammatory reactions are due to the activation of macrophages responsible for releasing various cytokines including IL-1β. The maturation of IL-1β is mediated by the multiprotein NLRP3 inflammasome. Here, we find that activation of the NLRP3 inflammasome by crystals and concomitant production of IL-1β depend on cell volume regulation via activation of the osmo-sensitive LRRC8 anion channels. Both pharmacological inhibition and genetic silencing of LRRC8 abolish NLRP3 inflammasome activation by crystals in vitro and in mouse models of crystal-induced inflammation. Activation of LRRC8 upon MSU/CPP crystal exposure induces ATP release, P2Y receptor activation and intracellular calcium increase necessary for NLRP3 inflammasome activation and IL-1β maturation. We identify a function of the LRRC8 osmo-sensitive anion channels with pathophysiological relevance in the context of joint crystal-induced inflammation.

CRISPR/Cas9 is the most popular genome editing platform for investigating gene function or improving traits in plants. The specificity of gene editing has yet to be evaluated at a genome-wide scale in seed-propagated Camelina sativa (L.) Crantz (camelina) or clonally propagated Solanum tuberosum L. (potato). In this study, seven potato and nine camelina stable transgenic Cas9-edited plants were evaluated for on and off-target editing outcomes using 55x and 60x coverage whole genome shotgun sequencing data, respectively. For both potato and camelina, a prevalence of mosaic somatic edits from constitutive Cas9 expression was discovered as well as evidence of transgenerational editing in camelina. CRISPR/Cas9 editing provided negligible off-target activity compared to background variation in both species. The results from this study guide deployment and risk assessment of genome editing in commercially relevant traits in food crops.

Background: Gonadal vein thrombosis (GVT) is an uncommon condition that has been associated with different risk factors (e.g., post-partum period, cancer, recent pelvic surgery, etc.). The optimal management of GVT remains unclear. We sought to assess the efficacy and safety of anticoagulation therapy in adult patients with GVT. Methods: A systematic search of MEDLINE, EMBASE and PubMed, from inception to February 2023 was performed. The primary efficacy outcome was recurrent venous thromboembolism (VTE). Bleeding outcomes were assessed in the form of major and clinically relevant non-major bleeding (CRNMB) events. Incidence rates of the outcomes were pooled using the random effects model and expressed as event per 100 patient-years with its associated 95 % confidence intervals (CI) using R software. Results: A total of 14 observational studies and one randomized controlled trial (1134 patients) with GVT met the inclusion criteria and were included in the review. Overall, 429 (37.8 %) patients were treated with anticoagulation. The rate of recurrent VTE was 3.1 per 100 patient-years (95 % CI, 1.6–6.3). The rate of major bleeding and CRNMB events were 1.0 (95 % CI; 0.2–4.5) and 9.9 (95 % CI; 2.6–37.8) per 100 patient-years, respectively. Conclusion: Gonadal vein thrombosis seems to be associated with a relatively low risk of recurrent VTE and bleeding complications. The risk benefit ratio of anticoagulant therapy remains unclear in this patient population.

Abstract Saturn Kilometric Radiation (SKR), being the dominant radio emission at Saturn, has been extensively investigated. The low‐frequency extension of SKR is of particular interest due to its strong association with Saturn's magnetospheric dynamics. However, the highly anisotropic beaming of SKR poses challenges for observations. In most cases, the propagation of SKR is assumed to follow straight‐line paths. We explore the propagation characteristics of SKR across different frequencies in this study. An extended equatorial shadow region for low‐frequency SKR is identified, resulting from the merging of the Enceladus plasma torus and the previously known equatorial shadow zone. Ray‐tracing simulations reveal that low‐frequency (≲100 kHz) SKR is unable to enter the shadow region and is instead reflected toward high latitudes. In contrast, high‐frequency SKR (≳100 kHz) generally propagates without hindrance. Observations suggest that some low‐frequency SKR can enter the shadow region through reflection by the magnetosheath or leakage from the plasma torus.

Background & Aims: Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs. lenvatinib in a large, multicenter real-world population. Methods: This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared. Results: In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib (p = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib (p = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort (p = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months. Conclusions: Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib. Impact and implications: The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib.

Introduction Verbal fluency, a cognitive function that reflects executive functions and the rapid retrieval of pertinent information from memory, has yielded inconsistent findings in previous research on autism spectrum disorder (ASD), however in schizophrenia (SCH) semantic fluency exhibits a more pronounced impairment compared to letter fluency. Objectives In this study we aim to comprehensively investigate verbal fluency in ASD, SCH, and neurotypical healthy control individuals (NTP). The primary objective is to investigate disparities in novel response generation, specifically between the ASD, SCH and NTP groups, using phonemic and semantic fluency tasks. Three central inquiries guide our research: (1) whether differences between groups (ASD, SCH, and NTP) can be identified in word productivity, clustering, errors, and perseverations; (2) whether participants with ASD and SCH exhibit different word production with elevated imageability and concreteness values; and (3) if individuals with ASD and schizophrenia demonstrate reduced productivity during the earlier phases of fluency tasks. Methods Forty participants with ASD (12 female, 24 male, 4 other, mean age: 30.5), 39 with SCH (10 female, 28 male, 1 other, mean age: 34.7) and 41 NTP (13 female, 28 male, mean age: 31.0) were recruited from the outpatient units of the Department of Psychiatry and Psychotherapy, Semmelweis University. Participants were requested to list as many words as they could on two phonemic and two semantic category conditions. Audio recordings were later transcribed. To assess concreteness and imageability, we employed a seven-point scale and recruited independent external raters to evaluate a total of 1481 words. Results Preliminary results indicate that the three study groups did not differ significantly in phonemic fluency (F(2, 119)= 0.983, p=0.377), during either time period. However, a significant difference was observed in semantic fluency (F(2, 119)= 6.531, p=0.002). Post-hoc tests (Tukey corrected) revealed that this difference stemmed from impaired performance in the SCH group. Participants with schizophrenia (SCH) exhibited reduced semantic word productivity compared to both neurotypical (NTP) individuals and participants with ASD (Figure 1). However, there were no significant differences between participants with ASD and NTP individuals. Image: Conclusions In conclusion, our study investigated the characteristics of verbal fluency in a transdiagnostic approach. While phonemic fluency did not reveal significant differences among the three groups, our analysis of semantic fluency unveiled a distinction. Specifically, individuals with schizophrenia exhibited impaired semantic word productivity. Our study highlights the complex nature of verbal fluency impairments in different conditions and the importance of considering more nuanced methods when assessing cognitive functions. Disclosure of Interest None Declared

The utilization of stem cells in tissue engineering holds great promise as efficient tools for tissue regeneration and in treating numerous musculoskeletal diseases. However, several limiting factors, such as precise delivery and control of differentiation of these stem cells as well as mimicking the microenvironment required to modulate stem cell behaviour in-vivo, have given rise to an urgent need for the development of new biomaterials which could be tailored to enhance cell renewal and/or direct cell fates. Keratin-rich biological materials offer several advantages, such as biocompatibility, tailorable mechanical properties, huge bioavailability, non-toxicity, non-immunogenic, and intrinsic tissue repair and/or regeneration capabilities, which makes them highly valued. In the present work, we report the preparation of keratin-based bio-materials from goat hair waste and its effectiveness as a coating material for in vitro culture and induced differentiation of mesenchymal stem cells (MSC's) and primary goat fibroblast cells. Since no known keratinase enzymes are expressed as such in human and/or animal systems, these keratin biomaterials could be used to slow the rate of degradation and deliver keratin-loaded stem cell scaffolds to induce their directed differentiation in vivo. The generated keratin materials have been characterized for surface morphology, protein structures, size and other properties using SDS-PAGE, LC/MS-MS, SEM, FTIR etc. Also, in vitro cell culture assays such as cell adhesion, viability using MTT, live dead assays, differentiation assays and in vitro scratch/wound healing assays were performed. Our results provide important data supporting tissue engineering applications of these keratinous biomaterials by combining the unique biological characteristics of goat hair-derived keratin material with the regenerative power of stem cells and their combinatorial use in applications such as disease treatment and injury repair as well as their use in the preparation of wound healing products, such as dressings and bandages, for management of clinical care in animals.

Abstract Background Gestational Trophoblastic Neoplasia (GTN) is a disease of the reproductive age group with an incidence rate of

Abstract Radio detection at high time-frequency resolutions is a powerful means of remotely studying electron acceleration processes. Radio bursts have characteristics (polarization, drift, periodicity) making them easier to detect than slowly variable emissions. They are not uncommon in solar system planetary magnetospheres, the powerful Jovian “short bursts (S-bursts)" induced by the Io-Jupiter interaction being especially well-documented. Here we present a detection method of drifting radio bursts in terabytes of high resolution time-frequency data, applied to one month of ground-based Jupiter observations. Beyond the expected Io-Jupiter S-bursts, we find decameter S-bursts related to the Ganymede-Jupiter interaction and the main Jovian aurora, revealing ubiquitous Alfvénic electron acceleration in Jupiter’s high-latitude regions. Our observations show accelerated electron energies are distributed in two populations, kilo-electron-Volts and hundreds of electron-Volts. This detection technique may help characterizing inaccessible astrophysical sources such as exoplanets.

Objectives: SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected. Methods: We periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance. Results: Among the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two. Conclusion: Three BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.

Before the commercialization of genetically modified crops, the events carrying the novel DNA must be thoroughly evaluated for agronomic, nutritional, and molecular characteristics. Over the years, polymerase chain reaction-based methods, Southern blot, and short-read sequencing techniques have been utilized for collecting molecular characterization data. Multiple genomic applications are necessary to determine the insert location, flanking sequence analysis, characterization of the inserted DNA, and determination of any interruption of native genes. These techniques are time-consuming and labor-intensive, making it difficult to characterize multiple events. Current advances in sequencing technologies are enabling whole-genomic sequencing of modified crops to obtain full molecular characterization. However, in polyploids, such as the tetraploid potato, it is a challenge to obtain whole-genomic sequencing coverage that meets the regulatory approval of the genetic modification. Here we describe an alternative to labor-intensive applications with a novel procedure using Samplix Xdrop® enrichment technology and next-generation Nanopore sequencing technology to more efficiently characterize the T-DNA insertions of four genetically modified potato events developed by the Feed the Future Global Biotech Potato Partnership: DIA_MSU_UB015, DIA_MSU_UB255, GRA_MSU_UG234, and GRA_MSU_UG265 (derived from regionally important varieties Diamant and Granola). Using the Xdrop® /Nanopore technique, we obtained a very high sequence read coverage within the T-DNA and junction regions. In three of the four events, we were able to use the data to confirm single T-DNA insertions, identify insert locations, identify flanking sequences, and characterize the inserted T-DNA. We further used the characterization data to identify native gene interruption and confirm the stability of the T-DNA across clonal cycles. These results demonstrate the functionality of using the Xdrop® /Nanopore technique for T-DNA characterization. This research will contribute to meeting regulatory safety and regulatory approval requirements for commercialization with small shareholder farmers in target countries within our partnership.

A crucial factor to predict the persistence and spread of infections in natural systems is the capacity of reservoir hosts to maintain the infection and transmit it to others. This is known to greatly vary within and between species and through time, although the latter part of the variation is often less well understood in the wild. Borrelia garinii is one of the causal agents of Lyme disease in humans and is transmitted among avian hosts by the hard tick Ixodes ricinus. Great tits are known to be a reservoir in Europe for B. garinii. For tick-borne pathogens like B. garinii, infectiousness or host-to-vector transmission can be measured using xenodiagnosis where pathogen-free vectors are fed on a host, and the blood-fed vectors are subsequently tested for the pathogen. Here we describe and evaluate a methodology to quantify infectiousness for tick-borne pathogens in individual wild great tits (Parus major), involving captures and recaptures of targeted individuals. The methodology can potentially be applied to other species where recapturing is sufficiently guaranteed. We successfully recaptured most of the infested great tits two to three days after initial infestation (i.e. just before ticks have fully fed) with sufficient numbers of I. ricinus larval ticks, which were subsequently screened for B. garinii using a newly developed B. garinii-specific real-time PCR assay. Higher larval tick numbers were recovered from birds during the breeding seasons than during the winter months. Our novel B. garinii-qPCR performed well, and greatly reduced the amount of Sanger sequencing needed. Preliminary results suggest both seasonal and individual variation in infectiousness; heterogeneity that needs to be unravelled to further understand the contribution of resident birds to the epidemiology of B. garinii.

Although many isolation techniques for algaeaxenic cultures of algae are known, successful isolation approaches are species and contaminant-specific. The commercially important alga Haematococcus lacustris has been intensively studied due to its natural production of the high-value carotenoid astaxanthin, yet there are no reports of axenic H. lacustris cultures. In this article, we describe the successful isolation of axenic H. lacustris, originally isolated in non-axenic form from its natural habitat and adopted to be used daily in vitro, in our laboratory. We verify the absence of bacteria and identify the bacterial communities in the non-axenic algal culture. using PCR amplification with selected universal primers for 16S rRNA gene amplification in the gDNA. Amplification of the 16S rRNA gene of the non-axenic culture showed the presence of bacteria with high identity to Massilia, Blastococcus and Deinococcus species. The bacteria which were identified in our strain further expand our knowledge of bacterial communities on algae, and because we established axenic H. lacustris culture, testing their effect on growth or astaxanthin accumulation in controlled co-cultures is now available. The isolation technique described herein can be applied to other green algal species to eliminate bacteria, and the selected primers can be used to verify the axenic nature of other green algal cultures. The resulting axenic culture is required for molecular genetics research and will be very valuable for establishing heterotrophic growth in laboratory or industrial bioreactors.

Abstract Resveratrol (RSV), a non-flavonoid stilbene polyphenol, possesses anti-carcinogenic activities against all the major stages of cancer. Zein nanoparticles (ZN NPs) have been utilized successfully in delivery of variant therapeuticals by virtue of their histocompatible nature. The goal of this work was to comparatively explore the antiproliferative, pro-apoptotic and oxidative stress potentials of RSV-ZN NPs versus RSV against human colorectal carcinoma HCT-116 cells. ZN-RSV NPs were developed and assayed for particle size analysis and RSV diffusion. The selected formula obtained 137.6 ± 8.3 nm as mean particle size, 29.4 ± 1.8 mV zeta potential, 92.3 ± 3.6% encapsulation efficiency. IC50 of the selected formula was significantly lower against HCT-116 cells versus Caco-2 cells. Also, significantly enhanced cellular uptake was generated from RSV-ZN NPs versus free RSV. Enhanced apoptosis was concluded due to increased percentage cells in G2-M and pre-G1 phases. The pro-apoptotic potential was explained by caspase-3 and cleaved caspase-3 increased mRNA expression in addition to NF-κB and miRNA125b decreased expression. Biochemically, ZN-RSV NPs induced oxidative stress as demonstrated by enhanced reactive oxygen species (ROS) generation and endothelial nitric oxide synthase (eNOS) isoenzyme increased levels. Conclusively, ZN-RSV NPs obtained cell cycle inhibition supported with augmented cytotoxicity, uptake and oxidative stress markers levels in HCT-116 tumor cells in comparison with free RSV. These results indicated intensified chemopreventive profile of RSV due to effective delivery utilizing ZN nano-dispersion against colorectal carcinoma HCT-116 cells.

Abstract The Matrix Metalloproteinases are important regulators of bone metabolism and can influence bone mass and bone remodeling. We investigate the role of Matrix Metalloproteinase 3 (MMP3) on bone in mice, by using Mmp3 knockout (Mmp3 KO) in the context of estrogen deficiency, and in human, by analyzing the association of promoter polymorphism with bone mineral density in postmenopausal women and with MMP3 expression. We presented evidence in this paper that Mmp3 KO significantly increases trabecular bone mass and trabecular number and does not affect cortical bone thickness. We also found that Mmp3 KO protects from the deleterious effects of ovariectomy on bone mineral density in mice by preventing deterioration of bone microarchitecture. The effect of Mmp3 KO does not involve bone formation parameters but instead acts by inhibition of bone resorption, leading to a reduced bone loss associated to ovariectomy. By studying a human cohort, we found that a polymorphism located in the promoter of the human MMP3 gene is associated with bone mineral density in postmenopausal women and found that MMP3 rs632478 promoter variants are associated with change in promoter activity in transfection experiments. In conclusion MMP3, although weakly expressed in bone cells, could be one of the important regulators of sex hormone action in bone and whose activity could be targeted for therapeutic applications such as in Osteoporosis.

The Gametophytic Self-Incompatibility (GSI) system in diploid potato (Solanum tuberosum L.) poses a substantial barrier in diploid potato breeding by hindering the generation of inbred lines. One solution is gene editing to generate self-compatible diploid potatoes which will allow for the generation of elite inbred lines with fixed favorable alleles and heterotic potential. The S-RNase and HT genes have been shown previously to contribute to GSI in the Solanaceae family and self-compatible S. tuberosum lines have been generated by knocking out S-RNase gene with CRISPR-Cas9 gene editing. This study employed CRISPR-Cas9 to knockout HT-B either individually or in concert with S-RNase in the diploid self-incompatible S. tuberosum clone DRH-195. Using mature seed formation from self-pollinated fruit as the defining characteristic of self-compatibility, HT-B-only knockouts produced little or no seed. In contrast, double knockout lines of HT-B and S-RNase displayed levels of seed production that were up to three times higher than observed in the S-RNase-only knockout, indicating a synergistic effect between HT-B and S-RNase in self-compatibility in diploid potato. This contrasts with compatible cross-pollinations, where S-RNase and HT-B did not have a significant effect on seed set. Contradictory to the traditional GSI model, self-incompatible lines displayed pollen tube growth reaching the ovary, yet ovules failed to develop into seeds indicating a potential late-acting self-incompatibility in DRH-195. Germplasm generated from this study will serve as a valuable resource for diploid potato breeding.

Intersex phenotypes are rarely observed in natural isopod populations and their expression is typically associated with infection of Wolbachia, a reproductive parasite that manipulates arthropod reproduction. During an intensive sampling effort of a natural population of the isopod Porcellio scaber, an adult individual was isolated that expressed both male and female traits. The intersex individual exhibited clearly developed external male genitalia and carried multiple eggs in its brood pouch. No Wolbachia infection could be identified in this individual, a result that needs to be approached with caution due to suboptimal DNA preservation for diagnostic PCR assays. Wolbachia were, however, detected in two adult females of the same population, and appear closely related to isolates that infect other terrestrial isopod species. This is the first demonstration that intersex phenotypes can arise under natural conditions in P. scaber.

The Himalayan region is a hotspot in terms of expected future hydrological and geomorphological variations induced by climate change on proglacial areas and the related implications for human societies established along the downstream rivers. Due to the remoteness of the proglacial zones in the Himalayas and the associated logistical problems in carrying out traditional field and UAV-based morphological monitoring activities, remote sensing here plays a crucial role to monitor past and current fluvial dynamics, which could be used to anticipate future changes; however, there has been, so far, limited research on morphological changes in Himalayan proglacial rivers. To address this gap, a morphological classification model was designed to classify recent changes in Himalayan proglacial rivers using the Google Earth Engine platform. The model is the first of its kind developed for the Himalayan region and uses multispectral S-2 satellite data to delineate submerged water channels, vegetated surfaces, and emerged, unvegetated sediment bars, and then to track their variations over time. The study focused on three training sites: Langtang-Khola (Nepal), Saltoro (Pakistan), and Nubra (Jammu and Kashmir) rivers, and one testing site, the Ganga-Bhagirathi River (India). A total of 900 polygons were used as training samples for the random forest classifier, which were further divided into 70% calibration and 30% validation datasets for the training sites, and a separate validation dataset was acquired from the testing site to assess the model performance. The model achieved high accuracy, with an average overall accuracy of 96% and a kappa index of 0.94, indicating the reliability of the S2 data for modeling proglacial geomorphic features in the Himalayan region. Therefore, this study provides a reliable tool to detect past and current morphological changes occurring in the Himalayan proglacial rivers, which will be of great value for both research and river management purposes.

The blastocladialean fungus P. sedebokerense is a facultative parasite of economically important microalgae and for this reason it has gained a lot of interest. P. sedebokerense has a complex life cycle which includes vegetative and resting stages. The resting cysts were assumed to play an essential role in survival by resisting drought, but this ability was never tested and the factors that trigger their formation were not evaluated. This study was aimed to induce resting cyst formation and germination in P. sedebokerense. At first, we tested the survival of P. sedebokerense liquid cultures and found that infectivity is retained for less than two months when the cultures were stored on the bench at room temperature. We noticed that dry cultures retained the infectivity for a longer time. We, thus, developed a method, which is based on dehydration and rehydration of the biomass, to produce, maintain, and germinate resting cysts of P. sedebokerense in both saprophytic and parasitic modes of growth. When the dry cultures were rehydrated and incubated at 30 °C, resting cysts asynchronously germinated after 5 h and the “endosporangium” was protruding outside of the cyst. Our method can be used to preserve P. sedebokerense for research purposes with the advantage of no need for expensive equipment.

Quantification of rare somatic mutations is essential for basic research and translational applications. Here the authors present Quantitative Blocker Displacement Amplification allowing for accurate detection of mutations below 0.01% VAF.

Abstract Acute myeloid leukemia (AML) with rearrangement of the lysine methyltransferase 2a gene (KMT2Ar) has adverse outcomes. However, reports on the prognostic impact of various translocations causing KMT2Ar are conflicting. Less is known about associated mutations and their prognostic impact. In a retrospective analysis, we identified 172 adult patients with KMT2Ar AML and compared them to 522 age-matched patients with diploid AML. KMT2Ar AML had fewer mutations, most commonly affecting RAS and FLT3 without significant impact on prognosis, except for patients with ≥2 mutations with lower overall survival (OS). KMT2Ar AML had worse outcomes compared with diploid AML when newly diagnosed and at relapse, especially following second salvage (median OS of 2.4 vs 4.8 months, P

The SPectrogram Analysis and Cataloguing Environment (SPACE) tool is an interactive python tool designed to label radio emission features of interest in a time-frequency map (called “dynamic spectrum”). The program uses Matplotlib’s Polygon Selector widget to allow a user to select and edit an undefined number of vertices on top of the dynamic spectrum before closing the shape (polygon). Multiple polygons may be drawn on any spectrum, and the feature name along with the coordinates for each polygon vertex are saved into a “.json” file as per the “Time-Frequency Catalogue” (TFCat) format along with other data such as the feature id, observer name, and data units. This paper describes the first official stable release (version 2.0) of the tool.

Purpose: The results of studies of sporadic radio emission of several types of space radio sources, including neutron stars and planets of the Solar System, are presented. The aim of this work is to review the latest achievements in the study of low-frequency radio emission of the Solar System planets and transient signals similar to pulsar pulses using the UTR-2 radio telescope. The importance of the development of the verification methods of the spaceborne radio emission in the study of sporadic signals from various sources is shown. Design/methodology/approach: The studies of sporadic signals of different nature are based on the common set of procedures for cleaning records from the terrestrial radio frequency interference (RFI) in the frequency-time pattern using the information on the nature of the particular type of sporadic radio emission, possible types of interference and signal distortion. Characteristic features of sporadic radio emission of different sources are given, and for each of them the optimal method of signal extraction is developed. The efficiency of the developed procedures for cleaning from noise using adjustable parameters is shown. This is done on the basis of observations of diverse types of space radio sources, such as lightnings in the atmospheres of planets, single pulses of neutron stars and sporadic radio emission of Jupiter. Findings: The developed methods of signal extraction detection in the presence of radio-interference have allowed obtaining the unique results such as: the distribution of the total intensity of single pulses of neutron stars depending on the galactic latitude; the automatic search of lightnings in the Saturn’s atmosphere in data due to the carefully elaborated RFI mitigation procedures, which made it possible to obtain the Saturn electrostatic discharge (SED) emission parameters based on the most complete set of events. Increased efficiency of the selection of Jupiter’s S-radiation signals despite the data corruption by the presence of radio-interference, which was reached due to the carefully chosen parameters of data cleaning procedures, have allowed us to detect short and intensive bursts, being the most informative for determining the physical parameters of radio emission in the area of their generation. Conclusions: The large effective area and high sensitivity of the UTR-2 radio telescope allow making the sporadic radio emission study with high temporal and frequency resolutions. Due to these factors we can apply a wide range of methods of space signals’ detection in the presence of terrestrial radio-frequency interference of natural and artificial origin. The data cleaning parameters allow accounting for the characteristic features of space signals and to obtain important and even unique scientific results.

Purpose: Review of investigations of cosmic sources radioemission scintillations due to interplanetary plasma irregularities made at the Institute of Radio Astronomy of the National Academy of Sciences of Ukraine, from the first observations in the mid-70s until now. Design/methodology/approach: In the course of preparation of this paper, the authors have reviewed, analyzed and summarized the information being published in the home and foreign publications, and reported at scientific conferences. Findings: The investigations of the interplanetary scintillations carried out at the Institute of Radio Astronomy, NAS Ukraine have been reviewed. A retrospective discussion has been made on how in the course of these researches the knowledge about the basic parameters of interplanetary scintillations in the decameter wavelength range, as well as that on the important parameters of the solar wind and its structure, have been obtained. Also, various methods of processing and analysis of experimental data were offered, and new means for receiving cosmic radiation were created. The place and importance of the discussed researches for the world science are shown. Conclusions: Over the years since the beginning of the research, the think tank of the Department of Low-Frequency Radio Astronomy of the Institute of Radio Astronomy, NAS Ukraine has obtained a number of new relevant results, which bring Ukraine into the cohort of world centers of interplanetary scintillation researches. The construction of a new GURT radio telescope, among other things, creates new prospects for the development of this relevant line of investigation.

Developmental cardiac tissue is regenerative while operating under low oxygen. After birth, ambient oxygen is associated with cardiomyocyte cell cycle exit and regeneration. Likewise, cardiac metabolism undergoes a shift with cardiac maturation. Whether there are common regulators of cardiomyocyte cell cycle linking metabolism to oxygen tension remains unknown. The objective of the study is to determine whether mitochondrial UCP2 is a metabolic oxygen sensor regulating cardiomyocyte cell cycle. Neonatal rat ventricular myocytes (NRVMs) under moderate hypoxia showed increased cell cycle activity and UCP2 expression. NRVMs exhibited a metabolic shift toward glycolysis, reducing citrate synthase, mtDNA, mitochondrial membrane potential (ΔΨm), and DNA damage/oxidative stress, while loss of UCP2 reversed this phenotype. Next, WT and mice from a global UCP2-KO mouse line (UCP2KO) kept under hypoxia for 4 weeks showed significant decline in cardiac function that was more pronounced in UCP2KO animals. Cardiomyocyte cell cycle activity was reduced, while fibrosis and DNA damage was significantly increased in UCP2KO animals compared with WT under hypoxia. Mechanistically, UCP2 increased acetyl-CoA levels and histone acetylation, and it altered chromatin modifiers linking metabolism to cardiomyocyte cell cycle under hypoxia. Here, we show a potentially novel role for mitochondrial UCP2 as an oxygen sensor regulating cardiomyocyte cell cycle activity, acetyl-CoA levels, and histone acetylation in response to moderate hypoxia.

Abstract The circadian clock is an internal molecular oscillator and coordinates numerous physiological processes through regulation of molecular pathways. Tissue‐specific clocks connected by mobile signals have previously been found to run at different speeds in Arabidopsis thaliana tissues. However, tissue variation in circadian clocks in crop species is unknown. In this study, leaf and tuber global gene expression in cultivated potato under cycling and constant environmental conditions was profiled. In addition, we used a circadian‐regulated luciferase reporter construct to study tuber gene expression rhythms. Diel and circadian expression patterns were present among 17.9% and 5.6% of the expressed genes in the tuber. Over 500 genes displayed differential tissue specific diel phases. Intriguingly, few core circadian clock genes had circadian expression patterns, while all such genes were circadian rhythmic in cultivated tomato leaves. Furthermore, robust diel and circadian transcriptional rhythms were observed among detached tubers. Our results suggest alternative regulatory mechanisms and/or clock composition is present in potato, as well as the presence of tissue‐specific independent circadian clocks. We have provided the first evidence of a functional circadian clock in below‐ground storage organs, holding important implications for other storage root and tuberous crops.