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Black holes have been found over a wide range of masses, from stellar remnants with masses of 5-150 solar masses (M ☉ ), to those found at the centres of galaxies with M > 10 5 M ☉ . However, only a few debated candidate black holes exist between 150M ☉ and 10 5 M ☉ . Determining the population of these intermediate-mass black holes is an important step towards understanding supermassive black hole formation in the early universe 1,2 . Several studies have claimed the detection of a central black hole in ω Centauri, the most massive globular cluster of the Milky Way 3-5 . However, these studies have been questioned because of the possible mass contribution of stellar mass black holes, their sensitivity to the cluster centre and the lack of fast-moving stars above the escape velocity 6-9 . Here we report the observations of seven fast-moving stars in the central 3 arcsec (0.08 pc) of ω Centauri. The velocities of the fast-moving stars are significantly higher than the expected central escape velocity of the star cluster, so their presence can be explained only by being bound to a massive black hole. From the velocities alone, we can infer a firm lower limit of the black hole mass of about 8,200M ☉ , making this a good case for an intermediate-mass black hole in the local universe., (© 2024. The Author(s).)

Background: The live-attenuated Rift Valley Fever Smithburn (SB) vaccine is one of the oldest products widely used in ruminants for control of RVF infections. Vaccinations with RVF Smithburn result in residual pathogenic effect and is limited for use in non-pregnant animals. Commercially available RVFV inactivated vaccines are considered safer options to control the disease. These products are prepared from virulent RVFV isolates and present occupational safety concerns. This research study evaluates the ability of an inactivated SB vaccine strain to elicit neutralising antibody response in sheep., Methods: The RVF Smithburn vaccine was inactivated with binary ethylenimine at 37 °C. Inactivated RVFV cultures were adjuvanted with Montande™ Gel-01 and aluminium hydroxide (Al (OH) 3 ) gel for immunogenicity and safety determination in sheep. The commercial RVF inactivated vaccine and a placebo were included as positive and negative control groups, respectively., Results: Inactivated RVFV vaccine formulations were safe with all animals showing no clinical signs of RVFV infection and temperature reactions following prime-boost injections. The aluminium hydroxide formulated vaccine induced an immune response as early as 14 days post primary vaccination with neutralising antibody titre of 1:20 and a peak antibody titre of 1:83 was reached on day 56. A similar trend was observed in the animal group vaccinated with the commercial inactivated RVF vaccine obtaining the highest antibody titre of 1:128 on day 56. The neutralizing antibody levels remained within a threshold for the duration of the study. Merino sheep vaccinated with Montanide™ Gel-01-Smithburn were characterised with overall lower immune response when compared to aluminium hydroxide vaccine emulsions., Conclusions: These finding suggests that the inactivated RVF Smithburn vaccine strain adjuvanted with aluminium-hydroxide can be used an alternative to the products prepared from virulent RVFV isolates for protection of ruminants against the disease. The vaccine can further be evaluated for safety in pregnant ewes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Adult-type diffuse gliomas, CNS WHO grade 4 are the most aggressive primary brain tumors and represent a particular challenge for therapeutic intervention., Methods: In a single-center retrospective study of matched pairs of initial and post-therapeutic glioma cases with a recurrence period greater than 1 year, we performed whole exome sequencing combined with mRNA and microRNA expression profiling to identify processes that are altered in recurrent gliomas., Results: Mutational analysis of recurrent gliomas revealed early branching evolution in 75% of the patients. High plasticity was confirmed at the mRNA and miRNA levels. SBS1 signature was reduced and SBS11 was elevated, demonstrating the effect of alkylating agent therapy on the mutational landscape. There was no evidence for secondary genomic alterations driving therapy resistance. ALK7/ACVR1C and LTBP1 were upregulated, whereas LEFTY2 was downregulated, pointing towards enhanced Tumor Growth Factor β (TGF-β) signaling in recurrent gliomas. Consistently, altered microRNA expression profiles pointed towards enhanced Nuclear Factor Kappa B and Wnt signaling that, cooperatively with TGF-β, induces epithelial to mesenchymal transition (EMT), migration, and stemness. TGF-β-induced expression of pro-apoptotic proteins and repression of antiapoptotic proteins were uncoupled in the recurrent tumor., Conclusions: Our results suggest an important role of TGF-β signaling in recurrent gliomas. This may have clinical implications since TGF-β inhibitors have entered clinical phase studies and may potentially be used in combination therapy to interfere with chemoradiation resistance. Recurrent gliomas show high incidence of early branching evolution. High tumor plasticity is confirmed at the level of microRNA and mRNA expression profiles., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

In the fall of 2020, a long-lasting and massive harmful algal bloom (HAB) with extensive fields of yellow sea foam was observed in relatively cold waters (7-13 °C) off the coasts of the Kamchatka Peninsula, Russia. According to the estimates based on bio-optical parameters in satellite imagery, the Kamchatka bloom 2020 lasted for two months and covered a vast area of more than 300 × 100 km. An abundance of dead fish and invertebrates, including sea urchins, sea anemones, chitons, cephalopods, bivalves were found on shore during the bloom. Animals suffered almost 100% mortality within a depth range between 5 and 20 m. To identify the causative microalgal species, light and scanning electron microscopy, Raman spectroscopy, and molecular phylogenetic approaches were used. The HAB area was estimated by the spectral analysis of satellite-derived imagery. The causative organisms were unarmored dinoflagellates of Karenia species. Their density and biomass reached 100-620 cells·mL -1 and 1300-7700 mg·m -3 , respectively, which accounted for 31-99% of the total cell density and 82-99% of the total phytoplankton biomass in late September to mid-October. The dominant species was Karenia selliformis, and the other co-occurring kareniacean species were K. cf. cristata, K. mikimotoi, K. papilionacea, K. longicanalis, and two unidentified morphotypes of Karenia spp. The molecular phylogeny inferred from LSU rDNA and ITS region showed that K. selliformis from Kamchatka in 2020 belonged to the cold-water group I and was identical to K. selliformis strains from Hokkaido, Japan, identified in 2021. This is the first HAB event caused by K. selliformis recorded from Russian coastal waters., Competing Interests: Declaration of Competing Interest The authors of the manuscript Tatiana V. Orlova, Anatoly L Aleksanin., Ekaterina V. Lepskaya, Kseniya V. Efimova, Marina S. Selina, Tatiana V. Morosova, Inna V. Stonik, Vasily A. Kachur, Alexander A. Karpenko, Kirill A. Vinnikov, Andrey V. Adrianov, Mitsunori Iwataki "A massive bloom of Karenia species (Dinophyceae) off the Kamchatka coast, Russia, in the fail of 2020" declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Bacterial secondary metabolites play a major role in the alleviation of diseases; however, the cytotoxicity of other metabolites cannot be ignored as such metabolites could be detrimental to human cells. Three Staphylococci strains Staphylococcus aureus , staphylococcus epidermidis and staphylococcus saprophyticus were used in the experiments. These strains are well known to cause hospital and community-acquired infections. Secondary metabolites from S. aureus isolated from milk of cows with clinical features of mastitis (swollen udders and the production of watery clotted milk), S. saprophyticus (ATCC 35552), and S. epidermidis (ATCC 51625) were exposed to a minimal medium then screened using Gas Chromatography High-Resolution Time-of-flight Mass Spectrometry (GC-HRTOF-MS) and identified with Nuclear Magnetic Resonance (NMR). From S. epidermidis , two compounds were isolated: oleamide and methyl palmitate; three from S. aureus, including fluoranthene, 3-methyl-2-phenyl-1H-pyrrole, and cyclo(L-Leu-L-Propyl); while S. saprophyticus yielded succinic acid, 1,2,6-hexantriol, veratramine, and 4-methyl-pentyl-amine. The secondary metabolites were tested for cytotoxicity using the Vero cell line. Fluoranthene exhibited toxicity with an LC 50 of 0.0167 mg/mL to Vero cells, while the other metabolites did not. Methyl palmitate was the least toxic of all of the metabolites. The results imply that none of the compounds, except fluoranthene, pose any danger to human cells.

The Lumpy Skin Disease Virus (LSDV) Neethling vaccine strains have been used for decades for prophylactic immunization of domestic ruminants against the disease. Commercial products against Lumpy skin disease are supplied as live attenuated vaccines and often are associated with adverse reactions warranting studies towards development of safe and efficacious vaccine alternatives. The present study was designed to investigate the ability of Montanide™ Gel 01 PR adjuvanted inactivated Neethling vaccine strain of the lumpy skin disease to induce immune response in rabbits. Complete virus inactivation was achieved following treatment of live vaccine strain with binary ethyleneimine (BEI) at 2 mM final concentration. Inactivated virus antigen, formulated with Montanide™ Gel 01 was injected at 1,00E + 05 and 1,00E + 06 TCID 50 per dose in rabbits. The second injection with same vaccine dosages was administered 21 days after the primary vaccination. Rabbits that received a 1,00E + 05 TCID 50 /dose of inactivated LSDV vaccine formulation induced maximum neutralizing antibody titres on day 13 post second vaccinations. Rabbits vaccinated and prime boosted with the 1,00E + 06 TCID 50 /dose of inactivated LSDV vaccine formulation, induced neutralizing antibody titres on day 14 after first vaccination. The maximum antibody titres for the 1,00E + 06 TCID 50 /dose of the inactivated LSDV vaccine formulation was obtained on day 35 post vaccination. The 1,00E + 06 TCID 50 dose of the inactivated LSDV vaccine Montanide™ Gel-01 PR formulation induced higher neutralizing antibodies. The Montanide TM Gel-01 PR offers safer profile to oil adjuvants and can be developed further to protect target animals against LSDV in non-endemic areas., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr L Naicker reports financial support was provided by National Research Foundation South Africa., (© 2022 The Author(s).)

Background: The COVID-19 pandemic caused by SARS-CoV-2 has greatly modified outpatient follow-ups. The aim of this retrospective study was to evaluate the organizational modalities and clinical effects of rearrangements of pacemaker (PM) and implantable cardioverter-defibrillator (ICD) outpatient visits performed in our centers at Ravenna and Lugo Hospitals, Italy, during the pandemic outbreak in 2020., Methods: All scheduled in-person device follow-up visits in March-December 2020 have been considered. On the basis of documented past functioning of each device and of remote monitoring (RM) capabilities, in-person visits were either performed or postponed at variable times. The characteristics of the follow-ups and the device-related clinically relevant events were analyzed, the latter being further divided into serious malfunction and problems to be corrected by device reprogramming., Results: Overall, 27% of in-person visits were postponed (n = 576) (36% of ICDs and 25% of PMs), peaking 62% in March-May 2020. RM compensated nearly all hold-ups in ICDs and just 63% of postponements in PMs. The postponement-caused delay between in-person visits was 5.6 ± 1.1 months for ICDs and 4.7 ± 1.2 months for PMs; in 24% of ICDs the time interval between in-person visits was ≥18 months. Clinically relevant events were 56 (18 [4.4%] in ICDs, 38 [2.1%] in PMs), with no deaths and 21 serious malfunctions (4 [1%] in ICDs, 15 [0.8%] in PMs). RM identified all ICD malfunctions, while it was not available in the affected PMs. In comparison with the year 2019, serious malfunctions increased, though the difference was not significant. Monthly RM transmissions increased by 2.3 fold., Conclusions: In our single-center experience during the COVID-19 pandemic, numerous in-person PM/ICD follow-up visits were postponed, and delays were well beyond the previously recommended time limits. However, device-related malfunctions did not increase, notably, when RM capabilities were used.

Thecadinium is a morphologically heterogenous marine benthic genus. Its polyphyly has been discussed. After redefinition of the sensu stricto genus, sensu lato taxa now need reclassification. Heterotrophic, morphologically closely related species were studied in detail. Molecular phylogenetic data for three of the four known species (T. ornatum, T. acanthium, T. ovatum) and new morphological data were obtained, leading to an emended thecal plate pattern, including the presence of an apical pore complex and an additional hypothecal plate. The results confirm the close relationship of the species and justify the description of Carinadinium gen. nov., characterized by the tabulation APC 3/4' 1/0a 6″ 6c 5s 5‴ 2'‴, an epithecal plate of special morphology, an apical flange, a ventral pore, antapical appendages, a descending cingulum and lateral cell flattening. The genus can be separated into two sub-clades, one with a third precingular 'dimple'-plate, four apical and no anterior intercalary plates and the other with a 'multi-pimple'-plate as third precingular or its homolog plate, three apical and one anterior intercalary plate. Carinadinium is phylogenetically related to the planktonic genera Protoceratium, Pentaplacodinium, and Ceratocorys (family Protoceratiaceae), and clearly belongs into the order Gonyaulacales, but with uncertain family affiliation., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Purpose: Generator impedance (Im) mapping with constant contact force (CF) by tip catheter at PV isolation (PVI) was assessed for a proposal of tissue characterization at PV-LA junction (PV-LAJ)., Methods: In this observational, prospective, single-center study, Im mapping at constant CF = 10 g (± 2 g) was performed before PVI at PV-LAJ. PV in-vein, PV ostium (PVos), and antrum (PVan) contours were manually traced based on the 3D electroanatomic map (3DEAM) integrating intracardiac echocardiography and computerized tomography. PVan contour-methods based on Im mapping was defined on 3DEAM as the atrial-like Im contour closest to PVos, and its distance from anatomical PVan contour > 5 mm was assumed as the non-concordance marker between contour and methods., Results: Sixty-two patients (62 ± 9 years; 43 males) were enrolled, and 244 PV-LAJ were assessed. From in-vein PV to LA and, less prominently, from PVos to PVan and LA, Im showed a unidirectional decrease with highly variable individual-specific distribution and values. PVan non-concordance was found in 59/665 segments (8.8%), 18% of PV-LAJs, and 53% of pts; it prevailed in superior PV-LAJ and measured on average 7.2 ± 1.1 mm. Im decrease patterns and non-concordance were not associated with any clinical or anatomical feature, including PV dimensions and shape., Conclusions: Im mapping of LA-PVJ at constant CF added to 3DEAM may consistently track the tissue transition from PV to LA. PVan identified by Im was often located more toward LA than the 3D anatomical PVan, particularly in LSPV, suggesting the potential advantage of avoiding ablation of venous-like tissue. Im mapping can deserve further investigation for target characterization at LA-PVJ., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Pseudothecadinium campbellii, a phototrophic, thecate, marine benthic species, has been found in the Sea of Japan, Russia. The morphological description of the species has been emended, and the thecal tabulation pattern is now APC 4' 2a 4″ 6c 6 s 5‴ 1⁗. Our study indicates that P. campbellii is related to Thecadinium kofoidii and Thecadiniopsis tasmanica, based on a unique morphological feature: incomplete precingular plate series. Previously, molecular data was not available for the taxa, and thus the phylogenetic position of P. campbellii within the Dinophyceae remained obscure. In this study, analyses of the rRNA gene sequences (partial 18S and 28S) revealed that unexpectedly, P. campbellii is most closely related to Halostylodinium arenarium. It formed a common clade with the Thecadinium sensu stricto clade comprising T. kofoidii and T. pseudokofoidii. This clade was placed within the order Gonyaulacales. However, almost no similarity in morphology was found between the two genetically closest species. In addition, they have different lifestyles: unlike P. campbellii, the nonmotile stage is dominant in the life cycle of H. arenarium. It has been shown that other genetically similar species (T. kofoidii, T. pseudokofoidii, T. yashimaense) exhibited some morphological features that unite them with gonyaulacoids., (Copyright © 2019 Elsevier GmbH. All rights reserved.)