Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma

Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. We also observed a continuum of stemness-related expression states that enabled us to identify putative regulators of stemness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.National Institutes of Health (U.S.) (U24 CA180922

A computational study of Si–H bonds as precursors for neutral E' centres in amorphous silica and at the Si/SiO2 interface

Using computational modelling we investigate whether Si–H Bonds can serve as precursors for neutral E′E′ centre formation in amorphous silica and at the Si/SiO2 interface. Classical inter-atomic potentials are used to construct models of a-SiO2 containing Si–H bonds. We then investigate the mechanism of dissociation of a Si–H bond to create a neutral E′E′ defect, that is a 3-coordinated silicon with an unpaired electron localised on it. We show that the Si–H bond is extremely stable, but as a result of hole injection it is significantly weakened and may dissociate, creating a neutral E′E′ centre and a proton attached to one of the nearby oxygen atoms. The proton can diffuse around the E′E′ centre and has a profound effect on the defect levels. We show that at a Si/SiO2 interface, the position of the proton can facilitate electron transfer from the Si substrate onto the defect, making it negatively charged

INFN What Next: Ultra-relativistic Heavy-Ion Collisions

This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

Recombination dynamics of a human Y-chromosomal palindrome:rapid GC-biased gene conversion, multi-kilobase conversion tracts, and rare inversions

The male-specific region of the human Y chromosome (MSY) includes eight large inverted repeats (palindromes) in which arm-to-arm similarity exceeds 99.9%, due to gene conversion activity. Here, we studied one of these palindromes, P6, in order to illuminate the dynamics of the gene conversion process. We genotyped ten paralogous sequence variants (PSVs) within the arms of P6 in 378 Y chromosomes whose evolutionary relationships within the SNP-defined Y phylogeny are known. This allowed the identification of 146 historical gene conversion events involving individual PSVs, occurring at a rate of 2.9-8.4×10(-4) events per generation. A consideration of the nature of nucleotide change and the ancestral state of each PSV showed that the conversion process was significantly biased towards the fixation of G or C nucleotides (GC-biased), and also towards the ancestral state. Determination of haplotypes by long-PCR allowed likely co-conversion of PSVs to be identified, and suggested that conversion tract lengths are large, with a mean of 2068 bp, and a maximum in excess of 9 kb. Despite the frequent formation of recombination intermediates implied by the rapid observed gene conversion activity, resolution via crossover is rare: only three inversions within P6 were detected in the sample. An analysis of chimpanzee and gorilla P6 orthologs showed that the ancestral state bias has existed in all three species, and comparison of human and chimpanzee sequences with the gorilla outgroup confirmed that GC bias of the conversion process has apparently been active in both the human and chimpanzee lineages

Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells

Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed

Polyphenol characterization and skin-preserving properties of hydroalcoholic flower extract from Himantoglossum robertianum (Orchidaceae)

Himantoglossum robertianum (Loisel.) P. Delforge is a Mediterranean orchid whose propagation in vitro has been achieved, making it eligible as a source of bioactive substances. Flowers were analyzed by light and SEM microscopy and used to obtain a polyphenol-rich, hydroalcoholic flower extract (HFE). HFE was characterized for total phenols, flavonoids and proanthocyanidins, and for polyphenol profile by RP-LC-DAD. Antioxidant assays, in vitro collagenase and elastase inhibition, and MTT and cell motility assays on HaCaT keratinocytes were done. Microscopy showed epidermal cells containing anthocyanins in the flower labellum. Flavonoids (flavones and flavan-3-ols) represented the most abundant compounds (42.91%), followed by scopoletin (33.79%), and phenolic acids (23.3%). Antioxidant assays showed strong activities, rating ORAC > FRAP > TEAC > \u3b2-carotene bleaching > DPPH > iron-chelation. Biological assays showed elastase and collagenase inhibition (up to 42% and 78%, respectively), improvement of HaCaT cell viability after treatment with 500 \u3bcM H2O2 (from 30% to 84% of control), and stimulation of cell migration rate up to 210% of control. In summary, HFE counteracted different free radicals, while protective properties were shown by cell-free and cell-based bioassays, suggesting the possible use of H. robertianum flowers for skin-preserving, repair, and anti-aging applications

Numerical study of oil spill in the Patos lagoon under flood and ebb conditions

Facing great obstacles to eradicate environmental hazards generated by oil spills, it is crucial to establish actions against such accidents. In this context, the focus of this study is to analyze oil spills at the harbor region of Rio Grande, Rio Grande do Sul. The Easy Coupling Oil System (ECOS) model was used to model the oil spills under different environmental conditions simulated by the hydrodynamic model Telemac-3D, with the intention to identify the main forces controlling the movement of the oil slicks over a year of averaged hydrodynamic conditions from 2003 to 2015. The computational domain comprises the Patos Lagoon, the harbor area of Rio Grande and the Southern Brazilian Shelf. For the oil spill simulations, eight distinct events were defined considering both flood and ebb conditions in the estuarine region of the Patos Lagoon. The oil spill simulations showed that, in ebb conditions, the oil slick movement is mainly ruled by the currents, moving towards the outflow. After a few hours, the wind action makes the slick move towards the margins of the waterway. In flood conditions, on the other hand, the oil slick drifts to the interior of the estuary, following the dominant currents and the local winds

Rifampicin-loaded electrospun polycaprolactone membranes: Characterization of stability, antibacterial effects and urotheliocytes proliferation

Pathological conditions such as infections, cancer, inflammation, or iatrogenic lesions, can hinder the cor-rect functionality of the ureter and its structural integrity. Several strategies for the regeneration of the ureter and the restoration of its functionality are available but the best strategy has not been reached yet. Among the proposed strategies, a promising one is the development of tubular scaffolds, in particular exploiting electrospinning technique. In this work, antibacterial electrospun polycaprolactone/rifampicin (PCL/Rif) membranes were prepared and characterized. The membranes are characterized by randomly oriented nanofibers with a homogeneous diameter, as determined by scanning electron microscopy. The mechanical characterization, performed with uniaxial tensile tests, showed a suitable stability over time and a proper deformability. The rifampicin release, investigated by UV spectrophotometry, showed a burst release in the first part of the experiment and a sustained release over time. The membranes are biocompatible and able to support the adhesion and proliferation of urotheliocytes. Moreover, PCL/Rif membranes showed an antibacterial activity against Escherichia coli and other bacterial strains belonging to the "ESKAPE" group. Considering the possibility to use the electrospinning for the production of tubu-lar scaffolds, the described membranes represent a promising starting point for the preparation of uret-eral scaffolds with antibacterial properties.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)