Divergent lncRNAs take the lead on pluripotent cell differentiation

[No abstract available

Poising and connectivity of enhancers upon naïve-to-primed transition in human embryonic stem cells (hESCs)

Enhancers are non-coding DNAelements that play crucial roles in transcriptional control, particularly in development. Patterns of histone modifications at enhancers are commonly used to infer their activity states and, poised enhancers (PEs) in particular display a ’bivalent’ chromatin state: the ’active’ H3K4me1 and the ’repressive’, Polycombassociated H3K27me3. Typically observed in pluripotent stem cells (PSCs), it was shown that PEs are required for gene activation later during differentiation. However, the function of the poised state of enhancers remains largely unknown. To trace the emergence of PEs in early development, I have extensively optimized a recently developed low-cell number Capture Hi-C protocol to perform Poised Enhancer Capture Hi-C (PECHi-C) in PSCs, in time course upon the naïve-to-primed transition, which is known to associate with a major shift in the localisation of Polycomb proteins, from a broader to a highly focal pattern. PECHi-C revealed that the PE-mediated regulatory circuitry undergoes significant reorganization between the two states. In particular, I detected three predominant patterns of PE-mediated interactions: the UP, DOWN and CONSTANT interaction classes. Integrating these results with Cut&Tag data on histone modifications revealed an interplay between the acquisition of the poised state at enhancers and their interaction dynamics whereby, at least in some cases, the acquisition of the bivalent signature occurs in parallel to the acquisition of their contacts. Moreover, the analyses suggested that day 3 of the transition is a pivotal point of the naïve-to-primed transition for the emergence of PEs. Overall, this thesis provided further insights into the emergence of PE-mediated regulatory circuitry during early embryogenesis. The different patterns of PE connectivity suggest the presence of diverse regulatory mechanisms of PEs, further suggesting that PEs might play a role at earlier stages of embryogenesis, by ensuring the correct transition from the ground state of pluripotency to the primed state.Open Acces

Preliminary investigation of Li4SiO4 pebbles structural performance

Abstract One of the main purposes of a breeder blanket is to remove the heat produced in the blanket by the fusion reaction neutrons, and to breed the tritium required to sustain it. To achieve these requirements, several breeder materials (solid or liquid lithium-bearing ones) have been investigated in the past decades. To date it has not yet been possible to identify a stable material, with high thermal conductivity and melting point. This paper deals with the mechanical characterization of the lithium orthosilicate (Li4SiO4) in form of pebbles, produced at the University of Pisa at room temperature by a drip casting forming technique, starting from an aqueous suspension of Li4SiO4 precursor prepared by a sol-gel synthesis method. To investigate also numerically, by means of FE code, the breeder blanket behaviour, it is of meaningful importance the mechanical characterization of such pebbles. To the purpose, either static or cyclic uniaxial compression tests, without radial constraints, have been performed on several produced pebbles of about 1.5 mm diameter in order to determine the collapse and crushing loads and the stiffness. Moreover, the carried-out post-test SEM examination allowed to evaluate the failure mode and the crack shapes on the contact surface. Results show the influence of the elastic properties and matrix flaw population on the crushing load. The pebbles produced by the sol-gel method showed also a high strength, the value of which is comparable to that of the pebbles obtained by melting process

Social Economy as Antidote to Criminal Economy: How Social Cooperation is Reclaiming Commons in the Context of Campania’s Environmental Conflicts

This article contributes to ongoing debates on how bottom-up social cooperation can halt and reverse processes of environmental and human degradation, dispossession and impoverishment, by proposing a synchronization of resistance and of commoning practices. The article moves from the empirical case of social and ecological conflicts currently unfolding in the so-called Land of Fires, an area in Southern Italy infamous for the socio-environmental impacts of two decades of waste disposal, mismanagement and contamination. Within this context, a coalition of grassroots movements is struggling to resist livelihoods degradation through an alliance with anti-Mafia social cooperatives. We provide an in-depth analysis of emerging social and economic networks that connect the strategies of grassroots movements for environmental justice with the work of social cooperatives that reclaim lands and assets confiscated to Mafia. The interests of environmental activists meet the interests of social cooperatives at the crossroad of territory reclamation with the spheres of social and economic production and reproduction. Framing the case as a cultural and physical re-appropriation of territory, we provide an analysis of strategies and limits for a symbolic and practical project of social re-appropriation of the commons

Sustaining the Spindle Assembly Checkpoint to improve cancer therapy

To prevent chromosome segregation errors, the spindle assembly checkpoint (SAC) delays mitosis exit until proper spindle assembly. We found that the FCP1 phosphatase and its downstream target WEE1 kinase oppose the SAC, promoting mitosis exit despite malformed spindles. We further showed that targeting this pathway might be useful for cancer therapy

Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword

Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy

Intravenous infusion of magnesium sulfate and its effect on horses with trigeminal-mediated headshaking.

BackgroundTrigeminal-mediated headshaking results from low-threshold firing of the trigeminal nerve resulting in apparent facial pain. Magnesium may have neuroprotective effects on nerve firing that potentially dampen signs of neuropathic pain. This hypothesis has not been investigated in horses with trigeminal-mediated headshaking.ObjectiveTo investigate head-shaking behavior in affected horses after IV magnesium sulfate infusion.AnimalsSix geldings with trigeminal-mediated headshaking.MethodsProspective randomized crossover study. Horses were controlled for diet and infused IV with 5% dextrose solution (DS; control solution at 2 mL/kg body weight [BW]) and MgSO4 50% solution (MSS at 40 mg/kg BW). Head-shaking behavior was recorded at times T0 (baseline, before infusion) and T15, T30, T60, and T120 minutes post-infusion. Venous blood variables such as pH, HCO3 - , standard base excess (SBE), Na+ , Cl- , K+ , Ca2+ , Mg2+ , total magnesium (tMg), glucose, and lactate were measured; strong ion difference (SID) and anion gap (AG) were calculated for each time point.ResultsBlood variables including pH, Na+ , Cl- , K+ , SID, AG, lactate, Ca2+ , tMg, and Mg2+ had significant changes with MSS as compared to DS treatment. Glucose, SBE, and HCO3 - did not have significant changes. A 29% reduction in head-shaking rate occurred after MSS treatment but no change occurred after DS treatment.Conclusions and clinical importanceAdministration of MSS IV increased plasma total and ionized magnesium concentrations and significantly decreased head-shaking behavior in horses with trigeminal-mediated headshaking

In vitro cancer cell growth inhibition and antioxidant activity of Bombax ceiba (Bombacaceae) flower extracts.

The flowers of Bombax ceiba were investigated for their chemical composition, antioxidant effects and antiproliferative activity against seven human cancer cell lines. The antiproliferative responses of diethyl ether (DE) and light petroleum (PE) extracts were evaluated by sulforhodamine B (SRB) assay against MCF-7, HeLa, COR-L23, C32, A375, ACHN, and LNCaP cells in comparison with a human normal cell line, 142BR. Moreover, extracts were characterized by GC-MS analysis and tested for their antioxidant properties by different in vitro systems, namely DPPH, Fe-chelating activity and β-carotene bleaching test. Both PE and DE extracts showed the highest antiproliferative activity against human renal adenocarcinoma (ACHN) in a concentration-dependent manner. PE extract showed the highest radical scavenging activity against the DPPH radical, while DE extract was more active in the β-carotene bleaching test. The presence of β-sitosterol and some fatty acids may contribute to the bioactivity of B. ceiba flower extracts

Carbon Source Influences Antioxidant, Antiglycemic, and Antilipidemic Activities of Haloferax mediterranei Carotenoid Extracts

Haloarchaeal carotenoids have attracted attention lately due to their potential antioxidant activity. This work studies the effect of different concentrations of carbon sources on cell growth and carotenoid production. Carotenoid extract composition was characterized by HPLC-MS. Antioxidant activity of carotenoid extracts obtained from cell cultures grown under different nutritional conditions was determined by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH), Ferric Reducing Ability Power (FRAP) and β-carotene bleaching assays. The ability of these carotenoid extracts to inhibit α-glucosidase, α-amylase, and lipase enzymes was also assessed to determine if they could be used to reduce blood glucose and lipid absorption. The maximum production of carotenoids (92.2 µg/mL) was observed combining 12.5% inorganic salts and 2.5% of glucose/starch. Antioxidant, hypoglycemic, and antilipidemic studies showed that higher carbon availability in the culture media leads to changes in the extract composition, resulting in more active haloarchaeal carotenoid extracts. Carotenoid extracts obtained from high-carbon-availability cell cultures presented higher proportions of all-trans-bacterioruberin, 5-cis-bacterioruberin, and a double isomeric bacterioruberin, whereas the presence 9-cis-bacterioruberin and 13-cis-bacterioruberin decreased. The production of haloarchaeal carotenoids can be successfully optimized by changing nutritional conditions. Furthermore, carotenoid composition can be altered by modifying carbon source concentration. These natural compounds are very promising in food and nutraceutical industries.This study was funded by Generalitat Valencia (PROMETEO/2021/055), Ministerio de Economía y Competitividad (RTI2018-099860-B-316 I00), and Universidad de Alicante (VIGROB-309). Generalitat Valenciana Predoctoral fellowship grant (G.N.ACIF/2019/043) and EMBO Short-Term Fellowship (8977) for M.G

Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions.

The aim of this study was to examine the bioactivity of the methanol fraction (MF) and n-hexane fraction (HF) of Thymus capitatus leaves in relation to their constituents analysed by gas chromatography and gas chromatography-mass spectrometry. The effects of T. capitatus on the growth of pathogenic bacteria associated with respiratory diseases (13 gram-positive and 4 gram-negative) were determined using a microdilution method. The MF was particularly effective on Streptococcus pneumoniae and Moraxella catarrhalis. The antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), ferric-reducing antioxidant power and β-carotene bleaching assays. A strong activity using β-carotene bleaching test was observed with the MF (IC50 of 0.7 μg/mL after 30 min of incubation). In the hypoglycaemic test, a selective α-amylase inhibitory activity was detected with the HF begging the most active (IC50 of 422.5 μg/mL). T. capitatus may represent a source of natural bioactive compounds