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The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo.

The 50 mK cryogenic focal plane anticoincidence detector of the Athena X-ray observatory (CryoAC) is a silicon-suspended absorber sensed by a network of 400 Ir/Au transition edge sensors (TES) and connected through silicon bridges to a surrounding silicon frame plated with gold. The device is shaped by deep reactive ion etching from a single silicon wafer of 500 μm. In operating test of prototypes of the demonstration model of the CryoAC, we have highlighted the importance of the phonon hot spot in the signal generation. A fast response to the cosmic particle of a large area of about 4 cm2 and a thin 0.5 mm silicon absorber covered by a TES array can be assured by matching the array configuration to the size and properties of the hot spot. In this article, we present the preparatory study of a proposal for measuring the phonon hot spot that is predicted by the particle-absorber interaction model.

ABSTRACTBackgroundHydroxyurea (HU) has been widely used in clinical practice to manage patients with non-transfusion dependent thalassemia (NTDT). Few data are available about the effects of its administration in Italian patients. We assessed hematological and non-hematological outcomes following short- and long-term exposure to HU.Research design and methodsWe considered 71 NTDT patients (30 females) enrolled in the Myocardial Iron Overload in Thalassemia Network and treated for >12 months with HU.ResultsThe mean duration of HU treatment was 8.23±5.79 years, starting at a mean age of 37.02±12.06 years. A significant increase in hemoglobin and mean corpuscular volume values and a down-regulation of all erythropoietic and/or hemolysis indices were detected after at least 12 months of treatment. In 28 patients the hemoglobin increase was ≥1.0 g/dl, associated with a higher HU dose. The hematological response dropped in long-term treatment. A favorable impact of HU treatment in limiting the progression of several complications typical of NTDT syndrome was observed.ConclusionOur findings seemed to suggest that in several NTDT patients HU could be still a valid option to limit the advance in overall disease clinical burden without carrying significant adverse events and increase in mortality.

Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin‐activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI).

For quality, interpretation, reproducibility and sharing value, microscopy images should be accompanied by detailed descriptions of the conditions that were used to produce them. Micro-Meta App is an intuitive, highly interoperable, open-source software tool that was developed in the context of the 4D Nucleome (4DN) consortium and is designed to facilitate the extraction and collection of relevant microscopy metadata as specified by the recent 4DN-BINA-OME tiered-system of Microscopy Metadata specifications. In addition to substantially lowering the burden of quality assurance, the visual nature of Micro-Meta App makes it particularly suited for training purposes.

Rigorous record-keeping and quality control are required to ensure the quality, reproducibility and value of imaging data. The 4DN Initiative and BINA here propose light Microscopy Metadata Specifications that extend the OME Data Model, scale with experimental intent and complexity, and make it possible for scientists to create comprehensive records of imaging experiments.

Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin‐activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI). Validate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study. Six centers from four countries analyzed samples with TSVT/ET from 81 nonanticoagulated patients with LA, patients with established antiphospholipid syndrome (APS), and proven persistent LA who were either not anticoagulated (n= 120) or were anticoagulated with VKAs (n= 180) or DFXaIs (n= 71). Additionally, 339 nonanticoagulated LA‐negative patients, and 575 anticoagulated non‐APS patients (172 VKA, 403 DFXaI) were tested. Anticoagulant spiking experiments were performed and 112 samples containing potential interferences (i.e., direct thrombin inhibitors) were tested. Results were evaluated against locally derived cutoffs. Imprecision was evaluated. Cutoffs were remarkably similar despite use of different analyzers and donor populations. Cutoffs for TSVT ratio, ET ratio, percent correction, and normalized TSVT ratio/ET ratio ranged between 1.08 and 1.10, 1.09 and 1.12, 9.3% and 14.8%, and 1.10 and 1.15, respectively. Coefficients of variation for TSVT and ET ratios were ≤5.0%. TSVT/ET exhibited sensitivity, specificity, and negative and positive predictive values of 78.2%/95.0%/86.3%/91.5%, respectively, with established APS as the LA‐positive population, and 86.9%/95.0%/76.8%/97.4%, respectively, with triple‐positive APS. Interference was seen with direct thrombin inhibitors, unfractionated heparin, and low molecular weight heparins, but not VKAs or DFXaIs. TSVT/ET are validated for LA detection in nonanticoagulated patients and those on VKAs or DFXaIs.

ABSTRACTCold-pressed Citrusessential oils namely lemon, bergamot, lime, grapefruit, mandarin, sweet and bitter orange are obtained from the peel of Citrusfruits. They were normally used in food, cosmetic, and pharmaceutical industries as ingredients. Essential oils extraction processes produce oils with different sensory qualities, and often these processes are expensive and have a low yield. For such a reason adulteration process are frequent, so careful attention must be paid to ensure the oils’ genuineness and authenticity. Moreover, psoralen levels are continuously monitored by opinions and regulations released from International Fragrance Association and the European Parliament due to their photoactivity.This review aims to browse the scientific literature of the past 30 years on the characterization of the non-volatile fraction of cold-pressed Citrusessential oils to discuss results achieved so far and highlight future prospect.

Miniaturized LC has evolved at an exponential rate over the last 50 years. In the past decade, it has received considerable attention in the field of bioanalytical separation science and technology due to the need to measure different classes of biomolecules present in a variety of matrixes on a global scale to gain a deeper understanding of complex biological processes. This field has become a dominant area underpinning the molecular omics research (e.g., proteomics, metabolomics, lipidomics, and foodomics), allowing key insights into the function and mechanism of small to very large biomolecules on a molecular level. This Feature highlights the recent advances in molecular omics focusing on miniaturized LC technology combined with mass spectrometry-based platforms, with a particular emphasis on the strategies adopted and applications using new and sensitive nanoscale analytical methodologies.

AbstractIn Queensland, Australia, a new senior Earth and Environmental Science (EES) syllabus has been approved for first implementation in 2019. Given the natural alignment between EES and Education for Sustainable Development (ESD), this study employs document analysis to investigate the extent to which the intended curriculum reflects the tenets of ESD. An exploratory content analysis examined the frequency of keywords to identify any prominent sustainability themes that might underpin the syllabus, while a curriculum key guided a deeper analysis according to four tenets of ESD: Learning content; Pedagogy and learning environments; Societal transformation; and Learning outcomes. These analyses found that the ESD tenets reflected in the syllabus is limited chiefly to sustainability learning content, while broader notions of ESD, like the promotion of transformative learning, are marginalised or absent. Instead, the syllabus reflects a technical orientation to curriculum, underpinned by a neoliberal agenda. It is argued that the Queensland EES syllabus represents a missed opportunity to engage students with ESD. In a policy climate where achievement and accountability dominate educational discourse, there is an inherent risk that ESD will fall by the wayside, given it is not prioritised in the intended curriculum. Implications for curriculum development are also discussed.

A comprehensive phytochemical investigation of aerial parts obtained from Centaurea siculaL. led to the isolation of 14 terpenoids (1–14) and nine polyphenols (15–23). The sesquiterpenoid group (1–11) included three structural families, namely, elemanolides (1–6), eudesmanolides (7and 8), and germacranolides (9–11) with four unreported secondary metabolites (5–8), whose structure has been determined by extensive spectroscopic analysis, including 1D/2D NMR, HR-MS, and chemical conversion. Moreover, an unprecedented alkaloid, named siculamide (24), was structurally characterized, and a possible biogenetic origin was postulated. Inspired by the traditional use of the plant and in the frame of ongoing research on compounds with potential activity on metabolic syndrome, all the isolated compounds were evaluated for their stimulation of glucose uptake, disclosing remarkable activity for dihydrocnicin (10) and the lignan salicifoliol (15).

•Adult plants respond differently to prolonged heat stress than young plants•Different physiological strategies can be employed in response to heat stress•Efficient photosynthetic mechanisms are crucial for stress tolerance in tomato•Key genes controlling heat tolerance were identified by GBS analysis

Bergamot (Citrus bergamia) is cultivated in Southern Italy almost exclusively to produce the prized essential oil, a top note in several perfumes. The juice of bergamot, until recently poorly studied, is the object of a growing scientific interest due to its claimed activity to treat metabolic syndrome. The aim of this investigation was a detailed characterization of bergamot juice polyphenolic fraction (BPF) based on a UPLC-DAD-MS analysis complemented by preparative chromatographic separations, followed by NMR characterization of the isolated compounds. The combination of these techniques efficiently covered different classes of secondary metabolites, leading to the identification of 39 components, several of which had never been reported from bergamot. One of them, bergamjuicin (35), is a new flavanone glycoside, whose structure has been determined by MS and NMR techniques. The reported results could provide a guide for future routine analyses of BPF, a material of great nutraceutical and industrial interest.

Ebola virus (EBOV) is a filovirus that causes a severe and rapidly progressing hemorrhagic syndrome; a recent epidemic illustrated the urgent need for novel therapeutic agents because no drugs have been approved for treatment of Ebola virus. A key contribution to the high lethality observed during EBOV outbreaks comes from viral evasion of the host antiviral innate immune response in which viral protein VP35 plays a crucial role, blocking interferon type I production, first by masking the viral double-stranded RNA (dsRNA) and preventing its detection by the pattern recognition receptor RIG-I. Aiming to identify inhibitors of the interaction of VP35 with the viral dsRNA, counteracting the VP35 viral innate immune evasion, we established a new methodology for high-yield recombinant VP35 (rVP35) expression and purification and a novel and robust fluorescence-based rVP35–RNA interaction assay (Z′ factor of 0.69). Taking advantage of such newly established methods, we screened a small library of Sardinian natural extracts, identifying Limonium morisianumas the most potent inhibitor extract. A bioguided fractionation led to the identification of myricetin as the component that can inhibit rVP35–dsRNA interaction with an IC50value of 2.7 μM. Molecular docking studies showed that myricetin interacts with the highly conserved region of the VP35 RNA binding domain, laying the basis for further structural optimization of potent inhibitors of VP35–dsRNA interaction.

Phytochemical investigation of the aerial parts of the Tunisian plant Daucus virgatusled to the isolation of eight new germacranolides named daucovirgolides A–H (1–8). The stereostructures of these sesquiterpene lactones, decorated by either one or two angeloyl groups, have been determined by a combination of MS, NMR spectroscopy, chemical derivatization, and comparison of experimental electronic circular dichroism curves with TDDFT-predicted data. Daucovirgolide G (7) proved to be the single member of this family to possess a marked inhibitory activity (92% at 50 μg/mL) on the development of Plasmodiumearly sporogonic stages, the nonpathogenic transmissible stages of malaria parasites, devoid of general cytotoxicity. The selective activity of daucovirgolide G points to the existence of strict structural requirements for this transmission-blocking activity and therefore of a well-defined, although yet unidentified, biological target.

The present work reports the heterologous expression and biochemical characterization of a novel phosphatidylinositol phospholipase C from Bacillus thuringiensisPL14 (PI-PLCBt) with potential for oil degumming. As degumming is a necessary refining step for all crude vegetable oils, enzymatic degumming tests were performed on crude soybean oil using rPI-PLCBt. Its efficiency was investigated by determining the phosphorus and diacylglycerol (DAG) contents after different types of treatment. Although the water and chemical degumming process can efficiently reduce the phosphorus content, a specific enzymatic process can still be selected giving its high degumming efficiency of 89.4%, with a noticeable reduction in phosphorus content to 13.7 mg kg−1, close to the values of the chemical approach, and a high increase in DAG. Accordingly, enzymatic degumming could be adopted as an alternative to traditional degumming making the process more efficient, eco-friendly and, at the same time, increasing the nutritional value of the final product.

Abstract. Chlorella sorokiniana Shihira & Krauss, strain 211/8K resuspended in a illuminated medium showed continuous growth, and concomitantly NH4 + in the medium depleted at a constant rate. Upon sulfate removal, i) growth declined, ceasing within 5 h; ii) NH4 + depletion became almost undetectable over 2 h; and iii) photosynthetic capacity (Pc) was reduced over 24 h by 80% in the light, but was reduced by only 30% in darkness. Over 24 h of S starvation the chlorophyll content of illuminated cells decreased by 50%, whereas that of darkened cells decreased by only 10%. Sulfate-deprivation over 24 h resulted in a noticeable increase in the starch content of the cell and a net increase in the pools of glutamate, glutamine, serine and asparagine. Cysteine content, in contrast, was decreased. Sulfate addition to cells starved of S for 24 h provoked a sudden time-dependent increase in Pc and in an immediate renewal of growth in light but not in darkness. Sulphate supply also caused a sudden enhancement of respiratory oxygen consumption and a prompt degradation of starch. Starch was degraded at a higher rate in illuminated than in darkened cells. After the S addition, depletion of NH4 + in the medium occurred at slowly increasing rates; amino acids decreased noticeably over 4 h, where in contrast, cysteine increased noticeably. Keywords: algal growth, algal respiration, sulfur assimilation, Chlorella sorokiniana, photosynthesis.

Nitrogen-limited continuous cultures of Cyanidium caldarium contained induced levels of glutamine synthetase and nitrate reductase when either nitrate or ammonia was the sole nitrogen source. Nitrate reductase occurred in a catalytically active form. In the presence of excess ammonia, glutamine synthetase and nitrate reductase were repressed, the latter enzyme completely. In the presence of excess nitrate, intermediate levels of glutamine synthetase activity occurred. Nitrate reductase was derepressed but occurred up to 60% in a catalytically inactive form.

A strain of Cyanidium caldarium has been studied which is able to grow in darkness using amino acids as sole energy sources. During growth ammonia was released into the external medium as a catabolic end product. With either threonine or glutamate similar rates of ammonia formation and similar kinetics of growth were observed. These observations suggest that the amounts of energy made available for cell growth from the two amino acids are equivalent.

Ammonium-induced inhibition of nitrate utilization was monitored in cell suspensions of the unicellular alga Cyanidium caldarium. It was found that the inhibition followed an exponential pattern with a t1/2 value of about 1.5 min in cells previously grown under conditions of excess nitrate, and of about 15 min in cells grown under conditions of severe nitrate limitation. In the latter cells only, a pretreatment with cycloheximide greatly increased the t1/2 value of inhibition. Also the resumption of nitrate utilization when ammonium was depleted followed an exponential pattern with a t1/2 value of about 4.5 min.