Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.     

金属间化合物TiAl(W,Si,B)合金的组织稳定性及其蠕变性能

Ti-45Al-2W-0.5Si-0.5B(ABB-23)铸造合金在800和900℃长期时效过程中发生组织失稳，包括α2板条断裂和合并，α2相转变为B2相，针状B2相球化和长大，γ等轴晶的生成以及片层间距的增加。ABB－23合金的热稳定性优于无B的ABB－2合金，表明添加B有利于提高合金的热稳定性。ABB－23合金在700－800℃范围内的抗蠕变能力超过同比密度的抗热腐蚀高温合金IN738LC，具有优异的高温蠕变性能。此外，还对比了ABB－23合金与其他几种TiAl基合金的高温蠕变性能。     

Evaluation of high- temperature behavior of CMSX4 + yttrium single- crystal nickel- base superalloy

CMSX4 + Y, a highly strengthened rhenium-containing second-generation single-crystal nickel-base su-peralloy, has been studied by creep, low-cycle, and thermomechanical fatigue in the temperature range 500 to 1100 °C. The alloy exhibits good high-temperature mechanical properties that are superior or com-parable to other single-crystal superalloys. Thermomechanical fatigue resistance is equivalent to low-cy-cle fatigue and is cycle-shape dependent. High-temperature mechanical properties have been studied using life prediction relationships that are frequently used for creep and low-cycle fatigue data evalu-ation. Examination of fracture surfaces revealed that fracture induced by creep damage is internal and starts from pore-initiated cracks; however, fatigue damage starts on the external surface and propagates inward in stage II mode.     

Effects of saline stress on mineral composition,phenolic acids and flavonoids in leaves of artichoke and cardoon genotypes grown in floating system

BACKGROUND: Cynara cardunculus is a species native to the Mediterranean basin. It includes globe artichoke and cultivated cardoon as well as their progenitor wild cardoon. The species is a source of biophenols, and its leaf extracts have been widely used in herbal medicine as hepatoprotectors and choleretics since ancient times. The aim of this study was to determine the effect of increasing the level of salinity in the nutrient solution (1 or 30 mmol L^?1 NaCl) on biomass production, mineral composition, radical‐scavenging activity, caffeoylquinic acids and flavonoids in three artichoke (‘Romolo’, ‘Violetto di Provenza’ and ‘Violetto di Romagna’) and three cultivated cardoon (‘Bianco Avorio’, ‘Bianco Gigante Inerme’ and ‘Gigante di Romagna’) cultivars grown in a floating system. RESULTS: Increased salinity in the nutrient solution decreased the leaf dry biomass and leaf number of artichoke and cultivated cardoon cultivars. Salinity reduced macro‐ and microelement accumulation in leaves (e.g. N, K, Ca, Mg, Fe, Mn and B) but improved their antioxidant activity, total polyphenols, chlorogenic acid, cynarin and luteolin. The cultivated cardoons, especially ‘Bianco Avorio’ and ‘Gigante di Romagna’, showed higher biomass and leaf number than those observed in artichoke genotypes. ‘Violetto di Provenza’ exhibited the highest content of chlorogenic acid, closely followed by ‘Violetto di Romagna’, whereas for cynarin content the highest values were recorded in ‘Violetto di Provenza’, ‘Bianco Avorio’ and ‘Gigante di Romagna’. The highest content of luteolin was recorded in ‘Gigante di Romagna’ and ‘Bianco Avorio’, while the highest content of apigenin was observed in ‘Gigante di Romagna’. CONCLUSION: The results showed that the floating system could be considered an effective tool to improve quality aspects through proper management of the salt concentration in the nutrient solution. They also suggest that specific cultivars should be selected to obtain the desired profile of bioactive compounds. © 2012 Society of Chemical Industry     

The L467F-F508del Complex Allele Hampers Pharmacological Rescue of Mutant CFTR by Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Patients: The Value of the Ex Vivo Nasal Epithelial Model to Address Non-Responders to CFTR-Modulating Drugs

Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety of molecular mechanisms involving altered expression, trafficking, and/or activity of the CFTR chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by a combination of three pharmacological agents that improve CFTR channel trafficking and gating, namely, elexacaftor, tezacaftor, and ivacaftor. This study was prompted by the evidence of two CF patients, compound heterozygous for F508del and a minimal function variant, who failed to obtain any beneficial effects following treatment with the triple drug combination. Functional studies on nasal epithelia generated in vitro from these patients confirmed the lack of response to pharmacological treatment. Molecular characterization highlighted the presence of an additional amino acid substitution, L467F, in cis with the F508del variant, demonstrating that both patients were carriers of a complex allele. Functional and biochemical assays in heterologous expression systems demonstrated that the double mutant L467F-F508del has a severely reduced activity, with negligible rescue by CFTR modulators. While further studies are needed to investigate the actual prevalence of the L467F-F508del allele, our results suggest that this complex allele should be taken into consideration as plausible cause in CF patients not responding to CFTR modulators.     

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.     

Rocket seedling production on the international space station: Growth and nutritional properties

Producing sprouts directly during space missions may represent an interesting opportunity to offer high-quality fresh ready to eat food to the astronauts. The goal of this work was to compare, in terms of growth and nutritional quality, rocket (Eruca sativa Mill.) seedlings grown in the International Space Station during the ENEIDE mission with those grown in a ground-based experiment (in presence and absence of clinorotation). The rocket seedlings obtained from the space-experiment were thinner and more elongated than those obtained in the ground-based experiment. Cotyledons were often closed in the seedlings grown in the space experiment. Quantitative (germination, fresh and dry weight) and qualitative (glucose, fructose, sucrose and starch) traits of rocket seedling were negatively affected by micrograv-ity, especially those recorded on seedlings grown under real microgravity conditions The total chlorophyll, and carotenoids of seedlings obtained in the space experiment were strongly reduced in comparison to those obtained in the ground-based experiment (presence and absence of clinorotation). The results showed that it is possible to produce rocket seedlings in the ISS; however, further studies are needed to define the optimal environmental conditions for producing rocket seedlings with high nutritional value     

Serum chemokines in patients with psoriatic arthritis treated with cyclosporin A

OBJECTIVE: To investigate the possible effects of neuropeptide Y on steroid release by human granulosa cells in culture. DESIGN: Prospective study. SETTING: A university laboratory and the division of obstetrics and gynecology in a hospital. PATIENT(S): Sixteen normally ovulating women. INTERVENTION(S): Ovulation induction for IVF-ET with an LH-releasing hormone analogue and gonadotropins. MAIN OUTCOME MEASURE(S): E2 and progesterone were assayed in the media conditioned by granulosa cells with the use of a double-antibody RIA. RESULT(S): Neuropeptide Y stimulates E2 production in a dose-dependent fashion. Preincubation for 3 hours with hCG led to a statistically significant increase in neuropeptide Y-induced E2 secretion. In contrast, whereas 3 hours of preincubation with 10(-7) mol/L of neuropeptide Y did not elicit a statistically significant increase in hCG-induced E2 secretion, coincubation for 48 hours significantly increased hCG-stimulated secretion. Unlike E2, progesterone secretion did not undergo any statistically significant or dose-dependent variation after treatment with neuropeptide Y. CONCLUSION(S): Neuropeptide Y plays a role in human ovarian steroidogenesis directly at the level of the granulosa cells of the follicles in the early stage of luteinization. In this way, neuropeptide Y could play an important role in controlling the positive feedback effect exerted by the ovarian steroids on LH-releasing hormone and gonadotropins in humans.     

Ketamine anesthesia in children with acute burns and scalds

The purpose of the study was to assess the value and the safety of ketamine as a single anesthetic in burned children in a war area. The material consists of 547 children admitted to the hospital in a 4-year period. The parameters studied were blood pressure, heart rate, pulseoxymetry, pre- and postoperative blood gases. Clinical observations were performed during anesthesia and recovery. The children were questioned about bad dreams.