Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

亲爱的景观,你非得是绿色的么

景观作为新地区开发的一种视觉和审美的品质,受到人们尤其是设计师专业人士的青睐,指出把景观等同于植物"绿色"是一种肤浅的观念。通过对智利圣地亚哥等地城市与建筑景观建设经验的追述,提出人类活动、自然元素、文化生态系统共同创造的空间动态平衡,才是"景观"的真谛。     

High resolution spatiotemporal patterns of flow at the landscape scale in montane non-perennial streams

Intermittent and ephemeral streams in dryland environments support diverse assemblages of aquatic and terrestrial life. Understanding when and where water flows provide insights into the availability of water, its response to external controlling factors, and potential sensitivity to climate change and a host of human activities. Knowledge regarding the timing of drying/wetting cycles can also be useful to map critical habitats for species and ecosystems that rely on these temporary water sources. However, identifying the locations and monitoring the timing of streamflow and channel sediment moisture remains a challenging endeavor. In this paper, we analyzed daily conductivity from 37 sensors distributed along 10 streams across an arid mountain front in Arizona (United States) to assess spatiotemporal patterns in flow permanence, defined as the timing and extent of water in streams. Conductivity sensors provide information on surface flow and sediment moisture, supporting a stream classification based on seasonal flow dynamics. Our results provide insight into flow responses to seasonal rainfall, highlighting stream reaches very reactive to rainfall versus those demonstrating more stable streamflow. The strength of stream responses to precipitation are explored in the context of surficial geology. In summary, conductivity data can be used to map potential stream habitat for water-dependent species in both space and time, while also providing the basis upon which sensitivity to ongoing climate change can be evaluated.     

Comprehensive analysis of the substituent distribution in the glucosyl units and along the polymer chain of hydroxyethylmethyl celluloses and statistical evaluation

Hydroxyethylmethyl celluloses (HEMC, DS(Me) 1.46-1.66, DS(HE) = 0.14-0.17) have been analyzed with respect to their methyl and hydroxyethyl pattern in the glucosyl units and along the polymer chain. Methyl groups were located by GLC/MS after direct hydrolysis, reduction, and acetylation, and the distribution of hydroxyethyl residues in the glucosyl units could be determined with enhanced sensitivity after permethylation to unify a certain HE pattern occurring in combination with various methyl patterns in a single peak. To get insight into the distribution of Me and HE along the cellulose chain, a method was developed which overcomes the strong discrimination of relative ion intensities caused by hydroxyalkyl groups and enables quantitative determination of the oligomer composition after random degradation for the first time. This comprises perdeuteriomethylation; partial acid hydrolysis; reductive amination with propylamine; and, finally, permethylation to yield completely O- and N-alkylated, permanently charged oligosaccharides. Although the methyl pattern can be determined by electrospray ionization ion-trap mass spectrometry (ESI-IT-MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS), as well, only MALDI-TOF-MS produced representative data for a quantitative evaluation of the HE pattern. Distribution of HE groups matches with a random distribution calculated from the monomer composition, whereas the methyl pattern was heterogeneous to a different extent.     

Case‐based decision support for fault diagnosis: Do salient ratings discourage situation analysis?

In the processing industry, frequent faults call for assistance in diagnosis, and case‐based reasoning (CBR) can provide solutions applied by other operators in the past. This study investigated whether salient case ratings promote an uncritical acceptance of solutions. In 2 experiments, subjects diagnosed faults with a simulated CBR system, and ratings were presented in graphical or verbal format. In most trials, the case with the highest rating provided the correct solution, while in catch‐trials, it did not. Graphical ratings were hypothesized to speed up solutions but discourage cross‐checking and lead to errors in catch‐trials. These hypotheses were not confirmed, even though Experiment 2 maximized the incentive of relying on case ratings. While graphical ratings led subjects to start with the most highly rated case, they did not impair situation analysis and accuracy. The results suggest that during fault diagnosis people are not easily misled into overtrusting a CBR system.     

Surface Chemistry Dictates the Osteogenic and Antimicrobial Properties of Palladium-, Platinum-, and Titanium-Based Bulk Metallic Glasses

Titanium alloys are commonly used as biomaterials in musculoskeletal applications, but their long-term efficacy can be limited by wear and corrosion, stress shielding, and bacterial colonization. As a promising alternative, bulk metallic glasses (BMGs) offer superior strength and corrosion resistance, but the influence of their chemical composition on their bioactivity remains largely unexplored. This study, therefore, aims to examine how the surface chemistry of palladium (Pd)-, platinum (Pt)-, and titanium (Ti)-based BMGs can steer their response to biological systems. The chemical composition of BMGs governs their thermophysical and mechanical properties, with Pd-based BMGs showing exceptional glass-forming ability suitable for larger implants, and all BMGs exhibiting a significantly lower Young's modulus than Ti-6Al-4 V (Ti64), suggesting a potential to reduce stress shielding. Although BMGs feature copper depletion at the near surface, their surface chemistry remains more stable than that of Ti64 and supports blood biocompatibility. Fibrin network formation is heavily dependent on BMGs’ chemical composition and Ti-based BMGs support thicker fibrin network formation than Ti64. Furthermore, BMGs outperform Ti64 in promoting mineralization of human bone progenitor cells and demonstrate antimicrobial properties against Staphylococcus aureus in a surface chemistry-dependent manner, thereby indicating their great potential as biomaterials for musculoskeletal applications.     

The Promises of Natural Killer Cell Therapy in Endometriosis

Endometriosis is a gynaecological disease defined by the growth of endometrium-like tissue outside the uterus. The disease is present in approximately 5–10% of women of reproductive age and causes pelvic pain and infertility. The pathophysiology is not completely understood, but retrograde menstruation and deficiency in natural killer (NK) cells that clear endometriotic cells in the peritoneal cavity play an important role. Nowadays, hormonal therapy and surgery to remove endometriosis lesions are used as treatment. However, these therapies do not work for all patients, and hormonal therapy prevents patients from getting pregnant. Therefore, new treatment strategies should be developed. Since the cytotoxicity of NK cells is decreased in endometriosis, we performed a literature search into the possibility of NK cell therapy. Available treatment options include the inhibition of receptor–ligand interaction for KIR2DL1, NKG2A, LILRB1/2, and PD-1/PD-L1; inhibition of TGF-β; stimulation of NK cells with IL-2; and mycobacterial treatment with BCG. In preclinical work, these therapies show promising results but unfortunately have side effects, which have not specifically been studied in endometriosis patients. Before NK cell treatment can be used in the clinic, more research is needed.     

Mineral oil migration from paper-based packaging into food,investigated by means of food simulants and model substances

ABSTRACT

Mineral oil hydrocarbons (MOH) are known to be mixtures of non-identified substances, which can migrate from, inter alia, recycled food packaging into food products. Such substances may have carcinogenic potential, which leads to a need to avoid their migration into food. In this article, we investigate the possible use of food simulants and model substances to simplify migration approaches. Tenax and Sorb-Star were chosen as simulant media. To stage the action of known components as a replacement for the migration of MOH, 16 single substances, including n-alkanes and aromatic compounds, were used. Kinetic studies were carried out at a maximum of 60°C with contact times of up to 14 days in touching contact with a medium or in gas-phase transfer to it. The results demonstrated that migration was predominantly a function of temperature, time and contact type, but it was also dependant on the molecular weight and polarity of the substances. Due to their low polarity, alkanes showed higher migration to the lipophilic food simulants than did pure aromatics without alkylation. Additionally, alkylated aromatics represent mineral oil aromatic hydrocarbons (MOAH) more realistically. In contrast to Tenax in the gas-phase transition, Tenax in touching contact may lead to overestimated values at higher temperatures. Migration values for Sorb-Star are in similar regions for both contact types. However, the values of the touching contact experiments were slightly higher than those of the gas-phase transfer. The results for Sorb-Star and Tenax with transport solely over the gas phase are also in good agreement. Sorb-Star generally represents an optimal simulant for chunky foods, whereas Tenax seems a good simulant for food types with a high contact surface. Temperatures up to 40°C are appropriate for most types of migration experiments, whereas 60°C should only be used as an option for experiments with Sorb-Star.