Attrition-enhanced total resolution leads to homochiral families of amino acid derivatives

The total resolution of five structurally similar racemizable amino acid derivatives, three of which have racemic crystal structures, was performed simultaneously. By enantioselective incorporation in an amino acid derivative that forms a conglomerate the other four were deracemized on attrition-induced grinding. The outcome of the resolution was random (R) or (S), but all compounds had the same absolute configuration and high enantiomeric purities.

Mediterranean alien harmful algal blooms:Origins and impacts

Harmful algal blooms (HABs) are mostly phytoplankton blooms, which have detrimental environmental and socioeconomic impacts. The Mediterranean Sea due to its enclosed nature is of special concern since it has an enormously rich native biodiversity. Though, it is also the world's most invaded marine ecosystem and is considered at very high risk of future invasions. The aim of this review study is to explore the origins, establishment, environmental, and socioeconomic impacts of HABs caused by nonnative algal species in the Mediterranean Sea. Based on this, it is also discussed whether HABs form an increasing threat in the basin, and what could possibly be done to prevent or to minimize their impacts. The increasing rate of their introduction and the harmful impacts that they have on the environment, economy, and human health makes it important to have accurate knowledge about HABs. Anthropogenic activities and climate change are considered the main contributors of alien invasions but also the main enablers of HAB events. Mediterranean HABs are adequately studied, but there are no studies purposefully concerning invasive microalgae species in the basin. In the present study, 20 species have been identified, and an attempt has been made to collect their introduction information, as well as known or suspected impacts. Future research should be focused on data mining, current legislation updates, and monitoring of Mediterranean coastlines

Evidence for inhibition of bacterial luminescence by allelochemicals from Fibrocapsa japonica (Raphidophyceae), and the role of light and microalgal growth rate

The marine microalga Fibrocapsa japonica Toriumi and Takano (Raphidophyceae) produces haemolysins, neurotoxins and reactive oxygen species (ROS). To quantify potential effects of such bioactive compounds on surrounding organisms the marine bacterium Vibrio fischeri was exposed to F. japonica culture samples. Inhibition of V. fischeri 's natural luminescence, indicative of impaired metabolism, was related to the number of F. japonica cells added. The effect was fast, within 15 min. It was caused by one, possibly several, excreted substances that were less active after heating. Freezing of culture supernatant partly inactivated these substances, but ROS-scavenging enzymes had no effect. Light enhanced the V. fischeri luminescence inhibition in two ways. The direct effect of light on the action of F. japonica luminescence inhibiter(s) could be described by a saturation curve with maximum effect above 20 mu mol photons m(-2) s(-1). Light also had an indirect effect: biomass production, dependent on light availability, was closely related to the amount of inhibiting compound(s) produced by the alga. Algal growth rate, rather than its cell density, determined the bacterial luminescence inhibition per F. japonica cell, resulting in a 5-fold stronger inhibition at maximum growth rates compared to cells that barely grew during the stationary growth phase. The bioassay with F. japonica and V. fischeri has allowed quantification of the negative effects on bacteria in the microalgal microenvironment. The results presented here suggest that at favourable growth conditions F. japonica releases bioactive compounds that improve its competitive abilities

Social Defeat during Adolescence and Adulthood Differentially Induce BDNF-Regulated Immediate Early Genes

Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats

Ballast Water Risk Indication for the North Sea

The ballast water from ships carries marine organisms that have invasivepotential. The International Maritime Organization Ballast WaterManagement Convention (2004) requires ballast water exchange orballast water management (BWM) systems either onboard or ashore.Ships can be exempted on the basis of risk assessment, when exclusivelysailing between specific ports or in an enclosed area. In reply to ourquestionnaire, the shipping sector argues that the North Sea isecologically homogeneous and exemptions could therefore be granted.This paper proposes that the North Sea area is, in fact, not homogeneousin terms of hydrographical and biological conditions; therefore, ballastwater is a relevant transport mechanism for organisms. Within the NorthSea, the short shipping routes indicate a high risk for survival. Weexamined actual simulation models for ballast water risk assessment inthe North Sea, and we have identified the major parameters that need tobe included in such models. These models provided a basis; they furtherneed to be combined and adapted for the purpose of evaluating therationale for an exemption. We concluded that exemptions from BWMare not recommended for the North Sea area. Anticipating the BallastWater Management Convention, ship owners might do well to studypossibilities for installing BWMsystems onboard

First record of the dynamics of domoic acid producing Pseudo-nitzschia spp. in Indonesian waters as a function of environmental variability

Within the past few decades, harmful algal blooms (HABs) have occurred frequently in Indonesian waters, resulting in environmental degradation, economic loss and human health problems. So far, HAB related studies mainly addressed ecological traits and species distribution, yet toxin measurements were virtually absent for Indonesian waters. The aim of the present study was to explore variability of the potentially toxic marine diatom genus Pseudo-nitzschia, as well as its neurotoxin domoic acid as a function of environmental conditions in Ambon Bay, eastern Indonesia. Weekly phytoplankton samples, oceanographic (CTD, nutrients) and meteorological (precipitation, wind) parameters were analyzed at 5 stations in the bay during the dry and wet seasons of 2018. Liquid chromatography – tandem mass spectrometry (LC–MS/MS) was used to detect particulate DA (pDA). Vegetative cells of Pseudo-nitzschia spp. and pDA were found in 98.6% and 51.4% of the samples, respectively. pDA levels were low, yet detected throughout the campaign, implying that Ambon Bay might potentially be subject to amnesic shellfish poisoning. The highest levels of both Pseudo-nitzschia spp. cell abundance and pDA were found in the wet season, showing a strong positive correlation between both parameters, compared to the dry season, (r = 0.87 and r = 0.66 (p < 0.01), respectively). Statistical analyses revealed that temperature and mixed layer depth positively correlated with Pseudo-nitzschia spp. and pDA during the dry season, while ammonium showed positive correlations in both seasons. This study represents the first successful investigation of the presence and variability of Pseudo-nitzschia spp. and its neurotoxin DA in Indonesian waters

Effectiveness and costs of a new framework for selecting absorbent urinary incontinence products compared with current practice:a cohort study

Objectives To improve continence care in the Netherlands, a new framework has been developed in which a shift has been made from incontinence severity as the sole criterion for selecting incontinence products to a focus on patient need for daily life activities. The impact of the framework on daily care has not been assessed. We aimed to compare treatment effectiveness and costs between participants who did and did not undergo re-evaluation according to the new framework. Design Cohort study Setting Twelve pharmacies in the Netherlands Participants Existing users of absorbent incontinence materials for urinary incontinence. Interventions Participants were offered the option to have their incontinence products re-evaluated within the new framework at their pharmacy. Primary and secondary outcome measures Effectiveness and cost outcomes were assessed at 3 and 6 months through questionnaires. These questionnaires included the International Consultation on Incontinence Questionnaire (ICIQ) Lower Urinary Tract Symptoms Quality of Life Module, ICIQ Urinary Incontinence Short Form, ICIQ Absorbent Pads, questions about satisfaction and the iPCQ and iMCQ. Results 303 users consented and 279 completed the baseline questionnaire. Of these participants, 72 agreed to a re-evaluation of their incontinence materials. There was a small improvement at 3 months in the re-evaluation group compared with the other group on most outcomes. However, these improvements were not clinically relevant. Moreover, these differences did not change much from 3 to 6 months. Small differences were also observed in the changes in costs, but with very wide CIs on both sides of zero (euro99.38; 95% CI -633.48 to 832.23). Conclusions The current study showed no clinically relevant effect of a newly implemented framework for selecting incontinence materials in pharmacies when compared with an existing method. Given that the study also showed no differences in effectiveness and costs, introducing the new framework in pharmacies may not lead to better incontinence care.</p

Synthetic Oligodeoxynucleotide CpG Motifs Activate Human Complement through Their Backbone Structure and Induce Complement-Dependent Cytokine Release

Bacterial and mitochondrial DNA, sharing an evolutionary origin, act as danger-associated molecular patterns in infectious and sterile inflammation. They both contain immunomodulatory CpG motifs. Interactions between CpG motifs and the complement system are sparsely described, and mechanisms of complement activation by CpG remain unclear. Lepirudin-anticoagulated human whole blood and plasma were incubated with increasing concentrations of three classes of synthetic CpGs: CpG-A, -B, and -C oligodeoxynucleotides and their GpC sequence controls. Complement activation products were analyzed by immunoassays. Cytokine levels were determined via 27-plex beads-based immunoassay, and CpG interactions with individual complement proteins were evaluated using magnetic beads coated with CpG-B. In whole blood and plasma, CpG-B and CpG-C (p 0.8 for all), led to time- and dose-dependent increase of soluble C5b-9, the alternative complement convertase C3bBbP, and the C3 cleavage product C3bc. GpC-A, -B, and -C changed soluble fluid-phase C5b-9, C3bBbP, and C3bc to the same extent as CpG-A, -B, and -C, indicating a DNA backbone–dependent effect. Dose-dependent CpG-B binding was found to C1q (r = 0.83; p = 0.006) and factor H (r = 0.93; p < 0.001). The stimulatory complement effect was partly preserved in C2-deficient plasma and completely preserved in MASP-2–deficient serum. CpG-B increased levels of IL-1β, IL-2, IL-6, IL-8, MCP-1, and TNF in whole blood, which were completely abolished by inhibition of C5 and C5aR1 (p < 0.05 for all). In conclusion, synthetic analogs of bacterial and mitochondrial DNA activate the complement system via the DNA backbone. We suggest that CpG-B interacts directly with classical and alternative pathway components, resulting in complement-C5aR1–dependent cytokine release

Development and validation of a prognostic score for long-term transplant-free survival in autoimmune hepatitis type 1

Background No prognostic score is currently available for long-term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni- & multivariate Cox regression in a 4-center Dutch cohort and validated in an independent 6-center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow-up 118 months; interquartile range 60-202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non-caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C-statistic 0.827; 95% CI 0.790-0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow-up of 74 months (interquartile range: 25-142 months). Predicted 5-year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%-24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%-9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%-11.4%); C-statistic 0.744 [95% CI 0.644-0.844]). Conclusions A Dutch-Belgian prognostic score for long-term transplant-free survival in AIH patients at diagnosis was developed and validated