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The digital divide in Indonesia is rather big. This study aims to investigate the demographic and socioeconomic determinants affecting the quantity of uses of the Internet in Indonesia. The data used are based on the National Socioeconomic Survey in 2021. The object of the analysis is population aged 15 years and above possessing at least one digital gadget. The dependent variable is the purpose of the Internet use. The independent variables included gender, age, number of household members, marital status, education, employment status, place of dwelling, island of residence, and number of types of digital gadgets owned. A binary logistic regression model was employed in the analysis. The results of the study indicate that a higher quantity of uses of the Internet is associated with a female sex, younger age, smaller number of household members, unmarried status, higher education, dwelling in urban areas, living in Java Island, and owning more than one type of digital gadgets. These findings suggest the need to improve access to the Internet among men, older people, ever-married individuals, rural dwellers, and Outer Java inhabitants, to promote family planning, to improve education and accessibility of more types of digital gadgets in order to bridge the digital divide and to boost the global competitiveness index 4.0 in Indonesia. more...

Fertilizers, pesticides and global warming are threatening freshwater aquatic ecosystems. Most of these are shallow ponds or slow-flowing streams or ditches dominated by submerged macrophytes, periphyton or phytoplankton. Regime shifts between the dominance of these primary producers can occur along a gradient of nutrient loading, possibly triggered by specific disturbances influencing their competitive interactions. However, phytoplankton dominance is less desirable due to lower biodiversity and poorer ecosystem function and services. In this study, we combined a microcosm experiment with a process-based model to test three hypotheses: 1) agricultural run-off (ARO), consisting of nitrate and a mixture of organic pesticides and copper, differentially affects primary producers and enhances the risk of regime shifts, 2) warming increases the risk of an ARO-induced regime shift to phytoplankton dominance and 3) custom-tailored process-based models support mechanistic understanding of experimental results through scenario comparison. Experimentally exposing primary producers to a gradient of nitrate and pesticides at 22°C and 26°C supported the first two hypotheses. ARO had direct negative effects on macrophytes, while phytoplankton gained from warming and indirect effects of ARO like a reduction in the competitive pressure exerted by other groups. We used the process-based model to test eight different scenarios. The best qualitative fit between modeled and observed responses was reached only when taking community adaptation and organism acclimation into account. Our results highlight the importance of considering such processes when attempting to predict the effects of multiple stressors on natural ecosystems. more...

Multiple stressors pose potential risk to aquatic ecosystems and are the main reasons for failing ecological quality standards. However, mechanisms how multiple stressors act on aquatic community structure and functioning are poorly understood. This is especially true for two important stressors types, hydrodynamic alterations and toxicants. Here we perform a mesocosm experiment in hydraulic flumes connected as a bypass to a natural stream to test the interactive effects of both factors on natural (inoculated from streams water) biofilms. Biofilms, i.e., the community of autotrophic and heterotrophic microorganisms and their extracellular polymeric substances (EPS) in association with substratum, are key players in stream functioning. We hypothesized (i) that the tolerance of biofilms toward toxicants (the herbicide Prometryn) decreases with increasing hydraulic stress. As EPS is known as an absorber of chemicals, we hypothesize (ii) that the EPS to cell ratio correlates with both hydraulic stress and herbicide tolerance. Tolerance values were derived from concentration-response assays. Both, the herbicide tolerance and the biovolume of the EPS significantly correlated with the turbulent kinetic energy (TKE), while the diversity of diatoms (the dominant group within the stream biofilms) increased with flow velocity. This indicates that the positive effect of TKE on community tolerance was mediated by turbulence-induced changes in the EPS biovolume. This conclusion was supported by a second experiment, showing decreasing effects of the herbicide to a diatom biofilm (Nitzschia palea) with increasing content of artificial EPS. We conclude that increasing hydrodynamic forces in streams result in an increasing tolerance of microbial communities toward chemical pollution by changes in EPS-mediated bioavailability of toxicants. more...

Abstract The PRISM project, funded by the EU’s Innovative Medicines Initiative, has identified a transdiagnostic, pathophysiological relationship between the integrity of the default mode network (DMN) and social dysfunction. To explore the causal link between DMN integrity and social behaviour, we employed a preclinical back-translation approach, using focal demyelination of the forceps minor to disrupt DMN connectivity in mice. By applying advanced techniques such as functional ultrasound imaging and automated analysis of social behaviour, we demonstrated that reduced DMN connectivity leads to impaired social interactions and increased anxiety in mice. Notably, these effects were reversible, indicating that the forceps minor, a critical fibre tract connecting key DMN regions in the prefrontal cortex, plays a crucial role in social function. This study provides direct evidence for a causal relationship between DMN integrity and social dysfunction, with potential implications for developing targeted treatments in precision psychiatry. more...

Abstract Reward processing dysfunctions e.g., anhedonia, apathy, are common in stress-related neuropsychiatric disorders including depression and schizophrenia, and there are currently no established therapies. One potential therapeutic approach is restoration of reward anticipation during appetitive behavior, deficits in which co-occur with attenuated nucleus accumbens (NAc) activity, possibly due to NAc inhibition of mesolimbic dopamine (DA) signaling. Targeting NAc regulation of ventral tegmental area (VTA) DA neuron responsiveness to reward cues could involve either the direct or indirect—via ventral pallidium (VP)—pathways. One candidate is the orphan G protein-coupled receptor GPR52, expressed by DA receptor 2 NAc neurons that project to VP. In mouse brain-slice preparations, GPR52 inverse agonist (GPR52-IA) attenuated evoked inhibitory postsynaptic currents at NAc-VP neurons, which could disinhibit VTA DA neurons. A mouse model in which chronic social stress leads to reduced reward learning and effortful motivation was applied to investigate GPR52-IA behavioral effects. Control and chronically stressed mice underwent a discriminative learning test of tone-appetitive behavior-sucrose reinforcement: stress reduced appetitive responding and discriminative learning, and these anticipatory behaviors were dose-dependently reinstated by GPR52-IA. The same mice then underwent an effortful motivation test of operant behavior-tone-sucrose reinforcement: stress reduced effortful motivation and GPR52-IA dose-dependently restored it. In a new cohort, GRABDA-sensor fibre photometry was used to measure NAc DA activity during the motivation test: in stressed mice, reduced motivation co-occurred with attenuated NAc DA activity specifically to the tone that signaled reinforcement of effortful behavior, and GPR52-IA ameliorated both deficits. These findings: (1) Demonstrate preclinical efficacy of GPR52 inverse agonism for stress-related deficits in reward anticipation during appetitive behavior. (2) Suggest that GPR52-dependent disinhibition of the NAc-VP-VTA-NAc circuit, leading to increased phasic NAc DA signaling of earned incentive stimuli, could account for these clinically relevant effects. more...

Abstract The Claustrum/dorsal endopiriform cortex complex (CLA) is an enigmatic brain region with extensive glutamatergic projections to multiple cortical areas. The transcription factor Nurr1 is highly expressed in the CLA, but its role in this region is not understood. By using conditional gene-targeted mice, we show that Nurr1 is a crucial regulator of CLA neuron identity. Although CLA neurons remain intact in the absence of Nurr1, the distinctive gene expression pattern in the CLA is abolished. CLA has been hypothesized to control hallucinations, but little is known of how the CLA responds to hallucinogens. After the deletion of Nurr1 in the CLA, both hallucinogen receptor expression and signaling are lost. Furthermore, functional ultrasound and Neuropixel electrophysiological recordings revealed that the hallucinogenic-receptor agonists’ effects on functional connectivity between prefrontal and sensorimotor cortices are altered in Nurr1-ablated mice. Our findings suggest that Nurr1-targeted strategies provide additional avenues for functional studies of the CLA. more...

Abstract Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology. more...

Abstract Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we used metatranscriptomics to investigate how IMMPs with different amounts of α − (1 → 6) glycosidic linkages affected microbial function during incubation with human fecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of α − (1 → 6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes. more...

The diversity and distribution of gelatinous macrozooplankton is described by presenting qualitative and quantitative data of the jellyfish and comb jelly community encountered in the North Sea and Skagerrak/Kattegat during January/February 2022. Data were generated as part of the North Sea Midwater Ring Net (MIK) survey [1], an ichthyoplankton survey conducted at night-time during the quarter 1 (Q1) International Bottom Trawl Survey (IBTS), aboard the Danish R/V DANA (DTU Aqua) and the Swedish R/V Svea (SLU). A total of 100 stations were investigated using a 13 m long Midwater Ring Net (MIK net) with an opening diameter of 2 m and a mesh size of 1.6 mm, which is 0.5 mm meshed for the last meter of the net and the cod end [2]. Samples were collected by double oblique hauls from the surface to 5 m above the seafloor [2]. Twelve gelatinous macrozooplankton species were encountered during the Q1 2022 survey. Species encountered included the hydrozoan jellyfish i) Aequorea vitrina, ii) Aglantha digitale, iii) Clytia spp., iv) Leuckartiara octona, v) Tima bairdii, vi) Muggiaea atlantica; the two scyphozoan jellyfish i) Cyanea capillata and ii) Cyanea lamarckii as well as the comb jelly (ctenophora) species i) Beroe spp., ii) Bolinopsis infundibulum, iii) Pleurobrachia pileus and iv) the non-indigenous Mnemiopsis leidyi. In total 4882 individual specimens from samples and sub-samples were analyzed and extrapolated to 71,888 records of gelatinous macrozooplankton in the investigation area. For rare species, the entire sample was analyzed, while for abundant taxa, sub-samples were used to assess abundances. The raw counts were converted to volume-specific densities (individuals m-3) and area-specific abundances (individuals m-2), based on calibrated flow meter recordings and recorded maximum depth of the MIK net during each haul. Further, size data for the different species were obtained from a total of 4775 individual gelatinous macrozooplankton organisms. Size data are presented in the accompanying database and was used to calculate species-specific wet weights, using published size-weight regressions [3]. In addition, we present spatial distribution patterns of the weight specific biomass for the total gelatinous macrozooplankton community as well as the sub-groups i) hydrozoa, ii) scyphozoa and iii) ctenophora across the investigation area. The presented data contribute to a baseline describing the gelatinous macrozooplankton diversity and distribution in the extended North Sea area during winter [3,4] and summer [5]. The data can contribute to address the question if gelatinous macrozooplankton densities increase due to global change pressures and will help to understand their interaction with commercially important fish species, which are assessed during the same surveys. As such, this data paper presents a valuable resource on biodiversity and non-indigenous species records and highlights the importance of monitoring gelatinous macrozooplankton to facilitate an ecosystem approach to assess if the ecosystem state meets a ‘good environmental status (GES)’, as demanded by the EU Marine Strategy Framework Directive (MSFD). more...

Seit dem 14.12.2019 sind die Mitgliedstaaten der EU verpflichtet, Erhebungen zu allen geregelten Unionsquarantäneschädlingen im Rahmen von Mehrjahresprogrammen durchzuführen. Damit hat sich die Anzahl der Erhebungen drastisch erhöht. In Deutschland wurden die Pflanzenschutzdienste als zuständige Behörden der Bundesländer, aber auch das Julius Kühn-Institut damit vor erhebliche Herausforderungen gestellt. Neben kritischen Aspekten der neuen Vorgaben im Erhebungsbereich, hat es sich aber auch gezeigt, dass in jedem Jahr Nachweise von Unionsquarantäneschädlingen basierend auf den Erhebungen erfolgen. Hinsichtlich einer erfolgreichen Tilgung eines Ausbruchs ist insbesondere die frühzeitige Feststellung eines Auftretens relevant. Hier können amtliche Erhebungen einen wichtigen Beitrag im Rahmen des Frühwarnsystems der EU und damit auch zu einer Verhinderung der Etablierung und weiteren Verbreitung von Unionsquarantäneschädlingen in Deutschland leisten. more...

Summary: Natural killer (NK) cells are critical for anti-metastatic immunity and can eliminate metastasizing tumor cells within circulation and sites of metastatic seeding. Here, we show that disseminated tumor cells (DTCs) colonizing the mouse lung secrete prostaglandin E2 (PGE2) to locally induce NK cell dysfunction, allowing outgrowing metastases to escape immune control and establish metastatic disease. Mechanistically, PGE2 signaling through its receptors EP2 and EP4 mediates NK cell dysfunction, which leads to reprogramming of NK cell gene expression and results in impaired production of anti-metastatic cytokines. In human cancer patients, the PGE2-EP2/EP4 axis is associated with NK cell dysfunction within distant organ metastases. Disabling EP2/EP4 signaling in NK cells prevents their dysfunction in DTC-colonized lungs and achieves effective NK cell-mediated control of metastatic disease. Our findings reveal a suppressive signaling axis exploited by metastasizing tumor cells to escape immune control in distant organs that could be targeted for metastatic cancer therapy. more...

Abstract Background Single-cell sequencing techniques are revolutionizing every field of biology by providing the ability to measure the abundance of biological molecules at a single-cell resolution. Although single-cell sequencing approaches have been developed for several molecular modalities, single-cell transcriptome sequencing is the most prevalent and widely applied technique. SPLiT-seq (split-pool ligation-based transcriptome sequencing) is one of these single-cell transcriptome techniques that applies a unique combinatorial-barcoding approach by splitting and pooling cells into multi-well plates containing barcodes. This unique approach required the development of dedicated computational tools to preprocess the data and extract the count matrices. Here we compare eight bioinformatic pipelines (alevin-fry splitp, LR-splitpipe, SCSit, splitpipe, splitpipeline, SPLiTseq-demultiplex, STARsolo and zUMI) that have been developed to process SPLiT-seq data. We provide an overview of the tools, their computational performance, functionality and impact on downstream processing of the single-cell data, which vary greatly depending on the tool used. Results We show that STARsolo, splitpipe and alevin-fry splitp can all handle large amount of data within reasonable time. In contrast, the other five pipelines are slow when handling large datasets. When using smaller dataset, cell barcode results are similar with the exception of SPLiTseq-demultiplex and splitpipeline. LR-splitpipe that is originally designed for processing long-read sequencing data is the slowest of all pipelines. Alevin-fry produced different down-stream results that are difficult to interpret. STARsolo functions nearly identical to splitpipe and produce results that are highly similar to each other. However, STARsolo lacks the function to collapse random hexamer reads for which some additional coding is required. Conclusion Our comprehensive comparative analysis aids users in selecting the most suitable analysis tool for efficient SPLiT-seq data processing, while also detailing the specific prerequisites for each of these pipelines. From the available pipelines, we recommend splitpipe or STARSolo for SPLiT-seq data analysis. more...

LiNixMnyCozO2 cathode materials combined with Si‐based anode materials are current state‐of‐the‐art high energy density chemistries for lithium ion batteries. Increasing the upper cut‐off voltage is an intriguing approach to achieve even higher energy density in lithium ion batteries. However, poor oxidation stability of the state‐of‐the‐art electrolytes leads to transition metal dissolution (TMD), migration, and deposition (TMDMD) on the negative electrode, followed by sudden and rapid capacity fade. Furthermore, the chemical instability of the lithium hexafluorophosphate causes hydro‐fluoric acid to develop, which targets the native SiOx layers on silicon anodes and breaks the chemical bond to the carboxymethylcellulose sodium salt binder. Herein, a fluorine‐rich electrolyte formulation consisting of lithium‐bis(fluorsulfonyl)imide with fluoroethylene carbonate (FEC): bis(2,2,2,) trifluoroethyl carbonate (BFEC) was applied in NMC811||10%SiOx‐90%graphite cells to achieve high oxidation stability and prevent TMD and deposition. Up‐to‐date, this is the premier electrochemical performance reported in literature with a capacity retention of 94.5% and 92.2% with 0.5 °C and 4.5 V upper cut‐off voltage cycling at 20 and 40 °C after 100 cycles, respectively. The post mortem analysis showed that stabilization is achieved by forming inorganic‐ and salt‐rich interphases that protect the electrolyte versus decomposition at the electrode. more...

ObjectivesThe aim of this study was to analyze the precipitation of Cerium(III)nitrate hexahydrate [Ce(NO3)3] or Samarium(III)nitrate hexahydrate [Sm(NO3)3] solutions on human enamel with and without a salivary pellicle. Investigated parameters were At%Ce and At%Sm measured using energy dispersive x-ray spectroscopy (EDX) after test solution (two concentrations) application.Materials and methodsPrecipitation of Ce(NO3)3 and Sm(NO3)3 solutions was examined on human enamel with and without a salivary pellicle. 6 enamel specimens each were obtained from 12 freshly extracted human third molars. These specimens were ground flat and polished. A salivary pellicle was created on 3 of the 6 specimens per tooth by storing the samples in human saliva. Subsequently, an aqueous solution of Ce(NO3)3 was applied to 2 of the 6 specimens (one with, one without salivary pellicle) for 60 s. The same was carried out with an aqueous solution of Sm(NO3)3 on 2 further specimens. The remaining 2 specimens from each tooth were treated with demineralized water (negative control). Ce(NO3)3 and Sm(NO3)3 solutions were applied at 25 or 50 wt% (aqueous solutions). The test materials and concentrations were distributed using a randomization table. After 60 s exposure and rinsing with demineralized water, the elemental composition (Ce, Sm, Ca, P, O, N, Na, Mg) of the enamel surface was analyzed by EDX. Atomic percentages (At%), differences (ΔAt%) and calcium/phosphorous-ratios (Ca/P-ratios) were calculated and analyzed non-parametrically (α = 0.05).Results2.0–2.3 At%Ce (median) was detected on Ce(NO3)3-treated enamel and 0.4–0.7 At% Sm (median) was detected on Sm(NO3)3-treated enamel. Ce was only detected on the surfaces after application of Ce(NO3)3, Sm only after application of Sm(NO3)3. The Ca/P-ratio was significantly lower (1.37–1.59; p = 0.028) after the application of 25% and 50%Ce(NO3)3 as well as 50%Sm(NO3)3 compared to the control treatment (demineralized water; 1.61–1.63). After treatment with Ce(NO3)3, At%Ca and At%Na were significantly lower (p ≤ 0.043) compared to treatment with Sm(NO3)3. No significant differences were found between specimens treated with 25% or 50% lanthanide nitrate solution. Presence of a salivary pellicle had no significant influence on the measured At% with the exception of specimens treated with 50% Sm(NO3)3 with increased At%Sm (p ≤ 0.046).ConclusionsCe(NO3)3 and Sm(NO3)3 precipitate on human enamel independently of the presence of a salivary pellicle. more...

BackgroundNeuropsychopharmacological compounds may exert complex brain-wide effects due to an anatomically and genetically broad expression of their molecular targets and indirect effects via interconnected brain circuits. Electrophysiological measurements in multiple brain regions using electroencephalography (EEG) or local field potential (LFP) depth-electrodes may record fingerprints of such pharmacologically-induced changes in local activity and interregional connectivity (pEEG/pLFP). However, in order to reveal such patterns comprehensively and potentially derive mechanisms of therapeutic pharmacological effects, both activity and connectivity have to be estimated for many brain regions. This entails the problem that hundreds of electrophysiological parameters are derived from a typically small number of subjects, making frequentist statistics ill-suited for their analysis.MethodsWe here present an optimized interpretable machine-learning (ML) approach which relies on predictive power in individual recording sequences to extract and quantify the robustness of compound-induced neural changes from multi-site recordings using Shapley additive explanations (SHAP) values. To evaluate this approach, we recorded LFPs in mediodorsal thalamus (MD), prefrontal cortex (PFC), dorsal hippocampus (CA1 and CA3), and ventral hippocampus (vHC) of mice after application of amphetamine or of the dopaminergic antagonists clozapine, raclopride, or SCH23390, for which effects on directed neural communication between those brain structures were so far unknown.ResultsOur approach identified complex patterns of neurophysiological changes induced by each of these compounds, which were reproducible across time intervals, doses (where tested), and ML algorithms. We found, for example, that the action of clozapine in the analysed cortico-thalamo-hippocampal network entails a larger share of D1—as opposed to D2-receptor induced effects, and that the D2-antagonist raclopride reconfigures connectivity in the delta-frequency band. Furthermore, the effects of amphetamine and clozapine were surprisingly similar in terms of decreasing thalamic input to PFC and vHC, and vHC activity, whereas an increase of dorsal-hippocampal communication and of thalamic activity distinguished amphetamine from all tested anti-dopaminergic drugs.ConclusionOur study suggests that communication from the dorsal hippocampus scales proportionally with dopamine receptor activation and demonstrates, more generally, the high complexity of neuropharmacological effects on the circuit level. We envision that the presented approach can aid in the standardization and improved data extraction in pEEG/pLFP-studies. more...

The motivation of this study was to solve the high $\rm I_{D,off}$ problem in 8 Volt N-channel MOSFET. We experimented with implanting nitrogen into LDD at various doses. As a result, $\rm I_{D,off}$ increases and $\rm BV_{DSS}$ decreases as the dose increases. When it exceeds 1.0E15 cm $^{-2}$ , the occurrence of tail-type $\rm I_{D,off}$ and $\rm BV_{DSS}$ that deviate from the normal distribution increases. Implanted nitrogen enhances the diffusion of dopants in the LDD bulk but suppresses it on the silicon surface. As a result, the depletion curvature at the LDD edge becomes a negative shape and increases the electric field. We performed the same experiment on logic MOSFETs to comprehensively analyze other electrical effects. Nitrogen improves the HCI immunity of MOSFETs but degrades for 2.5 Volt and 8 Volt MOSFETs when the dose is above 1.0E15 cm $^{-2}$ . The short-channel effect of 2.5 Volt MOSFET is insensitive to nitrogen but is suppressed in CORE MOSFET when the dose is over 1.3E15 cm $^{-2}$ . Nitrogen changes $\rm I_{D,sat}$ through interactions with co-implanted species and nitrogen dose. As a result, nitrogen co-implanted with phosphorus shows a parabolic-like $\rm I_{D,sat}$ trend. However, in the case of CORE MOSFET implanted with arsenic, $\rm I_{D,sat}$ does not show a parabolic-like trend but increases continuously. This experiment did not find much benefit from nitrogen implantation for 2.5 Volt and 8 Volt MOSFETs. For all MOSFETs, it is recommended that the nitrogen dosage not exceed 1.0E15 cm $^{-2}$ . more...

ABSTRACTThis paper analyses different categories of legacy from socialist central planning policies (SCPP) for urban development. How have city-specific measures by SCPP affected local economic systems, and have there been long-term consequences for cities even after their return to a market economy? Drawing from case studies of four East German cities, we identify several types of socialist policy measures that determine the local economic performance up to now. The impact of some measures was primarily displayed via ‘soft’ factors such as local image and identity and the attitudes of residents, local decision-makers. more...

Summary: Without data, knowing how to respond to the COVID-19 pandemic would have been impossible. Data were crucial to understanding how the disease spread and which efforts successfully protected people. Yet, national agencies often did not publish their data in an optimal way, which made responding to the pandemic challenging. Therefore, learning from what went well and what did not for the future is crucial. Drawing on our first-hand experience of republishing COVID-19 data, we identify seven best practices for how to publish data in an optimal way: collect the data that are relevant; make them comparable; clearly document the data; share them frequently and promptly; publish data at a stable location; choose a reusable format; and license others to reuse the data. These best practices are straightforward, inexpensive, and achievable, with some countries already having implemented most of them during the COVID-19 pandemic. More government agencies following these best practices will enable others to access their data and address the world's public health challenges—including the next pandemic. more...

Introducción: los glucocorticoides (GC) han sido ampliamente utilizados en el tratamiento de patologías oculares debido a sus efectos antiinflamatorios y anti-angiogénicos. Se ha sugerido que el mecanismo de acción antiangiogénico de los GC puede estar relacionado con la enzima fosfatidilinositol-3-cinasa (PI3K), la cual desempeña un papel crucial en la angiogénesis mediada por el receptor nicotínico de acetilcolina alfa 7 (α7-nAChR). La PI3K es una enzima lipoproteica heterodimérica compuesta por las subunidades; reguladora (p85) y catalítica (p110). Objetivo: esta revisión examina la evidencia de la interrelación entre los GC, y la vía de señalización de PI3K activada por α7-nAChR en la angiogénesis “in vitro”. Metodología: se realizó una revisión bibliográfica utilizando los motores de búsqueda PubMed y Web of Science, relacionando los conceptos “endothelial cell”, “α7-nAChR”, “PI3K”, y “glucocorticoid”. Resultados: se seleccionaron 30 artículos que informaron sobre la expresión de α7-nAChR y PI3K en células endoteliales humanas. Además, del efecto de dexametasona sobre las subunidades de PI3K y Akt en modelos humano, murino y porcino. A partir de estos hallazgos, se propuso un mecanismo mediante el cual los GC ejercen su efecto antiangiogénico a través de la modulación en la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR en células endoteliales humanas. Conclusión: los antecedentes evidencian que dexametasona, ejerce su mecanismo de acción anti-angiogénico mediante el incremento de la expresión de la subunidad inhibitoria p85 de PI3K activada por α7-nAChR. Estos hallazgos podrían contribuir a explicar la posible falla terapéutica en el área oftalmológica en pacientes fumadores. more...

The Bailiwick of Jersey (“Jersey”) and the UK face similar challenges when attributing criminal liability to corporate entities. Both jurisdictions have sought to meet some of these challenges by the introduction of deferred prosecution agreements (“DPAs”) and failure to prevent (“FTP”) offences. King and Lord (2020) provide an insightful and valid critique of the DPA regime in England and Wales and its application in practice by the courts of that jurisdiction. While the DPA regime in Jersey has been developed by building on the regime in England and Wales, there are significant differences. This paper provides an overview of DPAs in Jersey, highlighting aspects of the regime that address the weaknesses identified by King and Lord. Additionally, the paper uses a basic game-theoretic approach to analyse three different criminal justice environments: one without DPAs; one with English DPAs and one with Jersey DPAs (Appendix A). The results from this analysis are then considered against the idiosyncrasies of the different prosecution regimes: self-reporting requirements; the probability of a prosecution; deterrent effects and how DPAs modify the effectiveness of the criminal justice system. The impact on deterrence is illustrated by providing a simple example of a deterrence function (Appendix B). It is submitted that aspects of DPAs in Jersey better serve to increase the effectiveness of the criminal justice system. This discussion and the results regarding the effectiveness of the different DPA regimes is suggested as relevant for legislators and practitioners in other jurisdictions who are either contemplating the introduction of a DPA regime or the principles that underpin the approval of a DPA in practice. more...

Abstract LiNi1/3Mn1/3Co1/3O2 (NMC‐111) is one of the most popular cathode materials in Li‐ion batteries. However, chemical and structural instabilities of the cathode/electrolyte interface at high charge cut‐off voltages cause capacity fading. Surface modifications using metal oxides are promising candidates to suppress capacity fading. Here a systematic study on the degradation mechanism of an uncoated NMC‐111 powder electrode is presented. Moreover, the effect of an Al‐doped ZnO (Al:ZnO) coating layer on the structural and chemical stabilities of NMC‐111 electrode cycled at high charge cut‐off voltages is analyzed using X‐ray photoelectron spectroscopy, scanning electron microscopy and analytical transmission electron microscopy as well as electrochemical testing. The coating is applied to commercial NMC‐111 powder using a microwave‐assisted sol‐gel synthesis method. In the case of uncoated NMC‐111 electrodes, pitting corrosion due to hydrofluoric acid attacking the electrode surface, cation mixing, and an irreversible phase transformation from a trigonal layered to a rock‐salt phase occurs, causing capacity fading. While, in the case of Al:ZnO – coated NMC‐111 electrodes, pitting corrosion, cation mixing, and the irreversible phase transformation are mitigated. Therefore, the capacity retention and rate capability are improved as the coating layer protects the electrode surface from the direct electrolyte exposure. more...

Der vorliegende Beitrag liefert empirisch gestützte Hinweise, dass Hochschulen nicht nur zum Wissenschaftssystem gehören, sondern auch integraler Bestandteil des pädagogisch organisierten Systems des lebenslangen Lernens bzw. des Bildungswesens sind. Die hier tätige Leitprofession – die Professorenschaft – inkorporiert daher die soziale Identität eines(r) Pädagogen*in. Flankiert wird die Argumentation durch Hinweise, welche die prominente These vom Technologiedefizit der Pädagogik nachhaltig relativieren. more...

Abstract Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress. more...

Abstract Perennial energy crops (PECs) can reduce the negative impacts of intensive silage maize cultivation on agroecosystems in Central Europe. Furthermore, the remaining vegetation of PECs after harvest may provide suitable habitat and more beneficial overwintering conditions for arthropods than maize. It was hypothesized that after harvest and in winter, arthropod abundance and biomass are higher in PECs than in silage maize. In a field experiment arranged in a factorial split‐plot design of eight main plots (plot size: 240 m2), the two PECs cup plant (Silphium perfoliatum L.) and field grass were compared with silage maize (Zea mays L.) regarding their suitability as autumn (post‐harvest) and overwintering habitats for arthropods. Soil temperature, moisture as well as biomass and abundance of autumn‐active and overwintering arthropods were analyzed for these three crops. Suction sampling was used during autumn and emerging arthropods were sampled with emergence trap sets in spring. In PEC plots, soils were moister and less exposed to cold temperatures than in silage maize. Compared with silage maize, total arthropod abundance and biomass were higher in PEC plots for both sampling periods. Results were similar for most examined arthropod taxa. The results of this study demonstrate that, compared with silage maize, PECs provide suitable post‐harvest habitats and constitute more suitable overwintering habitats for arthropods. Differences are likely to be based on lack of disturbance and the provision of vegetation structures after harvest that function as overwintering habitats for arthropods. It can be concluded that the positive effects of PECs on ground arthropods are not limited to their growing time but continue to a certain extend after harvest and during winter. more...

Abstract Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. more...

Modular Cloning (MoClo) is based on libraries of standardized genetic parts that can be directionally assembled via Golden Gate cloning in one-pot reactions into transcription units and multigene constructs. Here, a team of bachelor students established a MoClo toolkit for the protist Leishmania tarentolae in the frame of the international Genetically Engineered Machine (iGEM) competition. Our modular toolkit is based on a domesticated version of a commercial LEXSY expression vector and comprises 34 genetic parts encoding various affinity tags, targeting signals as well as fluorescent and luminescent proteins. We demonstrated the utility of our kit by the successful production of 16 different tagged versions of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein in L. tarentolae liquid cultures. While highest yields of secreted recombinant RBD were obtained for GST-tagged fusion proteins 48 h post induction, C-terminal peptide tags were often degraded and resulted in lower yields of secreted RBD. Fusing secreted RBD to a synthetic O-glycosylation SP20 module resulted in an apparent molecular mass shift around 10 kDa. No disadvantage regarding the production of RBD was detected when the three antibiotics of the LEXSY system were omitted during the 48-h induction phase. Furthermore, the successful purification of secreted RBD from the supernatant of L. tarentolae liquid cultures was demonstrated in pilot experiments. In summary, we established a MoClo toolkit and exemplified its application for the production of recombinant proteins in L. tarentolae. more...

Summary: Developing an in vitro platform to study neuron-oligodendrocyte interaction, particularly myelination, is essential to understand aberrant myelination in neuropsychiatric and neurodegenerative diseases. Here, we provide a controlled, direct co-culture protocol for human induced-pluripotent-stem-cell (hiPSC)-derived neurons and oligodendrocytes on three-dimensional (3D) nanomatrix plates. We describe steps to differentiate hiPSCs into cortical neurons and oligodendrocyte lineage cells on 3D nanofibers. We then detail the detachment and isolation of the oligodendrocyte lineage cells, followed by neuron-oligodendrocyte co-culture in this 3D microenvironment. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. more...

IntroductionIndividual metabolism has been identified as a key variable for predicting responses of individuals and populations to climate change, particularly for aquatic ectotherms such as fishes. Predictions of organism standard metabolic rate (SMR), and the thermal sensitivity of metabolic rate are typically based on allometric scaling rules and respirometry-based measures of respiratory potential under laboratory conditions. The relevance of laboratory-based measurement and theoretical allometric rules to predict performance of free-ranging animals in complex natural settings has been questioned, but determining time averaged metabolic rate in wild aquatic animals is challenging.MethodsHere we draw on stable isotope compositions of aragonite in fish otoliths to estimate time averaged experienced temperature and expressed field metabolic rate (FMR) simultaneously and retrospectively at an individual level. We apply the otolith FMR proxy to a population of European plaice (Pleuronectes platessa) from the North Sea during a period of rapid warming between the 1980s to the mid-2000s, sampling otolith tissue grown in both juvenile and adult stages.ResultsAmong-individual variations in realized mass-specific FMR were large and independent of temperature and scaled positively with body size in adult life stages, contradicting simplistic assumptions that FMR follows scaling relationships inferred for standard metabolic rates (SMR). In the same individuals, FMR in the first summer of life co-varied positively with temperature.DiscussionWe find strong evidence for the presence of consistent metabolic phenotypes within the sampled population, as FMR in the first year of life was the strongest single predictor for among individual variation in FMR at the point of sampling. Nonetheless, best fitting models explained only 20% of the observed variation, pointing to large among-individual variation in FMR that is unexplained by body mass, temperature or metabolic phenotype. Stable isotope-derived estimates of field metabolic rate have great potential to expand our understanding of ecophysiology in general and especially mechanisms underpinning the relationships between animal performance and changing environmental and ecological conditions. more...

IntroductionS-ketamine has received great interest due to both its antidepressant effects and its potential to induce psychosis when administered subchronically. However, no studies have investigated both its acute and delayed effects using in vivo small-animal imaging. Recently, functional ultrasound (fUS) has emerged as a powerful alternative to functional magnetic resonance imaging (fMRI), outperforming it in sensitivity and in spatiotemporal resolution. In this study, we employed fUS to thoroughly characterize acute and delayed S-ketamine effects on functional connectivity (FC) within the same cohort at slow frequency bands ranging from 0.01 to 1.25 Hz, previously reported to exhibit FC.MethodsWe acquired fUS in a total of 16 healthy C57/Bl6 mice split in two cohorts (n = 8 received saline, n = 8 S-ketamine). One day after the first scans, performed at rest, the mice received the first dose of S-ketamine during the second measurement, followed by four further doses administered every 2 days. First, we assessed FC reproducibility and reliability at baseline in six frequency bands. Then, we investigated the acute and delayed effects at day 1 after the first dose and at day 9, 1 day after the last dose, for all bands, resulting in a total of four fUS measurements for every mouse.ResultsWe found reproducible (r > 0.9) and reliable (r > 0.9) group-average readouts in all frequency bands, only the 0.01–0.27 Hz band performing slightly worse. Acutely, S-ketamine induced strong FC increases in five of the six bands, peaking in the 0.073–0.2 Hz band. These increases comprised both cortical and subcortical brain areas, yet were of a transient nature, FC almost returning to baseline levels towards the end of the scan. Intriguingly, we observed robust corticostriatal FC decreases in the fastest band acquired (0.75 Hz–1.25 Hz). These changes persisted to a weaker extent after 1 day and at this timepoint they were accompanied by decreases in the other five bands as well. After 9 days, the decreases in the 0.75–1.25 Hz band were maintained, however no changes between cohorts could be detected in any other bands.DiscussionIn summary, the study reports that acute and delayed ketamine effects in mice are not only dissimilar but have different directionalities in most frequency bands. The complementary readouts of the employed frequency bands recommend the use of fUS for frequency-specific investigation of pharmacological effects on FC. more...

Molecular designs improving the performance of thermally activated delayed fluorescence (TADF) emitters are greatly desired for optoelectronic applications. The authors propose a molecular geometry with donor and acceptor moieties facing each other separated by an anthracene bridge, giving rise to hot exciplex states producing color pure and fast TADF emission. more...

This data article includes a qualitative and quantitative description of the gelatinous macrozooplankton community of the North Sea during January-February 2021. Sampling was conducted during the 1st quarter International Bottom Trawl Survey (IBTS) on board the Danish R/V DANA (DTU Aqua Denmark) and the Swedish R/V Svea (SLU Sweden), as part of the ichthyoplankton investigation during night-time. A total of 147 stations were investigated in the western, central and eastern North Sea as well as the Skagerrak and Kattegat. Sampling was conducted with a 13 m long Midwater Ring Net (MIK net, Ø 2 m, mesh size 1.6 mm, cod end with smaller mesh size of 500 µm), equipped with a flow meter. The MIK net was deployed in double oblique hauls from the surface to c. 5 m above the sea floor [1,2]. Samples were visually analysed unpreserved on a light table and/or with a stereomicroscope or magnifying lamp within 2 hours after catch. A total of 13,510 individuals were counted/sized. Twelve gelatinous macrozooplankton species or genera were encountered, namely the hydrozoan Aequorea vitrina, Aglantha digitale, Clytia spp., Leuckartiara octona, Tima bairdii, Muggiaea atlantica; the scyphozoans Cyanea capillata and Cyanea lamarckii and the ctenophores Beroe spp., Bolinopsis infundibulum, Mnemiopsis leidyi, Pleurobrachia pileus. Abundance data are presented on a volume specific (m−3) and area specific (m−2) basis. Size data have been used to estimate wet weights based on published length-weight regressions (see Table 1). For the groups i) hydrozoan jellyfish, ii) scyphozoan jellyfish, iii) ctenophores, as well as iv) grouped gelatinous macrozooplankton, spatial weight specific distribution patterns are presented. This unpublished dataset contributes baseline information about the gelatinous macrozooplankton diversity and its specific distribution patterns in the extended North Sea area during winter (January-February) 2021. These data can be an important contribution to address global change impacts on marine systems, especially considering gelatinous macrozooplankton abundance changes in relation to anthropogenic stressors. more...

Abstract Silicon (Si)‐based negative electrodes have attracted much attention to increase the energy density of lithium ion batteries (LIBs) but suffer from severe volume changes, leading to continuous re‐formation of the solid electrolyte interphase and consumption of active lithium. The pre‐lithiation approach with the help of positive electrode additives has emerged as a highly appealing strategy to decrease the loss of active lithium in Si‐based LIB full‐cells and enable their practical implementation. Here, the use of lithium squarate (Li2C4O4) as low‐cost and air‐stable pre‐lithiation additive for a LiNi0.6Mn0.2Co0.2O2 (NMC622)‐based positive electrode is investigated. The effect of additive oxidation on the electrode morphology and cell electrochemical properties is systematically evaluated. An increase in cycle life of NMC622||Si/graphite full‐cells is reported, which grows linearly with the initial amount of Li2C4O4, due to the extra Li+ ions provided by the additive in the first charge. Post mortem investigations of the cathode electrolyte interphase also reveal significant compositional changes and an increased occurrence of carbonates and oxidized carbon species. This study not only demonstrates the advantages of this pre‐lithiation approach but also features potential limitations for its practical application arising from the emerging porosity and gas development during decomposition of the pre‐lithiation additive. more...

Abstract Background The IκB kinase (IKK) complex, comprising the two enzymes IKKα and IKKβ, is the main activator of the inflammatory transcription factor NF-κB, which is constitutively active in many cancers. While several connections between NF-κB signaling and the oncogene c-Myc have been shown, functional links between the signaling molecules are still poorly studied. Methods Molecular interactions were shown by co-immunoprecipitation and FRET microscopy. Phosphorylation of c-Myc was shown by kinases assays and its activity by improved reporter gene systems. CRISPR/Cas9-mediated gene knockout and chemical inhibition were used to block IKK activity. The turnover of c-Myc variants was determined by degradation in presence of cycloheximide and by optical pulse-chase experiments.. Immunofluorescence of mouse prostate tissue and bioinformatics of human datasets were applied to correlate IKKα- and c-Myc levels. Cell proliferation was assessed by EdU incorporation and apoptosis by flow cytometry. Results We show that IKKα and IKKβ bind to c-Myc and phosphorylate it at serines 67/71 within a sequence that is highly conserved. Knockout of IKKα decreased c-Myc-activity and increased its T58-phosphorylation, the target site for GSK3β, triggering polyubiquitination and degradation. c-Myc-mutants mimicking IKK-mediated S67/S71-phosphorylation exhibited slower turnover, higher cell proliferation and lower apoptosis, while the opposite was observed for non-phosphorylatable A67/A71-mutants. A significant positive correlation of c-Myc and IKKα levels was noticed in the prostate epithelium of mice and in a variety of human cancers. Conclusions Our data imply that IKKα phosphorylates c-Myc on serines-67/71, thereby stabilizing it, leading to increased transcriptional activity, higher proliferation and decreased apoptosis. more...

As Vehicular Networks rely increasingly on sensed data to enhance functionality and safety, efficient and distributed data analysis is needed to effectively leverage new technologies in real-world applications. Considering the tens of GBs per hour sensed by modern connected vehicles, traditional analysis, based on global data accumulation, can rapidly exhaust the capacity of the underlying network, becoming increasingly costly, slow, or even infeasible. Employing the edge processing paradigm, which aims at alleviating this drawback by leveraging vehicles’ computational power, we are the first to study how to localize, efficiently and distributively, relevant data in a vehicular fleet for analysis applications. This is achieved by appropriate methods to spread requests across the fleet, while efficiently balancing the time needed to identify relevant vehicles, and the computational overhead induced on the Vehicular Network. We evaluate our techniques using two large sets of real-world data in a realistic environment where vehicles join or leave the fleet during the distributed data localization process. As we show, our algorithms are both efficient and configurable, outperforming the baseline algorithms by up to a $40\times $ speedup while reducing computational overhead by up to $3\times $ , while providing good estimates for the fraction of vehicles with relevant data and fairly spreading the workload over the fleet. All code as well as detailed instructions are available at https://github.com/dcs-chalmers/dataloc_vn. more...

There are several pathways for CO2 fixation in photoautotrophic and chemoautotrophic microorganisms. Here, the authors provide experimental demonstration for the operation of the reductive glycine pathway in a natural microorganism, Desulfovibrio desulfuricans. more...

WATARA-MODE ist ein dreijähriges Projekt am Fachinstitut für nationale und internationale Angelegenheiten der Pflanzengesundheit des Julius Kühn-Instituts (JKI) in Braunschweig. Ziel des Projektes ist die Durchführung von Waren- und Taxon basierten Risikoanalysen sowie die Modellierung quantifizierter Schäden an Pflanzen, um die Notwendigkeit und den Umfang pflanzengesundheitlicher Maßnahmen mit Hilfe einer dynamischen Kosten-Nutzen-Analyse besser einschätzen zu können. Das Projekt gliedert sich in zwei Bereiche: Im ersten Teil werden Frühwarnlisten bisher unbekannter potenzieller Quarantäneschadorganismen (QSO; Horizon Scanning) anhand zweier Fallstudien erstellt: In der ersten Studie sollen, basierend auf einem in dem EU-Projekt DROPSA (Strategies to develop effective, innovative, and practical approaches to protect major European fruit crops from pests and pathogens) entwickelten Priorisierungsverfahren,potentielle QSO ermittelt werden, die mit der Einfuhr von Bambus nach Deutschland und in die EU verschleppt werden könnten. Bambus wird mehr und mehr auch als Verpackungsmaterial verwendet, da es, anders als Verpackungen aus Holz, keinen pflanzengesundheitlichen Regelungen unterliegt. In der zweiten Studie soll die weltweit verbreitete und mehr als 3000 Arten umfassende Prachtkäfergattung Agrilus spp. auf potenzielle QSO gescreent werden. Im Projekt findet eine erste Abschätzung des pflanzengesundheitlichen Risikos durch die identifizierten Schadorganismen statt und es werden kurze Datenblätter für die relevanten Organismen erstellt, die der Europäischen und Mediterranen Pflanzenschutzorganisation (EPPO) zur Verfügung gestellt werden sollen. Die Risiken werden national und international kommuniziert. Dieses Verfahren hilft, mögliche Risiken rechtzeitig zu erkennen und vorsorglich Maßnahmen zu entwickeln, um ihnen frühzeitig zu begegnen. Im zweiten Teil des Projektes wird ein Modell zur Ermittlung von Schadensschwellen nicht-heimischer Pflanzenschadorganismen zur wissenschaftlichen Bewertung der Verhältnismäßigkeit von Maßnahmen (Kosten-Nutzen-Analyse) erstellt. Etablierungs- und Ausbreitungsmodellierung stellen zusammen mit der Populationsentwicklung und Wirtspflanzenverbreitung die Grundlage für eine Modellierung des potentiellen Schadens dar. Das Modell wird auf dem im bereits abgeschlossenen BMEL-Projekt ProgRAMM entwickelten Modell MoPSi basieren (Heß et al., 2020). Durch die Verknüpfung von Ausbreitungs-, Populations- und Wirtspflanzenmodellen mit einem zu entwickelnden Schadensanalysemodell können die durch die Schadorganismen verursachten Schäden abgeschätzt und die Auswirkungen verschiedener Behandlungsmöglichkeiten dargestellt werden (Abb. 1). Auf dieser Basis können Schwellenwerte für konkrete Handlungsempfehlungen ermittelt werden, z.B. ob Maßnahmen überhaupt durchgeführt werden sollen, welche Maßnahme oder Maßnahmenkombination in Frage kommt usw. Kern des zu entwickelnden Schadensanalysemodells ist die dynamische Gegenüberstellung ökonomischer, sozialer und ökologischer Schäden mit den Kosten unterschiedlicher pflanzengesundheitlicher Maßnahmen zur Schadensminimierung. Letztendlich soll das Modell eine Unterstützung bei der Identifizierung effizienter, praxistauglicher Strategien zur Vermeidung der Einschleppung oder weiteren Verbreitung (einschließlich Verringerung von Schäden) und zur Bekämpfung von Schadorganismen liefern. Der Fokus liegt dabei zunächst auf dem Asiatischen Laubholzbockkäfer (Anoplophora glabripennis), dem Japankäfer (Popilia japonica), der Marmorierten Baumwanze (Halyomorpha halys), der Mittelmeerfruchtfliege (Ceratitis capitata), dem Asiatischen Eschenprachtkäfer (Agrilus planipennis) und dem Bronzefarbenen Birkenbohrer (Agrilus anxius) sowie auf weiteren potentiell gefährlichen Arten, die durch das erste Teilprojekt identifiziert werden. WATARA-MODE (Förderkennzeichen: 2818716X19) ist eines der Projekte aus den Themenfeldern Pflanzenschutz und Pflanzengesundheit, gefördert im Rahmen des Programms zur Innovationsförderung des Bundesministeriums für Ernährung und Landwirtschaft. Projektträger ist die Bundesanstalt für Landwirtschaft und Ernährung (ptble). more...

In acid drainage environments, biosulfidogenesis by sulfate-reducing bacteria (SRB) attenuates the extreme conditions by enabling the precipitation of metals as their sulfides, and the neutralization of acidity through proton consumption. So far, only a handful of moderately acidophilic SRB species have been described, most of which are merely acidotolerant. Here, a novel species within a novel genus of moderately acidophilic SRB is described, Acididesulfobacillus acetoxydans gen. nov. sp. nov. strain INE, able to grow at pH 3.8. Bioreactor studies with strain INE at optimum (5.0) and low (3.9) pH for growth showed that strain INE alkalinized its environment, and that this was more pronounced at lower pH. These studies also showed the capacity of strain INE to completely oxidize organic acids to CO2, which is uncommon among acidophilic SRB. Since organic acids are mainly in their protonated form at low pH, which increases their toxicity, their complete oxidation may be an acid stress resistance mechanism. Comparative proteogenomic and membrane lipid analysis further indicated that the presence of saturated ether-bound lipids in the membrane, and their relative increase at lower pH, was a protection mechanism against acid stress. Interestingly, other canonical acid stress resistance mechanisms, such as a Donnan potential and increased active charge transport, did not appear to be active. more...

Due to alternative splicing, the SLCO1B3 gene encodes two protein variants; the hepatic uptake transporter liver-type OATP1B3 (Lt-OATP1B3) and the cancer-type OATP1B3 (Ct-OATP1B3) expressed in several cancerous tissues. There is limited information about the cell type-specific transcriptional regulation of both variants and about transcription factors regulating this differential expression. Therefore, we cloned DNA fragments from the promoter regions of the Lt-SLCO1B3 and the Ct-SLCO1B3 gene and investigated their luciferase activity in hepatocellular and colorectal cancer cell lines. Both promoters showed differences in their luciferase activity depending on the used cell lines. We identified the first 100 bp upstream of the transcriptional start site as the core promoter region of the Ct-SLCO1B3 gene. In silico predicted binding sites for the transcription factors ZKSCAN3, SOX9 and HNF1α localized within these fragments were further analyzed. The mutagenesis of the ZKSCAN3 binding site reduced the luciferase activity of the Ct-SLCO1B3 reporter gene construct in the colorectal cancer cell lines DLD1 and T84 to 29.9% and 14.3%, respectively. In contrast, using the liver-derived Hep3B cells, 71.6% residual activity could be measured. This indicates that the transcription factors ZKSCAN3 and SOX9 are important for the cell type-specific transcriptional regulation of the Ct-SLCO1B3 gene. more...

We report on a novel phase-locking technique for fiber-based Mach–Zehnder interferometers based on discrete single-photon detections, and demonstrate this in a setup. Our interferometer decodes relative-phase-encoded optical pulse pairs for quantum key distribution applications and requires no locking laser in addition to the weak received signal. Our new simple locking scheme is shown to produce an Ornstein–Uhlenbeck dynamic and achieve optimal phase noise for a given count rate. In case of wavelength drifts that arise during the reception of Doppler-shifted satellite signals, the arm-length difference gets continuously readjusted to keep the interferometer phase stable. more...

Mediolateral patella displacement is of interest for diagnostics and clinically relevant research questions. Apart from manual testing, no standardized method is currently available. Proper quantification of patella mobility is necessary to better understand pathologies at the patellofemoral joint. Patella mobility was assessed in 25 healthy individuals using a Patellostabilometer, a new prototype instrument for quantification of the mediolateral patella displacement. The participants underwent measurements of the mediolateral displacement three times using the Patellostabilometer. A maximal force of 10 N was applied for patella movement. Additionally, leg length and circumference of the knee, upper- and lower-leg were measured. Lateral patella displacement of 18.27 ± 3.76 mm (range 15.85–20.64 mm, interquartile range (IQR) of 4.79) was measured. The medial patella displacement showed 24.47 ± 6.59 mm (range 19.29–29.76 mm, IQR of 10.47). The test–retest measurement error was 2.32 ± 1.76 mm (IQR of 2.38 mm), with five outliers. There was greater test–retest variability between the measurements of the medial displacement compared to the lateral one. The test–retest variability reached 7% of the patella displacement. Other parameters provided no significant correlations. Based on the natural patellofemoral mobility, a precise and clinically relevant quantification of patella mobility is allowed. more...

Aqueous processing of positive electrode active materials (AMs) could enable a more economical and environmentally friendly production of lithium‐ion batteries. Intrinsically, aqueous processing of positive AMs is hampered by lithium‐proton exchange in the AM surface, leading to a poor electrochemical performance and a resulting strong increase in the pH value in the electrode paste, thereby corroding the aluminum current collector. Herein, the influence of different lithium salts as processing additive to tailor the pH value of the electrode paste, the manganese dissolution during processing, and the electrochemical performance is described for aqueous processing of LiNi0.5Mn1.5O4‐based positive electrodes. Positive electrodes, based on an aqueous LiNi0.5Mn1.5O4‐based electrode paste which is mixed with LiN(SO2CF3)2 (LiTFSI), achieve a comparable electrochemical performance to state‐of‐the‐art nonaqueous‐processed electrodes. Manganese dissolution into the electrode paste is examined by inductively coupled plasma‐mass spectrometry (ICP‐MS), showing that the addition of lithium salts to the electrode paste substantially decreases manganese leaching during processing. Furthermore, postmortem analysis shows that the addition of LiTFSI to the electrode paste has a positive effect not only during processing but also on charge/discharge cycling performance. more...

Abstract Genetic data have great potential for improving fisheries management by identifying the fundamental management units—that is, the biological populations—and their mixing. However, so far, the number of practical cases of marine fisheries management using genetics has been limited. Here, we used Atlantic cod in the Baltic Sea to demonstrate the applicability of genetics to a complex management scenario involving mixing of two genetically divergent populations. Specifically, we addressed several assumptions used in the current assessment of the two populations. Through analysis of 483 single nucleotide polymorphisms (SNPs) distributed across the Atlantic cod genome, we confirmed that a model of mechanical mixing, rather than hybridization and introgression, best explained the pattern of genetic differentiation. Thus, the fishery is best monitored as a mixed‐stock fishery. Next, we developed a targeted panel of 39 SNPs with high statistical power for identifying population of origin and analyzed more than 2,000 tissue samples collected between 2011 and 2015 as well as 260 otoliths collected in 2003/2004. These data provided high spatial resolution and allowed us to investigate geographical trends in mixing, to compare patterns for different life stages and to investigate temporal trends in mixing. We found similar geographical trends for the two time points represented by tissue and otolith samples and that a recently implemented geographical management separation of the two populations provided a relatively close match to their distributions. In contrast to the current assumption, we found that patterns of mixing differed between juveniles and adults, a signal likely linked to the different reproductive dynamics of the two populations. Collectively, our data confirm that genetics is an operational tool for complex fisheries management applications. We recommend focussing on developing population assessment models and fisheries management frameworks to capitalize fully on the additional information offered by genetically assisted fisheries monitoring. more...

Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine). Furthermore, exogenous compounds such as MPP+, ASP+ and Tetraethylammonium can be used as prototypic substrates to study the OCT1-mediated transport in vitro. Single-transfected cell lines recombinantly overexpressing OCT1 (e.g., HEK-OCT1) were established to study OCT1-mediated uptake and to evaluate transporter-mediated drug-drug interactions in vitro. Furthermore, double-transfected cell models simultaneously overexpressing basolaterally localized OCT1 together with an apically localized export protein have been established. Most of these cell models are based on polarized grown MDCK cells and can be used to analyze transcellular transport, mimicking the transport processes e.g. during the hepatobiliary elimination of drugs. Multidrug and toxin extrusion protein 1 (MATE1, gene symbol: SLC47A1) and the ATP-driven efflux pump P-glycoprotein (P-gp, gene symbol: ABCB1) are both expressed in the canalicular membrane of human hepatocytes and are described as transporters of organic cations. OCT1 and MATE1 have an overlapping substrate spectrum, indicating an important interplay of both transport proteins during the hepatobiliary elimination of drugs. Due to the important role of OCT1 for the transport of endogenous compounds and drugs, in vitro cell systems are important for the determination of the substrate spectrum of OCT1, the understanding of the molecular mechanisms of polarized transport, and the investigation of potential drug-drug interactions. Therefore, the aim of this review article is to summarize the current knowledge on cell systems recombinantly overexpressing human OCT1. more...

Aiming at streamlining GPCR production from E. coli inclusion bodies for structural analysis, we present a generic approach to assess and optimize refolding yield through thermostability analysis. Since commonly used hydrophobic dyes cannot be applied as probes for membrane protein unfolding, we adapted a technique based on reacting cysteins exposed upon thermal denaturation with fluorescent 7-Diethylamino-3-(4-maleimidophenyl)-4-methylcoumarin (CPM). Successful expression, purification and refolding is shown for two G protein-coupled receptors (GPCR), the sphingosine-1-phosphate receptor S1P1, and the orphan receptor GPR3. Refolded receptors were subjected to lipidic cubic phase crystallization screening. more...

The World Health Organization Global Action Plan recommends integrated surveillance programs as crucial strategies for monitoring antibiotic resistance. Although several national surveillance programs are in place for clinical and veterinary settings, no such schemes exist for monitoring antibiotic-resistant bacteria in the environment. In this transnational study, we developed, validated, and tested a low-cost surveillance and easy to implement approach to evaluate antibiotic resistance in wastewater treatment plants (WWTPs) by targeting cefotaxime-resistant (CTX-R) coliforms as indicators. The rationale for this approach was: i) coliform quantification methods are internationally accepted as indicators of fecal contamination in recreational waters and are therefore routinely applied in analytical labs; ii) CTX-R coliforms are clinically relevant, associated with extended-spectrum β-lactamases (ESBLs), and are rare in pristine environments. We analyzed 57 WWTPs in 22 countries across Europe, Asia, Africa, Australia, and North America. CTX-R coliforms were ubiquitous in raw sewage and their relative abundance varied significantly ( more...

Klimasensitive Schadorganismen sind Arten, deren Risiko einen Schaden zu verursachen sich aufgrund der vorhergesagten klimatischen Veränderungen voraussichtlich erheblich verändern wird. Damit stellen sie eine besondere Herausforderung für die Pflanzengesundheit dar. Zur Vorhersage des Etablierungs- und Ausbreitungspotenzials dieser Schadorganismen ist eine Bewertung unter verschiedenen Umwelt- und Managementszena­rien unerlässlich. Ein effizientes Werkzeug zur Unter­suchung des Risikos klimasensitiver Schadorganismen (SO) sind prozess-orientierte Simulationsmodelle. Im Rahmen des Projektes,,ProgRAMM“ wird ein solches Modell, das auf Grundlage artspezifischer physiologischer Parameter und Verbreitungseigenschaften arbeitet, entwickelt. Mit diesem Modell wird es möglich sein, die o.g. Vorhersagen und Szenarioanalysen zu realisieren und langfristig einen übertragbaren, verallgemeinerten Open-Source-Modellrahmen als Standardverfahren zur Unterstützung von pflanzengesundheitlichen Risikoanalysen klimasensitiver SO zu etablieren. Dabei steht beson­ders im Vordergrund, dass das Modell leicht erweiterbar ist und sich leicht mit einzelnen Wirtspflanzen, aktu­ellen Klimadatensätzen sowie neuen An-/Abwesenheitsdaten der SO koppeln lässt. Die Ergebnisse des Modells werden in Form von Verbreitungs- und Risikokarten grafisch dargestellt. Diese Karten dienen der verbesserten Abschätzung und Darstellung der wirtschaft­lichen und ökologischen Risiken durch die Schadorganismen in Risikoanalysen. Zusätzlich kann durch die Identifizierung von Hochrisikogebieten für die Ansiedlung von SO, die Planung von Monitoring-Aktivitäten unterstützt werden. Das Modell wird open-source gehalten und um verschiedene Untermodelle sowie artspezifische Funktionen und Parametrisierung erweiterbar sein, damit die Übertragbarkeit auf möglichst viele Schadorganismengruppen (Pilze, Insekten, Milben, Nematoden, Bakte­rien) sichergestellt ist. more...

Genetically modified mice have advanced our knowledge on platelets in hemostasis and beyond tremendously. However, mouse models harbor certain limitations, including availability of platelet specific transgenic strains, and off-target effects on other cell types. Transfusion of genetically modified platelets into thrombocytopenic mice circumvents these problems. Additionally, ex vivo treatment of platelets prior to transfusion eliminates putative side effects on other cell types. Thrombocytopenia is commonly induced by administration of anti-platelet antibodies, which opsonize platelets to cause rapid clearance. However, antibodies do not differentiate between endogenous or exogenous platelets, impeding transfusion efficacy. In contrast, genetic depletion with the inducible diphtheria toxin receptor (iDTR) system induces thrombocytopenia via megakaryocyte ablation without direct effects on circulating platelets. We compared the iDTR system with antibody-based depletion methods regarding their utility in platelet transfusion experiments, outlining advantages and disadvantages of both approaches. Antibodies led to thrombocytopenia within two hours and allowed the dose-dependent adjustment of the platelet count. The iDTR model caused complete thrombocytopenia within four days, which could be sustained for up to 11 days. Neither platelet depletion approach caused platelet activation. Only the iDTR model allowed efficient platelet transfusion by keeping endogenous platelet levels low and maintaining exogenous platelet levels over longer time periods, thus providing clear advantages over antibody-based methods. Transfused platelets were fully functional in vivo, and our model allowed examination of transgenic platelets. Using donor platelets from already available genetically modified mice or ex vivo treated platelets, may decrease the necessity of platelet-specific mouse strains, diminishing off-target effects and thereby reducing animal numbers. more...

Abstract Local energy markets (LEMs) aim at building up local balances of generation and demand close to real time. A bottom-up energy system made up of several LEMs could reduce energy transmission, renewable curtailment and redispatch measures in the long-term, if managed properly. However, relying on limited local resources, LEMs require flexibility to achieve a high level of self-sufficiency. We introduce demand response (DR) into LEMs as a means of flexibility in residential demand that can be used to increase local self-sufficiency, decrease residual demand power peaks, facilitate local energy balances and reduce the cost of energy supply. We present a simulation study on a 100 household LEM and show how local sufficiency can be increased up to 16% with local trading and DR. We study three German regulatory scenarios and derive that the electricity price and the annual residual peak demand can be reduced by up to 10c€/kWh and 40%. more...

Abstract Humans are not autonomous entities. We are all living in a complex environment, interacting not only with our peers, but as true holobionts; we are also very much in interaction with our coexisting microbial ecosystems living on and especially within us, in the intestine. Intestinal microorganisms, often collectively referred to as intestinal microbiota, contribute significantly to our daily energy uptake by breaking down complex carbohydrates into simple sugars, which are fermented to short-chain fatty acids and subsequently absorbed by human cells. They also have an impact on our immune system, by suppressing or enhancing the growth of malevolent and beneficial microbes. Our lifestyle can have a large influence on this ecosystem. What and how much we consume can tip the ecological balance in the intestine. A “western diet” containing mainly processed food will have a different effect on our health than a balanced diet fortified with pre- and probiotics. In recent years, new technologies have emerged, which made a more detailed understanding of microbial communities and ecosystems feasible. This includes progress in the sequencing of PCR-amplified phylogenetic marker genes as well as the collective microbial metagenome and metatranscriptome, allowing us to determine with an increasing level of detail, which microbial species are in the microbiota, understand what these microorganisms do and how they respond to changes in lifestyle and diet. These new technologies also include the use of synthetic and in vitro systems, which allow us to study the impact of substrates and addition of specific microbes to microbial communities at a high level of detail, and enable us to gather quantitative data for modelling purposes. Here, we will review the current state of microbiome research, summarizing the computational methodologies in this area and highlighting possible outcomes for personalized nutrition and medicine. more...