Systematic reviews have found quantitative evidence that low study quality may have introduced a bias into preclinical stroke research. Monitoring, auditing, and standard operating procedures (SOPs) are already key elements of quality control in randomized clinical trials and will hopefully be widely adopted by preclinical stroke research in the near future. Increasingly, funding bodies and review boards overseeing animal experiments are taking a proactive stance, and demand auditable quality control measures in preclinical research. Every good quality control system is based on its SOPs. This article introduces the concept of quality control and presents a SOP in experimental stroke research.

The search for neural correlates of operant and observational learning requires a combination of two (experimental) conditions that are very difficult to combine: stable recording from high order neurons and free movement of the animal in a rather natural environment. We developed a virtual environment (VE) that simulates a simplified 3D world for honeybees walking stationary on an air-supported spherical treadmill. We show that honeybees perceive the stimuli in the VE as meaningful by transferring learned information from free flight to the virtual world. In search for neural correlates of learning in the VE, mushroom body extrinsic neurons were recorded over days during learning. We found changes in the neural activity specific to the rewarded and unrewarded visual stimuli. Our results suggest an involvement of the mushroom body extrinsic neurons in operant learning in the honeybee (Apis mellifera).

We present a general experimental concept for jitter-free pump and probe experiments at free electron lasers. By generating pump and probe pulse from one and the same X-ray pulse using an optical split-and-delay unit, we obtain a temporal resolution that is limited only by the X-ray pulse lengths. In a two-color X-ray pump and X-ray probe experiment with sub 70 fs temporal resolution, we selectively probe the response of orbital and charge degree of freedom in the prototypical functional oxide magnetite after photoexcitation. We find electronic order to be quenched on a time scale of (30 ± 30) fs and hence most likely faster than what is to be expected for any lattice dynamics. Our experimental result hints to the formation of a short lived transient state with decoupled electronic and lattice degree of freedom in magnetite. The excitation and relaxation mechanism for X-ray pumping is discussed within a simple model leading to the conclusion that within the first 10 fs the original photoexcitation decays into low-energy electronic excitations comparable to what is achieved by optical pump pulse excitation. Our findings show on which time scales dynamical decoupling of degrees of freedom in functional oxides can be expected and how to probe this selectively with soft X-ray pulses. Results can be expected to provide crucial information for theories for ultrafast behavior of materials and help to develop concepts for novel switching devices.

The search for natural anticancer agents and nanocarrier uses are a part of the current strategies to overcome the side effects caused by chemotherapeutics. Liposomal nanocapsules loaded with purified tarin, a potential immunomodulatory and antitumoral lectin found in taro corms, were produced. Liposomes were composed by 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine, cholesterylhemisuccinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000 prepared by thin-film hydration. Small unilamellar vesicles were achieved by sonication and extrusion. Scanning electron microscopy evidenced round-shaped nanocapsules presenting a smooth surface, 150 nm diameter and polydispersity index <0.2, estimated by dynamic light scattering. Tarin entrapment rates were over 80% and leakage of ~3% under 40 days of storage at 4 °C. Entrapped tarin exhibited an 83% release after 6 h at pH 4.6–7.4 and 36 °C. Both free and encapsulated tarin exhibited no in vitro toxicity against healthy mice bone marrow and L929 cells but stimulated the production of fibroblast-like and large round-shaped cells. Encapsulated tarin resulted in inhibition of human glioblastoma (U-87 MG) and breast adenocarcinoma (MDA-MB-231) proliferation, with an IC50 of 39.36 and 71.38 µg/mL, respectively. The effectiveness of encapsulated tarin was similar to conventional chemotherapy drugs, such as cisplatin and temozolide. Tarin liposomal nanocapsules exhibited superior pharmacological activity compared to free tarin as a potential chemotherapy adjuvant

The timing regimes of precipitation can exert profound impacts on grassland ecosystems. However, it is still unclear how the peak aboveground biomass (AGBpeak) of alpine grasslands responds to the temporal variability of growing season precipitation (GSP) on the northern Tibetan Plateau. Here, the temporal variability of precipitation was defined as the number and intensity of precipitation events as well as the time interval between consecutive precipitation events. We conducted annual field measurements of AGBpeak between 2009 and 2016 at four sites that were representative of alpine meadow, meadow-steppe, alpine steppe, and desert-steppe. Thus, an empirical model was established with the time series of the field-measured AGBpeak and the corresponding enhanced vegetation index (EVI) (R2 = 0.78), which was used to estimate grassland AGBpeak at the regional scale. The relative importance of the three indices of the temporal variability of precipitation, events, intensity, and time interval on grassland AGBpeak was quantified by principal component regression and shown in a red–green–blue (RGB) composition map. The standardized importance values were used to calculate the vegetation sensitivity index to the temporal variability of precipitation (VSIP). Our results showed that the standardized VSIP was larger than 60 for only 15% of alpine grassland pixels and that AGBpeak did not change significantly for more than 60% of alpine grassland pixels over the past decades, which was likely due to the nonsignificant changes in the temporal variability of precipitation in most pixels. However, a U-shaped relationship was found between VSIP and GSP across the four representative grassland types, indicating that the sensitivity of grassland AGBpeak to precipitation was dependent on the types of grassland communities. Moreover, we found that the temporal variability of precipitation explained more of the field-measured AGBpeak variance than did the total amount of precipitation alone at the site scale, which implies that the mechanisms underlying how the temporal variability of precipitation controls the AGBpeak of alpine grasslands should be better understood at the local scale. We hypothesize that alpine grassland plants promptly respond to the temporal variability of precipitation to keep community biomass production more stable over time, but this conclusion should be further tested. Finally, we call for a long-term experimental study that includes multiple natural and anthropogenic factors together, such as warming, nitrogen deposition, and grazing and fencing, to better understand the mechanisms of alpine grassland stability on the Tibetan Plateau. View Full-Text

An efficient microwave-assisted one-step synthetic route toward Mannich bases is developed from 4-hydroxyacetophenone and different secondary amines in quantitative yields, via a regioselective substitution reaction. The reaction takes a short time and is non-catalyzed and reproducible on a gram scale. The environmentally benign methodology provides a novel alternative, to the conventional methodologies, for the synthesis of mono- and disubstituted Mannich bases of 4-hydroxyacetophenone. All compounds were well-characterized by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The structures of 1-{4-hydroxy-3-[(morpholin-4-yl)methyl]phenyl}ethan-1-one (2a) and 1-{4-hydroxy-3-[(pyrrolidin-1-yl)methyl]phenyl}ethan-1-one (3a) were determined by single crystal X-ray crystallography. Compound 2a and 3a crystallize in monoclinic, P21/n, and orthorhombic, Pbca, respectively. The most characteristic features of the molecular structure of 2a is that the morpholine fragment adopts a chair conformation with strong intramolecular hydrogen bonding. Compound 3a exhibits intermolecular hydrogen bonding, too. Furthermore, the computed Hirshfeld surface analysis confirms H-bonds and π–π stack interactions obtained by XRD packing analyses.

(1) Hope and optimism are strongly connected to physical and psychological health and have been much researched in the field of positive psychology. Research has shown that hope is connected to pro-environmental behavior and plays an important role in ESD. (2) In order to operationalize hope and optimism, in a survey, 2564 young people and 525 teachers in Germany assessed the probability and desirability of predefined future scenarios. (3) Only every fourth respondent is optimistic regarding the global future. The biggest discrepancy between expectation and desirability exists with regard to climate change. Latent class analysis revealed four classes, whereby 50% of the participants are &ldquo;sustainability-affine but disillusioned&rdquo;. This half of the sample has great potential to promote a sustainable future: For them, a positive socio-ecological future has by far the highest value. They report the strongest emotions regarding SD and want to take the most responsibility for SD. Surprisingly, they do not disclose more sustainable behavior in comparison to the other classes. (4) The low expectation of positive socio-ecological developments might be a central factor in preventing half of the sample from behaving more sustainable and indicating a strong potential for hope. The implications for Education for Sustainable Development are discussed.

Analysis Ready Data (ARD) have undergone the most relevant pre-processing steps to satisfy most user demands. The freely available software FORCE (Framework for Operational Radiometric Correction for Environmental monitoring) is capable of generating Landsat ARD. An essential step of generating ARD is atmospheric correction, which requires water vapor data. FORCE relies on a water vapor database obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS). However, two major drawbacks arise from this strategy: (1) The database has to be compiled for each study area prior to generating ARD; and (2) MODIS and Landsat commissioning dates are not well aligned. We have therefore compiled an application-ready global water vapor database to significantly increase the operational readiness of ARD production. The free dataset comprises daily water vapor data for February 2000 to July 2018 as well as a monthly climatology that is used if no daily value is available. We systematically assessed the impact of using this climatology on surface reflectance outputs. A global random sample of Landsat 5/7/8 imagery was processed twice (i) using daily water vapor (reference) and (ii) using the climatology (estimate), followed by computing accuracy, precision, and uncertainty (APU) metrics. All APU measures were well below specification, thus the fallback usage of the climatology is generally a sound strategy. Still, the tests revealed that some considerations need to be taken into account to help quantify which sensor, band, climate, and season are most or least affected by using a fallback climatology. The highest uncertainty and bias is found for Landsat 5, with progressive improvements towards newer sensors. The bias increases from dry to humid climates, whereas uncertainty increases from dry and tropic to temperate climates. Uncertainty is smallest during seasons with low variability, and is highest when atmospheric conditions progress from a dry to a wet season (and vice versa).

Core-virus like particles (VLPs) assembly is a kinetically complex cascade of interactions between viral proteins, nanoparticle’s surface and an ionic environment. Despite many in silico simulations regarding this process, there is still a lack of experimental data. The main goal of this study was to investigate the capsid protein of hepatitis B virus (HBc) assembly into virus-like particles with superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic core in relation to their characteristics. The native form of HBc was obtained via agroinfection of Nicotiana benthamiana with pEAQ-HBc plasmid. SPIONs of diameter of 15 nm were synthesized and functionalized with two ligands, providing variety in ζ-potential and hydrodynamic diameter. The antigenic potential of the assembled core-VLPs was assessed with enzyme-linked immunosorbent assay (ELISA). Morphology of SPIONs and core-VLPs was evaluated via transmission electron microscopy (TEM). The most successful core-VLPs assembly was obtained for SPIONs functionalized with dihexadecyl phosphate (DHP) at SPIONs/HBc ratio of 0.2/0.05 mg/mL. ELISA results indicate significant decrease of antigenicity concomitant with core-VLPs assembly. In summary, this study provides an experimental assessment of the crucial parameters guiding SPION-HBc VLPs assembly and evaluates the antigenicity of the obtained structures.

To build a representation of what we see, the human brain recruits regions throughout the visual cortex in cascading sequence. Recently, an approach was proposed to evaluate the dynamics of visual perception in high spatiotemporal resolution at the scale of the whole brain. This method combined functional magnetic resonance imaging (fMRI) data with magnetoencephalography (MEG) data using representational similarity analysis and revealed a hierarchical progression from primary visual cortex through the dorsal and ventral streams. To assess the replicability of this method, we here present the results of a visual recognition neuro-imaging fusion experiment and compare them within and across experimental settings. We evaluated the reliability of this method by assessing the consistency of the results under similar test conditions, showing high agreement within participants. We then generalized these results to a separate group of individuals and visual input by comparing them to the fMRI-MEG fusion data of Cichy et al (2016), revealing a highly similar temporal progression recruiting both the dorsal and ventral streams. Together these results are a testament to the reproducibility of the fMRI-MEG fusion approach and allows for the interpretation of these spatiotemporal dynamic in a broader context.

The oxygen-evolution reaction (OER) in the near-neutral pH-regime is of high interest, e.g., for coupling of OER and CO2-reduction in the production of non-fossil fuels. A simple model is proposed that assumes equal proton activities in the catalyst film and the near-surface electrolyte. Equations are derived that describe the limitations relating to proton transport mediated by fluxes of molecular “buffer bases” in the electrolyte. The model explains (1) the need for buffer bases in near-neutral OER and (2) the pH dependence of the catalytic current at high overpotentials. The latter is determined by the concentration of unprotonated buffer bases times an effective diffusion constant, which can be estimated for simple cell geometries from tabulated diffusion coefficients. The model predicts (3) a macroscopic region of increased pH close to the OER electrode and at intermediate overpotentials, (4) a Tafel slope that depends on the reciprocal buffer capacity; both predictions are awaiting experimental verification. The suggested first-order model captures and predicts major trends of OER in the near-neutral pH, without accounting for proton-transport limitations at the catalyst–electrolyte interface and within the catalyst material, but the full quantitative agreement may require refinements. The suggested model also may be applicable to further electrocatalytic processes. View Full-Text

Paratuberculosis is a major disease in cattle that severely affects animal welfare and causes huge economic losses worldwide. Development of alternative diagnostic methods is of urgent need to control the disease. Recent studies suggest that long non-coding RNAs (lncRNAs) play a crucial role in regulating immune function and may confer valuable information about the disease. However, their role has not yet been investigated in cattle with respect to infection towards Paratuberculosis. Therefore, we investigated the alteration in genomic expression profiles of mRNA and lncRNA in bovine macrophages in response to Paratuberculosis infection using RNA-Seq. We identified 397 potentially novel lncRNA candidates in macrophages of which 38 were differentially regulated by the infection. A total of 820 coding genes were also significantly altered by the infection. Co-expression analysis of lncRNAs and their neighbouring coding genes suggest regulatory functions of lncRNAs in pathways related to immune response. For example, this included protein coding genes such as TNIP3, TNFAIP3 and NF-κB2 that play a role in NF-κB2 signalling, a pathway associated with immune response. This study advances our understanding of lncRNA roles during Paratuberculosis infection.

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2 weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60 minute transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size.

Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.