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Coevolution is often found in parasite–host interactions, but has not yet been described for hemiparasitic plants and their hosts. Root hemiparasites like Rhinanthus alectorolophus perform photosynthesis but also parasitize other plant species, some of which (e.g. Plantago lanceolata) may defend themselves against parasite attack by blocking the haustoria of the parasites. We grew seedlings of the hemiparasite R. alectorolophus and the potential host P. lanceolata from seven grassland sites in a factorial design. To detect differences in host defence, we also included hosts from two 'naïve' populations from regions where the parasite does not occur. R. alectorolophus grew consistently larger and had higher fitness with sympatric than with allopatric hosts, suggesting parasite adaptation to local host populations. Moreover, R. alectorolophus remained smallest with allopatric hosts from the same region and reached intermediate sizes with allopatric hosts from other regions or naïve hosts, suggesting host adaptation to parasites at the regional scale. Parasite presence reduced the size of the host plants already after four weeks, but only that of hosts with 'experience' of the parasite, suggesting an early host response. Follow‐up experiments confirmed that parasites attach to hosts already after four weeks and hosts respond by changing belowground allocation patterns. However, parasite roots did not preferentially grow towards sympatric hosts. Our results suggest that local adaptation to hosts can occur even in generalist parasites and does not require specialization on individual hosts. We discuss the role of potential mechanisms, including variation in chemical signalling (early) and in host defence (late effects). [ABSTRACT FROM AUTHOR]

Geometric morphometrics (GMM) have been applied to understand morphological variation in biological structures. However, research studying cortical bone through geometric histomorphometrics (GHMM) is scarce. This research aims to develop a landmark‐based GHMM protocol to depict osteonal shape variation in the femoral diaphysis, exploring the role of age and biomechanics in bone microstructure. Proximal, midshaft, and distal anatomical segments from the femoral diaphysis of six individuals were assessed, with 864 secondary intact osteons from eight periosteal sampling areas being manually landmarked. Observer error was tested using Procrustes ANOVA. Average osteonal shape and anatomical segment‐specific variation were explored using principal component analysis. Osteon shape differences between segments were examined using canonical variate analysis (CVA). Sex differences were assessed through Procrustes ANOVA and discriminant function analysis (DFA). The impact of osteonal size on osteonal shape was investigated. High repeatability and reproducibility in osteon shape landmarking were reported. The average osteon shape captured was an elliptical structure, with PC1 reflecting more circular osteons. Significant differences in osteon shape were observed between proximal and distal segments according to CVA. Osteon shape differed between males and females, with DFA showing 52% cross‐validation accuracies. No effect of size on shape was reported. Osteonal shape variation observed in this study might be explained by the elderly nature of the sample as well as biomechanical and physiological mechanisms playing different roles along the femoral diaphysis. Although a larger sample is needed to corroborate these findings, this study contributes to the best of our knowledge on human microanatomy, proposing a novel GHMM approach. [ABSTRACT FROM AUTHOR]

Background: Ex vivo normothermic machine perfusion (NMP) is a promising tool for assessing an isolated kidney prior to transplantation. However, there is no consensus on the perfusate's optimal oxygen‐carrying capacity to support renal function. To investigate the association of hemoglobin levels with renal function parameters, a retrospective analysis of isolated, normothermically, perfused porcine kidneys was performed. Methods: Between 2015 and 2021, a total of 228 kidneys underwent 4 h of NMP with perfusates that varied in hemoglobin levels. A generalized linear model was used to determine the association of hemoglobin levels with time‐weighted means of renal function markers, such as fractional sodium excretion (FENa) and creatinine clearance (CrCl). Stratified by baseline hemoglobin level (<4.5, 4.5–6, or >6 mmol/L), these markers were modeled over time using a generalized linear mixed‐effects model. All models were adjusted for potential confounders. Results: Until a hemoglobin level of around 5 mmol/L was reached, increasing hemoglobin levels were associated with superior FENa and CrCl. Thereafter, this association plateaued. When hemoglobin levels were categorized, hemoglobin <4.5 mmol/L was associated with worse renal function. Hemoglobin levels were neither significantly associated with proteinuria during NMP nor with ATP levels at the end of NMP. Hemoglobin levels >6 mmol/L showed no additional benefits in renal function. Conclusion: In conclusion, we found an association between baseline hemoglobin levels and superior renal function parameters, but not injury, during NMP of porcine kidneys. Furthermore, we show that performing a retrospective cohort study of preclinical data is feasible and able to answer additional questions, reducing the potential use of laboratory animals. [ABSTRACT FROM AUTHOR]

Recruiters routinely use LinkedIn profiles to infer applicants' individual traits like narcissism and intelligence, two key traits in online network and organizational contexts. However, little is known about LinkedIn profiles' predictive potential to accurately infer individual traits. According to Brunswik's lens model, accurate trait inferences depend on (a) the presence of valid cues in LinkedIn profiles containing information about users' individual traits and (b) the sensitive and consistent utilization of valid cues. We assessed narcissism (self‐report) and intelligence (aptitude tests) in a sample of 406 LinkedIn users along with 64 LinkedIn cues (coded by three trained coders) that we derived from trait theory and previous empirical findings. We used a transparent, easy‐to‐interpret machine learning algorithm leveraging practical application potentials (elastic net) and applied state‐of‐the‐art resampling techniques (nested cross‐validation) to ensure robust results. Thereby, we uncover LinkedIn profiles' predictive potential: (a) LinkedIn profiles contain valid information about narcissism (e.g. uploading a background picture) and intelligence (e.g. listing many accomplishments), and (b) the elastic nets sensitively and consistently using these valid cues attain prediction accuracy (r = .35/.41 for narcissism/intelligence). The results have practical implications for improving recruiters' accuracy and foreshadow potentials and limitations of automated LinkedIn‐based assessments for selection purposes. [ABSTRACT FROM AUTHOR]

Polarized |S|=0.99±0.01$| S | = 0.99 \pm 0.01$, and unpolarized |S|=0.03±0.01$| S | = 0.03 \pm 0.01$ emission from a single emitter embedded in a single, cylindrically symmetric device design is presented. The polarization stems from a position offset of the single emitter with respect to the cavity center, which breaks the cylindrical symmetry, and a position‐dependent coupling to the frequency degenerate eigenmodes of the resonator structure is shown. The experimental results are interpreted by using numerical simulations and by experimental mapping of the polarization‐resolved far‐field emission patterns. The findings can be generalized to any nanophotonic structure where two orthogonal eigenmodes are not fully spatially overlapping. [ABSTRACT FROM AUTHOR]

Objectives: To attain a collective expert opinion on the use of air powder waterjet technology (APWT) with erythritol and glycine powders in the prophylaxis and therapy of periodontal and peri‐implant diseases. Material and Methods: In the first step, a modified one‐round online Delphi survey including 44 five‐point Likert scale questions was conducted among a group of 10 expert clinicians and researchers with thorough knowledge and experience in this topic. In the second step, the single questions and the survey results were discussed during a meeting, and consensus statements were formulated, respectively. Results: An agreement was reached on most items, especially opinions supporting glycine and erythritol powders as favorable with respect to efficiency, safety, and comfort. More scientific evidence is needed to support the improvement in clinical attachment on teeth and implants, especially when APWT with erythritol is used. In addition, APWT needs more long‐term evaluation and studies in terms of microbiome/microbiological effects as well as effects on the inflammatory response on natural teeth and implants, also in light of a guided biofilm therapy concept. Conclusions: In line with the expert opinions and supported by the evidence, it was concluded that the use of APWT with erythritol and glycine powders in nonsurgical periodontal and peri‐implant therapy and prophylaxis is patient compliant and efficient. [ABSTRACT FROM AUTHOR]

Human resource (HR) professionals regularly draw personality inferences from applicants' resumés. Building on the lens model, we illuminate resumés' potential for accurately inferring personality by examining valid resumé cues indicating personality. We assessed self‐reported big five traits and narcissism of 141 business students at career start applying with resumés for a fictional position. Drawing on personality theory and empirical findings, 70 resumé cues (e.g., appealing look and creative hobbies) were post hoc selected from a larger cue set comprising 160 cues coded by 11 trained coders. Computing bivariate correlations and multiple linear regressions, we identified easy‐to‐interpret valid resumé cues explaining substantial personality variance, with conscientiousness, openness, and narcissism being best explained by resumé cues (R2 > 20%). Although all considered personality traits were expressed in resumé cues, only a fraction of the cues (16 out of 70 cues) were related to personality traits. This suggests a rather mediocre upper limit to the potential of accurately inferring personality from resumés. We contribute to the literature on personality inferences at zero‐acquaintance by adding valid resumé cues to recruitment‐related information bases allowing to make (somewhat) accurate personality inferences. The results have practical implications for applying resumé‐based personality inferences in recruitment and improving HR professionals' accuracy. [ABSTRACT FROM AUTHOR]

Fractures can greatly impact fluid flow and pore pressure distribution in the upper crust. By conducting borehole hydraulic experiments, we can determine the ability of fractures to transport fluids and affect pressure diffusion under in situ conditions. We performed a series of periodic hydraulic tests in a borehole at the Bedretto Underground Laboratory for Geosciences and Geoenergies (Switzerland). We investigated the period‐ and pressure‐dependent response of a fractured granite by controlling the flow rate of harmonic and non‐harmonic oscillations, covering a wide range of periods as well as mean‐ and amplitude‐pressure values. By analyzing the phase and amplitude relation between the flow rate and fluid pressure in the injection interval, we found that the intersected fracture zone exhibits a period‐dependent hydraulic response close to radial flow perturbed by fracture‐related hydromechanical coupling effects. The main features of the interval's hydraulic response were reproduced by an uncoupled diffusion solution for radial flow, which was used to derive apparent hydraulic properties. The largest deviations from this model occur for the phase shifts and correlate with the pressure amplitude. This non‐linear expression of hydromechanical coupling associated with deformable fractures was interpreted in terms of a pressure‐dependent effective compliance of the fractures that affects their effective storativity. The period dependence is likely related to the spatial heterogeneity expected in fractured rocks and the varying sensitivity of the hydraulic response for different periods. Accounting for these effects is necessary for a correct hydraulic characterization in fractured environments and is valuable for inferring fracture mechanical behavior. Plain Language Summary: Fractures govern the hydraulic and mechanical behavior of rocks, and their characterization is crucial for understanding natural and anthropogenically induced processes involving stress and fluid pressure changes in fractured environments. Periodic pumping tests are specialized experiments used to quantify the ability of fractures to transport fluids and to affect pressure distribution in the subsurface. These experiments consist of recording the pressure response of a borehole interval to an injected oscillatory flow. We performed periodic pumping tests on fractures intersecting a borehole and analyzed their response to different testing parameters, such as, the period and amplitude of the oscillations and the type of oscillation. We found that the pressure‐flow rate relation can be fairly well explained by a simple model for porous rocks that ignores any complexity associated with the presence of fractures. Nevertheless, notable effects that cannot be explained by the model are found to be correlated with the period and amplitude of the oscillations. Capturing the period dependence is useful for characterizing heterogeneities away from the borehole, while the oscillation amplitude dependence shows the impact of the deformability of fractures exposed to pressure variations. Future modeling and experimental techniques should consider these findings to improve interpretation methods. Key Points: We conducted periodic pumping tests on fractures intersecting a borehole varying their period and the mean‐ and amplitude‐pressure valuesThe observed flow rate versus pressure behavior can largely be reproduced by an uncoupled diffusion solution for radial flowWe observed a dependence of the hydraulic response on the period and on the pressure amplitude likely related to fracture deformation [ABSTRACT FROM AUTHOR]

We describe the synthesis and biochemical and cellular profiling of five partially reduced or demethylated analogs of the marine macrolide (−)‐zampanolide (ZMP). These analogs were derived from 13‐desmethylene‐(−)‐zampanolide (DM‐ZMP), which is an equally potent cancer cell growth inhibitor as ZMP. Key steps in the synthesis of all compounds were the formation of the dioxabicyclo[15.3.1]heneicosane core by an intramolecular HWE reaction (67–95 % yield) and a stereoselective aza‐aldol reaction with an (S)‐BINOL‐derived sorbamide transfer complex, to establish the C(20) stereocenter (24–71 % yield). As the sole exception, for the 5‐desmethyl macrocycle, ring‐closure relied on macrolactonization; however, elaboration of the macrocyclization product into the corresponding zampanolide analog was unsuccessful. All modifications led to reduced cellular activity and lowered microtubule‐binding affinity compared to DM‐ZMP, albeit to a different extent. For compounds incorporating the reactive enone moiety of ZMP, IC50 values for cancer cell growth inhibition varied between 5 and 133 nM, compared to 1–12 nM for DM‐ZMP. Reduction of the enone double bond led to a several hundred‐fold loss in growth inhibition. The cellular potency of 2,3‐dihydro‐13‐desmethylene zampanolide, as the most potent analog identified, remained within a ninefold range of that of DM‐ZMP. [ABSTRACT FROM AUTHOR]

Damage to plant communities imposed by insect herbivores generally decreases from low to high latitudes. This decrease is routinely attributed to declines in herbivore abundance and/or diversity, whereas latitudinal changes in per capita food consumption remain virtually unknown. Here, we tested the hypothesis that the lifetime food consumption by a herbivore individual decreases from low to high latitudes due to a temperature‐driven decrease in metabolic expenses. From 2016 to 2019, we explored latitudinal changes in multiple characteristics of linear (gallery) mines made by larvae of the pygmy moth, Stigmella lapponica, in leaves of downy birch, Betula pubescens. The mined leaves were larger than intact leaves at the southern end of our latitudinal gradient (at 60°N) but smaller than intact leaves at its northern end (at 69°N), suggesting that female oviposition preference changes with latitude. No latitudinal changes were observed in larval size, mine length or area, and in per capita food consumption, but the larval feeding efficiency (quantified as the ratio between larval size and mine size) increased with latitude. Consequently, S. lapponica larvae consumed less foliar biomass at higher latitudes than at lower latitudes to reach the same size. Based on space‐for‐time substitution, we suggest that climate warming will increase metabolic expenses of insect herbivores with uncertain consequences for plant–herbivore interactions. [ABSTRACT FROM AUTHOR]

Plants or seeds produced in botanic gardens or nurseries have become an important source of plant material for reintroductions or population reinforcements. However, recent research has shown that these living collections bear the risk of being genetically impoverished and adapted to the artificial habitat. In particular, many studies have reported a decline of seed dormancy during ex situ cultivation, which may compromise their suitability for reintroduction programmes. However, the impact of those ex situ derived changes on the germination and establishment of reintroduced plant populations is still unclear.We studied the germination behaviour, population establishment and plant fitness over 3 years of reintroduced plants of the short‐lived perennial Digitalis lutea, comparing plants grown from (1) a 30‐year botanic garden population, (2) seeds from a seed bank representing the initial starting point of the botanic garden culture and (3) a re‐sampled corresponding wild population.Under laboratory conditions, wild‐collected seeds required cold stratification to germinate, whereas seeds from the garden population germinated without stratification. This pattern was strongly reduced in an outdoor pot experiment, where only few garden seeds germinated before winter, and all seeds remained dormant when seeded in the natural area of origin. In a transplant experiment, reintroduced plants from the wild population outperformed both, the garden and the seed bank plants, in their fitness in the first 3 years after reintroduction suggesting adaptation to current climatic conditions.Synthesis and applications. Our study demonstrates that trait changes that occurred during ex situ cultivation can negatively impact the establishment of reintroduced plants. We conclude that wild plant material collected from contemporary populations is best suited for reintroduction and should be preferred over ex situ cultivated and seed bank stored material, especially when the cultivation spanned multiple generations. However, our study also shows that germination requirements change in complex ways, and the loss of dormancy observed under laboratory conditions may not always be directly transferable to natural conditions. When established standards are respected, ex situ propagated material may thus still be a valuable resource, especially when wild material is not available in sufficient quantities. [ABSTRACT FROM AUTHOR]

Premise: Ex situ cultivation is important for plant conservation, but cultivation in small populations may result in genetic changes by drift, inbreeding, or unconscious selection. Repeated inbreeding potentially influences not only plant fitness, but also floral traits and interactions with pollinators, which has not yet been studied in an ex situ context. Methods: We studied the molecular genetic variation of Digitalis lutea from a botanic garden population cultivated for 30 years, a frozen seed bank conserving the original genetic structure, and two current wild populations including the source population. In a common garden, we studied the effects of experimental inbreeding and between‐population crosses on performance, reproductive traits, and flower visitation of plants from the garden and a wild population. Results: Significant genetic differentiation was found between the garden population and the wild population from which the seeds had originally been gathered. After experimental selfing, inbreeding depression was only found for germination and leaf size of plants from the wild population, indicating a history of inbreeding in the smaller garden population. Moreover, garden plants flowered earlier and had floral traits related to selfing, whereas wild plants had traits related to attracting pollinators. Bumblebees visited more flowers of outbred than inbred plants and of wild than garden plants. Conclusions: Our case study suggests that high levels of inbreeding during ex situ cultivation can influence reproductive traits and thus interactions with pollinators. Together with the effects of genetic erosion and unconscious selection, these changes may affect the success of reintroductions into natural habitats. [ABSTRACT FROM AUTHOR]

Peer‐teaching is widely established in anatomy teaching and offers well‐described advantages. Nevertheless, at Ulm University, Germany, a reduction in the number of peer teacher applicants for the dissection course was observed. This study examined factors related to the attractiveness of a position as a peer teacher for Generation Z students. Participants of the gross anatomy course were asked to evaluate factors influencing the attractiveness of a peer teacher position using a six‐point Likert scale. Additionally, open‐ended questions were analyzed qualitatively. Sex‐specific subgroup analysis was performed comparing students of low and high motivation to apply for a tutorship. Of the 374 students who participated in this study (response rate 53%), 38% stated that they were intending to apply as peer teachers. Data indicated that students displayed intrinsic motivation to apply for a tutorship because of the opportunity to improve their anatomy knowledge and/or their pleasure in teaching. In contrast, extrinsic factors like remuneration of the tutorship and its relevance for their curriculum vitae were least important. Anatomy educators underestimated the demotivating factor of the workload associated with the tutorship and encouraged students less frequently to apply than peer teachers. Only minor sex‐specific differences could be identified. Nevertheless, female students were encouraged less frequently to apply than their male peers. In summary, Generation Z students apply as peer teachers because they are enthusiastic about the task. To motivate students to commit to extracurricular activities like a tutorship, anatomy educators should actively encourage students—particularly females—more frequently to apply. [ABSTRACT FROM AUTHOR]

The entorhinal cortex (EC) is the main interface between the sensory association areas of the neocortex and the hippocampus. It is crucial for the evaluation and processing of sensory data for long‐term memory consolidation and shows damage in many brain diseases, for example, neurodegenerative diseases, such as Alzheimer's disease and developmental disorders. The pre‐alpha layer of the EC in humans (layer II) displays a remarkable distribution of neurons in islands. These cellular islands give rise to a portion of the perforant path—the major reciprocal data stream for neocortical information into the hippocampal formation. However, the functional relevance of the morphological appearance of the pre‐alpha layer in cellular islands and the precise timing of their initial appearance during primate evolution are largely unknown. Here, we conducted a comparative study of the EC from 38 nonhuman primates and Homo sapiens and found a strong relationship between gyrification index (GI) and the presence of the pre‐alpha cellular islands. The formation of cellular islands also correlated with brain and body weight as well as neopallial volume. In the two human lissencephalic cases, the cellular islands in the pre‐alpha layer were lacking. These findings emphasize the relationship between cortical folding and island formation in the EC from an evolutionary perspective and suggest a role in the pathomechanism of developmental brain disorders. [ABSTRACT FROM AUTHOR]

A main application area of ceramic open‐cell foams is the foundry, where the porous media are used for conditioning and filtration of the melt flow. As characterization of heat transfer in such high‐temperature applications requires consideration of thermal radiation, knowledge of the radiative properties of the foams is essential. Instead of elaborative measurements or simulations, empirical correlations often serve as a simple and fast method to predict extinction coefficients. However, significant differences up to 100 m−1 occur between calculated values of various models presented in the literature. Herein, it is aimed to characterize the radiation behavior of different ceramic foams experimentally and identify reliable, simple yet accurate methods for the prediction of extinction coefficients of these materials by comparison with experimental results. The influences of pore density (10 and 20 pores per inch [ppi]) and filter material (Al2O3, ZrO2, SiC, Al2O3−C) on the transmittance, reflectance, and extinction coefficients are investigated by spectroscopic measurements. Two models from the literature are determined, which are well suited to predict extinction coefficients with an average deviation of less than 20%. Furthermore, accurate estimation with an average deviation of 12% can be also achieved using a projection method based on computed tomography scans of the foams. [ABSTRACT FROM AUTHOR]

The arylomycin antibiotics are potent inhibitors of bacterial type I signal peptidase. These lipohexapeptides contain a biaryl structural motif reminiscent of glycopeptide antibiotics. We herein describe the functional and structural evaluation of AryC, the cytochrome P450 performing biaryl coupling in biosynthetic arylomycin assembly. Unlike its enzymatic counterparts in glycopeptide biosynthesis, AryC converts free substrates without the requirement of any protein interaction partner, likely enabled by a strongly hydrophobic cavity at the surface of AryC pointing to the substrate tunnel. This activity enables chemo‐enzymatic assembly of arylomycin A2 that combines the advantages of liquid‐ and solid‐phase peptide synthesis with late‐stage enzymatic cross‐coupling. The reactivity of AryC is unprecedented in cytochrome P450‐mediated biaryl construction in non‐ribosomal peptides, in which peptidyl carrier protein (PCP)‐tethering so far was shown crucial both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

One patient's therapy was stopped after three administrations because of a very good response.3 In two patients, therapy was temporarily interrupted after two doses for the same reason and later completed because of imminent relapse.3 Patient 3 later received another six doses of daratumumab as maintenance at an external hospital (Figure S2). Autoimmune haemolytic anaemia (AIHA) is an autoantibody-mediated autoimmune disorder characterized by red blood cell (RBC) destruction by the host's immune system. While patient 1 had insufficiently controlled graft-versus-host disease, patient 2 had a relapse of chronic myelomonocytic leukaemia associated with the occurrence of AIHA. [Extracted from the article]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which is still missing effective therapeutic strategies. Although manipulation of neuronal excitability has been tested in murine and human ALS models, it is still under debate whether neuronal activity might represent a valid target for efficient therapies. In this study, we exploited a combination of transcriptomics, proteomics, optogenetics and pharmacological approaches to investigate the activity‐related pathological features of iPSC‐derived C9orf72‐mutant motoneurons (MN). We found that human ALSC9orf72 MN are characterized by accumulation of aberrant aggresomes, reduced expression of synaptic genes, loss of synaptic contacts and a dynamic "malactivation" of the transcription factor CREB. A similar phenotype was also found in TBK1‐mutant MN and upon overexpression of poly(GA) aggregates in primary neurons, indicating a strong convergence of pathological phenotypes on synaptic dysregulation. Notably, these alterations, along with neuronal survival, could be rescued by treating ALS‐related neurons with the K+ channel blockers Apamin and XE991, which, respectively, target the SK and the Kv7 channels. Thus, our study shows that restoring the activity‐dependent transcriptional programme and synaptic composition exerts a neuroprotective effect on ALS disease progression. Synopsis: The lack of an effective treatment for ALS is calling for the development of novel therapeutic strategies. By using hiPSC‐derived motoneurons and focusing on synapse‐related processes, we provide new molecular targets rescuing the degenerative processes and neuronal loss in ALS. Human C9orf72‐mutant motoneurons are characterized by reduced expression of synaptic gene, progressive loss of CREB activity and synapse loss.Similar alterations are observed also in motoneurons harboring TBK1 pathogenic mutations, and in primary neurons upon overexpression of poly(GA) aggregates.The K+ channel blockers Apamin and XE991 revert the CREB‐dependent loss of synaptic contacts and rescue the degenerative phenotypes of ALS motoneurons. [ABSTRACT FROM AUTHOR]

Fungal lytic polysaccharide monooxygenases (LPMOs) depolymerise crystalline cellulose and hemicellulose, supporting the utilisation of lignocellulosic biomass as a feedstock for biorefinery and biomanufacturing processes. Recent investigations have shown that H2O2 is the most efficient cosubstrate for LPMOs. Understanding the reaction mechanism of LPMOs with H2O2 is therefore of importance for their use in biotechnological settings. Here, we have employed a variety of spectroscopic and biochemical approaches to probe the reaction of the fungal LPMO9C from N. crassa using H2O2 as a cosubstrate and xyloglucan as a polysaccharide substrate. We show that a single 'priming' electron transfer reaction from the cellobiose dehydrogenase partner protein supports up to 20 H2O2‐driven catalytic cycles of a fungal LPMO. Using rapid mixing stopped‐flow spectroscopy, alongside electron paramagnetic resonance and UV‐Vis spectroscopy, we reveal how H2O2 and xyloglucan interact with the enzyme and investigate transient species that form uncoupled pathways of NcLPMO9C. Our study shows how the H2O2 cosubstrate supports fungal LPMO catalysis and leaves the enzyme in the reduced Cu+ state following a single enzyme turnover, thus preventing the need for external protons and electrons from reducing agents or cellobiose dehydrogenase and supporting the binding of H2O2 for further catalytic steps. We observe that the presence of the substrate xyloglucan stabilises the Cu+ state of LPMOs, which may prevent the formation of uncoupled side reactions. [ABSTRACT FROM AUTHOR]

Competition simultaneously limits the availability of above‐ and below‐ground resources for plants. How plants respond to density with changes in patterns of biomass allocation is poorly understood. Previous studies had inconsistent results, but emphasised increased biomass allocation to stems in response to density. However, the response of plants to density may depend on environmental conditions and on characteristics of the species.We grew 43 herbaceous plant species at three densities (1, 8 and 64 individuals per pot) and two nutrient levels in a common garden and measured biomass allocation to roots (RMF), leaves (LMF) and stems (SMF), and specific root (SRL) and stem length (SSL). The species differed in functional group (grasses, forbs and legumes), life span and realised niche with respect to nutrients (Ellenberg's nutrient indicator value).Intraspecific competition and self‐thinning increased with nutrient supply. Overall, plants increased their RMF with density independent of nutrient level, indicating that competition was mainly for below‐ground resources. However, characteristics of the species influenced their responses to density and nutrients in terms of biomass allocation, SRL and SSL. At high densities, legumes were more productive than the other functional groups and hardly changed their allocation patterns, suggesting that they were less nutrient limited due to their mutualism with nitrogen‐fixing rhizobia. The SRL of perennials was lower, and their RMF was higher and increased more strongly in response to density than that of annuals, which could be interpreted as mechanisms to increase survival. The realised niche of species with respect to nutrients influenced the response to density and nutrients in terms of SMF, LMF, SRL and SSL in line with adaptations to both nutrient availability and competition for light in the typical habitats.Synthesis. We found that intraspecific competition was mainly for below‐ground resources, which may be typical for many species growing in moderately nutrient‐rich but high‐light habitats. Our results show that growth conditions, species characteristics and their interactions influence patterns of biomass allocation and plant morphology. [ABSTRACT FROM AUTHOR]

Probing the flow permeability of porous media with elastic waves is a formidable challenge, also because the wave‐induced oscillatory motion renders the permeability frequency dependent. Existing theoretical models for such a dynamic permeability assume that the frequency dependence is primarily controlled by a single characteristic length scale of the pore space. However, the fact that in most natural porous media there exists a distinct range of pore sizes is ignored. To overcome this limitation, we develop a dynamic permeability model that explicitly incorporates the pore size distribution. We show that the pore size distribution has a first‐order effect on the dynamic permeability. Since the pore size distribution can be deduced from techniques such as nuclear magnetic resonance, our results indicate the possibility to jointly use remote‐sensing technologies for improved permeability determination and cross‐fertilization of laboratory and in‐field techniques. Plain Language Summary: The flow rate of fluid through a porous material depends on the permeability. When the porous material is excited with elastic waves, there is an oscillatory fluid motion in the pore network. Then the permeability becomes frequency‐dependent, that is, a dynamic permeability. We develop a model for the dynamic permeability in porous materials with a range of pore sizes. We find that the pore sizes and their pore volume fraction have significant influence on the dynamic permeability. This is the first time to make connection between the elastic wave, whose velocity and attenuation are controlled by the dynamic permeability, and the nuclear magnetic resonance technique from which the pore size distribution can be inferred. Key Points: We propose a dynamic permeability model revealing that the pore size distribution has a first‐order effect on the dynamic permeabilityThe effect of wettability on the dynamic permeability is explored by the implementation of the slip boundary conditionThe proposed model builds a connection between signatures of elastic waves and techniques to obtain the pore size distribution such as NMR [ABSTRACT FROM AUTHOR]

Experimental investigations often reveal that there is a correlation between porosity and permeability in rocks. The most commonly used model to predict the porosity–permeability relation is due to Kozeny–Carman or its many modifications. However, these models are problematic because they always involve an empirical constant and, in macroscopically heterogeneous porous media with non‐uniform porosity, more than one empirical constant would be required. Moreover, the tensor character of the permeability is not accounted for when the permeability is conceptualized as a plain function of the porosity. To overcome these limitations, we devise an approach by analysing the drag force in the volume averaging framework of poroelasticity. This allows us to deduce an expression for the inverse permeability tensor. It is the sum of the inverse of the permeability pertaining to a representative volume element and the second spatial derivative of porosity. Therefore, the gradient of porosity changes the permeability depending on the variations of macroscopic porosity variations. This result is thought to be relevant in applications where porosity maps are converted into permeability maps. [ABSTRACT FROM AUTHOR]

Impairments in social relationships and awareness are features observed in autism spectrum disorders (ASDs). However, the underlying mechanisms remain poorly understood. Shank2 is a high‐confidence ASD candidate gene and localizes primarily to postsynaptic densities (PSDs) of excitatory synapses in the central nervous system (CNS). We show here that loss of Shank2 in mice leads to a lack of social attachment and bonding behavior towards pubs independent of hormonal, cognitive, or sensitive deficits. Shank2−/− mice display functional changes in nuclei of the social attachment circuit that were most prominent in the medial preoptic area (MPOA) of the hypothalamus. Selective enhancement of MPOA activity by DREADD technology re‐established social bonding behavior in Shank2−/− mice, providing evidence that the identified circuit might be crucial for explaining how social deficits in ASD can arise. Synopsis: Loss of the autism spectrum disorder linked gene Shank2 in mice leads to lack of social bonding due to functional changes in the social attachment neurocircuitry. Shank2−/− mice are unable to initiate social bonding towards pups.Shank2−/− mice show impaired glutamatergic signaling in the brain circuit social attachment circuit including the the medial preoptic area (MPOA) of the hypothalamus.The behavioral alterations seem to be independent of hormonal influences, and cognitive and sensory deficits.Chemogenetic activation of MPOA neurons rescues the loss of social bonding in Shank2−/− mice. [ABSTRACT FROM AUTHOR]

There is recent experimental evidence that the effective pressure coefficient for pore volume exceeds unity in limestones with dual porosity structure. Within the realm of linear poroelastcity, this means that the unjacketed pore modulus is negative. This would be a rather unusual rock behavior since it implies that the pore volume increases for a positive pressure increment during hydrostatic compression. Generally, any deviation of the unjacketed pore modulus from strictly positive mineral bulk modulus means that the deformation is inhomogeneous. We critically examine these observations by attempting to reconcile them with the poroelastic constitutive equations of micro‐inhomogeneous rocks that encompass inhomogeneous deformations. Consistency checks among measured poroelastic constants reveal that the measurement accuracy of pore volume changes concurring with the deformation experiments is not as high as desired. However, assigning moderate variations to the measured pore volume changes either due to random or systematic measurement errors, we show that the experimental observations are indeed reconcilable with the constitutive poroelastic equations. Hence, the negative unjacketed pore modulus observed is deemed plausible though overestimated. Within the poroelasticity framework for micro‐inhomogeneous rocks, a negative unjacketed pore modulus is the result of a partial localization of elastic strain energy in the fluid space. This in turn could be caused by dissolved calcite particles that block thin pore throats and thus generate temporary fluid pressure compartmentalization. A far‐reaching consequence of a negative unjacketed pore modulus is that description of the undrained bulk modulus in rocks with dual porosity structure is more complicated than previously thought. Key Points: Critical examination of recently reported laboratory measurements reveals a negative unjacketed pore modulus in micro‐inhomogeneous rockThis unusual rock behavior is reconcilable with the theory of poroelasticity of micro‐inhomogeneous rocksMicro‐inhomogeneity in mono‐mineralic rocks is due to variability of pore sizes [ABSTRACT FROM AUTHOR]

Solid oxide fuel cells (SOFC) convert chemical energy from hydrogen, methane, or other hydrocarbons directly into electrical energy and heat. Advantages are low noise during operation as well as relatively low pollutant emissions. This makes them interesting for stationary applications, eg combined heat and power plants for domestic use and for mobile applications, when there is a demand for integrating auxiliary power units. The high operating temperatures of about 850°C and the simultaneous presence by both, reducing and oxidizing atmospheres place high demands on the components of a SOFC. Due to these requirements, glass‐ceramics are proposed as sealants between interconnector and electrolyte. They provide lower costs and lower weight than commercially used silver solders. Furthermore, they have the following impressive benefits: The sealants are electrical insulating, chemical stable and by careful materials selection and adapted manufacturing processes, they adhere well on steel and on ceramic substrates. In order to characterize the adhesion of glass‐ceramic sealants on steel and on zirconia substrates, layer‐like composites are fabricated by screen‐printing and subsequent sintering in air. It turns out that the formation of crystalline phases at the interface is crucial for the adhesion behavior. [ABSTRACT FROM AUTHOR]

Metformin may act renoprotective prior to kidney transplantation by reducing ischemia‐reperfusion injury (IRI). This study examined whether metformin preconditioning and postconditioning during ex vivo normothermic machine perfusion (NMP) of rat and porcine kidneys affect IRI. In the rat study, saline or 300 mg/kg metformin was administered orally twice on the day before nephrectomy. After 15 minutes of warm ischemia, kidneys were preserved with static cold storage for 24 hours. Thereafter, 90 minutes of NMP was performed with the addition of saline or metformin (30 or 300 mg/L). In the porcine study, after 30 minutes of warm ischemia, kidneys were preserved for 3 hours with oxygenated hypothermic machine perfusion. Subsequently, increasing doses of metformin were added during 4 hours of NMP. Metformin preconditioning of rat kidneys led to decreased injury perfusate biomarkers and reduced proteinuria. Postconditioning of rat kidneys resulted, dose‐dependently, in less tubular cell necrosis and vacuolation. Heat shock protein 70 expression was increased in metformin‐treated porcine kidneys. In all studies, creatinine clearance was not affected. In conclusion, both metformin preconditioning and postconditioning can be done safely and improved rat and porcine kidney quality. Because the effects are minor, it is unknown which strategy might result in improved organ quality after transplantation. [ABSTRACT FROM AUTHOR]

Understanding the effect of temperature on physical properties of rocks is important to develop deep oil, gas, and geothermal resources. Velocity‐porosity relations are essential ingredients for a seismic rock physics model. However, relatively little effort has thus far been made to capture the temperature effect on velocity‐porosity relations. To overcome this limitation, we develop a double‐porosity model based on Biot's theory. This model is complemented with the Batzle‐Wang empirical equations for the pressure and temperature dependence of the pore fluid, as well as the David‐Zimmerman model to quantify temperature‐dependent microcrack density. The combined model is tested on carbonate and hyaloclastite samples, for which the variation of ultrasonic P‐wave velocity with temperature has been measured in the laboratory. Comparison of the predicted P‐wave velocity with the measured velocity shows that the proposed model is capable of quantitatively describing the rock velocity‐temperature and velocity‐porosity relations. We found that, for our rock samples, the temperature‐dependent change of microcrack porosity was not the dominant factor affecting the velocity‐porosity relation and that the temperature‐dependent fluid properties had a greater effect. The proposed model also predicts that the velocity dispersion and the attenuation peak of P‐waves in carbonate rock samples become less pronounced with increasing temperature. Key Points: We develop a temperature‐dependent double‐porosity model for analyzing joint effects of pore fluid and microcracks on rock anelasticityModeling experimental data shows that temperature‐dependence of fluids dominates velocity‐temperature relations in rocksFor different pore fluids, there is a characteristic trend of velocity‐porosity at different temperatures [ABSTRACT FROM AUTHOR]

We examine the effect of poroelastic boundary conditions when determining elastic properties of fluid‐saturated porous rocks from forced‐oscillation laboratory experiments. One undesired yet often unavoidable complication in the estimation of the undrained bulk modulus is due to the presence of the so‐called dead volume. It implies that some fluid mass can escape the rock sample under applying a confining pressure perturbation. Thus, the dead volume compromises the undrained state required to unambiguously determine the undrained bulk modulus. In this paper, we model data of recently performed low‐frequency (0.1 Hz) measurements. Therein, the dead volume has been systematically varied from 10% to 1000% of the pore volume. For the smallest dead volume, the inferred bulk modulus is close to the Biot–Gassmann undrained bulk modulus. With increasing dead volume, the experimentally inferred bulk modulus approaches the drained bulk modulus. We show that the transition from undrained to drained state as a function of dead volume can be modelled with a 1D poroelastic model for the rock sample‐dead volume system with a boundary condition that honours the continuity of the fluid volume flux. We discuss the limitations of the 1D model when applied to data recorded at higher frequencies (up to 100 Hz). [ABSTRACT FROM AUTHOR]

The cylinder test experiment is an excellent method to derive Jones‐Wilkins‐Lee‐parameters as the expansion work of the detonation products can be determined from the experimentally observed wall velocity by an analytic approach. However, the physical description of the problem is essential for a precise determination of the expansion work. A useful method to develop and validate such models is to perform hydrodynamic simulations. This work aims to provide an improved analytic model and to introduce a robust and accurate solver design to calculate JWL‐parameters in combination with an optimization of the experimental setup. An extended version of an already accurate literature model is presented, where the air gap is taken into account within the balance equations. Moreover, the surface angle of the cylinder wall is determined from geometric considerations instead of preliminary simulations for conventional explosives. Besides, an own empiric approach for the strain model is introduced, which leads to a smaller deviation between the expansion work from the cylinder test simulation and the calculated expansion work for the underlying equation of state. Regarding the derivation of JWL‐parameters and the determination of the Chapman‐Jouguet‐pressure, the complete workflow, including the global numerical optimization method, is described in detail and the accuracy and robustness of the solver are proven. The entire workflow is validated for different (full‐wall) geometries and conventional explosives to verify that the method scales. Finally, geometric considerations for the placement of the PDV‐gauges are provided to optimize the design and geometry of cylinder test experiments. [ABSTRACT FROM AUTHOR]

Redox active metalloenzymes catalyse a range of biochemical processes essential for life. However, due to their complex reaction mechanisms, and often, their poor optical signals, detailed mechanistic understandings of them are limited. Here, we develop a cryoreduction approach coupled to electron paramagnetic resonance measurements to study electron transfer between the copper centers in the copper nitrite reductase (CuNiR) family of enzymes. Unlike alternative methods used to study electron transfer reactions, the cryoreduction approach presented here allows observation of the redox state of both metal centers, a direct read‐out of electron transfer, determines the presence of the substrate/product in the active site and shows the importance of protein motion in inter‐copper electron transfer catalyzed by CuNiRs. Cryoreduction‐EPR is broadly applicable for the study of electron transfer in other redox enzymes and paves the way to explore transient states in multiple redox‐center containing proteins (homo and hetero metal ions). [ABSTRACT FROM AUTHOR]

Driven by significant innovations in manufacturing on the edge of a 'second machine age', automation will play a pivotal role in turning the world of work upside down. Digitized manufacturing is fundamentally changing relations between human and machine. The expected symbiosis has not yet been systematically organized, since human resource management has widely ignored the topic of automation. If HRM fails to answer the final call, it will lose its influence in smart factories, ultimately being replaced by other functions. Our theoretically derived concept of human‐automation resource management (HARM) discloses a possible way out by specifically tackling the conjunction between humans and machines. We will sketch HARM as the combination of HRM and automation management and, therefore, as the next evolutionary step in the advancement of HRM. After supporting the strategic integration by means of its synergistic benefits, we will determine the tasks HARM is expected to fulfill at the automation‐people‐nexus. [ABSTRACT FROM AUTHOR]

Standards for estimating mouth width and Cupid's bow width in craniofacial approximation and superimposition are limited. Currently, the only guideline for mouth width, using direct skeletal references, is a general rule indicating a 75% inter‐canine to mouth width ratio. The philtrum, which closely corresponds to the Cupid's bow, is said to be equal to the inter‐superior prominences of the maxillary central incisors. This study tested these guidelines against newly generated regression models and mean values. Cone‐beam CT scans of 120 black and 39 white southern African adults were used. Comparative hard and soft tissue measurements were taken using a 3D DICOM viewer. Regression equations accounting population, sex, and approximate age variables (20–39 and 40+ years), utilizing maxillary inter‐canine width to estimate mouth width and maxillary central–lateral incisor junction width to estimate Cupid's bow width, performed statistically best. The regression models were more reliable than existing standards in validation tests. [ABSTRACT FROM AUTHOR]

A HOT‐CAT (homogeneous thermal catalysis) screen using microwave‐heating and quantitative NMR (qNMR) analysis has been developed for identification and comparison of catalyst activity in homogeneous metal‐based catalysis. The hydration of terminal alkynes to ketones or aldehydes served as a model reaction in this proof‐of‐concept study. Key aspects of the screen are the use of a high‐temperature setting (e. g. 160 °C) at a fixed, short reaction time (e. g. 15 min) for all samples. Analysis of crude reaction mixtures by a standardized, quantitative 1H NMR protocol gives a comprehensive picture of catalyst chemo‐ and regioselectivity, which permits broad comparisons and the discovery of non‐target reactivity. For catalytic alkyne hydration, data for 105 runs involving 81 catalyst systems with 15 different metals is presented. The activity of all established catalyst systems was reproduced, and new catalyst systems with Markovnikov hydration selectivity were discovered and applied to preparative runs, namely Cu2O−CSA (CSA=camphorsulfonic acid), Co(OAc)2−tetraphenylporphyrin−CSA and [IrCl(COD)]−CSA. [ABSTRACT FROM AUTHOR]

Objective: Heterozygous SHANK3 mutations or partial deletions of the long arm of chromosome 22, also known as Phelan–McDermid syndrome, result in a syndromic form of the autism spectrum as well as in global developmental delay, intellectual disability, and several neuropsychiatric comorbidities. The exact pathophysiological mechanisms underlying the disease are still far from being deciphered but studies of SHANK3 models have contributed to the understanding of how the loss of the synaptic protein SHANK3 affects neuronal function. Methods and results: Diffusion tensor imaging‐based and automatic volumetric brain mapping were performed in 12 SHANK3‐deficient participants (mean age 19 ± 15 years) versus 14 age‐ and gender‐matched controls (mean age 29 ± 5 years). Using whole brain–based spatial statistics, we observed a highly significant pattern of white matter alterations in participants with SHANK3 mutations with focus on the long association fiber tracts, particularly the uncinate tract and the inferior fronto‐occipital fasciculus. In contrast, only subtle gray matter volumetric abnormalities were detectable. In a back‐translational approach, we observed similar white matter alterations in heterozygous isoform–specific Shank3 knockout (KO) mice. Here, in the baseline data sets, the comparison of Shank3 heterozygous KO vs wildtype showed significant fractional anisotropy reduction of the long fiber tract systems in the KO model. The multiparametric Magnetic Resonance Imaging (MRI) analysis by DTI and volumetry demonstrated a pathology pattern with severe white matter alterations and only subtle gray matter changes in the animal model. Interpretation: In summary, these translational data provide strong evidence that the SHANK3‐deficiency–associated pathomechanism presents predominantly with a white matter disease. Further studies should concentrate on the role of SHANK3 during early axonal pathfinding/wiring and in myelin formation. [ABSTRACT FROM AUTHOR]

Hand-held devices have revolutionized communication and education in the last decade. Consequently, mobile learning (m-learning) has become popular among medical students. Nevertheless, there are relatively few studies assessing students' learning outcomes using m-learning devices. This observational study presents an anatomy m-learning tool (eMed-App), an application developed to accompany an anatomy seminar and support medical students' self-directed learning of the skeletal system. Questionnaire data describe where, how frequently, and why students used the app. Multiple choice examination results were analyzed to evaluate whether usage of the app had an effect on test scores. The eMed-App application was used by 77.5% of the students, mainly accessed by Android smartphones, and at students' homes (62.2%) in order to prepare themselves for seminar sessions (60.8%), or to review learning content (67%). Most commonly, students logged on for less than 15 minutes each time (67.8%). Frequent app users showed better test results on items covering eMed-App learning content. In addition, users also achieved better results on items that were not related to the content of the app and, thus, gained better overall test results and lower failure rates. The top quartile of test performers used the eMed-App more frequently compared to students in lower quartiles. This study demonstrated that many students, especially the high-performing ones, made use of the eMed-App. However, the app itself did not result in better outcomes, suggesting that top students might have been more motivated to use the app than students who were generally weak in anatomy. [ABSTRACT FROM AUTHOR]

Most ene‐reductases belong to the Old Yellow Enzyme (OYE) family of flavin‐dependent oxidoreductases. OYEs use nicotinamide coenzymes as hydride donors to catalyze the reduction of alkenes that contain an electron‐withdrawing group. There have been many investigations of the structures and catalytic mechanisms of OYEs. However, the origin of coenzyme specificity in the OYE family is unknown. Structural NMR and X‐ray crystallographic data were used to rationally design variants of two OYEs, pentaerythritol tetranitrate reductase (PETNR) and morphinone reductase (MR), to discover the basis of coenzyme selectivity. PETNR has dual‐specificity and reacts with NADH and NADPH; MR accepts only NADH as hydride donor. Variants of a β‐hairpin motif in an active site loop of both these enzymes were studied using stopped‐flow spectroscopy. Specific attention was placed on the potential role of arginine residues within the β‐hairpin motif. Mutagenesis demonstrated that Arg130 governs the preference of PETNR for NADPH, and that Arg142 interacts with the coenzyme pyrophosphate group. These observations were used to switch coenzyme specificity in MR by replacing either Glu134 or Leu146 with arginine residues. These variants had increased (~15‐fold) affinity for NADH. Mutagenesis enabled MR to accept NADPH as a hydride donor, with E134R MR showing a significant (55‐fold) increase in efficiency in the reductive half‐reaction, when compared to the essentially unreactive wild‐type enzyme. Insight into the question of coenzyme selectivity in OYEs has therefore been addressed through rational redesign. This should enable coenzyme selectivity to be improved and switched in other OYEs. [ABSTRACT FROM AUTHOR]

How the dynamics of proteins assist catalysis is a contemporary issue in enzymology. In particular, this holds true for membrane‐bound enzymes, where multiple structural, spectroscopic and biochemical approaches are needed to build up a comprehensive picture of how dynamics influence enzyme reaction cycles. Of note are the recent studies of cytochrome P450 reductases (CPR)–P450 (CYP) endoplasmic reticulum redox chains, showing the relationship between dynamics and electron flow through flavin and haem redox centres and the impact this has on monooxygenation chemistry. These studies have led to deeper understanding of mechanisms of electron flow, including the timing and control of electron delivery to protein‐bound cofactors needed to facilitate CYP‐catalysed reactions. Individual and multiple component systems have been used to capture biochemical behaviour and these have led to the emergence of more integrated models of catalysis. Crucially, the effects of membrane environment and composition on reaction cycle chemistry have also been probed, including effects on coenzyme binding/release, thermodynamic control of electron transfer, conformational coupling between partner proteins and vectorial versus 'off pathway' electron flow. Here, we review these studies and discuss evidence for the emergence of dynamic structural models of electron flow along human microsomal CPR–P450 redox chains. [ABSTRACT FROM AUTHOR]

The decay of seismic amplitude is caused by a variety of physical phenomena that can be divided broadly into elastic transmission losses (including geometrical spreading, interface transmission losses and scattering attenuation) and intrinsic attenuation, where wave energy is converted into heat due to viscous friction. The so‐called statistical averaging method is currently considered as the most advanced sonic wave attenuation estimation method, and there exist various implementations of this method. But the way elastic transmission losses – that mask the true intrinsic attenuation – are compensated for appears to be an issue and in some cases this correction has been overlooked. In this paper, we revisit the statistical averaging method for intrinsic attenuation estimation with particular focus on the role of elastic transmission losses. Through synthetic examples, we demonstrate the importance of compensating for elastic transmission losses even if the variation of velocity and density with depth is not notable. Our implementation of the method uses finite‐difference simulations thereby providing a versatile and accurate way to generate synthetic seismograms. We use a combination of elastic and viscoelastic finite‐difference simulations to demonstrate the significant error without accurate compensation of the elastic transmission losses. We apply our implementation of the method to sonic waveforms acquired in an exploration well from Browse basin, Australia. The resulting intrinsic attenuation estimates are indeed indicative of gas‐saturated zones identified from petrophysical analysis in which viscous friction are thought to be of importance. [ABSTRACT FROM AUTHOR]

The exceptionally mild conditions of a titanium(III)‐catalyzed cyclization reaction paired with a convenient acid/base extraction have enabled the straightforward synthesis, isolation, and direct N‐functionalization of amino heterocycles such as 3‐aminoindoles and ‐pyrroles. The unprotected heterocycles are ideal building blocks for the installation of aminated indoles and pyrroles into target molecules, but their sensitivity has previously impeded their synthesis by modern catalytic methods. This full paper presents the development and extended scope of the new cyclization methodology. The transformation of the products into fused bis‐indoles is also demonstrated along with the discovery of an unusual palladium‐catalyzed reductive biphenyl coupling reaction. The titanium(III)‐catalyzed cyclization has also been applied to the synthesis of substituted 3‐iminoindolines, which are of potential interest for applications in natural product synthesis and exhibit tunable blue‐to‐green fluorescence properties. Success at last! A titanium(III)‐catalyzed imine–nitrile cyclization gives rise to free aminoindoles, aminopyrroles, and iminoindolines that are ideal but fragile building blocks for the installation of such motifs into target molecules. Herein, the development, extended scope, and application of this reaction are described. Moreover, the fluorescence properties of the iminoindoline products are briefly reported. [ABSTRACT FROM AUTHOR]

This work reports the first of its kind custom implantable cathodic voltage controlled electrical stimulator (iCVCES) for use with implanted orthopaedic devices. The iCVCES allows researchers to study DC cathodic voltage controlled electrical stimulation (CVCES) in vivo with no percutaneous leads. The iCVCES is a microcontroller-based potentiostat circuit with wireless (bluetooth) communication that controls the DC cathodic stimulation and monitors the environment around the implant. Comprising a single PCB with a coin cell battery, the device is able to hold a constant voltage as large as −1.8 V in a dynamic impedance environment. In vitro tests demonstrate functionality comparable to bench-top systems, and in vivo tests demonstrate operation in live rats, for up to 8 days, with the ability to provide constant stimulation with a maximum variation of 2 mV. [ABSTRACT FROM AUTHOR]

Abstract: Astrocytes are involved in non‐cell‐autonomous pathogenic cascades in amyotrophic lateral sclerosis (ALS); however, their role is still debated. We show that astrocytic NF‐κB activation drives microglial proliferation and leukocyte infiltration in the SOD1 (G93A) ALS model. This response prolongs the presymptomatic phase, delaying muscle denervation and decreasing disease burden, but turns detrimental in the symptomatic phase, accelerating disease progression. The transition corresponds to a shift in the microglial phenotype showing two effects that can be dissociated by temporally controlling NF‐κB activation. While NF‐κB activation in astrocytes induced a Wnt‐dependent microglial proliferation in the presymptomatic phase with neuroprotective effects on motoneurons, in later stage, astrocyte NF‐κB‐dependent microglial activation caused an accelerated disease progression. Notably, suppression of the early microglial response by CB2R agonists had acute detrimental effects. These data identify astrocytes as important regulators of microglia expansion and immune response. Therefore, stage‐dependent microglia modulation may be an effective therapeutic strategy in ALS. [ABSTRACT FROM AUTHOR]

Abstract: The benzylidyne complex [PhC≡W{OSi(OtBu)3}3] (1) catalyzed the cross‐metathesis between 1,4‐bis(trimethylsilyl)‐1,3‐butadiyne (2) and symmetrical 1,3‐diynes (3) efficiently, which gave access to TMS‐capped 1,3‐diynes RC≡C−C≡CSiMe3 (4). Diyne cross‐metathesis (DYCM) studies with 13C‐labeled diyne PhC≡13C−13C≡CPh (3*) revealed that this reaction proceeds through reversible carbon–carbon triple‐bond cleavage and formation according to the conventional mechanism of alkyne metathesis. The reaction between 1 and 3* afforded the 3‐phenylpropynylidyne complex PhC≡13C−13C≡W{OSi(OtBu)3}3] (5*), indicating that alkynylalkylidyne complexes are likely to act as catalytically active species. Attempts to isolate 5* from mixtures of 1 and 3* afforded crystals of the ditungsten 2‐butyne‐1,4‐diylidyne complex [(tBuO)3SiO}3W≡13C−13C≡13C−13C≡W{OSi(OtBu)3}3] (6*), which was additionally characterized by X‐ray diffraction analysis. Depolymerization‐macrocyclization of a carbazole‐butadiyne polymer, obtained from 3,6‐diethynyl‐9‐dodecylcarbazole (7) under copper‐catalyzed Hay coupling conditions, was also efficiently catalyzed by 1 and afforded a mixture of mono‐, diyne‐ and triyne‐containing tetrameric macrocycles, revealing that diyne disproportionation into monoynes and triynes occurs as a slow side reaction that interferes with a high diyne metathesis selectivity. Potential catalytic pathways were studied by means of quantum‐chemical calculations, and kinetic studies were performed to substantiate an α,α‐mechanism for the catalytic diyne metathesis reaction, which involves intermediate alkynylalkylidyne and α,α′‐dialkynylmetallacyclobutadiene intermediates. [ABSTRACT FROM AUTHOR]

Abstract: The Shank proteins are crucial scaffolding elements of the post‐synaptic density (PSD). One of the best‐characterized domains in Shank is the PDZ domain, which binds to C‐terminal segments of several other PSD proteins. We carried out a detailed structural analysis of Shank3 PDZ domain‐peptide complexes, to understand determinants of binding affinity towards different ligand proteins. Ligand peptides from four different proteins were cocrystallized with the Shank3 PDZ domain, and binding affinities were determined calorimetrically. In addition to conserved class I interactions between the first and third C‐terminal peptide residue and Shank3, side chain interactions of other residues in the peptide with the PDZ domain are important factors in defining affinity. Structural conservation suggests that the binding specificities of the PDZ domains from different Shanks are similar. Two conserved buried water molecules in PDZ domains may affect correct local folding of ligand recognition determinants. The solution structure of a tandem Shank3 construct containing the SH3 and PDZ domains showed that the two domains are close to each other, which could be of relevance, when recognizing and binding full target proteins. The SH3 domain did not affect the affinity of the PDZ domain towards short target peptides, and the schizophrenia‐linked Shank3 mutation R536W in the linker between the domains had no effect on the structure or peptide interactions of the Shank3 SH3‐PDZ unit. Our data show the spatial arrangement of two adjacent Shank domains and pinpoint affinity determinants for short PDZ domain ligands with limited sequence homology. [ABSTRACT FROM AUTHOR]

Many Anglo‐American universities have undertaken a paradigm shift in how the dissection of human material is approached, such that students are encouraged to learn about the lives of body donors, and to respectfully “personalize” them as human beings, rather than treating the specimens as anonymous cadavers. For the purposes of this study, this provision of limited personal information regarding the life of a body donor will be referred to as “personalization” of body donors. At this time, it is unknown whether this paradigm shift in the personalization of body donors can be translated into the German‐speaking world. A shift from donor anonymity to donor personalization could strengthen students' perception of the donor as a “first patient,” and thereby reinforce their ability to empathize with their future patients. Therefore, this study aimed to collect data about the current status of donation practices at German‐speaking anatomy departments (n = 44) and to describe the opinions of anatomy departments, students (n = 366), and donors (n = 227) about possible donor personalization in medical education. Anatomy departments in Germany, Austria, and Switzerland were invited to participate in an online questionnaire. One‐tenth of registered donors at Ulm University were randomly selected and received a questionnaire (20 items, yes‐no questions) by mail. Students at the University of Ulm were also surveyed at the end of the dissection course (31 items, six‐point Likert‐scale). The majority of students were interested in receiving additional information about their donors (78.1%). A majority of donors also supported the anonymous disclosure of information about their medical history (92.5%). However, this information is only available in about 28% of the departments surveyed and is communicated to the students only irregularly. Overall, 78% of anatomy departments were not in favor of undertaking donor personalization. The results appear to reflect traditional attitudes among anatomy departments. However, since students clearly preferred receiving additional donor information, and most donors expressed a willingness to provide this information, one could argue that a change in attitudes is necessary. To do so, official recommendations for a limited, anonymous personalization of donated cadaveric specimens might be necessary. Anat Sci Educ 11: 282–293. © 2017 American Association of Anatomists. [ABSTRACT FROM AUTHOR]

Polymethymethacrylate (PMMA) is one of the most important thermoplasts and a commonly used material in microsystem fabrication, for example, microfluidics owning mainly to its optical transparency, biocompatibility, low autofluorescence, and low cost. However, being a thermoplastic material PMMA is typically structured using industrial replication techniques making PMMA unsuitable for rapid prototyping. The fact that neither material nor processing technique can be directly transferred from laboratory to industrial state makes the research‐to‐business conversion often extremely difficult in microfluidics since material properties have a major impact on the final system behavior. This paper presents “Liquid PMMA,” a fast curing viscous PMMA prepolymer which can be used as a negative photoresist and directly structured using ultraviolet or visible light with tens of micron resolution and smooth surfaces. Using this technique microfluidic chips in PMMA can be fabricated within minutes. The cured Liquid PMMA parts show the same high optical transparency, low autofluorescence, and surface properties like commercial PMMA. In this way, microfluidic chips can be rapidly developed and optimized on the laboratory scale in the same material which is later on used on the industrial scale. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this paper is to investigate the impact of the unusually low interest rate environment on the soundness of the United States banking sector in terms of profitability and risk‐taking. Using both dynamic and static modelling approaches and various estimation techniques, we find that the low interest rate environment indeed impairs bank performance and compresses net interest margins. Nonetheless, banks have been able to maintain their overall level of profits, due to lower provisioning, which in turn may endanger financial stability. Banks did not compensate for their lower interest income by expanding operations to include trading activities with a higher risk exposure. [ABSTRACT FROM AUTHOR]