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The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit low in vivo signal-to-noise ratios, saturating activation kinetics and exclusion from postsynaptic densities. Using a multiassay screen in bacteria, soluble protein and cultured neurons, we generated variants with improved signal-to-noise ratios and kinetics. We developed surface display constructs that improve iGluSnFR's nanoscopic localization to postsynapses. The resulting indicator iGluSnFR3 exhibits rapid nonsaturating activation kinetics and reports synaptic glutamate release with decreased saturation and increased specificity versus extrasynaptic signals in cultured neurons. Simultaneous imaging and electrophysiology at individual boutons in mouse visual cortex showed that iGluSnFR3 transients report single action potentials with high specificity. In vibrissal sensory cortex layer 4, we used iGluSnFR3 to characterize distinct patterns of touch-evoked feedforward input from thalamocortical boutons and both feedforward and recurrent input onto L4 cortical neuron dendritic spines.

ABSTRACT Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens in vitro and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of Staphylococcus aureus. Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of S. aureus within minutes due to protonophore activity. Varying the salt species and concentrations in buffers revealed that not only protons are transported, and we demonstrate the binding of the monovalent cations K+, Na+, and Li+ to lugdunin. By comparing known ionophores with various ion transport mechanisms, we conclude that the ion selectivity of lugdunin largely resembles that of 15-mer linear peptide gramicidin A. Direct interference with the main bacterial metabolic pathways including DNA, RNA, protein, and cell wall biosyntheses can be excluded. The previously observed synergism of lugdunin with dermcidin-derived peptides such as DCD-1 in killing S. aureus is mechanistically based on potentiated membrane depolarization. We also found that lugdunin was active against certain eukaryotic cells, however strongly depending on the cell line and growth conditions. While adherent lung epithelial cell lines were almost unaffected, more sensitive cells showed dissipation of the mitochondrial membrane potential. Lugdunin seems specifically adapted to its natural environment in the respiratory tract. The ionophore mechanism is refractory to resistance development and benefits from synergy with host-derived antimicrobial peptides.IMPORTANCEThe vast majority of antimicrobial peptides produced by members of the microbiome target the bacterial cell envelope by many different mechanisms. These compounds and their producers have evolved side-by-side with their host and were constantly challenged by the host’s immune system. These molecules are optimized to be well tolerated at their physiological site of production, and their modes of action have proven efficient in vivo. Imbalancing the cellular ion homeostasis is a prominent mechanism among antibacterial natural products. For instance, over 120 naturally occurring polyether ionophores are known to date, and antimicrobial peptides with ionophore activity have also been detected in microbiomes. In this study, we elucidated the mechanism underlying the membrane potential-dissipating activity of the thiazolidine‐containing cycloheptapeptide lugdunin, the first member of the fibupeptides discovered in a commensal bacterium from the human nose, which is a promising future probiotic candidate that is not prone to resistance development.

Abstract Key message The application of material selection principles uncovered eight possible alternative tree species (two deciduous and six coniferous species) to substitute Norway spruce (Picea abies (L.) H. Karst.) and potentially prevent economic loss in European forest. Context Climate change is a major challenge for the Central European forest and timber industry. Increasing biotic (e.g. beetle damage) and abiotic (e.g. drought) calamities have led to major losses in forest value, especially on Norway spruce (Picea abies (L.) H. Karst.) stands. Therefore, a transition to climate change adapted forest management is necessary. Concurrently, neophytes (e.g. tree of heaven (Ailanthus altissima (Mill.) Swingle), Douglas fir (Pseudotsuga menziesii (Mirbel) Franco), grand fir (Abies grandis (Douglas ex D. Don) Lindl.) and Paulownia (Paulownia tomentosa (Thunb.) Steud.)) are increasing their dominance in forest communities and causing additional adaption of the forest ecosystem. Both factors will lead to significant changes in wood species distributions in Central European forests, mainly at the expanse of Norway spruce, over the next decades. Aims Choosing the “right” tree species for afforestation will become ever more complex and will require a holistic approach that combines forestry and technological aspects alike. Therefore, this review presents a selection approach based on available wood material data from literature and the material selection principles proposed by M. Ashby with the aim to identify suitable alternatives for Norway spruce (Picea abies (L.) H. Karst.) and further concisely assess their silvicultural relevance. Methods For this wood species comparison and selection process, dry and raw density, bending strength and modulus of elasticity were chosen as key properties. Beam- and plate-like components subjected to a bending load were chosen as representative use cases. Results European birch (Betula spp.), grand fir (Abies grandis (Douglas ex D. Don) Lindl.) and silver fir (Abies alba Mill.) were identified as suitable alternatives for Norway spruce (Picea abies (L.) H. Karst.) from a technological as well as silvicultural point of view. In addition, Paulownia (Paulownia tomentosa (Thunb.) Steud.), Sitka spruce (Picea sitchensis (Bong.) Carrière), yellow pine (Pinus strobus L.), western red cedar (Thuja plicata Donn ex D. Don in Lambert) and loblolly pine (Pinus taeda L.) offer a technological advantage but currently lack relevance in the forest sector. Conclusion The proposed selection process offers an evaluation of technical performance, and in combination with an assessment of the silvicultural relevance, it will be possible to optimize the wood-supply chain and prevent future economic loss of Central European forests.

In a scenario of increasing alarm about food waste due to rapid urbanization, population growth and lifestyle changes, this study aims to explore the valorization of waste from the retail sector as potential substrates for the biotechnological production of biosurfactants. With a perspective of increasingly contributing to the realization of the circular bioeconomy, a vegetable juice, derived from unsold fruits and vegetables, as a carbon source was used to produce lipopeptides such as surfactin and fengycin. The results from the shake flask cultivations revealed that different concentrations of vegetable juice could effectively serve as carbon sources and that the fed-batch bioreactor cultivation strategy allowed the yields of lipopeptides to be significantly increased. In particular, the product/substrate yield of 0.09 g/g for surfactin and 0.85 mg/g for fengycin was obtained with maximum concentrations of 2.77 g/L and 27.53 mg/L after 16 h, respectively. To conclude, this study provides the successful fed-batch cultivation of B. subtilis using waste product as the carbon source to produce secondary metabolites. Therefore, the consumption of agricultural product wastes might be a promising source for producing valuable metabolites which have promising application potential to be used in several fields of biological controls of fungal diseases.

Hydraulic testing of isolated sapwood from mature tree trunks is time-consuming and prone to errors, whereas the measurement of compression strength is a standardized and rapid wood technological application. In this study, we aimed to analyze if compression stress perpendicular to the grain relates to hydraulic vulnerability of mature Norway spruce (Picea abies) trunk wood with an expected narrow vulnerability range. The sample-set comprised 52 specimens originating from 34 trees harvested in Sweden. Before mechanical testing, the P50, i.e., the water potential resulting in 50 % of hydraulic conductivity loss, was estimated on small sapwood beams employing the air injection method. Compression strength perpendicular to the grain was defined as the first peak of a stress-strain curve (peak stress) when the wood is subjected to radial compression. Peak stress ranged between 1,65 MPa and 5,07 MPa, P50 between -2,98 MPa and -1,98 MPa. We found a good correlation between the peak stress and P50 (r = 0,80; P < 0,0001). This provides further evidence that peak stress in radial compression and P50 are both extremely dependent on the characteristics of the “weakest” wood part, i.e., the highly conductive earlywood. We conclude that the radial compression strength is a good proxy for P50 of mature Norway spruce trunk wood.

Abstract Polycyclic aromatic hydrocarbons, such as pyrenes, are a well‐known material class for non‐covalent modification of carbon surfaces in many applications. In electrochemical energy storage, pyrenes are mostly used in large polymeric structures. This work addresses the use of carboxy‐ and amino‐functionalized pyrenes for graphite electrodes for lithium‐ion batteries (LIBs). Pyrenes are explored as adsorbed species on graphite prior to electrode fabrication and as additives to the electrode composition. Thereby, 1‐pyrenecarboxylic acid, 1‐pyrenebutyric acid, 1‐aminopyrene, and 1‐pyrenebutylamine were under investigation. As additives, pyrenes do not influence the cycling performance of the electrode at low current but deteriorate the performance at high current, regardless of the functional group. However, when the pyrenes are adsorbed to the graphite surface, the influence of the different functional groups becomes clearly visible, revealing that an additional butyl group has a positive impact on the cycling performance and lithium‐ion transport of the electrodes. Electrodes with 1‐pyrenebutyric acid even enhanced the performance compared to the pristine electrode.

This introductory contribution to the inaugural issue of Languages and Peoples of the Eastern Himalayan Region (LPEHR) outlines the mission and goals of this new publication outlet. LPEHR takes over where the North East Indian Linguistics (NEIL) series left off. As such, this introduction also looks back on NEIL. An index of all articles published in the NEIL volumes is attached as supplemental material to this contribution.

For many purposes related to the bonding of wood substrates, one-component polyurethane adhesives (1C-PUR) are of great significance. 1C-PUR adhesives are widely used, especially in the cross laminated timber (CLT) production. One major benefit is their ability to be pressed at room temperature. However, not only pressing temperature but also the pressing time is an important economic aspect for manufacturers. Knowing the minimum possible press time offers an economic advantage, however, there have been only few publications on this topic so far. The aim of this work was to investigate and evaluate various aspects of a 1C-PUR adhesive with regard to the minimum pressing time comparing newly developed knowledge-based approaches. The analysis included the strength development of the advanced curing of the adhesive, the development of the final internal bond strength and the minimum required press time for bonded joints to withstand imposed stress. The influence of the wood moisture content and closed assembly time were also investigated. The present study found that closed assembly time had a favourable influence on the required press time period. With immediate testing of the glued joint it also revealed a quicker strength development with lower strength values at a higher wood moisture content. [ABSTRACT FROM AUTHOR]

Comparative analysis of the chemical and rheological curing kinetics of formaldehyde-based wood adhesives is crucial for assessing their respective performance. Differential scanning calorimetry (DSC) and rheometry are the conventional techniques used for monitoring the curing processes leading to crosslinking polymerization of the adhesives. However, the direct comparison of these techniques is inappropriate due to the intrinsic differences in their underlying procedures. To address this challenge, the two adhesive samples were sequentially cured, firstly with rheometry and followed by DSC. The observed higher curing degree in the subsequent DSC procedure underpins the incomplete curing of the samples during initial rheometry. Furthermore, the comparative assessment of the activation energies, molar ratios, and active groups of the two adhesives highlights the importance of the pre-exponential factor in addition to the activation energies, as it attributes to the probability of active groups coinciding at the appropriate spatial arrangement. [ABSTRACT FROM AUTHOR]

Person indexation in Monsang (Northwestern South-Central or “Kuki-Chin”) consists of a set of prefixes as well as a basic set of postverbal person markers with three variants. Based on which of these sets are used, this study finds four types of intransitive and four types of transitive paradigms of verbal person indexation. As for the three variants of postverbal person markers, a diachronic order is proposed: one set is clearly conservative; one set is clearly innovative and represents a fusion with a reconstructed palatal copula; and a third hybrid set appears to represent analogical change in the first person plural inclusive form. Finally, out of the four intransitive and four transitive types of person indexation, three of each closely match. In the case of the divergent intransitive type and transitive type, it is argued that the transitive type represents an innovative nominalization construction while the intransitive type did not undergo the same type of nominalization.

The papers in this issue document argument indexation or verb agreement systems in a set of relatively unknown Tibeto-Burman languages spoken in the hills along the eastern border of India. This introduction lays out the goals and scope of the contributions. In addition, an overview of a few topics of particular interest is given: the types of person marker sets found in these languages; number marking; clusivity; transitive and ditransitive indexation patterns; innovative speech-act participant object marking and portmanteau forms for particular person scenarios; inverse marking; and variation in indexation forms.

Magnetic resonance imaging (MR)-guided online adaptive radiotherapy is a promising technique in the field of radiation oncology providing excellent visualisation of soft-tissues, and allowing for online plan adaptation and tumour tracking. In order to facilitate the accurate dose delivery to the target volume while sparing healthy surrounding normal tissue in the brain or head-and-neck (H&N) region, precise patient immobilisation with good image quality is pertinent. Herein, we present a customised thermoplastic mask holder with an integrated anterior MR receiver coil support system for MR-guided online adaptive radiotherapy in the brain and head-and-neck region. The approved medical product was developed by Innovative Technologie Voelp (IT-V), Innsbruck, Austria. MR image uniformity measurements demonstrated improved image uniformity at the expense of decreased signal-to-noise ratio due to a more defined and larger distance between the anterior receiver coil and the phantom or patient. This integrated coil support system represents a practical solution facilitating stable and reproducible anterior coil placement while maintaining the thermoplastic mask holder functionality, a widely established immobilisation technique.

This is a collection of 18 fully analyzed and glossed Karbi texts that were recorded between 2009-2012. All of the texts represent Hills Karbi varieties. The genres include less-spontaneous folk stories, but also (personal) narratives, procedural texts, as well as fully spontaneous genres, i.e. an interview/conversation as well as a stimulus-based narration of the pear story film that was told while the speaker was watching the film. The texts represent the main corpus of 'A grammar of Karbi' (Konnerth 2014).

There have been recent advances in the phonological reconstruction of the South-Central (“Kuki-Chin”) branch of Trans-Himalayan (Tibeto-Burman), in particular by VanBik (2009). However, the Northwestern (“Old Kuki”) subgroup, generally considered to be conservative, is not represented in this work as reliable data have not been available. The present study provides a comprehensive documentation of the historical phonology of one Northwestern language, Monsang. The unexpected finding is that Monsang cannot be considered conservative in its phonological development. A large number of sound changes have occurred across all phonological domains. The majority of sound changes are mergers, and with small exceptions, no unusual sound changes are found. As a result, the diachronic development of Monsang can be considered a case of reduction in phonological complexity.