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The inner hair cells (IHCs) within the cochlea convey sound information and have been thought to be electrically and metabolically independent from each other. Here authors report that a subset of IHCs are electrochemically coupled in ‘mini-syncytia’.

Abstract The nonhydrostatic High‐Order Method Modeling Environment (HOMME‐NH) atmospheric dynamical core supports acoustic waves that propagate significantly faster than the advective wind speed, thus greatly limiting the time step size that can be used with standard explicit time integration methods. Resolving acoustic waves is unnecessary for accurate climate and weather prediction. This numerical stiffness is addressed herein by considering implicit‐explicit additive Runge‐Kutta (ARK IMEX) methods that can treat the acoustic waves in a stable manner without requiring implicit treatment of nonstiff modes. Various ARK IMEX methods are evaluated for their efficiency in producing accurate solutions, ability to take large time step sizes, and sensitivity to grid cell length ratio. Both the gravity wave test and baroclinic instability test from the 2012 Dynamical Core Model Intercomparison Project are used to recommend 5 of the 27 ARK IMEX methods tested for use in HOMME‐NH.

The skin is the largest organ in the human body and is colonized by a diverse microbiota that works in harmony to protect the skin. However, when skin damage occurs, the skin microbiota is also disrupted, and pathogens can invade the wound and cause infection. Probiotics or other beneficial microbes and their metabolites are one possible alternative treatment for combating skin pathogens via their antimicrobial effectiveness. The objective of our study was to evaluate the antimicrobial effect of seven multi-strain dietary supplements and eleven single-strain microbes that contain probiotics against 15 clinical wound pathogens using the agar spot assay, co-culturing assay, and agar well diffusion assay. We also conducted genera-specific and species-specific molecular methods to detect the DNA in the dietary supplements and single-strain beneficial microbes. We found that the multi-strain dietary supplements exhibited a statistically significant higher antagonistic effect against the challenge wound pathogens than the single-strain microbes and that lactobacilli-containing dietary supplements and single-strain microbes were significantly more efficient than the selected propionibacteria and bacilli. Differences in results between methods were also observed, possibly due to different mechanisms of action. Individual pathogens were susceptible to different dietary supplements or single-strain microbes. Perhaps an individual approach such as a ‘probiogram’ could be a possibility in the future as a method to find the most efficient targeted probiotic strains, cell-free supernatants, or neutralized cell-free supernatants that have the highest antagonistic effect against individual clinical wound pathogens.

Enteric viruses, including the rotavirus, norovirus, and adenoviruses, are the most common cause of acute gastroenteritis. The rotavirus disease is especially prevalent among children, and studies over the past decade have revealed complex interactions between rotaviruses and the gut microbiota. One way to treat and prevent dysbiosis is the use of probiotics as an antiviral agent. This review focuses on the latest scientific evidence on the antiviral properties of probiotics against rotavirus gastroenteric infections in children. A total of 19 studies exhibited a statistically significant antiviral effect of probiotics. The main probiotics that were effective were Saccharomyces cerevisiae var. boulardii, Lacticaseibacillus rhamnosus GG, and various multi-strain probiotics. The underlying mechanism of the probiotics against rotavirus gastroenteric infections in children included immune enhancement and modulation of intestinal microbiota leading to shortening of diarrhoea. However, several clinical studies also found no significant difference in the probiotic group compared to the placebo group even though well-known strains were used, thus showing the importance of correct dosage, duration of treatment, quality of probiotics and the possible influence of other factors, such as the production process of probiotics and the influence of immunisation on the effect of probiotics. Therefore, more robust, well-designed clinical studies addressing all factors are warranted.

At the end of the first larval stage, the nematode Caenorhabditis elegans developing in harsh environmental conditions is able to choose an alternative developmental path called the dauer diapause. Dauer larvae exhibit different physiology and behaviors from non-dauer larvae. Using focused ion beam-scanning electron microscopy (FIB-SEM), we volumetrically reconstructed the anterior sensory apparatus of C. elegans dauer larvae with unprecedented precision. We provide a detailed description of some neurons, focusing on structural details that were unknown or unresolved by previously published studies. They include the following: (1) dauer-specific branches of the IL2 sensory neurons project into the periphery of anterior sensilla and motor or putative sensory neurons at the sub-lateral cords; (2) ciliated endings of URX sensory neurons are supported by both ILso and AMso socket cells near the amphid openings; (3) variability in amphid sensory dendrites among dauers; and (4) somatic RIP interneurons maintain their projection into the pharyngeal nervous system. Our results support the notion that dauer larvae structurally expand their sensory system to facilitate searching for more favorable environments.

Abstract This paper describes the first implementation of the Δx = 3.25 km version of the Energy Exascale Earth System Model (E3SM) global atmosphere model and its behavior in a 40‐day prescribed‐sea‐surface‐temperature simulation (January 20 through February 28, 2020). This simulation was performed as part of the DYnamics of the Atmospheric general circulation Modeled On Non‐hydrostatic Domains (DYAMOND) Phase 2 model intercomparison. Effective resolution is found to be ∼6× the horizontal dynamics grid resolution despite using a coarser grid for physical parameterizations. Despite this new model being in an immature and untuned state, moving to 3.25 km grid spacing solves several long‐standing problems with the E3SM model. In particular, Amazon precipitation is much more realistic, the frequency of light and heavy precipitation is improved, agreement between the simulated and observed diurnal cycle of tropical precipitation is excellent, and the vertical structure of tropical convection and coastal stratocumulus look good. In addition, the new model is able to capture the frequency and structure of important weather events (e.g., tropical cyclones, extratropical cyclones including atmospheric rivers, and cold air outbreaks). Interestingly, this model does not get rid of the erroneous southern branch of the intertropical convergence zone nor the tendency for strongest convection to occur over the Maritime Continent rather than the West Pacific, both of which are classic climate model biases. Several other problems with the simulation are identified, underscoring the fact that this model is a work in progress.

Over the last few years, the development of micro-distilleries producing diverse spirits with various flavors has been observed. Versatile analytical techniques for the characterization of aroma compounds in such alcoholic beverages are therefore required. A model mixture embodying a theoretical distilled spirit was made according to the data found in literature to compare usual extraction techniques. When it was applied to the model liquor, the headspace solid phase microextraction (HS-SPME) extraction method was preferred to the liquid-liquid extraction (LLE), solid phase extraction (SPE) and stir bar/headspace sorptive extraction (SBSE/HSSE) methods according to efficiency, cost, and environmental criteria. An optimization study using the model mixture showed that the extraction was optimal with a divinylbenzene/carboxen/poly(dimethylsiloxane) DVB/CAR/PDMS fiber, during 60 min, at 35 °C and with the addition of 10% NaCl. This method was successfully applied to three different commercial liquors and led to the identification of 188 flavor compounds, including alcohols, esters, lactones, carbonyls, acetals, fatty acids, phenols, furans, aromatics, terpenoids, alkenes, and alkanes.

Microalgae are an attractive source of biomass for fossil fuel alternatives and renewable energy sources. Regardless of their potential, the development of microalgal biofuels has been limited due to the associated economic and environmental costs. We followed and compared the biomass properties of six Chlorellaceae strains with a specific interest in lipid-based biofuels. The strains were cultivated under balanced nutrient limitation inducing a gradual limitation of nutrients that triggered reserve accumulation. The final biomass of each strain was characterized by its elemental and biochemical composition. Due to its high lipid content and overall composition, Chlorella vulgaris NIES 227 was identified as an ideal feedstock for biofuels with the best energy-content biomass. Its fatty acid profile also showed superior qualities for biodiesel production. Balanced nutrient limitation promoted not only the accumulation of storage compounds in all strains, but also resulted in a low content of heteroatom precursors and ashes for biofuel applications.

Microalgae can be cultivated on waste dark fermentation effluents containing volatile fatty acids (VFA) such as acetate or butyrate. These VFA can however inhibit microalgae growth at concentrations above 0.5-1 gC.L–1. This study used the model strain Chlorella sorokiniana to investigate the effects of acetate or butyrate concentration on biomass growth rates and yields alongside C:N:P ratios and pH control. Decreasing undissociated acid levels by raising the initial pH to 8.0 allowed growth without inhibition up to 5 gC.L–1 VFAs. However, VFA concentration strongly affected biomass yields irrespective of pH control or C:N:P ratios. Biomass yields on 1.0 gC.L–1 acetate were around 1.3-1.5 gC.gC–1 but decreased by 26-48% when increasing initial acetate to 2.0 gC.L–1. This was also observed for butyrate with yields decreasing up to 25%. This decrease in yield in suggested to be due to the prevalence of heterotrophic metabolism at high organic acid concentration, which reduced the amount of carbon fixed by autotrophy. Finally, the effects of C:N:P on biomass, lipids and carbohydrates production dynamics were assessed using a mixture of both substrates. In nutrient replete conditions, C. sorokiniana accumulated up to 20.5% carbohydrates and 16.4% lipids while nutrient limitation triggered carbohydrates accumulation up to 45.3%.

The near infrared spectra of thirty-three freeze-dried and ground organic waste samples of various biochemical composition were collected on four different optical systems, including a laboratory spectrometer, a transportable spectrometer with two measurement configurations (an immersed probe, and a polarized light system) and a micro-spectrometer. The provided data contains one file per spectroscopic system including the reflectance or absorbance spectra with the corresponding sample name and wavelengths. A reference data file containing carbohydrates, lipid and nitrogen content, biochemical methane potential (BMP) and chemical oxygen demand (COD) for each sample is also provided. This data enables the comparison of the optical systems for predictive model calibration based for example on Partial Least Squares Regression (PLS-R) [1], but could be used more broadly to test new chemometrics methods. For example, the data could be used to evaluate different transfer functions between spectroscopic systems [2]. This dataset enabled the research work reported by Mallet et al. 2021 [3].

Branched-chain amino acid (BCAA) biosynthesis is important for pathogenic fungi to successfully cause disease in human and plant hosts. The enzymes for their production are absent from humans and, therefore, provide potential antifungal targets.

The surface morphology of faults controls the spatial anisotropy of their frictional properties and hence their mechanical stability. Such anisotropy is only rarely studied in seismology models of fault slip, although it might be paramount to understand the seismic rupture in particular areas, notably where slip occurs in a direction different from that of the main striations of the fault. To quantify how the anisotropy of fault surfaces affects the friction coefficient during sliding, we sheared synthetic fault planes made of plaster of Paris. These fault planes were produced by 3D-printing real striated fault surfaces whose 3D roughness was measured in the field at spatial scales from millimeters to meters. Here, we show how the 3D-printing technology can help for the study of frictional slip. The results show that fault anisotropy controls the coefficient of static friction, with μS//, the friction coefficient along the striations being three to four times smaller than μS⊥, the friction coefficient along the orientation perpendicular to the striations. This is true both at the meter and the millimeter scales. The anisotropy in friction and the average coefficient of static friction are also shown to decrease with the normal stress applied to the faults, as a result of the increased surface wear under increased loading.

Digital publishing in the humanities has become an established and widely used component of scholarly communication. A digital publishing culture has become an integral part of scientific work. However, not all questions about digital publishing have been answered and many experimental approaches still exist. This working paper by the Digital Publishing Working Group of the Digital Humanities Association in the German-speaking countries (DHd) aims to re-examine digital publishing and look at current developments, discourses and best practice examples.

ABSTRACT The glucose-xylose metabolic transition is of growing interest as a model to explore cellular adaption since these molecules are the main substrates resulting from the deconstruction of lignocellulosic biomass. Here, we investigated the role of the XylR transcription factor in the length of the lag phases when the bacterium Escherichia coli needs to adapt from glucose- to xylose-based growth. First, a variety of lag times were observed when different strains of E. coli were switched from glucose to xylose. These lag times were shown to be controlled by XylR availability in the cells with no further effect on the growth rate on xylose. XylR titration provoked long lag times demonstrated to result from phenotypic heterogeneity during the switch from glucose to xylose, with a subpopulation unable to resume exponential growth, whereas the other subpopulation grew exponentially on xylose. A stochastic model was then constructed based on the assumption that XylR availability influences the probability of individual cells to switch to xylose growth. The model was used to understand how XylR behaves as a molecular switch determining the bistability set-up. This work shows that the length of lag phases in E. coli is controllable and reinforces the role of stochastic mechanism in cellular adaptation, paving the way for new strategies for the better use of sustainable carbon sources in bioeconomy. IMPORTANCE For decades, it was thought that the lags observed when microorganisms switch from one substrate to another are inherent to the time required to adapt the molecular machinery to the new substrate. Here, the lag duration was found to be the time necessary for a subpopulation of adapted cells to emerge and become the main population. By identifying the molecular mechanism controlling the subpopulation emergence, we were able to extend or reduce the duration of the lags. This work is of special importance since it demonstrates the unexpected complexity of monoclonal populations during growth on mixed substrates and provides novel mechanistic insights with regard to bacterial cellular adaptation.

In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon-myelin unit contribute to the phenotype of Plpnull/y mice.

Abstract We derive a formulation of the nonhydrostatic equations in spherical geometry with a Lorenz staggered vertical discretization. The combination conserves a discrete energy in exact time integration when coupled with a mimetic horizontal discretization. The formulation is a version of Dubos and Tort (2014, https://doi.org/10.1175/MWR-D-14-00069.1) rewritten in terms of primitive variables. It is valid for terrain following mass or height coordinates and for both Eulerian or vertically Lagrangian discretizations. The discretization relies on an extension to Simmons and Burridge (1981, https://doi.org/10.1175/1520-0493(1981)1092.0.CO;2) vertical differencing, which we show obeys a discrete derivative product rule. This product rule allows us to simplify the treatment of the vertical transport terms. Energy conservation is obtained via a term‐by‐term balance in the kinetic, internal, and potential energy budgets, ensuring an energy‐consistent discretization up to time truncation error with no spurious sources of energy. We demonstrate convergence with respect to time truncation error in a spectral element code with a horizontal explicit vertically implicit implicit‐explicit time stepping algorithm.

In recent years, interest in Cannabis sativa L. has been rising, as legislation is moving in the right direction. This plant has been known and used for thousands of years for its many active ingredients that lead to various therapeutic effects (pain management, anti-inflammatory, antioxidant, etc.). In this report, our objective was to optimize a method for the extraction of cannabinoids from a clone of Cannabis sativa L. #138 resulting from an agronomic test (LaFleur, Angers, FR). Thus, we wished to identify compounds with anticancer activity on human pancreatic tumor cell lines. Three static maceration procedures, with different extraction parameters, were compared based on their median inhibitory concentration (IC50) values and cannabinoid extraction yield. As CBD emerged as the molecule responsible for inducing apoptosis in the human pancreatic cancer cell line, a CBD-rich cannabis strain remains attractive for therapeutic applications. Additionally, while gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest in G0/G1, CBD also activates the cell signaling cascade to lead to programmed cell death. Our results emphasize the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce G1 cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.

In view of the extensive use of hexagonal boron nitride (hBN) in 2D material electronics, it becomes important to refine its dielectric characterization in terms of low-field permittivity and high-field strength and conductivity up to the breakdown voltage. The present study aims at filling this gap using DC and RF transport in two Au-hBN-Au capacitor series of variable thickness in the 10–100 nm range, made of large high-pressure, high-temperature (HPHT) crystals and a polymer derivative ceramics (PDC) crystals. We deduce an out-of-plane low field dielectric constant ϵ _∥ = 3.4 ± 0.2 consistent with the theoretical prediction of Ohba et al , that narrows down the generally accepted window ϵ _∥ = 3–4. The DC-current leakage at high-field is found to obey the Frenkel-Pool law for thermally-activated trap-assisted electron transport with a dynamic dielectric constant ϵ _∥ ≃ 3.1 and a trap energy Φ _B ≃ 1.3 eV, that is comparable with standard technologically relevant dielectrics.

Recirculation of solid digestate through digesters has been demonstrated to be a potential simple strategy to increase continuous stirred-tank reactor biogas plant efficiency. This study extended this earlier work and investigated solid digestate post-treatment using liquid isolated ligninolytic aerobic consortia in order to increase methane recovery during the recirculation. Based on sampling in several natural environments, an enrichment and selection method was implemented using a Lab-scale Automated and Multiplexed (an)Aerobic Chemostat system to generate ligninolytic aerobic consortia. Then, obtained consortia were further cultivated under liquid form in bottles. Chitinophagia bacteria and Sordariomycetes fungi were the two dominant classes of microorganisms enriched through these steps. Finally, these consortia where mixed with the solid digestate before a short-term aerobic post-treatment. However, consortia addition did not increase the efficiency of aerobic post-treatment of solid digestate and lower methane yields were obtained in comparison to the untreated control. The main reason identified is the respiration of easily degradable fractions (e.g., sugars, proteins, amorphous cellulose) by the selected consortia. Thus, this paper highlights the difficulties of constraining microbial consortia to sole ligninolytic activities on complex feedstock, such as solid digestate, that does not only contain lignocellulosic structures.

Abstract Background Recently, mammalian orthoreoviruses (MRVs) were detected for the first time in European bats, and the closely related strain SI-MRV01 was isolated from a child with severe diarrhoea in Slovenia. Genetically similar strains have also been reported from other mammals, which reveals their wide host distribution. The aim of this study was to retrospectively investigate the occurrence and genetic diversity of MRVs in bats in Slovenia, from samples obtained throughout the country in 2008 to 2010, and in 2012 and to investigate the occurrence of the novel SI-MRV01 MRV variant in Slovenian bats. Results The detection of MRVs in bat guano was based on broad-range RT-PCR and specific bat MRV real-time RT-PCR. Subsequently, MRV isolates were obtained from cell culture propagation, with detailed molecular characterisation through whole-genome sequencing. Overall, bat MRVs were detected in 1.9% to 3.8% of bats in 2008, 2009 and 2012. However, in 2010 the prevalence was 33.0%, which defined an outbreak of the single SI-MRV01 strain. Here, we report on the identification of five MRV isolates of different serotypes that are designated as SI-MRV02, SI-MRV03, SI-MRV04, SI-MRV05 and SI-MRV06. There is high genetic variability between these characterised isolates, with evident genome reassortment seen across their genome segments. Conclusions In conclusion, we have confirmed the presence of the SI-MRV01 strain in a Slovenian bat population. Moreover, according to genetic characterisation of S1 genome segment, all three MRV serotypes were present in the bat population. In this study, five independent MRV isolates were obtained and detailed whole genome analysis revealed high diversity between them. This study generates new information about the epidemiology and molecular characteristics of emerging bat MRV variants, and provides important molecular data for further studies of their pathogenesis and evolution.

Abstract Hybridization between wild species and their domestic congeners is considered a major threat for wildlife conservation. Genetic integrity of the European wildcat, for instance, is a concern as they are outnumbered by domestic cats by several orders of magnitude throughout its range. We genotyped 1,071 individual wildcat samples obtained from hair traps and roadkills collected across the highly fragmented forests of western Central Europe, in Germany and Luxembourg, to assess domestic cat introgression in wildcats in human‐dominated landscapes. Analyses using a panel of 75 autosomal SNPs suggested a low hybridization rate, with 3.5% of wildcat individuals being categorized as F1, F2, or backcrosses to either parental taxon. We report that results based on a set of SNPs were more consistent than on a set of 14 microsatellite markers, showed higher accuracy to detect hybrids and their class in simulation analyses, and were less affected by underlying population structure. Our results strongly suggest that very high hybridization rates previously reported for Central Europe may be partly due to inadequate choice of markers and/or sampling design. Our study documents that an adequately selected SNP panel for hybrid detection may be used as an alternative to commonly applied microsatellite markers, including studies relying on noninvasively collected samples. In addition, our finding of overall low hybridization rates in Central European wildcats provides an example of successful wildlife coexistence in human‐dominated, fragmented landscapes.

Summary: Genome-edited human pluripotent stem cells (hPSCs) have broad applications in disease modeling, drug discovery, and regenerative medicine. We present and characterize a robust method for rapid, scarless introduction or correction of disease-associated variants in hPSCs using CRISPR/Cas9. Utilizing non-integrated plasmid vectors that express a puromycin N-acetyl-transferase (PAC) gene, whose expression and translation is linked to that of Cas9, we transiently select for cells based on their early levels of Cas9 protein. Under optimized conditions, co-delivery with single-stranded donor DNA enabled isolation of clonal cell populations containing both heterozygous and homozygous precise genome edits in as little as 2 weeks without requiring cell sorting or high-throughput sequencing. Edited cells isolated using this method did not contain any detectable off-target mutations and displayed expected functional phenotypes after directed differentiation. We apply the approach to a variety of genomic loci in five hPSC lines cultured using both feeder and feeder-free conditions. : In this article, Saha and colleagues describe a workflow for isolation of hPSC clones containing scarless, HDR-mediated, genome edits without the use of FACS or high-throughput sequencing technologies. They demonstrate that transient expression of a puromycin-resistance gene, from a non-integrated CRISPR/Cas9 plasmid, enables stringent selection for clones precisely edited with a single-stranded donor DNA template. Keywords: genome editing, human pluripotent stem cells, disease modeling, CRISPR/Cas9, scarless, transient selection, puromycin

Different species of microalgae are highly efficient in removing nutrients from wastewater streams and are able to grow using flue gas as a CO2 source. These features indicate that application of microalgae has a promising outlook in wastewater treatment. However, practical aspects and process of integration of algae cultivation into an existing wastewater treatment line have not been investigated. The Climate-KIC co-funded Microalgae Biorefinery 2.0 project developed and demonstrated this integration process through a case study. The purpose of this paper is to introduce this process by phases and protocols, as well as report on the challenges and bottlenecks identified in the case study. These standardized technical protocols detailed in the paper help to assess different aspects of integration including biological aspects such as strain selection, as well as economic and environmental impacts. This process is necessary to guide wastewater treatment plants through the integration of algae cultivation, as unfavourable parameters of the different wastewater related feedstock streams need specific attention and management. In order to obtain compelling designs, more emphasis needs to be put on the engineering aspects of integration. Well-designed integration can lead to operational cost saving and proper feedstock treatment enabling algae growth.

Objectives: The aim of this prospective case series was to evaluate single-piece zirconia implants restored with lithium disilicate CAD/CAM crowns through a long-term follow-up. Methods: In this trial, 20 one-piece zirconia implants were placed in 20 patients. Implants were restored (i) immediately with lithium disilicate CAD/CAM provisionals, and (ii) permanently four months after surgery. Patients were followed for 11 years. Clinical parameters and radiological measurements of the zirconia implants were assessed. For the statistical analysis, paired t-test was applied. Results: Four implants were counted as implant failure due to the loss of implant stability, resulting in a Kaplan–Meier survival rate of 80% up to 11 years. The mean bleeding on probing values were 19.1% (SD ± 13.1) and 18.2% (SD ± 17.6) 96 and 11 years after implant placement, respectively. The plaque index revealed a significant decrease over time (p < 0.001) with a value between 25.9% (SD ± 5.7) and 12.6% (SD ± 10.0) at baseline and 11-years follow-up respectively. The marginal bone level revealed a significant decrease 4, 8, and 11 years after implant insertion (p = 0.001, p = 0.019, and p = 0.027, respectively). Conclusions: Immediately loaded zirconia single-piece implants showed a suitable success rate in clinical and radiographic outcomes.