bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of per- and polyfluoroalkyl substances (PFAS) in a terrestrial food web
Authors: Ecke Frauke , Skrobonja Alexandra , Malmsten Jonas , Ahrens Lutz 
Published: December 2023

AbstractPer– and polyfluoroalkyl substances (PFAS) are synthetic organofluorine chemical compounds that are broadly used in amongst others aqueous firefighting foam, cosmetics, textiles, carpets, coatings, plastics, and ski wax. Their chemical properties make them persistent organic pollutants that are potential bioaccumulative and toxic. Most studies on PFAS have been performed in groundwater, surface water and aquatic biota. Our knowledge on the terrestrial fate of PFAS is therefore limited.We sampled soil, berries, mushrooms, and wildlife on the island Frösön, central Sweden, in 2021 and 2022, to study the fate of 22 PFAS in a terrestrial food web. Groundwater, surface water and fish on Frösön have previously shown high PFAS concentrations. Soil, berries, and mushrooms were also concurrently sampled in a reference area in northern Sweden.Overall, concentrations of the sum of PFAS were low in berries and mushrooms. In moose (Alces alces), roedeer (Capreolus capreolus), and bank vole (Myodes glareolus), concentrations were highest in liver. The maximum levels for PFOS in offal as set by the European Commission (50 ng/g ww) were exceeded in the liver of two of 10 roedeer. Bank voles (n= 12 pools) that were sampled in the vicinity of a firefighting training site showed partly extreme concentrations with none of the samples having liver concentrations <474 ng/g ww (maximum 11,600 ng/g ww). Bioaccumulation factors (BAFs) for multiple PFAS in bank voles were higher for the studied mushrooms and soil compared to studied berries and were >100 for 27 out of 265 calculated BAFs. BAFs in the ungulate species were generally lower than those for bank voles but were >1 for several PFAS from the mushroom.The exact origin of PFAS in bank voles could not be identified in our study, but the BAFs are supported by the feeding and behaviour ecology of bank voles, i.e., there is likely bioaccumulation and biomagnification from soil and mushrooms to bank voles. The measured PFAS concentrations and BAFs, especially those in bank voles are worrying from an ecosystem and One Health perspective considering that voles are staple food for multiple predators.
Protein search processes mediated by chromatin topology
Authors: Dutta Shuvadip , Adarshkrishnan R. , Padinhateeri Ranjith , Mitra Mithun K. 
Published: December 2023

AbstractWe investigate the role of compaction of chromatin domains in modulating search kinetics of proteins. Collapsed conformations of chromatin, characterised by long loops which bring distant regions of the genome into contact, and manifested structurally as Topologically Associated Domains (TADs) affect search kinetics of DNA associated transcription factors and other proteins. In this study, we investigate the role of the compactness of chromatin on the dynamics of proteins using a minimal model. Using analytical theory and simulations, we show that an optimal compaction exists for which the residence time of proteins on a chromatin-like polymer backbone is minimum. We show that while bulk diffusion is an advantageous search strategy for extended polymers, for highly folded polymer domains, intersegmental transfers allow optimal search. We extend these results to more detailed polymer models - using the Freely Rotating Chain model, a Lennard-Jones bead-spring polymer model, which approximates chromatin behavior. We show that our results continue to hold for these polymer models, with a minimum residence time at an optimum polymer compaction. Finally, we also analyse the dynamics of proteins on networks generated using experimental chromatin conformation data from 8355 TADs extracted from human chromosomes. Our analysis suggests that TADs exist near this zone of optimality, indicating that chromatin conformations can play a crucial role in modulating protein search strategies.
Selection bias in reporting of median waiting times in organ transplantation
Authors: Schwab Simon , Elmer Andreas , Sidler Daniel , Straumann Lisa , Stürzinger Ueli , Immer Franz 
Published: December 2023

Median organ waiting times published by transplant organizations around the world may be biased when death or censoring is disregarded. This can lead to too optimistic waiting times for all organ waiting lists, but most strikingly in kidney transplantation, and as a consequence, may deceive patients on the waiting list, transplant physicians, and healthcare policy maker. In this cohort study of all trans-plant candidates in Switzerland, we use competing risk multistate models for the analysis of time-to-event data of the organ waiting list. The resulting cumulative incidences are probabilities for transplantation or death by a given time are a more accurate description of the events occurring on the waiting list. In accordance with the concept of median survival time in survival analysis in clinical trials, we suggest the median time to transplantation (MTT), the waiting time duration at which the transplant probability is 0.50, as a measure of average waiting time.Summary pointsTransplant candidates on the waiting list, healthcare professionals and policy makers may be interested in the accurate assessment of the probabilities of transplantation and undesirable events.The median waiting time based on the median calculated across the waiting durations of transplanted individuals may be misleading due to selection bias, ignoring death and censored observations.Competing risk multistate models based on the Aalen-Johansen estimator are effective in assessing the waiting list with multiple competing events.From the cumulative incidence curve the probabilities of transplantation or death can be determined for any time period.We propose to report both the median time to transplantation (MTT), i.e. the waiting time duration at which the transplant probably is 50%, as well as the probabilities of other competing events during MTT.National transplant organizations around the world may consider changing their reporting policy regarding waiting list statistics.
Functional imaging of nine distinct neuronal populations under a miniscope in freely behaving animals
Authors: Phillips Mary L. , Urban Nicolai T. , Salemi Taddeo , Dong Zhe , Yasuda Ryohei 
Published: December 2023

AbstractHead-mounted miniscopes have allowed for functional fluorescence imaging in freely moving animals. However, current capabilities of state-of-the-art technology can record only up to two, spectrally distinct fluorophores. This severely limits the number of cell types identifiable in a functional imaging experiment. Here we present a pipeline that enables the distinction of nine neuronal subtypes from regions defined by behaviorally relevant cells duringin vivoGCaMP imaging. These subtypes are identified utilizing unique fluorophores that are co-expressed with GCaMP, unmixed by spectral imaging on a confocal microscope and co-registering these spectral fingerprints with functional data obtained on miniaturized microscopes. This method facilitates detailed analyses of circuit-level encoding of behavior.
Rate Dependent Cochlear Outer Hair Cell Force Generation: Models and Parameter Estimation
Authors: Cai Wen , Grosh Karl 
Published: December 2023

AbstractThe outer hair cells (OHCs) of the mammalian cochlea are the mediators of an active, nonlinear electromechanical process necessary for sensitive, frequency specific hearing. The membrane protein prestin conveys to the OHC a piezoelectric-like behavior hypothesized to actuate a high frequency, cycle-by-cycle conversion of electrical to mechanical energy to boost cochlear responses to low-level sound. This hypothesis has been debated for decades, and we address two key remaining issues: the influence of the rate dependence of conformal changes in prestin and the OHC transmembrane impedance. We develop a theoretical electromechanical model of the OHC that explicitly includes rate dependence of conformal transitions, viscoelasticity, and piezoelectricity. Using this theory, we show the influence of rate dependence and viscoelasticity on electromechanical force generation. Further, we stress the importance of using the correct mechanical boundary conditions when estimating the transmembrane capacitance. Finally, a set of experiments is described to uniquely estimate the constitutive properties of the OHC from whole-cell measurements.
Harnessing light-activated gallium porphyrins to combat intracellularStaphylococcus aureusin dermatitis: Insights from a simplified model
Authors: Szymczak Klaudia , Rychłowski Michał , Zhang Lei , Nakonieczna Joanna 
Published: December 2023

AbstractStaphylococcus aureuscan survive inside nonprofessional phagocytes such as keratinocytes, demonstrating a novel strategy for evading antibiotic pressure. When antibiotic treatment ends, reinfection with staphylococci begins from the intracellular inoculum. This phenomenon is responsible for recurrent infections. The development of new antibacterial methods that can eliminate intracellular bacteria, including those with a multidrug-resistant phenotype, is necessary. In this study, we characterized and used a model of keratinocytes (both wild type and mutants with reduced filaggrin expression) infected with methicillin-resistantS. aureus(MRSA) to verify the possibility of using light-activated compounds, exemplified here by heme-mimetic gallium (III) porphyrin (Ga3+CHP) and visible light, an approach known as antimicrobial photodynamic inactivation (aPDI), to eliminate intracellular MRSA. We observed that Ga3+CHP accumulated more in infected cells than in uninfected cells. Moreover, Ga3+CHP accumulated in cells that harbored intracellularS. aureus. Using flow cytometry and fluorescence microscopy, we found that intracellular MRSA and Ga3+CHP mainly colocalized in lysosomal structures, and we showed that under the influence of aPDI, MRSA exhibited reduced adhesion to host cells and a significantly reduced (by 70%) GFP signal originating from intracellular bacteria. Moreover, the use of light-activated Ga3+CHP resulted in a significant reduction in the number of extracellular bacteria in the infection system, lowering the potential for further infection of host cells. For the first time, we used the infectious model to analyze the toxicity of aPDI in real time, showing that this approach is not significantly cyto-or phototoxic.Author SummaryStaphylococcus aureusis a highly virulent pathogen that is responsible for approximately 80% of all skin infections. During antibiotic treatment, one of the defense mechanisms ofS. aureusis the invasion of keratinocytes. Intracellular bacteria are not accessible to antibiotics, which poorly penetrate the interior of host cells. Consequently, such bacteria contribute to recurrent infections. In our study, we proposed using a combination of a light-activated porphyrin compound loaded with gallium ions, Ga3+CHP, and visible light as a strategy to eliminate intracellular staphylococci. We demonstrated that the tested compound colocalized with the pathogen in the infected cells, which was an essential condition for the effective elimination of intracellular bacteria. We showed that the proposed approach effectively reduced the infection of keratinocytes with methicillin-resistantS. aureus(MRSA), as well as its adhesion to host cells, while maintaining host cells. The results presented here provide a basis for developing an effective therapy against staphylococci.
Knowing what you don’t know: Estimating the uncertainty of feedforward and feedback inputs with prediction-error circuits
Authors: Hertäg Loreen , Wilmes Katharina A. , Clopath Claudia 
Published: December 2023

AbstractAt any moment, our brains receive a stream of sensory stimuli arising from the world we interact with. Simultaneously, neural circuits are shaped by feedback signals carrying predictions about the same inputs we experience. Those feedforward and feedback inputs often do not perfectly match. Thus, our brains have the challenging task of integrating these conflicting streams of information according to their reliabilities. However, how neural circuits keep track of both the stimulus and prediction uncertainty is not well understood. Here, we propose a network model whose core is a hierarchical prediction-error circuit. We show that our network can estimate the variance of the sensory stimuli and the uncertainty of the prediction using the activity of negative and positive prediction-error neurons. In line with previous hypotheses, we demonstrate that neural circuits rely strongly on feedback predictions if the perceived stimuli are noisy and the underlying generative process, that is, the environment is stable. Moreover, we show that predictions modulate neural activity at the onset of a new stimulus, even if this sensory information is reliable. In our network, the uncertainty estimation, and, hence, how much we rely on predictions, can be influenced by perturbing the intricate interplay of different inhibitory interneurons. We, therefore, investigate the contribution of those inhibitory interneurons to the weighting of feedforward and feedback inputs. Finally, we show that our network can be linked to biased perception and unravel how stimulus and prediction uncertainty contribute to the contraction bias.
Response diversity in the context of multifarious environmental change
Authors: Polazzo Francesco , Limberger Romana , Pennekamp Frank , Ross Samuel R. P.-J. , Simpson Gavin L. , Petchey Owen L. 
Published: December 2023

1.AbstractResponse diversity represents the inter- and intraspecific trait variation in organismal responses to the environment. Assemblages composed of organisms displaying large variation in their response to the environment (that is, having high response diversity) are expected to have higher temporal stability of aggregate community and ecosystem properties such as ecosystem functioning (i.e., an insurance effect). Yet, response diversity is not commonly measured in empirical studies, and when it is measured, this is done in different ways. Moreover, most proposed measures of response diversity concern situations with only one driver of environmental change. Thus far, no specific approach exists to measure response diversity in the context of multiple simultaneously changing (multifarious) environmental drivers. Here, we propose a new method to empirically quantify response diversity in the context of multifarious environmental change. First, we illustrate this method using simulated data. Next, we reveal the role of the direction of environmental change in shaping response diversity when multiple drivers of environmental change fluctuate over time. We show that, when the direction of the environmental change is unknown (that is, there is no information ora prioriexpectation about how an environmental condition has changed or will change in future), we can quantify thepotentialresponse diversity for a given community under any possible future environmental change scenario. That is, we can estimate the potential response capacity of a system under a range of extreme or realistic environmental changes, capturing its complete insurance capacity, with utility for predicting future responses to even multifarious environmental change. Finally, we investigate the drivers of response diversity in a multifarious environmental change context, showing how response diversity depends on: 1) the diversity of species responses to each environmental variable considered, 2) the relative effect of each environmental variable on species’ performance, 3) the correlation between the diversity in species’ responses to different environmental variables, and 4) the mean temporal value of the environmental variable. In doing so, we take an important step towards understanding the insurance capacity of ecological communities exposed to multifarious environmental change.
A barley MLA receptor is targeted by a non-ribosomal peptide effector of the necrotrophic spot blotch fungus for disease susceptibility
Authors: Leng Yueqiang , Kümmel Florian , Zhao Mingxia , Molnár István , Doležel Jaroslav , Logemann Elke , Köchner Petra , Xi Pinggen , Yang Shengming , Moscou Matthew J. , Fiedler Jason D. , Du Yang , Steuernagel Burkhard , Meinhardt Steven , Steffenson Brian J. , Schulze-Lefert Paul , Zhong Shaobin 
Published: December 2023

AbstractThe evolutionary history of plant interactions with necrotrophic pathogens that feed on dying host cells and their virulence mechanisms remains fragmentary. We have isolated the barley geneScs6, which is required for the necrotrophic fungusBipolaris sorokinianaisolate ND90Pr to cause spot blotch disease.Scs6is located at the disease resistance gene locusMildew locus a(Mla) and encodes an intracellular nucleotide-binding leucine-rich repeat receptor (NLR). In transgenic barley,Scs6is sufficient to confer susceptibility to ND90Pr in accessions naturally lacking the receptor, resulting in infection-associated host cell death. Expression ofScs6in evolutionarily distantNicotiana benthamianareconstitutes a cell death response to an uncharacterized non-ribosomal peptide effector produced by ND90Pr-specific non-ribosomal peptide synthetases (NRPSs) encoded at theVHv1virulence locus. Our data suggest that the heat-resistant effector directly activates the SCS6 receptor.Scs6is an allelic variant of functionally diversifiedMlaresistance genes each conferring strain-specific immunity to barley powdery mildew isolates with a matching proteinaceous pathogen effector. Domain swaps between MLA and SCS6 NLRs and expression of the resulting hybrid proteins inN. benthamianareveal that the SCS6 leucine-rich repeat domain is a specificity determinant for the NRPS-derived effector to activate the receptor.Scs6evolved after the divergence of barley from wheat and is maintained in several wild barley populations with an incidence of 8%, suggesting a beneficial function for the host. Evolution of thebona fideimmune receptor SCS6 targeted by the NRPS-derived effector was key for the emergence of strain-specific spot blotch disease in domesticated barley.
The prefoldin-like protein AtURI exhibits characteristics of instrinsically disordered proteins
Authors: Gómez-Mínguez Yaiza , Palacios-Abella Alberto , Costigliolo-Rojas Cecilia , Barber Mariana , Hernández-Villa Laura , Úrbez Cristina , Alabadí David 
Published: December 2023

AbstractThe prefoldin-like protein UNCONVENTIONAL PREFOLDIN RPB5 INTERACTOR (URI) participates in diverse cellular functions, including protein homeostasis, transcription, translation, and signal transduction. Thus, URI is a highly versatile protein, although the molecular basis of this versatility remains unknown. In this work, we show thatArabidopsis thaliana(Arabidopsis) URI (AtURI) possesses a large intrinsically disordered region (IDR) spanning most of the C-terminal part of the protein, a feature conserved in yeast and human orthologs. Our findings reveal two key characteristics of disordered proteins in AtURI: promiscuity in interacting with partners and protein instability. We propose that these two features contribute to providing AtURI with functional versatility.
In vitro, Evaluation for Consumption Ratio for certain plants and Toxicity and Biochemical Parameters of some Insecticides onEobania vermiculata
Authors: Bashandy A.S. 
Published: December 2023

ABSTRACTLand snails are one of the most harmful agricultural pests to crops, causing economic devastation to a variety of plants. The purpose of this study is to determine the optimal food preference of land snails,Eobania vermiculata, and evaluate the mortality and biochemical activity of five pesticides using a leaf dipping technique against them in vitro. The findings revealed that in “no-choice feeding,” it was observed that land snails consumed a significantly higher amount of Cos lettuce leaves compared to leaves from other plants. However, chicory leaves were found to be the least preferred by the snails. On the other hand, “free choice feeding,” revealed that land snails showed a preference for Cos lettuce and cabbage leaves, which were consumed more frequently. Conversely, Komatsuna leaves had the lowest acceptance among the snails. Also, the results indicated the mortality rate increased with an increased concentration during exposure time. After three days, the lower concentrations of Sulfoxaflor and Fipronil caused a high mortality percentage in the animals compared with other pesticides, respectively. Moreover, after one month of exposure to 1000 ppm/100 ml, Chlorantraniliprole caused 46.43% mortality. But Sulfoxaflor and Fipronil exhibited (42.86%) mortality. They achieved LC50(1010.48, 2501.93, and 1444.66 ppm/100ml), against tested snails, respectively. Nevertheless, Spinetoram and Spirotetramat caused a lower mortality rate. During seven days of exposure to LC25for five pesticides by leaf dipping on E. vermiculata. They impacted some of the biochemical activity of two enzymes: alanine amino transaminase (ALT), aspartate amino transaminase (AST), total proteins (LP), and the lipid profile of E. vermiculata. The results showed that the activities of ALT, AST, and Triglycerides rose by 50%, with 108 u/l, 407 u/l, and 2064 mg/dl, respectively. Compared to the control and other compounds, Spirotetramat raised total cholesterol by 33 mg/dl. ALT and AST activity and Triglycerides lowered following Spinetoram and Fipronil treatment at 13 u/l, 32u/l, and (4 mg/dl) of TL, respectively. However, no substantial treatments or controls that influence TP, (Total cholesterol and LDH) or LP levels after the exposure period are available. Ultimately, the results indicated that both Cos lettuce and cabbage leaves were the preferred food choices for land snails, as observed in both feeding methods. However, it is important to note that these findings also highlight the need to consider the impact of insecticides on land snails. Incorporating these insecticides into a comprehensive management strategy to mitigate any negative effects of land snails while ensuring the overall well-being of the environment.
NeMu: A Comprehensive Pipeline for Accurate Reconstruction of Neutral Mutation Spectra from Evolutionary Data
Authors: Efimenko Bogdan , Popadin Konstantin , Gunbin Konstantin 
Published: December 2023

ABSTRACTOne of the most important characteristics of each contemporary model of molecular evolution is the assumption that mutations occur in a constant manner; however, in the real world, the mutations are determined by the combination of the effects of DNA replication and repair. This affects the nucleotide composition of the genome and guides not just neutral but adaptive evolution1. Mutation accumulation experiments are the de facto standard for the neutral mutation spectra estimation. However, recent studies have demonstrated that the mutation fraction under selection pressure is significantly underestimated in mutation accumulation experiments, and, therefore the precise extraction of neutral mutation spectra from mutation accumulation experiments is not trivial2. To unravel the neutral mutation spectra, it is very important to analyze all the mutations available in depth, based on the evolutionary timescale, taking into consideration all the existing knowledge. In order to facilitate this analysis, we have created a novel pipeline, called NeMu (https://biopipelines.kantiana.ru/nemu/).