bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heme Hopping Falls Short: What Explains Anti-Arrhenius Conductivity in a Multi-heme Cytochrome Nanowire?
Authors: Guberman-Pfeffer Matthew J. 
Published: August 2022

AbstractA helical homopolymer of the outer-membrane cytochrome type S (OmcS) was proposed to electrically connect a common soil bacterium, Geobacter sulfurreducens, with minerals and other microbes for biogeochemically important processes. OmcS exhibits a surprising rise in conductivity upon cooling from 300 to 270 K that has recently been attributed to a restructuring of H-bonds, which in turn modulates heme redox potentials. This proposal is more thoroughly examine herein by (1) analyzing H-bonding at 13 temperatures encompassing the entire experimental range; (2) computing redox potentials with quantum mechanics/molecular mechanics for 10-times more (3000) configurations sampled from 3-times longer (2 μs) molecular dynamics, as well as 3 μs of constant redox and pH molecular dynamics; and (3) modeling redox conduction with both single-particle diffusion and multi-particle flux kinetic schemes. Upon cooling by 30 K, the connectivity of the intra-protein H-bonding network was highly (86%) similar. An increase in the density and static dielectric constant of the filament’s hydration shell caused a −0.002 V/K shift in heme redox potentials, and a factor of 2 decrease in charge mobility. Revision of a too-far negative redox potential in prior work (−0.521 V; expected = −0.350 – +0.150 V; new Calc. = −0.214 V vs. SHE) caused the mobility to be greater at high versus low temperature, opposite to the original prediction. These solution-phase redox conduction models failed to reproduce the experimental conductivity of electrode-absorbed, partially dehydrated, and possibly aggregated OmcS filaments. Some improvement was seen by neglecting reorganization energy from the solvent to model dehydration. Correct modeling of the physical state is suggested to be a prerequisite for reaching a verdict on the operative charge transport mechanism and the molecular basis of its temperature response.
ASM-3D: An attentional search model fashioned after what and where/how pathways for target search in 3D environment
Authors: Kumari Sweta , Shobha Amala V Y , Nivethithan M , Chakravarthy V. Srinivasa 
Published: August 2022

AbstractWe propose a biologically inspired attentional search model for target search in a 3D environment, which has two separate channels for object classification, analogous to the “what” pathway in the human visual system, and for prediction of the next location of the camera, analogous to the “where” pathway. We generated 3D Cluttered Cube datasets that consist of an image on one vertical face, and clutter images on the other faces. The camera goes around each cube on a circular orbit centered on the cube and determines the identity of the image and the face on which it is located. The images pasted on the cube faces were drawn from three: MNIST handwriting digit, QuickDraw, and RGB MNIST handwriting digit datasets. The attentional input of 3 concentric cropped windows resembling the high-resolution central fovea and low-resolution periphery of the retina, flows through a Classifier Network and a Camera Motion Network. The Classifier Network classifies the current view into one of the classes or clutter. The Camera Motion Network predicts the camera’s next position on the orbit (varying the azimuthal angle or ‘θ’). Here the camera performs one of three actions: move right, move left, or don’t move. The Camera-Position Network adds the camera’s current θ information into the higher features level of the Classifier Network and the Camera Motion Network. The Camera Motion Network is trained using Q-learning where the reward is 1 if the classifier network gives the correct classification, otherwise 0. Total loss is computed by adding the mean square loss of temporal difference and cross entropy loss. Then the total loss is backpropagated using Adam optimizer. Results on two grayscale image datasets and one RGB image dataset show that the proposed model is successfully able to discover the desired search pattern to find the target face on the cube, and also classify the target face accurately.
Swim bladder resonance enhances hearing in crucian carp (Carassius auratus)
Authors: Li Hongquan , Gao Zhanyuan , Song Zhongchang , Su Yingnan , Ou Wenzhan , Zhang Jinhu , Zhang Yu 
Published: August 2022

ABSTRACTSound sensing is vital for fish and more effort is necessary to address the hearing mechanism in fish. Here, we performed auditory evoked potentials (AEP) measurement, micro-computed tomography (Micro-CT) scanning, and numerical simulation to investigate the resonance of swim bladder and its influence on auditory sensitivity in crucian carp (Carassius auratus). The AEP results showed that at the tested frequency range up to 1000 Hz, the mean auditory thresholds of control fishes with an intact swim bladder were lower than that of treated fishes with a deflated swim bladder by 0.38–30.52 dB re 1 μPa. At the high frequency end, control fishes had a high but measurable auditory threshold. Correspondingly, numerical simulations showed that the intact swim bladder had a mean resonance frequency of 826±13.6 Hz, ranging from 810 to 840 Hz while the deflated swim bladder had no predominant resonance peak below 1000 Hz. The amplitude of received sound pressure at the resonance frequency for a sample in control group was 34.3 dB re 1 μPa higher than that for a treated sample, and the acceleration at the asteriscus of the control fish was higher than the treat fish by 43.13 dB re 1 m s-2. Both AEP experiment and modeling results showed that hearing sensitivity is enhanced through resonance of swim bladder in crucian carp and provided additional understandings on hearing mechanism in fish.Summary statementWe used AEP measurement, Micro-CT scanning, and numerical simulation to demonstrate that the resonance of swim bladder can enhance hearing in crucian carp.
Global Protein-Turnover Quantification inEscherichia coliReveals Cytoplasmic Recycling under Nitrogen Limitation
Authors: Gupta Meera , Johnson Alex , Cruz Edward , Costa Eli , Guest Randi , Li Sophia Hsin-Jung , Hart Elizabeth M , Nguyen Thao , Stadlmeier Michael , Bratton Benjamin P. , Silhavy Thomas J. , Wingreen Ned S. , Gitai Zemer , Wühr Martin 
Published: August 2022

SummaryProtein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studiedE. coli, proteome-wide measurements remain scarce. Here, we quantify the degradation rates of ∼3.2kE. coliproteins under 12 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway inE. coliremains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we introduce broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates inE. coli, complementary to genomics data, that will allow researchers to decipher the control of proteostasis.
The genomic landscape ofSaccharomyces paradoxusintrogression in geographically diverseSaccharomyces cerevisiaestrains
Authors: Clark Anne , Dunham Maitreya J. , Akey Joshua M. 
Published: August 2022

AbstractNatural hybrids between many pairs of theSaccharomycesspecies have been observed. Hybridization can allow for rapid adaptation to new environments, and when followed by repeated backcrossing can lead to small pieces of introgressed sequence from an individual of one species remaining in the genome of an individual of another species. Introgressed sequences that persist over time are interesting both because they provide evidence of past hybridization events and because they may contribute to functional and phenotypic diversity. Previous studies have identified some examples of introgressed sequences inS. cerevisiae, but we sought to gain a more comprehensive understanding of the landscape of introgression in this species. We developed a simple, flexible approach based on a hidden Markov model to identify introgression in yeast genomes. We used our method to look for introgression in 93 diverseS. cerevisiaegenomes from its closest relative,S. paradoxus. We found evidence of introgression in all strains we considered, but the amount and location of introgression varied widely. We show that introgression contributes substantially to the total genetic diversity within these strains, and has the potential to confound inferences of their evolutionary relationships. Further characterizing introgression across diverseSaccharomycesspecies may help us better understand their evolution and the role that hybridization has played in adaptation to new environments.
Comparative genomics of tarakihi (Nemadactylus macropterus) and five New Zealand fish species: assembly contiguity affects the identification of genic features but not transposable elements
Authors: Papa Yvan , Wellenreuther Maren , Morrison Mark A. , Ritchie Peter A. 
Published: August 2022

AbstractComparative analysis of whole-genome sequences can provide valuable insights into the evolutionary patterns of diversification and adaptation of species, including the genome contents and the regions under selection. However, such studies are lacking for fishes in New Zealand. To supplement the recently sequenced genome of tarakihi (Nemadactylus macropterus), the genomes of five additional percomorph species native to New Zealand (king tarakihi (Nemadactylus n.sp.), blue moki (Latridopsis ciliaris), butterfish (Odax pullus), barracouta (Thyrsites atun), and kahawai (Arripis trutta)) were determined and assembled using Illumina sequencing. While the proportion of repeat elements was highly correlated with the genome size (R2 = 0.97, P < 0.01), most of the metrics for the genic features (e.g. number of exons or intron length) were significantly correlated with assembly contiguity (| R2| = 0.79–0.97). A phylogenomic tree including eight additional high-quality fish genomes was reconstructed from sequences of shared gene families. The radiation of Percomorpha was estimated to have occurred c. 112 mya (mid-Cretaceous), while the Latridae have diverged from true Perciformes c. 83 mya (late Cretaceous). Evidence of positive selection was found in 65 genes in tarakihi and 209 genes in Latridae: the largest portion of these are involved in the ATP binding pathway and the integral structure of membranes. These results and the de novo genome sequences can be used to (1) inform future studies on both the strength and shortcomings of scaffold-level assemblies for comparative genomics and (2) provide insights into the evolutionary patterns and processes of genome evolution in bony fishes.
Genomic selection in organisms with biphasic lifecycles: a Saccharina latissima (sugar kelp) case study
Authors: Huang Mao , Robbins Kelly R , Li Yaoguang , Umanzor Schery , Marty-Rivera Michael , Bailey David , Aydlett Margaret , Schmutz Jeremy , Grimwood Jane , Yarish Charles , Lindell Scott , Jannink Jean-Luc 
Published: August 2022

AbstractSugar kelp (Saccharina latissima) has a biphasic life cycle, allowing selection on both the diploid sporophytes (SPs) and haploid gametophytes (GPs). We trained a genomic selection (GS) model from farm-tested SP phenotypic data and used a mixed-ploidy additive relationship matrix to predict GP breeding values. Top-ranked GPs were used to make crosses for further farm evaluation. The relationship matrix included 866 individuals: a) founder SPs sampled from the wild; b) progeny GPs from founders; c) Farm-tested SPs crossed from b); and d) progeny GPs from farm-tested SPs. The complete pedigree-based relationship matrix was estimated for all individuals. A subset of founder SPs (n = 58) and GPs (n = 276) were genotyped with Diversity Array Technology and whole genome sequencing, respectively. We evaluated GS prediction accuracy via cross validation on farm-tested SPs in two years using a basic GBLUP model. We also estimated the general combining ability (GCA) and specific combining ability (SCA) variances of parental GPs. A total of 11 yield-related and morphology traits were evaluated. The cross validation accuracies for dry weight per meter (r ranged from 0.16 to 0.35) and wet weight per meter (r ranged 0.19 to 0.35) were comparable to GS accuracy for yield traits in terrestrial crops. For morphology traits, cross validation accuracy exceeded 0.18 in all scenarios except for blade thickness in the second year. Accuracy in a third validation year for dry weight per meter over a confirmation set of 87 individuals was 0.31.
High interest in Long-Acting Injectable PrEP among Filipina Transfeminine Adults
Authors: Restar Arjee Javellana , Quilantang Ma Irene , Wickersham Jeffrey , Adia Alex , Guigayoma John , Bermudez Amiel Nazer , Galárraga Omar , Flores Dalmacio Dennis , Cu-Uvin Susan , Nazareno Jennifer , Operario Don , Sison Olivia 
Published: August 2022

AbstractTransfeminine adults are impacted by the HIV epidemic in the Philippines, and newly approved modalities of pre-exposure prophylaxis (PrEP), including long-acting injectable (LAI-PrEP), could be beneficial for this group. We utilized secondary data from the #ParaSaAtin survey that sampled Filipina transfeminine adults (n=139) and conducted a series of multivariable logistic regressions with lasso selection to explore factors independently associated with PrEP outcomes, including awareness, discussion with trans friends, and interest in LAI-PrEP. Overall, 53% of Filipina transfeminine respondents were aware of PrEP, 39% had discussed PrEP with their trans friends, and 73% were interested in LAI-PrEP. PrEP awareness was associated with being non-Catholic, having previously been HIV tested, discussing HIV services with a provider, and having high HIV knowledge (p<0.05). Discussing PrEP with friends was associated with older age, having experienced healthcare discrimination due to transgender identity, having HIV tested, and having discussed HIV services with a provider (p<0.05). Interest in LAI-PrEP was associated with living in Central Visayas, having discussed HIV services with a provider, and having discussed HIV services with a sexual partner were associated (p<0.05). Implementing LAI-PrEP in the Philippines requires addressing systemic improvements across personal, interpersonal, social, and structural levels in healthcare access, including efforts to create healthcare settings and environments with providers who are trained and competent in transgender health and can address the social and structural drivers of trans health inequities, including HIV and barriers to LAI-PrEP.
Fast and Accurate Maximum-Likelihood Estimation of Multi-Type Birth-Death Epidemiological Models from Phylogenetic Trees
Authors: Zhukova Anna , Hecht Frédéric , Maday Yvon , Gascuel Olivier 
Published: August 2022

AbstractMulti-type birth-death (MTBD) models are phylodynamic analogies of compartmental models in classical epidemiology. They serve to infer such epidemiological parameters as the average number of secondary infectionsReand the infectious time from a phylogenetic tree (a genealogy of pathogen sequences). The representatives of this model family focus on various aspects of pathogen epidemics. For instance, the birth-death exposed-infectious (BDEI) model describes the transmission of pathogens featuring an incubation period (when there is a delay between the moment of infection and becoming infectious, as for Ebola and SARS-CoV-2), and permits its estimation along with other parameters.With constantly growing sequencing data, MTBD models should be extremely useful for unravelling information on pathogen epidemics. However, existing implementations of these models in a phylodynamic framework have not yet caught up with the sequencing speed. Computing time and numerical instability issues limit their applicability to medium data sets (≤500 samples), while the accuracy of estimations should increase with more data.We propose a new highly parallelizable formulation of ordinary differential equations for MTBD models. We also extend them to forests to represent situations when a (sub-)epidemic started from several cases (e.g., multiple introductions to a country). We implemented it for the BDEI model in a maximum likelihood framework using a combination of numerical analysis methods for efficient equation resolution. Our implementation estimates epidemiological parameter values and their confidence intervals in two minutes on a phylogenetic tree of 10 000 samples. Comparison to the existing implementations on simulated data shows that it is not only much faster, but also more accurate. An application of our tool to the 2014 Ebola epidemic in Sierra-Leone is also convincing, with very fast calculation and precise estimates. As MTBD models are closely related to Cladogenetic State Speciation and Extinction (ClaSSE)-like models, our findings could also be easily transferred to the macroevolution domain.
Does sugar control arrest complications in type 2 diabetes? Examining rigor in statistical and causal inference in clinical trials
Authors: Ojha Akanksha , Vidwans Harshada , Watve Milind 
Published: August 2022

AbstractIn contrast with type 1 diabetes mellitus (T1DM), in type 2 (T2DM) the success of intensive glucose normalization in arresting diabetic complications is marginal and inconsistent across multiple clinical trials. However, glucose regulation still largely remains the main target of treatment for T2DM in clinical practice. We examine the scientific rigor behind the design, conduct and inferences of 6 major clinical trials targeting glucose normalization and following up for diabetic complications and mortality. We find and discuss multiple flaws in reporting the results, their statistical treatment and clinically useful recommendations. The most serious flaw is the inability to recognize the limitations of statistical inferences when multiple comparisons are involved. Further we show using simulations that when different outcomes are not independent of each other, significance gets overestimated. We also suggested alternative ways to assess the effect of antihyperglycemic treatment, if any. Using more sound and elaborate statistical methods and inferential logic we find no support to the prevalent belief that intensive glucose normalization has any benefit in terms of reducing the frequency of any of the complications. Furthermore, alternative interpretations of the results have not been considered and evaluated in any of the clinical trials or their meta-analysis so far. Because of failure to show consistent significant benefit across multiple trials, we should now treat the hypothesis that glucose normalization prevents complications in T2DM as decisively falsified. This necessitates rethinking about some of the fundamental beliefs about the pathophysiology of diabetic complications and facilitate novel alternative lines of research.
Continuously perfusable, customisable and matrix-free vasculature on a chip platform
Authors: Chesnais Francois , Joel Jordan , Hue Jonas , Shakib Sima , Di-Silvio Lucy , Grigoriadis Agamemnon E. , Coward Trevor , Veschini Lorenzo 
Published: August 2022

AbstractCreating vascularised cellular environments in vitro is a current challenge in tissue engineering and a bottleneck towards developing functional stem cell-derived microtissues for regenerative medicine and basic investigations. Here we have developed a new workflow to manufacture Vasculature on Chip (VoC) systems efficiently, quickly, and inexpensively. We have employed 3D printing for fast-prototyping of bespoke VoC and coupled them with a refined organotypic culture system (OVAA) to grow patent capillaries in vitro using tissue-specific endothelial and stromal cells. Furthermore, we have designed and implemented a pocket-size flow driver to establish physiologic perfusive flow throughout our VoC-OVAA with minimal medium use and waste. Using our platform, we have created vascularised microtissues and perfused them at physiologic flow rates for extended times and observed flow-dependent vascular remodelling. Overall, we present for the first time a scalable and customisable system to grow vascularised and perfusable microtissues, a key initial step to grow mature and functional tissues in vitro. We envision that this technology will empower fast prototyping and validation of increasingly biomimetic in vitro systems, including interconnected multi-tissue systems.
In vivo Quantification of Neural Criticality and Complexity in Mouse Cortex and Striatum in a Model of Cocaine Abstinence
Authors: Smith Wesley C. 
Published: August 2022

AbstractSelf-organized criticality is a hallmark of complex dynamic systems at phase transitions. Systems that operate at or near criticality have large-scale fluctuations or “avalanches”, the frequency and duration power of which are best fit with a power law revealing them to be scale-free and fractal, and such power laws are ubiquitous. It is an attractive concept in neuroscience since spiking avalanches are exhibited by neural tissue, and may underpin how minuscule events could scale up to circuits and provide adaptive psychobiological function. Much is yet to be understood about criticalityin vivoin the healthy brain and in disorders such as addiction, as drugs may alter the critical state’s “tuning” to generate drug seeking and dysphoria. Thus, here a novel toolset was developed to use neural avalanches and their self-similarity, rather than power law fit slope exponents as is canonically done, to quantify criticality in a previously collected high-density electrophysiologicalin vivocorticostriatal dataset from a mouse model of early cocaine abstinence. During behavioral quiescence, in the prefrontal cortex but not ventral striatum of cocaine-dosed mice, it was found that critical tuning is enhanced compared to drug-free controls. Additionally, an empirical biological demonstration of complexity’s theoretical correlation to criticality was shown in drug-free mice, was exponentially enhanced in drug-treated cortex, but was absent in the drug-treated striatum. As shown, quantifying criticality grants experimental support for the “critical brain hypothesis” and allows for statistical interpretation of inter-subject variability and development of further testable hypotheses in systems neuroscience.Significance StatementThe “critical brain hypothesis” asserts neural networks are comparable to material in phase transitions at a critical point, their “avalanches” of system-wide spike bursts best seen in log-log plots of probability vs. avalanche size or duration, with slope following a scale-free or fractal power law. In discussing criticality, “critical tuning” is mentioned but quantification thereof left for later experimentation, despite being necessary for a scientific hypothesis. Presented are methods to quantify critical tuning through assessing similarity or fractalness among corticostriatal avalanches collected using high-density electrophysiology in cocaine-conditioned mice, along with an empiricalin vivoconfirmation of the mathematical concept that data complexity correlates with criticality. Interestingly, cocaine enhances critical tuning in cortex and aberrantly modifies complexity in a region-specific manner.