bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated Simulation of Multi-Electrode Arrays Using Sparse and Low-Rank Matrix Techniques
Authors: Jensen Nathan , Chen Zhijie Charles , Kochnev Goldstein Anna , Palanker Daniel 
Published: July 2024

AbstractObjectiveModeling of Multi-Electrode Arrays used in neural stimulation can be computationally challenging since it may involve incredibly dense circuits with millions of intercon-nected resistors, representing current pathways in an electrolyte (resistance matrix), coupled to nonlinear circuits of the stimulating pixels themselves. Here, we present a method for accelerating the modeling of such circuits with minimal error by using a sparse plus low-rank approximation of the resistance matrix.MethodsWe prove that thresholding of the resistance matrix elements enables its sparsification with minimized error. This is accomplished with a sorting algorithm, implying efficient O (N log (N)) complexity. The eigenvalue-based low-rank compensation then helps achieve greater accuracy without significantly increasing the problem size.Results:Utilizing these matrix techniques, we reduced the computation time of the simulation of multi-electrode arrays by about 10-fold, while maintaining an average error of less than 0.3% in the current injected from each electrode. We also show a case where acceleration reaches at least 133 times with additional error in the range of 4%, demonstrating the ability of this algorithm to perform under extreme conditions.ConclusionCritical improvements in the efficiency of simulations of the electric field generated by multi-electrode arrays presented here enable the computational modeling of high-fidelity neural implants with thousands of pixels, previously impossible.Significance:Computational acceleration techniques described in this manuscript were developed for simulation of high-resolution photovoltaic retinal prostheses, but they are also immediately applicable to any circuits involving dense connections between nodes, and, with modifications, more generally to any systems involving non-sparse matrices.
On branch lengths assignment methods for trees with fixed topology and related biological applications
Authors: Wei Wei , Koslicki David 
Published: July 2024

AbstractDistance-guided tree construction with unknown tree topology and branch lengths has been a long studied problem. In contrast, distance-guided branch lengths assignment with fixed tree topology has not yet been systematically investigated, despite having significant applications. In this paper, we provide a formal mathematical formulation of this problem and propose two representative methods for solving this problem, each with its own strength. We evaluate the performance of these two methods under various settings using simulated data, providing guidance for the choice of methods in respective cases. We demonstrate a practical application of this operation through an extension we termed FunUniFrac, which quantifies the differences in functional units between metagenomic samples over a functional tree with assigned branch lengths, allowing clustering of metagenomic samples by functional similarity instead of taxonomic similarity in traditional methods, thus expanding the realm of comparative studies in metagenomics.
Deciphering Reductive Dehalogenase Specificity Through Targeted Mutagenesis of Chloroalkane Reductases
Authors: Picott Katherine , Bowers Connor , Edwards Elizabeth A. 
Published: July 2024

AbstractReductive dehalogenases (RDases) are essential in the anaerobic degradation of various organohalide contaminants. This family of enzymes has broad sequence diversity, but high structural conservation. There have been few studies assessing how RDase peptide sequences affect their substrate selectivity. Here we focus on two chloroalkane RDases, CfrA and DcrA, which have 95% protein sequence identity but have diverged to hold distinct substrate preferences. CfrA will dechlorinate chloroform and 1,1,1-trichloroethane, whilst DcrA will dechlorinate 1,1-dichloroethane. We mutated several residues in the active site of CfrA to investigate a change in substrate preference and to identify which wild-type residues contribute the most to substrate specialization. We determined that no individual residue solely dictates substrate discrimination, but both Y80W and F125W mutations were needed to force CfrA to prefer 1,1-dichloroethane as a substrate. This double mutation also altered the transformation pathway of 1,1,2-trichloroethane from hydrogenolysis (forms 1,2-dichloroethane) to dihaloelimination (forms vinyl chloride). We use predictive protein models and substrate docking to predict what interactions are made between the enzyme and substrate to aid in selection. The residues of significance identified in this study are consistent with those identified from chloroethene RDases, suggesting residue locations with a particularly high impact on activity.ImportanceReductive dehalogenases play an integral role in the removal of chlorinated solvents from the environment. These enzymes have specificity towards different chlorinated compounds, and it is known that small natural changes in their peptide sequence can change their activity drastically. How these specific sequence variations influence activity is largely unknown. In this study, we demonstrate that mutating a few residues within the active site of CfrA—a chloroform and trichloroethane-specific dehalogenase—changes its substrate preference to dichloroethane. We determine that only two mutations are needed to disrupt the native activity, underscoring the nuances in substrate-structure relationships in reductive dehalogenases. Though we are still far from predicting function from the sequence, this knowledge can give some insight into engineering reductive dehalogenases for new target contaminants.
Low-side and multitone suppression in the base of the gerbil cochlea
Authors: Strimbu C. Elliott , Olson Elizabeth S. 
Published: July 2024

AbstractThe cochlea’s mechanical response to sound stimulation is nonlinear, likely due to saturation of the mechano-electric transduction current that is part of an electromechanical feedback loop. The ability of a second tone or tones to reduce the response to a probe tone is one manifestation of nonlinearity, termed suppression. Using optical coherence tomography to measure motion within the organ of Corti, regional motion variations have been observed. Here, we report on the suppression that occurs within the organ of Corti when a high sound level, low frequency suppressor tone was delivered along with a sweep of discreet single-tones. Responses were measured in the base of the gerbil cochlea at two characteristic frequency locations, with two different directions of observation relative to the sensory tissue’s anatomical axes. Suppression extended over a wide frequency range in the outer hair cell region, whereas it was typically limited to the characteristic frequency peak in the reticular lamina region and at the basilar membrane. Aspects of the observed suppression were consistent with the effect of a saturating nonlinearity. Recent measurements have noted the three-dimensional nature of organ of Corti motion. The effects of suppression observed here could be due to a combination of reduced motion amplitude and altered vibration axis.Significance StatementThe mammalian auditory organ, the cochlea, relies on a nonlinear active process to achieve sensitivity to low-level sounds and sharp frequency selectivity. Recent work using novel interferometric techniques has revealed complex and nonlinear vibration patterns within the cochlea’s sensory tissue. In this study, the motion response to a pure tone was reduced by additional ”suppressor” tones. The observed motion reduction was consistent with the effect of a saturating nonlinearity, possibly compounded by alterations in the axis of cellular vibration, and thus underscoring the 3-dimensional character of cell-based cochlear mechanical activity.
Gustatory Thalamic Neurons Mediate Aversive Behaviors
Authors: Cao Feng , Park Sekun , Pauli Jordan L. , Seo Eden Y. , Palmiter Richard D. 
Published: July 2024

ABSTRACTThe parvicellular part of the ventral posteromedial nucleus (VPMpc) of the thalamus, also known as the gustatory thalamus, receives input from the parabrachial nucleus and relays taste sensation to the gustatory (or insular) cortex. Prior research has focussed on the role of the VPMpc in relaying taste signals. Here we provide evidence showing that VPMpc also mediates aversive behaviors. By recording calcium transientsin vivofrom single neurons in mice, we show that neurons expressing cholecystokinin and the mu-opioid receptor in the VPMpc respond to various noxious stimuli and fear memory. Chemogenetic and optogenetic activation of these neurons enhances the response to aversive stimuli, whereas silencing them attenuates aversive behaviors. The VPMpc neurons directly innervate neurons in the insular cortex and rostral lateral amygdala. This study expands the role of the VPMpc to include mediating aversive and threating signals to the insular cortex and lateral amygdala.
Unravelling the neurocognitive mechanisms underlying counterconditioning in humans
Authors: Wirz Lisa , Houtekamer Maxime C. , de Vos Jette , Dunsmoor Joseph E. , Homberg Judith R. , Henckens Marloes J.A.G. , Hermans Erno J. 
Published: July 2024

AbstractCounterconditioning (CC) aims to enhance extinction of threat memories by establishing new associations of opposite valence. While its underlying neurocognitive mechanisms remain largely unexplored, previous studies suggest qualitatively different mechanisms from regular extinction. In this functional MRI study, participants underwent categorical threat conditioning (CS+/CS-: images of animals/tools), followed by either CC (CS+ images reinforced with monetary rewards, n=24) or regular extinction (n=24). The following day, we assessed spontaneous recovery of threat responses and episodic memory for CS+ and CS-category exemplars. While the ventromedial prefrontal cortex (vmPFC) was activated during regular extinction, participants undergoing CC showed persistent CS+-specific deactivation of the vmPFC and hippocampus, and CS+-specific activation of the nucleus accumbens (NAcc). The following day, physiological threat responses returned in the regular extinction group, but not in the CC group. Counterconditioning furthermore strengthened episodic memory for CS+ exemplars presented during CC, and retroactively also for CS+ exemplars presented during the threat conditioning phase. Our findings confirm that CC leads to more persistent extinction of threat memories, as well as altered consolidation of the threat conditioning episode. Crucially, we show a qualitatively different activation pattern during CC versus regular extinction, with a shift away from the vmPFC and towards the NAcc.
Deletion of Setd7 protects against cardiac hypertrophy via inhibiting lipid oxidation
Authors: Su Haibi , Wang Jinghuan , Zhang Yuyu , Xu Jie , Liu Jiayao , Li Yuhui , Xiao Chenxi , Wang Caiyun , Chang Jun , Liu Xinhua 
Published: July 2024

AbstractSetd7, a catalytic enzyme responsible for histone H3K4 methylation, is implicated in various cardiac diseases. However, the role of Setd7 in pathological cardiac hypertrophy remains unclear. In this study, we observed that Setd7 is significantly elevated in pathological hypertrophy stimuli cardiomyocytes and mouse failing hearts. Subsequently, we found that mice lacking Setd7 remarkably preserved cardiac function after transverse aortic constriction, as demonstrated by improving myocardial hypertrophy and fibrosis, whereas Setd7 overexpression in cardiomyocytes deteriorated hypertrophy phenotype. Further in vitro analyses revealed that Setd7 mediated-E2F1 activation induces E3 ubiquitin protein ligases WWP2 expression to catalyze the lipid-peroxide-reducing enzyme GPx4 ubiquitination degradation, ultimately causing widespread lipid peroxidation and boosting pathological cardiac hypertrophy. Remarkably, loss of activity of GPx4 blunted the Setd7 knockdown exerts antihypertrophic effect in pathological cardiomyocytes hypertrophy, further confirming an important role of lipid peroxidation in Setd7-mediated failing hearts. In summary, the role of Setd7 in pressure overload-induced cardiac hypertrophy is regulated by the Setd7-E2F1-WWP2-GPx4 signaling pathway, suggesting that targeting Setd7 is a promising therapeutic strategy to attenuate pathological cardiac hypertrophy and heart failure.
Nutrition induced changes in the microbiota can cause dysbiosis and disease development
Authors: Lachnit Tim , Ulrich Laura , Willmer Fiete M. , Hasenbein Tim , Steiner Leon X. , Wolters Maria , Herbst Eva M. , Deines Peter 
Published: July 2024

AbstractThe increasing global prevalence of inflammatory and autoimmune diseases highlights the need to understand their origins. The overfeeding hypothesis suggests that disturbances in the microbiota due to diet may initiate these diseases. Using the model organismHydra, we established a causal link between environmental alterations in the microbiota and disease development. Relocating Hydra to natural lakes caused significant microbial shifts due to new colonizers and nutrients. Nutrient manipulation removed the competitive advantage of the well-adapted resident microbiota, disrupted its nutrient-blocking capacity and triggered specific microbiota changes leading to disease. L-arginine supplementation alone transformedPseudomonasfrom a commensal microbe into a pathogen, showing pathogenicity as context-dependent. Our findings support the overfeeding hypothesis, highlighting the role of microbial and nutrient dynamics in disease development.
2,2-Di-Fluoro-Derivatives of Fucose Can Inhibit Cell Surface Fucosylation Without Causing Slow Transfer to Acceptors
Authors: Liu Yanyan , Sweet Igor , Boons Geert-Jan 
Published: July 2024

ABSTRACTFucosyltransferases (FUTs) are enzymes that transfer fucose (Fuc) from GDP-Fuc to acceptor substrates resulting in fucosylated glycoconjugates that are involved in myriad of physiological and disease processes. Previously, it has been shown that per-O-acetylated 2-F-Fuc can be taken up by cells and converted into GDP-2-F-Fuc which is a competitive inhibitor of FUTs. Furthermore, it can act as a feedback inhibitor ofde-novobiosynthesis of GDP-Fuc resulting in reduced glycoconjugate fucosylation. GDP-2-F-Fuc and several other reported analogs are slow substrates, which can result in unintended incorporation of unnatural fucosides. Here, we describe the design, synthesis, and biological evaluation of GDP-2,2-di-F-Fuc and corresponding prodrugs as inhibitor of FUTs. This compound lacks the slow transfer activity observed for the mono-fluorinated counterpart. Furthermore, it was found that GDP-2-F-Fuc and GDP-2,2-di-F-Fuc have similar Kivalues for the various human fucosyl transferases while the corresponding phosphate prodrugs exhibit substantial differences in inhibition of cell surface fucosylation. Quantitative sugar nucleotides analysis by LC-MS indicates that the 2,2-di-F-Fuc prodrug has substantial greater feedback inhibitory activity. It was also found that by controlling the concentration of the inhibitor, varying degrees of inhibition of the biosynthesis of different types of fucosylatedN-glycan structures can be achieved. These findings open new avenues for the modulation of fucosylation of cell surface glycoconjugates.
ADAM17 regulates hepatic DNA damage repair and tumour formation
Authors: Reichert Manuel , Halwachs Birgit , Bolik Julia , Senftleben Anke , Krause Freia , Conrady Luisa , Bauer Renate , Rachmilewitz Jacob , Horejs-Hoeck Jutta , Rose-John Stefan , Schmidt-Arras Dirk 
Published: July 2024

AbstractBackgroundHepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Still, therapy options for this tumour entity are limited and novel therapeutic options are highly sought after. Genomic instability of hepatocytes promotes oncogenic transformation and underlies the regulation of micro-environmental signalling cues. The membrane-bound a disintegrin and metalloprotease (ADAM) 17 is a major regulator of micro-environmental signals through the proteolytic release of paracrine factors. However, its role in hepatic DNA damage repair and its contribution to hepatic tumourigenesis is still unclear.MethodsWe investigated the effect of ADAM17 on diethylnitrosamine (DEN)-induced acute DNA damage and subsequent DNA damage repair by utilizing mice with ubiquitous or myeloid-specific genetic deficiency in ADAM17. DNA double strand breaks and inflammation were investigated by immunofluorescence of liver tissue sections. tumourigenesis in mice with myeloid-specific ADAM17-deficiency was investigated in a chemically induced hepatocarcinogenesis model.ResultsADAM17 on myeloid cells, in particular Kupffer cells is essentially involved in the non-cell autonomous regulation of DNA damage repair in hepatocytes. Parenchymal ADAM17 regulates hepatocyte fate and recruitment of infiltrating myeloid cells. Furthermore, myeloid ADAM17 promotes hepatic tumour initiation and correlates with poor prognosis in human HCC.ConclusionsWe identified ADAM17, in particular on myeloid cells as an essential driver of hepatic tumourigenesis and as a potential novel drug target for the treatment of hepatic malignancies.
Human-likeAPOBEC3gene expression and anti-viral responses following replacement of mouseApobec3with the 7-gene humanAPOBEC3locus
Authors: Kirkwood Nerissa K , Prosser Haydn M , Yap Melvyn W , Gibson Jane , Cook Ross , Reddin Ian , Stranger Ane , Howes Emma , Zainal Nur , Periyasamy Manikandan , Conticello Silvestro G , Thomas Gareth J. , Scott James , Bishop Kate N , Ali Simak , Bradley Allan , Fenton Tim R 
Published: July 2024

AbstractThe seven human APOBEC3 (hA3) genes encode polynucleotide cytidine deaminases that play vital roles in restricting replication of viruses and retrotransposons. However, off-target A3 deamination of the cellular genome is a major source of somatic mutations in human cancer. The ability to study A3 biologyin vivois hindered by the fact that the solitary murineApobec3gene (mA3) encodes a cytoplasmic enzyme, with no apparent mutagenic activity. Transgenic expression of individual hA3 genes in mice has helped to confirm their oncogenic potential but important questions including which hA3 genes are active in different tissue contexts and how they function in concert when under control of their cognate promoters cannot be addressed using these models. Here we describe humanization of the mouse mA3 locus by integration of a modified BAC clone encompassing the entire 7-gene hA3 locus from human chromosome 22 replacing mA3 on mouse chromosome 15. APOBEC3 mice are viable and fertile and hA3 gene expression in cells and tissues correlates strongly with expression in corresponding human cells and tissues, indicating human-like regulation of hA3 gene expression in the mice. Splenocytes from this line display a functional human A3 response to Friend Murine Leukaemia Virus (F-MLV) infection. We propose that the Hs-APOBEC3 mouse will uniquely model the function of the complete hA3 locus in a living organism and that it will serve as a useful background upon which to model human cancer, as well as assisting drug discovery efforts.
The corrosion behavior of AZ91 bulk alloy and thin films
Authors: Yang Zhenlei , Du Yuzhou , Ma Bo , Wang Qian , Yang Chao 
Published: July 2024

Purpose
The purpose of this study is to campare the corrosion behavior of Az91 films and bulk sample, in the objective to provide reference for the corrosion resistance improvement of Mg alloys.

Design/methodology/approach
AZ91 films with various thickness values are produced by magnetron sputtering technique, and the corrosion behavior was characterized by immersion tests and electrochemical measurements.

Findings
The AZ91 films exhibited a preferred orientation with basal planes parallel to the surface and increased densification with the increase of thickness, and a superior corrosion resistance for the AZ91 films compared with the bulk sample.

Originality/value
The preferred (0002) basal planes in AZ91 films benefited the corrosion resistance and the nanoscale AZ91 films facilitated the development of a dense passivation film. Consequently, AZ91 film exhibited a superior corrosion resistance.
De-othering: indigenous perspectives on diversity, equity and inclusion
Authors: Henry Ella , Leroy-Dyer Sharlene 
Published: July 2024

Purpose
The purpose of this paper is to share two Indigenous perspectives on diversity, equity and inclusion (DEI). It is grounded in aspirations for de-othering and de-colonisation. De-othering is the unpicking of the status of “other” bestowed upon us by the dominant culture, and de-colonisation involves the deconstruction of the ways the settler states in which we live have defined and oppressed us.

Design/methodology/approach
The methodology is a critical self-reflection, drawing on the lived experience of two Indigenous scholars in business fields outside of the international business discipline.

Findings
The findings explore policies, like affirmative action emerging in the 1960s, to the pantheon of DEI theory and strategies developed, as tools of the dominant culture, albeit well-meaning, that perpetuate the dependency of the “other” on the largesse of the “dominant”, which ultimately maintain relations of oppression.

Research limitations/implications
The limitations of the paper include, that we cannot speak for all Indigenous peoples. This paper is a personal viewpoint and is not a meta-analysis of theory and literature. The authors draw on the personal, which for Indigenous peoples is also the political, perspectives, that are steeped in their cultural histories and identities, and underpinned by their aspirations for social change and social justice for their peoples.

Practical implications
The authors offer practical implications for those Indigenous Peoples and allies looking to develop empowering strategies for de-othering individuals and communities defined by dominant cultures as “others”, which in turn has social implications for engagement in truly empowering work in social justice at the borderlands of power, particularly in terms of international business guided by ethics and social responsibility.

Social implications
In this paper, the authors use the following terms: Maori, Aboriginal and Torres Strait Islander, First Peoples and Indigenous Peoples. They use the term Peoples to denote that they are not one homogenous People but a collective society that consists of many distinct communities, peoples and nations.

Originality/value
The authors offer practical implications for those Indigenous Peoples and allies looking to develop empowering strategies for de-othering those defined by dominant cultures as “others”, which in turn has social implications for those engaged in truly empowering work for social justice at the borderlands of power, particularly in terms of international business guided by ethics and social responsibility. They make no apologies for this paper, as it is entirely based on personal viewpoints.