bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diel disconnect between cell growth and division inAureococcusis interrupted by giant virus infection
Authors: Truchon Alexander R. , Chase Emily E. , Stark Ashton R. , Wilhelm Steven W. 
Published: May 2024

ABSTRACTViruses of eukaryotic algae have become an important topic due to their roles in nutrient cycling and top-down control of algal blooms. Omics-based studies have identified a boon of genomic and transcriptional potential among theNucleocytoviricota, a phylum of large dsDNA viruses which have been shown to infect algal and non-algal eukaryotes. However, little is still understood regarding the infection cycle of these viruses, particularly in how they take over a metabolically active host and convert it into a virocell state. Of particular interest are the roles light and the diel cycle in virocell development. Yet despite such a large proportion ofNucleocytoviricotainfecting phototrophs, little work has been done to tie infection dynamics to the presence, and absence, of light. Here, we examine the role of the diel cycle on the physiological and transcriptional state of the pelagophyteAureococcus anophagefferenswhile undergoing infection byKratosvirus quantuckense. Our observations demonstrate how infection by the virus interrupts the diel growth and division of this cell line, and that infection further complicates the system by enhancing export of cell biomass.
Cryo-EM Reveals the Mechanochemical Cycle of Reactive Full-length Human Dynein-1
Authors: Chai Pengxin , Yang Jun , Geohring Indigo C. , Markus Steven M. , Wang Yue , Zhang Kai 
Published: May 2024

AbstractDynein-driven cargo transport plays pivotal roles in diverse cellular activities, central to which is dynein’s mechanochemical cycle. Here, we performed a systematic cryo-electron microscopic investigation of the conformational landscape of full-length human dynein-1 in reaction, under various nucleotide conditions, on and off microtubules. Our approach reveals over 40 high-resolution structures, categorized into eight states, providing a dynamic and comprehensive view of dynein throughout its mechanochemical cycle. The novel intermediate states reveal important mechanistic insights into dynein function, including a ‘backdoor’ phosphate release model that coordinates linker straightening, how microtubule binding enhances ATPase activity through a two-way communication mechanism, and the crosstalk mechanism between AAA1 and the regulatory AAA3 site. Our findings also lead to a substantially revised model for the force-generating powerstroke and reveal a means by which dynein exhibits unidirectional stepping. These results substantially improve our understanding of dynein and provide a more complete model of its mechanochemical cycle.
Dorsomedial Striatum CB1R signaling is required for Pavlovian outcome devaluation in male Long Evans rats and reduces inhibitory synaptic transmission in both sexes
Authors: Stapf Catherine A. , Keefer Sara E. , McInerney Jessica M , Cheer Joseph F. , Calu Donna J. 
Published: May 2024

ABSTRACTCannabinoid-1 receptor (CB1R) signaling in the dorsal striatum regulates the shift from flexible to habitual behavior in instrumental outcome devaluation. Based on prior work establishing individual, sex, and experience-dependent differences in Pavlovian behaviors, we predicted a role for dorsomedial striatum CB1R signaling in driving rigid responding in Pavlovian autoshaping and outcome devaluation. We trained male and female Long Evans rats in Pavlovian Lever Autoshaping (PLA). We gave intra-dorsomedial striatum (DMS) infusions of the CB1R inverse agonist, rimonabant, before satiety-induced outcome devaluation test sessions, where we sated rats on training pellets or home cage chow and tested them in brief nonreinforced Pavlovian Lever Autoshaping sessions. Overall, inhibition of DMS CB1R signaling prevented Pavlovian outcome devaluation but did not affect behavior in reinforced PLA sessions. Males were sensitive to devaluation while females were not and DMS CB1R inhibition impaired devaluation sensitivity in males. We then investigated how DMS CB1R signaling impacts local inhibitory synaptic transmission in male and female Long Evans rats. We recorded spontaneous inhibitory postsynaptic currents (sIPSC) from DMS neurons at baseline and before and after application of a CB1R agonist, WIN 55,212-2. We found that male rats showed decreased sIPSC frequency compared to females, and that CB1R activation reduced DMS inhibitory transmission independent of sex. Altogether our results demonstrate that DMS CB1Rs regulate Pavlovian devaluation sensitivity and inhibitory synaptic transmission and suggest that basal sex differences in inhibitory synaptic transmission may underly sex differences in DMS function and behavioral flexibility.
Brain rewiring during developmental transitions: A Comparative Analysis of Larva and AdultDrosophila melanogaster
Authors: Yadav Prateek , Shinde Pramod , Singh Aradhana 
Published: May 2024

AbstractThe brain’s ability to adapt through structural rewiring during developmental transitions is a fundamental aspect of neuroscience. Our study conducts a detailed comparison ofDrosophila melanogaster‘s brain networks during larval and adult stages, revealing significant changes in neuronal wiring during developmental phases. The degree distribution of the larval brain deviates significantly from power-law behavior and fits well with the Weibull distribution. In contrast, the adult brain exhibits power-law behavior in its degree distribution, with the exponent for the out-degree distribution lying in the scale-free regime and the exponent for the in-degree distribution being close to this regime. This difference reflects a change in the robustness of brain development from larval to adult phases. The core of these networks also changes during development in terms of their cell composition and topological influence. The larval core comprises Mushroom Body neurons, while the adult core mainly has Antennal Lobe neurons. Moreover, all the core neurons in the larval brain are also part of the rich-club neurons, a group of neurons with high in/out degrees that are well connected, whereas the same is not true for the adult brain network. Additionally, the core of the larval brain displays a more heterogeneous connectivity profile in its second-order neighbors compared to adult brain neurons, indicating greater diversity in larval brain connectivity. Our work stands as a step forward in understanding the rewiring of brain networks across the life stages ofDrosophila melanogaster.
Two-Metal Ion Mechanism of DNA Cleavage by Activated, Filamentous SgrAI
Authors: Shan Zelin , Rivero-Gamez Andres , Lyumkis Dmitry , Horton N. C. 
Published: May 2024

AbstractEnzymes that form filamentous assemblies with modulated enzymatic activities have gained increasing attention in recent years. SgrAI is a sequence specific type II restriction endonuclease that forms polymeric filaments. SgrAI filamentation increases enzymatic activity by up to three orders of magnitude and additionally expands its DNA sequence specificity. Prior studies have suggested a mechanistic model linking the structural changes accompanying SgrAI filamentation to its accelerated DNA cleavage activity. In this model, the conformational changes that are specific to filamentous SgrAI maximize contacts between different copies of the enzyme within the filament and create a second divalent cation binding site in each subunit, which in turn facilitates the DNA cleavage reaction. However, our understanding of the atomic mechanism of catalysis is incomplete. Herein, we present two new structures of filamentous SgrAI solved using cryo-electron microscopy (cryo-EM). The first structure, resolved to 3.3 Å, is of filamentous SgrAI containing an active site mutation that is designed to stall the DNA cleavage reaction, which reveals the enzymatic configuration prior to DNA cleavage. The second structure, resolved to 3.1 Å, is of WT filamentous SgrAI containing cleaved substrate DNA, which reveals the enzymatic configuration at the end of the enzymatic cleavage reaction. Both structures contain the phosphate moiety at the cleavage site and the biologically relevant divalent cation cofactor Mg2+and define how the Mg2+cation reconfigures during enzymatic catalysis. The data support a model for the activation mechanism that involves binding of a second Mg2+in the SgrAI active site as a direct result of filamentation induced conformational changes.
Silicone Wire Embolization-induced Acute Retinal Artery Ischemia and Reperfusion Model in Mouse: Gene Expression Provides Insight into Pathological Processes
Authors: Wang Yuedan , Li Ying , Feng Jiaqing , Wang Chuansen , Wan Yuwei , Lv Bingyang , Li Yinming , Xie Hao , Chen Ting , Wang Faxi , Li Ziyue , Yang Anhuai , Xiao Xuan 
Published: May 2024

AbstractAcute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60-minutes of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.
Endoplasmic Reticulum contact sites facilitate the coordinated division ofSalmonella-containing vacuole
Authors: Chopra Umesh , Bhansali Priyanka , Gangi Setty Subba Rao , Chakravortty Dipshikha 
Published: May 2024

AbstractSalmonellaTyphimurium (STM) resides in a membrane-bound compartment calledSalmonellacontaining vacuole (SCV) in several infected cell types. Within host cells, the division of bacteria and SCV are synchronous to maintain the single bacterium per vacuole. However, the mechanism regulating the synchronous fission and the machinery is not well understood. The fission of several intracellular organelles is regulated by the dynamic nature of the tubular endoplasmic reticulum (ER). In this study, we have evaluated the role of ER in controlling SCV fission. Interestingly,Salmonella-infected cells show the activation of unfolded protein response (UPR) with expanded ER tubules compared to the uninfected cells. Further, changing the expression of ER morphology regulators, such as reticulon-4a (Rtn4a) and CLIMP63, affected bacterial proliferation significantly, suggesting a potential role for tubular ER in facilitating the SCV division. Live-cell imaging analysis shows the marking of tubular ER precisely at the center of the majority of SCV division (78%) sites. We have investigated the role of SteA (a knownSalmonellaeffector in modulating the membrane dynamics) in coordinating the SCV division. We observed that SteA resides on the SCV membranes and helps in making membrane contact sites between SCV and ER. Accordingly, the colocalization of ER with SCV enclosing SteA mutantSalmonellawas significantly reduced compared to SCV-formed by wild-typeSalmonella. Depletion ofsteAinSalmonellaresulted in profound defects in SCV division, resulting in multiple bacteria residing in a single vacuole with defects in proliferation compared to the wild-type strain in epithelial cells. Also, duringin vivoinfection, the STMΔsteAmutant shows a defect in colonization in the spleen and liver and affects the initial survival rate of mice. Overall, this study suggests a coordinated role of bacterial effector SteA in promoting the ER contact sites with SCVs and thus regulating the successful division of SCV.Abstract FigureGraphical Abstract
Optimal experimental designs for characterising ion channel gating by filling the phase-voltage space of model dynamics
Authors: Mirams Gary R. , Clerx Michael , Whittaker Dominic G. , Lei Chon Lok 
Published: May 2024

AbstractVoltage-clamp waveforms are imposed in the patch-clamp electrophysiology technique to provoke ion currents, the particular waveform that is used is known as the ‘voltage-clamp protocol’. Designing protocols to probe and quantify how gating for a particular ion channel occurs has typically been done manually and results in a suite of long protocols. It is desirable to gain the same, or even more, information in a shorter time, and also to automate the process of designing these protocols. In this paper we introduce a new optimal experimental design objective for ion channel characterisation, which involves considering a 3-dimensional phase space for the channel states combined with the voltage, using room-temperature hERG/Kv11.1 currents as an example. A range of designs are proposed, the best of which visits 82% of the discretised phase-voltage space in a 9 second protocol. This new protocol design strategy results in a simulated current visiting a wide range of channel gating states, at a wide variety of voltages, and we therefore expect these designs to be very useful in characterising ion currents, parameterising models, as well as being a challenging test of assumptions made about ion channel gating.
Transient lagging chromosomes cause primary microcephaly
Authors: Doria Elena , Ivanova Daria , Thomas Alexandre , Meraldi Patrick 
Published: May 2024

ABSTRACTPrimary microcephaly is caused by the depletion of neuronal progenitor cells during brain development, resulting in reduced brain size and impaired cognitive abilities. It arises due to recessive loss-of-function mutations of cell division genes, that are thought to cause neuronal progenitor loss either because of aneuploidy-driven apoptosis, spindle orientation defects, or prolonged mitotic timing. Loss of the two most frequently impaired microcephaly genes,WDR62andASPM, elicits, however, none of these phenotypes in human cells. Instead, their loss slows down poleward microtubule flux and results in transient lagging chromosomes in anaphase. Whether these defects cause primary microcephaly is, however, unknown. Here we show that slower poleward microtubule flux rates lead to transient lagging anaphase chromosomes that elicit an Aurora-B dependent activation of 53BP1 and the p53-target p21, impairing cell proliferation. Co-depletion of CAMSAP1, an inhibitor of microtubule depolymerization at spindle poles, restores normal poleward flux rates, suppresses the lagging chromosomes, silences 53BP1 and p21 activation, and allows normal cell proliferation in WDR62-depleted cells. InDrosophila melanogasterlarvae knock-down of the CAMSAP1 ortholog Patronin suppresses the small brain, the neuroblast depletion, and the impaired cognitive phenotype associated with WDR62 loss. We thus postulate that poleward microtubule flux defects in neuronal progenitor cells drive primary microcephaly due to the activation of 53BP1 and p21 in response to transient lagging chromosomes in anaphase. Since loss of most cell division genes associated with primary microcephaly can lead to such transient lagging chromosomes, we speculate that they might represent a common cause of this disease.
Asteroid mining vs the carbon bubble: ethical considerations for space resource extraction
Authors: Kendal Evie 
Published: May 2024

PurposeThe purpose of this paper is to consider the ethical and environmental implications of allowing space resource extraction to disrupt existing fuel economies, including how companies can be held accountable for ensuring the responsible use of their space assets. It will also briefly consider how such assets should be taxed, and the cost/benefit analyses required to justify the considerable expense of supporting this emerging space industry.Design/methodology/approachThis paper adopts theoretical bioethics methodologies to explore issues of normative ethics and the formulation of moral rules to govern individual, collective and institutional behaviour. Specifically, it considers social justice and social contract theory, consequentialist and deontological accounts of ethical evaluation. It also draws on sociological and organisational literature to discuss Dowling and Pfeffer’s (1975) and Suchman’s (1995) theories of pragmatic, cognitive and moral legitimacy as they may be applied to off-world mining regulations and the handling of space assets.FindingsThe findings of this conceptual paper indicate there is both a growing appetite for tighter resource extraction regulations to address climate change and wealth concentration globally, and an opportunity to establish and legitimise new ethical norms for commercial activity in space that can avoid some of the challenges currently facing fossil fuel divestment movements on Earth.Originality/valueBy adopting methodologies from theoretical bioethics, sociology and business studies, including applying a legitimacy lens to the issue of off-world mining, this paper synthesises existing knowledges from these fields and brings them to the new context of the future space resource economy.
Comparison of a quasi Newton method using Broyden’s update formula and an adjoint method for determining local magnetic material properties of electrical steel sheets
Authors: Gschwentner Andreas , Kaltenbacher Manfred , Kaltenbacher Barbara , Roppert Klaus 
Published: May 2024

Purpose
Performing accurate numerical simulations of electrical drives, the precise knowledge of the local magnetic material properties is of utmost importance. Due to the various manufacturing steps, e.g. heat treatment or cutting techniques, the magnetic material properties can strongly vary locally, and the assumption of homogenized global material parameters is no longer feasible. This paper aims to present the general methodology and two different solution strategies for determining the local magnetic material properties using reference and simulation data.

Design/methodology/approach
The general methodology combines methods based on measurement, numerical simulation and solving an inverse problem. Therefore, a sensor-actuator system is used to characterize electrical steel sheets locally. Based on the measurement data and results from the finite element simulation, the inverse problem is solved with two different solution strategies. The first one is a quasi Newton method (QNM) using Broyden's update formula to approximate the Jacobian and the second is an adjoint method. For comparison of both methods regarding convergence and efficiency, an artificial example with a linear material model is considered.

Findings
The QNM and the adjoint method show similar convergence behavior for two different cutting-edge effects. Furthermore, considering a priori information improved the convergence rate. However, no impact on the stability and the remaining error is observed.

Originality/value
The presented methodology enables a fast and simple determination of the local magnetic material properties of electrical steel sheets without the need for a large number of samples or special preparation procedures.
Nexus between climate change and mitigation approaches for sustainable development: a bibliometric review
Authors: Kaur Arvinder , Sharma Vikas 
Published: May 2024

Purpose
Today’s world is struggling with the hardship of climate change that has drastically disturbed human life, wildlife and the earth’s biological system. This study aims to show how implementing climate change mitigation strategies and environmental protection measures can ensure sustainable development through collaborative efforts between governmental authorities and the nation’s populace.

Design/methodology/approach
An extensive literature review of studies is conducted from across the world concentrating on holistic, sustainable development, enabling a showcase of various conferences, action plans initiated and resolutions passed. VOSviewer software is used to quantify the results of bibliometric analysis and cluster analysis. A total of 260 research studies released between 1993 and 2022 on the Scopus platform are quantified in terms of topmost publications, collaborations among authors, citations index and year-wise publication. The search string has keywords including “climate change,” “sustainable development” and “environment protection.”

Findings
The study results revealed a steep increase in research publications in the last three years, from 2017 to 2021, which serves as the basis of the emergence of high-impact articles. The most cited document in this context throws light on assessing vulnerability to climatic risk and building adaptive capacity. It also draws attention to voluntary carbon markets’ rationale while condemning emission trading systems for climate change due to structural flaws, negative consequences and questionable emission-cutting effectiveness. Low energy demand, zero energy buildings and shared socioeconomic pathways should be implemented as strategies for sustainable development.

Practical implications
This study provides a significant opportunity to construct a valuable addition to mitigate climate change. Also, it shows a positive and significant correlation between mitigation and adaptation policies by analyzing publication efforts worldwide considering local climate risks and national adaptation mandates.

Originality/value
The originality of this study lies in its comprehensive approach, combining literature review, bibliometric analysis and cluster analysis to provide insights into current research trends, challenges and potential strategies for addressing climate change and promoting sustainable development. The study’s emphasis on the correlation between mitigation and adaptation policies adds practical significance to its findings.