bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurons expressing mu opioid receptors of the habenula promote negative affect in a projection-specific manner
Authors: Bailly Julie , Allain Florence , Tirel Chloé , Petit Florence , Darcq Emmanuel , Kieffer Brigitte 
Published: September 2021

ABSTRACTBACKGROUNDThe mu opioid receptor (MOR) is central to hedonic balance, and produces euphoria by engaging reward circuits. MOR signaling may also influence aversion centers, and notably the medial habenula (MHb) where the receptor is highly dense, however this was not investigated. Our prior data suggest that the inhibitory activity of MOR in the MHb limits aversive states. Here we therefore tested the hypothesis that neurons expressing MOR in the MHb (MHb-MOR neurons) promote negative affective states.METHODSUsingOprm1-Cre knock-in mice, we combined tracing and optogenetics with behavioral testing to investigate consequences of MHb-MOR neuron stimulation in approach/avoidance (real-time place preference), anxiety-related responses (open field, elevated plus maze and marble burying) and despair-like behavior (tail suspension).RESULTSOpto-stimulation of MHb-MOR neurons elicited avoidance behavior, demonstrating that these neurons promote aversive states. Anterograde tracing showed that, in addition to the interpeduncular nucleus (IPN), MHb-MOR neurons project to the dorsal raphe nucleus (DRN), uncovering a yet unreported connection of MHb to a main mood center. Opto-stimulation of MHb-MOR/IPN neurons triggered avoidance and despair-like responses with no anxiety-related effect, whereas light-activation of MHb-MOR/DRN neurons increased levels of anxiety with no effect on other behaviors, revealing two dissociable pathways controlling negative affect.CONCLUSIONSThis study demonstrates aversive activity of MHb neurons that respond to MOR opioids. We propose that inhibition of these neurons by endogenous or exogenous opioids relieves negative affect via two distinct MHb microcircuits, contributing to despair-like behavior (MHb-MOR/IPN) and anxiety (MHb-MOR/DRN). This mechanism has implications for hedonic homeostasis and addiction.
Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival
Authors: Kubinyecz Oana , Santos Fatima , Drage Deborah , Reik Wolf , Eckersley-Maslin Melanie A 
Published: September 2021

AbstractZygotic Genome Activation (ZGA) represents the initiation of transcription following fertilisation. Despite its importance in shifting developmental control from primarily maternal stores in the oocyte to the embryo proper, we know little of the molecular events that initiate ZGA in vivo. Recent in vitro studies in mouse embryonic stem cells (ESCs) have revealed Developmental Pluripotency Associated 2 and 4 (Dppa2/4) as key regulators of ZGA-associated transcription. However, their roles in initiating ZGA in vivo remain unexplored. We reveal Dppa2/4 proteins are present in the nucleus at all stages of preimplantation development and associate with mitotic chromatin. We generated single and double maternal knockout mouse models to deplete maternal stores of Dppa2/4. Importantly, while fertile, Dppa2/4 maternal knockout mice had reduced litter sizes, indicating decreased offspring survival. Immunofluorescence and transcriptome analyses of 2-cell embryos revealed while ZGA took place there were subtle defects in embryos lacking maternal Dppa2/4. Strikingly, heterozygous offspring that inherited the null allele maternally had higher preweaning lethality than those that inherited the null allele paternally. Together our results show that while Dppa2/4 are dispensable for ZGA transcription, maternal stores have an important role in offspring survival, potentially via epigenetic priming of developmental genes.
Common micro- and macroscale principles of connectivity in the human brain
Authors: Scholtens Lianne H. , Pijnenburg Rory , de Lange Siemon C. , Huitinga Inge , van den Heuvel Martijn P. ,   Netherlands Brain Bank (NBB)
Published: September 2021

AbstractThe brain requires efficient information transfer between neurons and between large-scale brain regions. Brain connectivity follows predictable organizational principles: at the cellular level, larger supragranular pyramidal neurons have larger dendritic trees, more synapses, more complex branching and perform more complex neuronal computations; at the macro-scale, region-to-region connections are suggested to display a diverse architecture with highly connected hub-areas facilitating complex information integration and computation. Here, we explore the hypothesis that the branching structure of large-scale region-to-region connectivity follows similar organizational principles as known for the neuronal scale. We examine microscale connectivity of basal dendritic trees of supragranular pyramidal neurons (300+) across ten cortical areas in five human donor brains (1M/4F). Dendritic complexity was quantified as the number of branch points, tree length, spine count, spine density and overall branching complexity. High-resolution diffusion-weighted MRI was used to construct ‘white matter trees’ of cortico-cortical wiring. Examining the complexity of the resulting white matter trees using the same measures as for dendritic trees shows multimodal association areas to have larger, more complexly branched white matter trees than primary areas (all p<0.0001) and regional macroscale complexity to run in parallel with microscale measures, in terms of number of inputs (r=0.677, p=0.032), branch points (r=0.790, p=0.006), total tree length (r=0.664, p=0.036) and branching complexity (r=0.724, p=0.018). Our findings support the integrative theory that brain connectivity is structured following similar ‘principles of connectivity’ at the neuronal and macroscale level, and provide a framework to study connectivity changes in brain conditions at multiple levels of brain organization.
Drought restricted sucrose transport from outer cottonseed coat to fiber and further inhibited cellulose synthesis during cotton fiber thickening
Authors: Zhu Honghai , Hu Wei , Li Yuxia , Zou Jie , He Jiaqi , Wang Youhua , Meng Yali , Chen Binglin , Zhao Wenqing , Wang Shanshan , Zhou Zhiguo 
Published: September 2021

AbstractThe formation of cotton fiber strength largely relies on continuous and steady sucrose supply to cellulose synthesis and is greatly impaired by drought. However, the effects of drought on sucrose import into fiber and its involvement in cellulose biosynthesis within fiber remain unclear. To end this, moisture deficiency experiments were conducted using two Gossypium hirsutum cultivars of Dexiamian 1 (drought-tolerant) and Yuzaomian 9110 (drought-sensitive). Fiber strength was significantly decreased under drought. The results of 13C isotope labeling indicated that drought notably reduced sucrose efflux from cottonseed coat to fiber, and this was caused by down-regulation of sucrose transporter genes (GhSWEET10 and GhSWEET15) in the outer cottonseed coat, finally leading to decreased sucrose accumulation in fiber. Further, under drought, the balance of sucrose allocation within fiber was disrupted by increasing the flow of sucrose into β-1,3-glucan synthesis and lignin synthesis but hindering that into cellulose synthesis in both cultivars. Additionally, glycolysis and starch synthesis were specifically enhanced by drought in Yuzaomian 9110, which further reduced the flow of sucrose into cellulose synthesis. Under drought, the cellulose deposition was decreased due to promoted cellulose degrading process in Dexiamian 1 and stunted cellulose synthesis in Yuzaomian 9110. Consequently, reduced cellulose content was measured in drought-stressed fibers for both cultivars. In summary, the inhibited cellulose accumulation caused by drought was mainly due to reduced sucrose translocation from the outer cottonseed coat to fiber, and less sucrose partitioned to cellulose synthesis pathway under the condition of intensified competition for sucrose by different metabolic pathways within fiber, finally degrading the fiber strength.HighlightThis article revealed the path of sucrose flow from cottonseed coat to cotton fiber and sucrose competition patterns within cotton fiber under drought and their relationships with fiber strength loss.
Single Nucleotide Substitutions Effectively Block Cas9 and Allow for Scarless Genome Editing inCaenorhabditis elegans
Authors: Medley Jeffrey C. , Hebbar Shilpa , Sydzyik Joel T. , Zinovyeva Anna Y. 
Published: September 2021

AbstractInCaenorhabditis elegans, germline injection of Cas9 complexes is reliably used to achieve genome editing through homology-directed repair of Cas9-generated DNA breaks. To prevent Cas9 from targeting repaired DNA, additional blocking mutations are often incorporated into homologous repair templates. Cas9 can be blocked either by mutating the PAM sequence that is essential for Cas9 activity or by mutating the guide sequence that targets Cas9 to a specific genomic location. However, it is unclear how many nucleotides within the guide sequence should be mutated, since Cas9 can recognize “off-target” sequences that are imperfectly paired to its guide. In this study, we examined whether single-nucleotide substitutions within the guide sequence are sufficient to block Cas9 and allow for efficient genome editing. We show that a single mismatch within the guide sequence effectively blocks Cas9 and allows for recovery of edited animals. Surprisingly, we found that a low rate of edited animals can be recovered without introducing any blocking mutations, suggesting a temporal block to Cas9 activity inC. elegans. Furthermore, we show that the maternal genome of hermaphrodite animals is preferentially edited over the paternal genome. We demonstrate that maternally provided haplotypes can be selected using balancer chromosomes and propose a method of mutant isolation that greatly reduces screening efforts post-injection. Collectively, our findings expand the repertoire of genome editing strategies inC. elegansand demonstrate that extraneous blocking mutations are not required to recover edited animals when the desired mutation is located within the guide sequence.
Hidden conformations differentiate day and night in a circadian pacemaker
Authors: Swan Jeffrey A. , Sandate Colby R. , Chavan Archana G. , Freeberg Alfred M. , Etwaru Diana , Ernst Dustin C. , Palacios Joseph G. , Golden Susan S. , LiWang Andy , Lander Gabriel C. , Partch Carrie L. 
Published: September 2021

AbstractThe AAA+ protein KaiC is the central pacemaker for cyanobacterial circadian rhythms. Composed of two hexameric rings with tightly coupled activities, KaiC undergoes changes in autophosphorylation on its C-terminal (CII) domain that restrict binding of of clock proteins on its N-terminal (CI) domain to the evening. Here, we use cryo-electron microscopy to investigate how daytime and nighttime states of CII regulate KaiB binding to CI. We find that the CII hexamer is destabilized during the day but takes on a rigidified C2-symmetric state at night,concomitant with ring-ring compression. Residues at the CI-CII interface are required for phospho-dependent KaiB association, coupling ATPase activity on CI to cooperative KaiB recruitment. Together these studies reveal how daily changes in KaiC phosphorylation regulate cyanobacterial circadian rhythms.One-Sentence SummaryCryo-EM structures of KaiC in its day and night states reveal the structural basis for assembly of clock regulatory complexes.
The morning burst: Shifting daily patterns of ATP production in Drosophila and temporal windows for their improvement in ageing
Authors: Shinhmar Harpreet , Kam Jaimie Hoh , Mitrofanis John , Hogg Chris , Jeffery Glen 
Published: September 2021

AbstractMitochondria produce energy for cell function via adenosine triphosphate (ATP) and are regulated by a molecular 24h clock. Here we use Drosophila melanogaster to reveal shifts in whole animal ATP production over 24h, showing a marked peak in the morning that declines around midday and remains low from then through to the following morning. Mitochondrial membrane potential and ATP production has been shown previously to improve after long wavelength exposure, but apparently not at all times. Hence, to explore this further we exposed flies to 670nm at different times. Exposures between 08.00 and 11.00 resulted in a significant increase in ATP, while exposures at other times had no effect. Within the morning window, not all times were equally effective, however, 670nm exposure mid-morning when ATP production was maximal did not increase ATP, possibly because mitochondria lacked spare capacity at this time. Hence, in the morning there is a complex dynamic relationship between long wavelength light and mitochondria. Mitochondrial function and the influence of long wavelengths are conserved across species from fly to human, and determining the time points for light administration to improve function in ageing and disease is of key importance. Our data progress this search and reveal the outline of these times.
Effects ofCatha Edulis Forskon Spatial Cognition and correlation with serum electrolytes in Wild- type Male White Albino Rats
Authors: Limenie Abebaye Aragaw , Dugul Tesfaye Tolessa , Eshetu Eyasu Mekonnen 
Published: September 2021

BackgroundThe burdens of psychostimulant use disorders are becoming a worldwide problem. One of the psychostimulants widely consumed in Ethiopia and East African countries isCatha edulis Forsk(khat). However, no studies have been conducted on the cognitive effects of khat and its correlation with serum electrolytes. The present study was aimed to evaluate the effects of khat on cognitive functions and its correlation with serum electrolytes.Materials and MethodsA total of 36 adult (7-8 weeks) wild-type male Swiss albino rats weighing between 213 and 229g were used in this study. The rats were received crude khat extract subchronically (kesc) (100 mg/kg, 200 mg/kg and 300 mg/kg b.w), khat juice (khJ 2.5 mL/kg) and 2% tween 80 in distilled water (T80W- v/v, vehicle) and khat extract subacutely (kesa) (300 mg/kg). Spatial learning and memory were measured using Morris water maze model and serum electrolytes were measured using Cobas 6000. The data were analyzed using SPSS version 21.0 and Microsoft Excel.ResultsSpatial learning was improved with trials across the groups, while average escape latency (s) and swim path-length (cm) of rats that received kesc 200 mg/kg (p<0.001 and p<0.001) and kesc 300 mg/kg (p<0.01 and p<0.001) was significantly greater than rats that received the vehicle. However, there was no significant difference in the latency between rats that received kesa 300mg/kg and vehicle (p>0.05). Thigmotaxis was significantly higher in rats that received all doses of khat extract (p<0.001). The time spent in the target quadrant in rats that received kesc 300 mg/kg was significantly reduced (p<0.05). Serum calcium level was inversely correlated with the escape latency (R=−0.417, p<0.05) in rats that received khat.Conclusionskhat extract and juice administered subchronically, but not subacute administration, impaired learning and memory in rats and was associated with serum calcium reduction. The neuronal basis for such alteration should be investigated.
SDR enzymes oxidize specific lipidic alkynylcarbinols into cytotoxic protein-reactive species
Authors: Demange Pascal , Joly Etienne , Marcoux Julien , Zanon Patrick R. A. , Listunov Dymytrii , Rullière Pauline , Barthes Cécile , Noirot Céline , Izquierdo Jean-Baptiste , Pradines Karen , Hee Romain , de Brito Maria Vieira , Marcellin Marlène , Serre Rémi-Félix , Bouchez Olivier , Burlet-Schiltz Odile , Oliveira Maria Conceição Ferreira , Ballereau Stéphanie , Bernardes-Génisson Vania , Maraval Valérie , Calsou Patrick , Hacker Stephan M. , Génisson Yves , Chauvin Remi , Britton Sébastien 
Published: September 2021

ABSTRACTHundreds of cytotoxic natural or synthetic lipidic compounds contain chiral alkynylcarbinol motifs, but the mechanism of action of those potential therapeutic agents remains unknown. Using a genetic screen in haploid human cells, we discovered that the enantiospecific cytotoxicity of numerous terminal alkynylcarbinols, including the highly cytotoxic dialkynylcarbinols, involves a bioactivation by HSD17B11, a short-chain dehydrogenase/reductase (SDR) known to oxidize the C-17 carbinol center of androstan-3-alpha,17-beta-diol to the corresponding ketone. A similar oxidation of dialkynylcarbinols generates dialkynylketones, that we characterize as highly protein-reactive electrophiles. We established that, once bioactivated in cells, the dialkynylcarbinols covalently modify several proteins involved in protein-quality control mechanisms, resulting in their lipoxidation on cysteines and lysines through Michael addition. For some proteins, this triggers their association to cellular membranes and results in endoplasmic reticulum stress, unfolded protein response activation, ubiquitin-proteasome system inhibition and cell death by apoptosis. Finally, as a proof-of-concept, we show that generic lipidic alkynylcarbinols can be devised to be bioactivated by other SDRs, including human RDH11 and HPGD/15-PGDH. Given that the SDR superfamily is one of the largest and most ubiquitous, this unique cytotoxic mechanism-of-action could be widely exploited to treat diseases, in particular cancer, through the design of tailored prodrugs.
Graphical abstract
Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates
Authors: Chiuppesi Flavia , Nguyen Vu H. , Park Yoonsuh , Contreras Heidi , Karpinski Veronica , Faircloth Katelyn , Nguyen Jenny , Kha Mindy , Johnson Daisy , Martinez Joy , Iniguez Angelina , Zhou Qiao , Kaltcheva Teodora , Frankel Paul , Kar Swagata , Sharma Ankur , Andersen Hanne , Lewis Mark G. , Shostak Yuriy , Wussow Felix , Diamond Don J. 
Published: September 2021

AbstractSecond-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.
Exploring accountability of Australia and New Zealand's temporary labour mobility programmes in Samoa using a talanoa approach
Authors: Perkiss Stephanie , Taule’alo Tautalaaso , Dun Olivia , Klocker Natascha , Liki Asenati , Tanima Farzana 
Published: September 2021

PurposeTemporary labour mobility programmes (TLMPs) are initiated by high-income nations to fill their labour demands by offering temporary work opportunities to migrants from low-income nations. TLMPs also seek to contribute to economic development in workers' home countries. This paper aims to assess the accountability of New Zealand's Recognised Seasonal Employer (RSE) Scheme and Australia's Seasonal Worker Programme (SWP) in reaching their economic development objectives in one sending nation, Samoa.Design/methodology/approachA qualitative study with RSE and SWP workers and key informants (collectively stakeholders) in Samoa was undertaken to assess the contributions of these schemes to economic development. An interdisciplinary research approach was taken using the Pacific methodology of talanoa. Talanoa was used to “operationalise engagement” and empower local stakeholder accounts.FindingsTalanoa supported the elicitation of accounts that contributed nuanced insights into the accountability of TLMPs. Specifically, stakeholder accounts revealed limitations in the ability of the RSE Scheme and SWP to meet their economic development objectives for Samoan communities and workers. Adjustments are necessary to meet Pacific nations' economic development objectives.Practical implicationsThis study responds to calls for on-the-ground accounts of stakeholders involved in TLMPs. It provides insights that may contribute to the development of more effective TLMPs, particularly regarding economic development in workers' home countries.Originality/valueDrawing on dialogic accounting literature, which calls for engagement with the marginalised, a talanoa approach has been engaged to assess TLMPs via on-the-ground participant accounts in a specific context. This paper introduces talanoa to the critical and social accounting literature, to move beyond a typical accounting qualitative interview process and encourage greater engagement and collaboration with Pacific scholars and partners.
Deterrents to the adoption of green walls: a hybrid fuzzy-based approach
Authors: Tabatabaee Sanaz , Ashour Mojtaba , Mohandes Saeed Reza , Sadeghi Haleh , Mahdiyar Amir , Hosseini M. Reza , Ismail Syuhaida 
Published: September 2021

PurposeGreen walls (GWs), comprising living walls and green facades, have been touted as environmentally friendly products in architectural design. GWs can be viable in every aspect of sustainability; they provide residents of buildings with a wide range of economic, social and environmental benefits. Despite this, the adoption rate of GW is still in its infancy stage, and the existing literature concerning the hindrances inhibiting GW adoption is very limited. To address these gaps, the aim of this paper is to identify and prioritize the hindrances to GW adoption in Hong Kong.Design/methodology/approachAfter identifying 17 hindrances through an in-depth review of literature, the fuzzy Delphi method (FDM) is employed to refine the hindrances based on the local context with the help of 21 qualified experts in the field. Subsequently, Fuzzy Parsimonious Analytic Hierarchy Process (FPAHP) is exploited as a recently developed technique to prioritize the identified hindrances.FindingsResults reveal that the most significant hindrances to the adoption of GW are maintenance cost, high installation cost, difficulties in maintenance, sophisticated implementation and inducement to fire. Findings call for scholars to address ways to improve GW installation practices and methods in order to eradicate the hindrances and provide lessons for policymakers, assisting them in facilitating the larger-scale adoption of GW.Originality/valueConsidering the dearth of studies on hindrances to the adoption of GWs, this paper provides a comprehensive outlook of the issue, providing knowledge that can be used as a building block for future scholars within the field. It also provides valuable insights for stakeholders within the construction industry about the hindrances to the adoption of GWs which could direct their efforts toward better implementation of it.