bluuebunny/crossref_metadata_2025_split huggingface dataset:
Female and maleSirex noctiliouse age and size to select a mate
Authors: Queffelec Joséphine , Allison Jeremy D. , Slippers Bernard , Greeff Jaco M. 
Published: February 2021

ABSTRACTWhile male mate choice in insects is a widely accepted concept, there is still limited evidence showing that lek formation is compatible with the evolution of male mate choice. In the woodwaspSirex noctilio, males form leks that are used by females to select a mate. However, males have been observed to ignore certain females, suggesting the presence of male mate choice despite the presence of a lek mating system. In this study we demonstrate that males only attempt to mate with certain females. To understand the criteria used by males and females to select a mate, we also tested the effect of age, size, and male to female size ratio on the number of mating attempts made by males and on female receptivity. We demonstrate that size and age play a role in both male and female mate choice. Our results suggest that males must reach sexual maturity after emergence and are neither receptive nor attractive to females during the first few days of their lives. We also show that older females become less attractive to males, suggesting that femaleS. noctilioswitch to a strict host location phase sometime after emergence. Our results show that male and female size, and the ratio between them, play a role in mate choice. While larger males are more motivated to mate, their large size can physically prevent them from mating with small females. Small females are also more attractive and more receptive to males, consistent with the presence of convenience polyandry inS. noctilio.
The Kinetic Landscape of Nucleosome Assembly: A Coarse-Grained Molecular Dynamics Study
Authors: Brandani Giovanni B. , Tan Cheng , Takada Shoji 
Published: February 2021

AbstractThe organization of nucleosomes along the Eukaryotic genome is maintained over time despite disruptive events such as replication. During this complex process, histones and DNA can form a variety of non-canonical nucleosome conformations, but their precise molecular details and roles during nucleosome assembly remain unclear. In this study, employing coarse-grained molecular dynamics simulations and Markov state modeling, we characterized the complete kinetics of nucleosome assembly. On the nucleosome-positioning 601 DNA sequence, we observe a rich transition network among various canonical and non-canonical tetrasome, hexasome, and nucleosome conformations. A low salt environment makes nucleosomes stable, but the kinetic landscape becomes more rugged, so that the system is more likely to be trapped in off-pathway partially assembled intermediates. We find that the co-operativity between DNA bending and histone association enables positioning sequence motifs to direct the assembly process, with potential implications for the dynamic organization of nucleosomes on real genomic sequences.
Optical activation of TrkB neurotrophin receptor in mouse ventral hippocampus promotes plasticity and facilitates fear extinction
Authors: Umemori Juzoh , Didio Giuliano , Winkel Frederike , Pou Maria Llach , Harkki Juliana , Russo Giacomo Lo , Verie Maarten , Antila Hanna , Buj Chloe , Taira Tomi , Lauri Sari E. , Guirado Ramon , Castrén Eero 
Published: February 2021

AbstractSuccessful extinction of traumatic memories depends on neuronal plasticity in the fear extinction network. However, the mechanisms involved in the extinction process remain poorly understood. Here, we investigated the fear extinction network by using a new optogenetic technique that allows temporal and spatial control of neuronal plasticityin vivo. We optimized an optically inducible TrkB (CKII-optoTrkB), the receptor of the brain-derived neurotrophic factor, which can be activated upon blue light exposure to increase plasticity specifically in pyramidal neurons. The activation of CKII-optoTrkB facilitated the induction of LTP in Schaffer collateral-CA1 synapses after brief theta-burst stimulation and increased the expression of FosB in the pyramidal neurons of the ventral hippocampus, indicating enhanced plasticity in that brain area. We showed that optical stimulation of the CA1 region of the ventral hippocampus during fear extinction training led to an attenuated conditioned fear memory. This was a specific effect only observed when combining extinction training with CKII-optoTrkB activation, and not when using either intervention alone. Thus, TrkB activation in ventral CA1 pyramidal neurons promotes a state of neuronal plasticity that allows extinction training to guide neuronal network remodeling to overcome fear memories. Our methodology is a powerful tool to induce neuronal network remodeling in the adult brain, and can attenuate neuropsychiatric symptoms caused by malfunctioning networks.
ALG-097111, a potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitor exhibitsin vivoefficacy in a Syrian Hamster model
Authors: Vandyck Koen , Abdelnabi Rana , Gupta Kusum , Jochmans Dirk , Jekle Andreas , Deval Jerome , Misner Dinah , Bardiot Dorothée , Foo Caroline S. , Liu Cheng , Ren Suping , Beigelman Leonid , Blatt Lawrence M. , Boland Sandro , Vangeel Laura , Dejonghe Steven , Chaltin Patrick , Marchand Arnaud , Serebryany Vladimir , Stoycheva Antitsa , Chanda Sushmita , Symons Julian A. , Raboisson Pierre , Neyts Johan 
Published: February 2021

AbstractThere is an urgent need for antivirals targeting the SARS-CoV-2 virus to fight the current COVID-19 pandemic. The SARS-CoV-2 main protease (3CLpro) represents a promising target for antiviral therapy. The lack of selectivity for some of the reported 3CLpro inhibitors, specifically versus cathepsin L, raises potential safety and efficacy concerns. ALG-097111 potently inhibited SARS-CoV-2 3CLpro (IC50= 7 nM) without affecting the activity of human cathepsin L (IC50> 10 μM). When ALG-097111 was dosed in hamsters challenged with SARS-CoV-2, a robust and significant 3.5 log10(RNA copies/mg) reduction of the viral RNA copies and 3.7 log10(TCID50/mg) reduction in the infectious virus titers in the lungs was observed. These results provide the first in vivo validation for the SARS-CoV-2 3CLpro as a promising therapeutic target for selective small molecule inhibitors.
Ongoing habenular activity is driven by forebrain networks and modulated by olfactory stimuli
Authors: Bartoszek Ewelina Magdalena , Jetti Suresh Kumar , Chau Khac Thanh Phong , Yaksi Emre 
Published: February 2021

SUMMARYOngoing neural activity, which represents internal brain states, is constantly modulated by the sensory information that is generated by the environment. In this study, we show that the habenular circuits act as a major brain hub integrating the structured ongoing activity of the limbic forebrain circuitry and the olfactory information. We demonstrate that ancestral homologs of amygdala and hippocampus in zebrafish forebrain are the major drivers of ongoing habenular activity. We also reveal that odor stimuli can modulate the activity of specific habenular neurons that are driven by this forebrain circuitry. Our results highlight a major role for the olfactory system in regulating the ongoing activity of the habenula and the forebrain, thereby altering brain’s internal states.
The relationship between dynamic functional network connectivity and spatial orientation in healthy young adults
Authors: Sendi Mohammad S. E. , Ellis Charles A. , Miller Robyn L. , Salat David H. , Calhoun Vince D. 
Published: February 2021

ABSTRACTSpatial orientation is essential to interacting with a physical environment, and better understanding it could contribute to a better understanding of a variety of diseases and disorders that are characterized by deficits in spatial orientation. Many previous studies have focused on the relationship between spatial orientation and individual brain regions, though in recent years studies have begun to examine spatial orientation from a network perspective. This study analyzes dynamic functional network connectivity (dFNC) values extracted from over 800 resting-state fMRI recordings of healthy young adults (age 22-37 years) and applies unsupervised machine learning methods to identify neural brain states that occur across all subjects. We estimated the occupancy rate (OCR) for each subject, which was proportional to the amount of time that they spent in each state, and investigated the link between the OCR and spatial orientation and the state-specific FNC values and spatial orientation controlling for age and sex. Our findings showed that the amount of time subjects spent in a state characterized by increased connectivity within and between visual, auditory, and sensorimotor networks and within the default mode network while at rest corresponded to their performance on tests of spatial orientation. We also found that increased sensorimotor network connectivity in two of the identified states negatively correlated with decreased spatial orientation, further highlighting the relationship between the sensorimotor network and spatial orientation. This study provides insight into how the temporal properties of the functional brain connectivity within and between key brain networks may influence spatial orientation.
EZH2 Engages TGFβ Signaling to Promote Breast Cancer Bone Metastasis via Integrin β1-FAK Activation
Authors: Zhang Lin , Qu Jingkun , Qi Yutao , Huang Yu-Wen , Zhou Zhifen , Li Ping , Yao Jun , Huang Beibei , Zhang Shuxing , Yu Dihua 
Published: February 2021

ABSTRACTBone metastasis is a frequent complication of breast cancer, occurring in about 50-70% of breast cancer patients with late-stage disease. The lack of effective therapy suggests that the precise molecular mechanisms underlying bone metastasis are still unclear. Enhancer of zeste homolog 2 (EZH2) is considered a breast cancer oncogene and its expression is correlated with metastasis of breast cancer, but its function in bone metastasis has not been well explored. Herein we report that EZH2 promotes osteolytic metastasis of breast cancer through regulating transforming growth factor beta (TGFβ) signaling, a key pathway in bone metastasis. Knocking down EZH2 decreases bone metastasis incidence and outgrowthin vivo. EZH2 induces cancer cell proliferation and osteoclast maturation, when breast cancer cells are co-cultured with osteoblasts and osteoclasts togetherin vitro. Mechanistically, EZH2 increases transcription ofITGB1, which encodes for integrin β1. Integrin β1 activates focal adhesion kinase (FAK), which phosphorylates TGFβ receptor type I (TGFβRI) at tyrosine 182, thus enhances the binding of TGFβRI to TGFβ receptor type II (TGFβRII), therefore activates Smad2 and increases parathyroid hormone-like hormone (PTHLH) expression. Clinically applicable FAK inhibitors but not EZH2 methyltransferase inhibitor effectively inhibits breast cancer bone metastasisin vivo. Overall, our data signify integrin β1-FAK as a new downstream effector of EZH2 in breast cancer cells, and EZH2-integrin β1-FAK axis cooperates with TGFβ signaling pathway to promote bone metastasis of breast cancer.
Individual variability of neural computations in the primate retina
Authors: Shah Nishal , Brackbill Nora , Samarakoon Ryan , Rhoades Colleen , Kling Alexandra , Sher Alexander , Litke Alan , Singer Yoram , Shlens Jonathon , Chichilnisky E.J. 
Published: February 2021

AbstractVariation in the neural code contributes to making each individual unique. We probed neural code variation using ∼100 neural population recordings from major ganglion cell types in the macaque retina, combined with an interpretable computational representation of individual variability using machine learning. This representation captured individual variation and covariation in properties such as nonlinearity, temporal dynamics, and spatial receptive field size, while preserving invariances, such as asymmetries between ON and OFF cells. The covariation of response properties in different cell types was associated with the proximity of lamination of their synaptic inputs. Surprisingly, male retinas exhibited higher firing rates and faster temporal integration than female retinas. Exploiting data from previously recorded macaque retinas enabled efficient characterization of a new macaque retina, and of a human retina. Simulations indicated that combining a vast dataset of healthy macaque recordings with behavioral feedback could be used to identify the neural code and thus improve retinal implants for vision restoration.
An allosteric ligand stabilizes distinct conformations in the M2 muscarinic acetylcholine receptor
Authors: Xu Jun , Hübner Harald , Hu Yunfei , Niu Xiaogang , Gmeiner Peter , Jin Changwen , Kobilka Brian 
Published: February 2021

AbstractAllosteric modulators provide therapeutic advantages over orthosteric drugs. A plethora of allosteric modulators have been identified for several GPCRs, particularly for muscarinic receptors (mAChRs)1,2. To study the molecular mechanisms governing allosteric modulation, we utilized a recently developed NMR system to investigate the conformational changes in the M2 muscarinic receptor (M2R) in response to the positive allosteric modulator (PAM) LY2119620. Our studies provide the first biophysical data showing that LY2119620 can substantially change the structure and dynamics of M2R in both the extracellular and G-protein coupling domains during the activation process. These NMR data suggest that LY2119620 may function by stabilizing distinct sets of conformations not observed in the presence of orthosteric agonists alone, which may account for the different signaling behaviors of the M2R when bound to LY2119620. Our studies provide new structural information for understanding the mechanism of GPCR allostery, and may facilitate the rational design of allosteric therapeutics targeting muscarinic receptors.
Perspectives for microbeam irradiation at the SYRMEP beamline
Authors: Schültke Elisabeth , Fiedler Stefan , Menk Ralf Hendrik , Jaekel Felix , Dreossi Diego , Casarin Katia , Tromba Giuliana , Bartzsch Stefan , Kriesen Stephan , Hildebrandt Guido , Arfelli Fulvia 
Published: February 2021

It has been shown previously both in vitro and in vivo that microbeam irradiation (MBI) can control malignant tumour cells more effectively than the clinically established concepts of broad beam irradiation. With the aim to extend the international capacity for microbeam research, the first MBI experiment at the biomedical beamline SYRMEP of the Italian synchrotron facility ELETTRA has been conducted. Using a multislit collimator produced by the company TECOMET, arrays of quasi-parallel microbeams were successfully generated with a beam width of 50 µm and a centre-to-centre distance of 400 µm. Murine melanoma cell cultures were irradiated with a target dose of approximately 65 Gy at a mean photon energy of ∼30 keV with a dose rate of 70 Gy s−1 and a peak-to-valley dose of ∼123. This work demonstrated a melanoma cell reduction of approximately 80% after MBI. It is suggested that, while a high energy is essential to achieve high dose rates in order to deposit high treatment doses in a short time in a deep-seated target, for in vitro studies and for the treatment of superficial tumours a spectrum in the lower energy range might be equally suitable or even advantageous.
Digital transformation and value-based selling activities: seller and buyer perspectives
Authors: Alamäki Ari , Korpela Pentti 
Published: February 2021

PurposeThis study aimed to examine the digital transformation of business-to-business (B2B) sales and its effects on the management of value-based selling.Design/methodology/approachThe study adopted a qualitative interview research design. A total of two participant groups—one consisting of sales management professionals and the other consisting of buyers—were created to conduct abductive data analysis to gain a new understanding of B2B sales management.FindingsAs a result of the digital transformation of sales, companies are shifting B2B sales towards value-based selling using a more proactive, continuous process wherein digital value co-creation activities play a big role. Similarly, their buyers now expect more proactive communication about new value propositions, but social media channels are of little importance to most B2B buyers. The management of digital value co-creation activities should be addressed from the sales ecosystem perspective, where non-sellers tend to have a strong role in communicating new value propositions.Research limitations/implicationsThere needs to be further research on digital value co-creation activities in the sales ecosystem, as value-based selling requires that selling organizations focus more on educational digital content marketing and engagement with non-sellers via both marketing and sales activities.Practical implicationsCompanies rarely exploit experts and project personnel when implementing digital sales strategies; however, they often meet with customers personally and network with them. This requires a broader perspective on sales management.Originality/valueThis is one of the first studies to explore the management of value-based selling from both seller and buyer perspectives.
How do large corporations manage disruption? The perspective of manufacturing executives in Finland
Authors: Wallin Arto , Pihlajamaa Matti , Malmelin Nando 
Published: February 2021

PurposeThe article explores what forms of disruption are prioritized by top executives of large manufacturing companies in Finland and what strategies they consider appropriate for the management of disruptive threats and opportunities.Design/methodology/approachThe empirical study was based on interviews with top executives in some of Finland's largest manufacturing companies.FindingsBased on the data, we identify exploitative and explorative strategies in four dimensions that executives consider important in anticipating and responding to disruptions: internal development efforts, stance on new entrants, ecosystems and institutional change. Due to the presence of multiple potential disruptions, which often generate conflicting demands, executives have to consider them simultaneously and balance between them when making strategic decisions. They therefore do not necessarily have a specific response strategy, but their aim is to develop their companies' capabilities so that they are well-placed to face the future with confidence.Originality/valueThe findings indicate that the executives envision a disruption landscape that is more complex than typically described in the literature. In addition, it answers the call for a more systematic understanding of incumbents' response strategies by linking different disciplinary views with well-grounded empirical data.
Strength of auditing and reporting standards, ethical behavior of firms and sustainability: a cross-country investigation
Authors: Guidara Achraf , Ammari Anis El , Khlif Hichem 
Published: February 2021

PurposeThis paper aims to examine the association between the strength of auditing and reporting standards (SARS, hereafter) and sustainability and investigates whether ethical behavior of firms moderates relationship between SARS and sustainability.Design/methodology/approachThe sample consists of 500 country-year observations over the period of 2014–2017. Sustainability is collected from the Global Sustainable Competitiveness Index Reports for 2014, 2015, 2016 and 2017, while SARS and ethical behaviors are collected from the Global Competitiveness Reports for the same years.FindingsThe findings of this study suggest that the SARS is associated with sustainability. Similarly, ethical behavior of firms has a positive and significant effect on sustainability. When testing for the moderating effect of ethical behavior of firms on the association between SARS and sustainability, the results show that the positive association SARS becomes positive and more significant for countries where firms operate with high ethical behaviors, while the association becomes insignificant for settings where firms operate with low ethical behaviors.Originality/valueThe findings emphasize the role played by SARS and business ethics in improving sustainability. These results may have policy implications for governments aiming to improve sustainability by strengthening auditing and reporting standards and enforcing laws obliging firms to act ethically.
Darcy-Forchheimer porous medium effect on rotating hybrid nanofluid on a linear shrinking/stretching sheet
Authors: Ali Lund Liaquat , Omar Zurni , Khan Ilyas 
Published: February 2021

PurposeThe purpose of this study is to find the multiple branches of the three-dimensional flow of Cu-Al2O3/water rotating hybrid nanofluid perfusing a porous medium over the stretching/shrinking surface. The extended model of Darcy due to Forchheimer and Brinkman has been considered to make the hybrid nanofluid model over the pores by considering the porosity and permeability effects.Design/methodology/approachThe Tiwari and Das model with the thermophysical properties of spherical particles for efficient dynamic viscosity of the nanoparticle is used. The linear similarity transformations are applied to convert the partial differential equations into ordinary differential equations (ODEs). The system of governing ODEs is solved by using the three-stage Lobatto IIIa scheme in MATLAB for evolving parameters.FindingsThe system of governing ODEs produces dual branches. A unique stable branch is identified with help of stability analysis. The reduced heat transfer rate has been shown to increase with the reducedϕ2in both branches. Further, results revealed that the presence of multiple branches depends on the ranges of porosity, suction and stretching/shrinking parameters for the particular value of the rotating parameter.Originality/valueDual branches of the three-dimensional flow of Cu-Al2O3/water rotating hybrid nanofluid have been found. Therefore, stability analysis of the branches is also conducted to know which branch is appropriate for the practical applications. To the best of the authors’ knowledge, this research is novel and there is no previously published work relevant to the present study.