bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brevibacillin 2V, a novel antimicrobial lipopeptide with an exceptional low hemolytic activity
Authors: Zhao Xinghong , Wang Xiaoqi , Shukla Rhythm , Kumar Raj , Weingarth Markus , Breukink Eefjan , Kuipers Oscar P. 
Published: April 2021

AbstractBacterial non-ribosomally produced peptides (NRPs) form a rich source of antibiotics, including more than twenty of these antibiotics that are used in the clinic, such as penicillin G, colistin, vancomycin, and chloramphenicol. Here we report the identification, purification, and characterization of a novel NRP, i.e., brevibacillin 2V, fromBrevibacillus laterosporusDSM 25. Brevibacillin 2V has strong antimicrobial activity against Gram-positive bacterial pathogens, including difficult-to-treat antibiotic-resistantEnterococcus faecium, Enterococcus faecalis, andStaphylococcus aureus. Notably, brevibacillin 2V has a much lower hemolytic activity to eukaryotic cells than previously reported NRPs of the lipo-tridecapeptide family, including other brevibacillins, which makes it a promising candidate for antibiotic development. In addition, our results demonstrate that brevibacillins display synergistic action with established antibiotics against Gram-negative bacterial pathogens. Thus, we identified and characterized a novel and promising antibiotic candidate (brevibacillin 2V) with a low hemolytic activity, which can be used either on its own or as a template for further total synthesis and modification.
Texture is encoded in precise temporal spiking patterns in primate somatosensory cortex
Authors: Long Katie H. , Lieber Justin D. , Bensmaia Sliman J. 
Published: April 2021

AbstractWe are exquisitely sensitive to the microstructure and material properties of surfaces. In the peripheral nerves, two separate mechanisms convey texture information: coarse textural features are encoded in spatial patterns of activation that reflect their spatial layout and fine features are encoded in highly repeatable, texture specific temporal spiking patterns evoked as the skin moves across the surface. In the present study, we examined whether this temporal code is preserved in the responses of neurons in somatosensory cortex. To this end, we scanned a diverse set of everyday textures across the fingertip of awake macaques while recording the responses evoked in individual cortical neurons. We found that temporal spiking patterns are highly repeatable across multiple presentations of the same texture, with millisecond precision. As a result, texture identity can be reliably decoded from the temporal patterns themselves, even after information carried in the spike rates is eliminated. However, the combination of rate and timing does is more informative than either code in isolation. The temporal precision of the texture response is heterogenous across cortical neurons and depends on the submodality composition of their input and on their location along the somatosensory neuraxis. Furthermore, temporal spiking patterns in cortex dilate and contract with decreases and increases in scanning speed and this systematic relationship between speed and patterning may contribute to the observed perceptual invariance to speed. Finally, we find that the quality of a texture percept can be better predicted when these temporal patterns are taken into consideration. We conclude that high-precision spike timing complements rate-based signals to encode texture in somatosensory cortex.
In vivo Monitoring of Glucose using Ultrasound-induced Resonance in Implantable Smart Hydrogel Microstructures
Authors: Farhoudi Navid , Laurentius Lars B. , Magda Jules J. , Reiche Christopher F. , Solzbacher Florian 
Published: April 2021

AbstractA novel glucose sensor is presented that uses smart hydrogels as a biocompatible implantable sensing element, which completely eliminates the need for any implanted electronics and uses an external conventional medical-grade ultrasound transducer for readout. The readout mechanism makes use of resonance absorption of ultrasound waves in glucose-sensitive hydrogels. Changes in in vivo glucose concentration in the interstitial tissue lead to swelling and de-swelling of the gels which in turn lead to changes in resonance behavior. The hydrogels are designed and shaped such as to exhibit specific mechanical resonance frequencies while remaining sonolucent to other frequencies. Thus, they allow conventional and continued ultrasound imaging, while yielding a sensing signal at specific frequencies that is correlated with glucose concentration. The resonance frequencies can be tuned by changing the shape and mechanical properties of the gel structures, such as to allow for multiple, co-located implanted hydrogels with different sensing characteristics or targets to be employed and read out, without interference, using the same ultrasound transducer, by simply toggling frequencies. The fact that there is no need for any implantable electronics, also opens the path towards future use of biodegradable hydrogels, thus creating a platform that allows injection of sensors that do not need to be retrieved when they reach the end of their useful lifespan.
Cypripedium wardii(Orchidaceae) employs pseudopollen with both reward and deception to attract both flis and bees as pollinators
Authors: Zheng Chen-Chen , Luo Yi-Bo , Gao Yun-Dong , Bernhardt Peter , Li Shi-Qi , Xu Bo , Gao Xin-Fen 
Published: April 2021

AbstractFlowering plants always attract animals providing rewards or deceptive signals to gain reproductive success. However, there is no well-documented reporting about a pollination mechanism with both rewards and deceptive signals by a same object. We foundCypripedium wardiiflowers seem to attract visitors by the white pseudopollenlike trichomes on labella in our preliminary field observation.To explore the pollination mechanism ofCypripedium wardii, especially, the ecological function of the pseudopollen-like trichomes, we conducted field observations, analyses of the traits of visitors and flowers, and breeding system experiments.The white trichomes composed by multicellular moniliform hairs on the floral labella played a crucial role to attract pollinators, causing a high natural fruit set ratio inC. wardii. We established the direct connection of the white trichomes and real pollen.We propose that flowers ofC. wardiiprovide pseudopollen to attract suitable bees and hoverflies as pollinators. And our evidence indicate that the pseudopollen owns both deceptive and rewarding ecological functions. Our study provide a clear pollination mechanism with both rewards and deceptive signals by a same object in angiosperm for the first time. However, an inbreeding depression seem to be caused by this strategy. And we speculated that the pollen mimicry strategy with both rewarding and deceptive functions inC. wardiimay be an adaptation to the habitat fragmentation of this species to gain a reproductive assurance.
The PD-L1 and TLR7 dual-targeting nanobody-drug conjugate exerts potent antitumor efficacy by orchestrating innate and adaptive immune responses
Authors: Yu Xiaolu , Long Yiru , Chen Binfan , Tong Yongliang , Jia Xiaomin , Zhou Ji , Tang Feng , Xu Pan , Cao Yuhan , Huang Wei , Ren Jin , Wan Yakun , Sun Jianhua , Jin Guangyi , Gong Likun 
Published: April 2021

AbstractA variety of tumors are insensitive to immune checkpoint blockade (ICB) therapy. We propose that ICB therapy alone is insufficient to fully reactivate antitumor T cells, while effective mobilization of antigen-presenting cells (APCs) to assist adaptive immune cell activation can lead to potent antitumor effects with broad responsiveness. The Toll-like receptor 7 (TLR7) agonist SZU-101 we developed can induce the innate immune response against tumors and increase the immunogenicity of tumors. Interestingly, SZU-101-induced upregulation of programmed death ligand 1 (PD-L1) expression in tumor tissues can further enhance the response rate of the PD-L1 antibody. In addition, PD-L1 nanobodies have better solid tumor penetration ability, and because of this ability, they can be used to precisely deliver SZU-101 to tumor tissues. Therefore, a PD-L1 and TLR7 dual-targeting nanobody-drug conjugate (NDC), a novel drug molecule, was developed. We found that TLR7 agonists and PD-L1 nanobodies act synergistically and that NDC treatment reshapes the tumor immune microenvironment, activates both innate and adaptive immune cells, and exerts antitumor effects in both “hot” and “cold” tumors primarily through CD8+T cells and natural killer (NK) cells. Our data show that a PD-L1 and TLR7 dual-targeting NDC can exhibit potent antitumor efficacy by orchestrating innate and adaptive immune responses and shows good prospects for clinical development.One Sentence SummaryBased on results showing that TLR7 agonists and PD-L1 nanobodies exert synergistic antitumor effects, a PD-L1 and TLR7 dual-targeting nanobody-drug conjugate that we developed shows good prospects for clinical development because it can orchestrate innate and adaptive immune responses, reshape the tumor immune microenvironment, and exert potent antitumor effects against both “hot” and “cold” tumors.
Expression of the ACE2 virus entry protein in the nervus terminalis reveals the potential for an alternative route to brain infection in COVID-19
Authors: Bilinska Katarzyna , von Bartheld Christopher S. , Butowt Rafal 
Published: April 2021

AbstractPrevious studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections should be considered as a potential alternative route from the nose to the brain. Nervus terminalis neurons in postnatal mice were double-labeled with antibodies against ACE2 and two nervus terminalis markers, gonadotropin-releasing hormone (GnRH) and choline acetyltransferase (CHAT). We show that a small fraction of CHAT-labeled nervus terminalis neurons, and the large majority of GnRH-labeled nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2 and cathepsins B and L. Nervus terminalis neurons therefore may provide a direct route for the virus from the nasal epithelium, possibly via innervation of Bowman’s glands, to brain targets, including the telencephalon and diencephalon. This possibility needs to be examined in suitable animal models and in human tissues.
DAnIEL: A User-Friendly Web Server for Fungal ITS Amplicon Sequencing Data
Authors: Loos Daniel , Zhang Lu , Beemelmanns Christine , Kurzai Oliver , Panagiotou Gianni 
Published: April 2021

AbstractTrillions of microbes representing all kingdoms of life are resident in, and on, humans holding essential roles for host development and physiology. The last decade over a dozen online tools and servers, accessible via public domain, have been developed for the analysis of bacterial sequences, however, the analysis of fungi is still in its infancy. Here we present a web server dedicated to the comprehensive analysis of the human mycobiome for (i) translating raw sequencing reads to data tables and high-standard figures; (ii) integrating statistical analysis and machine learning with a manually curated relational database; (iii) comparing the user’s uploaded datasets with publicly available from the Sequence Read Archive. Using 2,048 publicly available ITS samples, we demonstrated the utility of DAnIEL web server on large scale datasets and show the differences in fungal communities between human gut, skin, nasopharynx, and oral body sites.
Acyl Carrier Protein is essential for MukBEF action inEscherichia colichromosome organization-segregation
Authors: Prince Josh P. , Bolla Jani R. , Fisher Gemma L. M. , Mäkelä Jarno , Robinson Carol V. , Arciszewska Lidia K. , Sherratt David J. 
Published: April 2021

AbstractStructural Maintenance of Chromosomes (SMC) complexes contribute ubiquitously to chromosome organization-segregation. SMC proteins have a conserved architecture, with a dimerization hinge and an ATPase head domain separated by a long antiparallel intramolecular coiled-coil. Dimeric SMC proteins interact with essential accessory proteins, kleisins that bridge the two subunits of an SMC dimer, and HAWK/KITE accessory proteins that interact with kleisins. The ATPase activity of theEscherichia coliSMC protein, MukB, is essential forin vivofunction and is regulated by interactions with its dimeric kleisin, MukF, and KITE, MukE. Here we demonstrate that, in addition, MukB interacts with Acyl Carrier Protein (AcpP) that has essential functions in fatty acid synthesis. We characterize the AcpP interaction site at the joint of the MukB coiled-coil and show that the interaction is essential for MukB ATPase and for MukBEF functionin vivo. Therefore, AcpP is an essential co-factor for MukBEF action in chromosome organization-segregation.
An autonomous tail-beating cycle period expressed by a region- specific swimming pattern generator in theCionalarva
Authors: Hara Takashi , Hasegawa Shuya , Iwatani Yasushi , Nishino Atsuo S. 
Published: April 2021

ABSTRACTSwimming locomotion in aquatic vertebrates, such as fish and tadpoles, is expressed through orchestrated operations of central pattern generators. These parallel neuronal circuits are ubiquitously distributed and mutually coupled along the spinal cord to express undulation patterns accommodated to efferent and afferent inputs. While such sets of schemes have been shown in vertebrates, the evolutionary origin of those mechanisms along the chordate phylogeny remains unclear. Ascidians, representing a sister group of vertebrates, give rise to tadpole larvae that freely swim in seawater. In this study, we tried to locate the swimming pattern generator in larvae of the ascidianCionaby examining locomotor ability of segmented body fragments. Our experiments demonstrated necessary and sufficient pattern generator activity in a short region (∼10% of the body length as the longest estimation) including the trunk-tail junction but excluding most of the trunk and tail with major sensory apparatuses therein. Moreover, we found that these “mid-piece” body fragments express periodic tail beating bursts with ∼20-s intervals without any exogenous stimuli. Comparisons among temporal patterns of tail beating bursts expressed by the mid-piece fragments and by whole larvae placed under different sensory conditions suggested that the presence of parts other than the critical mid-piece had effects to shorten swimming burst intervals, especially in the dark, and also to expand the variance in burst durations. We propose thatCionalarvae perform swimming as modified representations of autonomous and periodic pattern generator drives, which operate locally in the region of the trunk-tail junction.Summary statementMid-piece fragments of tadpole larvae of the ascidianCiona, lacking most of the anterior trunk and posterior tail, autonomously and periodically express tail beating bursts.
Do female executives and CEO tenure matter for corporate cash holdings? Insight from a Southeast Asian country
Authors: Suherman Suherman , Usman Berto , Mahfirah Titis Fatarina , Vesta Renhard 
Published: April 2021

PurposeThis paper aims to investigate the relationship between female executives, chief executive officer (CEO) tenure and corporate cash holdings in the context of the developing Southeast Asian capital market (Indonesia).Design/methodology/approachThe sample was screened from 231 publicly listed companies in the Indonesian Stock Exchange. The period of observation was 2011–2017. Two measures were applied for corporate cash holdings: the ratio of cash and cash equivalent to total assets and cash and cash equivalent to net assets. Three surrogate indicators were used for female executives: female CEO, the proportion of female members in the board of management and the number of female members in the board of management. CEO tenure is the length of time a CEO has been a member of the board of management. This study uses panel data regression analysis, including the fixed effect model with clustered standard errors.FindingsThe empirical evidence indicates that female executives and CEO tenure are positively and negatively associated with corporate cash holdings, respectively, and both are significantly related. Additional analysis using lagged independent variables remains consistent with the main analysis, suggesting that corporate cash holding becomes higher as a female presence in the board of management increases.Research limitations/implicationsEmpirical tests set in Indonesia suggest that female executives are more conservative and risk-averse, thereby holding more cash with a precautionary motive. The findings also imply that CEOs with long tenure focus on long-term performance such as increasing research and development investments or capital expenditure, thus holding less cash. Accordingly, policymakers and regulators should promote diversity issues proportionally and advance to the board level.Originality/valueThis study contributes to the field of executive and CEO studies by enriching the empirical findings in related topics. In addition, to the best of the authors’ knowledge, this is one of the first studies applying two measures of cash holdings in the setting of a developing Southeast Asian capital market (Indonesia).
Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox‐LDL‐induced endothelial dysfunction in atherosclerosis by functioning as a miR‐876‐3p sponge
Authors: Gao Yanhui , Li Guangnan , Fan Shasha , Wang Yu , Wei Hong , Li Mingyang , Li Xueqi 
Published: April 2021

AbstractCircular RNAs (circRNAs) are widely expressed in mammals and act as regulatory targets in the atherogenesis. The objective of this study was to research the biological role and molecular mechanism of circ_0093887 in oxidized low‐density lipoprotein (ox‐LDL)‐induced atherosclerosis (AS) of human aortic endothelial cells (HAECs). Cell viability detection was performed by CCK‐8 assay. Inflammatory molecules were examined using ELISA. Flow cytometry was used to measure cell‐cycle progression and cell apoptotic rate. Caspase 3 activity was determined using caspase 3 activity assay. The expression levels of circ_0093887, miR‐876‐3p, CCND2 and SUCNR1 were assayed by quantitative real‐time polymerase chain reaction (qRT‐PCR). Dual‐luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull‐down assays were used for the target analysis. EdU assay, wound healing assay/transwell assay and tube formation assay were, respectively, used to assess the effects of circ_0093887/miR‐876‐3p axis on cell proliferation, migration and tube formation. Oxidized low‐density lipoprotein inhibited cell viability and cell‐cycle progression but induced the inflammatory response and cell apoptosis. Circ_0093887 was downregulated and miR‐876‐3p was upregulated in AS patients and ox‐LDL‐treated HAECs. Functionally, the overexpression of circ_0093887 abrogated the cell injury of HAEC exposed to ox‐LDL. For the functional mechanism, we found that circ_0093887 was a sponge for miR‐876‐3p and miR‐876 targeted CCND2 or SUCNR1. The reverted experiment indicated that the function of circ_0093887 was achieved by sponging miR‐876‐3p. Meanwhile, miR‐876‐3p inhibitor relieved the inhibitory regulation of circ_0093887 knockdown in cell proliferation, migration and tube formation. Downregulation of miR‐876‐3p also alleviated the ox‐LDL‐induced cell injury by upregulating the expression of CCND2 or SUCNR1. Furthermore, circ_0093887 was validated to regulate the levels of CCND2 and SUCNR1 via the sponge effect on miR‐876‐3p. The protective effects of circ_0093887 on HAECs from ox‐LDL were also ​alleviated by repressing the CCND2 and SUCNR1 levels. These findings suggested that circ_0093887 protected HAEC against the ox‐LDL‐induced inflammatory and apoptotic damages by targeting the miR‐876‐3p/CCND2 or miR‐876/SUCNRA axis. Circ_0093887 could act as a potential therapeutic biomarker for AS patients.
Do party supporters accept policy compromises in coalition governments?
Authors: PLESCIA CAROLINA , ECKER ALEJANDRO , MEYER THOMAS M. 
Published: April 2021

AbstractGovernment formation in multi‐party systems often requires coalition negotiations and finding common ground among coalition partners. Supporters of parties involved in the government formation process face a trade‐off when evaluating such bargaining processes: on the one hand, voters usually prefer seeing their party being in government rather than in opposition; on the other hand, negotiations require coalition compromises that they might dislike. In this paper, we study voters’ willingness to accept policy compromises during government formation processes. We argue that voters’ acceptance of policy compromises depends on both the strength of their party attachment and the importance they assign to the issue at stake during the coalition negotiations. Not giving in on important issues is key, especially for supporters of challenger parties, who hold strong policy preferences on a selected number of issues. To test these expectations, we collected original survey data immediately after the Spanish general election in November 2019. The results show support for the hypothesized effects, shed light on the pressure potential coalition partners face during government formation and help explain the failures of government formation attempts in increasingly polarized societies.
Juvenile hormone regulates photoperiod‐mediated male reproductive diapause via the methoprene‐tolerant gene in the ladybeetle Harmonia axyridis
Authors: Gao Qiao , Li Bei , Wei Bing‐Xin , Liu Wen , Wang Pan , Wang Jia‐Lu , Zhou Xing‐Miao , Wang Xiao‐Ping 
Published: April 2021

AbstractJuvenile hormone (JH) absence induces photoperiod‐mediated reproductive diapause, which is characterized by reproductive cessation. Although the role of methoprene‐tolerant (Met)‐mediated JH signaling in photoperiod‐mediated female reproduction has been well documented, its role in male reproduction remains unclear. In this study, we investigated the role of JH in regulating photoperiod‐mediated development of the male internal reproductive system (IRS) in the predatory ladybeetle Harmonia axyridis (Pallas). In a previous study, we found that adult male H. axyridis reared under either a short‐day (SD) or long‐day (LD) photoperiod had obvious differences in IRS development, but we were unable to identify the regulators of male reproductive diapause. In this study, we found that beetles reared under an SD photoperiod had significantly lower JH titer and a relatively undeveloped male IRS compared with those reared under an LD photoperiod. Additionally, application of the JH analog (JHA) methoprene promoted IRS development. Furthermore, Met knockdown strongly blocked JH signaling in males reared under the LD photoperiod, thereby slowing IRS development. Moreover, exogenous JHA did not reverse the suppressed development of the male IRS caused by Met knockdown. These results indicate that photoperiod regulates male IRS development in H. axyridis through a conserved Met‐dependent JH signaling pathway.