bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of a complex of Apoptosis Inducing Factor 1 (AIFM1) with cytochrome c oxidase of the mitochondrial respiratory chain
Authors: Hevler Johannes F. , Chiozzi Riccardo Zenezeni , Cabrera-Orefice Alfredo , Brandt Ulrich , Arnold Susanne , Heck Albert J.R. 
Published: April 2021

AbstractCombining mass spectrometry based chemical cross-linking and complexome profiling, we analyzed the interactome of heart mitochondria. We focused on complexes of oxidative phosphorylation and found that dimeric apoptosis inducing factor 1 (AIFM1) forms a defined complex with ~10% of monomeric cytochromecoxidase (COX), but hardly interacts with respiratory chain supercomplexes. Multiple AIFM1 inter-crosslinks engaging six different COX subunits provided structural restraints to build a detailed atomic model of the COX-AIFM12complex. Application of two complementary proteomic approaches thus provided unexpected insight into the macromolecular organization of the mitochondrial complexome. Our structural model excludes direct electron transfer between AIFM1 and COX. Notably however, the binding site of cytochromecremains accessible allowing formation of a ternary complex. The discovery of the previously overlooked COX-AIFM12complex and clues provided by the structural model hint at a role of AIFM1 in OXPHOS biogenesis and in programmed cell death.
The genetic basis ofDrosophila melanogasterdefense againstBeauveria bassianaexplored through evolve and resequence and quantitative trait locus mapping
Authors: Shahrestani Parvin , King Elizabeth , Ramezan Reza , Phillips Mark , Riddle Melissa , Thornburg Marisa , Greenspan Zachary , Estrella Yonathan , Garcia Kelly , Chowdhury Pratik , Malarat Glen , Zhu Ming , Rottshaefer Susan M. , Wraight Stephen , Griggs Michael , Vandenberg John , Long Anthony D. , Clark Andrew G. , Lazzaro Brian P. 
Published: April 2021

AbstractMany of the molecular mechanisms for antifungal immunity inDrosophila melanogasterhave been defined, but relatively little is known about the genetic basis for variation in antifungal immunity in natural populations. Using two population genetic approaches, Quantitative Trait Locus (QTL) Mapping and Evolve and Resequence (E&R), we explored the genetics underlyingD. melanogasterimmune defense against infection with the fungusBeauveria bassiana. Immune defense was highly variable both in the recombinant inbred lines from the Drosophila Synthetic Population Resource used for our QTL Mapping and in the synthetic outbred populations used in our E&R study. Survivorship of infection improved dramatically over just 10 generations in the E&R study, and continued to increase for an additional 9 generations, revealing a trade-off with uninfected longevity. Populations selected for increased defense againstB. bassianaevolved cross resistance to a second, distinctB. bassianastrain but not to bacterial pathogens. The QTL mapping study revealed that sexual dimorphism in defense depends on host genotype, and the E&R study indicated that dimorphism also depends on the specific pathogen to which the host is exposed. Both the QTL Mapping and E&R experiments generated lists of potentially causal candidate genes, although these lists were non-overlapping.
Ankle muscles drive mediolateral center of pressure control to ensure stable steady state gait
Authors: van Leeuwen A.M. , van Dieën J.H. , Daffertshofer A. , Bruijn S.M. 
Published: April 2021

AbstractDuring steady-state walking, mediolateral gait stability can be maintained by controlling the center of pressure (CoP). The CoP modulates the moment of the ground reaction force, which brakes and reverses movement of the center of mass (CoM) towards the lateral border of the base of support. In addition to foot placement, ankle moments serve to control the CoP. We hypothesized that, during steady-state walking, single stance ankle moments establish a CoP shift to correct for errors in foot placement. We expected ankle muscle activity to be associated with this complementary CoP shift. During treadmill walking, full-body kinematics, ground reaction forces and electromyography were recorded in thirty healthy participants. We found a negative relationship between preceding foot placement error and CoP displacement during single stance; steps that were too medial were compensated for by a lateral CoP shift and vice versa, steps that were too lateral were compensated for by a medial CoP shift. Peroneus longus, soleus and tibialis anterior activity correlated with these CoP shifts. As such, we identified an (active) ankle strategy during steady-state walking. As expected, absolute explained CoP variance by foot placement error decreased when walking with shoes constraining ankle moments. Yet, contrary to our expectations that ankle moment control would compensate for constrained foot placement, the absolute explained CoP variance by foot placement error did not increase when foot placement was constrained. We argue that this lack of compensation reflects the interdependent nature of ankle moment and foot placement control. We suggest that single stance ankle moments do not only compensate for preceding foot placement errors, but also assist control of the subsequent foot placement. Foot placement and ankle moment control are ‘caught’ in a circular relationship, in which constraints imposed on one will also influence the other.
Glycosylated Antibiotics: New Promising Bacterial Efflux Pumps Inhibitors
Authors: Kamaz Zahraa Ali , Umar Haruna Isiyaku , Doshi Parth , Suri Praveenya 
Published: April 2021

AbstractBackgroundAntimicrobial resistance is considered a major concern problem; bacteria have evolved mechanisms to overcome antibiotics’ action through evolutionary process. One main resistance mechanism that bacteria developed is the pumping of the antibiotics out of bacterial cells by transmembrane transporter proteins known as efflux pumps.Materials and methodsTo overcome bacterial resistance guided by efflux pumps, efflux pumps inhibitors (EPIs) are small molecules that obstruct efflux pumps binding sites and its structural assembly leading to disability in the efflux pumps normal function, new EPIs which under the current study are created by modifying the chemical structure of most common antibiotics including Ampicillin, Penicillin, Chloramphenicol, Ciprofloxacin and Tetracycline, such antibiotics are modified by adding N-acetyl glucose amine moiety to acceptor OH group of the respective antibiotic, the newly modified antibiotics are glycosylated EPIs. To test the effectiveness of the new EPIs in inhibiting AcrB-TolC and MexA-OprM efflux pumps functions, ADME properties for all of glycosylated antibiotics have been measured through applying Lipinski’s role of 5, docking and simulation studies have been included as well.ResultsDocked glycosylated tetracycline has given the highest binding energy in the active sites of both pumps, with −9.4 against AcrB and −8.8 against MexA. The simulation study has confirmed the binding of the glycosylated tetracycline in the active sites of both pumps, as well as its stability during the biological dynamicity of both pumps (opening and closing channels).ConclusionThe results validation requires a long simulation time about 50 ns or more which was un applicable due to cost limitation, however, the newly glycosylated antibiotics have promising results that might make it eligible as drug candidates to overcome bacterial resistance.
Unipolar peptidoglycan synthesis in the Rhizobiales requires an essential class A penicillin-binding protein
Authors: Williams Michelle A. , Aliashkevich Alena , Krol Elizaveta , Kuru Erkin , Bouchier Jacob M. , Rittichier Jonathan , Brun Yves V. , VanNieuwenhze Michael S. , Becker Anke , Cava Felipe , Brown Pamela J. B. 
Published: April 2021

ABSTRACTMembers of the Rhizobiales are polarly-growing bacteria that lack homologs of the canonical rod complex. To investigate the mechanisms underlying polar cell wall synthesis, we systematically probed the function of cell wall synthesis enzymes in the plant-pathogenAgrobacterium tumefaciens. The development of fluorescentd-amino acid dipeptide (FDAAD) probes, which are incorporated into peptidoglycan by penicillin-binding proteins inA. tumefaciens, enabled us to monitor changes in growth patterns in the mutants. Use of these fluorescent cell wall probes and peptidoglycan compositional analysis convincingly demonstrate that a single class A penicillin-binding protein is essential for polar peptidoglycan synthesis. Furthermore, we find evidence of an alternative mode of cell wall synthesis that likely requiresld-transpeptidase activity. Genetic analysis and cell wall targeting antibiotics reveal that the mechanism of unipolar growth is conserved inSinorhizobiumandBrucella. This work provides insights into unipolar peptidoglycan biosynthesis employed by the Rhizobiales during cell elongation.
Competitive dynamics underlie cognitive improvements during sleep
Authors: Chen Pin-Chun , Niknazar Hamid , Alaynick William A. , Whitehurst Lauren N. , Mednick Sara C. 
Published: April 2021

AbstractWe provide evidence that human sleep is a competitive arena where cognitive domains vie for limited resources. Using pharmacology and effective connectivity analysis, we demonstrate that long-term memory and working memory are served by distinct offline neural mechanisms that are mutually antagonistic. Specifically, we administered zolpidem to increase central sigma activity and demonstrated targeted suppression of autonomic vagal activity. With effective connectivity, we determined the central activity has greater causal influence over autonomic activity, and the magnitude of this influence during sleep produced a behavioral trade-off between offline long-term and working memory processing. These findings show the first evidence of a sleep switch mechanism that toggles between central sigma-dependent long-term memory and autonomic vagal-dependent working memory processing.Significant StatementSleep facilitates both long-term episodic memory consolidation and short-term working memory functioning. However, the mechanism by which the sleeping brain performs both complex feats, and which sleep features are associated with these processes remain unclear. Using a pharmacological approach, we demonstrate that long-term and working memory are served by distinct offline neural mechanisms, and that these mechanisms are mutually antagonistic. We propose a Sleep Switch model in which the brain toggles between the two memory processes via a complex interaction at the synaptic, systems, and mechanistic level, with implications for research on cognitive disturbances observed in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease, both of which involve the decline of sleep.
Antagonistic inhibitory subnetworks control cooperation and competition across cortical space
Authors: Mossing Daniel P. , Veit Julia , Palmigiano Agostina , Miller Kenneth D. , Adesnik Hillel 
Published: April 2021

AbstractThe cortical microcircuit can dynamically adjust to dramatic changes in the strength, scale, and complexity of its input. In the primary visual cortex (V1), pyramidal cells (PCs) integrate widely across space when signals are weak, but narrowly when signals are strong, a phenomenon known as contrast-dependent surround suppression. Theoretical work has proposed that local interneurons could mediate a shift from cooperation to competition of PCs across cortical space, underlying this computation. We combined calcium imaging and electrophysiology to constrain a stabilized supralinear network model that explains how the four principal cell types in layer 2/3 (L2/3) of mouse V1– somatostatin (SST), parvalbumin (PV), and vasoactive intestinal peptide (VIP) interneurons, and PCs– transform inputs from layer 4 (L4) PCs to encode drifting gratings of varying size and contrast. Using bidirectional optogenetic perturbations, we confirmed key predictions of the model. Our data and modeling showed that recurrent amplification drives a transition from a positive PC→VIP⊣SST⊣PC feedback loop at small size and low contrast to a negative PC→SST⊣PC feedback loop at large size and high contrast to contribute to this flexible computation. This may represent a widespread mechanism for gating competition across cortical space to optimally meet task demands.
An alphavirus replicon-based vaccine expressing a stabilized Spike antigen induces sterile immunity and prevents transmission of SARS-CoV-2 between cats
Authors: Langereis Martijn A. , Stachura Ken , Miller Suzan , Bosco-Lauth Angela M. , Albulescu Irina C. , Hartwig Airn E. , Porter Stephanie M. , Stammen-Vogelzangs Judith , Mogler Mark , van Kuppeveld Frank J.M. , Bosch Berend-Jan , Vermeij Paul , de Groof Ad , Bowen Richard A. , Davis Randy , Xu Zach , Tarpey Ian 
Published: April 2021

AbstractEarly in the global SARS-CoV-2 pandemic concerns were raised regarding infection of other animal hosts and whether these could play a significant role in the viral epidemiology. Infection of animals could be detrimental by causing clinical disease but also of concern if they become a viral reservoir allowing further mutations, plus having the potential to infect other animals or humans. The first reported animals to be infected both under experimental conditions and from anecdotal field evidence were cats described in China early in 2020. Given the concerns this finding raised and the close contacts between humans and cats, we aimed to determine whether a vaccine candidate could be developed that was suitable for use in multiple susceptible animal species and whether this vaccine could reduce infection of cats in addition to preventing spread to other cats.Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus (VEEV), known to be safe and efficacious for use in a variety of animals, expressing a stabilised Spike antigen, could induce neutralising antibody titers in guinea pigs and cats. After two intramuscular vaccinations, virus neutralising antibodies were detected in the respiratory tract of the guinea pigs and a cell mediated immune response was induced. The design of the SARS-CoV-2 antigen was shown to be critical in developing a strong neutralising antibody response. Vaccination of cats was able to induce a serum neutralising antibody response which lasted for the course of the experiment. Interestingly, in contrast to control animals, infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after challenge. Moreover, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit virus. The results show that the RP vaccine induces sterile immunity preventing SARS-CoV-2 infection and transmission. This data suggests that this RP vaccine could be a multi-species vaccine useful for preventing spread to and between other animals should that approach be required.
The neutralization potency of anti-SARS-CoV-2 therapeutic human monoclonal antibodies is retained against novel viral variants
Authors: Makdasi Efi , Zvi Anat , Alcalay Ron , Noy-Porat Tal , Peretz Eldar , Mechaly Adva , Levy Yinon , Epstein Eyal , Chitlaru Theodor , Tennenhouse Ariel , Aftalion Moshe , Gur David , Paran Nir , Tamir Hadas , Zimhony Oren , Weiss Shay , Mandelboim Michal , Mendelson Ella , Zuckerman Neta , Nemet Ital , Kliker Limor , Yitzhaki Shmuel , Shapira Shmuel C. , Israely Tomer , Fleishman Sarel J. , Mazor Ohad , Rosenfeld Ronit 
Published: April 2021

SummaryA wide range of SARS-CoV-2 neutralizing monoclonal antibodies (mAbs) were reported to date, most of which target the spike glycoprotein and in particular its receptor binding domain (RBD) and N-terminal domain (NTD) of the S1 subunit. The therapeutic implementation of these antibodies has been recently challenged by emerging SARS-CoV-2 variants that harbor extensively mutated spike versions. Consequently, the re-assessment of mAbs, previously reported to neutralize the original early-version of the virus, is of high priority.Four previously selected mAbs targeting non-overlapping epitopes, were evaluated for their binding potency to RBD versions harboring individual mutations at spike positions 417, 439, 453, 477, 484 and 501. Mutations at these positions represent the prevailing worldwide distributed modifications of the RBD, previously reported to mediate escape from antibody neutralization. Additionally, thein vitroneutralization potencies of the four RBD-specific mAbs, as well as two NTD-specific mAbs, were evaluated against two frequent SARS-CoV-2 variants of concern (VOCs): (i) the B.1.1.7 variant, emerged in the UK and (ii) the B.1.351 variant, emerged in South Africa. Variant B.1.351 was previously suggested to escape many therapeutic mAbs, including those authorized for clinical use. The possible impact of RBD mutations on recognition by mAbs is addressed by comparative structural modelling. Finally, we demonstrate the therapeutic potential of three selected mAbs by treatment of K18-hACE2 transgenic mice two days post infection with each of the virus strains.Our results clearly indicate that despite the accumulation of spike mutations, some neutralizing mAbs preserve their potency against SARS-CoV-2. In particular, the highly potent MD65 and BL6 mAbs are shown to retain their ability to bind the prevalent novel viral mutations and to effectively protect against B.1.1.7 and B.1.351 variants of high clinical concern.
Tension mediated mechanical activation and pocket delipidation lead to an analogous MscL state
Authors: Wang Bolin , Lane Benjamin J. , Kapsalis Charalampos , Ault James R. , Sobott Frank , El Mkami Hassane , Calabrese Antonio N. , Kalli Antreas C. , Pliotas Christos 
Published: April 2021

AbstractThe MscL channel gates in response to membrane tension changes to allow the exchange of molecules through its pore. Lipid removal from transmembrane pockets leads to a MscL response. However, it is unknown whether there is correlation between the tension mediated state and the state derived by pocket delipidation in the absence of tension. Transitions between MscL states may follow a similar pathway to cover the available conformational space but may not necessarily sample the same discrete intermediates. Here, we combined pulsed-EPR and HDX-MS measurements on MscL, coupled with molecular dynamics under membrane tension, to investigate the changes associated with the distinctively derived states. Whether it is tension or pocket delipidation, we find that MscL samples a similar expanded state, which is the final step of the delipidation pathway but only an intermediate stop of the tension mediated path. Our findings hint at synergistic modes of regulation in mechanosensitive channels.
Heritage assets in financial reporting: a critical analysis of the IPSASB's consultation paper
Authors: Biondi Lucia , Grandis Fabio Giulio , Mattei Giorgia 
Published: April 2021

PurposeWithin the stream of research on public sector accounting standards, heritage asset accounting represents a difficult and challenging issue. This paper intends to join the debate on heritage reporting by carrying out a critical review of the Consultation Paper (CP) “Financial Reporting for Heritage in the Public Sector” issued by the International Public Sector Accounting Standards Board (IPSASB) in order to highlight its strengths and weaknesses and to make recommendations.Design/methodology/approachTo this end, the current study adopts document analysis as a qualitative research method by referring to Italy as a typical and critical case study. Moreover, the authors actively took part in the Italian working group on heritage assets reporting, so they are well-informed people about the Italian point of view as well as the broad discussion underpinning the Italian response.FindingsEvidence demonstrates that, although the proposals included in the CP represent a new step towards an organic regulation of heritage asset reporting, if these preliminary views are confronted with the reality of an emblematic context, as in the Italian case, much room for improvement remains regarding the definition, recognition, measurement and disclosure of such assets.Originality/valueThe originality of the paper lies in its contribution to overcoming the current controversial aspects of heritage assets reporting and the issuing of an accounting standard. In doing so, the authors also attempt to answer the call made by Anessi-Pessina et al. (2019) to investigate in detail an individual country experience to better understand the state of the art in national and international accounting standards on heritage assets.
Cable reverberations during wireline distributed acoustic sensing measurements: their nature and methods for elimination
Authors: Martuganova Evgeniia , Stiller Manfred , Bauer Klaus , Henninges Jan , Krawczyk Charlotte M. 
Published: April 2021

ABSTRACTThe application of distributed acoustic sensing in borehole measurements allows for the use of fibre optic cables to measure strain. This is more efficient in terms of time and costs compared with the deploying of conventional borehole seismometers. Nevertheless, one known drawback for temporary deployment is represented by the freely hanging wireline cable slapping and ringing inside the casing, which introduces additional coherent coupling noise to the data. The present study proposes an explanation for the mechanism of noise generation and draws an analogy with similar wave propagation processes and phenomena, such as ghost waves in marine seismics. This observation allows to derive a ringing noise filter function, to study its behaviour and to consider known effects of the gauge length filter. After examining existing methods aimed at eliminating ringing noise and results of their application, we propose a two‐step approach: (1) developing a denoising method based on a matching pursuit decomposition with Gabor atoms and (2) subtracting the noise model for imaging improvement. The matching pursuit method focuses on decomposing the original input signal into a weighted sum of Gabor functions. Analysing Gabor atoms properties for frequency, amplitude and position in time provides the opportunity to distinguish parts of the original signal denoting noise caused by the vibrating cable. The matching pursuit decomposition applied to the distributed acoustic sensing‐vertical seismic profiling data at the geothermal test site Groß Schönebeck provides a versatile processing instrument for noise suppression.