bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two promoters integrate multiple enhancer inputs to drive wild-typeknirpsexpression in theD. melanogasterembryo
Authors: Li Lily , Waymack Rachel , Elabd Mario , Wunderlich Zeba 
Published: March 2021

AbstractProper development depends on precise spatiotemporal gene expression patterns. Most genes are regulated by multiple enhancers and often by multiple core promoters that generate similar transcripts. We hypothesize that these multiple promoters may be required either because enhancers prefer a specific promoter or because multiple promoters serve as a redundancy mechanism. To test these hypotheses, we studied the expression of theknirpslocus in the earlyDrosophila melanogasterembryo, which is mediated by multiple enhancers and core promoters. We found that one of these promoters resembles a typical “sharp” developmental promoter, while the other resembles a “broad” promoter usually associated with housekeeping genes. Using synthetic reporter constructs, we found that some, but not all, enhancers in the locus show a preference for one promoter. By analyzing the dynamics of these reporters, we identified specific burst properties during the transcription process, namely burst size and frequency, that are most strongly tuned by the specific combination of promoter and enhancer. Using locus-sized reporters, we discovered that even enhancers that show no promoter preference in a synthetic setting have a preference in the locus context. Our results suggest that the presence of multiple promoters in a locus is both due to enhancer preference and a need for redundancy and that “broad” promoters with dispersed transcription start sites are common among developmental genes. Our results also imply that it can be difficult to extrapolate expression measurements from synthetic reporters to the locus context, where many variables shape a gene’s overall expression pattern.
Cation and anion channelrhodopsins: Sequence motifs and taxonomic distribution
Authors: Govorunova Elena G. , Sineshchekov Oleg A. , Li Hai , Wang Yumei , Brown Leonid S. , Palmateer Alyssa , Melkonian Michael , Cheng Shifeng , Carpenter Eric , Patterson Jordan , Wong Gane K.-S. , Spudich John L. 
Published: March 2021

ABSTRACTCation and anion channelrhodopsins (CCRs and ACRs, respectively) primarily from two algal species, Chlamydomonas reinhardtii and Guillardia theta, have become widely used as optogenetic tools to control cell membrane potential with light. We mined algal and other protist polynucleotide sequencing projects and metagenomic samples to identify 75 channelrhodopsin homologs from three channelrhodopsin families, including one revealed in dinoflagellates in this study. We carried out electrophysiological analysis of 33 natural channelrhodopsin variants from different phylogenetic lineages and 10 metagenomic homologs in search of sequence determinants of ion selectivity, photocurrent desensitization, and spectral tuning in channelrhodopsins. Our results show that association of a reduced number of glutamates near the conductance path with anion selectivity depends on a wider protein context, because prasinophyte homologs with the identical glutamate pattern as in cryptophyte ACRs are cation-selective. Desensitization is also broadly context-dependent, as in one branch of stramenopile ACRs and their metagenomic homologs its extent roughly correlates with phylogenetic relationship of their sequences. Regarding spectral tuning, two prasinophyte CCRs exhibit red-shifted spectra to 585 nm, although their retinal-binding pockets do not match those of previously known similarly red-shifted channelrhodopsins. In cryptophyte ACRs we identified three specific residue positions in the retinal-binding pocket that define the wavelength of their spectral maxima. Lastly, we found that dinoflagellate rhodopsins with a TCP motif in the third transmembrane helix and a metagenomic homolog exhibit channel activity.IMPORTANCEChannelrhodopsins are widely used in neuroscience and cardiology as research tools and are considered as prospective therapeutics, but their natural diversity and mechanisms remain poorly characterized. Genomic and metagenomic sequencing projects are producing an ever-increasing wealth of data, whereas biophysical characterization of the encoded proteins lags behind. In this study we used manual and automated patch clamp recording of representative members of four channelrhodopsin families including a family that we report in this study in dinoflagellates. Our results contribute to a better understanding of molecular determinants of ionic selectivity, photocurrent desensitization, and spectral tuning in channelrhodopsins.
Impact of increased membrane realism on conformational sampling of proteins
Authors: Weigle Austin T. , Carr Matthew , Shukla Diwakar 
Published: March 2021

ABSTRACTThe realism and accuracy of lipid bilayer simulations through molecular dynamics (MD) is heavily dependent on the lipid composition. While the field is pushing towards implementing more heterogeneous and realistic membrane compositions, a lack of high-resolution lipidomic data prevents some membrane protein systems from being modeled with the highest level of realism. Given the additional diversity of real-world cellular membranes and protein-lipid interactions, it is still not fully understood how altering membrane complexity affects modeled membrane protein function or if it matters over long timescale simulations. This is especially true for organisms whose membrane environments have little to no computational study, such as the plant plasma membrane. Tackling these issues in tandem, a generalized, realistic, and asymmetric plant plasma with more than 10 different lipid species membrane is constructed herein. Classical MD simulations of pure membrane constructs were performed to evaluate how altering the compositional complexity of the membrane impacted the plant membrane properties. The apo form of a plant sugar transporter, OsSWEET2b, was inserted into membrane models where lipid diversity was calculated in either a size-dependent or -independent manner. An adaptive sampling simulation regime validated by Markov-state models was performed to capture the gating dynamics of OsSWEET2b in each of these membrane constructs. In comparison to previous OsSWEET2b simulations performed in a pure POPC bilayer, we confirm that simulations performed within a native-like membrane composition alter the stabilization of apo OsSWEET2b conformational states by ~1 kcal/mol. The free energy barriers of intermediate conformational states decrease when realistic membrane complexity is simplified, albeit roughly within sampling error, suggesting that protein-specific responses to membranes differ due to altered packing caused by compositional fluctuations. This work serves as a case study where a more realistic bilayer composition makes unbiased conformational sampling easier to achieve than with simplified bilayers.
Isolation and Characterization of Cross-Neutralizing Coronavirus Antibodies from COVID-19+ Subjects
Authors: Jennewein Madeleine F. , MacCamy Anna J. , Akins Nicholas R. , Feng Junli , Homad Leah J. , Hurlburt Nicholas K. , Seydoux Emily , Wan Yu-Hsin , Stuart Andrew B. , Edara Venkata Viswanadh , Floyd Katharine , Vanderheiden Abigail , Mascola John R. , Doria-Rose Nicole , Wang Lingshu , Yang Eun Sung , Chu Helen Y. , Torres Jonathan L. , Ozorowski Gabriel , Ward Andrew B. , Whaley Rachael E. , Cohen Kristen W. , Pancera Marie , McElrath M. Juliana , Englund Janet A. , Finzi Andrés , Suthar Mehul S. , McGuire Andrew T. , Stamatatos Leonidas 
Published: March 2021

SUMMARYSARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency rather than the antibody epitope specificity regulates thein vivoprotective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
The proteome of remyelination is different from that of developmental myelination
Authors: de Faria Joana Paes , Azevedo Maria M. , Bausch-Fluck Damaris , Seixas Ana , Domingues Helena S. , Monteiro Maria A. , Pedrioli Patrick G.A. , Lopes Eduarda , Fernandes Rui , Zhao Chao , Franklin Robin J. M. , Wollscheid Bernd , Relvas Joao B. , Montani Laura 
Published: March 2021

AbstractLoss of myelin underlies the pathology of several neurological disorders of diverse etiology. CNS remyelination by adult oligodendrocyte progenitor cells (OPCs) can occur but it differs from developmental myelination carried out by neonatal OPCs. We asked whether the myelin proteome of remyelinated regions is changed. We compared the myelin proteome formed during development to the remyelination proteome attained after lysolecithin-induced demyelination in the mouse spinal cord. Mass-spectrometry analysis of iTRAQ labelled myelin protein lysates showed that the proteome of remyelination is different from that of developmental myelination, leading to profound changes in myelin protein content. Aside from known mediators of oligodendrocyte differentiation, we found proteome alterations included modulators of metabolism, cell signaling and actin cytoskeleton dynamics. Downregulating one candidate (FSCN1/Fascin1) was sufficient to partially hamper oligodendrocytesin-vitro. In summary, we identify the difference in the proteome of remyelinating oligodendrocytes as a novel potential contributor to the pathophysiology of demyelinating disorders, thus providing new potential therapeutic targets for future studies.
B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies
Authors: Zhou Hao , Dcosta Belinda M. , Samanovic Marie I. , Mulligan Mark J. , Landau Nathaniel R. , Tada Takuya 
Published: March 2021

AbstractDNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein together with four novel point mutations and with an E484K or S477N mutation in the receptor binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer as compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of wide-spread vaccination.
A polyyne toxin produced by an antagonistic bacterium blinds and lyses a green microalga
Authors: Hotter Vivien , Zopf David , Kim Hak Joong , Silge Anja , Schmitt Michael , Aiyar Prasad , Fleck Johanna , Matthäus Christian , Hniopek Julian , Yan Qing , Loper Joyce , Sasso Severin , Hertweck Christian , Popp Jürgen , Mittag Maria 
Published: March 2021

AbstractMicroalgae are key contributors to global carbon fixation and the basis of many food webs. In nature, their growth is often supported or suppressed by other microorganisms. The bacteriumPseudomonas protegensPf-5 arrests the growth of the green algaChlamydomonas reinhardtii, deflagellates the alga by the cyclic lipopeptide orfamide A, and alters its morphology. Using a combination of Raman microspectroscopy, genome mining and mutational analysis, we discovered a novel polyyne toxin we name protegencin that is secreted byP. protegensand penetrates algal cells to destroy their primitive visual system, the eyespot. Together with secreted orfamide A, protegencin prevents the phototactic behavior ofC. reinhardtiineeded to perform optimal photosynthesis. A protegencin-deficient biosynthetic mutant ofP. protegensdoes not affect growth or eyespot carotenoids ofC. reinhardtii. Thus, protegencin acts in a direct and destructive way, and reveals at least a two-pronged molecular strategy used by algicidal bacteria.
RNA Pol IV has antagonistic parent-of-origin effects on Arabidopsis endosperm
Authors: Satyaki Prasad R.V. , Gehring Mary 
Published: March 2021

AbstractGene expression in endosperm – a seed tissue that mediates transfer of maternal resources to offspring – is under complex epigenetic control. We show here that plant-specific RNA Polymerase IV mediates parental control of endosperm gene expression. Pol IV is required for the production of small interfering RNAs that typically direct DNA methylation. We compared small RNAs, DNA methylation, and mRNAs inA. thalianaendosperm from reciprocal heterozygotes produced by crossing wild-type plants to Pol IV mutants. We find that maternally and paternally acting Pol IV have divergent effects on endosperm. Losses of maternal and paternal Pol IV impact sRNAs and DNA methylation at distinct genomic sites. Strikingly, maternally and paternally-acting Pol IV have antagonistic impacts on gene expression at some loci, divergently promoting or repressing endosperm gene expression. Antagonistic parent-of-origin effects have only rarely been described and are consistent with a gene regulatory system evolving under parental conflict.
Four-point dynamic leveling method for drilling platform application
Authors: Li Dongmin , Ma Guofang , Li Jia 
Published: March 2021

Purpose
It is essential to level the drilling platform across which a drilling robot travels in a slant underground coal mine tunnel to ensure smooth operation of the drill rod. However, existing leveling methods do not provide dynamic performance under the drilling conditions of the underground coal mine. A four-point dynamic leveling algorithm is presented in this paper based on the platform attitude and support rod displacement (DLAAD). An experimental drilling robot demonstrates its dynamic leveling capability and ability to ensure smooth drill rod operations.

Design/methodology/approach
The attitude coordinate of the drilling robot is established according to its structure. A six-axis combined sensor is adopted to detect the platform attitude, thus revealing the three-axis Euler angles. The support rod displacement values are continuously detected by laser displacement sensors to obtain the displacement increment of each support rod as needed. The drilling robot is leveled according to the current support rod displacement and three-dimensional (3 D) attitude detected by the six-axis combined sensor dynamically.

Findings
Experimental results indicate that the DLAAD algorithm is correct and effectively levels the drilling platform dynamically. It can thus provide essential support in resolving drill rod sticking problems during actual underground coal mine drilling operations.

Practical implications
The DLAAD algorithm supports smooth drill rod operations in underground coal mines, which greatly enhances safety, reduces power consumption, and minimizes cost. The approach proposed here thus represents considerable benefits in terms of coal mine production and shows notable potential for application in similar fields.

Originality/value
The novel DLAAD algorithm and leveling control method are the key contributions of this work, they provide dynamical 3 D leveling and help to resolve drill rod sticking problems.
ELMOPP: an application of graph theory and machine learning to traffic light coordination
Authors: Sheriff Fareed 
Published: March 2021

PurposeThis paper presents the Edge Load Management and Optimization through Pseudoflow Prediction (ELMOPP) algorithm, which aims to solve problems detailed in previous algorithms; through machine learning with nested long short-term memory (NLSTM) modules and graph theory, the algorithm attempts to predict the near future using past data and traffic patterns to inform its real-time decisions and better mitigate traffic by predicting future traffic flow based on past flow and using those predictions to both maximize present traffic flow and decrease future traffic congestion.Design/methodology/approachELMOPP was tested against the ITLC and OAF traffic management algorithms using a simulation modeled after the one presented in the ITLC paper, a single-intersection simulation.FindingsThe collected data supports the conclusion that ELMOPP statistically significantly outperforms both algorithms in throughput rate, a measure of how many vehicles are able to exit inroads every second.Originality/valueFurthermore, while ITLC and OAF require the use of GPS transponders and GPS, speed sensors and radio, respectively, ELMOPP only uses traffic light camera footage, something that is almost always readily available in contrast to GPS and speed sensors.
Consumer-led eco-development of food products: a case study to propose a framework
Authors: Thomas Chloé , Maître Isabelle , Symoneaux Ronan 
Published: March 2021

PurposeThe purpose of this paper is to propose an agile methodology for the development of food products that has two key characteristics: (1) consumers are included as co-creators and (2) the assessment of environmental impacts plays a central role.Design/methodology/approachIn collaboration with a French small-to-mid-size enterprise, a research-intervention approach was used to test the agile methodology designed, which features three iterative runs of food product development. In each run, prototypes were presented and modified with consumers during focus groups. Life cycle analysis assessed the relative environmental impacts of the prototypes. The research data from consumers were mainly qualitative.FindingsThe main result of this work is the implementation of a methodology to develop new food products in an efficient way by integrating consumers' insights and environmental concerns simultaneously. The method was successful in integrating consumers as co-creators and in drawing attention to the potential environmental effects of different prototypes for the decision-making process.Research limitations/implicationsThe research is based on a single case study. Thus, generalisation to other companies is limited. The authors invite further research focussed on different types of companies. The methodology and the tools could be modified to suit a variety of contexts.Originality/valueThis work addresses the need for guidelines to integrate consumers and environmental considerations into the food development process by testing an agile methodology with a company. It contributes to the scope of sustainable and consumer-oriented food innovation management.
How perceived information transparency and psychological attitude impact on the financial well-being: mediating role of financial self-efficacy
Authors: Zia-ur-Rehman Muhammad , Latif Khalid , Mohsin Muhammad , Hussain Zahid , Baig Sajjad Ahmad , Imtiaz Izma 
Published: March 2021

PurposeThe basic intention of this research is to investigate the role of information transparency of financial institutions and psychological attitude of the individuals toward their attention to saving and borrowing. This study also tries to know how an individual's psychological factor affects a person's attitude to motivate them to save or borrow and contribute to well-being by giving them confidence that they can face financial challenges. So, the main concern of this study is to explore different factors that ultimately contribute to the financial well-being (FWB) of individual.Design/methodology/approachA survey was conducted by using a well-structured questionnaire to collect data and test the developed hypotheses by using SmartPLS. Data were collected from 120 customers of seven different commercial banks in Pakistan.FindingsThe findings of this study show that perceived information transparency positively affects FWB. It is also because transparent shared information creates positive change in individuals' perceived self-efficacy and leads to FWB. Furthermore, an individual's psychological attitude toward borrowing and saving did not contribute to the FWB of people who belong to Pakistan.Research limitations/implicationsThe research area is limited to one city of Pakistan and analysis is done with small numbers of sample, it can be increased and more areas can be explored.Practical implicationsThis research provides significant implications for people and economists by providing awareness about the antecedents of FWB. The policymakers or managers who work in financial institutions should provide more transparent information and create less risky opportunities to improve the individual's well-being. If person, manager and financial institution can properly utilize the information of this study, then they are able to improve their FWB. By providing more transparent services and favorable experience with your dealings, it could help to obtain and retain more loyal internal (employees) and external customers. The loyal customers and sincere employees can increase the productivity level of organization. The more productive organizations in countries means better society and progress in the economy.Originality/valueThis research contributes to the body of knowledge that how perceived information transparency and psychological attitude of borrowing create improvement and upward changes in the FWB of a person.