bluuebunny/crossref_metadata_2025_split huggingface dataset:
A paradigm for regulation at the effector interface with RNA-binding proteins
Authors: Shah Kriti , He Shiyang , Turner David J. , Corbo Joshua , Rebbani Khadija , Bateman Joseph M. , Cheloufi Sihem , Igreja Cátia , Valkov Eugene , Murn Jernej 
Published: September 2023

ABSTRACTRNA-binding proteins (RBPs) are key regulators of gene expression, but how RBPs convey regulatory instructions to the core effectors of RNA processing is unclear. Here we document the existence and functions of a multivalent RBP–effector interface. We show that the effector interface of a deeply conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of ‘dual-purpose’ peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by the recruiting RBP. Systems analyses reveal that multivalent RBP–effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP–effector interface, with implications for the evolution and function of RBP-operated regulatory networks.
Computational design of sequence-specific DNA-binding proteins
Authors: Glasscock Cameron J. , Pecoraro Robert , McHugh Ryan , Doyle Lindsey A. , Chen Wei , Boivin Olivier , Lonnquist Beau , Na Emily , Politanska Yuliya , Haddox Hugh K. , Cox David , Norn Christoffer , Coventry Brian , Goreshnik Inna , Vafeados Dionne , Lee Gyu Rie , Gordan Raluca , Stoddard Barry L. , DiMaio Frank , Baker David 
Published: September 2023

AbstractSequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize specific target sequences through interactions with bases in the major groove, and employ this method in conjunction with experimental screening to generate binders for 5 distinct DNA targets. These binders exhibit specificity closely matching the computational models for the target DNA sequences at as many as 6 base positions and affinities as low as 30–100 nM. The crystal structure of a designed DBP-target site complex is in close agreement with the design model, highlighting the accuracy of the design method. The designed DBPs function in bothEscherichia coliand mammalian cells to repress and activate transcription of neighboring genes. Our method is a substantial step towards a general route to small and hence readily deliverable sequence-specific DBPs for gene regulation and editing.
Low Shear in Short-Term Impacts Endothelial Cell Traction and Alignment in Long-Term
Authors: Chandurkar Mohanish K. , Mittal Nikhil , Royer-Weeden Shaina P. , Lehmann Steven D. , Rho Yeonwoo , Han Sangyoon J. 
Published: September 2023

AbstractWithin the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction—a measure of cellular tension that plays a crucial role in how endothelial cells respond to mechanical stimuli. By integrating traction force microscopy (TFM) with a custom-built flow chamber, we analyzed how human umbilical vein endothelial cells (HUVECs) adjust their traction in response to shifts from low to high shear stress. We discovered that initial exposure to low FSS prompts a marked increase in traction force, which continues to rise over 10 hours before slowly decreasing. In contrast, immediate exposure to high FSS causes a quick spike in traction followed by a swift reduction, revealing distinct patterns of traction behavior under different shear conditions. Importantly, the direction of traction forces and the resulting cellular alignment under these conditions indicate that the initial shear experience dictates long-term endothelial behavior. Our findings shed light on the critical influence of short-lived low-shear stress experiences in shaping endothelial function, indicating that early exposure to low FSS results in enduring changes in endothelial contractility and alignment, with significant consequences for vascular health and the development of cardiovascular diseases.
Advancing GABA-edited MRS Research through a Reconstruction Challenge
Authors: Berto Rodrigo Pommot , Bugler Hanna , Dias Gabriel , Oliveira Mateus , Ueda Lucas , Dertkigil Sergio , Costa Paula D. P. , Rittner Leticia , Merkofer Julian P. , Sande Dennis M. J. van de , Amirrajab Sina , Drenthen Gerhard S. , Veta Mitko , Jansen Jacobus F. A. , Breeuwer Marcel , Sloun Ruud J. G. van , Qayyum Abdul , Rodero Cristobal , Niederer Steven , Souza Roberto , Harris Ashley D. 
Published: September 2023

AbstractPurposeTo create a benchmark for the comparison of machine learning-based Gamma-Aminobutyric Acid (GABA)-edited Magnetic Resonance Spectroscopy (MRS) reconstruction models using one quarter of the transients typically acquired during a complete scan.MethodsThe Edited-MRS reconstruction challenge had three tracks with the purpose of evaluating machine learning models trained to reconstruct simulated (Track 1), homogeneousin vivo(Track 2), and heterogeneousin vivo(Track 3) GABA-edited MRS data. Four quantitative metrics were used to evaluate the results: mean squared error (MSE), signal-to-noise ratio (SNR), linewidth, and a shape score metric that we proposed. Challenge participants were given three months to create, train and submit their models. Challenge organizers provided open access to a baseline U-NET model for initial comparison, as well as simulated data,in vivodata, and tutorials and guides for adding synthetic noise to the simulations.ResultsThe most successful approach for Track 1 simulated data was a covariance matrix convolutional neural network model, while for Track 2 and Track 3in vivodata, a vision transformer model operating on a spectrogram representation of the data achieved the most success. Deep learning (DL) based reconstructions with reduced transients achieved equivalent or better SNR, linewidth and fit error as conventional reconstructions with the full amount of transients. However, some DL models also showed the ability to optimize the linewidth and SNR values without actually improving overall spectral quality, pointing to the need for more robust metrics.ConclusionThe edited-MRS reconstruction challenge showed that the top performing DL based edited-MRS reconstruction pipelines can obtain with a reduced number of transients equivalent metrics to conventional reconstruction pipelines using the full amount of transients. The proposed metric shape score was positively correlated with challenge track outcome indicating that it is well-suited to evaluate spectral quality.
Regulatory Mechanisms Orchestrating Cellular Diversity in Cd36+ Olfactory Sensory Neurons Revealed by Single-Cell Multi-omics Analysis
Authors: Yang Jiawen , Shi Peiyu , Li Yiheng , Zuo Yachao , Xu Tao , An Ziyang , Peng Dongjie , Zhang Weixing , Xu Yicong , Tang Zhongjie , Li Anan , Xu Jin 
Published: September 2023

AbstractThe olfactory system relies on the precise expression of olfactory receptor (OR) genes in individual olfactory sensory neurons (OSNs) to detect and discriminate a vast array of odorants. Recent discoveries have revealed remarkable complexity and diversity within OSNs, including the existence of two distinct OSN populations based on high-affinity receptor Cd36 expression. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive.To address these questions, we conducted single-cell multi-omics analyses of mature OSNs in the mouse olfactory epithelium. Firstly, we systematically revealed the transcriptome diversity and spatial distribution of Cd36+ OSNs and found a specific subset of olfactory receptors co-expressed with Cd36 in a deterministic manner. scATAC-seq profiling of chromatin landscape demonstrated a divergence between Cd36+ OSNs and Cd36- OSNs, including differential accessibility of cis-elements. By integrating transcriptome and epigenome profiling of OSN lineage-associated cell types, we revealed that the processes governing this diversity are initiated at the immature OSNs stage, where cellular diversity was first set by the lineage-specific binding of Lhx2 at Hdac9 enhancer. Hdac9, which is specifically expressed in the Cd36- OSN lineage, functions as a histone deacetylase and may repress the transcription of Mef2-dependent genes that contribute to Cd36+ OSN diversity. By gene regulation network analysis, we revealed Mef2a and Tshz1 as the key transcription factors, orchestrating the transcriptome diversity of Cd36+ OSNs. Remarkably, we identified and confirmed Tshz1 as a critical transcription factor that directly promotes Cd36 expression in OSNs through enhancer binding. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system. These findings provide valuable insights into the regulation principles underlying neuronal heterogeneity and its functional implications.
Amino acid residues for specific binding to ssDNA facilitate topological loading of bacterial condensin MukB
Authors: Akiyama Koichiro , Yano Koichi , Niki Hironori 
Published: September 2023

ABSTRACTThe bacterial condensin MukB facilitates proper chromosome segregation inEscherichia coli. A portion of the MukB proteins localize at a specific chromosome region, binding to DNA in a non-sequence-specific manner. However, it is unclear how MukB localizes at a particular site without sequence specificity. Like other structural maintenance of chromosome (SMC) proteins, MukB topologically loads onto DNA, and It has an intrinsic property of preferential topological loading onto the single-stranded DNA (ssDNA). We consider it crucial for the localization of a specific region. To investigate the property of MukB, we attempted to identify positively charged amino acid residues responsible for ssDNA binding. We created a series of mutated MukB proteins in which a single positively charged amino acid was replaced with a negatively charged one. The results showed that some substitutions located on the inner surface of the MukB head domain impacted ssDNA-binding activity, leading to deficiencies in cell growth and nucleoid segregation. The efficiency of topological loading onto ssDNA was also decreased when the positive charges were replaced with negative ones. These amino acid residues align with and bind to ssDNA when the MukB dimer secures ssDNA within its ring, thereby likely strengthening the ssDNA-binding ability of MukB.
Local endoreduplication of the host is a conserved process during Phytomyxea-host interaction
Authors: Hittorf M , Garvetto A , Magauer M , Kirchmair M , Salvenmoser W , Murúa P , Neuhauser S 
Published: September 2023

ABSTRACTEndoreduplication is a modified cell cycle in which cells duplicate their DNA without subsequent mitosis. This process is common in plants and can also be found in other organisms like algae and animals. Biotrophic plant pathogens have been shown to induce endoreduplication in their host to gain space and/or nutrients. Phytomyxea (divided into the Plasmodiophorida, the Phagomyxida, and theMarinomyxaclade) are obligate biotrophic parasites of plants, diatoms, brown algae, and oomycetes. Here, we tested if phytomyxids induce local endoreduplication in two distant hosts (plants and brown algae). By combining fluorescent in situ hybridisation (FISH) coupled with nuclear area measurements and flow cytometry, we confirmed that endoreduplication is induced byPlasmodiophora brassicae(Plasmodiophorida) in infected plants and demonstrate this process in combination withMaullinia ectocarpiiandMaullinia braseltonii(Phagomyxida) in brown algae. We identified molecular signatures of endoreduplication in RNA-seq datasets ofP. brassicae-infectedBrassica oleraceaeandM. ectocarpii-infectedEctocarpus siliculosus. Cell cycle switch proteins (CCS52A1 and B in plants and CCS52 in algae) as well as the protein kinase WEE1 (in plants) were identified as genes potentially important for the phytomyxean-induced switch from the mitotic cell cycle to the endocycle. Their expression pattern changed in infected plants and brown algae accordingly. In this study we expand the knowledge on Phytomyxea-host interactions by showing that induced endoreduplication in the host is a conserved feature in phytomyxid infections. The induction of this cellular mechanism by phytomyxid parasites in phylogenetically distant hosts further points at a fundamental importance of endoreduplication in these biotrophic interactions.
PGR5 is required to avoid photosynthetic oscillations during light transitions
Authors: Degen Gustaf E. , Pastorelli Federica , Johnson Matthew P. 
Published: September 2023

AbstractThe production of ATP and NADPH by the light reactions of photosynthesis and their consumption by the Calvin-Benson-Bassham (CBB) cycle and other downstream metabolic reactions requires careful regulation. Environmental shifts perturb this careful balance, leading to photo-oxidative stress and losses in CO2assimilation. Imbalances in the production and consumption of ATP and NADPH manifest themselves as transient instability in the chlorophyll fluorescence, P700, electrochromic shift and CO2uptake signals recorded on leaves. These oscillations can be induced in wild-type plants by sudden shifts in CO2concentration or light intensity, however mutants exhibiting increased oscillatory behaviour have yet to be reported. This has precluded an understanding of the regulatory mechanisms employed by plants to suppress oscillations. Here we show that the Arabidopsispgr5mutant, which is deficient in PGR5-dependent cyclic electron transfer (CET), exhibits increased oscillatory behaviour. In contrast, mutants lacking the NDH-dependent CET are largely unaffected. The absence of oscillations in thehope2mutant, which likepgr5, lacks photosynthetic control and exhibits high ATP synthase conductivity, ruled out loss of these photoprotective mechanisms as causes. Instead, we observed slower formation of proton motive force and by inference ATP synthesis inpgr5following environmental perturbation, leading to the transient reduction of the electron transfer chain and photosynthetic oscillations. PGR5-dependent CET therefore plays a major role in damping the effect of environmental perturbations on photosynthesis to avoid losses in CO2fixation.
Multi-signal regulation of the GSK-3β homolog Rim11 governs meiosis entry in yeast
Authors: Kociemba Johanna , Jørgensen Andreas Christ Sølvsten , Tadic Nika , Harris Anthony , Sideri Theodora , Chan Wei Yee , Ibrahim Fairouz , Unal Elcin , Skehel Mark , Shahrezaei Vahid , Arguello-Miranda Orlando , van Werven Folkert J. 
Published: September 2023

AbstractStarvation of budding yeast diploid cells induces the cell-fate program that drives meiosis and spore formation. Transcription activation of early meiotic genes (EMGs) requires the transcription activator Ime1, its DNA-binding partner Ume6, and GSK-3β kinase Rim11. Phosphorylation of Ume6 by Rim11 is key for EMG activation. We report that Rim11 integrates multiple input signals to control Ume6 phosphorylation and EMG transcription. Under nutrient-rich conditions PKA represses Rim11 to low levels while TORC1 keeps Rim11 localized to the cytoplasm. Inhibiting PKA and TORC1 induces Rim11 expression and nuclear localization. Remarkably, nuclear Rim11 is required, but not sufficient, for Rim11-dependent Ume6 phosphorylation. Additionally, Ime1 is an essential anchor protein for phosphorylating Ume6. Subsequently, Ume6-Ime1 coactivator complexes form that drive EMG transcription. Our results demonstrate how varied signalling inputs (PKA/TORC1/Ime1) integrated by Rim11 determine EMG expression and entry into meiosis. We propose that the signalling-regulatory network described here generates robustness in cell-fate control.
Decoding corruption in Brazilian construction multinationals
Authors: Barboza Tania , Da Rocha Angela 
Published: September 2023

PurposeThis study aims to investigate whether firms involved in a major corruption scandal, with broad ramifications across several emerging and advanced markets, design the content of their corporate codes of conduct to either improve corporate ethical standards and practices or merely manipulate the impression of stakeholders.Design/methodology/approachThis study adopts an impression management perspective. It uses content analysis techniques to examine the codes of conduct adopted by seven Brazilian engineering and construction multinationals accused of corruption. The analysis covered five major themes: (1) forms of corruption, (2) values or principles, (3) interested parties, (4) procedures and routines and (5) punitive action.FindingsThe study provides detailed evidence that the codes of conduct adopted by these firms are mere artifices that aimed at meeting legal requirements but do not target the relevant corporate audience involved in grand corruption. At best, such a code may impede petty and bureaucratic corruption.Originality/valueThis research contributes to improving the understanding of how Latin American multinationals adopted codes of conduct after a major scandal and how they failed—at least to some extent—to design codes complying with established corporate governance principles. It shows that management manipulated the impression of stakeholders by selectively adopting or omitting certain terms, examining or concealing various issues and addressing mainly petty crimes rather than grand corruption. It also identifies areas where Western ethical values conflict with established practices and cultural norms in Latin America.
The effect of self-construal on solo dining intentions: an empirical study of Chinese consumers
Authors: Yan An , Ren Zhanzhi , Pei Feng , Zhu Xiaoxi 
Published: September 2023

PurposeThis study aims to examine the effect of self-construal on solo dining intentions and its underlying mechanism through consumer emotions. Furthermore, the study also investigates the moderating effect of the composition of other diners on the relationship between self-construal and solo dining intentions.Design/methodology/approachA 2 (self-construal: independent vs interdependent) × 2 (other diners: solo diners vs social diners) between-subjects experimental design was adopted to test the hypotheses. The data were collected from 317 Chinese consumers, followed by an analysis using IBM SPSS 23.0 and AMOS 23.0.FindingsThe findings indicate that consumers with an independent self-construal are more likely to have the intention to dine alone at a restaurant. Nevertheless, this effect is contingent upon the composition of other diners. The effect is significant only when nearby diners are social diners, and perceived enjoyment partly mediates the relationship. Conversely, when nearby diners are also solo diners, consumers' self-construals do not significantly affect their solo dining intentions. Moreover, the results indicate that consumers generally experience low levels of perceived stress when dining alone.Originality/valueThis study incorporates individual personality traits into research on solo diners and highlights the crucial role of positive emotions in solo dining, which provides insights for relevant enterprises to develop effective marketing strategies.
A performance-driving model for public-sector construction framework procurement in England
Authors: Lam Terence Y.M. , Gale Keith S. 
Published: September 2023

PurposeConstruction frameworks are recognised by the UK Government as an integrated procurement path to deliver efficiency, collaboration and sustainability. This research paper aims to develop a performance-driving model for framework procurement to align with the government construction policy objectives.Design/methodology/approachA quantitative hierarchical regression analysis was conducted to examine the causal relationships between project outcomes and performance drivers. A successive qualitative multiple-case study involving eight typical construction framework projects was examined to further explain casual relationships.FindingsConclusive results from the quantitative and qualitative analyses validated the performance-driving model, generalising a framework procurement principle that project outcomes of time, cost, quality, sustainability and closer relationships are significantly driven by supplier's task and contextual performance drivers, and client's organisational drivers.Research limitations/implicationsThe investigation followed two major public-sector organisations in the UK: infrastructure offices of local authorities and estate offices of universities. Further research should be extended to other public-sector situations to enhance the model further.Practical implicationsUsing this model, framework managers can drive project outcomes by applying task and contextual performance drivers in order to select the best suppliers at the procurement phase, and by adopting the client's organisational factors at both procurement and construction monitoring phases.Social implicationsThe empirical evidence supports the use of frameworks by public sector policymakers as a key strategy to develop the performance drivers further and improve efficiency and quality outcomes.Originality/valueThe results will be of value to support the policy of public-sector works organisations contemplating using framework procurement for executing continuing construction activities.