bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of programmed and spontaneous ribosome sliding along the mRNA
Authors: Senyushkina Tamara , Samatova Ekaterina , Klimova Maria , Rodnina Marina V 
Published: May 2024

Abstract
The ribosome can slide along mRNA without establishing codon-anticodon interactions. This movement can be regulated (programmed) by the elements encoded in the mRNA, as observed in bypassing of non-coding gap in gene 60 of bacteriophage T4, or occur spontaneously, such as during traversal by the 70S ribosome of the 3′UTRs or upon re-initiation on bacterial polycistronic genes. In this study, we investigate the kinetic mechanism underlying the programmed and spontaneous ribosome sliding. We show that the translation rate of gene 60 mRNA decreases as the ribosome approaches the take-off site, especially when the KKYK regulatory sequence in the nascent peptide reaches the constriction site in the ribosome exit tunnel. However, efficiency of bypassing increases when the ribosome traverses the gap quickly. With the non-coding gap exceeding the natural 50 nt, the processivity of sliding remains high up to 56 nt, but drops sharply beyond that due to the loss of mRNA elements support. Sliding efficiency is temperature-dependent; while temperature regulates the number of ribosomes initiating programmed bypassing, traversing the long gaps becomes increasingly unfavorable at lower temperatures. This data offers novel insights into the kinetic determinants of programmed and spontaneous ribosome sliding along the mRNA.
SLiMAn 2.0: meaningful navigation through peptide-protein interaction networks
Authors: Reys Victor , Pons Jean-Luc , Labesse Gilles 
Published: May 2024

Abstract
Among the myriad of protein–protein interactions occurring in living organisms, a substantial amount involves small linear motifs (SLiMs) recognized by structured domains. However, predictions of SLiM-based networks are tedious, due to the abundance of such motifs and a high portion of false positive hits. For this reason, a webserver SLiMAn (Short Linear Motif Analysis) was developed to focus the search on the most relevant SLiMs. Using SLiMAn, one can navigate into a given (meta-)interactome and tune a variety of parameters associated to each type of SLiMs in attempt to identify functional ELM motifs and their recognition domains. The IntAct and BioGRID databases bring experimental information, while IUPred and AlphaFold provide boundaries of folded and disordered regions. Post-translational modifications listed in PhosphoSite+ are highlighted. Links to PubMed accelerate scrutiny into the literature, to support (or not) putative pairings. Dedicated visualization features are also incorporated, such as Cytoscape for macromolecular networks and BINANA for intermolecular contacts within structural models generated by SCWRL 3.0. The use of SLiMAn 2.0 is illustrated on a simple example. It is freely available at https://sliman2.cbs.cnrs.fr.
MolModa: accessible and secure molecular docking in a web browser
Authors: Kochnev Yuri , Ahmed Mayar , Maldonado Alex M , Durrant Jacob D 
Published: May 2024

Abstract
Molecular docking advances early-stage drug discovery by predicting the geometries and affinities of small-molecule compounds bound to drug-target receptors, predictions that researchers can leverage in prioritizing drug candidates for experimental testing. Unfortunately, existing docking tools often suffer from poor usability, data security, and maintainability, limiting broader adoption. Additionally, the complexity of the docking process, which requires users to execute a series of specialized steps, often poses a substantial barrier for non-expert users. Here, we introduce MolModa, a secure, accessible environment where users can perform molecular docking entirely in their web browsers. We provide two case studies that illustrate how MolModa provides valuable biological insights. We further compare MolModa to other docking tools to highlight its strengths and limitations. MolModa is available free of charge for academic and commercial use, without login or registration, at https://durrantlab.com/molmoda.
Next-generation IEDB tools: a platform for epitope prediction and analysis
Authors: Yan Zhen , Kim Kevin , Kim Haeuk , Ha Brendan , Gambiez Anaïs , Bennett Jason , de Almeida Mendes Marcus Fabiano , Trevizani Raphael , Mahita Jarjapu , Richardson Eve , Marrama Daniel , Blazeska Nina , Koşaloğlu-Yalçın Zeynep , Nielsen Morten , Sette Alessandro , Peters Bjoern , Greenbaum Jason A 
Published: May 2024

Abstract
The Next-Generation (NG) IEDB Tools website (https://nextgen-tools.iedb.org) provides users with a redesigned interface to many of the algorithms for epitope prediction and analysis that were originally released on the legacy IEDB Tools website. The initial release focuses on consolidation of all tools related to HLA class I epitopes (MHC binding, elution, immunogenicity, and processing), making all of these predictions accessible from a single application and allowing for their simultaneous execution with minimal user inputs. Additionally, the PEPMatch tool for identifying highly similar epitopes in a set of curated proteomes, as well as a tool for epitope clustering, are available on the site. The NG Tools site allows users to build data pipelines by sending the output of one tool as input for the next. Over the next several years, all pre-existing IEDB Tools, and any newly developed tools, will be integrated into this new site. Here we describe the philosophy behind the redesign and demonstrate the utility and productivity enhancements that are enabled by the new interface.
DDMut-PPI: predicting effects of mutations on protein–protein interactions using graph-based deep learning
Authors: Zhou Yunzhuo , Myung YooChan , Rodrigues Carlos H M , Ascher David B 
Published: May 2024

Abstract
Protein–protein interactions (PPIs) play a vital role in cellular functions and are essential for therapeutic development and understanding diseases. However, current predictive tools often struggle to balance efficiency and precision in predicting the effects of mutations on these complex interactions. To address this, we present DDMut-PPI, a deep learning model that efficiently and accurately predicts changes in PPI binding free energy upon single and multiple point mutations. Building on the robust Siamese network architecture with graph-based signatures from our prior work, DDMut, the DDMut-PPI model was enhanced with a graph convolutional network operated on the protein interaction interface. We used residue-specific embeddings from ProtT5 protein language model as node features, and a variety of molecular interactions as edge features. By integrating evolutionary context with spatial information, this framework enables DDMut-PPI to achieve a robust Pearson correlation of up to 0.75 (root mean squared error: 1.33 kcal/mol) in our evaluations, outperforming most existing methods. Importantly, the model demonstrated consistent performance across mutations that increase or decrease binding affinity. DDMut-PPI offers a significant advancement in the field and will serve as a valuable tool for researchers probing the complexities of protein interactions. DDMut-PPI is freely available as a web server and an application programming interface at https://biosig.lab.uq.edu.au/ddmut_ppi.
CASTpFold: Computed Atlas of Surface Topography of the universe of protein Folds
Authors: Ye Bowei , Tian Wei , Wang Boshen , Liang Jie 
Published: May 2024

Abstract
Geometric and topological properties of protein structures, including surface pockets, interior cavities and cross channels, are of fundamental importance for proteins to carry out their functions. Computed Atlas of Surface Topography of proteins (CASTp) is a widely used web server for locating, delineating, and measuring these geometric and topological properties of protein structures. Recent developments in AI-based protein structure prediction such as AlphaFold2 (AF2) have significantly expanded our knowledge on protein structures. Here we present CASTpFold, a continuation of CASTp that provides accurate and comprehensive identifications and quantifications of protein topography. It now provides (i) results on an expanded database of proteins, including the Protein Data Bank (PDB) and non-singleton representative structures of AlphaFold2 structures, covering 183 million AF2 structures; (ii) functional pockets prediction with corresponding Gene Ontology (GO) terms or Enzyme Commission (EC) numbers for AF2-predicted structures and (iii) pocket similarity search function for surface and protein–protein interface pockets. The CASTpFold web server is freely accessible at https://cfold.bme.uic.edu/castpfold/.
A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match
Authors: Verheyden Nikita A , Klostermann Melina , Brüggemann Mirko , Steede Hanna M , Scholz Anica , Amr Shady , Lichtenthaeler Chiara , Münch Christian , Schmid Tobias , Zarnack Kathi , Krueger Andreas 
Published: May 2024

Abstract
MicroRNAs (miRNAs) are critical post-transcriptional regulators in many biological processes. They act by guiding RNA-induced silencing complexes to miRNA response elements (MREs) in target mRNAs, inducing translational inhibition and/or mRNA degradation. Functional MREs are expected to predominantly occur in the 3′ untranslated region and involve perfect base-pairing of the miRNA seed. Here, we generate a high-resolution map of miR-181a/b-1 (miR-181) MREs to define the targeting rules of miR-181 in developing murine T cells. By combining a multi-omics approach with computational high-resolution analyses, we uncover novel miR-181 targets and demonstrate that miR-181 acts predominantly through RNA destabilization. Importantly, we discover an alternative seed match and identify a distinct set of targets with repeat elements in the coding sequence which are targeted by miR-181 and mediate translational inhibition. In conclusion, deep profiling of MREs in primary cells is critical to expand physiologically relevant targetomes and establish context-dependent miRNA targeting rules.
The activity of CobB1 protein deacetylase contributes to nucleoid compaction in Streptomyces venezuelae spores by increasing HupS affinity for DNA
Authors: Duława-Kobeluszczyk Julia , Strzałka Agnieszka , Tracz Michał , Bartyńska Magdalena , Pawlikiewicz Katarzyna , Łebkowski Tomasz , Wróbel Sara , Szymczak Justyna , Zarek Anna , Małecki Tomasz , Jakimowicz Dagmara , Szafran Marcin J 
Published: May 2024

Abstract
Streptomyces are soil bacteria with complex life cycle. During sporulation Streptomyces linear chromosomes become highly compacted so that the genetic material fits within limited spore volume. The key players in this process are nucleoid-associated proteins (NAPs). Among them, HU (heat unstable) proteins are the most abundant NAPs in the cell and the most conserved in bacteria. HupS, one of the two HU homologues encoded by the Streptomyces genome, is the best-studied spore-associated NAP. In contrast to other HU homologues, HupS contains a long, C-terminal domain that is extremely rich in lysine repeats (LR domain) similar to eukaryotic histone H2B and mycobacterial HupB protein. Here, we have investigated, whether lysine residues in HupS are posttranslationally modified by reversible lysine acetylation. We have confirmed that Streptomyces venezuelae HupS is acetylated in vivo. We showed that HupS binding to DNA in vitro is controlled by the acetylation. Moreover, we identified that CobB1, one of two Sir2 homologues in Streptomyces, controls HupS acetylation levels in vivo. We demonstrate that the elimination of CobB1 increases HupS mobility, reduces chromosome compaction in spores, and affects spores maturation. Thus, our studies indicate that HupS acetylation affects its function by diminishing DNA binding and disturbing chromosome organization.
MinActionPath2: path generation between different conformations of large macromolecular assemblies by action minimization
Authors: Koehl Patrice , Navaza Rafael , Tekpinar Mustafa , Delarue Marc 
Published: May 2024

Abstract
Recent progress in solving macromolecular structures and assemblies by cryogenic electron microscopy techniques enables sampling of their conformations in different states that are relevant to their biological function. Knowing the transition path between these conformations would provide new avenues for drug discovery. While the experimental study of transition paths is intrinsically difficult, in-silico methods can be used to generate an initial guess for those paths. The Elastic Network Model (ENM), along with a coarse-grained representation (CG) of the structures are among the most popular models to explore such possible paths. Here we propose an update to our software platform MinActionPath that generates non-linear transition paths based on ENM and CG models, using action minimization to solve the equations of motion. The new website enables the study of large structures such as ribosomes or entire virus envelopes. It provides direct visualization of the trajectories along with quantitative analyses of their behaviors at http://dynstr.pasteur.fr/servers/minactionpath/minactionpath2_submission.
Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells
Authors: Cinar Munevver , Martinez-Medina Lourdes , Puvvula Pavan K , Arakelyan Arsen , Vardarajan Badri N , Anthony Neil , Nagaraju Ganji P , Park Dongkyoo , Feng Lei , Sheff Faith , Mosunjac Marina , Saxe Debra , Flygare Steven , Alese Olatunji B , Kaufman Jonathan L , Lonial Sagar , Sarmiento Juan M , Lossos Izidore S , Vertino Paula M , Lopez Jose A , El-Rayes Bassel , Bernal-Mizrachi Leon 
Published: May 2024

Abstract
The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.
Comparing the Fagerström Test and Heaviness of Smoking Index in Predicting Smoking Abstinence in Cancer Patients
Authors: Rodríguez-Cano Rubén , Kypriotakis George , Robinson Jason D , Karam-Hage Maher , Blalock Janice A , Minnix Jennifer A , Beneventi Diane , Cinciripini Paul M 
Published: May 2024

Abstract

Introduction
People with cancer who smoke exhibit greater cigarette dependence than people without cancer who smoke, a crucial factor in smoking cessation. Research is limited on the predictive potential of the Fagerström Test for Cigarette Dependence (FTCD) and the Heaviness of Smoking Index (HSI) on smoking abstinence in cancer patients undergoing smoking cessation treatment.

Aims and Methods
We analyzed data from 5934 cancer patients seeking smoking cessation treatment at The University of Texas MD Anderson Cancer Center (female 52.08%; Mean age = 55.52, SD = 11.17). We evaluated the predictive accuracy of FTCD and HSI on abstinence at 3, 6, and 9 months from the first consultation, and assessed the concordance between these tools in measuring cigarette dependence using Cohen’s kappa test and different correlation and regression models. We also analyzed variations across sex at birth and race/ethnicity.

Results
Both the FTCD and the HSI demonstrated comparable predictive accuracy for smoking cessation at all follow-ups, with neither showing high accuracy (Areas Under the Curve scores around 0.6). Concordance analysis revealed substantial agreement between FTCD and HSI scores (Cohen’s kappa ~ 0.7), particularly at lower levels of dependence. However, this agreement varied by race, with reduced concordance observed in non-Hispanic Blacks.

Conclusions
Our results indicate that both the FTCD and HSI are effective tools for predicting smoking cessation in cancer patients, with the HSI offering a less burdensome assessment option. Nevertheless, the findings suggest the need for tailored approaches in assessing cigarette dependence that could predict smoking cessation more accurately, considering racial differences.

Implications
The burden of assessing cigarette dependence in cancer care settings can be reduced by using the HSI instead of the FTCD. In addition, both instruments could be substantially interchanged and used for meta-analytic studies examining dependence and abstinence, but race/ethnicity should be considered.
A Review of the Toxicity of Ingredients in e-Cigarettes, Including Those Ingredients Having the FDA’s “Generally Recognized as Safe (GRAS)” Regulatory Status for Use in Food
Authors: Kassem Nada O F , Strongin Robert M , Stroup Andrea M , Brinkman Marielle C , El-Hellani Ahmad , Erythropel Hanno C , Etemadi Arash , Exil Vernat , Goniewicz Maciej L , Kassem Noura O , Klupinski Theodore P , Liles Sandy , Muthumalage Thivanka , Noël Alexandra , Peyton David H , Wang Qixin , Rahman Irfan , Valerio Luis G 
Published: May 2024

Abstract
Some firms and marketers of electronic cigarettes (e-cigarettes; a type of electronic nicotine delivery system (ENDS)) and refill liquids (e-liquids) have made claims about the safety of ingredients used in their products based on the term “GRAS or Generally Recognized As Safe” (GRAS). However, GRAS is a provision within the definition of a food additive under section 201(s) (21 U.S.C. 321(s)) of the U.S. Federal Food Drug and Cosmetic Act (FD&C Act). Food additives and GRAS substances are by the FD&C Act definition intended for use in food, thus safety is based on oral consumption; the term GRAS cannot serve as an indicator of the toxicity of e-cigarette ingredients when aerosolized and inhaled (ie, vaped). There is no legal or scientific support for labeling e-cigarette product ingredients as “GRAS.” This review discusses our concerns with the GRAS provision being applied to e-cigarette products and provides examples of chemical compounds that have been used as food ingredients but have been shown to lead to adverse health effects when inhaled. The review provides scientific insight into the toxicological evaluation of e-liquid ingredients and their aerosols to help determine the potential respiratory risks associated with their use in e-cigarettes.
Mechanistic Insights into the Function of 14-3-3 Proteins as Negative Regulators of Brassinosteroid Signaling in Arabidopsis
Authors: Obergfell Elsa , Hohmann Ulrich , Moretti Andrea , Chen Houming , Hothorn Michael 
Published: May 2024

Abstract
Brassinosteroids (BRs) are vital plant steroid hormones sensed at the cell surface by a membrane signaling complex comprising the receptor kinase BRI1 and a SERK family co-receptor kinase. Activation of this complex lead to dissociation of the inhibitor protein BKI1 from the receptor and to differential phosphorylation of BZR1/BES1 transcription factors by the glycogen synthase kinase 3 protein BIN2. Many phosphoproteins of the BR signaling pathway, including BRI1, SERKs, BKI1 and BZR1/BES1 can associate with 14-3-3 proteins. In this study, we use quantitative ligand binding assays to define the minimal 14-3-3 binding sites in the N-terminal lobe of the BRI1 kinase domain, in BKI1, and in BZR1 from Arabidopsis thaliana. All three motifs require to be phosphorylated to specifically bind 14-3-3s with mid- to low-micromolar affinity. BR signaling components display minimal isoform preference within the 14-3-3 non-ε subgroup. 14-3-3λ and 14-3-3 ω isoform complex crystal structures reveal that BKI1 and BZR1 bind as canonical type II 14-3-3 linear motifs. Disruption of key amino acids in the phosphopeptide binding site through mutation impairs the interaction of 14-3-3λ with all three linear motifs. Notably, quadruple loss-of-function mutants from the non-ε group exhibit gain-of-function BR signaling phenotypes, suggesting a role for 14-3-3 proteins as overall negative regulators of the BR pathway. Collectively, our work provides further mechanistic and genetic evidence for the regulatory role of 14-3-3 proteins at various stages of the BR signaling cascade.
An insertion in the promoter of a malate dehydrogenase gene regulates malic acid content in apple fruit
Authors: Gao Meng , Yang Nanxiang , Shao Yingli , Shen Tian , Li Wenxin , Ma Baiquan , Wei Xiaoyu , Ruan Yong-Ling , Ma Fengwang , Li Mingjun 
Published: May 2024

Abstract
Malic acid is an important flavor determinant in apple (Malus × domestica Borkh.) fruit. One known variation controlling malic acid is the A/G single nucleotide polymorphism in an aluminum-activated malate transporter gene (MdMa1). Nevertheless, there are still differences in malic acid content in apple varieties with the same Ma1 genotype (Ma1/Ma1 homozygous), such as ‘Honeycrisp’ (high malic acid content) and ‘Qinguan’ (low malic acid content), indicating that other loci may influence malic acid and fruit acidity. Here, the F1 (Filial 1) hybrid generation of ‘Honeycrisp’ × ‘Qinguan’ was used to analyze quantitative trait loci for malic acid content. A major locus (Ma7) was identified on chromosome 13. Within this locus, a malate dehydrogenase gene, MDH1 (MdMa7), was the best candidate for further study. Subcellular localization suggested that MdMa7 encodes a cytosolic protein. Overexpression and RNA interference of MdMa7 in apple fruit increased and decreased malic acid content, respectively. An insertion/deletion (indel) in the MdMa7 promoter was found to affect MdMa7 expression and malic acid content in both hybrids and other cultivated varieties. The insertion and deletion genotypes were designated as MA7 and ma7, respectively. The transcription factor MdbHLH74 was found to stimulate MdMa7 expression in the MA7 genotype but not in the ma7 genotype. Transient transformation of fruit showed that MdbHLH74 affected MdMa7 expression and malic acid content in ‘Gala’ (MA7/MA7) but not in ‘Fuji’ (ma7/ma7). Our results indicated that genetic variation in the MdMa7 (MDH1) promoter alters the binding ability of the transcription factor MdbHLH74, which alters MdMa7 (MDH1) transcription and the malic acid content in apple fruit, especially in Ma1/Ma1 homozygous accessions.
Cyclicity and Exponent of Elliptic Curves Modulo p in Arithmetic Progressions
Authors: Wong Peng-Jie 
Published: May 2024

Abstract
In this article, we study the cyclicity problem of elliptic curves $E/\mathbb{Q}$ modulo primes in a given arithmetic progression. We extend the recent work of Akbal and Güloğlu by proving an unconditional asymptotic for such a cyclicity problem over arithmetic progressions for elliptic curves E, which also presents a generalization of the previous works of Akbary, Cojocaru, M.R. Murty, V.K. Murty and Serre. In addition, we refine the conditional estimates of Akbal and Güloğlu, which gives log-power savings (for small moduli) and consequently improves the work of Cojocaru and M.R. Murty. Moreover, we study the average exponent of E modulo primes in a given arithmetic progression and obtain several conditional and unconditional estimates, extending the previous works of Freiberg, Kim, Kurlberg and Wu.