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Bibliometric quantification is frequently used as metrics for the evaluation of the scientific performance of researchers and institutions. The researchers' merit is usually assessed by the analysis of quantitative parameters such as the number of publications, the impact factor of journals, the total number of citations, or the h-index, although the limitations in translating these indicators into the impact of the outcome of scientific production are a matter of harsh criticism. To assess, based on factual evidences, the validity of traditional bibliometric analyses to conclude on the impact of papers to advance the state of the art, we carried out an innovative methodology on selected publications (test set). This methodology is based on identifying those citations of the test set papers that truly embed the methods, concepts, or hypotheses to build new knowledge and formulate conclusions. The results show that the percentage of citations that reflect the real impact of the papers of the test set has an average value of 12.4% of total citations and is not related to the impact factor of the journal where the test set papers were published. In conclusion, our analysis demonstrates factually, using experimental data, the total failure of using quantitative bulk citation analyses to conclude on the scientific impact of publications. Only a careful analysis of how the work described in papers was embedded on the subsequent work and/or conclusions of others can tell about the real contribution of a published work to the development of new knowledge and advancement of science., (© 2020 Federation of European Biochemical Societies.)

In the first instalment of the Words of Advice series, we feature the essentials of good manuscript writing with practical tips on how to plan, organise and write a standout scientific paper. [ABSTRACT FROM AUTHOR]

Methods and equations for analysing the kinetics of enzyme-catalysed reactions were developed at the beginning of the 20th century in two centres in particular; in Paris, by Victor Henri, and, in Berlin, by Leonor Michaelis and Maud Menten. Henri made a detailed analysis of the work in this area that had preceded him, and arrived at a correct equation for the initial rate of reaction. However, his approach was open to the important objection that he took no account of the hydrogen-ion concentration (a subject largely undeveloped in his time). In addition, although he wrote down an expression for the initial rate of reaction and described the hyperbolic form of its dependence on the substrate concentration, he did not appreciate the great advantages that would come from analysis in terms of initial rates rather than time courses. Michaelis and Menten not only placed Henri's analysis on a firm experimental foundation, but also defined the experimental protocol that remains standard today. Here, we review this development, and discuss other scientific contributions of these individuals. The three parts have different authors, as indicated, and do not necessarily agree on all details, in particular about the relative importance of the contributions of Michaelis and Menten on the one hand and of Henri on the other. Rather than force the review into an unrealistic consensus, we consider it appropriate to leave the disagreements visible., (© 2013 FEBS.)

The FEBS Journal, a leading multidisciplinary journal in the life sciences, publishes high‐impact papers on diverse topics relating to molecular mechanisms underpinning biological processes. Here, Editor‐in‐Chief Seamus Martin discusses the critical importance of data provenance and data integrity to the scientific method and discusses some of the highlights from 2021 at The FEBS Journal. [ABSTRACT FROM AUTHOR]

Hyaluronidase (E.C. 3.2.1.35), one of the three major allergens of yellow jacket venom, is a glycoprotein of 45 kDa that is largely responsible for the cross-reactivity of wasp and bee venoms with sera of allergic patients. The asparagine-linked carbohydrate often appears to constitute the common IgE-binding determinant. Using a combination of MALDI MS and HPLC of 2-aminopyridine-labelled glycans, we found core-difucosylated paucimannosidic glycans to be the major species in the 43–45 kDa band of Vespula vulgaris and also in the corresponding bands of venoms from five other wasp species ( V. germanica, V. maculifrons, V. pensylvanica, V. flavopilosa and V. squamosa). Concomitant peptide mapping of the V. vulgaris 43 kDa band identified the known hyaluronidase, Ves v 2 (SwissProt P49370), but only as a minor component. De novo sequencing by tandem MS revealed the predominating peptides to resemble a different, yet homologous, sequence. cDNA cloning retrieved a sequence with 58 and 59% homology to the previously known isoform and to the Dolichovespula maculata and Polistes annularis hyaluronidases. Close homologues of this new, putative hyaluronidase b (Ves v 2b) were also the major isoform in the other wasp venoms. [ABSTRACT FROM AUTHOR]

Metrics play a vital part in the valuation and funding of research for scientists worldwide. We review the challenges that metrics pose in providing a fair and equitable system for research funding. We highlight the attempts with declarations, including the San Francisco Declaration on Research Assessment (SF‐DORA), to improve the research environment and specific impacts that metric choice can have on the evaluation and progression of Early Career Lecturers (ECLs). While there is much evidence that metrics will never be entirely satisfactory, we conclude there are opportunities that would benefit ECLs and reason for optimism for researchers. [ABSTRACT FROM AUTHOR]

Wikipedia is a widely used online reference work which cites hundreds of thousands of scientific articles across its entries. The quality of these citations has not been previously measured, and such measurements have a bearing on the reliability and quality of the scientific portions of this reference work. Using a novel technique, a massive database of qualitatively described citations, and machine learning algorithms, we analyzed 1 923 575 Wikipedia articles which cited a total of 824 298 scientific articles in our database and found that most scientific articles cited by Wikipedia articles are uncited or untested by subsequent studies, and the remainder show a wide variability in contradicting or supporting evidence. Additionally, we analyzed 51 804 643 scientific articles from journals indexed in the Web of Science and found that similarly most were uncited or untested by subsequent studies, while the remainder show a wide variability in contradicting or supporting evidence. [ABSTRACT FROM AUTHOR]

One of the hottest topics in biomedical research is to decipher the functional implications of the Gasdermin (GSDM) protein family in human pathologies. These proteins are the key effectors of a lytic and pro‐inflammatory cell death type termed pyroptosis (also known as "Gasdermin‐mediated programmed cell death"). However, ever‐growing evidence showed that GSDMs can play multiple and complex roles in a context‐dependent manner. In this sense, Gasdermin‐B (GSDMB; the only GSDM gene absent in mice and rats) has been implicated in antibacterial defense, numerous inflammatory pathologies (e.g., asthma, ulcerative colitis), and cancer, but both cell death‐dependent and ‐independent functions have been reported in these diseases, fueling the debate on whether GSDMB has genuine pyroptotic capacity. Recently, a series of seminal papers cast light on the GSDMB multitasking capacity by showing that different GSDMB transcriptional isoforms have distinct biological activities. Nonetheless, there are still obscure areas to be clarified on the precise functional involvement of GSDMB translated variants in physiological and pathological conditions. In this viewpoint, we critically discuss the most recent and exciting data on this topic and propose a series of relevant challenges that need to be overcome before GSDMB‐driven biomedical applications (as a biomarker of disease risk/progression/outcome or as specific therapeutic target) become a reality in clinical settings. [ABSTRACT FROM AUTHOR]

Human metallothioneins (MTs) are involved in binding the essential elements, Cu(I) and Zn(II), and the toxic element, Cd(II), in metal‐thiolate clusters using 20 reduced cysteines. The brain‐specific MT3 binds a mixture of Cu(I) and Zn(II) in vivo. Its metallation properties are critically important because of potential connections between Cu, Zn and neurodegenerative diseases. We report that the use of isotopically pure 63Cu(I) and 68Zn(II) greatly enhances the element resolution in the ESI‐mass spectral data revealing species with differing Cu:Zn ratios but the same total number of metals. Room temperature phosphorescence and circular dichroism spectral data measured in parallel with ESI‐mass spectral data identified the presence of specific Cu(I)‐thiolate clusters in the presence of Zn(II). A series of Cu(I)‐thiolate clusters form following Cu(I) addition to apo MT3: the two main clusters that form are a Cu6 cluster in the β domain followed by a Cu4 cluster in the α domain. 63Cu(I) addition to 68Zn7‐MT3 results in multiple species, including clustered Cu5Zn5‐MT3 and Cu9Zn3‐MT3. We assign the domain location of the metals for Cu5Zn5‐MT3 as a Cu5Zn1‐β cluster and a Zn4‐α cluster and for Cu9Zn3‐MT3 as a Cu6‐β cluster and a Cu3Zn3‐α cluster. While many reports of the average MT3 metal content exist, determining the exact Cu,Zn stoichiometry has proven very difficult even with native ESI‐MS. The work in this paper solves the ambiguity introduced by the overlap of the naturally abundant Cu(I) and Zn(II) isotopes. Contrary to other reports, there is no indication of a major fraction of Cu4‐β‐Znn‐α‐MT3 forming. [ABSTRACT FROM AUTHOR]

Single‐cell RNA sequencing (scRNA‐seq) is a technique that has proven to be a powerful tool for a wide range of fields and research studies. However, scRNA‐seq data analysis has been dominated by scientists highly trained in bioinformatics or those with extensive computational experience and understanding. Recently, this trend has begun to shift as more user‐friendly web‐based scRNA‐seq analysis tools have been developed that require little computational experience to use. However, barriers persist for nonbioinformaticians in using this technique. Complex, unfamiliar language and scarce comprehensive literature guidance to provide a framework for understanding scRNA‐seq analysis outputs are among the obstacles. This work introduces many popular web‐based tools for scRNA‐seq and provides a general overview of their user interfaces and features. Then, a comprehensive start‐to‐finish introductory scRNA‐seq analysis pipeline is described in detail, which aims to enable researchers to carry out scRNA‐seq analysis, regardless of computational experience. Companion video tutorials can be found at "EasyScRNAseqTutorials" on YouTube (https://www.youtube.com/@scrnaseqtutorials). However, as scRNA‐seq continues to penetrate new fields and expand in importance, there remains a need for more literature to help overcome barriers to its use by explaining further the highly complex and advanced analyses that are introduced within this paper. [ABSTRACT FROM AUTHOR]

The document is the issue information for Volume 291 Number 9 of the FEBS Journal, published in May 2024. It includes the editorial board members, guidelines for authors, and the scope of the journal. The journal focuses on publishing high-quality papers in the molecular life sciences and welcomes interdisciplinary research. The issue also includes state-of-the-art reviews, mini-reviews, commentaries, and original articles on various topics in biochemistry, molecular biology, and other related fields. [Extracted from the article]

John F. Cryan is Chair of the Department of Anatomy and Neuroscience, Principal Investigator in the APC Microbiome Ireland Institute and Vice President for Research and Innovation at University College of Cork, Ireland. He obtained his bachelor's and doctoral degrees (in Biochemistry and Pharmacology, respectively) from the University of Galway and undertook postdoctoral research experience in the USA, at the University of Pennsylvania and The Scripps Research Institute. He was also a visiting fellow at the Department of Psychiatry, University of Melbourne, for a couple of years post‐PhD. In 2002, John took up a position in industry as a laboratory head at the Novartis Institutes for BioMedical Research in Basel, Switzerland. After a 4‐year stint at Novartis, he returned to academia in late 2005 as a Lecturer and then Senior Lecturer in Pharmacology at University College Cork (UCC). The Cryan lab now focuses on determining the impact of the gut microbiota on the human brain and behaviour, with a particular interest in the brain–gut–microbiome axis in the context of depression. John has published more than 600 peer‐reviewed papers and has received many honours and accolades in recognition of his contributions to neuropharmacology and microbiome research, including the Datta lecture award from FEBS in 2022. In this interview, he outlines how he became interested in the role of the microbiome in brain development and disease, provides advice to budding scientists and highlights the broader public health implications of his research. [ABSTRACT FROM AUTHOR]

In this special interview series, we profile members of TheFEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Eli Arama is an Associate Professor at the Weizmann Institute of Science in Rehovot, Israel. He has served as an editorial board member of TheFEBS Journal since 2018. [ABSTRACT FROM AUTHOR]

B Cover Illustration b Dissected trachea from hypoxia-treated wild-type (blue) and LUBEL-mutant (white) I Drosophila i larvae. M1-ubiquitination is induced in response to hypoxia in wild-type flies. Read the paper by Annika Meinander and co-authors in this issue (pages 5180-5197). [Extracted from the article]

Protein coding mutations in leucine‐rich repeat kinase 2 (LRRK2) cause familial Parkinson's disease (PD), and noncoding variations around the gene increase the risk of developing sporadic PD. It is generally accepted that pathogenic LRRK2 mutations increase LRRK2 kinase activity, resulting in a toxic hyperactive protein that is inferred to lead to the PD phenotype. LRRK2 has long been linked to different membrane trafficking events, but the specific role of LRRK2 in these events has been difficult to resolve. Recently, several papers have reported the activation and translocation of LRRK2 to cellular organelles under specific conditions, which suggests that LRRK2 may influence intracellular membrane trafficking. Here, we review what is known about the role of LRRK2 at various organelle compartments. [ABSTRACT FROM AUTHOR]

In this last issue of 2017, we're celebrating the 50th anniversary of The FEBS Journal. This Editorial considers how the journal has grown and changed from volume 1, issue 1 and outlines our exciting plans for the future. [ABSTRACT FROM AUTHOR]

Andrew Wyllie was a key figure in the discovery of the programmed cell death process termed apoptosis. He pioneered the study of apoptosis when this was a little‐known phenomenon and discovered the first biochemical marker of the process, internucleosomal DNA degradation. Andrew recently passed away, aged 78, but leaves a legacy of scientific achievement that opened up a new field of research. [ABSTRACT FROM AUTHOR]

Auxiliary sections that support the reader's understanding of the review, such as keywords and glossaries, are also useful to include, and author contributions and any conflicts of interest should be clearly outlined, usually in dedicated sections of the review. This shouldn't preclude early career researchers from writing review articles, with the mentorship of experienced colleagues - gaining experience in writing review articles early on in your career is a great way to hone your analytical and writing skills. Literature reviews are valuable resources for the scientific community. The advice given here is mostly relevant for the writing of a traditional literature-based review rather than other forms of review such as a systematic review or meta-analysis, which have their own criteria and guidelines [2,3]. [Extracted from the article]

The FEBS Journal publishes high impact research on diverse topics in the life sciences, with a focus on molecular mechanisms underpinning biological processes. Here, Editor‐in‐Chief Seamus Martin discusses highlights of the journal from the past year and gives a glimpse into what's in store for 2023. [ABSTRACT FROM AUTHOR]

Previous studies have shown that high physiological levels of reactive oxygen species (ROS) in the brain promote pupal diapause, which extends the pupal lifespan. However, the molecular mechanisms of ROS generation are unclear. In this paper, we found that mitochondrial ROS (mtROS) levels in the brains of Helicoverpa armigera diapause‐destined pupae (DP) were higher and that the expression of cytochrome oxidase subunit IV (COXIV) was lower than in NP. In addition, downregulating COXIV caused mitochondrial dysfunction which elevated mtROS levels. Protein kinase A (PKA) was downregulated in DP, which led to the downregulated expression of the mitochondrial transcription factor TFAM. Low TFAM activity failed to promote COXIV expression and resulted in the high ROS levels that induced diapause. In addition, low sirtuin 2 expression suppressed glucose‐6‐phosphate dehydrogenase (G6PD) deacetylation at K382, which led to reduced G6PD activity and low NADPH levels, thereby maintaining high levels of ROS. Two proteins, COXIV and G6PD, thus play key roles in the elevated accumulation of ROS that induce diapause and extend the pupal lifespan. [ABSTRACT FROM AUTHOR]

The scientific literature contains a tremendous amount of kinetic data describing the dynamic behaviour of biochemical reactions over time. These data are needed for computational modelling to create models of biochemical reaction networks and to obtain a better understanding of the processes in living cells. To extract the knowledge from the literature, biocurators are required to understand a paper and interpret the data. For modellers, as well as experimentalists, this process is very time consuming because the information is distributed across the publication and, in most cases, is insufficiently structured and often described without standard terminology. In recent years, biological databases for different data types have been developed. The advantages of these databases lie in their unified structure, searchability and the potential for augmented analysis by software, which supports the modelling process. We have developed the SABIO- RK database for biochemical reaction kinetics. In the present review, we describe the challenges for database developers and curators, beginning with an analysis of relevant publications up to the export of database information in a standardized format. The aim of the present review is to draw the experimentalist's attention to the problem (from a data integration point of view) of incompletely and imprecisely written publications. We describe how to lower the barrier to curators and improve this situation. At the same time, we are aware that curating experimental data takes time. There is a community concerned with making the task of publishing data with the proper structure and annotation to ontologies much easier. In this respect, we highlight some useful initiatives and tools. [ABSTRACT FROM AUTHOR]

The paper that introduced biochemists to the idea of allosteric feedback inhibition [Monod J, Changeux J-P & Jacob F (1963) J Mol Biol 6, 306-329] is now 50 years old, and the two papers on models for enzyme cooperativity that followed it [Monod J, Wyman J & Changeux J-P (1965) J Mol Biol 12, 88-118; Koshland DE, Némethy G & Filmer D (1966) Biochemistry 5, 365-385] are almost as old. All of these papers continue to be heavily cited today - more in the 21st century than they were in the last two decades of the 20th. This is because they continue to be central for understanding enzyme regulation, and increasingly important in the age of systems biology. [ABSTRACT FROM AUTHOR]

The paper 'A C‐Terminal Fragment of Adhesion Protein Fibulin‐7 Inhibits Growth of Murine Breast Tumor by Regulating Macrophage Reprogramming' by Chakraborty et al. highlights that Fbln7‐C could be explored as a potential immunomodulatory agent against various solid cancers and have shown its abilities to regulate tumor microenvironment reprogramming of TAMs in a breast cancer model. Fbln7, which is a secreted glycoprotein, has been shown to be anti‐angiogenic and has an immunomodulatory role regulating various functional properties of monocytes, macrophages, and neutrophils, thereby influencing inflammation. In this study, the authors have shown that in a murine breast tumor model, intravenous administration of Fbln7‐C significantly reduces the size of tumors via macrophage reprogramming. Comment on: https://doi.org/10.1111/febs.15333. [ABSTRACT FROM AUTHOR]

Protein–protein interactions are key in mycobacterial physiology, notably during the biosynthesis of the very peculiar mycobacterial cell wall. In this paper, we demonstrate that MSMEG_1285 interacts with PonA1, a bifunctional penicillin‐binding protein involved in peptidoglycan biosynthesis. Deletion of MSMEG_1285 enhances Mycobacterium smegmatis resistance to penicillin antibiotics, a phenotype that is exacerbated by the additional deletion of hbhA. This also led to a substantial decrease in the amounts of porins in the cell wall, which are necessary for the import of small and hydrophilic β‐lactams. Deletion of both MSMEG_1285 and hbhA provoked an over‐representation of several enzymes involved in peptidoglycan degradation. Thus, we propose that MSMEG_1285 is part of a protein scaffold, which also involves PonA1 and HbhA, and that it is responsible for the tight regulation of peptidoglycan hydrolysis. This study provides a better understanding of the mycobacterial physiology, which is an essential step for strengthening the action of drugs that specifically target peptidoglycan biosynthesis. [ABSTRACT FROM AUTHOR]

Seriously flawed and even fictional models of biomolecular crystal structures, although rare, still persist in the record of structural repositories and databases. The ensuing problems of database contamination and persistence of publications based on incorrect structure models must be effectively addressed. The burden cannot be simply left to the critical voices who take the effort to contribute dissenting comments that are mostly ignored. The entire structural biology community, and particularly the journal editors who exercise significant power in this respect, must engage in a constructive dialog lest structural biology lose its credibility as an evidence-based empirical science. [ABSTRACT FROM AUTHOR]

Heatmap of differentially expressed genes between cetuximab‐resistant and cetuximab‐sensitive patients; image adapted from the Regular Paper by Kwang‐Hyun Cho and co‐authors (pp. 1305–1318). [ABSTRACT FROM AUTHOR]

Inhibiting necroptosis in IL‐33‐dependent allergic airway inflammation – anti‐necroptosis treated (left) vs untreated (right) lung; see the related research paper here (pp. 507–522). Image provided by Motti Gerlic. [ABSTRACT FROM AUTHOR]

In an accompanying paper [du Preez et al., (2012) FEBS J 279, 2810-2822], we adapt an existing kinetic model for steady-state yeast glycolysis to simulate limit-cycle oscillations. Here we validate the model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out-of-phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose- and acetaldehyde-driven forced oscillations, glucose and acetaldehyde quenching, and cell-free extract oscillations (including complex oscillations and mixed-mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets. Database The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at . [ABSTRACT FROM AUTHOR]

The clinical efficacy of sulfa drugs as antimalarials has declined owing to the evolution of resistance in Plasmodium falciparum (Pf) malaria parasites. In order to understand the basis of this resistance and to design more effective antimalarials, we have solved 13 structures of the bifunctional enzyme 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphokinase (HPPK)–dihydropteroate synthase (DHPS) from wild‐type (WT) P. falciparum and sulfa‐resistant mutants, both as apoenzyme and as complexes with pteroate (PTA) and sulfa derivatives. The structures of these complexes show that PTA, which effectively inhibits both the WT and mutants, stays in active sites without steric constraint. In contrast, parts of the sulfa compounds situated outside of the substrate envelope are in the vicinity of the resistance mutations. Steric conflict between compound and mutant residue along with increased flexibility of loop D2 in the mutants can account for the reduced compound binding affinity to the mutants. Kinetic data show that the mutants have enhanced enzyme activity compared with the WT. These PfDHPS structural insights are critical for the design of novel, substrate envelope–compliant DHPS inhibitors that are less vulnerable to resistance mutations. Databases: The data reported in this paper have been deposited in the Protein Data Bank, www.wwpdb.org. PDB ID codes: 6JWQ for apoWT; 6JWR, 6JWS, and 6JWT for PTA complexes of WT, A437G (3D7), and V1/S; 6JWU, 6JWV, and 6JWW for STZ‐DHP complexes of WT, 3D7, and V1/S; 6JWX, 6JWY, and 6JWZ for SDX‐DHP complexes of WT, 3D7, and W2; 6KCK, 6KCL, and 6KCM for Pterin/pHBA complexes of WT, TN1, and W2. [ABSTRACT FROM AUTHOR]

Crystallographic models of biological macromolecules have been ranked using the quality criteria associated with them in the Protein Data Bank (PDB). The outcomes of this quality analysis have been correlated with time and with the journals that published papers based on those models. The results show that the overall quality of PDB structures has substantially improved over the last ten years, but this period of progress was preceded by several years of stagnation or even depression. Moreover, the study shows that the historically observed negative correlation between journal impact and the quality of structural models presented therein seems to disappear as time progresses. [ABSTRACT FROM AUTHOR]

The paper 'Interaction of N‐acetyl‐l‐glutamate kinase with the PII signal transducer in the non‐photosynthetic alga Polytomella parva: Co‐evolution towards a hetero‐oligomeric enzyme' by Selim et al. highlights how the study of a true taxonomic oddity, the heterotrophic unicellular alga P. parva, has been instrumental in uncovering the large potential for adaptive variation in the signaling complex of PII with the enzyme N‐acetylglutamate kinase (NAGK). This complex modifies the regulatory properties of NAGK, allowing nitrogen stockpiling as arginine. In P. parva, a stable PII‐NAGK complex is formed which lacks regulation by canonical PII effectors but which exhibits novel adaptive responses to nitrogen abundance mediated by glutamine, a neo‐effector of PII proteins of photosynthetic eukaryotes. [ABSTRACT FROM AUTHOR]

Neutrophil activity, including trapping of damage‐associated molecular patterns by neutrophil extracellular traps (NETs), is an important response to microbial infection. Most activated neutrophils commit to apoptosis and are removed by activated macrophages in the process of efferocytosis. Improper clearance of apoptotic neutrophils often causes an unnecessary and exaggerated immune response and subsequent chronic inflammation. Effective macrophage mobility toward activated neutrophils, which is triggered by binding of 'find‐me' signals to receptors such as P2Y2, is a crucial step for the timely clearance of apoptotic neutrophils. In this paper, we investigated the effect of 1‐palmitoyl‐2‐linoleoyl‐3‐acetyl‐rac‐glycerol (PLAG) on efferocytosis and the underlying molecular mechanisms. In a coculture of apoptotic neutrophils with macrophages, PLAG treatment increased levels of efferocytosis of apoptotic neutrophils. PLAG induced faster translocation of P2Y2 from lipid rafts to nonlipid raft plasma membrane domains in macrophages. This repositioning of P2Y2 enables the polarization of the cytoskeleton by association of the receptor with cytoskeletal proteins such as α‐tubulin and actin to improve the mobility of macrophages. The formation of vesicular, chylomicron‐like structures by PLAG was a prerequisite for the induction of this macrophage activity, as none of these effects was seen when the vesicle receptor GPIHBP1 was absent. Taken together, these data showed that PLAG is a powerful immune resolvent that triggers the prompt clearance of apoptotic neutrophils by enhanced efferocytosis activity. PLAG could therefore be an effective lipid‐based efferocytosis enhancer for use as a therapeutic drug to prevent inflammatory disease caused by uncontrolled immune responses. [ABSTRACT FROM AUTHOR]

Horizontal gene transfer (HGT) is widespread among prokaryotes driving their evolution. In this paper, we review the potential impact in humans of the HGT between prokaryotes living in close association with humans in two scenarios: horizontal transfer in human microbiomes and transfer between microbes living in human managed environments. Although our vision is focused on the possible impact of these transfers in the propagation of antibiotic resistance genes or pathogenicity determinants, we also discuss possible human physiological adaptations via gene transfer between resident and occasional bacteria in the human microbiome. [ABSTRACT FROM AUTHOR]

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research and perspectives on the journal and more. Albert Heck is Professor of Chemistry and Pharmaceutical Sciences at Utrecht University, Scientific Director of the Netherlands Proteomics Center, and Head of the Biomolecular Mass Spectrometry and Proteomics group in Utrecht University since September 1998. He has served as Editorial Board Member of The FEBS Journal since 2020. [ABSTRACT FROM AUTHOR]

The past 12 months have seen a number of new developments at The FEBS Journal, including our State‐of‐the‐Art Review series. The FEBS Journal continues to grow in visibility and impact and is one of the leading journals in its class. Why not become one of our authors in 2015 by submitting your next paper to The FEBS Journal. [ABSTRACT FROM AUTHOR]

The recently described clustered regularly interspaced short palindromic repeats ( CRISPR)/Cas9 technology has proven to be an exquisitely powerful and invaluable method of genetic manipulation and/or modification. As such, many researchers have realized the potential of using the CRISPR/Cas9 system as a novel screening method for the identification of important proteins in biological processes and have designed short guide RNA libraries for an in vitro screening. The seminal papers describing these libraries offer valuable information regarding methods for generating the short guide RNA libraries, creating cell lines containing these libraries, and specific details regarding the screening workflow. However, certain considerations are often overlooked that may be important when planning and performing a screen, including which CRISPR library to use and how to best analyze the resulting screen data. In this review, we offer suggestions to answer some of these questions that are not covered as deeply in the papers describing the available CRISPR libraries for an in vitro screening. [ABSTRACT FROM AUTHOR]

Cyclotides are plant-derived, cyclic miniproteins with three interlocking disulfide bonds that have attracted great interests because of their excellent stability and potential as peptide therapeutics. In this study, we characterize the cyclotides of the medicinal plant Clitoria ternatea (butterfly pea) and investigate their biological activities. Using a combined proteomic and transcriptomic method, we identified 41 novel cyclotide sequences, which we named cliotides, making C. ternatea one of the richest cyclotide-producing plants to date. Selected members of the cationic cliotides display potent antibacterial activity specifically against Gram-negative bacteria with minimal inhibitory concentrations as low as 0.5 μ m. Remarkably, they also possess prominent immunostimulating activity. At a concentration of 1 μ m, cationic cliotides are capable of augmenting the secretion of various cytokines and chemokines in human monocytes at both resting and lipopolysaccharide-stimulated states. Chemokines such as macrophage inflammatory proteins 1α and 1β, interferon γ-induced protein 10, interleukin 8 and tumor necrosis factor α were among the most upregulated with up to 129-fold increase in secretion level. These findings suggest cyclotides can serve as potential candidates for novel immunomodulating therapeutics. Database The protein sequences reported in this paper (cT13-cT21) are available in the UniProt Knowledgebase under the accession numbers , , , , , , , and , respectively. The transcriptome data in this paper are available at the Sequence Read Archive database ( NCBI) under accession number . The protein precursors reported in this paper (ctc13, ctc15, ctc17-ctc19, ctc21-ctc53) are available at GenBank under the accession numbers , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , and , respectively. [ABSTRACT FROM AUTHOR]

The motto of this Virtual Issue of The FEBS Journal is a paraphrase of the statement made in 1897 by Mark Twain, which is usually quoted as 'Reports of my death have been greatly exaggerated'. With the incredible progress in the utilization of cryo‐EM for the determination of high‐resolution macromolecular structures that led to the award of the Nobel Prize in Chemistry to Jacques Dubochet, Joachim Frank, and Richard Henderson in 2017, it became a common assumption that crystallography was dead. However, as this Virtual Issue should show very clearly, that is emphatically not the case. To put the current relative importance of different technologies of determination of macromolecular structures into perspective, 78% of structures deposited in the Protein Data Bank since January 2020 were still determined by X‐ray crystallography. The reasons why that is the case will be clear after reading the papers gathered here. [ABSTRACT FROM AUTHOR]

As FEBS celebrates its 50th anniversary, it also marks the launch 3 years ago of its newest journal, FEBS Open Bio. This online‐only open access journal is now indexed in Web of Science. Papers originally submitted to The FEBS Journal can be transferred to FEBS Open Bio together with any reviewer reports, offering authors a fast‐track alternative for publication of their work. [ABSTRACT FROM AUTHOR]

B Cover Illustration b Mechanisms of NET formation and how they relate to other cell death pathways, reviewed by Gabriel Sollberger and co-authors. [Extracted from the article]

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Rudi Beyaert is Full Professor in Molecular Biology at the Department of Biomedical Molecular Biology, Faculty of Sciences, of the University of Ghent (Belgium). He also serves as Vice‐Science Director of the Center for Inflammation Research of the VIB in Ghent, where he is heading the Unit of Molecular Signal Transduction in Inflammation. He has served as an Editorial Board Member of The FEBS Journal since 2016. [ABSTRACT FROM AUTHOR]

Mounting evidence points to increased rates of cardiovascular disease (CVD) among people living with HIV/AIDS (PLWHA). Endothelial dysfunction (loss of endothelium‐dependent vascular relaxation in response to provasodilatory stimuli) constitutes an early pathophysiological event in atherogenesis and CVD. Both HIV‐1 infection and antiretroviral therapy (ART) are implicated in the development of endothelial dysfunction; however, conclusions are frequently drawn from associations shown in epidemiological studies. In this narrative review of mainly in vitro and animal studies, we report on the current understanding of how various HIV‐1 proteins, HIV‐1‐induced proinflammatory cytokines and common antiretroviral drugs directly impact vascular endothelial cells. Proposed cellular mechanisms underlying the switch to a dysfunctional state are discussed, including oxidative stress, impaired expression and regulation of endothelial nitric oxide (NO) synthase (eNOS) and increased expression of vascular adhesion molecules. From the literature, it appears that increased reactive oxygen species (ROS) production, linked to decreased NO bioavailability and ensuing endothelial dysfunction, may be proposed as a putative final common pathway afflicting the vascular endothelium in PLWHA. The HIV‐1‐proteins Tat, Gp120 and Nef in particular, the proinflammatory cytokine, TNF‐α, and the antiretroviral drugs Efavirenz and Lopinavir, most commonly postulated to be primary causal agents of endothelial dysfunction, are also discussed. We conclude that, despite existing evidence from basic research papers, a significant gap remains in terms of the exact underlying cellular mechanisms involved in HIV‐1 and ART induced endothelial dysfunction. Bridging this gap could help pave the way for future strategies to prevent and treat early cardiovascular changes in PLWHA. Endothelial dysfunction is considered an early pathophysiological event in the development of cardiovascular disease, increased rates of which have been observed among people living with HIV/AIDS. HIV‐1 proteins, HIV‐1‐induced proinflammatory cytokines and common antiretroviral drugs have all been linked to endothelial dysfunction, with increased reactive oxygen species production and consequent reduced nitric oxide (NO) bioavailability emerging as the common link. [ABSTRACT FROM AUTHOR]

In this Editorial, Editor‐in‐Chief Seamus Martin reviews developments over the past year at The FEBS Journal and highlights some ongoing challenges in the current landscape of scientific publishing. [ABSTRACT FROM AUTHOR]

In the present paper, the biological effects of three different naphthalene diimides (NDIs) G‐quadruplex (G4) ligands (H‐NDI‐Tyr, H‐NDI‐NMe2, and tetra‐NDI‐NMe2) were comparatively evaluated to those exerted by RHPS4, a well‐characterized telomeric G4‐ligand, in an in vitro model of glioblastoma. Data indicated that NDIs were very effective in blocking cell proliferation at nanomolar concentrations, although displaying a lower specificity for telomere targeting compared to RHPS4. In addition, differently from RHPS4, NDIs failed to enhance the effect of ionizing radiation, thus suggesting that additional targets other than telomeres could be involved in the strong NDI‐mediated anti‐proliferative effects. In order to test telomeric off‐target action of NDIs, a panel of genes involved in tumor progression, DNA repair, telomere maintenance, and cell‐cycle regulation were evaluated at transcriptional and translational level. Specifically, the compounds were able to cause a marked reduction of TERT and BCL2 amounts as well as to favor the accumulation of proteins involved in cell cycle control. A detailed cytofluorimetric analysis of cell cycle progression by means of bromodeoxyuridine (BrdU) incorporation and staining of phospho‐histone H3 indicated that NDIs greatly reduce the progression through S‐phase and lead to G1 accumulation of BrdU‐positive cells. Taken together, these data indicated that, besides effects on telomeres and oncogenes such as Tert and Bcl2, nanomolar concentrations of NDIs determined a sustained block of cell proliferation by slowing down cell cycle progression during S‐phase. In conclusion, our data indicate that NDIs G4‐ligands are powerful antiproliferative agents, which act through mechanisms that ultimately lead to altered cell‐cycle control. The effect of different telomeric G‐quadruplex (G4) ligands (three naphthalene diimides (NDIs) derivatives and RHPS4), were comparatively evaluated in radio‐resistant U251MG glioblastoma cells. Although displaying a lower than RHPS4 specificity for telomeric G4 and absence of radio‐sensitization potential, NDIs were very effective in blocking cell proliferation through the deregulation of proteins involved in cell‐cycle control and the slow‐down of cell‐cycle progression through the S phase. [ABSTRACT FROM AUTHOR]