- Last updated:
- 18 August 2016
- Last updated:
- 1 January 2016
The FEBS Journal is pleased to present this Virtual Issue of reviews and original articles specially selected from our 2015 pages. This collection showcases the journal's broad scope, highlighting the cutting-edge research and timely, authoritative review articles published in the past year. We are grateful to our authors, reviewers and editorial board members for their contributions, and to our readership for their interest in these pieces.
- Last updated:
- 31 March 2015
An editorial by Seamus Martin, Editor-in-Chief of The FEBS Journal, on the highlights of articles published by The FEBS Journal in 2014 can be read here.
- Last updated:
- 1 November 2013
The term “epigenetics” was coined by Conrad Waddington in the 1940s, to describe the causal mechanisms of development from the fertilized egg to adult. Epigenetics is now used to refer to heritable chromatin modifications that control gene expression without changes in DNA sequence. The study of epigenetics, building on genomics and molecular biology, holds great promise in understanding the normal and diseased state of life.
Distinct epigenetic processes include chemical modifications of DNA or DNA-associated proteins, such as histones. Methylation of DNA, histone modifications and higher-order chromatin structure are central to the regulation of mammalian genome organization. The combination of epigenetic modifications in a genome comprises the epigenome, which adds an extra layer of supervision and complexity to the genome of a cell by altering, revising and rewriting the genomic language written in the DNA sequence. Epigenetic modifications (epigenetic marks) are critical for cell development and specialization during embryogenesis as well as for normal processes such as X-chromosome inactivation in female mammals. They are transmitted transgenerationally, but the epigenetic state of cells can also be altered by environmental stresses and by physiological aging.
The relevance of epigenetic alterations in the initiation and progression of cancer and other pathologies is increasingly being acknowledged. In response to changes in the external environment, chromatin and chromosomes experience profound and dynamic organizational modifications. During the division of a cell, chromosomes condense and relax. Damaged DNA acquires a particular conformation that assists its repair. Central for the functionality of the cell, a significant part of the genome must be maintained in a repressed state, which differs between distinct cell types. Conversely, other genes need to be maintained in a transcriptionally active state. These repressive/activating epigenetic processes are finely controlled to preserve the genome’s integrity and the relevant cell function. The epigenetic signature of any cell reveals key insights into its cellular state and fitness. Increasing our understanding of the epigenome will greatly enlarge our knowledge of health and disease.
Currently, the field of epigenetics is transiting through a documentation phase, a common characteristic of a branch of science that is evolving rapidly. Despite great advancement in recent years, we still do not really understand how the genome and epigenome interact and how this interaction confers plasticity and adaptability to a cell. It is still not clear whether specific epigenetic modifications can be classified as adaptive or adverse. Given the effort devoted to epigenetics research, these areas of ignorance will hopefully be clarified in the near future.
This Virtual Issue comprises a collection of research papers and reviews recently published in the FEBS Journal on the influence of chromatin and chromosome organization on gene expression and the roles of epigenetic mechanisms in development and disease.
- Last updated:
- 1 August 2013
MicroRNAs (miRNAs) were discovered in the early 1990s in Caenorhabditiselegans and about a decade later their expression in mammals was reported. The literature on miRNA function has since grown exponentially and miRNAs have been implicated as gene regulators in all cellular pathways. Subsequently, miRNAs were found to be mis-regulated in many different diseases including almost all forms of cancer. Today, miRNAs are viewed as fundamental gene regulators embedded into large regulatory networks. Imbalance within such networks leads to cellular malfunctions and to the development of diseases.
miRNAs derive from specific genes, miRNA gene clusters containing more than one miRNA gene or intronic sequences. They are transcribed as primary miRNA transcripts (pri-miRNAs), which are processed by the RNase III enzyme Drosha to stem-loop-structured miRNA precursors (pre-miRNAs). Pre-miRNAs are transported to the cytoplasm, where Dicer, another RNase III enzyme, cleaves off the loop of the pre-miRNA and generates a double-stranded RNA of 18-23 nucleotides. This short-lived intermediate is unwound and one strand is incorporated into the RNA-induced silencing complex (RISC). The other strand, (often referred to as miRNA*), is typically degraded from the cell. In rare cases, however, both strands can give rise to functional miRNAs. Within RISC, the miRNA interacts with a member of the Argonaute (Ago) protein family. miRNAs function as guides for RISC and identify and bind partially complementary sequences typically located in the 3’ untranslated region (UTR) of target mRNAs. As soon as the RISC complex reaches the mRNA, Ago proteins interact with a member of the Glycine-tryptophan repeat (GW) protein family, which mediates all following downstream silencing events. As a consequence, enzymes that remove the poly(A) tail are recruited to the mRNA. Removed poly(A) tails lead to mRNA decapping and subsequent mRNA decay.
In parallel, miRNAs can also affect translation, without reducing mRNA levels. It is believed that one specific miRNA can regulate multiple mRNAs simultaneously. Estimations range from 10 to more than 100 targets per individual miRNA, suggesting that a large portion of the mRNA population is regulated by miRNAs. In cancer, miRNAs can promote or inhibit cancer progression, depending on the targets they regulate. Many such examples have been reported during the last few years and interfering with such miRNAs might develop into a novel strategy for cancer therapy. This virtual issue comprises a collection of papers recently published in the FEBS Journal on specific roles of miRNAs in different forms of cancer, in stem cell biology, in neuronal function or in adipogenesis. Also included are several publications that identified important mechanistical aspects of miRNA function and two review articles that discuss the fundamental roles of miRNAs in fibrosis and epigenetics.
- Last updated:
- 1 March 2013
Systems biology aims at the understanding of complex cellular networks as a whole. For this purpose, one has to examine the interplay of various components, resulting in a quantitative and dynamic picture of the processes occurring in a living cell. This is almost impossible without the aid of computational methods, particularly modeling, which are therefore core ingredients in all systems biology research. This computational approach is particularly successful in biochemistry. Many computational methods that are commonly used in systems biology originate from the study of metabolic pathways and are now applied to signal transduction systems and genetic networks. Thus, it is not surprising that FEBS Journal, with a long tradition of publishing biochemical research papers, was an early supporter of the emerging field of systems biology.
Over the years, many original articles and reviews of systems biology have been published in FEBS Journal. Last year, in conjunction with the International Conference on Systems Biology 2011 – the largest systems biology conference so far – FEBS Journal published a Special Issue of systems biology papers resulting from the advanced studies reported at this conference.
This Virtual Issue contains a variety of systems biology papers, with special emphasis on those published in 2011 and 2012. Many of the selected studies exemplify the successful integration of quantitative experimentation and computational modeling applied to systems as diverse as signalling pathways and metabolic networks, cell division and growth. In addition, advances in methodology – both experimental and computational – are highlighted in some articles. These research articles are complemented by a series of reviews which either survey specific research topics or provide a general overview of the field. We hope the Virtual Issue will encourage authors to submit high quality original papers and reviews in systems biology to FEBS Journal.
- Last updated:
- 1 December 2012
It is impossible to imagine a biochemistry journal that would not devote a significant fraction of its pages to description of macromolecular structures and, indeed, many non-structural papers also rely very much on the availability of structural data. That has not always been the case – after all, protein crystallography is just over 50 years old, it has been less than 35 years since the first protein structure was determined by NMR, and high-resolution electron microscopy applications are even more recent. However, the number of macromolecular structures deposited in the Protein Data Bank (PDB) now approaches 90,000 and other repositories contain structures obtained by NMR, electron microscopy, or molecular modelling.
FEBS Journal has been traditionally publishing many structural papers and this Virtual Issue highlights the original work published here in 2012. As special anchors we present four reviews aimed at non-specialists that describe the main techniques used in the determination of high-resolution protein structures. A vast majority of the structures presented in the original articles were solved using molecular replacement with models based on related proteins. Although these structures may not be truly novel, they are often very important, since they can elucidate enzymatic properties through analysis of inhibitor binding, compare related proteins from several species with the aim of creating selective inhibitors, or explain the biophysical properties such as thermostability or cold adaptation. Such results are crucial in both enhancing our understanding of the ways protein fold and work, as well as in practical applications such as drug design.
Some structures published here are still solved from scratch through the application of methods such as isomorphous replacement or anomalous scattering, and they represent proteins with less well studied folds. NMR was used for the determination of novel structures, for investigation of dynamic properties of macromolecules, and for elucidating intermolecular interactions. What is not shown in this Virtual Issue are many papers (actually, a fairly large fraction of all papers published in this journal) that contain figures showing protein structures that are used to interpret a variety of biological, biochemical, or biophysical data, although these papers do not report structural studies at all.
The fact that the availability of structural data is now taken completely for granted and that such structures are routinely used for interpretation of a wide range of phenomena testifies to the success of the last 50-odd years of the modern techniques of structure determination.
- Last updated:
- 1 May 2012
- Last updated:
- 1 February 2012
To some, carbohydrate modifications of proteins are an annoying nuisance that prevents functional recombinant protein expression or complicates normal protein purification and characterization. To others, the complex, branched stereospecific linkages of glycans are beautiful puzzles to decode and study their function. The field of glycobiology continues to expand at an ever increasing rate. My college biochemistry textbook written in 1990, although touting the great accomplishments of the field in the prior 20 years, could only give a few classic examples of glycoprotein modifications with known function such as the role of proteoglycans in cartilage, the protective role of mucins in epithelium, and antifreeze glycoproteins of arctic fishes. That 1990 textbook in fact indicated that the function of the carbohydrates moieties on most glycoproteins remained “enigmatic”.
While many questions still remain, carbohydrate modifications of proteins have begun to lose their “enigmatic” classification. With the decoding of the human genome and a number of genomes from other species in the last decade and the ever-expanding toolbox to study the chemistry of glycan moieties, the rich diversity of protein glycosylation, the function of the enzymes mediating these beautiful functional decorations on proteins, and the critical role glycosylation in normal biology and human disease is becoming increasingly evident. The identification of important human genetic diseases caused by abnormal glycosylation, such as the multi-syndrome Congenital Disorders of Glycosylation, several forms of muscular dystrophy, glycosaminoglycan diseases such as Ehlers-Danlos Syndrome and chondrodysplasias, and many others, have pointed to the critical role of glycosylation in human health and disease. Furthermore, while many membrane proteins utilize glycans to interact with their extracellular environment, many pathogenic organisms, such as influenza, hemorrhagic fever viruses, and bacteria causing leprosy, hijack these same interactions to gain entry into cells. The growing diverse list of the roles of glycans in important human diseases makes the study of their synthesis, structure, and impact on protein and cellular function critical to our understanding of pathogenic mechanisms.
Our journal’s submissions in the field of glycobiology have reflected this rich diversity, with papers ranging from the study of the roles of glycoproteins in human disease and cellular biology, to explaining how glycans affect the production of the smell of ripe tomatoes (Louveau et al FEBSJ 2011), and the function of hormones in stick bugs (Munte et al FEBSJ 2008). To fully capture this diversity of manuscripts in a single Virtual Issue is impossible. Therefore, this Issue highlights recent papers in the journal demonstrating:
1) how state-of-the-art high-throughput and high-sensitivity glycomic approaches are deciphering new glycomic profiles to shed light on biological mechanisms and pathomechanisms of disease.
2) the mechanisms of how important cellular and protein functions are directly mediated by post-translational protein glycosylation
3) the translation of these newly found mechanisms toward novel “glyco- therapies” for treating important human diseases
- Last updated:
- 1 August 2011
Immunology is the study of the immune system, and the mechanisms by which it cultivates our vast internal populations of commensal organisms while eliminating the occasional invading pathogen. Microbes evolve quicker than mammals and with time can evade the immune response. Inevitably, the immune system is suboptimal and each human being is destined to suffer from infectious disease throughout their lifetime. On top of this, are the chronic diseases of autoimmunity and allergy, as well as infections that don’t go away, like those caused by HIV and HCV, which arise from either an over zealous or inadequate immune response.
The papers in this virtual issue of the FEBS journal run the temporal gamut of the immune response, from the early secretion of anti-microbial peptides when infection is first detected, through to the formation of terminally differentiated plasma cells whose high affinity antibodies provide the ultimate weapon for shutting down infection for good. In preparing this virtual issue, I endeavoured to sort the papers into two sections corresponding to innate immunity (inflammation) and adaptive immunity (B cells and T cells), a division that has historically served to separate the earlier and later phases of the immune response. But in the end I gave up.
Although innate immunity emerged long before adaptive immunity, the latter has still been around for some 500 million years. During that time innate and adaptive immunity have continuously co-evolved under pressure from pathogens and become considerably, if not inextricably, intertwined. That is certainly the picture at the cutting edge of immunological research, where as these papers show investigators find themselves investigating receptors, signaling molecules, and transcription factors that cross the traditional pedagogical boundaries. A further important trend, illustrated by several papers in this virtual issue, is the vital contribution made by cells and molecules of the immune system to reproductive systems of humans, mice and other placental mammals.
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- Congratulations to Antoinette Fong, Diego Estrada-Rivadeneyra and V Mitheera for winning our 50th Anniversary Science Communication Competition! Take a look at their entertaining, educational entries.
- Our Special Issue on Malaria is out!
Check out these excellent reviews and primary research articles covering the latest advances in malaria research
- Our Special Issue on Proteases and Proteolysis in Health and Disease is out! Check out these excellent reviews that cover a broad range of topics in this field
- The winner of the 2017 Richard Perham Prize has been announced - congratulations to Sebastian Bittner of University Hospital of Regensburg, Germany! Read his winning paper.
- Check out our Special Issue on CRISPR/Cas9 Gene Editing!
Nine free reviews cover topics from the initial discovery of CRISPR in bacteria to designing guide RNAs...
- The FEBS Journal Special Issue on Cell Death Control is out!
The thirteen specially commissioned reviews from experts in the field cover a broad spectrum of topics.