A year in the molecular life sciences: 2024 highlights.

The FEBS Journal editorial team reviews the articles we published in 2024 and reflects on the year's highlights. The articles summarised here broadly cluster in three themes-molecular and cell biology across species, immunology, and cutting-edge methods-whilst still showcasing the diversity of the scientific fields the journal covers. We look forward to many more excellent articles in 2025 and hope these highlights will inspire you to submit your next manuscript to The FEBS Journal.

The FEBS Journal in 2025: in all science, error precedes the truth.

The FEBS Journal publishes primary papers as well as reviews in the molecular life sciences relating to the molecules and mechanisms underpinning biological processes. Editor-in-Chief Seamus Martin shares some thoughts on the nature of conducting research, some highlights of the past year at the journal, and what is in store for 2025.

Rewarding excellence: the 2024 FEBS Journal Richard Perham prize.

This editorial highlights and celebrates the winner of the 2024 Richard Perham prize. This was selected from shortlisted original articles that were published in The FEBS Journal in 2023 and received prize nominations from the Editorial Board. The winning paper, by Matteo Brindisi, Luca Frattaruolo, Federica Sotgia, Michael P Lisanti, Anna Rita Cappello and colleagues, shows how high cholesterol levels promote breast cancer aggressiveness.

Protocol for analyzing TRAIL- and Fas-induced signaling complexes by immunoprecipitation from human cells.

Engagement of TRAIL or Fas death receptors can trigger the assembly of cytoplasmic caspase-8/FADD/RIPK1 (FADDosome) signaling complexes that promote nuclear factor κB (NF-κB) activation. Here, we present a protocol for immunoprecipitation of TRAIL- or Fas-induced FADDosomes from human cell lines. We describe steps for stimulating human cells with TRAIL or Fas ligand, followed by preparation of membrane death receptor-associated, as well as cytoplasmic FADDosome, signaling complexes.

The FEBS Journal in 2024: maintaining standards and taking the road less travelled.

The FEBS Journal publishes research on diverse topics in the molecular life sciences relating to the molecules and mechanisms underpinning biological processes. Editor-in-Chief Seamus Martin discusses the rewards of pursuing a career in basic research, some highlights of the past year at the journal, and what's in store for 2024.

Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry.

Apoptosis is a mode of programmed cell death that plays important roles in tissue sculpting during development, in the maintenance of tissue homeostasis in the adult, and in the eradication of injured or infected cells during pathological processes. Numerous physiological as well as pathological stimuli trigger apoptosis, such as engagement of plasma-membrane-associated Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, radiation, and exposure to diverse cytotoxic drugs. Apoptosis is coordinated by members of the caspase family of cysteine proteases, which, upon activation, trigger a series of dramatic morphological and biochemical changes including retraction from the substratum, cell shrinkage, extensive and protracted plasma membrane blebbing, chromatin condensation, DNA hydrolysis, nuclear fragmentation, and proteolytic cleavage of numerous caspase substrates.

cFLIP acts as a suppressor of TRAIL- and Fas-initiated inflammation by inhibiting assembly of caspase-8/FADD/RIPK1 NF-κB-activating complexes.

TRAIL and FasL are potent inducers of apoptosis but can also promote inflammation through assembly of cytoplasmic caspase-8/FADD/RIPK1 (FADDosome) complexes, wherein caspase-8 acts as a scaffold to drive FADD/RIPK1-mediated nuclear factor κB (NF-κB) activation. cFLIP is also recruited to FADDosomes and restricts caspase-8 activity and apoptosis, but whether cFLIP also regulates death receptor-initiated inflammation is unclear. Here, we show that silencing or deletion of cFLIP leads to robustly enhanced Fas-, TRAIL-, or TLR3-induced inflammatory cytokine production, which can be uncoupled from the effects of cFLIP on caspase-8 activation and apoptosis.

Unleashing dendritic cell-mediated tumor clearance by targeting Bcl-2.

Bcl-2 family proteins serve as key regulators of apoptosis and are frequently overexpressed in cancer. Consequently, small-molecule Bcl-2-antagonists (BH3 mimetics) have emerged as a new class of targeted therapeutics. A recent study by Zhao et al.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

The FEBS Journal in 2023: building back better.

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.

Myeloid cell-derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement.

Interleukin-1 (IL-1) family cytokines are key barrier cytokines that are typically expressed as inactive, or partially active, precursors that require proteolysis within their amino termini for activation. IL-37 is an enigmatic member of the IL-1 family that has been proposed to be activated by caspase-1 and to exert anti-inflammatory activity through engagement of the IL-18R and SIGIRR. However, here we show that the longest IL-37 isoform, IL-37b, exhibits robust proinflammatory activity upon amino-terminal proteolysis by neutrophil elastase or cathepsin S.

IL-1α and IL-36 Family Cytokines Can Undergo Processing and Activation by Diverse Allergen-Associated Proteases.

Inflammation driven by environmental allergens is an important source of morbidity in diseases such as asthma and eczema. How common allergens promote inflammation is still poorly understood, but previous studies have implicated the protease activity associated with many allergens as an important component of the pro-inflammatory properties of these agents. The IL-1 family cytokine, IL-33, has recently been shown to undergo processing and activation by proteases associated with multiple common allergens.

SARS-CoV-2 spike and nucleocapsid proteins fail to activate human dendritic cells or γδ T cells.

γδ T cells are thought to contribute to immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanisms by which they are activated by the virus are unknown. Using flow cytometry, we investigated if the two most abundant viral structural proteins, spike and nucleocapsid, can activate human γδ T cell subsets, directly or in the presence of dendritic cells (DC). Both proteins failed to induce interferon-γ production by Vδ1 or Vδ2 T cells within fresh mononuclear cells or lines of expanded γδ T cells generated from healthy donors, but the same proteins stimulated CD3+ cells from COVID-19 patients.

IL-1 family cytokines serve as 'activity recognition receptors' for aberrant protease activity indicative of danger.

Members of the extended IL-1 cytokine family play key roles as instigators of inflammation in numerous infectious and sterile injury contexts and are highly enriched at barrier surfaces such as the skin, lungs and intestinal mucosa. Because IL-1 family cytokines do not possess conventional ER-golgi trafficking and secretory signals, these cytokines are typically released into the extracellular space due to tissue damage resulting in necrosis, or pathogen detection resulting in pyroptosis. The latter feature, in combination with other factors, suggests that IL-1 family cytokines serve as canonical damage-associated molecular patterns (DAMPs), which instigate inflammation in response to tissue damage.

Professor Dame Janet Thornton to receive 'The FEBS Journal Open Science Award'.

Professor Dame Janet Thornton has been named as the inaugural recipient of 'The FEBS Journal Open Science Award' for her major role in the development of ELIXIR, the pan-European infrastructure for biological data, as well as the creation of freely available computational tools and knowledge resources.

The FEBS Journal in 2022: trust the science and treasure the data.

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.

TRAIL signaling promotes entosis in colorectal cancer.

Entosis is a form of nonphagocytic cell-in-cell (CIC) interaction where a living cell enters into another. Tumors show evidence of entosis; however, factors controlling entosis remain to be elucidated. Here, we find that besides inducing apoptosis, TRAIL signaling is a potent activator of entosis in colon cancer cells.

Dr. Alexander Wlodawer-celebrating five decades of service to the structural biology community.

This 75th birthday tribute to our Editorial Board member Alexander Wlodawer recounts his decades-long service to the community of structural biology researchers. His former and current colleagues tell the story of his upbringing and education, followed by an account of his dedication to quality and rigor in crystallography and structural science. The FEBS Journal Editor-in-Chief Seamus Martin further highlights Alex's outstanding contributions to the journal's success over many years.

The FEBS Journal in 2021: a sharp reminder that science really matters.

The FEBS Journal, a leading multidisciplinary journal in the life sciences, continues to grow in visibility and impact. Here, the Editor-in-Chief Seamus Martin discusses developments at the journal over the past year and the impact of the COVID-19 crisis on research activities.

TRAIL Receptors Serve as Stress-Associated Molecular Patterns to Promote ER-Stress-Induced Inflammation.

Inflammation triggered by infection or cellular necrosis is initiated by a battery of pattern-recognition receptors, such as Toll-like receptors or IL-1 family receptors. Diverse forms of cell stress, such as ER stress or mitochondrial stress, can also promote inflammatory responses that contribute to the chronic inflammation observed in cancer, obesity, and other conditions. However, the molecular mechanisms of cell-stress-induced inflammation are poorly understood.

The FEBS Journal in 2020: Open Access and quality versus quantity publishing.

Seamus Martin holds the Smurfit Chair of Medical Genetics at the Smurfit Institute of Genetics, Trinity College Dublin, Ireland. His laboratory works on diverse aspects of cell death control, including the role of 'death receptors' as initiators of inflammation and the role of IL-1 family cytokines as key initiators of inflammation in the context of necrotic cell death. Seamus received the GlaxoSmithKline Award of The Biochemical Society (2006) and The RDS-Irish Times Boyle Medal (2015) for his work on the role of caspases in apoptosis and was elected to the Royal Irish Academy in 2006 and EMBO in 2009.

How to prepare and deliver a great talk.

Giving effective and interesting talks are key skills for scientists at every stage of their career. This installment of the Words of Advice series provides some insights into preparing and delivering compelling presentations, as well as alleviating pretalk nerves.

The FEBS Journal in 2019: ensuring that casks of vintage wine remain unspoiled.

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.

To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps.

Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold.