Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

/pdf/complement-a-key-system-for-immune-surveillance-and-56fp7muk7t.pdf

Complement: a key system for immune surveillance and homeostasis

■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.

Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

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Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Autophagy is a mechanism by which cellular material is delivered to lysosomes for degradation, leading to the basal turnover of cell components and providing energy and macromolecular precursors. Autophagy has opposing, context-dependent roles in cancer, and interventions to both stimulate and inhibit autophagy have been proposed as cancer therapies. This has led to the therapeutic targeting of autophagy in cancer to be sometimes viewed as controversial. In this Review, we suggest a way forwards for the effective targeting of autophagy by understanding the context-dependent roles of autophagy and by capitalizing on modern approaches to clinical trial design.

/pdf/targeting-autophagy-in-cancer-2pjcn0h04a.pdf

Targeting autophagy in cancer

Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. Cell necroptosis features receptor-interacting protein (RIPK) 1 activation and necroptosome formation. This leads to loss of plasma membrane integrity, the release of cell contents into the extracellular space, and subsequent increased inflammation. Here, we report an intra-PMN mechanism of negative regulation of necroptosis mediated through TBK1/IKKe. Using an in vivo mouse model of intratracheal injection (i.t.) of LPS and in vitro LPS stimulation of mouse PMN, we found that LPS-TLR4 signaling in PMNs activates and phosphorylates TBK1 and IKKe, which in turn suppress LPS-induced formation of the RIPK1-RIPK3-MLKL (necrosome) complex. TBK1 dysfunction by knockdown or inhibitor significantly increases the phosphorylation of RIPK1 (∼67%), RIPK3 (∼68%), and MLKL (∼50%) and promotes RIPK1-RIPK3 and RIPK3-MLKL interactions and increases PMN necroptosis (∼83%) in response to LPS, with subsequent augmented lung inflammation. These findings suggest that the LPS-TLR4-TBK1 axis serves as a negative regulator for PMN necroptosis and might be a therapeutic target for modulating PMN death and inflammation.

TBK1/IKKε Negatively Regulate LPS-Induced Neutrophil Necroptosis and Lung Inflammation.

ABSTRACT Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of urologic cancer. With low survival rates among patients in advanced stages of disease, and increasing rate of morbidity and mortality worldwide, novel therapeutic targets for ccRCC clinical intervention are necessary. In this study, we investigated the functional role of circZKSCAN1 in ccRCC progression. Our results suggested that circZKSCAN1 was abundantly expressed in ccRCC tumor tissues and cells. CircZKSCAN1 knockdown significantly inhibited cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition of renal cell carcinoma (RCC) cells, whereas potentiated Natural Killer (NK) cell-mediated cytotoxicity against RCC cells in vitro and repressed tumor growth in vivo. Furthermore, we identified a novel circZKSCAN1/miR-1294/PIM1 axis was identified in RCC progression, showing that the expression of circZKSCAN1 expression in RCC cells was transcriptionally regulated by Kruppel-like factor 2. The results of our study may provide new insights for ccRCC basic research. Abbreviations: ccRCC: clear cell renal cell carcinoma; ChIP: chromatin immunoprecipitation; circRNA: circular RNA; EDU: 5‐ethynyl‐2’‐deoxyuridine; EMT: epithelial-mesenchymal transition; FBS: fetal bovine serum; FISH: RNA fluorescent in situ hybridization; KLF2: Kruppel-like factor 2; NC: normal control; NK cell: natural killer cell; NOD/SCID: nonobese severe diabetic/severe combined immunodeficiency; PIM1: Pim-1 proto-oncogene, serine/threonine kinase; RCC: renal cell carcinoma; ZKSCAN1: zinc finger with KRAB and SCAN domains 1

KLF2-induced circZKSCAN1 potentiates the tumorigenic properties of clear cell renal cell carcinoma by targeting the miR-1294/PIM1 axis

Timothy R. Billiar and Mark A. WilsonHackam, Yoram Vodovotz, Huan Yang, Kevin J. Tracey, Jie Fan, Yuehua Li, Ryan M. Levy, Janet J. Fan, David J.http://www.jimmunol.org/content/178/10/6573J Immunol€2007; 178:6573-6580; ;Referenceshttp://www.jimmunol.org/content/178/10/6573.full#ref-list-1This article cites 61 articles, 30 of which you can access for free at: Subscriptionshttp://jimmunol.org/subscriptionsInformation about subscribing to The Journal of Immunology is online at: Permissionshttp://www.aai.org/ji/copyright.htmlSubmit copyright permission requests at: Email Alertshttp://jimmunol.org/cgi/alerts/etocReceive free email-alerts when new articles cite this article. Sign up at:

Oxidase Activation in Neutrophils: Role of Hemorrhagic Shock Induces NAD(P)H

In the original publication the bands in Fig. 1J and Fig. 2B were not visible. The correct versions of Fig. 1J and Fig. 2B are provided in this correction.

/pdf/correction-to-egfr-signaling-augments-tlr4-cell-surface-259ccm85fu.pdf

Correction to: EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation

Topological-material-based Josephson junctions have the potential to be used to host Majorana zero modes and to construct topological qubits. For operating the topological qubits at an appropriate timescale to avoid decoherence and quasiparticle poisoning, one would eventually go to the time domain and embed the topological qubits into quantum electrodynamic circuits. Here, we constructed a topological-insulator-nanowire-based transmon qubit and demonstrated its strong coupling to a coplanar waveguide resonator. The flux-tunable spectrum and Rabi oscillations with a qubit lifetime [Formula: see text] of [Formula: see text] were observed. Such a hybrid platform, containing topological materials and quantum electrodynamic circuits, can further be used to study the physical properties such as Majorana zero modes in topological quantum circuits.

https://pubs.aip.org/aip/apl/article-pdf/doi/10.1063/5.0140079/16821343/154001_1_5.0140079.pdf

Jie Fan

Papers

TBK1/IKKε Negatively Regulate LPS-Induced Neutrophil Necroptosis and Lung Inflammation.

KLF2-induced circZKSCAN1 potentiates the tumorigenic properties of clear cell renal cell carcinoma by targeting the miR-1294/PIM1 axis

Oxidase Activation in Neutrophils: Role of Hemorrhagic Shock Induces NAD(P)H

Correction to: EGFR signaling augments TLR4 cell surface expression and function in macrophages via regulation of Rab5a activation

Realization of superconducting transmon qubits based on topological insulator nanowires