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.

/pdf/molecular-definitions-of-cell-death-subroutines-q5g428rlyi.pdf

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

College of Life Sciences, Nankai University, Tianjin 300071, China Department of Biochemistry, Rush University, Chicago, IL 60612 State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases, Chinese Academy of Medical Sciences, Tianjin 300020, China Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15240 Hematology/Oncology, Indiana University School of Medicine, Indianapolis, IN, 46202

Critical Role of AKT in Myeloma-induced Osteoclast Formation and Osteolysis

Abstract We demonstrate that superconducting gatemon qubits based on superconductor-semiconductor-superconductor Josephson junctions can be constructed on hole-type Ge/Si core/shell nanowires. The frequency of the qubit can be set firstly by controlling the diffusion of Al in the nanowire via thermal annealing, which yields a suitable critical supercurrent allowing the qubit frequency to be within the experimentally accessible range, and then by fine tuning of a gate voltage, by which an accurate adjustment of the frequency can be realized. On the resulted qubit, Rabi oscillation with an energy relaxation time $${T}_{1} \sim 180\,{\rm{ns}}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mi>T</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> </mml:mrow> </mml:msub> <mml:mo>~</mml:mo> <mml:mn>180</mml:mn> <mml:mspace /> <mml:mi>ns</mml:mi> </mml:mrow> </mml:math> was observed in the time domain, an average decoherence time $${T}_{2}^{* } \sim 15\,{\rm{ns}}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msubsup> <mml:mrow> <mml:mi>T</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>*</mml:mo> </mml:mrow> </mml:msubsup> <mml:mo>~</mml:mo> <mml:mn>15</mml:mn> <mml:mspace /> <mml:mi>ns</mml:mi> </mml:mrow> </mml:math> was obtained, and the gate voltage dependence of both $${T}_{1}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow> <mml:mi>T</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>1</mml:mn> </mml:mrow> </mml:msub> </mml:math> and $${T}_{2}^{* }$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msubsup> <mml:mrow> <mml:mi>T</mml:mi> </mml:mrow> <mml:mrow> <mml:mn>2</mml:mn> </mml:mrow> <mml:mrow> <mml:mo>*</mml:mo> </mml:mrow> </mml:msubsup> </mml:math> was investigated. Such a hole-type superconducting gatemon qubit, based on materials with strong spin-orbit coupling and potentially the absence of hyperfine interaction after isotope purification, could be used for exploring the quantum coherence phenomena of hole-gas and even Majorana physics in Ge-based quantum devices. 

/pdf/hole-type-superconducting-gatemon-qubit-based-on-ge-si-core-2l26nzbv.pdf

Hole-type superconducting gatemon qubit based on Ge/Si core/shell nanowires


 With thermal fluctuation strongly suppressed, low temperature environment is essential for studies of condensed matter physics and developments of quantum technologies. Ultra-low temperature below 20 mK has demonstrated its importance and significance in physical sciences and information techniques. Dilution refrigeration is by far the best feasible and reliable method to generate and keep lattice temperature in this range. With a potential shortage of helium supply, cryogen-free dilution refrigerator (CFDR), eliminating the necessity of regular helium refill, becomes the main facility for the purpose of creating ultralow temperature environments. Here we describe our successful construction of a CFDR which reached a base temperature of around 10.9 mK for continuous circulation and 8.6 mK for single-shot operation. We describe its operating mechanism and the designs of key components, especially some unique designs including heat switch and alumina thermal link. Possible improvements in the future are also discussed.

Development of a Cryogen-free Dilution Refrigerator

Majorana zero modes have been attracting considerable attention because of their prospective applications in fault-tolerant topological quantum computing. In recent years, some schemes have been proposed to detect and manipulate Majorana zero modes using superconducting qubits. However, manipulating and reading the Majorana zero modes must be kept in the time window of quasiparticle poisoning. In this work, we study the problem of quasiparticle poisoning in a split transmon qubit containing hybrid Josephson junctions involving Majorana zero modes. We show that Majorana coupling will cause parity mixing and 4𝜋 Josephson effect. In addition, we obtained the expression of qubit parameter-dependent parity switching rate, and demonstrated that quasiparticle poisoning can be greatly suppressed by reducing 𝐸 J /𝐸 C via qubit design.

Jie Fan

Papers

Critical Role of AKT in Myeloma-induced Osteoclast Formation and Osteolysis

Hole-type superconducting gatemon qubit based on Ge/Si core/shell nanowires

Development of a Cryogen-free Dilution Refrigerator

Quasiparticle poisoning rate in a superconducting transmon qubit involving Majorana zero modes