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

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

Listeria pathogenesis and molecular virulence determinants

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research

(Table 2) Seasonal flux data and percentages of major bulk components of total flux at the mesotrophic sediment trap site CB from 1988 - 2012

A more than two-decadal sediment trap record from the Eastern Boundary Upwelling Ecosystem (EBUE) off Cape Blanc, Mauritania, is analysed with respect to deep ocean mass fluxes, flux components and their variability on seasonal to decadal timescales. The total mass flux revealed interannual fluctuations which were superimposed by fluctuations on decadal timescales. High winter fluxes of biogenic silica (BSi), used as a measure of marine production (mostly by diatoms) largely correspond to a positive North Atlantic Oscillation (NAO) index (December-March). However, this relationship is weak. The highest positive BSi anomaly was in winter 2004-2005 when the NAO was in a neutral state. More episodic BSi sedimentation events occurred in several summer seasons between 2001 and 2005, when the previous winter NAO was neutral or even negative. We suggest that distinct dust outbreaks and deposition in the surface ocean in winter and occasionally in summer/autumn enhanced particle sedimentation and carbon export on short timescales via the ballasting effect. Episodic perturbations of the marine carbon cycle by dust outbreaks (e.g. in 2005) might have weakened the relationships between fluxes and large-scale climatic oscillations. As phytoplankton biomass is high throughout the year, any dry (in winter) or wet (in summer) deposition of fine-grained dust particles is assumed to enhance the efficiency of the biological pump by incorporating dust into dense and fast settling organic-rich aggregates. A good correspondence between BSi and dust fluxes was observed for the dusty year 2005, following a period of rather dry conditions in the Sahara/Sahel region. Large changes of all bulk fluxes occurred during the strongest El Niño-Southern Oscillation (ENSO) in 1997-1999 where low fluxes were obtained for almost 1 year during the warm El Niño and high fluxes in the following cold La Niña phase. For decadal timescales, Bakun (1990) suggested an intensification of coastal upwelling due to increased winds (''Bakun upwelling intensification hypothesis''; Cropper et al., 2014) and global climate change. We did not observe an increase of any flux component off Cape Blanc during the past 2 and a half decades which might support this. Furthermore, fluxes of mineral dust did not show any positive or negative trends over time which might suggest enhanced desertification or ''Saharan greening'' during the last few decades