Centrioles: active players or passengers during mitosis?

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as “the organ for cell division”. However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues

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

Further validation of the affective bias test for predicting antidepressant and pro-depressant risk: effects of pharmacological and social manipulations in male and female rats

Rationale: Affective biases are hypothesised to contribute to the cause and treatment of mood disorders. We have previously found that affective biases, associated with learning and memory, are observed following acute treatments with a range of antidepressant and prodepressant manipulations.Objective: This study aimed to test if similar biases are observed in male and female Sprague Dawley (SD) rats. We also test whether the stress hormone, corticosterone induces a negative bias in the affective bias test (ABT) consistent with its putative role in the development of depression. We then use a meta-analysis to compare our findings with data published for the Lister Hooded rats.Methods: The affective bias test uses a within-subject study design where animals learn to associate distinct digging substrates, encountered on different days, with the same value food reward. Exposure to one substrate is paired with a treatment manipulation (drug or environmental) and the other with a control condition. A preference test is used to test if the treatment has induced a positive or negative bias.Results: Consistent with previous data, both male and female SD rats exhibit similar positive affective biases following treatment with the antidepressant, venlafaxine and social play and negative affective biases following FG7142 (benzodiazepine inverse agonist) and social stress. Acute treatment with corticosterone induced a negative bias.Conclusions: These data add to the translational validity of the ABT and suggest that corticosterone can induce a negative affective bias following acute treatment, an effect which may contribute to its long term effects on mood

Selective Y centromere inactivation triggers chromosome shattering in micronuclei and repair by non-homologous end joining

Chromosome missegregation into a micronucleus can cause complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms remain unresolved. Here we developed an inducible Y centromere-selective inactivation strategy by exploiting a CENP-A/histone H3 chimaera to directly examine the fate of missegregated chromosomes in otherwise diploid human cells. Using this approach, we identified a temporal cascade of events that are initiated following centromere inactivation involving chromosome missegregation, fragmentation, and re-ligation that span three consecutive cell cycles. Following centromere inactivation, a micronucleus harbouring the Y chromosome is formed in the first cell cycle. Chromosome shattering, producing up to 53 dispersed fragments from a single chromosome, is triggered by premature micronuclear condensation prior to or during mitotic entry of the second cycle. Lastly, canonical non-homologous end joining (NHEJ), but not homology-dependent repair, is shown to facilitate re-ligation of chromosomal fragments in the third cycle. Thus, initial errors in cell division can provoke further genomic instability through fragmentation of micronuclear DNAs coupled to NHEJ-mediated reassembly in the subsequent interphase.National Institutes of Health (U.S.) (Grant HG007852