Recombinase technology: applications and possibilities

The use of recombinases for genomic engineering is no longer a new technology. In fact, this technology has entered its third decade since the initial discovery that recombinases function in heterologous systems (Sauer in Mol Cell Biol 7(6):2087–2096, 1987). The random insertion of a transgene into a plant genome by traditional methods generates unpredictable expression patterns. This feature of transgenesis makes screening for functional lines with predictable expression labor intensive and time consuming. Furthermore, an antibiotic resistance gene is often left in the final product and the potential escape of such resistance markers into the environment and their potential consumption raises consumer concern. The use of site-specific recombination technology in plant genome manipulation has been demonstrated to effectively resolve complex transgene insertions to single copy, remove unwanted DNA, and precisely insert DNA into known genomic target sites. Recombinases have also been demonstrated capable of site-specific recombination within non-nuclear targets, such as the plastid genome of tobacco. Here, we review multiple uses of site-specific recombination and their application toward plant genomic engineering. We also provide alternative strategies for the combined use of multiple site-specific recombinase systems for genome engineering to precisely insert transgenes into a pre-determined locus, and removal of unwanted selectable marker genes

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

Impact of genomic damage and ageing on stem cell function

Item does not contain fulltextImpairment of stem cell function contributes to the progressive deterioration of tissue maintenance and repair with ageing. Evidence is mounting that age-dependent accumulation of DNA damage in both stem cells and cells that comprise the stem cell microenvironment are partly responsible for stem cell dysfunction with ageing. Here, we review the impact of the various types of DNA damage that accumulate with ageing on stem cell functionality, as well as the development of cancer. We discuss DNA-damage-induced cell intrinsic and extrinsic alterations that influence these processes, and review recent advances in understanding systemic adjustments to DNA damage and how they affect stem cells

Sex differences in heart failure

Heart failure (HF) represents a global pandemic health problem with a high impact on health-care costs, affecting about 26 million adults worldwide. The overall HF prevalence and incidence are ~2% and ~0.2% per year, respectively, in Western countries, with half of the HF population with reduced ejection fraction (HFpEF) and half with preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Sex differences may exist in HF. More males have HFrEF or HFmrEF and an ischemic etiology, whereas more females have HFpEF and hypertension, diastolic dysfunction, and valvular pathologies as HF etiologies. Females are generally older, have a higher EF, higher frequency of HF-related symptoms, and lower NYHA functional status. Generally, it is observed that female HF patients tend to have more comorbidities such as atrial fibrillation, diabetes, hypertension, anemia, iron deficiency, renal disease, arthritis, frailty, depression, and thyroid abnormalities. However, overall, females have better prognosis in terms of mortality and hospitalization risk compared with men, regardless of EF. Potential sex differences in HF characteristics may be underestimated because of the underrepresentation of females in cardiovascular research and, in particular, the sex imbalance in clinical trial enrollment may avoid to identify sex-specific differences in treatments’ benefit