Eosinophil Morphology Eosinophil granules and degranulation

Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize aging. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions and how these ultimately affect the physiology of cells and tissues. Here we have addressed these questions by investigating the hematopoietic system of mice deficient for Rev1, a core factor in DNA translesion synthesis (TLS), the postreplicative bypass of damaged nucleotides. Rev1 hematopoietic stem and progenitor cells displayed compromised proliferation, and replication stress that could be rescued with an antioxidant. The additional disruption of Xpc, essential for global-genome nucleotide excision repair (ggNER) of helix-distorting nucleotide lesions, resulted in the perinatal loss of hematopoietic stem cells, progressive loss of bone marrow, and fatal aplastic anemia between 3 and 4 months of age. This was associated with replication stress, genomic breaks, DNA damage signaling, senescence, and apoptosis in bone marrow. Surprisingly, the collapse of the Rev1Xpc bone marrow was associated with progressive mitochondrial dysfunction and consequent exacerbation of oxidative stress. These data reveal that, to protect its genomic and functional integrity, the hematopoietic system critically depends on the combined activities of repair and replication of helix-distorting oxidative nucleotide lesions by ggNER and Rev1-dependent TLS, respectively. The error-prone nature of TLS may provide mechanistic understanding of the accumulation of mutations in the hematopoietic system upon aging

Is Sequestrectomy a Viable Alternative to Microdiscectomy?:A Systematic Review of the Literature

BACKGROUND: Traditionally, lumbar discectomy involves removal of the free disc fragment followed by aggressive or conservative excision of the intervertebral disc. In selected patients, however, it is possible to remove only the free fragment or sequester without clearing the intervertebral disc space. However, there is some controversy about whether that approach is sufficient to prevent recurrent symptoms and to provide adequate pain relief. QUESTIONS/PURPOSES: This systematic review was designed to pose two questions: (1) Does performing a sequestrectomy only without conventional microdiscectomy lead to an increased reherniation rate; and (2) is there a difference in the patient-reported levels of radicular pain? METHODS: Systematic MEDLINE and EMBASE searches were carried out to identify all articles published in peer-reviewed journals reporting the outcomes of interest for conventional microdiscectomy versus sequestrectomy for lumbar disc herniation from L2 to the sacrum (Level III evidence and above); hand-searching of bibliographies was also performed. A minimum of Level II evidence was required with a followup rate of greater than 75%. Followup in all studies was from 18 to 86 months. Seven studies met the inclusion criteria for this review. The studies were analyzed for operating time, hospital stay, pre- and postoperative visual analog scale, and reherniation rate. RESULTS: Patients in both the microdiscectomy and sequestrectomy groups showed comparable improvement of visual analog scale (VAS) score for leg pain. VAS score improvement ranged from 5.6 to 6.5 points in the microdiscectomy groups and 5.5 to 6.6 in the sequestrectomy group. The reherniation rate in the microdiscectomy group ranged from 2.3% to 11.8% and in the sequestrectomy groups from 2% to 12.5%. CONCLUSIONS: This review of the available literature suggests that, compared with conventional microdiscectomy, microsurgical lumbar sequestrectomy can achieve comparable reherniation rates and reduction in radicular pain when a small breach in the posterior fibrous ring is found intraoperatively

Mutagenic replication: target for tumor therapy?

A study published in Cell by Wojtaszek et al. provides a proof of principle that cancer cells can be sensitized to DNA-damaging chemotherapy by the drug-induced inhibition of mutagenic DNA translesion synthesis, a process that endows tolerance of DNA damage. However, the risk/benefit profile of such a combination therapy should be thoroughly evaluated.Genome Instability and Cance

Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis (vol 7, 2017)

Genome Instability and Cance