Every repeat is unique: Exploring the genomic impact of human L1 retrotransposons at locus-specific resolution.

Fully understanding the impact of the human retrotransposon L1 requires that each of ∼500,000 L1 copies be evaluated as a potentially unique genomic entity. In this issue of Cell Genomics, Lanciano et al.1 strive toward this goal, illuminating the reciprocal regulatory influence between individual L1s and their genomic integration sites.

RNA sequencing and expression analysis reveal a role for Lhx9 in the haploinsufficient adult mouse ovary.

Understanding the molecular pathways that underpin ovarian development and function is vital for improving the research approaches to investigating fertility. Despite a significant improvement in our knowledge of molecular activity in the ovary, many questions remain unanswered in the quest to understand factors influencing fertility and ovarian pathologies such as cancer. Here, we present an investigation into the expression and function of the developmental transcription factor LIM Homeobox 9 (LHX9) in the adult mouse ovary. We have characterized Lhx9 expression in several cell types of the mature ovary across follicle stages. To evaluate possible LHX9 function in the adult ovary, we investigated ovarian anatomy and transcription in an Lhx9+/- knockout mouse model displaying subfertility. Despite a lack of gross anatomical differences between genotypes, RNA-sequencing found that 90 differentially expressed genes between Lhx9+/ - and Lhx9+/+ mice. Gene ontology analyses revealed a reduced expression of genes with major roles in ovarian steroidogenesis and an increased expression of genes associated with ovarian cancer. Analysis of the ovarian epithelium revealed Lhx9+/ - mice have a disorganized epithelial phenotype, corresponding to a significant increase in epithelial marker gene expression. These results provide an analysis of Lhx9 in the adult mouse ovary, suggesting a role in fertility and ovarian epithelial cancer.

LC-FACSeq is a method for detecting rare clones in leukemia.

Detecting, characterizing, and monitoring rare populations of cells can increase testing sensitivity, give insight into disease mechanism, and inform clinical decision making. One area that can benefit from increased resolution is management of cancers in clinical remission but with measurable residual disease (MRD) by multicolor FACS. Detecting and monitoring genomic clonal resistance to treatment in the setting of MRD is technically difficult and resource intensive due to the limited amounts of disease cells. Here, we describe limited-cell FACS sequencing (LC-FACSeq), a reproducible, highly sensitive method of characterizing clonal evolution in rare cells relevant to different types of acute and chronic leukemias. We demonstrate the utility of LC-FACSeq for broad multigene gene panels and its application for monitoring sequential acquisition of mutations conferring therapy resistance and clonal evolution in long-term ibrutinib treatment of patients with chronic lymphocytic leukemia. This technique is generalizable for monitoring of other blood and marrow infiltrating cancers.

Snuff box radial artery access for arteriovenous fistula intervention.

PURPOSE: The aim of this article is to retrospectively compare snuff box radial artery access with direct fistula access for radiocephalic fistula intervention. MATERIALS AND METHODS: Review of 68 consecutive radiocephalic interventions between April 2013 and April 2017 was performed. The snuff box radial access was performed under ultrasound guidance with the hand in a neutral position (thumb up). The snuff box radial artery was entered distal to the extensor pollicis longus, over the trapezium bone. Hand held pressure was applied for hemostasis. The procedure times, success, and complications of snuff box radial artery access procedures were reviewed. RESULTS: Snuff box radial artery access was used in 25% (17/68) of radiocephalic fistula interventions. All access procedures were successful. Snuff box radial artery access was only used in cases involving the proximal fistula. Lesions treated from snuff box radial artery access approach included 19% (10/54) of fistula stenosis, 50% (1/2) thrombosis, 63% (5/8) immature fistulae, 100% (1/1) steal syndrome, and none of the (0/5) symptomatic outflow occlusions. The mean procedure times for snuff box radial artery access and direct fistula access were not significant at 29.1 ± 16.3 min (range = 10-81) and 26.8 ± 14.0 min (range = 5-70), respectively (p < 0.57). Minor hematoma occurred in 12% (2/17) snuff box radial artery access and 2% (1/51) direct fistula access. There were no major complications. CONCLUSION: Snuff box radial access was used successfully for radiocephalic fistula intervention with procedure times similar to direct fistula access without major complications.

The molecular pathways underlying early gonadal development.

The body of knowledge surrounding reproductive development spans the fields of genetics, anatomy, physiology and biomedicine, to build a comprehensive understanding of the later stages of reproductive development in humans and animal models. Despite this, there remains much to learn about the bi-potential progenitor structure that the ovary and testis arise from, known as the genital ridge (GR). This tissue forms relatively late in embryonic development and has the potential to form either the ovary or testis, which in turn produce hormones required for development of the rest of the reproductive tract. It is imperative that we understand the genetic networks underpinning GR development if we are to begin to understand abnormalities in the adult. This is particularly relevant in the contexts of disorders of sex development (DSDs) and infertility, two conditions that many individuals struggle with worldwide, with often no answers as to their aetiology. Here, we review what is known about the genetics of GR development. Investigating the genetic networks required for GR formation will not only contribute to our understanding of the genetic regulation of reproductive development, it may in turn open new avenues of investigation into reproductive abnormalities and later fertility issues in the adult.