The little skate genome and the evolutionary emergence of wing-like fins

Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins—including gene expression, chromatin occupancy and three-dimensional conformation—we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait

Does accreditation stimulate change? A study of the impact of the accreditation process on Canadian healthcare organizations

<p>Abstract</p> <p>Background</p> <p>One way to improve quality and safety in healthcare organizations (HCOs) is through accreditation. Accreditation is a rigorous external evaluation process that comprises self-assessment against a given set of standards, an on-site survey followed by a report with or without recommendations, and the award or refusal of accreditation status. This study evaluates how the accreditation process helps introduce organizational changes that enhance the quality and safety of care.</p> <p>Methods</p> <p>We used an embedded multiple case study design to explore organizational characteristics and identify changes linked to the accreditation process. We employed a theoretical framework to analyze various elements and for each case, we interviewed top managers, conducted focus groups with staff directly involved in the accreditation process, and analyzed self-assessment reports, accreditation reports and other case-related documents.</p> <p>Results</p> <p>The context in which accreditation took place, including the organizational context, influenced the type of change dynamics that occurred in HCOs. Furthermore, while accreditation itself was not necessarily the element that initiated change, the accreditation process was a highly effective tool for (i) accelerating integration and stimulating a spirit of cooperation in newly merged HCOs; (ii) helping to introduce continuous quality improvement programs to newly accredited or not-yet-accredited organizations; (iii) creating new leadership for quality improvement initiatives; (iv) increasing social capital by giving staff the opportunity to develop relationships; and (v) fostering links between HCOs and other stakeholders. The study also found that HCOs' motivation to introduce accreditation-related changes dwindled over time.</p> <p>Conclusions</p> <p>We conclude that the accreditation process is an effective leitmotiv for the introduction of change but is nonetheless subject to a learning cycle and a learning curve. Institutions invest greatly to conform to the first accreditation visit and reap the greatest benefits in the next three accreditation cycles (3 to 10 years after initial accreditation). After 10 years, however, institutions begin to find accreditation less challenging. To maximize the benefits of the accreditation process, HCOs and accrediting bodies must seek ways to take full advantage of each stage of the accreditation process over time.</p

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

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

Intraoperative maximal urethral closing pressure measurement: a new technique of tape tension adjustment in transobturator sling surgery?

PURPOSE: Tape tension adjustment is an essential procedure in mid-urethral sling surgery. The goal of this study was to determine if intraoperative maximal urethral closing pressure (MUCP) elevation could be used as a reference value for adequate tape tension adjustment and predict transobturator (TOT) sling surgery outcome. MATERIALS AND METHODS: A prospective study was performed using MUCP measurements just before tape insertion and just after tension adjustment during surgery. Clinical data including preoperative urodynamic results were collected. The cure rate was determined by questionnaire. Patients were divided into two groups. The MUCP elevation group included patients with a MUCP elevation of more than 10 cmH2O before tape insertion; the others were regarded as the non-elevation group. The cure rate and pre- and postoperative clinical variables were compared between the two groups. RESULTS: A total of 48 patients had TOT surgery. The MUCP elevation group (n=19) and the non-elevation group (n=29) were similar with regard to patient characteristics and the preoperative parameters including age, mixed incontinence prevalence, Q-tip angle, peak flow rate, MUCP and the valsalva leak point pressure (VLPP). The mean follow-up period was nine months. The cure rate was significantly higher in the group with MUCP elevation than in the non-elevation group (84% vs. 52%, p=0.02). There was no significant difference in the mean postoperative peak flow rate between the two groups and there was no retention episode. CONCLUSIONS: MUCP elevation of more than 10 cmH2O just after tape insertion was a prognostic factor