Saddleback syndrome in yellowfin bream [Acanthopagrus australis (Günther, 1859)] in Moreton Bay,Australia: its form,occurrence, association with other abnormalities and cause

The aim of this study was to determine if saddleback syndrome (SBS) in a wild population of yellowfin bream (Acanthopagrus australis) was the result of a developmental defect or caused by physical injury. Information was collected in 2012 on the incidence of SBS and other abnormalities in this species in Moreton Bay, Australia. Abnormalities in adult fish (>250 mm Total Length, TL) with SBS (n = 47) were compared with those without SBS (n = 30). A sample of juvenile fish (n = 404) was checked for the presence of SBS. The results show that scale loss, scale pattern misalignment, lateral line fracture and pectoral fin abnormality were closely associated with SBS. SBS was uncommon (<2%) in juveniles <70 mm TL, but common (>12%) in the larger juveniles (70–215 mm TL). These results, together with the findings that scale loss associated with SBS in adult fish occurred in the range 80–245 mm back‐calculated TL, indicate that SBS and the related abnormalities in yellowfin bream are a result of physical injuries to larger juveniles (>70 mm TL). The reduction in the incidence of SBS from approximately 12% in the larger juveniles to 5% in adults is evidence of mortality associated with SBS.     

Bronchoabsorption; a novel bronchoscopic technique to improve biomarker sampling of the airway

Background

Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely.

Methods

Eight healthy smokers aged 40–65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1β), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis.

Results

A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL.

Conclusions

The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression.

Trial registration

NHS Health Research Authority (13/LO/0256).     

Targeting mutant fibroblast growth factor receptors in cancer

Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.     

Spatial determinants in morphogenesis: recovery from plasmolysis in the diatom Ditylum

Ditylum cells are enclosed in a rigid wall consisting of two "valves" (end walls) connected by "girdle bands." A hollow spine, the Labiate Process (LP), extends from each valve and a stable cytoplasmic strand connects its base with the nucleus. We investigated whether cells might possess "spatial determinants" for controlling their internal organization and wall morphogenesis. Upon plasmolysis, cells contracted into a spherical protoplast detached from the wall. Recovery was initiated by growing filopodia that "searched" the inside of the wall. Some attached to the inside corners, generating tension that could temporarily displace the protoplast. Others consolidated into the strand connecting nucleus with the LP. The protoplasts soon expanded and cells recovered: some divided immediately, the rest within 24 h. When recently divided cells were plasmolysed, their nascent valves were exocytosed. These were ignored by the filopodia during recovery. Later, protoplasts secreted a new valve, while the nascent valves were discarded. The interphase microtubule (MT) cytoskeleton radiates from a central Microtubule Center. A thicker bundle connects the nucleus to each LP. Plasmolysis destroyed the MT cytoskeleton; its re-establishment matched growth of the filopodia. The anti-MT drug oryzalin prevented filopodial extension while existing filopodia retracted, except those stabilized by attachment to the corners of the cell and the LP. Several anti-actin agents had relatively little effect. However, one, mycalolide B, caused the nucleus to be extruded from the protoplast by a bundle of MTs. We conclude that the geometry of the wall could provide spatial information to which the MT-cytoskeleton/filopodia respond.