Zebrafish Hagoromo mutants upregulate fgf8 post-embryonically and develop neuroblastoma

We screened an existing collection of zebrafish insertional mutants for cancer susceptibility by histologic examination of heterozygotes at 2 years of age. As most mutants had no altered cancer predisposition, this provided the first comprehensive description of spontaneous tumor spectrum and frequency in adult zebrafish. Moreover, the screen identified four lines, each carrying a different dominant mutant allele of Hagoromo previously linked to adult pigmentation defects, which develop tumors with high penetrance and that histologically resemble neuroblastoma. These tumors are clearly neural in origin, although they do not express catecholaminergic neuronal markers characteristic of human neuroblastoma. The zebrafish tumors result from inappropriate maintenance of a cell population within the cranial ganglia that are likely neural precursors. These neoplasias typically remain small but they can become highly aggressive, initially traveling along cranial nerves, and ultimately filling the head. The developmental origin of these tumors is highly reminiscent of human neuroblastoma. The four mutant Hagoromo alleles all contain viral insertions in the fbxw4 gene, which encodes an F-box WD40 domain–containing protein. However, although one allele clearly reduced the levels of fbxw4 mRNA, the other three insertions had no detectable effect on fbw4 expression. Instead, we showed that all four mutations result in the postembryonic up-regulation of the neighboring gene, fibroblast growth factor 8 (fgf8). Moreover, fgf8 is highly expressed in the tumorigenic lesions. Although fgf8 overexpression is known to be associated with breast and prostate cancer in mammals, this study provides the first evidence that fgf8 misregulation can lead to neural tumors. (Mol Cancer Res 2009;7(6):841–50)National Cancer Institute (U.S.) (Grant CA106416

To fly or not to fly : Factors influencing the flight capacity of carabid beetles (Coleoptera: Carabidae)

This review considers factors affecting the flight capacity of carabid beetles and the implications of flight for carabids. Studies from the Dutch polders in particular show that young populations of carabids consist predominantly of macropterous species and macropterous individuals of wing-dimorphic species. Also populations of wing-dimorphic carabid species at the periphery of their geographical range contain high proportions of macropterous individuals. However, studies from Baltic archipelagos show that older populations of even highly isolated island habitats contain considerable proportions of brachypterous species and individuals. This suggests that macroptery is primarily an adaptation for dispersal and that there exists a mechanism for subsequently reducing the ratio of macropterous to brachypterous species under stable conditions, due to the competitive advantage of brachyptery. Populations in isolated habitats, such as islands and mountains, have high proportions of brachypterous species. Many macropterous species do not possess functional flight muscles. Species of unstable habitats, such as tree canopies and wet habitats, are mostly macropterous. Brachypterous species tend to disappear from disturbed habitats. There is uncertainty regarding the extent to which carabid dispersal is directed and how much passive. Both Den Boer and Lindroth recognized that mostly macropterous individuals of macropterous and wing-dimorphic species disperse and found new populations, after which brachyptery tends to rapidly appear and proliferate in the newly founded population. It is most likely that the allele for brachyptery would arrive via the dispersal of gravid females which had mated with brachypterous males prior to emigration. Whilst many studies consider wing morphology traits of carabid beetles to be species-specific and permanent, a number of studies have shown that the oogenesis flight syndrome, whereby females undertake migration and subsequently lose their flight muscles by histolysis before eventually regenerating them after reproducing, has been reported for a growing number of carabid species. Wing morphology of carabid beetles clearly offers strong potential for the study of population dynamics. This field of study flourished during the 1940's to the late 1980's. Whilst a considerable amount of valuable research has been performed and published, the topic clearly holds considerable potential for future study.Peer reviewe

Salmonella Strains Isolated from Galápagos Iguanas Show Spatial Structuring of Serovar and Genomic Diversity

It is thought that dispersal limitation primarily structures host-associated bacterial populations because host distributions inherently limit transmission opportunities. However, enteric bacteria may disperse great distances during food-borne outbreaks. It is unclear if such rapid long-distance dispersal events happen regularly in natural systems or if these events represent an anthropogenic exception. We characterized Salmonella enterica isolates from the feces of free-living Galápagos land and marine iguanas from five sites on four islands using serotyping and genomic fingerprinting. Each site hosted unique and nearly exclusive serovar assemblages. Genomic fingerprint analysis offered a more complex model of S. enterica biogeography, with evidence of both unique strain pools and of spatial population structuring along a geographic gradient. These findings suggest that even relatively generalist enteric bacteria may be strongly dispersal limited in a natural system with strong barriers, such as oceanic divides. Yet, these differing results seen on two typing methods also suggests that genomic variation is less dispersal limited, allowing for different ecological processes to shape biogeographical patterns of the core and flexible portions of this bacterial species' genome

A roadmap for island biology: 50 fundamental questions after 50 years of The Theory of Island Biogeography

Aims The 50th anniversary of the publication of the seminal book, The Theory of Island Biogeography, by Robert H. MacArthur and Edward O. Wilson, is a timely moment to review and identify key research foci that could advance island biology. Here, we take a collaborative horizon-scanning approach to identify 50 fundamental questions for the continued development of the field. Location Worldwide. Methods We adapted a well-established methodology of horizon scanning to identify priority research questions in island biology, and initiated it during the Island Biology 2016 conference held in the Azores. A multidisciplinary working group prepared an initial pool of 187 questions. A series of online surveys was then used to refine a list of the 50 top priority questions. The final shortlist was restricted to questions with a broad conceptual scope, and which should be answerable through achievable research approaches. Results Questions were structured around four broad and partially overlapping island topics, including: (Macro)Ecology and Biogeography, (Macro)Evolution, Community Ecology, and Conservation and Management. These topics were then subdivided according to the following subject areas: global diversity patterns (five questions in total); island ontogeny and past climate change (4); island rules and syndromes (3); island biogeography theory (4); immigration–speciation–extinction dynamics (5); speciation and diversification (4); dispersal and colonization (3); community assembly (6); biotic interactions (2); global change (5); conservation and management policies (5); and invasive alien species (4). Main conclusions Collectively, this cross-disciplinary set of topics covering the 50 fundamental questions has the potential to stimulate and guide future research in island biology. By covering fields ranging from biogeography, community ecology and evolution to global change, this horizon scan may help to foster the formation of interdisciplinary research networks, enhancing joint efforts to better understand the past, present and future of island biotas

Role of preoperative intravenous iron therapy to correct anemia before major surgery: a systematic review and meta-analysis

Abstract Background Preoperative anemia is a common comorbidity that often necessitates allogeneic blood transfusion (ABT). As there is a risk associated with blood transfusions, preoperative intravenous iron (IV) has been proposed to increase the hemoglobin to reduce perioperative transfusion; however, randomized controlled trials (RCT) investigating this efficacy for IV iron are small, limited, and inconclusive. Consequently, a meta-analysis that pools these studies may provide new and clinically useful information. Methods/design Databases of MEDLINE, EMBASE, EBM Reviews; Cochrane-controlled trial registry; Scopus; registries of health technology assessment and clinical trials; Web of Science; ProQuest Dissertations and Theses; Clinicaltrials.gov; and Conference Proceedings Citation Index-Science (CPCI-S) were searched. Also, we screened all the retrieved reference lists. Selection criteria Titles and abstracts were screened for relevance (i.e., relevant, irrelevant, or potentially relevant). Then, we screened full texts of those citations identified as potentially applicable. Results Our search found 3195 citations and ten RCTs (1039 participants) that met our inclusion criteria. Preoperative IV iron supplementation significantly decreases ABT by 16% (risk ratio (RR): 0.84, 95% confidence interval [CI]: 0.71, 0.99, p = 0.04). In addition, preoperatively, hemoglobin levels increased after receiving IV iron (mean difference [MD] between the study groups: 7.15 g/L, 95% CI: 2.26, 12.04 g/L, p = 0.004) and at follow-up >  4 weeks postoperatively (MD: 6.46 g/L, 95% CI: 3.10, 9.81, p = 0.0002). Iron injection was not associated with increased incidence of non-serious or serious adverse effects across groups (RR: 1.13, 95% CI: 0.78, 1.65, p = 0.52) and (RR: 0.96, 95% CI: 0.44, 2.10, p = 0.92) respectively. Conclusions With moderate certainty, due to the high risk of bias in some studies in one or two domains, we found intravenous iron supplementation is associated with a significant decrease in the blood transfusions rate, and modest hemoglobin concentrations rise when injected pre-surgery compared with placebo or oral iron supplementation. However, further full-scale randomized controlled trials with robust methodology are required. In particular, the safety, quality of life, and cost-effectiveness of different intravenous iron preparations require further evaluation

Neurovascular dysfunction and neuroinflammation in a Cockayne syndrome mouse model

Cockayne syndrome (CS) is a rare, autosomal genetic disorder characterized by premature aging-like features, such as cachectic dwarfism, retinal atrophy, and progressive neurodegeneration. The molecular defect in CS lies in genes associated with the transcription-coupled branch of the nucleotide excision DNA repair (NER) pathway, though it is not yet clear how DNA repair deficiency leads to the multiorgan dysfunction symptoms of CS. In this work, we used a mouse model of severe CS with complete loss of NER (Csa−/−/Xpa−/−), which recapitulates several CS-related phenotypes, resulting in premature death of these mice at approximately 20 weeks of age. Although this CS model exhibits a severe progeroid phenotype, we found no evidence of in vitro endothelial cell dysfunction, as assessed by measuring population doubling time, migration capacity, and ICAM-1 expression. Furthermore, aortas from CX mice did not exhibit early senescence nor reduced angiogenesis capacity. Despite these observations, CX mice presented blood brain barrier disruption and increased senescence of brain endothelial cells. This was accompanied by an upregulation of inflammatory markers in the brains of CX mice, such as ICAM-1, TNFα, p-p65, and glial cell activation. Inhibition of neovascularization did not exacerbate neither astro- nor microgliosis, suggesting that the pro-inflammatory phenotype is independent of the neurovascular dysfunction present in CX mice. These findings have implications for the etiology of this disease and could contribute to the study of novel therapeutic targets for treating Cockayne syndrome patients.ISSN:1945-458