New zebrafish models of neurodegeneration

In modern biomedicine, the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on the society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here, we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited. We shall do so by citing and commenting on recent breakthroughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms

Incidence and risk factors of periparturient conditions in smallholder dairy cattle herds in Kikuyu Division of Kiambu District, Kenya

A study was carried out on 117 smallholder dairy cattle herds in Kikuyu Division of Kiambu District Kenya between April 2004 and December 2004 to determine the incidence of periparturient conditions (downer cow syndrome, dystocia, milk fever and retained placenta among others) in smallholder dairy cattle herds and the associated factors (plausible predictor variables; age, parity and management systems among others) from a total of 206 dairy cattle. Data were collected during farm visits by observation, interviews using semi-structured questionnaires and clinical examination of animals. The most common conditions encountered were downer cow syndrome (12.6 %), dystocia (17.0 %), mastitis (9.5 %), metritis (7.3 %) milk fever (13 %) and retained afterbirth (26.6 %). The overall cumulative incidence of the periparturient conditions was 67 %. Animals with milk fever were 5 times more likely to develop retained placenta (P=0.04) while those with a history of having developed retained placenta in a previous parturition were at 2 times more likely to develop retained afterbirth (P=0.05). Cows with milk fever were 9 times more likely to develop owner cow syndrome (P <0.001) while those that were not given supplemental feed in the last trimester were 4.8 times more likely to develop downer cow syndrome (P=0.007). Animals that had dystocia were 3.9 times more likely to develop metritis (P=0.02) and while those with retained placenta were 5.2 times more likely to develop metritis (P=0.03). In addition, animals with dystocia were 10.55 times more likely to develop postpartum haemorrhage (P=0.01) and 58.9 times more likely to develop injuries to the birth canal (P<0.01). From this study it can be concluded that downer cow syndrome, dystocia, mastitis, metritis, milk fever and retained placenta were the most common periparturient conditions in smallholder dairy cattle herds in Kikuyu division of Kiambu district

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Early warning indicators of decadal shifts in the planktonic assemblage of the Cabo Frio upwelling ecosystem

Long-term monitoring of coupled environmental and biological components in upwelling ecosystems is critical for early warning under the global warming context. Temperature, salinity, nutrients, and plankton populations are promising indicators of the ecosystem state that help us to address the current status of the oceans and construct better predictions for the future. The Cabo Frio Upwelling System (CFUS) is a regionally productive wind-driven coastal upwelling ecosystem on the northern boundary of the South Brazilian Shelf sustaining diverse marine life including large stocks of fish and squid. Like other cold marine ecosystems, most of its functioning is likely threatened by ocean warming which emphasizes the need for ecological indicators. This study aimed to analyze the causal relationships between the temporal changes in the physical and chemical properties and the dominant planktonic communities leveraging long-term observations (20 years). The results suggested a link between the temporal changes in the ecosystem conditions and the composition of the plankton assemblage, notably an increasing proportion of dinoflagellates relative to diatoms and cladocerans relative to copepods. This increase in the proportional abundance of dinoflagellates and cladocerans over time suggests a regime shift in the plankton assemblages during the 2000s, highlighting some large phytoplankton and zooplankton groups as early indicators of productivity shifts in upwelling ecosystem

Mutability and Importance of a Hypermutable Cell Subpopulation that Produces Stress-Induced Mutants in Escherichia coli

In bacterial, yeast, and human cells, stress-induced mutation mechanisms are induced in growth-limiting environments and produce non-adaptive and adaptive mutations. These mechanisms may accelerate evolution specifically when cells are maladapted to their environments, i.e., when they are are stressed. One mechanism of stress-induced mutagenesis in Escherichia coli occurs by error-prone DNA double-strand break (DSB) repair. This mechanism was linked previously to a differentiated subpopulation of cells with a transiently elevated mutation rate, a hypermutable cell subpopulation (HMS). The HMS could be important, producing essentially all stress-induced mutants. Alternatively, the HMS was proposed to produce only a minority of stress-induced mutants, i.e., it was proposed to be peripheral. We characterize three aspects of the HMS. First, using improved mutation-detection methods, we estimate the number of mutations per genome of HMS-derived cells and find that it is compatible with fitness after the HMS state. This implies that these mutants are not necessarily an evolutionary dead end, and could contribute to adaptive evolution. Second, we show that stress-induced Lac+ mutants, with and without evidence of descent from the HMS, have similar Lac+ mutation sequences. This provides evidence that HMS-descended and most stress-induced mutants form via a common mechanism. Third, mutation-stimulating DSBs introduced via I-SceI endonuclease in vivo do not promote Lac+ mutation independently of the HMS. This and the previous finding support the hypothesis that the HMS underlies most stress-induced mutants, not just a minority of them, i.e., it is important. We consider a model in which HMS differentiation is controlled by stress responses. Differentiation of an HMS potentially limits the risks of mutagenesis in cell clones