Analysis of the FGF gene family provides insights into aquatic adaptation in cetaceans

Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair. An evolutionary analysis revealed signatures of positive selection for FGF3 and FGF11, genes related to ear and tooth development and hypoxia, respectively. We found a D203G substitution in cetacean FGF9, which was predicted to affect FGF9 homodimerization, suggesting that this gene plays a role in the acquisition of rigid flippers for efficient manoeuvring. Cetaceans utilize low bone density as a buoyancy control mechanism, but the underlying genes are not known. We found that the expression of FGF23, a gene associated with reduced bone density, is greatly increased in the cetacean liver under hypoxic conditions, thus implicating FGF23 in low bone density in cetaceans. Altogether, our results provide novel insights into the roles of FGFs in cetacean adaptation to the aquatic environment.ope

Rare and common vertebrates span a wide spectrum of population trends

Conservation biologists often assume that rare (or less abundant) species are more likely to be declining under anthropogenic change. Here, the authors synthesise population trend data for ~2000 animal species to show that population trends cover a wide spectrum of change from losses to gains, which are not related to species rarity

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Skeleton of an unusual cat-sized marsupial relative (Metatheria: Marsupialiformes) from the middle Eocene (Lutetian: 44-43 million years ago) of Turkey

We describe a near-complete, three-dimensionally preserved skeleton of a metatherian (relative of modern marsupials) from the middle Eocene (Lutetian: 44–43 million years ago) Lülük member of the Uzunçarşıdere Formation, central Turkey. With an estimated body mass of 3–4 kg, about the size of a domestic cat (Felis catus) or spotted quoll (Dasyurus maculatus), it is an order of magnitude larger than the largest fossil metatherians previously known from the Cenozoic of the northern hemisphere. This new taxon is characterised by large, broad third premolars that probably represent adaptations for hard object feeding (durophagy), and its craniodental morphology suggests the capacity to generate high bite forces. Qualitative and quantitative functional analyses of its postcranial skeleton indicate that it was probably scansorial and relatively agile, perhaps broadly similar in locomotor mode to the spotted quoll, but with a greater capacity for climbing and grasping. Bayesian phylogenetic analysis of a total evidence dataset comprising 259 morphological characters and 9kb of DNA sequence data from five nuclear protein-coding genes, using both undated and “tip-and-node dating” approaches, place the new taxon outside the marsupial crown-clade, but within the clade Marsupialiformes. It demonstrates that at least one metatherian lineage evolved to occupy the small-medium, meso- or hypo-carnivore niche in the northern hemisphere during the early Cenozoic, at a time when there were numerous eutherians (placentals and their fossil relatives) filling similar niches. However, the known mammal fauna from Uzunçarşıdere Formation appears highly endemic, and geological evidence suggests that this region of Turkey was an island for at least part of the early Cenozoic, and so the new taxon may have evolved in isolation from potential eutherian competitors. Nevertheless, the new taxon reveals previously unsuspected ecomorphological disparity among northern hemisphere metatherians during the first half of the Cenozoic

Characterisation of secreted exosomes from the intestinal nematode Heligmosomoides polygyrus

The parasite secretome has been shown to play a key role in both pathogenicity and the regulation of host defence, allowing pathogens, such as helminths, to establish a chronic infection within the host. The recently discovered presence of extracellular vesicles within parasite-derived excretory-secretory products introduces a new mechanism of potential cross-species communication. Extracellular vesicles (EVs), such as exosomes, facilitate cellular communication through the transfer of small RNAs, lipids and proteins between cells and organisms across all three kingdoms of life. In addition to their roles in normal physiology, EVs also transport molecules from pathogens to hosts, presenting parasite antigens and transferring infectious agents. Here, I examine secreted vesicles from the murine gastrointestinal nematode Heligmosomoides polygyrus, and their potential role in the host-helminth interactions. Transmission electron microscopy reveals vesicle-like structures of 50- 100 nM in the ultracentrifuged secretory product, and potential evidence of multi-vesicular bodies in the worm intestine. This, coupled with information from the exoproteome, helped support the hypothesis that exosomes originate from the parasite intestinal tract. I have completed a series of studies looking at the fundamental properties of exosome-cell interactions, providing comparative studies between mammalian and H. polygyrus-derived exosomes. I have determined some of the key factors influencing exosome uptake, including time of incubation, cell type and exosome origin. Through microarray analysis of H. polygyrus exosome-treated small intestinal epithelial cells, we see significant gene expression changes, including those involved in the regulation of signalling and the immune response, such as DUSP1 (dual-specificity phosphatase) and IL1RL1 (the receptor for IL-33). The modest reduction of inflammatory cytokine responses by exosomes in small intestinal cell lines was amplified in immune cells, such as macrophages. Exosomes can significantly reduce expression of classical activation markers, as well as inflammatory cytokine production in the macrophage cell line RAW 264.7, and this is further supported by similar responses in bone marrow-derived macrophages. Owing to their suppressive nature, I demonstrate that immunization of mice with an exosome/alum conjugate generates significant protection from a subsequent H. polygyrus larval challenge, as seen through a reduction in egg counts and worm burden. I have investigated the role of the IL33 receptor (IL-33R); a key molecule associated with parasitic resistance that is suppressed by exosomes in type-2 associated immune responses. Uptake of H. polygyrus-derived exosomes by alternatively activated macrophages caused the suppression of type 2 cytokine/protein release and the reduction of key genes associated with this phenotype. In addition, there was also significant repression of both transcript and surface T1/ST2, a subunit of the IL-33R). Using a model of lung inflammation, in vivo studies demonstrate that, in both prophylactic and co-administration experiments, exosomes modulate the innate cellular response. This is represented by changes in the number of innate lymphoid cells (ILCs), bronchoalveolar lavage eosinophils and type-2 cytokine output. In this system, the expression of T1/ST2 on type 2 ILCs was also significantly reduced. I have extended the investigation on exosome-IL-33R responses by using T1/ST2 knockout mice. Despite generating strong antibody responses, vaccination against exosomes could not protect T1/ST2 knockout mice against a subsequent infection. This work suggests that exosomes secreted by nematodes could mediate the transfer and uptake of parasite products into host cells, establishing cross-species communication to suppress the host ‘danger’ or inflammatory response

Exploring the impact of fossil constraints on the divergence time estimates of derived liverworts

In this study, we evaluate the impact of fossil assignments and different models of calibration on divergence time estimates carried out as Bayesian analyses. Estimated ages from preceding studies and liverwort inclusions from Baltic amber are used as constraints on a molecular phylogeny of Cephaloziineae (Jungermanniopsida) obtained from sequences of two chloroplast coding regions: rbcL and psbA. In total, the comparison of 12 different analyses demonstrates that an increased reliability of the chronograms is linked to the number of fossils assigned and to the accuracy of their assignments. Inclusion of fossil constraints leads to older ages of most crown groups, but has no influence on lineage through time plots suggesting a nearly constant accumulation of diversity since the origin of Cephaloziineae in the early to Middle Jurassic. Our results provide a note of caution regarding the interpretation of chronograms derived from DNA sequence variation of extant species based on a single calibration point and/or low accuracy of the assignment of fossils to nodes in the phylogeny

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

Contains fulltext : 171518.PDF (publisher's version ) (Open Access)In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species