Holocephalan (Chondrichthyes) dental plates with hypermineralized dentine as a substitute for missing teeth through developmental plasticity

All extant holocephalans (Chimaeroidei) have lost the ability to make individual teeth, as tooth germs are not part of the embryonic development of the dental plates or of their continuous growth. Instead, a hypermineralized dentine with a unique mineral, whitlockin, is specifically distributed within a dentine framework into structures that give the dental plates their distinctive, species-specific morphology. Control of the regulation of this distribution must be cellular, with a dental epithelium initiating the first outer dentine, and via contact with ectomesenchymal tissue as the only embryonic cell type that can make dentine. Chimaeroids have three pairs of dental plates within their mouth, two in the upper jaw and one in the lower. In the genera Chimaera, Hydrolagus and Harriotta, the morphology and distribution of this whitlockin within each dental plate differs both between different plates in the same species and between species. Whitlockin structures include ovoids, rods and tritoral pads, with substantial developmental changes between these. For example, rods appear before the ovoids and result from a change in the surrounding trabecular dentine. In Harriotta, ovoids form separately from the tritoral pads, but also contribute to tritor development, while in Chimaera and Hydrolagus, tritoral pads develop from rods that later are perforated to accommodate the vasculature. Nevertheless, the position of these structures, secreted by the specialized odontoblasts (whitloblasts), appears highly regulated in all three species. These distinct morphologies are established at the aboral margin of the dental plate, with proposed involvement of the outer dentine. We observe that this outer layer forms into serially added lingual ridges, occurring on the anterior plate only. We propose that positional, structural specificity must be contained within the ectomesenchymal populations, as stem cells below the dental epithelium, and a coincidental occurrence of each lingual, serial ridge with the whitlockin structures that contribute to the wear-resistant oral surface.     

Conformational dynamics of the human propeller telomeric DNA quadruplex on a microsecond time scale

The human telomeric DNA sequence with four repeats can fold into a parallel-stranded propeller-type topology. NMR structures solved under molecular crowding experiments correlate with the crystal structures found with crystal-packing interactions that are effectively equivalent to molecular crowding. This topology has been used for rationalization of ligand design and occurs experimentally in a number of complexes with a diversity of ligands, at least in the crystalline state. Although G-quartet stems have been well characterized, the interactions of the TTA loop with the G-quartets are much less defined. To better understand the conformational variability and structural dynamics of the propeller-type topology, we performed molecular dynamics simulations in explicit solvent up to 1.5 μs. The analysis provides a detailed atomistic account of the dynamic nature of the TTA loops highlighting their interactions with the G-quartets including formation of an A:A base pair, triad, pentad and hexad. The results present a threshold in quadruplex simulations, with regards to understanding the flexible nature of the sugar-phosphate backbone in formation of unusual architecture within the topology. Furthermore, this study stresses the importance of simulation time in sampling conformational space for this topology.     

Integrating multiple data sources to assess the distribution and abundance of bottlenose dolphins Tursiops truncatus in Scottish waters

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Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6

Cholesterol homeostasis is crucial for cellular function and organismal health. The key regulator for the cholesterol biosynthesis is sterol-regulatory element binding protein (SREBP)-2. The biochemical process and physiological function of SREBP-2 have been well characterized; however, it is not clear how this gene is epigenetically regulated. Here we have identified sirtuin (Sirt)6 as a critical factor for Srebp2 gene regulation. Hepatic deficiency of Sirt6 in mice leads to elevated cholesterol levels. On the mechanistic level, Sirt6 is recruited by forkhead box O (FoxO)3 to the Srebp2 gene promoter where Sirt6 deacetylates histone H3 at lysines 9 and 56, thereby promoting a repressive chromatin state. Remarkably, Sirt6 or FoxO3 overexpression improves hypercholesterolemia in diet-induced or genetically obese mice. In summary, our data suggest an important role of hepatic Sirt6 and FoxO3 in the regulation of cholesterol homeostasis.     

Dysbiosis Signature of Fecal Microbiota in Colorectal Cancer Patients

The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R?=?0.462, P?=?0.046?<?0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.     

Pyrosequencing Analysis of the Salivary Microbiota of Healthy Chinese Children and Adults

Describing the biogeography of bacterial communities within the human body is critical for establishing healthy baselines from which to detect differences associated with diseases. Little is known, however, about the baseline of normal salivary microbiota from healthy Chinese children and adults. With parallel barcoded 454 pyrosequencing, the bacterial diversity and richness of saliva were thoroughly investigated from ten healthy Chinese children and adults. The overall taxonomic distribution of our metagenomic data demonstrated that the diversity of salivary microbiota from children was more complex than adults, while the composition and richness of salivary microbiota were similar in children and adults, especially for predominant bacteria. A large number of bacterial phylotypes were shared by healthy children and adults, indicating the existence of a core salivary microbiome. In children and adults, the vast majority of sequences in salivary microbiota belonged to Streptococcus, Prevotella, Neisseria, Haemophilus, Porphyromonas, Gemella, Rothia, Granulicatella, Fusobacterium, Actinomyces, Veillonella, and Aggregatibacter, which constituted the major components of normal salivary microbiota. With the exception of Actinomyces, the other seven non-predominant bacteria including Moraxella, Leptotrichia, Peptostreptococcus, Eubacterium, and members of Neisseriaceae, Flavobacteriaceae, and SR1 showed significant differences between children and adults (p?<?0.05). We first established the framework of normal salivary microbiota from healthy Chinese children and adults. Our data represent a critical step for determining the diversity of healthy microbiota in Chinese children and adults, and our data established a platform for additional large-scale studies focusing on the interactions between health and diseases in the future.     

An immunoaffinity purification method for the proteomic analysis of ubiquitinated protein complexes

Protein ubiquitination plays an important role in the regulation of many cellular processes, including protein degradation, cell cycle regulation, apoptosis, and DNA repair. To study the ubiquitin proteome we have established an immunoaffinity purification method for the proteomic analysis of endogenously ubiquitinated protein complexes. A strong, specific enrichment of ubiquitinated factors was achieved using the FK2 antibody bound to protein G-beaded agarose, which recognizes monoubiquitinated and polyubiquitinated conjugates. Mass spectrometric analysis of two FK2 immunoprecipitations (IPs) resulted in the identification of 296 FK2-specific proteins in both experiments. The isolation of ubiquitinated and ubiquitination-related proteins was confirmed by pathway analyses (using Ingenuity Pathway Analysis and Gene Ontology-annotation enrichment). Additionally, comparing the proteins that specifically came down in the FK2 IP with databases of ubiquitinated proteins showed that a high percentage of proteins in our enriched fraction was indeed ubiquitinated. Finally, assessment of protein–protein interactions revealed that significantly more FK2-specific proteins were residing in protein complexes than in random protein sets. This method, which is capable of isolating both endogenously ubiquitinated proteins and their interacting proteins, can be widely used for unraveling ubiquitin-mediated protein regulation in various cell systems and tissues when comparing different cellular states.     

The epidemiology underlying age‐related avian malaria infection in a long‐lived host: the mute swan Cygnus olor

Quantifying the factors that predict parasite outbreak and persistence is a major challenge for both applied and fundamental biology. Key to understanding parasite prevalence and disease outbreaks is determining at what age individuals show signs of infection, and whether or not they recover. Age‐dependent patterns of the infection of a host population by parasites can indicate among‐individual heterogeneities in their susceptibility to, or rate of recovery from, parasite infections. Here, we present a cross‐sectional study of avian malaria in a long‐lived bird species, the mute swan Cygnus olor, examining age‐related patterns of parasite prevalence and modelling patterns of infection and recovery. One‐hundred and fifteen swans, ranging from one to nineteen years old, were screened for infection with Plasmodium, Haemoproteus and Leucocytozoon parasites. Infections with three cytochrome‐b lineages of Haemoproteus were found (pooled prevalence 67%), namely WW1 (26%), which is common in passerine birds, and two new lineages closely related to WW1: MUTSW1 (25%) and MUTSW2 (16%). We found evidence for age‐related infection in one lineage, MUTSW1. Catalytic models examining patterns of infection and recovery in the population suggested that infections in this population were not life‐long – recovery of individuals was included in the best fitting models. These findings support the results of recent studies that suggest hosts can clear infections, although patterns of infection‐related mortality in older birds remain to be studied in more detail.     

Use of Mangroves by Lemurs

Despite an increasing recognition of the ecosystem services provided by mangroves, we know little about their role in maintaining terrestrial biodiversity, including primates. Madagascar’s lemurs are a top global conservation priority, with 94 % of species threatened with extinction, but records of their occurrence in mangroves are scarce. I used a mixed-methods approach to collect published and unpublished observations of lemurs in mangroves: I carried out a systematic literature search and supplemented this with a targeted information request to 1243 researchers, conservation and tourism professionals, and others who may have visited mangroves in Madagascar. I found references to, or observations of, at least 23 species in 5 families using mangroves, representing >20% of lemur species and >50% of species whose distributions include mangrove areas. Lemurs used mangroves for foraging, sleeping, and traveling between terrestrial forest patches, and some were observed as much as 3 km from the nearest permanently dry land. However, most records were anecdotal and thus tell us little about lemur ecology in this habitat. Mangroves are more widely used by lemurs than has previously been recognized and merit greater attention from primate researchers and conservationists in Madagascar.