Host genetics and diet,but not immunoglobulin A expression,converge to shape compositional features of the gut microbiome in an advanced intercross population of mice

Background

Individuality in the species composition of the vertebrate gut microbiota is driven by a combination of host and environmental factors that have largely been studied independently. We studied the convergence of these factors in a G₁₀ mouse population generated from a cross between two strains to search for quantitative trait loci (QTLs) that affect gut microbiota composition or ileal Immunoglobulin A (IgA) expression in mice fed normal or high-fat diets.

Results

We found 42 microbiota-specific QTLs in 27 different genomic regions that affect the relative abundances of 39 taxa, including four QTL that were shared between this G₁₀ population and the population previously studied at G₄. Several of the G₁₀ QTLs show apparent pleiotropy. Eight of these QTLs, including four at the same site on chromosome 9, show significant interaction with diet, implying that diet can modify the effects of some host loci on gut microbiome composition. Utilization patterns of IghV variable regions among IgA-specific mRNAs from ileal tissue are affected by 54 significant QTLs, most of which map to a segment of chromosome 12 spanning the Igh locus. Despite the effect of genetic variation on IghV utilization, we are unable to detect overlapping microbiota and IgA QTLs and there is no significant correlation between IgA variable pattern utilization and the abundance of any of the taxa from the fecal microbiota.

Conclusions

We conclude that host genetics and diet can converge to shape the gut microbiota, but host genetic effects are not manifested through differences in IgA production.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0552-6) contains supplementary material, which is available to authorized users.     

Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western' and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with Western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term Western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either Western or high fat feeding. Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with Western diet.     

Heard but not seen: an acoustic survey of the African forest elephant population at Kakum Conservation Area, Ghana

This study, designed to survey forest elephants ( Loxodonta africana cyclotis ) at Kakum Conservation Area, Ghana, is the first to apply acoustic methods to elephant abundance estimation and to compare results with independent survey estimates. Nine acoustic sensors gathered sound continuously for 38 days. Low-frequency calling rates have been established as useful elephant abundance indices at a Namibian watering hole and a central African forest clearing. In this study, we estimated elephant population size by applying an abundance index model and detection function developed in central Africa to data from simultaneous sampling periods on Kakum sensors. The sensor array recorded an average of 1.81 calls per 20-min sampling period from an effective detection area averaging 10.27 km². The resulting estimate of 294 elephants (95% CI: 259–329) falls within confidence bounds of recent dung-based surveys. An extended acoustic model, estimating the frequency with which elephants are silent when present, yields an estimate of 350 elephants (95% CI: 315–384). Acoustic survey confidence intervals are at least half as wide as those from dung-based surveys. This study demonstrates that acoustic surveying is a valuable tool for estimating elephant abundance, as well as for detecting other vocal species and anthropogenic noises that may be associated with poaching.     

Phosphorylation of Cdc6 at serine 74, but not at serine 106, drives translocation of Cdc6 to the cytoplasm

Phosphorylation‐dependent cytoplasmic translocation of human Cdc6 during S phase is sufficient to control its activity after origin firing. Export from the nucleus also serves as a mechanism for preventing re‐replication in mammalian cells. Phosphorylation of the CDK consensus serine residues 54, 74, and 106 has been suggested to be involved in the cytoplasmic translocation of Cdc6. To determine the relative importance of the three phosphorylation sites, we have generated Cdc6 variants by substituting one or more of the three serine residues with alanine or aspartic acid and have assessed their cytoplasmic translocation behavior. Phosphorylation of serine 74 mainly contributes to the cytoplasmic translocation of Cdc6, while serine 54 phosphorylation provides a minor contribution. In contrast, phosphorylation at serine 106 does not affect the nuclear export of Cdc6. Comparative results were found in cells coexpressing the phosphorylation defective mutants of Cdc6 and cyclin A as well as in non‐transfected cells synchronized by their release from a double thymidine block. We conclude that Cdk‐mediated phosphorylation of Cdc6 at serine 74 is required for the cytoplasmic translocalization of Cdc6 during the cell cycle. Phosphorylation of Cdc6 at serine 54 plays a minor role and phosphorylation of serine 106 plays no role in the cytoplasmic localization of Cdc6. The phosphorylation of S74 in Cdc6 could be important for binding to the nuclear export protein for translocalization. J. Cell. Physiol. 228: 1221–1228, 2013. © 2012 Wiley Periodicals, Inc.     

广西顶蛳山遗址人骨的龋齿病理观察

顶蛳山遗址位于广西壮族自治区南宁市邕宁区,保存了丰富的新石器时代文化遗存以及大量的古人类骨骼遗存。本文主要从龋齿研究入手,对顶蛳山二、三期文化(8-7 ka BP)中大于15岁的169个体的2737枚恒齿进行了观察。分别统计了龋齿等级和个体和牙齿患龋率以评估人群患龋情况,进而分析顶蛳山遗址人群的口腔健康状况,并探讨了食物构成、饮食行为与社会经济等。统计结果表明,顶蛳山遗址人群的个体和牙齿患龋率都较高。患龋率在两性、葬式、年龄段间都存在差异,女性患龋程度要高于男性;不同葬式之间差异也显著,随着年龄的增长患龋的比例和程度也随之加深。通过与其他8组新石器时代国内遗址人群的个体和牙齿患龋率的对比,我们看到包含顶蛳山在内的三组华南渔猎采集遗址的个体和牙齿患龋率都要高于其他遗址,农业遗址的人群要低于华南遗址的患龋率,而混合经济遗址的患龋率最低。龋齿的出现与人类饮食中的碳水化合物关系密切。据此,我们推测顶蛳山及其他两组华南遗址的高患龋与碳水化合物的摄入关系密切,但这与一般所认为的农业的出现没有联系。三组遗址都是以渔猎采集主导的社会经济形态,并且这时期农业并未传播至华南地区。因此我们的分析表明高患龋率与农业并没有必然联系,而华南地区当时人群所食用的碳水化合物可能源于当地的块茎类和含蔗糖类植物。     

C. albicans increases cell wall mannoprotein, but not mannan, in response to blood, serum and cultivation at physiological temperature

The cell wall of Candida albicans is central to the yeasts ability to withstand osmotic challenge, to adhere to host cells, to interact with the innate immune system and ultimately to the virulence of the organism. Little is known about the effect of culture conditions on the cell wall structure and composition of C. albicans. We examined the effect of different media and culture temperatures on the molecular weight (Mw), polymer distribution and composition of cell wall mannan and mannoprotein complex. Strain SC5314 was inoculated from frozen stock onto yeast peptone dextrose (YPD), blood or 5% serum agar media at 30 or 37°C prior to mannan/mannoprotein extraction. Cultivation of the yeast in blood or serum at physiologic temperature resulted in an additive effect on Mw, however, cultivation media had the greatest impact on Mw. Mannan from a yeast grown on blood or serum at 30°C showed a 38.9 and 28.6% increase in Mw, when compared with mannan from YPD-grown yeast at 30°C. Mannan from the yeast pregrown on blood or serum at 37°C showed increased Mw (8.8 and 26.3%) when compared with YPD mannan at 37°C. The changes in Mw over the entire polymer distribution were due to an increase in the amount of mannoprotein (23.8-100%) and a decrease in cell wall mannan (5.7-17.3%). We conclude that C. albicans alters the composition of its cell wall, and thus its phenotype, in response to cultivation in blood, serum and/or physiologic temperature by increasing the amount of the mannoprotein and decreasing the amount of the mannan in the cell wall.     

The likely financial effects on individuals,industry and commerce of the use of genetic information.

In this paper I look at the financial implications of genetic testing, particularly in the employment and pensions fields. I have generally not covered life insurance, as that is covered in other papers in this Discussion Meeting. However, the issues are similar, although the emphasis is different. Inevitably there is an element of speculation involved; genetic testing is in its infancy and so we cannot predict either what information we will be able to obtain through genetic testing, nor the uses that may be devised for this information.     

Management and husbandry of ruffed lemurs,Varecia variegata,at the San Diego Zoo. I. Captive population,San Diego Zoo housing and diet

The captive history of the ruffed lemur is presented with concentration on taxonomy, captive population and husbandry of the San Diego Zoo population. At the conclusion of 1985, the living population of black and white ruffed lemurs numbered 358; red ruffed lemurs totaled 125. The San Diego Zoo population, established between 1965 and 1970, began with two pairs of each subspecies. Intensive breeding at the Primate Propagation Center resulted in the birth of 135 black and white ruffed lemur infants and 95 red ruffed lemur infants as of January 7, 1986. Housing specifications are presented for the off-exhibit 96-unit breeding facility, describing enclosure size, material, nest box composition, and enclosure furniture. The diet is described, which emphasizes high-protein, high-fiber foods and leaves.     

The roads and bridges of science. Research infrastructures are key components of Europe's future research, but their funding is not guaranteed

Research infrastructures are a crucial component of modern biological research, but the EU has not yet figured out how to fund and maintain them.The development of recombinant gene technology in the 1970s heralded a new era of application-oriented research for molecular biology, with a huge economic impact. During the decades that have followed, biological research and development have become a major enterprise, with an increasing demand for sophisticated technologies, databases, tissue banks and other tools that range from microscopes and DNA sequencers to bioinformatics services and mutant collections. Biology has followed in the footsteps of physics and astronomy, which share costly instrumentation such as particle accelerators, observatories and satellites. A key difference is that biological research infrastructures are often distributed across several sites and are less costly to establish. Nevertheless, they are expensive to operate and maintain, and need long-term financial support.There is no doubt among scientists that research infrastructures are essential for biomedicine and the life sciencesThe European Union (EU) regards biomedical research as an important component of its future economic and social development as part of its ''Innovation Union'' strategy (EC, 2010), but the necessary creation and operation of research infrastructures is not keeping pace. European biologists have been highlighting the problem for years (van Dyck, 2005), to the effect that some pan-European infrastructures for biomedical research and the life sciences have been created, such as the European Bioinformatics Institute (EBI; Hinxton, UK). The European Commission (EC) also established the European Strategy Forum on Research Infrastructures (ESFRI) in 2002, to define the infrastructures required for international research (ESFRI, 2006, 2011). However, most of the planned projects for the biomedical and life sciences (ESFRI, 2011)

The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

Published analyses of the sequences of three genes from the 1918 Spanish influenza virus have cast doubt on the theory that it came from birds immediately before the pandemic. They showed that the virus was of the H1N1 subtype lineage but more closely related to mammal-infecting strains than any known bird-infecting strain. They provided no evidence that the virus originated by gene reassortment nor that the virus was the direct ancestor of the two lineages of H1N1 viruses currently found in mammals; one that mostly infects human beings, the other pigs. The unusual virulence of the virus and why it produced a pandemic have remained unsolved. We have reanalysed the sequences of the three 1918 genes and found conflicting patterns of relatedness in all three. Various tests showed that the patterns in its haemagglutinin (HA) gene were produced by true recombination between two different parental HA H1 subtype genes, but that the conflicting patterns in its neuraminidase and non-structural-nuclear export proteins genes resulted from selection. The recombination event that produced the 1918 HA gene probably coincided with the start of the pandemic, and may have triggered it.     

Calmodulin antagonists decrease the binding of epidermal growth factor to transformed, but not to normal, human fibroblasts.

Four psychoactive agents which inhibit calmodulin activity were used to study their effect on the binding of epidermal growth factor (EGF) to normal and simian-virus-40-transformed human fibroblasts (WI38). These calmodulin antagonists decreased the binding of 125I-labelled EGF to the transformed, but not to the normal, cell in a dose-dependent manner. The mechanism of this effect appears to be due to a decrease in the apparent affinity of the plasma-membrane EGF receptor for the EGF molecule.     

The university-promoted patent at the crossroads of the research results and immediate industrial use

The departments, indeed the laboratories of the public research institutions, no longer are satisfied with displaying a certain number of annual scientific publications meant to highlight their expertise and know-how. In effect, for some years now, a new trend has been in vogue: stimulated by all the national and international public bodies, they are calling increasingly on the “patent pending” solution to make optimum use of the results of specific researches on the one hand and, on the other hand, to assert their excellence vis-à-vis the Ministry of Research of their country which is supposed to finance them.However, caught up in the euphoria of the research results, and lost in their formulae and practices, these researchers lose sight of the basis for a patent and its real reason for being (patent charter). A patent necessarily must be of service to the community, that is to say that essentially it must contribute to the improvement of the quality of life of the population. To achieve this goal, going through certain stages is a must, namely that to start with a patent must be absolutely profitable to industry in order that, subsequently, it be consistent with its being of service to the community. In this context, its validity is set at 10 years renewable for another 10 years based on specific parameters as stipulated by the national and international patent institutions, indeed by the EPO (European Patent Office) the headquarters of which is in Munich. Its use by industry ensures proceeds for 10, even 20 years and must represent the material fruit of the applicant's effort. Beyond this period, the patent becomes public and therefore available to everyone. But the crucial problem is this: when can a patent really be used and how to do so as best as possible to guarantee profits for both parties involved and thus justify its reason for being?The purpose of this work thus is to incite university researchers to think about the real usefulness of a patent on the one hand and, on the other hand, to ponder over the best way of using, in close cooperation with industry, the fruit of the research and the registering of the patent, both financed by public funds. For the latter, owing to their nature, demand that there be no wastage and cautious management thereof.     

The 'destruction box' of cyclin A allows B-type cyclins to be ubiquitinated, but not efficiently destroyed.

The destruction of mitotic cyclins by programmed proteolysis at the end of mitosis is an important element in cell cycle control. This proteolysis depends on a conserved motif of nine residues known as the 'destruction box', which is located 40-50 residues from the N-terminus. The sequences of the A- and B-type destruction boxes are slightly different, which might account for the differences in timing of their destruction. When the cyclin A-type destruction box was substituted for the normal one in cyclin B1 or B2, however, the resulting constructs were unexpectedly stable, although the converse substitution of B-type destruction boxes in cyclin A permitted normal degradation. We compared the ubiquitination of various cyclin constructs, and found that whereas mutation of the highly conserved residues in the destruction box strongly reduced the level of ubiquitinated intermediates, the stable destruction box 'swap' constructs did form such adducts. Thus, while ubiquitination is probably necessary for cyclin destruction, it is not sufficient. We also found that poly-ubiquitinated cyclin derivatives are still bound to p34cdc2, which is not detectably ubiquitinated itself, raising the questions of how cyclin and cdc2 dissociate from one another, and at what stage, in the process of degradation.     

Insulin stimulates proteolysis of the alpha-subunit, but not the beta-subunit, of its receptor at the cell surface in rat liver.

Insulin receptors in rat liver plasma membranes contain two alpha- and two beta-subunits held together by interchain disulphide bonds ([alpha beta]2 receptors). Affinity-labelled receptors were digested with chymotrypsin or elastase and then exposed to dithiothreitol before solubilization from membranes and SDS/polyacrylamide-gel electrophoresis. This resulted in partial reduction and isolation of Mr-225,000 alpha beta, Mr-200,000 alpha 1 beta, Mr-165,000 alpha beta 1 and Mr-145,000 alpha 1 beta 1 receptor halves containing intact (alpha, beta) or degraded (alpha 1, beta 1) subunits. The ability to identify half-receptor complexes containing intact or degraded subunits made it possible to assay each subunit simultaneously for insulin-induced proteolysis in isolated plasma membranes or during perfusion of rat liver in situ with insulin. In liver membranes, insulin binding increased the fraction of receptors containing degraded alpha-subunits to about one-third of the total population during 2 h of incubation at 23 degrees C. beta-Subunit proteolysis increased only minimally during this time. Plasma membranes isolated from livers perfused with insulin at 37 degrees C contained degraded alpha-subunits but only intact beta-subunits, showing that insulin induced cell-surface proteolysis of the binding, but not the kinase, domain of its receptor. Since previous observations [Lipson, Kolhatkar & Donner (1988) J. Biol. Chem 263, 10495-10501] have shown that receptors containing degraded alpha-subunits are internalized but do not recycle, it is possible that cell-surface degradation may play a role in the regulation of insulin-receptor number in hepatic tissue. Proteolysis of the beta-subunit is not a likely mechanism by which receptor-kinase activity may be attenuated under physiological conditions.     

The biology and use of zebrafish, Brachydanio rerio in fisheries research.

PREFACE TO THE REVIEW BY PROFESSOR H. LAALE ON THE BIOLOGY AND USE OF THE ZEBRAFISH, BRACHYDANIO RERIO IN FISHERIES RESEARCH
The growing demand for increasingly sophisticated information on the toxic hazards of potential water pollutants has focused attention on the need for a suitable 'standard' animal model which could be accepted internationally. The Zebrafish, Brachydanio rerio (Hamilton-Buchanan, 1822, 1823) is considered to be the most likely candidate. It is relatively easy to maintain and breed in laboratory aquaria and it has proved to be responsive to a wide range of mutagens, carcinogens and teratogens, as well as direct toxicants. B. rerio has been the subject of a considerable number of investigations involving a diverse spectrum of disciplines in a number of countries. Professor Hans Laale, who has himself contributed to our knowledge of the embryopathology of B. rerio , has summarized and collated the findings of 450 publications, a number of which are unlikely to have become available to fishery scientists. We hope the publication of this review will aid those who are working with B. rerio and provide comprehensive data on the advantages and limitations of B. rerio as a contender for the standard laboratory fish for the safety evaluation of aquatic pollutants.
T he E ditor