Helicobacter pylori therapy demystified

We discuss the role of comparators in Helicobacter pylori treatment trials and why anti-H. pylori therapeutic trials (an infectious disease) are fundamentally different from common gastrointestinal diseases (e.g., the absence of a placebo response, the expectation that cure rates in excess of 95%, and the ability to understand why treatment fails). No comparator is absolutely required other than to 100% success and comparison trials should be limited to comparisons between therapies that reliably achieve 90% or greater success (i.e., good therapies). Comparisons with known low success regimens (i.e., bad therapies) are unethical as is withholding information from the subject regarding current effectiveness of a regimen even if that information would reduce the likelihood that the subject would volunteer. We also discuss how it is possible to predict the outcome of a published but locally untried new regimen. The reason for different outcomes of typical gastrointestinal therapies is shrouded in mystery. In contrast, treatment success for H. pylori should be predictable and treatment failures explainable. For too long expectations and analyses of H. pylori therapy has been confused with what is appropriate for gastrointestinal disease such as constipation or irritable bowel syndrome rather than for infectious diseases such as pneumonia.     

Sequential application of NaHCO3, CaCl2 and Candida oleophila (isolate 13L) affects significantly Penicillum expansum growth and the infection degree in apples

The employment of biocontrol agents to restrain postharvest pathogens is an encouraging approach, although, efficacy and consistency are still below those of synthetic pesticides. Up to date, the 'integrated control strategy' seems to be the most promising way to overcome this gap. Here, we report the feasibility to control postharvest decay caused by Penicillium expansum in apples by a 2 min, single or sequential, immersion in water with an antagonistic yeast (Candida oleophila, isolate '13L'), 2% NaHCO3 (SBC) or 1% CaCl2. The treatments were carried out, on appels cv 'Miali' either un-wounded, wounded or wound-pathogen inoculated and then stored at 2 degrees C for 30 d followed by a 6 d simulated marketing period at 20 degrees C or alternatively stored only for 7 d at 20 degrees C. As a general role, the best results were attained when CaCl2 was applied with the yeast or when preceded by the SBC treatment. When the wounding and inoculation took place 24 h before the treatment, the latter application sequence of the two salts was three times more effective compared to the treatment with the sole antagonist, and one time when performed 24 h after the treatment. Interestingly, apples immersed in the sole 2% SBC solution had the highest percentage of decay during storage and when inoculated before moving to the simulated marketing period at 20 degrees C.     

IL28B, HLA-C, and KIR variants additively predict response to therapy in chronic hepatitis C virus infection in a European Cohort: a cross-sectional study

Background

To date, drug response genes have not proved as useful in clinical practice as was anticipated at the start of the genomic era. An exception is in the treatment of chronic hepatitis C virus (HCV) genotype 1 infection with pegylated interferon-alpha and ribavirin (PegIFN/R). Viral clearance is achieved in 40%–50% of patients. Interleukin 28B (IL28B) genotype predicts treatment-induced and spontaneous clearance. To improve the predictive value of this genotype, we studied the combined effect of variants of IL28B with human leukocyte antigen C (HLA-C), and its ligands the killer immunoglobulin-like receptors (KIR), which have previously been implicated in HCV viral control.

Methods and Findings

We genotyped chronic hepatitis C (CHC) genotype 1 patients with PegIFN/R treatment-induced clearance (n = 417) and treatment failure (n = 493), and 234 individuals with spontaneous clearance, for HLA-C C1 versus C2, presence of inhibitory and activating KIR genes, and two IL28B SNPs, rs8099917 and rs12979860. All individuals were Europeans or of European descent. IL28B SNP rs8099917 “G” was associated with absence of treatment-induced clearance (odds ratio [OR] 2.19, p = 1.27×10⁻⁸, 1.67–2.88) and absence of spontaneous clearance (OR 3.83, p = 1.71×10⁻¹⁴, 2.67–5.48) of HCV, as was rs12979860, with slightly lower ORs. The HLA-C C2C2 genotype was also over-represented in patients who failed treatment (OR 1.52, p = 0.024, 1.05–2.20), but was not associated with spontaneous clearance. Prediction of treatment failure improved from 66% with IL28B to 80% using both genes in this cohort (OR 3.78, p = 8.83×10⁻⁶, 2.03–7.04). There was evidence that KIR2DL3 and KIR2DS2 carriage also altered HCV treatment response in combination with HLA-C and IL28B.

Conclusions

Genotyping for IL28B, HLA-C, and KIR genes improves prediction of HCV treatment response. These findings support a role for natural killer (NK) cell activation in PegIFN/R treatment-induced clearance, partially mediated by IL28B. Please see later in the article for the Editors'' Summary     

PCR gut analysis reveals that Tenuiphantes tenuis (Araneae: Linyphiidae) is a potentially significant predator of Argentine stem weevil,Listronotus bonariensis (Coleoptera: Curculionidae), in New Zealand pastures

Polymerase chain reaction (PCR) gut analysis was conducted on specimens of the introduced spider Tenuiphantes tenuis collected from dairy pasture in Canterbury, New Zealand. PCR primers were specifically designed to amplify a fragment of the mitochondrial gene cytochrome c oxidase subunit 1 (COI) from Listronotus bonariensis and revealed that this major pasture pest species is consumed in the field by T. tenuis. The field predation rate of L. bonariensis by T. tenuis was estimated from our PCR results together with published data on the degradation of DNA and the density of T. tenuis in Canterbury pastures. We found that T. tenuis is a potentially significant predator of L. bonariensis in New Zealand pastures.     

Step on it: can footprints from tracking tunnels be used to identify lizard species?

There are few effective or efficient established methods for monitoring cryptic herpetofauna. Footprint tracking tunnels are routinely used to index small mammal populations, but also have potential for monitoring herpetofauna. We evaluated the utility of tracking tunnels for identification of New Zealand lizards using captive- and wild-sourced animals (four skink and eight gecko species). All skink prints that we obtained were indistinct or obscure, but we obtained relatively clear, measurable prints for all gecko species. We found that identification to species level was possible for the two gecko species for which we had a large sample—Naultinus gemmeus and Woodworthia ‘Otago large’—using linear discriminant analysis (the best model correctly assigned 96.1% of individuals). Our findings suggest that footprints from tracking tunnels may be used to distinguish between species of geckos. Additional research is needed to assess the ability to further discriminate intra- and inter-genera lizard footprints from tracking tunnels, and the utility of the technique for surveying and monitoring lizard populations.     

The State of Ethnoprimatology: Its Use and Potential in Today’s Primate Research

The human–primate interface is an increasingly relevant theme in primatological research. To understand the extent of ethoprimatological studies in contemporary primatology, we explored 7 years of primatological literature through a systematic review. We reviewed original research papers published in the American Journal of Primatology, the International Journal of Primatology, Primates, and Folia Primatologica between January 2010 and December 2016 for the presence of 14 search terms relevant to the ethnoprimatological approach. We sorted research papers into topical categories to identify trends in the recent primatological literature. Of the 1551 papers that met the criteria for inclusion in this review, 12 papers (0.8%) self-identified as an ethnoprimatological study by using the term in the title or keywords, and only 17 papers (1.1%) used the term anywhere in their text. However, the presence of other relevant keywords—anthropogenic (16.3%), crop (9.1%), disturbance (18.7%), conflict (6.2%), human–nonhuman (0.5%), human–primate (1.0%), interface (1.5%), perception (2.5%), culture (2.6%), ethnography (0.1%), trade (6.8%), provision (16.1%), and tourism (4.6%)—in a variety of research papers suggests that the human–primate dimension is salient for many, if not most, areas of primatological interest. The ethnoprimatological approach is relevant to every research trend we identified in today’s primatology. We highlight existing literature that exemplifies ethnoprimatological engagement and present potential research questions in each area, demonstrating that primatology as a whole would benefit from greater attention to the human dimension.     

Ethnoprimatology without Conservation: The Political Ecology of Farmer–Green Monkey (<Emphasis Type="Italic">Chlorocebus sabaeus</Emphasis>) Relations in St. Kitts,West Indies

The driving force behind the mixed-methods ethnoprimatological endeavor is to effectively conserve nonhuman primates. In this article, I argue that ethnoprimatological research can meet this goal only by discarding the purely science views of conservation that dominate the current literature. By considering more than local ecological perceptions, their ideological agendas, and their levels of power via a political ecology framework, ethnoprimatologists can simultaneously socialize the ecosystems we study and contribute our ethological skills to advance traditionally humanist disciplines’ increased attention to a wider field of agents and structures that matter. I support these arguments through an examination of farmer–green monkey (Chlorocebus sabaeus) relations in St. Kitts. Kittitian farmers’ narrative revealed three scales that collectively construct what is locally known as “the monkey problem:” increased rates of local contact between farmers and monkeys on farms, contestations over the future of St. Kitts’ land, and global debates over appropriate strategies to manage the monkey population. I show that although “the monkey problem” in St. Kitts does not involve an endangered or threatened species, my analysis of this construct has implications for primate populations that are threatened. This is because the root cause of this “problem”—the globalized discourse of nature conservation overpowering and problematizing local views about people–animal interactions—characterizes so many of the locales home to primates of conservation concern.     

Phylogenetic analysis of slippage-like sequence variation in the V4 rRNA expansion segment in tiger beetles (Cicindelidae)

Sequence variation in the middle part of the small-subunit rRNA was studied for representatives of the major groups in the family Cicindelidae (Coleoptera). All taxa exhibited a much expanded segment in variable region V4 compared to D. melanogaster. This expanded segment was not found in other groups of beetles, including three taxa in the closely related Carabidae. Secondary structure predictions indicate that the expanded segment folds into a single stem-loop structure in all taxa. Despite its structural conservation, the fragment differs strongly in primary sequence, even between closely related sister taxa. Several features of these sequences are consistent with slippage replication as the mechanism that has generated this sequence variation: the level of internal sequence repetition as measured by the relative simplicity factor (RSF), its variation in length between close relatives, and the strong nucleotide bias compared to the remainder of the gene. With few exceptions, there was also a correlation between sequence length and the level of sequence repetition, frequently interpreted as the result of slippage. Phylogenies inferred from the expansion segment were not consistent with existing hypotheses from other molecular data for the group. This indicates that DNA sequences in this region are not homologous throughout the entire Cicindelidae, but it leaves open the possibility that this expansion segment can be used for phylogeny reconstruction within subgroups. The implications of a phylogenetic approach to the understanding of slippage-like evolution are discussed.      

Quality control of microbiota metagenomics by k-mer analysis

Background

The biological and clinical consequences of the tight interactions between host and microbiota are rapidly being unraveled by next generation sequencing technologies and sophisticated bioinformatics, also referred to as microbiota metagenomics. The recent success of metagenomics has created a demand to rapidly apply the technology to large case–control cohort studies and to studies of microbiota from various habitats, including habitats relatively poor in microbes. It is therefore of foremost importance to enable a robust and rapid quality assessment of metagenomic data from samples that challenge present technological limits (sample numbers and size). Here we demonstrate that the distribution of overlapping k-mers of metagenome sequence data predicts sequence quality as defined by gene distribution and efficiency of sequence mapping to a reference gene catalogue.

Results

We used serial dilutions of gut microbiota metagenomic datasets to generate well-defined high to low quality metagenomes. We also analyzed a collection of 52 microbiota-derived metagenomes. We demonstrate that k-mer distributions of metagenomic sequence data identify sequence contaminations, such as sequences derived from “empty” ligation products. Of note, k-mer distributions were also able to predict the frequency of sequences mapping to a reference gene catalogue not only for the well-defined serial dilution datasets, but also for 52 human gut microbiota derived metagenomic datasets.

Conclusions

We propose that k-mer analysis of raw metagenome sequence reads should be implemented as a first quality assessment prior to more extensive bioinformatics analysis, such as sequence filtering and gene mapping. With the rising demand for metagenomic analysis of microbiota it is crucial to provide tools for rapid and efficient decision making. This will eventually lead to a faster turn-around time, improved analytical quality including sample quality metrics and a significant cost reduction. Finally, improved quality assessment will have a major impact on the robustness of biological and clinical conclusions drawn from metagenomic studies.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1406-7) contains supplementary material, which is available to authorized users.     

Comparative genomics and experimental promoter analysis reveal functional liver-specific elements in mammalian hepatic lipase genes

Background

Array-based comparative genomic hybridization (aCGH) is a high-throughput method for measuring genome-wide DNA copy number changes. Current aCGH methods have limited resolution, sensitivity and reproducibility. Microarrays for aCGH are available only for a few organisms and combination of aCGH data with expression data is cumbersome.

Results

We present a novel method of using commercial oligonucleotide expression microarrays for aCGH, enabling DNA copy number measurements and expression profiles to be combined using the same platform. This method yields aCGH data from genomic DNA without complexity reduction at a median resolution of approximately 17,500 base pairs. Due to the well-defined nature of oligonucleotide probes, DNA amplification and deletion can be defined at the level of individual genes and can easily be combined with gene expression data.

Conclusion

A novel method of gene resolution analysis of copy number variation (graCNV) yields high-resolution maps of DNA copy number changes and is applicable to a broad range of organisms for which commercial oligonucleotide expression microarrays are available. Due to the standardization of oligonucleotide microarrays, graCNV results can reliably be compared between laboratories and can easily be combined with gene expression data using the same platform.