ALBERT

Description: Background: In the last decade, a great number of methods for reconstructing gene regulatory networks from expression data have been proposed. However, very few tools and datasets allow to evaluate accurately and reproducibly those methods. Hence, we propose here a new tool, able to perform a systematic, yet fully reproducible, evaluation of transcriptional network inference methods. Results: Our open-source and freely available Bioconductor package aggregates a large set of tools to assess the robustness of network inference algorithms against different simulators, topologies, sample sizes and noise intensities. Conclusions: The benchmarking framework that uses various datasets highlights the specialization of some methods toward network types and data. As a result, it is possible to identify the techniques that have broad overall performances.

Description: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence o...

Description: Evolutionary processes, including selection and differential fitness, shape the introgression of genetic material across a hybrid zone, resulting in the exchange of some genes but not others. Differential intr...

Description: Background: Salmonella enterica is the second most common foodborne pathogen. The use of biocides is crucial to prevent spread of foodborne pathogens, and it would be devastating for food safety if Salmonella would become resistant to the disinfectants used. Another concern is that exposure to disinfectants might lead to decreased susceptibility to antibiotics.The current study aimed to identify genetic changes causing high level triclosan resistance in S. enterica serovar Typhimurium and evaluate how these affected antibiotic resistance and efflux pump activity. Results: Wild type strains S. Typhimurium 4/74 and DTU3 were adapted to increasing concentrations of the biocide triclosan by serial passage. High level triclosan resistant isolates (MIC 〉 1000 μg/ml) were obtained. Strains were genome sequenced, and SNPs in fabI, rpoS and rpoD were found to be associated with high level resistance. However, work with defined mutants revealed that a SNP in fabI was not sufficient to obtain high level resistance. This required additional mutations in the sigma factors rpoS or rpoD. The adapted strains showed triclosan-dependent increased efflux, increased fabI expression and reduced susceptibility towards the antibiotics enrofloxacin and sulphamethoxazole/trimethoprim. Conclusions: Medium level triclosan resistance could be obtained by fabI mutations in S. Typhimurium, however, high level resistance was found to require sigma factor mutations in addition to a fabI mutation. Reduced antibiotic sensitivity was observed for the adapted strains, which could be associated with increased efflux.

Description: Background: Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs). Activin A is also elevated in myeloma patients with advanced disease and is involved in myeloma bone disease. Results: In this study we investigated effects of activin A binding to receptors that are shared with BMPs using myeloma cell lines with well-characterized BMP-receptor expression and responses. Activin A antagonized BMP-6 and BMP-9, but not BMP-2 and BMP-4. Activin A was able to counteract BMPs that signal through the type 2 receptors ACVR2A and ACVR2B in combination with ALK2, but not BMPs that signal through BMPR2 in combination with ALK3 and ALK6. Conclusions: We propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling.

Description: Background: Postoperative ileus is common after surgery. One non-pharmacological intervention that has shown promising results in reducing the duration of postoperative ileus is chewing gum after surgery. However, this has not been investigated in upper gastrointestinal surgery such as pancreatic surgery. Hence the aim of this study was to investigate the effects of chewing gum treatment on patients undergoing pancreaticoduodenectomy ad modum whipple due to pancreatic or periampullary cancer. Methods: This study was conducted as a phase III trial that was terminated early. Patients diagnosed with pancreatic tumours scheduled for pancreaticoduodenectomy ad modum whipple were included. The treatment group received chewing gum postoperatively and standard care. Controls received glucose solution and standard care. Chewing gum and glucose were used four times a day during the whole hospital stay. Time to first flatus and stool was defined as the primary outcome. The secondary outcome was start with clear liquids, start with liquid diet and length of hospital stay. Results: No statistically significant differences could be observed between the chewing gum intervention group and the control group. However, a numerical difference in mean time was observed in first flatus, first stool, start of clear fluids, and start of liquid diet and length of hospital stay in favour of the intervention group. Conclusions: Although this study did not find statistically significant differences favouring the use of chewing gum for postoperative ileus, a positive trend was observed of a reduction of the impact of postoperative ileus among patients after pancreatic surgery. It also contributes valuable methodological experience that is important for future studies of chewing gum interventions during recovery after pancreatic surgery.Trial registrationClinicalTrials.gov identifier: NCT02319512, publication date 2014-12-17.

Description: Background: Mycobacterium avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah) are environmental mycobacteria and significant opportunistic pathogens. Mycobacterium avium infections in humans and pigs are mainly due to Mah. It is not known whether this is caused by a difference in virulence or difference in exposure to the two subspecies. The aim of the present study was to investigate the ability of the M. avium subspecies to replicate intracellularly and to characterise the gene expression program triggered by infection of human primary macrophages. Results: All isolates were able to invade and persist within human macrophages. However, intracellular replication was only evident in cells infected with the two Maa isolates. Transcriptional responses to the isolates were characterized by upregulation of genes involved in apoptosis, immune- and inflammatory response, signal transduction and NF-kB signaling, cell proliferation and T-cell activation. Although similar pathways and networks were perturbed by the different isolates, the response to the Maa subspecies was exaggerated, and there was evidence of increased activation of type I and II interferon signaling pathways. Conclusion: Mycobacterium avium isolates of different genetic characteristics invaded monocytes and induced different degree of macrophage activation. Isolates of Maa were able to replicate intracellularly suggesting that differences in exposure, uptake or induction of adaptive immunity are more likely explanations for the difference in prevalence between M. avium subspecies.

Description: Background: Fibropapillomatosis (FP) is a neoplastic disease characterized by cutaneous tumours that has been documented to infect all sea turtle species. Chelonid fibropapilloma-associated herpesvirus (CFPHV) is believed to be the aetiological agent of FP, based principally on consistent PCR-based detection of herpesvirus DNA sequences from FP tumours. We used a recently described PCR-based assay that targets 3 conserved CFPHV genes, to survey 208 green turtles (Chelonia mydas). This included both FP tumour exhibiting and clinically healthy individuals. An additional 129 globally distributed clinically healthy individual sea turtles; representing four other species were also screened. Results: CFPHV DNA sequences were obtained from 37/37 (100%) FP exhibiting green turtles, and 45/300 (15%) clinically healthy animals spanning all five species. Although the frequency of infected individuals per turtle population varied considerably, most global populations contained at least one CFPHV positive individual, with the exception of various turtle species from the Arabian Gulf, Northern Indian Ocean and Puerto Rico.Haplotype analysis of the different gene markers clustered the CFPHV DNA sequences for two of the markers (UL18 and UL22) in turtles from Turks and Caicos separate to all others, regardless of host species or geographic origin. Conclusion: Presence of CFPHV DNA within globally distributed samples for all five species of sea turtle was confirmed. While 100% of the FP exhibiting green turtles yielded CFPHV sequences, surprisingly, so did 15% of the clinically healthy turtles. We hypothesize that turtle populations with zero (0%) CFPHV frequency may be attributed to possible environmental differences, diet and/or genetic resistance in these individuals. Our results provide first data on the prevalence of CFPHV among seemingly healthy turtles; a factor that may not be directly correlated to the disease incidence, but may suggest of a long-term co-evolutionary latent infection interaction between CFPHV and its turtle-host across species. Finally, computational analysis of amino acid variants within the Turks and Caicos samples suggest potential functional importance in a substitution for marker UL18 that encodes the major capsid protein gene, which potentially could explain differences in pathogenicity. Nevertheless, such a theory remains to be validated by further research.

Description: IntroductionCalanus finmarchicus, a highly abundant copepod that is an important primary consumer in North Atlantic ecosystems, has a flexible life history in which copepods in the last juvenile developmental stage (fifth copepodid, C5) may either delay maturation and enter diapause or molt directly into adults. The factors that regulate this developmental plasticity are poorly understood, and few tools have been developed to assess the physiological condition of individual copepods. Results: We sampled a cultured population of C. finmarchicus copepods daily throughout the C5 stage and assessed molt stage progression, gonad development and lipid storage. We used high-throughput sequencing to identify genes that were differentially expressed during progression through the molt stage and then used qPCR to profile daily expression of individual genes. Based on expression profiles of twelve genes, samples were statistically clustered into three groups: (1) an early period occurring prior to separation of the cuticle from the epidermis (apolysis) when expression of genes associated with lipid synthesis and transport (FABP and ELOV) and two nuclear receptors (ERR and HR78) was highest, (2) a middle period of rapid change in both gene expression and physiological condition, including local minima and maxima in several nuclear receptors (FTZ-F1, HR38b, and EcR), and (3) a late period when gonads were differentiated and expression of genes associated with molting (Torso-like, HR38a) peaked. The ratio of Torso-like to HR38b strongly differentiated the early and late groups. Conclusions: This study provides the first dynamic profiles of gene expression anchored with morphological markers of lipid accumulation, development and gonad maturation throughout a copepod molt cycle. Transcriptomic profiling revealed significant changes over the molt cycle in genes with presumed roles in lipid synthesis, molt regulation and gonad development, suggestive of a coupling of these processes in Calanus finmarchicus. Finally, we identified gene expression profiles that strongly differentiate between early and late development within the C5 copepodid stage. We anticipate that these findings and continued development of robust gene expression biomarkers that distinguish between diapause preparation and continuous development will ultimately enable novel studies of the intrinsic and extrinsic factors that govern diapause initiation in Calanus finmarchicus.