Transcriptomic analysis of Clostridium thermocellum ATCC 27405 cellulose fermentation

<p>Abstract</p> <p>Background</p> <p>The ability of C<it>lostridium thermocellum </it>ATCC 27405 wild-type strain to hydrolyze cellulose and ferment the degradation products directly to ethanol and other metabolic byproducts makes it an attractive candidate for consolidated bioprocessing of cellulosic biomass to biofuels. In this study, whole-genome microarrays were used to investigate the expression of <it>C. thermocellum </it>mRNA during growth on crystalline cellulose in controlled replicate batch fermentations.</p> <p>Results</p> <p>A time-series analysis of gene expression revealed changes in transcript levels of ~40% of genes (~1300 out of 3198 ORFs encoded in the genome) during transition from early-exponential to late-stationary phase. K-means clustering of genes with statistically significant changes in transcript levels identified six distinct clusters of temporal expression. Broadly, genes involved in energy production, translation, glycolysis and amino acid, nucleotide and coenzyme metabolism displayed a decreasing trend in gene expression as cells entered stationary phase. In comparison, genes involved in cell structure and motility, chemotaxis, signal transduction and transcription showed an increasing trend in gene expression. Hierarchical clustering of cellulosome-related genes highlighted temporal changes in composition of this multi-enzyme complex during batch growth on crystalline cellulose, with increased expression of several genes encoding hydrolytic enzymes involved in degradation of non-cellulosic substrates in stationary phase.</p> <p>Conclusions</p> <p>Overall, the results suggest that under low substrate availability, growth slows due to decreased metabolic potential and <it>C. thermocellum </it>alters its gene expression to (i) modulate the composition of cellulosomes that are released into the environment with an increased proportion of enzymes than can efficiently degrade plant polysaccharides other than cellulose, (ii) enhance signal transduction and chemotaxis mechanisms perhaps to sense the oligosaccharide hydrolysis products, and nutrient gradients generated through the action of cell-free cellulosomes and, (iii) increase cellular motility for potentially orienting the cells' movement towards positive environmental signals leading to nutrient sources. Such a coordinated cellular strategy would increase its chances of survival in natural ecosystems where feast and famine conditions are frequently encountered.</p

The Newcomb-Benford Law in Its Relation to Some Common Distributions

An often reported, but nevertheless persistently striking observation, formalized as the Newcomb-Benford law (NBL), is that the frequencies with which the leading digits of numbers occur in a large variety of data are far away from being uniform. Most spectacular seems to be the fact that in many data the leading digit 1 occurs in nearly one third of all cases. Explanations for this uneven distribution of the leading digits were, among others, scale- and base-invariance. Little attention, however, found the interrelation between the distribution of the significant digits and the distribution of the observed variable. It is shown here by simulation that long right-tailed distributions of a random variable are compatible with the NBL, and that for distributions of the ratio of two random variables the fit generally improves. Distributions not putting most mass on small values of the random variable (e.g. symmetric distributions) fail to fit. Hence, the validity of the NBL needs the predominance of small values and, when thinking of real-world data, a majority of small entities. Analyses of data on stock prices, the areas and numbers of inhabitants of countries, and the starting page numbers of papers from a bibliography sustain this conclusion. In all, these findings may help to understand the mechanisms behind the NBL and the conditions needed for its validity. That this law is not only of scientific interest per se, but that, in addition, it has also substantial implications can be seen from those fields where it was suggested to be put into practice. These fields reach from the detection of irregularities in data (e.g. economic fraud) to optimizing the architecture of computers regarding number representation, storage, and round-off errors

Cryo Electron Tomography of Herpes Simplex Virus during Axonal Transport and Secondary Envelopment in Primary Neurons

During herpes simplex virus 1 (HSV1) egress in neurons, viral particles travel from the neuronal cell body along the axon towards the synapse. Whether HSV1 particles are transported as enveloped virions as proposed by the ‘married’ model or as non-enveloped capsids suggested by the ‘separate’ model is controversial. Specific viral proteins may form a recruitment platform for microtubule motors that catalyze such transport. However, their subviral location has remained elusive. Here we established a system to analyze herpesvirus egress by cryo electron tomography. At 16 h post infection, we observed intra-axonal transport of progeny HSV1 viral particles in dissociated hippocampal neurons by live-cell fluorescence microscopy. Cryo electron tomography of frozen-hydrated neurons revealed that most egressing capsids were transported independently of the viral envelope. Unexpectedly, we found not only DNA-containing capsids (cytosolic C-capsids), but also capsids lacking DNA (cytosolic A-/B-capsids) in mid-axon regions. Subvolume averaging revealed lower amounts of tegument on cytosolic A-/B-capsids than on C-capsids. Nevertheless, all capsid types underwent active axonal transport. Therefore, even few tegument proteins on the capsid vertices seemed to suffice for transport. Secondary envelopment of capsids was observed at axon terminals. On their luminal face, the enveloping vesicles were studded with typical glycoprotein-like spikes. Furthermore, we noted an accretion of tegument density at the concave cytosolic face of the vesicle membrane in close proximity to the capsids. Three-dimensional analysis revealed that these assembly sites lacked cytoskeletal elements, but that filamentous actin surrounded them and formed an assembly compartment. Our data support the ‘separate model’ for HSV1 egress, i.e. progeny herpes viruses being transported along axons as subassemblies and not as complete virions within transport vesicles

Pregnancy and Breast Cancer: when They Collide

Women of childbearing age experience an increased breast cancer risk associated with a completed pregnancy. For younger women, this increase in breast cancer risk is transient and within a decade after parturition a cross over effect results in an ultimate protective benefit. The post-partum peak of increased risk is greater in women with advanced maternal age. Further, their lifetime risk for developing breast cancer remains elevated for many years, with the cross over to protection occurring decades later or not at all. Breast cancers diagnosed during pregnancy and within a number of years post-partum are termed pregnancy-associated or PABC. Contrary to popular belief, PABC is not a rare disease and could affect up to 40,000 women in 2009. The collision between pregnancy and breast cancer puts women in a fear-invoking paradox of their own health, their pregnancy, and the outcomes for both. We propose two distinct subtypes of PABC: breast cancer diagnosed during pregnancy and breast cancer diagnosed post-partum. This distinction is important because emerging epidemiologic data highlights worsened outcomes specific to post-partum cases. We reported that post-partum breast involution may be responsible for the increased metastatic potential of post-partum PABC. Increased awareness and detection, rationally aggressive treatment, and enhanced understanding of the mechanisms are imperative steps toward improving the prognosis for PABC. If we determine the mechanisms by which involution promotes metastasis of PABC, the post-partum period can be a window of opportunity for intervention strategies

Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.Daniel D. Buchanan, Kevin Sweet, Musa Drini, Mark A. Jenkins, Aung Ko Win, Dallas R. English, Michael D. Walsh, Mark Clendenning, Diane M. McKeone, Rhiannon J. Walters, Aedan Roberts, Sally-Ann Pearson, Erika Pavluk, John L. Hopper, Michael R. Gattas, Jack Goldblatt, Jill George, Graeme K. Suthers, Kerry D. Phillips, Sonja Woodal, Julie Arnold, Kathy Tucker, Amanda Muir, Michael Field, Sian Greening, Steven Gallinger, Renee Perrier, John A. Baron, John D. Potter, Robert Haile, Wendy Franke, Albert de la Chapelle, Finlay Macrae, Christophe Rosty, Neal I. Walker, Susan Parry and Joanne P. Youn