Base pairing involving artificial bases and .

Herein we report the synthesis of -glycosylated 8-aza-deoxyguanosine (-8-aza-dG) and 8-aza-9-deaza-deoxyguanosine (-8-aza-9-deaza-dG) nucleotides and their base pairing properties with 5-methyl-isocytosine (d-isoC), 8-amino-deoxyinosine (8-NH-dI), 1--methyl-8-amino-deoxyinosine (1-Me-8-NH-dI), 7,8-dihydro-8-oxo-deoxyinosine (8-Oxo-dI), 7,8-dihydro-8-oxo-deoxyadenosine (8-Oxo-dA), and 7,8-dihydro-8-oxo-deoxyguanosine (8-Oxo-dG), in comparison with the d-isoC:d-isoG artificial genetic system. As demonstrated by measurements, the -8-aza-dG:d-isoC base pair formed less stable duplexes as the C:G and d-isoC:d-isoG pairs. Incorporation of 8-NH-dI the -8-aza-dG nucleoside resulted in a greater reduction in stability, compared to d-isoC:d-isoG.

Phase Behavior of DNA in the Presence of DNA-Binding Proteins.

To characterize the thermodynamical equilibrium of DNA chains interacting with a solution of nonspecific binding proteins, we implemented a Flory-Huggins free energy model. We explored the dependence on DNA and protein concentrations of the DNA collapse. For physiologically relevant values of the DNA-protein affinity, this collapse gives rise to a biphasic regime with a dense and a dilute phase; the corresponding phase diagram was computed.

The CRISPR-Cas9 technology: Closer to the ultimate toolkit for targeted genome editing.

The first period of plant genome editing was based on Agrobacterium; chemical mutagenesis by EMS (ethyl methanesulfonate) and ionizing radiations; each of these technologies led to randomly distributed genome modifications. The second period is associated with the discoveries of homing and meganuclease enzymes during the 80s and 90s, which were then engineered to provide efficient tools for targeted editing. From 2006 to 2012, a few crop plants were successfully and precisely modified using zinc-finger nucleases.

Abundant toxin-related genes in the genomes of beneficial symbionts from deep-sea hydrothermal vent mussels.

Bathymodiolus mussels live in symbiosis with intracellular sulfur-oxidizing (SOX) bacteria that provide them with nutrition. We sequenced the SOX symbiont genomes from two Bathymodiolus species. Comparison of these symbiont genomes with those of their closest relatives revealed that the symbionts have undergone genome rearrangements, and up to 35% of their genes may have been acquired by horizontal gene transfer.

Dynamics and Energy Contributions for Transport of Unfolded Pertactin through a Protein Nanopore.

To evaluate the physical parameters governing translocation of an unfolded protein across a lipid bilayer, we studied protein transport through aerolysin, a passive protein channel, at the single-molecule level. The protein model used was the passenger domain of pertactin, an autotransporter virulence protein. Transport of pertactin through the aerolysin nanopore was detected as transient partial current blockades as the unfolded protein partially occluded the aerolysin channel.

Effects of pre-exercise alkalosis on the decrease in VO2 at the end of all-out exercise.

Purpose: This study determined the effects of pre-exercise sodium bicarbonate ingestion (ALK) on changes in oxygen uptake (VO2) at the end of a supramaximal exercise test (SXT).

Methods: Eleven well-trained cyclists completed a 70-s all-out cycling effort, in double-blind trials, after oral ingestion of either 0.3 g kg(-1) of sodium bicarbonate (NaHCO3) or 0.

A Sense of Balance: Experimental Investigation and Modeling of a Malonyl-CoA Sensor in Escherichia coli.

Production of value-added chemicals in microorganisms is regarded as a viable alternative to chemical synthesis. In the past decade, several engineered pathways producing such chemicals, including plant secondary metabolites in microorganisms have been reported; upscaling their production yields, however, was often challenging. Here, we analyze a modular device designed for sensing malonyl-CoA, a common precursor for both fatty acid and flavonoid biosynthesis.

Is there a role for a handheld gamma camera (TReCam) in the SNOLL breast cancer procedure?

Background: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) and radio-guided occult lesion localization (ROLL). The safety and benefits of radio-guided localization in the surgical treatment of non-palpable breast cancer have been confirmed. The aim of this study was to evaluate the potential role for an intra-operative handheld tumor resection gamma camera (TReCam) in SNOLL procedures.

Blood lactate and acid-base balance of world-class amateur boxers after three 3-minute rounds in international competition.

To examine the blood metabolic responses of world-class boxers involved in international competition (Test match), 33 male boxers (mean ± SD) competing internationally across all the official weight categories were studied on 2 different occasions: Test match 1 (team A against team B) and Test match 2 (team A against team C). Blood samples were collected after the third round for both Test matches for all teams except team B. For all Test matches and boxers, mean blood lactate concentration ([BLac]), bicarbonate concentration, hemoglobin O2 saturation (SaO2), partial pressure for CO2 (PCO2), and pH were 13.

Hypoxic culture conditions enhance the generation of regulatory T cells.

The generation of large amounts of induced CD4  CD25  Foxp3 regulatory T (iTreg) cells is of great interest for several immunotherapy applications, therefore a better understanding of signals controlling iTreg cell differentiation and expansion is required. There is evidence that oxidative metabolism may regulate several key signalling pathways in T cells. This prompted us to investigate the effects of oxygenation on iTreg cell generation by comparing the effects of atmospheric (21%) or of low (5%) O concentrations on the phenotype of bead-stimulated murine splenic CD4 T cells from Foxp3-KI-GFP T-cell receptor transgenic mice.

Validation of RetroPath, a computer-aided design tool for metabolic pathway engineering.

Metabolic engineering has succeeded in biosynthesis of numerous commodity or high value compounds. However, the choice of pathways and enzymes used for production was many times made ad hoc, or required expert knowledge of the specific biochemical reactions. In order to rationalize the process of engineering producer strains, we developed the computer-aided design (CAD) tool RetroPath that explores and enumerates metabolic pathways connecting the endogenous metabolites of a chassis cell to the target compound.

Computer-aided design for metabolic engineering.

The development and application of biotechnology-based strategies has had a great socio-economical impact and is likely to play a crucial role in the foundation of more sustainable and efficient industrial processes. Within biotechnology, metabolic engineering aims at the directed improvement of cellular properties, often with the goal of synthesizing a target chemical compound. The use of computer-aided design (CAD) tools, along with the continuously emerging advanced genetic engineering techniques have allowed metabolic engineering to broaden and streamline the process of heterologous compound-production.

Members of the uncultured bacterial candidate division WWE1 are implicated in anaerobic digestion of cellulose.

Clones of the WWE1 (Waste Water of Evry 1) candidate division were retrieved during the exploration of the bacterial diversity of an anaerobic mesophilic (35 ± 0.5°C) digester. In order to investigate the metabolic function of WWE1 members, a 16S rRNA gene -based stable isotope probing (SIP) method was used.

JEPETTO: a Cytoscape plugin for gene set enrichment and topological analysis based on interaction networks.

Summary: JEPETTO (Java Enrichment of Pathways Extended To TOpology) is a Cytoscape 3.x plugin performing integrative human gene set analysis. It identifies functional associations between genes and known cellular pathways, and processes using protein interaction networks and topological analysis.

Prevalence of cardio-respiratory factors in the occurrence of the decrease in oxygen uptake during supra-maximal, constant-power exercise.

Purpose: To investigate the physiological mechanisms that explain the end-exercise decrease in oxygen uptake [Formula: see text] during strenuous constant-power exercise, we recruited eleven trained, track cyclists.

Methods: On two separated days they performed 1) resting spirometric measures, followed by an incremental test on a cycle ergometer to determine the power output at [Formula: see text] and 2) an exhaustive isokinetic supramaximal cycling exercise (Tlimsupra) at 185 ± 24% of [Formula: see text] (i.e.

Synergistic Synthetic Biology: Units in Concert.

Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship.

Cardiac output and performance during a marathon race in middle-aged recreational runners.

Purpose: Despite the increasing popularity of marathon running, there are no data on the responses of stroke volume (SV) and cardiac output (CO) to exercise in this context. We sought to establish whether marathon performance is associated with the ability to sustain high fractional use of maximal SV and CO (i.e, cardiac endurance) and/or CO, per meter (i.

A retrosynthetic biology approach to therapeutics: from conception to delivery.

De novo biosynthetic pathways are designed, assembled and optimized to produce high-value compounds such as drugs and chemical building blocks from renewable resources. Microorganisms are used as synthetic platforms of systems biology where biochemical pathways are engineered into the host metabolic network. Retrosynthetic biology offers a creative pathway design concept that has gained interest because of its potential to identify novel metabolic ways for therapeutic production.

Weighted-LASSO for structured network inference from time course data.

We present a weighted-LASSO method to infer the parameters of a first-order vector auto-regressive model that describes time course expression data generated by directed gene-to-gene regulation networks. These networks are assumed to own prior internal structures of connectivity which drive the inference method. This prior structure can be either derived from prior biological knowledge or inferred by the method itself.

Central and peripheral contributions to neuromuscular fatigue induced by a 24-h treadmill run.

This experiment investigated the fatigue induced by a 24-h running exercise (24TR) and particularly aimed at testing the hypothesis that the central component would be the main mechanism responsible for neuromuscular fatigue. Neuromuscular function evaluation was performed before, every 4 h during, and at the end of the 24TR on 12 experienced ultramarathon runners. It consisted of a determination of the maximal voluntary contractions (MVC) of the knee extensors (KE) and plantar flexors (PF), the maximal voluntary activation (%VA) of the KE and PF, and the maximal compound muscle action potential amplitude (Mmax) on the soleus and vastus lateralis.

The dark side of the salad: Salmonella typhimurium overcomes the innate immune response of Arabidopsis thaliana and shows an endopathogenic lifestyle.

Salmonella enterica serovar typhimurium contaminated vegetables and fruits are considerable sources of human infections. Bacteria present in raw plant-derived nutrients cause salmonellosis, the world wide most spread food poisoning. This facultative endopathogen enters and replicates in host cells and actively suppresses host immune responses.

Robert Rosen in the age of systems biology.

The widespread use of the term Systems Biology (SB) signals a welcome recognition that organisms must be understood as integrated systems. Although just what this is taken to mean varies from one group to another, it generally implies a focus on biological functions and processes rather than on biological parts and a reliance on mathematical modeling to arrive at an understanding of these biological processes based on biological observations or measurements. SB, thus, falls directly in the line of reflection carried out by Robert Rosen throughout his work.

Nonlinear dynamics of heart rate and oxygen uptake in exhaustive 10,000 m runs: influence of constant vs. freely paced.

We hypothesized that a freely paced 10,000 m running race would induce a smaller physiological strain (heart rate and oxygen uptake) compared with one performed at the same average speed but with an imposed constant pace. Furthermore, we analyzed the scaling properties with a wavelet transform algorithm computed log2 (wavelet transform energy) vs. log2 (scale) to get slope alpha, which is the scaling exponent, a measure of the irregularity of a time series.

Changes in internal mechanical cost during overground running to exhaustion.

Purpose: The purpose of this study was to determine, during an overground supra-threshold run, whether a change in the internal mechanical cost could occur during an exhaustive run and whether this change was related to the increase in the energy cost of running (C(r)).

Methods: The Cr of 14 endurance runners was measured from pulmonary gas exchange using a breath-by-breath portable gas analyzer (Cosmed K4b, Rome, Italy), at the third and the last minute of an exhaustive exercise performed at their velocity corresponding to 95% of the maximal oxygen uptake (4.88 +/- 0.

Heart rate deflection point as a strategy to defend stroke volume during incremental exercise.

The purpose of this study was to examine whether the heart rate (HR) deflection point (HRDP) in the HR-power relationship is concomitant with the maximal stroke volume (SV(max)) value achievement in endurance-trained subjects. Twenty-two international male cyclists (30.3 +/- 7.