Levels and limits in artificial selection of communities

Artificial selection of individuals has been determinant in the elaboration of the Darwinian theory of natural selection. Nowadays, artificial selection of ecosystems has proven its efficiency and could contribute to a theory of natural selection at several organisation levels. Here, we were not interested in identifying mechanisms of adaptation to selection, but in establishing the proof of principle that a specific structure of interaction network emerges under ecosystem artificial selection. We also investigated the limits in ecosystem artificial selection to evaluate its potential in terms of managing ecosystem function. By artificially selecting microbial communities for low CO₂ emissions over 21 generations (n = 7560), we found a very high heritability of community phenotype (52%). Artificial selection was responsible for simpler interaction networks with lower interaction richness. Phenotype variance and heritability both decreased across generations, suggesting that selection was more likely limited by sampling effects than by stochastic ecosystem dynamics.     

Molecular interactions between Neisseria meningitidis and its human host

Neisseria meningitidis is a Gram‐negative bacterium that asymptomatically colonises the nasopharynx of humans. For an unknown reason, N. meningitidis can cross the nasopharyngeal barrier and invade the bloodstream where it becomes one of the most harmful extracellular bacterial pathogen. This infectious cycle involves the colonisation of two different environments. (a) In the nasopharynx, N. meningitidis grow on the top of mucus‐producing epithelial cells surrounded by a complex microbiota. To survive and grow in this challenging environment, the meningococcus expresses specific virulence factors such as polymorphic toxins and MDAΦ. (b) Meningococci have the ability to survive in the extra cellular fluids including blood and cerebrospinal fluid. The interaction of N. meningitidis with human endothelial cells leads to the formation of typical microcolonies that extend overtime and promote vascular injury, disseminated intravascular coagulation, and acute inflammation. In this review, we will focus on the interplay between N. meningitidis and these two different niches at the cellular and molecular level and discuss the use of inhibitors of piliation as a potent therapeutic approach.     

ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells

Acute promyelocytic leukemia (APL) results from a blockade of granulocyte differentiation at the promyelocytic stage. All-trans retinoic acid (ATRA) induces clinical remission in APL patients by enhancing the rapid differentiation of APL cells and the clearance of PML-RARα, APL's hallmark oncoprotein. In the present study, we demonstrated that both autophagy and Beclin 1, an autophagic protein, are upregulated during the course of ATRA-induced neutrophil/granulocyte differentiation of an APL-derived cell line named NB4 cells. This induction of autophagy is associated with downregulation of Bcl-2 and inhibition of mTOR activity. Small interfering RNA-mediated knockdown of BECN1 expression enhances apoptosis triggered by ATRA in NB4 cells but does not affect the differentiation process. These results provide evidence that the upregulation of Beclin 1 by ATRA constitutes an anti-apoptotic signal for maintaining the viability of mature APL cells, but has no crucial effect on the granulocytic differentiation. This finding may help to elucidate the mechanisms involved in ATRA resistance of APL patients, and in the ATRA syndrome caused by an accumulation of mature APL cells.     

Differential Protein Phosphorylation Regulates Chloroplast Movement in Response to Strong Light and Darkness in Arabidopsis thaliana

Phototropin-dependent chloroplast movement is essential to the photosynthetic acclimation of mesophyll cells to incident light. Chloroplast movement involves many cellular actors, such as chloroplast-associated actin filaments and proteins that mediate signalling between phototropins and chloroplast motion. In the past few years, genetic approaches have identified several key proteins but the intrinsic mechanisms of the signalling cascade, such as phosphorylation events, remain undefined. Here, we took advantage of phosphoproteomics to examine the involvement of protein phosphorylation in chloroplast movement in darkness or under high light, at different CO₂ mole fractions (100, 380 or 1,000 ppm) to vary photosynthetic activity. Amongst the 100 relevant identified phosphopeptides, 19 (corresponding to 8 proteins) were differentially phosphorylated in darkness vs. high light. There was no significant CO₂ effect on the observed phosphorylation patterns. We further characterized the phosphorylation sites in THRUMIN1, which is believed to be crucial for the attachment of chloroplast-associated actin filaments to the plasma membrane and thus for chloroplast movements. The mutant thrumin1 was complemented with a mutated protein in which phospho-sites were substituted to a phosphomimetic (Asp) or a non-phosphorylatable (Ala) residue. While the phosphomimetic substitution altered the chloroplast response in the light only, both light and dark responses were altered with the non-phosphorylatable substitution. Our data suggest a key role of protein phosphorylation, including that of THRUMIN1, in the light/dark control of chloroplast movements.     

Filtering redundancies for sequence similarity search programs

Database scanning programs such as BLAST and FASTA are used nowadays by most biologists for the post-genomic processing of DNA or protein sequence information (in particular to retrieve the structure/function of uncharacterized proteins). Unfortunately, their results can be polluted by identical alignments (called redundancies) coming from the same protein or DNA sequences present in different entries of the database. This makes the efficient use of the listed alignments difficult. Pretreatment of databases has been proposed to suppress strictly identical entries. However, there still remain many identical alignments since redundancies may occur locally for entries corresponding to various fragments of the same sequence or for entries corresponding to very homologous sequences but differing at the level of a few residues such as ortholog proteins. In the present work, we show that redundant alignments can be indeed numerous even when working with a pretreated non-redundant data bank, going as high as 60% of the output results according to the query and the bank. Therefore the accuracy and the efficiency of the post-genomic work will be greatly increased if these redundancies are removed. To solve this up to now unaddressed problem, we have developed an algorithm that allows for the efficient and safe suppression of all the redundancies with no loss of information. This algorithm is based on various filtering steps that we describe here in the context of the Automat similarity search program, and such an algorithm should also be added to the other similarity search programs (BLAST, FASTA, etc...).     

Chemical Variability of the Essential Oil of Pituranthos scoparius from Algeria

The chemical composition of 93 oil samples from the aerial parts of Pituranthos scoparius, harvested in three regions of Algeria, was investigated by GC‐FID, GC/MS and ¹³C‐NMR. Monoterpene hydrocarbons dominated in association with phenylpropanoids and a chemical variability was found highlighting three clusters. The composition of group I (36 samples) exhibited an atypical composition characterized by a very high contents of 6‐methoxyelemicine (13.0 – 59.6%), followed by sabinene (1.1 – 43.0%) and limonene (6.6 – 39.0%), while the samples of group II (12 samples) contained a high content of limonene (9.2 – 44.0%), followed by myristicine (0.0 – 29.4%) and a lower amount of sabinene (0.8 – 2.3%). Group III (45 samples) could be divided in two subgroups. Subgroup SGIIIA was characterized by a very high content of sabinene (28.0 – 55.6%), followed by elemicine (0.0 – 29.1%), while the samples belonging to SGIIIB were characterized by the lower content of sabinene (6.2 – 35.5%) and a significant content of myristicine (1.5 – 32.4%), α‐pinene (4.2 – 31.0%) and dill apiole (0.1 – 31.4%). Each harvested region was characterized by a different chemical composition.     

Use of inert gas jets to measure the forces required for mechanical gene transfection

Background

Abnormal blood glucose (BG) concentrations have been associated with increased morbidity and mortality in both critically ill adults and infants. Furthermore, hypoglycaemia and glycaemic variability have both been independently linked to mortality in these patients. Continuous Glucose Monitoring (CGM) devices have the potential to improve detection and diagnosis of these glycaemic abnormalities. However, sensor noise is a trade-off of the high measurement rate and must be managed effectively if CGMs are going to be used to monitor, diagnose and potentially help treat glycaemic abnormalities.

Aim

To develop a tool that will aid clinicians in identifying unusual CGM behaviour and highlight CGM data that potentially need to be interpreted with care.

Methods

CGM data and BG measurements from 50 infants at risk of hypoglycaemia were used. Unusual CGM measurements were classified using a stochastic model based on the kernel density method and historical CGM measurements from the cohort. CGM traces were colour coded with very unusual measurements coloured red, highlighting areas to be interpreted with care. A 5-fold validation of the model was Monte Carlo simulated 25 times to ensure an adequate model fit.

Results

The stochastic model was generated using ~67,000 CGM measurements, spread across the glycaemic range ~2-10?mmol/L. A 5-fold validation showed a good model fit: the model 80% confidence interval (CI) captured 83% of clinical CGM data, the model 90% CI captured 91% of clinical CGM data, and the model 99% CI captured 99% of clinical CGM data. Three patient examples show the stochastic classification method in use with 1) A stable, low variability patient which shows no unusual CGM measurements, 2) A patient with a very sudden, short hypoglycaemic event (classified as unusual), and, 3) A patient with very high, potentially un-physiological, glycaemic variability after day 3 of monitoring (classified as very unusual).

Conclusions

This study has produced a stochastic model and classification method capable of highlighting unusual CGM behaviour. This method has the potential to classify important glycaemic events (e.g. hypoglycaemia) as true clinical events or sensor noise, and to help identify possible sensor degradation. Colour coded CGM traces convey the information quickly and efficiently, while remaining computationally light enough to be used retrospectively or in real-time.     

Endogenous ARF6 interacts with Rac1 upon angiotensin II stimulation to regulate membrane ruffling and cell migration

ARF6 and Rac1 are small GTPases known to regulate remodelling of the actin cytoskeleton. Here, we demonstrate that these monomeric G proteins are sequentially activated when HEK 293 cells expressing the angiotensin type 1 receptor (AT(1)R) are stimulated with angiotensin II (Ang II). After receptor activation, ARF6 and Rac1 transiently form a complex. Their association is, at least in part, direct and dependent on the nature of the nucleotide bound to both small G proteins. ARF6-GTP preferentially interacts with Rac1-GDP. AT(1)R expressing HEK293 cells ruffle, form membrane protrusions, and migrate in response to agonist treatment. ARF6, but not ARF1, depletion using small interfering RNAs recapitulates the ruffling and migratory phenotype observed after Ang II treatment. These results suggest that ARF6 depletion or Ang II treatment are functionally equivalent and point to a role for endogenous ARF6 as an inhibitor of Rac1 activity. Taken together, our findings reveal a novel function of endogenously expressed ARF6 and demonstrate that by interacting with Rac1, this small GTPase is a central regulator of the signaling pathways leading to actin remodeling.     

Variation in the ontogenetic allometry of horn length in bovids along a body mass continuum

Allometric relationships describe the proportional covariation between morphological, physiological, or life‐history traits and the size of the organisms. Evolutionary allometries estimated among species are expected to result from species differences in ontogenetic allometry, but it remains uncertain whether ontogenetic allometric parameters and particularly the ontogenetic slope can evolve. In bovids, the nonlinear evolutionary allometry between horn length and body mass in males suggests systematic changes in ontogenetic allometry with increasing species body mass. To test this hypothesis, we estimated ontogenetic allometry between horn length and body mass in males and females of 19 bovid species ranging from ca. 5 to 700 kg. Ontogenetic allometry changed systematically with species body mass from steep ontogenetic allometries over a short period of horn growth in small species to shallow allometry with the growth period of horns matching the period of body mass increase in the largest species. Intermediate species displayed steep allometry over long period of horn growth. Females tended to display shallower ontogenetic allometry with longer horn growth compared to males, but these differences were weak and highly variable. These findings show that ontogenetic allometric slope evolved across species possibly as a response to size‐related changes in the selection pressures acting on horn length and body mass.