Circadian Clock Genes Modulate Human Bone Marrow Mesenchymal Stem Cell Differentiation,Migration and Cell Cycle

Many of the components that regulate the circadian clock have been identified in organisms and humans. The influence of circadian rhythm (CR) on the regulation of stem cells biology began to be evaluated. However, little is known on the role of CR on human mesenchymal stem cell (hMSCs) properties. The objective of this study was to investigate the influence of CR on the differentiation capacities of bone marrow hMSCs, as well as the regulation of cell cycle and migration capabilities. To that, we used both a chemical approach with a GSK-3β specific inhibitor (2’E,3’Z-6-bromoindirubin-3’-oxime, BIO) and a knockdown of CLOCK and PER2, two of the main genes involved in CR regulation. In these experimental conditions, a dramatic inhibition of adipocyte differentiation was observed, while osteoblastic differentiation capacities were not modified. In addition, cell migration was decreased in PER2^-/- cells. Lastly, downregulation of circadian clock genes induced a modification of the hMSCs cell cycle phase distribution, which was shown to be related to a change of the cyclin expression profile. Taken together, these data showed that CR plays a role in the regulation of hMSCs differentiation and division, and likely represent key factor in maintaining hMSCs properties.     

The role of diet and temperature in shaping cranial diversification of South American human populations: an approach based on spatial regression and divergence rate tests

Aim Understanding the importance of ecological factors in the origin and maintenance of patterns of phenotypic variation among populations, in an explicit geographical context, is one of the main goals of human biology, ecology and evolutionary biology. Here we study the ecological factors responsible for craniofacial variation among human populations from South America. Location South America. Methods We studied a dataset of 718 males from 40 South American populations, coming from groups that inhabited different geographical and ecological regions. Cranial size and shape variation were studied using 30 cranial measurements. We first used spatial correlograms and interpolated maps to address spatial patterns. We then regressed the shape (principal component scores) and size variables against ecology (mean annual temperature and diet) using multiple and multivariate spatial regression. Finally, the expected magnitudes of shape and size divergence under the influence of genetic drift and mutations alone were evaluated using neutral expectation for the divergence rate. Results The spatial correlograms showed a cline affecting the entire South American distribution. Interpolated maps showed that size and allometric shape vary from south‐east to north‐west. Multiple and multivariate regression analyses suggested that diet has the largest and most significant effect on this pattern of size and allometric shape variation. Finally, the results of the divergence rate test suggested that random processes alone cannot account for the morphological divergence exhibited by cranial size and allometric shape scores among southernmost populations. Main conclusions Correlograms, spatial regression and divergence rate analyses showed that although local factors (neutral processes or local environmental conditions) are important to explain spatial interpopulation differentiation in cranial characteristics among these populations, there is significant correlation of cranial size and allometric shape variation with diet. Gene flow among human populations, or local environmental conditions, could explain spatial variation mainly at smaller spatial scales, whereas the large‐scale pattern of the South American dataset is mainly related to the high proportion of carbohydrates and low proportion of proteins consumed.     

Persistence of Infectious Shiga Toxin-Encoding Bacteriophages after Disinfection Treatments

In Shiga toxin-producing Escherichia coli (STEC), induction of Shiga toxin-encoding bacteriophages (Stx phages) causes the release of free phages that can later be found in the environment. The ability of Stx phages to survive different inactivation conditions determines their prevalence in the environment, the risk of stx transduction, and the generation of new STEC strains. We evaluated the infectivity and genomes of two Stx phages (Φ534 and Φ557) under different conditions. Infectious Stx phages were stable at 4, 22, and 37°C and at pH 7 and 9 after 1 month of storage but were completely inactivated at pH 3. Infective Stx phages decreased moderately when treated with UV (2.2-log₁₀ reduction for an estimated UV dose of 178.2 mJ/cm²) or after treatment at 60 and 68°C for 60 min (2.2- and 2.5-log₁₀ reductions, respectively) and were highly inactivated (3 log₁₀) by 10 ppm of chlorine in 1 min. Assays in a mesocosm showed lower inactivation of all microorganisms in winter than in summer. The number of Stx phage genomes did not decrease significantly in most cases, and STEC inactivation was higher than phage inactivation under all conditions. Moreover, Stx phages retained the ability to lysogenize E. coli after some of the treatments.     

Effective strategy to assign 1H-15N heteronuclear correlation NMR signals from lysine side-chain NH3 + groups of proteins at low temperature

Recent studies have shown that lysine side-chain NH₃ ⁺ groups are excellent probes for NMR investigations of dynamics involving hydrogen bonds and ion pairs relevant to protein function. However, due to rapid hydrogen exchange, observation of ¹H-¹⁵N NMR cross peaks from lysine NH₃ ⁺ groups often requires use of a relatively low temperature, which renders difficulty in resonance assignment. Here we present an effective strategy to assign ¹H and ¹⁵N resonances of NH₃ ⁺ groups at low temperatures. This strategy involves two new ¹H/¹³C/¹⁵N triple-resonance experiments for lysine side chains. Application to a protein-DNA complex is demonstrated.     

Tracking algorithms chase down pathogens

Understanding subcellular dynamic processes governing pathogenic mechanisms is a necessary step towards the development of new drugs and strategies against infectious diseases. Subcellular pathogenic mechanisms, such as viral invasion processes involve highly dynamic nanometric-scale objects and rapid molecular interactions that require the study of individual particle paths. Single-particle tracking methods allow visualizing and characterizing the dynamics of biological objects, and provide a straightforward and accurate means to understand subcellular processes. This review describes a number of particle-tracking methods in time-lapse microscopy sequences and provides examples of using such techniques to investigate mechanisms of host-pathogen interactions.     

Evolutionary Perspective on the Interplay Between Family Life,and Parent and Offspring Personality

Consistent inter‐individual variation in behaviour over time and across contexts has been reported for a wide variety of animals, a phenomenon commonly referred to as personality. As behavioural patterns develop inside families, rearing conditions could have lasting effects on the expression of adult personality. In species with parental care, conflicts among family members impose selection on parental and offspring behaviour through coadaptation. Here, we argue that the interplay between the evolution of personality traits (i.e. boldness, exploration, activity, aggressiveness and sociability) expressed outside the family context and the specialized behaviours expressed inside families (i.e. offspring begging behaviour and parental response to offspring solicitations) can have important evolutionary consequences. Personality differences between parents may relate to the typically observed variation in the way they respond to offspring demand, and dependent offspring may already express personality differences, which may relate to the way they communicate with their parents and siblings. However, there has been little research on how personality relates to parental and offspring behaviours. Future research should thus focus on how and why personality may be related to the specialized parent and offspring behaviour that evolved as adaptations to family life.     

“Ensemble” iterative relaxation matrix approach: A new NMR refinement protocol applied to the solution structure of crambin

The structure in solution of crambin, a small protein of 46 residues, has been determined from 2D NMR data using an iterative relaxation matrix approach (IRMA) together with distance geometry, distance bound driven dynamics, molecular dynamics, and energy minimization. A new protocol based on an “ensemble” approach is proposed and compared to the more standard initial rate analysis approach and a “single structure” relaxation matrix approach. The effects of fast local motions are included and R-factor calculations are performed on NOE build-ups to describe the quality of agreement between theory and experiment. A new method for stereospecific assignment of prochiral groups, based on a comparison of theoretical and experimental NOE intensities, has been applied. The solution structure of crambin could be determined with a precision (rmsd from the average structure) of 0.7 Å on backbone atoms and 1.1 Å on all heavy atoms and is largely similar to the crystal structure with a small difference observed in the position of the side chain of Tyr-29 which is determined in solution by both J-coupling and NOE data. Regions of higher structural variability (suggesting higher mobility) are found hi the solution structure, in particular for the loop between the two helices (Gly-20 to Pro-22). © 1993 Wiley-Liss, Inc.     

Intra-individual variation in body temperature and pectoral muscle size in nestling Alpine swifts Apus melba in response to an episode of inclement weather

The Alpine swift (Apus melba) forages on insects caught exclusively on the wing, implying that dependent nestlings face acute food shortage in periods of cold and rainy weather. Therefore, there should be strong selection on nestling swifts to evolve physiological strategies to cope with periods of undernutrition. We have investigated intra-individual changes in nestling pectoral muscle and body temperature in response to a 1-week period of inclement weather. The pectoral muscle is the largest reserves of proteins, and nestlings have to devote a large amount of energy in the maintenance of body temperature. The results show that nestling pectoral muscle size and body temperature were significantly reduced during the episode of inclement weather. Assuming that these physiological changes are adaptive, our study suggests that nestling swifts spare energy by a pronounced reduction (up to 18°C) in body temperature and use proteins from the pectoral muscle as a source of extra energy to survive prolonged periods of fasting.