On the evolution of morphogenetic models: mechano-chemical interactions and an integrated view of cell differentiation, growth, pattern formation and morphogenesis

In the 1950s, embryology was conceptualized as four relatively independent problems: cell differentiation, growth, pattern formation and morphogenesis. The mechanisms underlying the first three traditionally have been viewed as being chemical in nature, whereas those underlying morphogenesis have usually been discussed in terms of mechanics. Often, morphogenesis and its mechanical processes have been regarded as subordinate to chemical ones. However, a growing body of evidence indicates that the biomechanics of cells and tissues affect in striking ways those phenomena often thought of as mainly under the control of cell-cell signalling. This accumulation of data has led to a revival of the mechano-transduction concept in particular, and of complexity in general, causing us now to consider whether we should retain the traditional conceptualization of development. The researchers' semantic preferences for the terms 'patterning', 'pattern formation' or 'morphogenesis' can be used to describe three main 'schools of thought' which emerged in the late 1970s. In the 'molecular school', the term patterning is deeply tied to the positional information concept. In the 'chemical school', the term 'pattern formation' regularly implies reaction-diffusion models. In the 'mechanical school', the term 'morphogenesis' is more frequently used in relation to mechanical instabilities. Major differences among these three schools pertain to the concept of self-organization, and models can be classified as morphostatic or morphodynamic. Various examples illustrate the distorted picture that arises from the distinction among differentiation, growth, pattern formation and morphogenesis, based on the idea that the underlying mechanisms are respectively chemical or mechanical. Emerging quantitative approaches integrate the concepts and methods of complex sciences and emphasize the interplay between hierarchical levels of organization via mechano-chemical interactions. They draw upon recent improvements in mathematical and numerical morphogenetic models and upon considerable progress in collecting new quantitative data. This review highlights a variety of such models, which exhibit important advances, such as hybrid, stochastic and multiscale simulations.     

Frequency-dependent payoffs and sequential decision-making favour consistent tactic use

Although natural selection should have favoured individuals capable of adjusting the weight they give to personal and social information according to circumstances, individuals generally differ consistently in their individual weighting of both types of information. Such individual differences are correlated with personality traits, suggesting that personality could directly affect individuals' ability to collect personal or social information. Alternatively, the link between personality and information use could simply emerge as a by-product of the sequential decision-making process in a frequency-dependent context. Indeed, when the gains associated with behavioural options depend on the choices of others, an individual's sequence of arrival could constrain its choice of options leading to the emergence of correlated behaviours. Any factor such as personality that affects decision order could thus be correlated with information use. To test this new explanation, we developed an individual-based model that simulates a group of animals engaged in a game of sequential frequency-dependent decision: a producer-scrounger game. Our results confirm that the sequence of decision, in this case enforced by the order in which animals enter a foraging area, consistently influences their mean tactic use and their individual plasticity, an outcome reminiscent of the correlation reported between personality and social information use.     

Identification and characterization of microRNAs and their target genes in Brassica oleracea

The microRNAs are a new class of small non-coding endogenous RNAs with lengths of approximately ~21 nt. MicroRNAs perform their biological function via the degradation of the target mRNAs or by inhibiting protein translation. Until recently, only limited numbers of miRNAs were identified in Brassica oleracea, a vegetable widely cultivated around the world. In present study, 193 potential miRNA candidates were identified from 17 expressed sequence tag (ESTs) and 152 genome survey sequences (GSSs) in B. oleracea. These miRNA candidates were classified into 70 families using a well-defined comparative genome-based computational analysis. Most miRNAs belong to the miRNA169, miR5021, miR156 and miR158 families. Of these, 36 miRNA families are firstly found in Brassica species. Around 1393 B. oleracea genes were predicted as candidate targets of 175 miRNAs. The mutual relationship between miRNAs and the candidate target genes was verified by checking differentially expression levels using quantitative real-time polymerase chain reaction (qRT-PCR) and 5' RLM-RACE analyses. These target genes participate in multiple biological and metabolic processes, including signal transduction, stress response, and plant development. Gene Ontology analysis shows that the 818, 514, and 265 target genes are involved in molecular functions, biological processes, and cellular component respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis suggests that these miRNAs might regulate 186 metabolic pathways, including those of lipid, energy, starch and sucrose, fatty acid and nitrogen.     

Genome-based phylogeny of dsDNA viruses by a novel alignment-free method

Sequence alignment is not directly applicable to whole genome phylogeny since several events such as rearrangements make full length alignments impossible. Here, a novel alignment-free method derived from the standpoint of information theory is proposed and used to construct the whole-genome phylogeny for a population of viruses from 13 viral families comprising 218 dsDNA viruses. The method is based on information correlation (IC) and partial information correlation (PIC). We observe that (i) the IC-PIC tree segregates the population into clades, the membership of each is remarkably consistent with biologist's systematics only with little exceptions; (ii) the IC-PIC tree reveals potential evolutionary relationships among some viral families; and (iii) the IC-PIC tree predicts the taxonomic positions of certain “unclassified” viruses. Our approach provides a new way for recovering the phylogeny of viruses, and has practical applications in developing alignment-free methods for sequence classification.     

The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River

The study determined heavy metal concentrations and MT1 nucleotide sequence [phylogeny] in liver of the Kafue lechwe. Applicability of MT1 as a biomarker of pollution was assessed. cDNA-encoding sequences for lechwe MT1 were amplified by RT-PCR to characterize the sequence of MT1 which was subjected to BLAST searching at NCBI. Phylogenetic relationships were based on pairwise matrix of sequence divergences calculated by Clustal W. Phylogenetic tree was constructed by NJ method using PHILLIP program. Metals were extracted by acid digestion and concentrations of Cr, Co, Cu, Zn, Cd, Pb, and Ni were determined using an AAS. MT1 mRNA expression levels were measured by quantitative comparative real-time RT-PCR. Lechwe MT1 has a length of 183bp, which encode for MT1 proteins of 61AA, which include 20 cysteines. Nucleotide sequence of lechwe MT1 showed identity with sheep MT (97%) and cattle MT1E (97%). Phylogenetic tree revealed that lechwe MT1 was clustered with sheep MT and cattle MT1E. Cu and Ni concentrations and MT1 mRNA expression levels of lechwe from Blue Lagoon were significantly higher than those from Lochinvar (p<0.05). Concentrations of Cd and Cu, Co and Cu, Co and Pb, Ni and Cu, and Ni and Cr were positively correlated. Spearman's rank correlations also showed positive correlations between Cu and Co concentrations and MT mRNA expression. PCA further suggested that MT mRNA expression was related to Zn and Cd concentrations. Hepatic MT1 mRNA expression in lechwe can be used as biomarker of heavy metal pollution.     

Polymorphisms of the insulin-like growth factor-binding protein 3 gene (IGFBP3) in gayal (Bos frontalis)

The gene coding for insulin-like growth factor-binding protein 3 (IGFBP3) is important for regulation of growth, development and metabolism in mammals. The present investigation was conducted to study nucleotide polymorphism of the IGFBP3 in gayal (Bos frontalis) and to compare the variations with those which occur in other ruminants. A fragment of 645 base pairs of the IGFBP3 covering a part of exon 2, the complete intron 2 and exon 3 and a part of intron 3 was amplified, sequenced (n=46) and digested (n=79) with HaeIII restriction enzyme from 125 collected gayal samples. Nine single nucleotide polymorphisms (SNPs) [C14T, A122C, C137T, G144C, C155T, G213A, C279A, G334A and G460A] were identified and located in intron 2, revealing high genetic variability. The alignment of nucleotide sequences was found to be very similar to those for other bovid species. Sequencing and HaeIII digestion showed that frequency of alleles C and A [consisting of fragments of sizes 56, 64, 228, 264, 282, 298 and 497 bp (CC genotype)] was 0.96 and 0.04 for the SNP C279A. Moreover, the genotype frequency of the SNP C279A in gayal was compared with that in other ruminants and it appears that this polymorphism may be associated with low fat content and rapid growth in this rare species.     

Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP)

The major hallmark of cellular senescence is an irreversible cell cycle arrest and thus it is a potent tumor suppressor mechanism. Genotoxic insults, e.g. oxidative stress, are important inducers of the senescent phenotype which is characterized by an accumulation of senescence-associated heterochromatic foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). Interestingly, senescent cells secrete pro-inflammatory factors and thus the condition has been called the senescence-associated secretory phenotype (SASP). Emerging data has revealed that NF-κB signaling is the major signaling pathway which stimulates the appearance of SASP. It is known that DNA damage provokes NF-κB signaling via a variety of signaling complexes containing NEMO protein, an NF-κB essential modifier, as well as via the activation of signaling pathways of p38MAPK and RIG-1, retinoic acid inducible gene-1. Genomic instability evoked by cellular stress triggers epigenetic changes, e.g. release of HMGB1 proteins which are also potent enhancers of inflammatory responses. Moreover, environmental stress and chronic inflammation can stimulate p38MAPK and ceramide signaling and induce cellular senescence with pro-inflammatory responses. On the other hand, two cyclin-dependent kinase inhibitors, p16INK4a and p14ARF, are effective inhibitors of NF-κB signaling. We will review in detail the signaling pathways which activate NF-κB signaling and trigger SASP in senescent cells.     

Acetylation of αA-crystallin in the human lens: Effects on structure and chaperone function

α-Crystallin is a major protein in the human lens that is perceived to help to maintain the transparency of the lens through its chaperone function. In this study, we demonstrate that many lens proteins including αA-crystallin are acetylated in vivo. We found that K70 and K99 in αA-crystallin and, K92 and K166 in αB-crystallin are acetylated in the human lens. To determine the effect of acetylation on the chaperone function and structural changes, αA-crystallin was acetylated using acetic anhydride. The resulting protein showed strong immunoreactivity against a N^ε-acetyllysine antibody, which was directly related to the degree of acetylation. When compared to the unmodified protein, the chaperone function of the in vitro acetylated αA-crystallin was higher against three of the four different client proteins tested. Because a lysine (residue 70; K70) in αA-crystallin is acetylated in vivo, we generated a protein with an acetylation mimic, replacing Lys70 with glutamine (K70Q). The K70Q mutant protein showed increased chaperone function against three client proteins compared to the Wt protein but decreased chaperone function against γ-crystallin. The acetylated protein displayed higher surface hydrophobicity and tryptophan fluorescence, had altered secondary and tertiary structures and displayed decreased thermodynamic stability. Together, our data suggest that acetylation of αA-crystallin occurs in the human lens and that it affects the chaperone function of the protein.     

中国地鼠山医群体近交系E繁殖性状的遗传力估计

目的对中国地鼠山医群体近交系E的一些繁殖性状进行遗传力估计分析。方法采用平均信息约束最大似然法（AIREML）,利用WOMBAT软件进行处理。结果产仔数、离乳数、胎间隔2-1和胎间隔3-2的遗传力均较低,分别为0.05、0.096、0.182和0.116。结论中国地鼠山医群体近交系E繁殖性状的遗传力均属于低遗传力。