Intragenic codon bias in a set of mouse and human genes

To better conceptualize the mechanism underlying the evolution of synonymous codons, we have analysed intragenic codon usage in chosen "regions" of some mouse and human genes. We divided a given gene into two regions: one consisting of a trinucleotide repeat (TNR) and the other consisting of the "rest of the coding region" (RCR). Usually, a TNR is composed of a repetitive single codon, which may reflect its frequency in a gene. In contrast, a non-random frequency of a codon in the RCR versus TNR (or vice versa) of a gene should indicate a bias for that codon within the TNR. We examined this scenario by comparing codon frequency between the RCR and the cognate TNR(s) for a set of human and mouse genes. A TNR length of six amino acids or more was used to identify genes from the Genbank database. Twenty nine human and twenty one mouse genes containing TNRs coding for nine different amino acid runs were identified. The ratio of codon frequency in a TNR versus the corresponding RCR was expressed as "fold change" which was also regarded as a measure of codon bias (defined as preferential use either in TNR or in RCR). Chi-square values were then determined from the distribution of codon frequency in a TNR vs. the cognate RCR. At p<0.001, 22% and 27%, respectively, of human and mouse TNRs showed codon bias. Greater than 40% of the TNRs (29 out of 69 in human, and 18 of 42 in mouse) showed codon bias at p<0.05. In addition, we identify eight single-codon TNRs in mouse and ten in human genes. Thus, our results show intragenic codon bias in both mouse and human genes expressed in diverse tissue types. Since our results are independent of the Codon Adaptation Index (CAI) and starvation CAI, and since the tRNA repertoire in a cell or in a tissue is constant, our data suggest that other constraints besides tRNA abundance played a role in creating intragenic codon bias in these genes.     

Cell surface adhesion molecules and adhesion-initiated signaling: understanding of anoikis resistance mechanisms and therapeutic opportunities

Cells express various cell surface adhesion molecules (receptors) that not only mechanically serve as contacting sites between the cell and extracellular matrix (ECM) or adjacent cells, but also initiate intracellular signaling pathways modulating important cellular events including survival and proliferation. Normal cells undergo apoptosis when lacking ECM attachment. This type of cell death has been termed anoikis. Anoikis can be viewed as a normal process which ensures tissue homeostasis and failure to execute the anoikis program or resistance to anoikis could result in adherent cells surviving under suspension condition and proliferating at ectopic sites where the matrix proteins are different from those the cells originally contact. Resistance to anoikis is emerging as a hallmark of metastatic cancers which enables cancer cells to disseminate to distant organs through systemic circulation. In this review, we will discuss the molecular basis of adhesion-initiated signaling, the impact of loss of cell-ECM adhesion on normal cell survival, the role of cancer cell aggregate formation via intercellular adhesion under non-adherent condition, and mechanisms of anoikis resistance developed in metastatic cancer cells. Understanding of these aspects will provide opportunities to find new potential molecular targets, and therapeutic strategies based on these findings will likely prove to be more specific and effective.     

Microbes inside—from diversity to function: the case of Akkermansia

The human intestinal tract is colonized by a myriad of microbes that have developed intimate interactions with the host. In healthy individuals, this complex ecosystem remains stable and resilient to stressors. There is significant attention on the understanding of the composition and function of this intestinal microbiota in health and disease. Current developments in metaomics and systems biology approaches allow to probe the functional potential and activity of the intestinal microbiota. However, all these approaches inherently suffer from the fact that the information on macromolecules (DNA, RNA and protein) is collected at the ecosystem level. Similarly, all physiological and other information collected from isolated strains relates to pure cultures grown in vitro or in gnotobiotic systems. It is essential to integrate these two worlds of predominantly chemistry and biology by linking the molecules to the cells. Here, we will address the integration of omics- and culture-based approaches with the complexity of the human intestinal microbiota in mind and the mucus-degrading bacteria Akkermansia spp. as a paradigm.     

Recent advances in three-dimensional multicellular spheroid culture for biomedical research

Many types of mammalian cells can aggregate and differentiate into 3-D multicellular spheroids when cultured in suspension or a nonadhesive environment. Compared to conventional monolayer cultures, multicellular spheroids resemble real tissues better in terms of structural and functional properties. Multicellular spheroids formed by transformed cells are widely used as avascular tumor models for metastasis and invasion research and for therapeutic screening. Many primary or progenitor cells on the other hand, show significantly enhanced viability and functional performance when grown as spheroids. Multicellular spheroids in this aspect are ideal building units for tissue reconstruction. Here we review the current understanding of multicellular spheroid formation mechanisms, their biomedical applications, and recent advances in spheroid culture, manipulation, and analysis techniques.     

纤维堆囊菌的多细胞形态发生过程

粘细菌是具有复杂多细胞行为的革蓝氏阴性细菌,纤维堆囊菌是粘细菌中唯一能够降解纤维素的粘细菌种属。本文通过扫描电子显微镜和相差光学显微镜,分析了纤维堆囊菌在纤维素基质上的生长和子实体形态发生的多细胞行为特征,给出了生长和子实体发育的模式图谱。     

单细胞动物和多细胞动物的激素印迹

激素印迹是单细胞动物和多细胞动物的一种生理现象,也是选择参与信号识别过程分子的工具。激素印迹后,受体记忆将遗传给子孙后代,因此其对进化的作用可能是很大的。同时,激素印迹还有利于物种的维持。另外,激素印迹过程还是具有终身效应的临时开放系统的一部分。没有印迹,就没有完全的受体成熟,而不成熟的受体是不能和适量的激素结合的。在围 期诸如治疗药物和环境污染剂等人工合成的物质分子易致错误或病理印迹。许多研究表明错误印迹对生物体具有重要的影响。当然,单细胞动物的激素印迹过程与多细胞动物并不完全一样。     

The calculative nature of microbial biofilms and bioaggregates

Biological proliferation is optimized at various levels of organization, including the molecule (e.g. nucleic acids, prions), the cell (e.g. prokaryotic cells, eukaryotic cells), and the community (e.g. microbial biofilms, bioaggregates). Although it was initially assumed that this occurred through the genesis of information within DNA alone, it now appears that innovative design originates at other levels of organization in addition to DNA. For example, the recombination of community structures affects the proliferation rate of genetic structures; and the recombination of genetic structures affects the proliferation rate of community structures. This feedback mechanism computes compromises between the form and function of both community and nucleic acid. A nested series of proliferating objects (e.g. genetic structure, cell structure, community structure) is thus capable of continually updating the form of each object in the series. This accounts for the calculative nature of prokaryotic cells, eukaryotic cells, biofilms, bioaggregates, microbial consortia, and most other complex adaptive systems. Electronic Publication     

Genetic and evolutionary consequences of symbiosis

Permanent stable symbioses, primarily microbial, are analyzed as parasexual phenomena from the evolutionary point of view. Such associations bring together in single individuals heritable traits of high selective advantage in certain environments. By convergent evolution several types of associations have repeatedly arisen: motile photosynthetic forms, nitrogen fixing and wood digesting complexes, and so forth. Many examples are discussed from the point of view of the number of originally independent genomes that comprise the recognizable individuals.The level of partner integration in many associations is analyzed. Examples of many levels: genic, gene product, metabolite, behavioral, and the methods by which they can be distinguished are discussed.The literature concerning a large number of associations is reviewed: Methanobacillus; predatory and consortia bacteria; blue green algal sheath dwelling bacteria; anaerobic worm-bacterial; algal, and foreign chloroplast retention by heterotrophic eukaryotes (ciliates, coelenterates, mollusks); the double nucleated photosynthetic dinoflagellate (Peridinium balticum); hindgut microbes in termites and woodroaches (Pyrsonympha, Barbulanympha and their associated spirochetes and other bacteria); sand dwelling and other ciliates and their associated bacteria; and so forth. The status of observations and artificial systems claiming evidence for transfer of genes between very distantly related organisms is critically discussed.A continuum from nearly completely autonomous partners (e.g., zoochlorellae in invertebrate animals) to nearly unrecognizable merged components (e.g., gamma particles in Blastocladiella) is found to exist among examples of extant organisms. The diversity and prevalence of such associations support the concept that there are many precedents for the steps hypothesized in the serial endosymbiotic theory of the origin of eukaryotic cells.     

Effects of exogenously applied salicylic acid and putrescine alone and in combination with rhizobacteria on the phytoremediation of heavy metals and chickpea growth in sandy soil

The present attempt was made to study the role of exogenously applied salicylic acid (SA) and putrescine (Put) on the phytoremediation of heavy metals and on the growth parameters of chickpea grown in sandy soil. The SA and Put were applied alone as well as in combination with plant growth promoting rhizobacteria (PGPR). The PGPRs, isolated from the rhizosphere of chickpea, were characterized on the basis of colony morphology and biochemical traits through gram staining, catalase and oxidase tests, and identified by 16S-rRNA gene sequencing as Bacillus subtilis, Bacillus thuringiensis and Bacillus megaterium. The chickpea seeds were soaked in 24 h old fresh cultures of isolates for 2–3 h prior to sowing. The growth regulators (PGRs), SA and Put (150 mg/L), were applied to the seedlings as foliar spray at three-leaf stage. The result revealed that plants treated with SA and Put alone or in combination with PGPRs, significantly enhanced the accumulation of heavy metals in plant shoot. PGPR induces Ni accumulation in sensitive variety and Pb in both the varieties, the PGR in combination augment the bioremediation effects of PGPR and both sensitive and tolerant variety showed significant accumulation of Ni, Cd, and Pb. SA was more effective in accumulating Ni and Cd whereas, significant accumulation of Pb was recorded in Put. PGPRs further augmented the PGRs induced accumulation of heavy metals and macronutrients in chickpea shoot and in rhizosphere. SA increased the proline content of tolerant variety while decreasing the lipid peroxidation and proline content of the sensitive variety but decreased the stimulating effect of PGPR in proline production. Interactive effects of PGPR and PGRs are recommended for inducing phytoremediation in chickpea plants under drought stress.