Compositional variation in bacterial genes and proteins with potential expression level

Usage of guanine and cytosine at three codon sites in eubacterial genes vary distinctly with potential expressivity, as predicted by Codon Adaptation Index (CAI). In bacteria with moderate/high GC-content, G(3) follows a biphasic relationship, while C(3) increases with CAI. In AT-rich bacteria, correlation of CAI is negative with G(3), but non-specific with C(3). Correlations of CAI with residues encoded by G-starting codons are positive, while with those by C-starting codons are usually negative/random. Average Size/Complexity Score and aromaticity of gene-products decrease with CAI, confirming general validity of cost-minimization principle in free-living eubacteria. Alcoholicity of bacterial gene-products usually decreases with expressivity.     

A large-scale analysis of codon usage bias in 4868 bacterial genomes shows association of codon adaptation index with GC content,protein functional domains and bacterial phenotypes

Multiple synonymous codons code for the same amino acid, resulting in the degeneracy of the genetic code and in the preferred used of some codons called codon bias usage (CBU). We performed a large-scale analysis of codon usage bias analysing the distribution of the codon adaptation index (CAI) and the codon relative adaptiveness index (RA) in 4868 bacterial genomes. We found that CAI values differ significantly between protein functional domains and part of the protein outside domains and show how CAI, GC content and preferred usage of polymerase III alpha subunits are related. Additionally, we give evidence of the association between CAI and bacterial phenotypes.     

江苏下扬子区寒武系-三叠系牙形刺色变指标(CAI)图及其意义

本文对多年来积累的江苏下扬子区寒武系－三叠系牙形刺CAI材料进行了系统收集和整理,并采用Anita Harris建立的统一标准,编制了本区寒武系－三叠系的5幅牙形刺CAI图;进而结合牙形刺CAI与镜质组反射率（Ro)的对应关系,对上述各系的有机质成熟度进行了评价,对本区海相中、古生界油气勘探具有十分重要的意义。     

Molecular evolution of the carbonic anhydrase genes: Calculation of divergence time for mouse carbonic anhydrase I and II

Summary A cDNA clone in pBR322 that cross-hybridizes with a mouse carbonic anhydrase form II (CAII) probe has been sequenced and identified as mouse carbonic anhydrase form I (CAI). The 1224-base-pair clone encodes the entire 260-amino-acid protein and appears to contain an Alu-like element in the 3 untranslated region. The deduced amino acid sequence exhibits 77% homology to human CAI and contains 17 of the 20 residues that are considered unique to and invariant for all mammalian CAI isozymes. The results of a detailed comparison of the nucleic acid sequences spanning the coding regions of mouse CAI and rabbit CAI have been used to calibrate an evolutionary clock for the carbonic anhydrases (CAs). These data have been applied to a comparison of the mouse CAI and CAII nucleic acid sequences to calculate the divergence time between the two genes. The divergence-time calculation provides the first estimation of the evolutionary relationship between CAs based entirely on nucleotide sequence comparison.     

动物学CAI课件制作及其在教学中的应用

介绍了动物学CAI(Computer-Assisted Instruction)课件的制作和使用特点。阐述了CAI课件在动物学课堂教学中的意义和地位,探讨了其在高校动物学课堂教学中实施素质教育和使用双语教学新模式的应用特点,并讨论了动物学CAI课件在未来的发展趋势。     

Biochemical and Population Genetics of the Rabbit, Oryctolagus cuniculus, Carbonic Anhydrases I and II, from the Iberian Peninsula and France

Available studies on the biochemical and electrophoretic characterization of European rabbit (Oryctolagus cuniculus) carbonic anhydrases I and II (CAI, CAII) show contradictory results about their relative electrophoretic mobility and substrate specificity. After positive identification of carbonic anhydrase activity by CO2 hydration, the differential esterase activity of CAI and CAII toward beta-napththyl acetate and flourescein diacetate,respectively, were used to identify the banding patterns corresponding to each locus. Electrophoretic and hybrid isoelectric focusing analyses of the CAI and CAII loci in 1 domestic and 19 wild rabbit populations led to the recognition of genetic polymorphism at the CAI locus and of extensive variability at the CAII locus. Four and nine alleles at the CAI and CAII loci, respectively, are described. The geographic distribution of genetic variability is consistent with the existence of two evolutionary groups within O. cuniculus.     

Ligand and antagonist driven regulation of the Vibrio cholerae quorum-sensing receptor CqsS

Quorum sensing, a bacterial cell–cell communication process, controls biofilm formation and virulence factor production in Vibrio cholerae, a human pathogen that causes the disease cholera. The major V. cholerae autoinducer is (S)‐3‐hydroxytridecan‐4‐one (CAI‐1). A membrane bound two‐component sensor histidine kinase called CqsS detects CAI‐1, and the CqsS → LuxU → LuxO phosphorelay cascade transduces the information encoded in CAI‐1 into the cell. Because the CAI‐1 ligand is known and because the signalling circuit is simple, consisting of only three proteins, this system is ideal for analysing ligand regulation of a sensor histidine kinase. Here we reconstitute the CqsS → LuxU → LuxO phosphorylation cascade in vitro. We find that CAI‐1 inhibits the initial auto‐phosphorylation of CqsS whereas subsequent phosphotransfer steps and CqsS phosphatase activity are not CAI‐1‐controlled. CAI‐1 binding to CqsS causes a conformational change that renders His194 in CqsS inaccessible to the CqsS catalytic domain. CqsS mutants with altered ligand detection specificities are faithfully controlled by their corresponding modified ligands in vitro. Likewise, pairing of agonists and antagonists allows in vitro assessment of their opposing activities. Our data are consistent with a two‐state model for ligand control of histidine kinases.     

Regulation of the pro-angiogenic microenvironment by carboxyamido-triazole

Anti-angiogenic agents regulate tumor growth by inhibiting endothelial cell proliferation and invasion. Carboxyamido-triazole (CAI), an inhibitor of non-voltage-operated calcium entry and calcium influx-mediated pathways, has angiogenesis and invasion inhibitory activity. We hypothesized that CAI may express its anti-angiogenic effects through negative regulation of pro-angiogenic cytokine production and/or function. In vivo, orally administered CAI prevented A2058 human melanoma xenograft growth and concomitantly resulted in a marked reduction in circulating vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). In vitro, A2058 cell secretion of VEGF was inhibited by CAI treatment under limiting micronutrient conditions that approximate the tumor microenvironment, media restriction, and acidification to pH 6.8 (P=0.0003 and P=0.0006, respectively). VEGF and HIF-1alpha message and protein were also reduced by CAI treatment. Oral CAI treatment reduced vascular ingrowth in vivo into VEGF-containing Matrigel plugs. Commensurate with those findings, human umbilical vein endothelial cell (HUVEC) migration towards VEGF was reduced below background by exposure to CAI in the migration chamber (P<0.0001). An 88% reduction in circulating IL-8 concentration was measured in CAI-treated animals. However, IL-8 protein secretion and gene expression were increased by CAI treatment in culture (P< or =0.01), where CAI caused a dose-dependent acidification of the culture milieu (P< or =0.005). This paradox suggests that IL-8 production in vitro may be more sensitive to ambient pH than cytosolic calcium. These observations suggest that CAI inhibition of tumor cell VEGF production and endothelial cell response to VEGF results in disruption of signaling between the tumor and its microenvironment, causing a net anti-angiogenic effect.     

Deficiency of a carbonic anhydrase (CAI) isoenzyme in the chinchilla

1. A marked deficiency of the low activity carbonic anhydrase isoenzyme (CAI) has been found in chinchillas, resulting in a 90% reduction in CAI.
2. The trace of CAI found in deficient animals exhibits a similar immunological reaction and electrophoretic migration to the usual CAI (+).     

Deficits in reaction time due to increased motor time of peroneus longus in people with chronic ankle instability

The purpose of this study was to investigate whether neuromuscular adaptations at the site of injury or neural adaptation remote to the injury are affected in individuals with chronic ankle instability (CAI). Electromyography data were collected from the peroneus longus (PL) and tibialis anterior during an ankle joint reaction time task in 12 participants with unilateral CAI and 12 healthy control participants. Following an auditory cue, time to onset of muscle activity (pre-motor time) and time from onset of muscle activity to movement (motor time) were measured during rapid ankle eversion and dorsiflexion. Reaction time for ankle eversion on the affected side was significantly slower in the CAI group than the control group, due to significantly slower motor time for the PL. Changes in motor time for the affected PL in participants with CAI may be attributed to a combination of factors associated with local tissue changes.     

E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI)

Background  

The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values.     

A peptide inhibitor of HIV-1 assembly in vitro

Formation of infectious HIV-1 involves assembly of Gag polyproteins into immature particles and subsequent assembly of mature capsids after proteolytic disassembly of the Gag shell. We report a 12-mer peptide, capsid assembly inhibitor (CAI), that binds the capsid (CA) domain of Gag and inhibits assembly of immature- and mature-like capsid particles in vitro. CAI was identified by phage display screening among a group of peptides with similar sequences that bind to a single reactive site in CA. Its binding site was mapped to CA residues 169-191, with an additional contribution from the last helix of CA. This result was confirmed by a separate X-ray structure analysis showing that CAI inserts into a conserved hydrophobic groove and alters the CA dimer interface. The CAI binding site is a new target for antiviral development, and CAI is the first known inhibitor directed against assembly of immature HIV-1.     

Codon use and the rate of divergence of land plant chloroplast genes

Codon fitnesses for chloroplast genes were estimated using the relative synonymous codon use of psbA, which has a different pattern of codon use than other chloroplast genes and is the major translation product of the chloroplast. These estimates were used to calculate the codon adaptation index (CAI) of chloroplast genes from Marchantia polymorpha, Nicotiana tabacum, and Chlamydomonas reinhardtii. The genes with the highest CAI values in M. polymorpha correspond to those that are expressed at the highest levels. The rate of divergence between M. polymorpha and both C. reinhardtii and N. tabacum is inversely related to the CAI value of the M. polymorpha gene. The data suggest that selection is acting on the synonymous codon use of the highly expressed genes of the M. polymorpha chloroplast genome. The data set is inconclusive about N. tabacum genes, but, as there is a weaker correspondence between CAI value and expression level, it suggests that selection is not operating in this lineage.      

Preferential usage of some minor codons in bacteria

In many bacterial species, such as Deinococcus radiodurans, Haemophilus influenzae, and Methanobacterium thermoautotrophicum, some minor codons are preferentially used near the initiation codon. Among these codons, there are some minor codons that have strong preference for the initiation site in the high codon adaptation index (CAI) group (comprising of highly expressed genes) rather than in the low CAI genes group (comprising of low expressing genes). In the present study, codon usage in the initiation site and in the rest of the gene was systematically compared in the 27 complete bacterial genomes and Saccharomyces cerevisiae genome. Furthermore, we classified genes into two groups according to the CAI values and conducted the same analysis for each of the two groups. Our results suggest a role for some minor codons in the initiation site of the regulating translation system in many bacteria. We have summarized codons that are preferentially used in the initiation site and probably play a role in regulating genes expression in these organisms.     

Neural excitability of lower extremity musculature in individuals with and without chronic ankle instability: A systematic review and meta-analysis

This systematic review and meta-analysis examined differences in lower extremity neural excitability between ankles with and without chronic ankle instability (CAI). We searched the literature for studies that compared corticomotor or spinal reflexive excitability between a CAI group and controls or copers, or between limbs of a CAI group. Random effects meta-analyses calculated pooled effect sizes for each outcome. Nineteen studies were included. Meta-analyses of motor thresholds of the fibularis longus (Z = 1.17, P = 0.24) and soleus (Z = 0.47, P = 0.64) exhibited no differences between ankles with and without CAI. Pooled data indicate that ankles with CAI had reduced soleus spinal reflexive excitability (Z = 2.18, P = 0.03) and significantly less modulation of the soleus (Z = 6.96, P < 0.01) and fibularis longus (Z = 4.75, P < 0.01) spinal reflexive excitability when transitioning to more challenging stances. Pre-synaptic inhibition was facilitated in ankles with CAI (Z = 4.05, P < 0.01), but no difference in recurrent inhibition existed (Z = 1.50, P = 0.13). Soleus spinal reflexive activity is reduced in those with CAI. Reduced ability of ankles with CAI to modulate soleus and fibularis longus reflexive activity may contribute to impaired balance.     

CqsA–CqsS quorum‐sensing signal‐receptor specificity in Photobacterium angustum

Quorum sensing (QS) is a process of bacterial cell–cell communication that relies on the production, detection and population‐wide response to extracellular signal molecules called autoinducers. The QS system commonly found in vibrios and photobacteria consists of the CqsA synthase/CqsS receptor pair. Vibrio cholerae CqsA/S synthesizes and detects (S)‐3‐hydroxytridecan‐4‐one (C10‐CAI‐1), whereas Vibrio harveyi produces and detects a distinct but similar molecule, (Z)‐3‐aminoundec‐2‐en‐4‐one (Ea‐C8‐CAI‐1). To understand the signalling properties of the larger family of CqsA–CqsS pairs, here, we characterize the Photobacterium angustum CqsA/S system. Many photobacterial cqsA genes harbour a conserved frameshift mutation that abolishes CAI‐1 production. By contrast, their cqsS genes are intact. Correcting the P. angustum cqsA reading frame restores production of a mixture of CAI‐1 moieties, including C8‐CAI‐1, C10‐CAI‐1, Ea‐C8‐CAI‐1 and Ea‐C10‐CAI‐1. This signal production profile matches the P. angustum CqsS receptor ligand‐detection capability. The receptor exhibits a preference for molecules with 10‐carbon tails, and the CqsS Ser¹⁶⁸ residue governs this preference. P. angustum can overcome the cqsA frameshift to produce CAI‐1 under particular limiting growth conditions presumably through a ribosome slippage mechanism. Thus, we propose that P. angustum uses CAI‐1 signalling for adaptation to stressful environments.     

Effects of carboxyamidotriazole on in vitro models of imatinib-resistant chronic myeloid leukemia

Although imatinib mesylate (IM) has revolutionized the treatment of chronic myeloid leukemia (CML), some patients develop resistance with progression of leukemia. Alternative or additional targeting of signaling pathways deregulated in bcr-abl-driven CML cells may provide a feasible option for improving clinical response and overcoming resistance. In this study, we show that carboxyamidotriazole (CAI), an orally bioavailable calcium influx and signal transduction inhibitor, is equally effective in inhibiting the proliferation and bcr-abl dependent- and independent-signaling pathways in imatinib-resistant CML cells. CAI inhibits phosphorylation of cellular proteins including STAT5 and CrkL at concentrations that induce apoptosis in IM-resistant CML cells. The combination of imatinib and CAI also down-regulated bcr-abl protein levels. Since CAI is already available for clinical use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of CML.     

Rat liver carbonic anhydrase I is not sexually dimorphic but is estrogen repressible

Carbonic anhydrase (CA) isozymes CAII and CAIII are known to exhibit sexual dimorphism in rat liver, and the levels o f these isozymes are affected by sex hormones. In this paper we show that the isozyme CAI is present at low levels in rat liver, with no difference in concentration between male and female rats. Estrogen and diethylstilbestrol reduce CAI levels in both sexes.     

Kinematic,kinetic and electromyographic differences between young adults with and without chronic ankle instability during walking

The objective of this study was to quantify the kinematic, kinetic and electromyography differences between individuals with and without chronic ankle instability (CAI) during comfortable (CW) and fast (FW) walking. Twenty-one individuals with CAI and 21 healthy controls were recruited to walk at CW and FW speeds. The dependent variables were gluteus medius, vastus lateralis, gastrocnemius lateralis, gastrocnemius medialis, peroneus longus and tibialis anterior muscles mean activity, ankle and knee angles and moments. Kinematic, kinetic and electromyography variables were compared between groups with a one-dimensional statistical non-parametric mapping analysis. The CAI group exhibited no significant difference for ankle angles and moments compared to the control group. However, the CAI group showed less external knee rotation from 56 to 100% (CW) and 51 to 98% (FW) and more knee abduction moment from 1 to 6% and 7 to 9% (CW) and 1 to 2% (FW) of the stance phase. Less gluteus medius muscle activity was also observed from 6 to 9% and 99 to 100% (CW) of the stance phase for the CAI group. These results suggest proximal biomechanical compensations and will help better understand the underlying deficits associated with CAI. They also indicate that regardless of walking speeds, individuals with CAI exhibit similar differences compared to healthy participants.