Computational identification of rare codons of Escherichia coli based on codon pairs preference

<p>Abstract</p> <p>Background</p> <p>Codon bias is believed to play an important role in the control of gene expression. In <it>Escherichia coli</it>, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in <it>Escherichia coli</it>.</p> <p>Results</p> <p>In <it>Escherichia coli</it>, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F_rare) was developed. Through comparison with the classical indices we found a significant negative correlation between F_rareand the indices which depend on reference datasets.</p> <p>Conclusions</p> <p>Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F_rare) could be a useful index of codon bias regardless of the lack of expression abundance information.</p

Water management affects arsenic and cadmium accumulation in different rice cultivars

Paddy rice (Oryza sativa L.) is a staple food and one of the major sources of dietary arsenic (As) and cadmium (Cd) in Asia. A field experiment was conducted to investigate the effects of four water management regimes (aerobic, intermittent irrigation, conventional irrigation and flooding) on As and Cd accumulation in seven major rice cultivars grown in Zhejiang province, east China. With increasing irrigation from aerobic to flooded conditions, the soil HCl-extractable As concentrations increased significantly and the HCl-extractable Cd concentrations decreased significantly. These trends were consistent with the As and Cd concentrations in the straw, husk and brown rice. Water management both before and after the full tillering stage affected As and Cd accumulation in the grains. The intermittent and conventional treatments produced higher grain yields than the aerobic and flooded treatments. Cd concentrations in brown rice varied 13.1-40.8 times and As varied 1.75-8.80 times among the four water management regimes. Cd and As accumulation in brown rice varied among the rice cultivars, with Guodao 6 (GD6) was a low Cd but high-As-accumulating cultivar while Indonesia (IR) and Yongyou 9 (YY9) were low As but high-Cd-accumulating cultivars. Brown rice Cd and As concentrations in the 7 cultivars were significantly negatively correlated. The results indicate that As and Cd accumulated in rice grains with opposite trends that were influenced by both water management and rice cultivar. Production of 'safe' rice with respect to As and Cd might be possible by balancing water management and rice cultivar according to the severity of soil pollution.Paddy rice (Oryza sativa L.) is a staple food and one of the major sources of dietary arsenic (As) and cadmium (Cd) in Asia. A field experiment was conducted to investigate the effects of four water management regimes (aerobic, intermittent irrigation, conventional irrigation and flooding) on As and Cd accumulation in seven major rice cultivars grown in Zhejiang province, east China. With increasing irrigation from aerobic to flooded conditions, the soil HCl-extractable As concentrations increased significantly and the HCl-extractable Cd concentrations decreased significantly. These trends were consistent with the As and Cd concentrations in the straw, husk and brown rice. Water management both before and after the full tillering stage affected As and Cd accumulation in the grains. The intermittent and conventional treatments produced higher grain yields than the aerobic and flooded treatments. Cd concentrations in brown rice varied 13.1-40.8 times and As varied 1.75-8.80 times among the four water management regimes. Cd and As accumulation in brown rice varied among the rice cultivars, with Guodao 6 (GD6) was a low Cd but high-As-accumulating cultivar while Indonesia (IR) and Yongyou 9 (YY9) were low As but high-Cd-accumulating cultivars. Brown rice Cd and As concentrations in the 7 cultivars were significantly negatively correlated. The results indicate that As and Cd accumulated in rice grains with opposite trends that were influenced by both water management and rice cultivar. Production of 'safe' rice with respect to As and Cd might be possible by balancing water management and rice cultivar according to the severity of soil pollution

Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatmePeer ReviewedPostprint (published version

Longitudinal Serum Proteome Characterization of COVID-19 Patients With Different Severities Revealed Potential Therapeutic Strategies

The COVID-19 pandemic caused by SARS-CoV-2 is exerting huge pressure on global healthcare. Understanding of the molecular pathophysiological alterations in COVID-19 patients with different severities during disease is important for effective treatment. In this study, we performed proteomic profiling of 181 serum samples collected at multiple time points from 79 COVID-19 patients with different severity levels (asymptomatic, mild, moderate, and severe/critical) and 27 serum samples from non-COVID-19 control individuals. Dysregulation of immune response and metabolic reprogramming was found in severe/critical COVID-19 patients compared with non-severe/critical patients, whereas asymptomatic patients presented an effective immune response compared with symptomatic COVID-19 patients. Interestingly, the moderate COVID-19 patients were mainly grouped into two distinct clusters using hierarchical cluster analysis, which demonstrates the molecular pathophysiological heterogeneity in COVID-19 patients. Analysis of protein-level alterations during disease progression revealed that proteins involved in complement activation, the coagulation cascade and cholesterol metabolism were restored at the convalescence stage, but the levels of some proteins, such as anti-angiogenesis protein PLGLB1, would not recovered. The higher serum level of PLGLB1 in COVID-19 patients than in control groups was further confirmed by parallel reaction monitoring (PRM). These findings expand our understanding of the pathogenesis and progression of COVID-19 and provide insight into the discovery of potential therapeutic targets and serum biomarkers worth further validation

Regular Patterns for Proteome-Wide Distribution of Protein Abundance across Species

A proteome of the bio-entity, including cell, tissue, organ, and organism, consists of proteins of diverse abundance. The principle that determines the abundance of different proteins in a proteome is of fundamental significance for an understanding of the building blocks of the bio-entity. Here, we report three regular patterns in the proteome-wide distribution of protein abundance across species such as human, mouse, fly, worm, yeast, and bacteria: in most cases, protein abundance is positively correlated with the protein's origination time or sequence conservation during evolution; it is negatively correlated with the protein's domain number and positively correlated with domain coverage in protein structure, and the correlations became stronger during the course of evolution; protein abundance can be further stratified by the function of the protein, whereby proteins that act on material conversion and transportation (mass category) are more abundant than those that act on information modulation (information category). Thus, protein abundance is intrinsically related to the protein's inherent characters of evolution, structure, and function

Relationships between Hematopoiesis and Hepatogenesis in the Midtrimester Fetal Liver Characterized by Dynamic Transcriptomic and Proteomic Profiles

In fetal hematopoietic organs, the switch from hematopoiesis is hypothesized to be a critical time point for organogenesis, but it is not yet evidenced. The transient coexistence of hematopoiesis will be useful to understand the development of fetal liver (FL) around this time and its relationship to hematopoiesis. Here, the temporal and the comparative transcriptomic and proteomic profiles were observed during the critical time points corresponding to the initiation (E11.5), peak (E14.5), recession (E15.5), and disappearance (3 ddp) of mouse FL hematopoiesis. We found that E11.5-E14.5 corresponds to a FL hematopoietic expansion phase with distinct molecular features, including the expression of new transcription factors, many of which are novel KRAB (Kruppel-associated box)-containing zinc finger proteins. This time period is also characterized by extensive depression of some liver functions, especially catabolism/utilization, immune and defense, classical complement cascades, and intrinsic blood coagulation. Instead, the other liver functions increased, such as xenobiotic and sterol metabolism, synthesis of carbohydrate and glycan, the alternate and lectin complement cascades and extrinsic blood coagulation, and etc. Strikingly, all of the liver functions were significantly increased at E14.5-E15.5 and thereafter, and the depression of the key pathways attributes to build the hematopoietic microenvironment. These findings signal hematopoiesis emigration is the key to open the door of liver maturation

Casein Hydrolysate Alleviates Adipose Chronic Inflammation in High Fat-Diet Induced Obese C57BL/6J Mice through MAPK Pathway

Obesity-induced adipose chronic inflammation is closely related to the development of insulin resistance and T2DM. Tripeptides l-valyl-l-prolyl-l-proline (VPP) and l-isoleucyl-l-prolyl-L-proline (IPP) derived from bovine casein have been reported to prevent inflammatory changes and mitigate insulin resistance in adipocytes. In this study, we aimed to investigate the influence of casein hydrolysates (CH) containing VPP and IPP on a high fat diet (HFD)-induced obese mice and cytokine TNF-α-induced adipocytes. Our data showed that CH alleviated chronic inflammation both in vivo and in vitro. 4% CH suppressed HFD-induced systemic inflammatory factors, hypertrophic white adipocytes, and macrophage infiltration. More importantly, CH was able to improve adipocyte dysfunction induced by TNF-α by increasing the expression of CCAAT/enhancer binding protein α (C/EBP-α) rather than peroxisome proliferator-activated receptor γ (PPAR-γ). Furthermore, CH also dose-dependently suppressed mitogen-activated protein kinase (MAPK)-c-Jun N-terminal kinase (JNK) phosphorylation and enhanced the phosphorylation of Erk 1/2, but not nuclear factor-kappa B (NF-κB) p65 phosphorylation, in TNF-α-induced 3T3-L1 cells. These results indicated that CH could ameliorate adipose chronic inflammation through the MAPK pathway. Altogether, our findings suggested that 4% CH supplementation for 6 weeks exerted a protective role in preventing obesity-related inflammation and adipose dysfunction