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PubMed2024

Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations.

Disease-causing bacteria secrete numerous toxins to invade and subjugate their hosts. Unlike many smaller toxins, the secretion machinery of most large toxins remains enigmatic. By combining genomic editing, proteomic profiling and cryo-electron tomography of the insect pathogen Yersinia entomophaga, we demonstrate that a specialized subset of these cells produces a complex toxin cocktail, including the nearly ribosome-sized Tc toxin YenTc, which is subsequently exported by controlled cell lysis using a transcriptionally coupled, pH-dependent type 10 secretion system (T10SS). Our results dissect the Tc toxin export process by a T10SS, identifying that T10SSs operate via a previously unknown lytic mode of action and establishing them as crucial players in the size-insensitive release of cytoplasmically folded toxins. With T10SSs directly embedded in Tc toxin operons of major pathogens, we anticipate that our findings may model an important aspect of pathogenesis in bacteria with substantial impact on agriculture and healthcare.

Proteomics↗

PubMed1999

Translational induction of heat shock transcription factor sigma32: evidence for a built-in RNA thermosensor.

Induction of heat shock proteins in Escherichia coli is primarily caused by increased cellular levels of the heat shock sigma-factor sigma32 encoded by the rpoH gene. Increased sigma32 levels result from both enhanced synthesis and stabilization. Previous work indicated that sigma32 synthesis is induced at the translational level and is mediated by the mRNA secondary structure formed within the 5'-coding sequence of rpoH, including the translation initiation region. To understand the mechanism of heat induction of sigma32 synthesis further, we analyzed expression of rpoH-lacZ gene fusions with altered stability of mRNA structure before and after heat shock. A clear correlation was found between the stability and expression or the extent of heat induction. Temperature-melting profiles of mRNAs with or without mutations correlated well with the expression patterns of fusion genes carrying the corresponding mutations in vivo. Furthermore, temperature dependence of mRNA-30S ribosome-tRNAfMet complex formation with wild-type or mutant mRNAs in vitro agreed well with that of the expression of gene fusions in vivo. Our results support a novel mechanism in which partial melting of mRNA secondary structure at high temperature enhances ribosome entry and translational initiation without involvement of other cellular components, that is, intrinsic mRNA stability controls synthesis of a transcriptional regulator.

Bacterial Proteins↗

PubMed2004

Therapeutic implications of macrolide resistance in pneumococcal community-acquired lower respiratory tract infections.

Macrolide anti-bacterials are widely used for the empirical treatment of lower respiratory tract infections (RTIs) due to their activity against Streptococcus pneumoniae and other common respiratory pathogens and good safety/tolerability profile. However, the prevalence of macrolide resistance, particularly pneumococcal macrolide resistance, is increasing all around the world. The mechanisms underlying macrolide resistance include efflux pump, methylase activity and, less commonly, ribosomal mutation, which produce differing levels of resistance. Growth in macrolide resistance has been linked to the increased use of these agents, and several risk factors for the development of resistance have been identified. There are emerging data to suggest that in vitro macrolide resistance may increase the likelihood of treatment failure in patients with lower RTIs. However, at present, treatment failure is rare and randomised; intervention-based trials investigating the impact of anti-bacterial resistance on clinical outcomes are lacking. Strategies to promote appropriate use of macrolides and other anti-bacterials are needed, both to maximise therapeutic impact and to minimise the development of resistance. Furthermore, there is a need for alternative anti-bacterial agents which have high efficacy against respiratory pathogens (including resistant strains) and a low potential to induce resistance.

Community-Acquired Infections↗

PubMed1986

Effect of nutrient deprivation on lipid, carbohydrate, DNA, RNA, and protein levels in Vibrio cholerae.

The response of Vibrio cholerae to low nutrient levels was determined by measuring the concentrations of lipids, carbohydrates, DNA, RNA, and proteins over a 30-day starvation period. Ultrastructural integrity was observed by transmission electron microscopy. Total lipids and carbohydrates declined rapidly within the first 7 days, while DNA and protein exhibited a more constant decline over the 30 days of starvation. In contrast, RNA showed little decrease upon starvation. Although neutral lipids were lost, the percentage of neutral lipids did not decline as rapidly as the phospholipids. Detectable levels of poly-beta-hydroxybutyrate disappeared completely by 7 days. Carbohydrate profiles revealed the relative loss of the five-carbon sugar ribose and N-acetylglucosamine and a relative increase in the total six-carbon sugars, especially glucose. Morphologically, ribosomes appeared to exhibit no structural change, while inclusion bodies and mesosomelike structures disappeared completely, and cell wall and membrane integrity was lost. The data suggest that V. cholerae differs somewhat from other marine vibrios in its response to low nutrients but shares some characteristics in common with them. The data also suggest that certain lipids and carbohydrates may provide the endogenous energy sources needed for dormancy preparation and cell maintenance under nutrient starvation.

Bacterial Proteins↗

PubMed1999

In situ analysis of phototrophic sulfur bacteria in the chemocline of meromictic Lake Cadagno (Switzerland).

Comparative sequence analysis of a 16S rRNA gene clone library from the chemocline of the meromictic Lake Cadagno (Switzerland) revealed the presence of a diverse number of phototrophic sulfur bacteria. Sequences resembled those of rRNA of type strains Chromatium okenii DSM169 and Amoebobacter purpureus DSM4197, as well as those of four bacteria forming a tight cluster with A. purpureus DSM4197 and Lamprocystis roseopersicina DSM229. In situ hybridization with fluorescent (Cy3 labeled) oligonucleotide probes indicated that all large-celled phototrophic sulfur bacteria in the chemocline of Lake Cadagno were represented by C. okenii DSM169, while small-celled phototrophic sulfur bacteria consisted of four major populations with different distribution profiles in the chemocline indicating different ecophysiological adaptations.

Bacteria↗

PubMed2005

Explorative multifactor approach for investigating global survival mechanisms of Campylobacter jejuni under environmental conditions.

Explorative approaches such as DNA microarray experiments are becoming increasingly important in microbial research. Despite these major technical advancements, approaches to study multifactor experiments are still lacking. We have addressed this problem by using rotation testing and a novel multivariate analysis of variance (MANOVA) approach (50-50 MANOVA) to investigate interacting experimental factors in a complex experimental design. Furthermore, a new rotation testing based method was introduced to calculate false-discovery rates for each response. This novel analytical concept was used to investigate global survival mechanisms in the environment of the major food-borne pathogen C. jejuni. We simulated nongrowth environmental conditions by investigating combinations of the factors temperature (5 and 25 degrees C) and oxygen tension (anaerobic, microaerobic, and aerobic). Data were generated with DNA microarrays for information about gene expression patterns and Fourier transform infrared (FT-IR) spectroscopy to study global macromolecular changes in the cell. Microarray analyses showed that most genes were either unchanged or down regulated compared to the reference (day 0) for the conditions tested and that the 25 degrees C anaerobic condition gave the most distinct expression pattern with the fewest genes expressed. The few up-regulated genes were generally stress related and/or related to the cell envelope. We found, using FT-IR spectroscopy, that the amount of polysaccharides and oligosaccharides increased under the nongrowth survival conditions. Potential mechanisms for survival could be to down regulate most functions to save energy and to produce polysaccharides and oligosaccharides for protection against harsh environments. Basic knowledge about the survival mechanisms is of fundamental importance in preventing transmission of this bacterium through the food chain.

Bacterial Proteins↗

PubMedDate not supplied

[Role gene expression changes in development of human brain gliomas].

The identification and characterization of genes either induced or repressed in human brain tumors are important in understanding the mechanism of tumor initiation and progression, stages of malignancy, in developing new approaches to the diagnosis and treatment of tumors. In this paper, differential hybridization of arrayed human fetal brain and postnatal brain and postnatal brain cDNA libraries revealed differences in the rate of hybridization signals with total cDNA probes of the human brain and glioblastoma multiforme for more than 150 cDNA clones. Sixteen nucleotide sequences with changed contents in tumors were identified by repeated differential hybridization of the cDNA clones selected by primary screening with the same total cDNA probes of the human brain and glioblastoma multiforme and by Northern-hybridization of RNA samples from the human and glial tumors. The results of an analysis of the increased expression of the gene encoding apolipoprotein E. DNA-binding protein B, mitochondrial (16S and 12S) and cytoplasmic 28S rRNAs, Alu-containing transcripts, inactivation of cullin 1 gene and potential tumor suppressor gene TSC-22 are described.

Alu Elements↗

PubMed2005

Evaluation of p16 and Id1 status and endogenous reference genes in human chondrosarcoma by real-time PCR.

Both the tumour suppressor, p16, and the helix-loop-helix transcription factor, Id1, have been assigned roles in tumour growth in general and appear to be involved in chondrosarcoma. Id1 has further been found to repress the expression of p16. Therefore, the mRNA expression of these two genes was studied by real-time PCR in a search for prognostic markers in human chondrosarcoma. To get reliable quantitative data, however, the choice of endogenous reference gene for use in the assay is important. Therefore, eleven different endogenous reference genes were evaluated in chondrosarcoma cells and articular chondrocytes. 18S rRNA appeared to be the best choice to use as endogenous reference gene, since it was suitable for both kinds of cells. Several of the other reference genes tested showed variation between individuals or between normal chondrocytes and chondrosarcoma cells. This demonstrates the importance of using a correct endogenous reference gene to get reliable results from quantitative measurements. Both p16 and Id1 showed varied gene expression patterns among the samples and none of these genes could be significantly correlated to prognosis.

Bone Neoplasms↗

PubMed2004

Characterization of a wild-type strain of Francisella tularensis isolated from a cat.

Francisella tularensis type A is the primary cause of tularemia in animals and humans in North America. The majority of research on F. tularensis has been done with the attenuated live vaccine strain (LVS), which is a type B, but very few wild-type F. tularensis strains have been characterized. A gram-negative coccobacillus that was isolated in pure culture from the lungs of a cat that died after being lost for 5 days was received for identification at the Virginia-Maryland Regional College of Veterinary Medicine Teaching hospital. The isolate (strain TI0902) was not identified (or was misidentified) by commercial identification systems; however, it was identified as F. tularensis subspecies tularensis (type A) by sequencing a portion of the 16S ribosomal RNA gene. Furthermore, repetitive extragenic palindromic sequences-polymerase chain reaction amplified a 4-kb DNA fragment from TI0902 that was characteristic of F. tularensis type A but not type B. The electrophoretic profile of the lipopolysaccharide of strain TI0902 was identical to that of the LVS by Western blotting with antiserum to LVS. The protein-enriched outer membrane of strain TI0902 contained 6-8 proteins, which were similar in molecular size to those from the LVS. Electron microscopy of negatively stained and alcian blue-stained LVS and TI0902 cells showed that both strains were coccobacillary in shape and may be encapsulated. However, after mouse challenge, the TI0902 strain was clearly more virulent than the LVS strain. Results of this study indicate that the genotype and phenotype of wild-type F. tularensis type A strain TI0902 is similar, but not identical, to that of the LVS strain. Further studies will help determine whether pathogenesis and host-pathogen interactions are also similar between the 2 strains.

Animals↗

PubMed2001

Numerical analysis of grassland bacterial community structure under different land management regimens by using 16S ribosomal DNA sequence data and denaturing gradient gel electrophoresis banding patterns.

Bacterial diversity in unimproved and improved grassland soils was assessed by PCR amplification of bacterial 16S ribosomal DNA (rDNA) from directly extracted soil DNA, followed by sequencing of ~45 16S rDNA clones from each of three unimproved and three improved grassland samples (A. E. McCaig, L. A. Glover, and J. I. Prosser, Appl. Environ. Microbiol. 65:1721-1730, 1999) or by denaturing gradient gel electrophoresis (DGGE) of total amplification products. Semi-improved grassland soils were analyzed only by DGGE. No differences between communities were detected by calculation of diversity indices and similarity coefficients for clone data (possibly due to poor coverage). Differences were not observed between the diversities of individual unimproved and improved grassland DGGE profiles, although considerable spatial variation was observed among triplicate samples. Semi-improved grassland samples, however, were less diverse than the other grassland samples and had much lower within-group variation. DGGE banding profiles obtained from triplicate samples pooled prior to analysis indicated that there was less evenness in improved soils, suggesting that selection for specific bacterial groups occurred. Analysis of DGGE profiles by canonical variate analysis but not by principal-coordinate analysis, using unweighted data (considering only the presence and absence of bands) and weighted data (considering the relative intensity of each band), demonstrated that there were clear differences between grasslands, and the results were not affected by weighting of data. This study demonstrated that quantitative analysis of data obtained by community profiling methods, such as DGGE, can reveal differences between complex microbial communities.

Bacteria↗

PubMed2026

From immature to mature epithelium: unveiling structural dynamics and transcriptional programs in rainbow trout intestinal barrier.

The intestinal epithelium is crucial for nutrient absorption, immune defense, and barrier function in farmed fish. However, the molecular mechanisms underlying its development and maturation in salmonids remain poorly characterized, hindering our ability to address pervasive gut health challenges in aquaculture. In this study, we use the RTgutGC cell line to implement an epithelial maturation model with the aim of characterizing the global transcriptional program in rainbow trout (Oncorhynchus mykiss). We evaluated in vitro culture conditions to generate a polarized epithelial barrier with high transepithelial electrical resistance (TEER = 75.8 Ω × cm2), low permeability (6.2 × 10-6 cm/s), and well-defined apical specializations, including microvilli-like structures and clusters of these structures (brush border). Comparative transcriptomic profiling between immature (7 days post-seeding, dps) and mature (28 dps) epithelia revealed 3,817 differentially expressed genes (DEGs). Functional enrichment analysis showed that maturation was characterized by the downregulation of proliferative and ribosomal pathways and the concerted upregulation of processes critical for barrier function, including transmembrane transport, proteolysis, cell adhesion, extracellular matrix organization, and tight junction assembly. We identified a core set of 60 genes indicators of epithelial maturation, encompassing solute transporters (slc26a6, slc43a2), tight junction proteins (tjp1, cldn1, cldn3, cldn5, cldn18, among others), and structural components essential for microvilli formation and polarization (cdhr5b, pard6a). By integrating ultrastructural, functional, and transcriptomic data, this study established a framework for future mechanistic investigations into gut development and maturation in vitro. This set of mature epithelium indicators has diverse applications, such as the design of nutritional and pharmacological interventions to improve gut health and resilience in farmed fish.

Animals↗

PubMed2005

Capillary electrophoretic analysis of fragment length polymorphism in ribosomal markers of Cryptosporidium from humans.

Cryptosporidium oocyst DNA samples (n=80) from humans with cryptosporidiosis in Australia and the UK were characterized genetically and categorized by capillary electrophoretic (CE) analysis of part of the small subunit gene (pSSU; approximately 300bp) and second internal transcribed spacer (pITS-2; approximately 230bp) of nuclear ribosomal DNA. The amplicons were heat denatured and subjected to capillary electrophoresis in LPA matrix (Amersham) in a MegaBACEtrade mark 1000 system (Amersham). The chromatograms captured were stored electronically and then analysed using MegaBACEtrade mark Fragment Profiler software. Using reference DNA control samples representing Cryptosporidium hominis and Cryptosporidium parvum, particular peaks in the profiles were defined for their specific identification and differentiation. The two species could be readily differentiated based on their profile in the pSSU, the peak differences being associated with a nucleotide difference of <1.7%. While no variation was detectable in the pSSU profiles within each species, significant intraspecific variability in the positions of peaks in the pITS-2 chromatograms was displayed. For the 80 samples subjected to CE analysis of the pITS-2, four different genetic variants (genotypes) were detected within C. hominis and seven within C. parvum. Based on CE analysis of either pSSU and pITS-2 amplicons, it was readily possible to detect both species in 'mixed samples'. This CE method is time- and cost-effective, and may find applicability as a tool for the high throughput analysis of oocyst DNA samples for epidemiological surveys and for the monitoring of cryptosporidiosis outbreaks.

Animals↗

PubMed2006

Following the dynamics of changes in solvent accessibility of 16 S and 23 S rRNA during ribosomal subunit association using synchrotron-generated hydroxyl radicals.

We have probed the structure and dynamics of ribosomal RNA in the Escherichia coli ribosome using equilibrium and time-resolved hydroxyl radical (OH) RNA footprinting to explore changes in the solvent-accessible surface of the rRNA with single-nucleotide resolution. The goal of these studies is to better understand the structural transitions that accompany association of the 30 S and 50 S subunits and to build a foundation for the quantitative analysis of ribosome structural dynamics during translation. Clear portraits of the subunit interface surfaces for 16 S and 23 S rRNA were obtained by constructing difference maps between the OH protection maps of the free subunits and that of the associated ribosome. In addition to inter-subunit contacts consistent with the crystal structure, additional OH protections are evident in regions at or near the subunit interface that reflect association-induced conformational changes. Comparison of these data with the comparable difference maps of the solvent-accessible surface of the rRNA calculated for the Thermus thermophilus X-ray crystal structures shows extensive agreement but also distinct differences. As a prelude to time-resolved OH footprinting studies, the reactivity profiles obtained using Fe(II)EDTA and X-ray generated OH were comprehensively compared. The reactivity patterns are similar except for a small number of nucleotides that have decreased reactivity to OH generated from Fe(II)EDTA compared to X-rays. These nucleotides are generally close to ribosomal proteins, which can quench diffusing radicals by virtue of side-chain oxidation. Synchrotron X-ray OH footprinting was used to monitor the kinetics of association of the 30 S and 50 S subunits. The rates individually measured for the inter-subunit contacts are comparable within experimental error. The application of this approach to the study of ribosome dynamics during the translation cycle is discussed.

Crystallography, X-Ray↗

PubMed1981

Ribosomal protein modification in Escherichia coli. III. Studies of mutants lacking an acetylase activity specific for protein L12.

Among mutants of E. coli selected for temperature-sensitive growth, four were found to possess alterations in ribosomal proteins L7/L12. Of these, three apparently lack protein L7, the acetylated form of protein L12. Genetic analyses have revealed that the mutation responsible for this alteration maps at a locus around 34 min of the current E. coli genetic map, which is clearly different from the location for the structural gene for protein L7/L12 which is situated at 89 min. Hence, the gene affected in these mutants was termed rimL. Tryptic and thermolysin fingerprints of the protein L12 purified from the rimL mutants showed a profile indistinguishable from that of wild-type protein. It was found that the assayed in vitro, in the high-speed supernatant prepared from mutant cells. These results indicated that the three mutants contain mutations in the gene rimL codes for an acetylating enzyme specific for ribosomal protein L12.

Bacterial Proteins↗

PubMed1990

An investigation of nosocomial infection with Corynebacterium jeikeium in surgical patients using a ribosomal RNA gene probe.

Twelve strains of multi-resistant Corynebacterium jeikeium isolated during a one year period in a surgical unit in Innsbruck were analyzed with regard to their plasmid content, antibiotic susceptibility, and the use of ribosomal ribonucleic acid (rRNA) to probe restriction fragment length polymorphism (RFLP). Plasmids were detected in five of the strains. Southern blotting of genomic DNA digested with HindIII or PvuII and hybridized with a biotin-labelled cDNA probe derived from total rRNA revealed characteristic banding patterns. Seven of the 12 strains showed similar RFLP profiles, consistent with them being related epidemiologically. The minor changes in RFLP profiles observed in these seven strains suggest that Corynebacterium jeikeium may be subject to genetic drift over a relatively short time span. Strains from other sources, included for comparison, differed markedly from those from Innsbruck. Patterns of antibiotic susceptibility which appeared not to be plasmid encoded, correlated broadly with RFLP profiles. This study suggests that strains of Corynebacterium jeikeium may be transferred between hospital patients.

Corynebacterium↗

PubMed2005

Intraspecies genetic variability of Ornithobacterium rhinotracheale in commercial birds in Peru.

Strains of the bacterium Ornithobacterium rhinotracheale (ORT), a causal agent of respiratory diseases in birds, were microbiologically isolated, identified, and molecularly characterized. Blood-enriched culture media and biochemistry tests were used for microbiologic identification. Polymerase chain reaction (PCR) and repetitive extragenic palindromic PCR (rep-PCR) techniques were used for molecular identification and characterization, respectively, of the microorganism. ORT strains were isolated in enriched media from the trachea and air sacs of broilers, breeders, and layers from several geographic zones of Peru. Of the original 75 strains isolated from 75 clinical samples from which ORT was recovered during 1998-2000, 25 were selected for further study based on ORT as the primary pathogenic isolate (no other pathogens were detected). Selected isolates were molecularly identified and characterized by PCR using specific primers designed from the conserved zones of the 16S ribosomal genes. Primers used for the identification of ORT produced a specific fragment of 784 base pair (bp), which did not appear in Haemophilus paragallinarum or Pasteurella multocida, microorganisms with similar morphologic and biochemical characteristics that produce dinical signs identical to those of ORT. All 25 strains of ORT tested with rep-PCR had a genetic profile similar to that of ORT American Type Culture Collection 51463, indicating the presence of only one genotype in the ORT strains studied.

Animals↗

PubMed2004

Phase I trial of intravenous aviscumine (rViscumin) in patients with solid tumors: a study of the European Organization for Research and Treatment of Cancer New Drug Development Group.

BACKGROUND: Aviscumine is an Escherichia coli-derived recombinant type II ribosome-inactivating protein with potent antitumor activity in vitro and in vivo. It is the recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the intravenous (i.v.) administration of aviscumine in cancer patients. Translational research included the evaluation of pharmacokinetics and monitoring of plasma cytokine and anti-aviscumine antibody induction after administration of the drug. PATIENTS AND METHODS: Aviscumine was given twice weekly as a 1 h central i.v. infusion in patients with advanced, refractory progressive, solid malignant tumors who had not been previously exposed to natural mistletoe preparations. They had histologically or cytologically verified disease, were > or =18 years old, had an Eastern Cooperative Oncology Group performance status < or =2 and adequate bone marrow, liver and renal function. DLT was defined as any non-hematological grade 3-4 toxicity (National Cancer Institute Common Toxicity Criteria version 2.0), neutrophil count <500/microl for > or =7 days, febrile neutropenia or thrombocytopenia grade 4. The MTD was defined as the dose at which >20% of patients experienced DLT during the first treatment cycle. The Continual Reassessment Method was used to determine the number of patients required per dose level. RESULTS: Forty-one fully eligible patients (19 male, 22 female) with a median age of 56 years (range 37-74) were enrolled. Colorectal, ovarian, renal cell and breast cancer were the most common tumor types. Dose levels of aviscumine ranged from 10 to 6400 ng/kg. The median number of cycles was two (range one to eight). Common clinical toxicities in cycle 1 were fatigue, fever, nausea, vomiting and allergic reactions. Fatigue grade 3 was dose limiting in one of six patients at 4000 ng/kg and reversible grade 3 liver toxicity (elevation in alkaline phosphatase, transaminases and/or gamma-glutamyltransferase) occurred in one of 10 patients at 4800 ng/kg and in two of five patients at 6400 ng/kg. The best response (RECIST criteria) was stable disease in 11 patients, lasting for two to eight cycles. The pharmacokinetic evaluation revealed a short alpha half-life of 13 min and linear kinetics on dose levels > or =1600 ng/kg. Aviscumine stimulated the immune system with a release of cytokines such as interleukin (IL)-1beta, IL-6 and interferon-gamma, and induced immunoglobulin (Ig) G- and/or IgM-anti-aviscumine antibodies of uncertain clinical relevance. CONCLUSIONS: The recommended dose for further clinical trials is 5600 ng/kg twice weekly. Based on the short half-life of the recombinant protein observed in this trial, the exploration of prolonged infusion schedules of aviscumine is warranted.

Adjuvants, Immunologic↗

PubMed2003

Gene expression profile of human cells irradiated in G1 and G2 phases of cell cycle.

The response of cells to ionizing radiation has long been known to result in alterations in gene expression. Here we examined the expression patterns of synchronized HeLa cells in G1 or G2, after exposure to 2Gy of X-rays on microarrays allowing evaluation of over 12,000 human genes. The analysis showed induction of at least twofold for 257 different genes, after irradiation of cells in G1 and down-regulation of 42. The altered transcription patterns involved genes belonging to cell cycle pathways, DNA repair, oncogenes, histones, heat shock genes, mitochondrial and ribosomal proteins, transcription and translational regulators and genes encoding cytoskeleton components. HeLa cells are deficient in p53 and none of the induced genes have previously been identified as regulated by p53. One hundred and seventy-seven genes were up-regulated and 26 genes were down-regulated after irradiation in G2. Surprisingly most of the up-regulated genes in both phases of the cell cycle encode ribosomal proteins. These studies have revealed cell cycle dependence on radiation-induced gene induction and have permitted the identification of previously known as well as unknown genes associated with radiation-induced altered expression.

Cell Cycle Proteins↗