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At least 1,639 records · Page 91Linked to original sources
PubMed2002

Lifespan extension by caloric restriction: an aspect of energy metabolism.

Caloric restriction (CR) may retard aging processes and extend lifespan in organisms by altering energy-metabolic pathways. In CR rodents, glucose influx into tissues is not reduced, as compared with control animals fed ad libitum (AL), although plasma concentrations of glucose and insulin are lower. Gene expression profiles in rodents have suggested that CR promotes gluconeogenesis and fatty acid biosynthesis in skeletal muscle. In the liver, CR promotes gluconeogenesis but decreases fatty acid synthesis and glycolysis. In lower organisms such as yeasts and nematodes, incomplete blocks in steps of insulin/insulin-like growth factor-1 (IGF-1) signal pathway extend lifespan. The life-prolonging effect of CR in yeasts requires NPT1 and SIR2 genes, both of which relate to sensing energy status and silencing genes. These findings stress the substantial role of energy metabolism on CR. Future studies on metabolic adaptation and gene silencing with regard to lower caloric intake will be warranted to understand the mechanisms of the anti-aging and life-prolonging effects of CR.

Aging↗
PubMed2007

Lethality in Drosophila melanogaster/Drosophila simulans species hybrids is not associated with substantial transcriptional misregulation.

The cross of Drosophila melanogaster females to Drosophila simulans males produces lethal F1 hybrid males. These lethal phenotypes can be suppressed by mutations in the D. melanogaster gene Hybrid male rescue (Hmr), demonstrating that Hmr has a major role in causing lethality in this hybridization. We performed parallel crosses to generate viable (Hmr-) and lethal (Hmr+) hybrid male larvae and used microarrays to compare whole-genome transcriptional profiles between these two samples. This comparison was done to investigate two questions: whether hybrid lethality is associated with substantial gene misregulation, and whether a mechanistic basis for hybrid lethality can be inferred from the identities of differentially expressed individual transcripts. We report that a surprisingly small number of genes have a significant difference in transcript abundance between lethal and viable hybrid males. There is a significant over-representation of genes encoding proteosome subunits among those upregulated in lethal hybrids relative to viable hybrids. Genetic tests, however, failed to fully support the hypothesis that this overexpression is causing hybrid lethality. Hybrid females were previously reported to have a significantly different expression pattern of sex-biased genes compared to the parental species. We find no such differences between lethal and viable hybrid males. We did find a significant deficit of X chromosome genes among those downregulated in lethal hybrids, but not among those upregulated. We suggest that while interspecific hybrids may have substantial amounts of gene misregulation compared to their parental species, many of these transcriptional differences may be only indirectly related to hybrid incompatibility phenotypes.

Animals↗
PubMed2006

Comparison of Schwann cell and sciatic nerve transcriptomes indicates that mouse is a valid model for the human peripheral nervous system.

High-throughput gene expression analyses of murine models of the peripheral nervous system (PNS), and its cellular components, have yielded enormous amounts of expression data of the PNS in various conditions. These data provided clues for future research directions to further decipher this complex organ in relation to acquired and inherited PNS diseases. Various studies addressing the validity of mouse models for human conditions in other tissues and cell types have indicated that in many cases the mouse model only poorly represents the human situation. To determine how well the mouse can serve as model to study the biological processes occurring in the PNS, we compared the gene expression profiles that we generated for mouse and human sciatic nerve and cultured Schwann cells derived thereof. A two-way analysis based on the differentially expressed genes between the sciatic nerve and the cultured Schwann cell, and which takes into account the differential expression between mouse and man, indicates that the human PNS is well represented by that of the mouse in terms of the "biological processes" ontology.

Animals↗
PubMed2004

Insights into Pseudomonas putida KT2440 response to phenol-induced stress by quantitative proteomics.

To gain insight into the global mechanism underlying phenol toxicity and tolerance in bacteria, we have generated a two-dimensional protein reference map and used it to identify variations in protein expression levels in Pseudomonas putida KT2440 following exposure to sub-lethal inhibitory concentrations of this solvent. Inspection of the two-dimensional gel electrophoresis gels revealed that 1 h following sudden cell exposure to two different concentrations of phenol, leading to the inhibition of exponential growth (600 mg/L) or to growth arrest for, at least, 4 h before inhibited growth resumption (800 mg/L), the amount of 68 proteins was increased while the amount of 13 proteins was reduced. The up-regulated proteins include proteins involved in the: (i) oxidative stress response (AhpC, SodB,Tpx and Dsb); (ii) general stress reponse (UspA, HtpG, GrpE and Tig); (iii) energetic metabolism (AcnB, AtpH, Fpr, AceA, NuoE, and MmsA-1); (iv) fatty acid biosynthesis (FabB, AccC-1 and FabBx1); (v) inhibition of cell division (MinD); (vi) cell envelope biosynthesis (LpxC, VacJ, and MurA); (vii) transcription regulation (OmpR and Fur); and (viii) transport of small molecules (TolC, BraC, AotJ, AapJ, FbpA and OprQ). Among the down-regulated proteins are those involved in nucleotide biosynthesis (PurM, PurL, PyrH and Dcd) and cell motility (FliC). The information emerging from this genome expression profiling and the detailed investigation of the biological role of candidate genes, as targets of phenol toxicity or as determinants of phenol resistance in P. putida KT2440, will allow more rationale strategies for developing bacteria with greater solvent tolerance with impact in bioremediation and whole-cell biotransformations in media with organic solvents.

Anti-Infective Agents, Local↗
PubMed2006

Minimum reporting requirements for proteomics: a MIAPE primer.

Amongst other functions, the Human Proteome Organization's Proteomics Standards Initiative (HUPO PSI) facilitates the generation by the proteomics community of guidelines that specify the appropriate level of detail to provide when describing the various components of a proteomics experiment. These guidelines are codified as the MIAPE (Minimum Information About a Proteomics Experiment) specification, the first modules of which are now finalized. This primer describes the structure and scope of MIAPE, places it in context amongst reporting specifications for other domains, briefly discusses related informatics resources and closes by considering the ramifications for the proteomics community.

Databases, Protein↗
PubMed2024

Histopathologic Features and Transcriptomic Signatures Do Not Solve the Issue of Magnetic Resonance Imaging-Invisible Prostate Cancers: A Matched-Pair Analysis.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI. METHODS: We performed a retrospective matched-pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group ≥ 2) from 2015 to 2020, in our tertiary-referral center. We screened for inclusion in the "mpMRI-invisible" cohort all consecutive men (N = 45) having a negative preoperative mpMRI. The "mpMRI-visible" cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open-label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell-type profiling). We compared the clinical-pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter. RESULTS: We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD] = 7.7), 7.1 ng/mL (SD = 3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell-type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI-invisible cancers. CONCLUSIONS: No PCa pathological or gene-expression hallmarks explaining mp-MRI invisibility were identified. Aggressive features can be present both in mpMRI-invisible and -visible tumors.

Humans↗
PubMed2002

Identification of 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive genes in mouse liver by serial analysis of gene expression.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic environmental pollutants that causes various biological effects on mammals. To identify the genes involved in hepatotoxicity and hepatocarcinogenesis induced by TCDD, we have conducted here serial analysis of gene expression of mouse liver 7 days after treatment with a single oral dose of 20 microg TCDD/kg body weight. We have sequenced total of 113,067 tags, including 56,420 tags and 56,647 tags from normal liver and TCDD-treated liver library, respectively. Statistical analysis showed that TCDD significantly altered 346 transcripts (p < 0.05) including 94 ESTs. The genes regulated by TCDD were not only the genes encoding drug metabolizing enzymes and stress response genes but also a wide variety of genes encoding cytoskeleton related proteins, signal transduction, and plasma proteins. This comprehensive gene expression analysis would provide novel genes that may help to clarify the mechanism of TCDD effects on mammalian liver, and also give a new approach for prevention and treatment.

Animals↗
PubMed1999

Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome.

The human homologue (MNBH/DYRK1) of the Drosophila minibrain gene maps to human chromosome 21 within the Down syndrome (DS) critical region and is within the region minimally deleted in chromosome 21-linked microcephaly. As a first step in gaining insight into the role that MNBH may have in human neurogenesis, and as a lead-up to the development of mouse models for MNBH overexpression, we have characterized the gene at the molecular level. We describe here the MNBH full-length transcript, alternative splicing, expression profile, and genomic organization. The full-length cDNA of MNBH is 5. 2 kb and is composed of 17 exons spanning 150 kb, between markers D21S335 and D21S337. Transcripts MNBHa and MNBHb arise from the use of different first exons in the 5'-UTR and are differentially expressed. MNBHa is expressed ubiquitiously in a broad spectrum of tissues and is apparently under the control of a CpG island. MNBHb is expressed only in heart and skeletal muscle and is apparently under the control of a TATA-like box. Four alternative splicing events affecting the C-terminus of the protein yield at least four isoforms of MNBH (MNBH-iso1, MNBH-iso2, MNBH-iso3, and MNBH-iso4). A PEST sequence, potentially involved in the rapid degradation of the protein, is present in all the isoforms. A histidine repeat and a serine/threonine domain are present only in the largest form of the protein (MNBH-iso1). MNBH was overexpressed 1.5-fold in DS brains and Dyrk1 about 2.1-fold in the brains of the Ts65Dn mice. The information provided here should be valuable for MNBH mutation studies and aid in the development of DS animal models.

3' Untranslated Regions↗
PubMed2005

Pharmacogenomics.

So far no pharmacogenetic/genomic study has been conducted specifically for anxiety disorders. Some of the presented results, however, do pertain to such disorders. For example, pharmacokinetic aspects of antidepressant drug therapy likely also apply to patients with anxiety disorders, and several genetic polymorphisms in the cytochrome P450 (CYP) gene family and drug transporter molecules, such as the multidrug resistance (MDR) gene type 1, have been reported to influence the pharmacokinetics of antidepressant drugs. At this stage of pharmacogenomics research, it is difficult to interpret the relevance of pharmacodynamic-genetic association studies conducted in depressed patients for anxiety disorders. A number of studies have reported an influence of polymorphisms of genes mostly in the serotonergic pathway on the response to antidepressant drugs in patients suffering from depression. In order to know whether they can be extrapolated to patients with anxiety disorders, clinical studies are warranted. Despite all the shortcomings of the currently available pharmacogenetic studies, this field holds great promise for the treatment of anxiety disorders. In the future, psychiatrists may be able to base treatment decisions (i.e., the type and dose of prescribed drug) on more objective parameters than only the diagnostic algorithms used now. This will limit unwanted side effects and adverse drug reactions, and could reduce time to response, resulting in a more individualized pharmacotherapy.

Cytochrome P-450 Enzyme System↗
PubMed2006

Prediction of response to neoadjuvant chemotherapy in carcinomas of the upper gastrointestinal tract.

Multimodal treatment protocols are increasingly employed to improve the survival of patients with locally advanced adenocarcinomas of the upper gastrointestinal tract, however, only 30-40% per year of the patients respond to 5-FU and cisplatin-based neoadjuvant chemotherapy. The goal of our studies is the identification of reliable genetic markers, on the genomic DNA-level, mRNA, or protein level that could predict response of upper gastrointestinal carcinomas prior to neoadjuvant chemotherapy. In esophageal carcinomas, a higher gene expression of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, was more frequently found in responding patients. In addition high gene expression of caldesmon and of the two drug carrier proteins, MRP1 and MDR1 was associated with response to therapy. By performing a genome-wide profiling on the protein level in a small group of patients, new potential markers were identified, which have to be validated in ongoing studies. In gastric carcinomas, mutations of the p53 gene revealed no association with response or survival, but tumors with a high rate of loss of heterozygosity (LOH), determined by microsatellite analysis, showed a better response to a cisplatin-based chemotherapy. Analysis of expression of 5-FU-(e.g., TS, DPD, and TP) and cisplatin-(e.g., ERCC1, ERCC4, GADD45A, and KU80) related genes, demonstrated an association of DPD expression with response and survival. The combined consideration of TP and GADD45 gene expression, showed the most obvious association with therapy response in this tumor. Our studies point to promising markers with potential use for chemotherapy response prediction of adenocarcinomas of the upper gastrointestinal tract, but prospective studies for validation are necessary.

Antineoplastic Agents↗
PubMed1996

Detection of SHV-5 extended-spectrum beta-lactamase in Klebsiella pneumoniae strains isolated in Italy.

Thirty-five Klebsiella pneumoniae strains isolated during 1993-1994 in intensive care units of a large Italian hospital were examined for the presence of extended-spectrum beta-lactamases. Five strains showed a high level of simultaneous resistance to beta-lactam agents, including ceftazidime and aztreonam, conferred by a large (130 kb) self-transferable plasmid (in 4 of 5 strains). Isoelectrofocusing and hybridisation studies suggest that these enzymes can be identified as SHV-5 extended-spectrum beta-lactamases. Pulsed-field get electrophoresis analysis showed three different genomic fingerprinting profiles, while plasmid restriction enzyme digestion revealed three different patterns, demonstrating that the diffusion of SHV-5 beta-lactamase is not the result of a single strain or plasmid dissemination.

Conjugation, Genetic↗
PubMed1994

Analysis of nosocomial outbreaks with multiply and methicillin-resistant Staphylococcus aureus (MRSA) in Germany: implications for hospital hygiene.

Two outbreaks of nosocomial infections with MRSA, one in a urological unit in connection with transurethral prostatectomy and the other in an orthopaedic clinic with infections after implantation of prosthetic hips, have been analyzed on the basis of typing MRSA by phage-patterns, plasmid profiles and genomic DNA fragment patterns. Main reasons for these outbreaks were obviously mistakes in hospital hygiene and an inappropriate antibiotic prophylaxis (in the first outbreak a quinolone over about 7 days, in the second a third generation cephalosporin). Both outbreaks could be stopped by measures of hospital hygiene including isolated or cohort nursing of affected patients, and change in antibiotic prophylaxis. Intensive care units (ICUs) are more often affected by MRSA than other clinical settings. As described by the example of an outbreak with MRSA in a municipal hospital, ICUs can play a special role in intrahospital spread of MRSA. The recently observed inter-regional clonal interhospital dissemination of MRSA in Germany is mainly due to a transfer of patients between hospitals; prewarning of the hospital of destination and a number of hygiene measures can prevent further spread.

Anti-Bacterial Agents↗
PubMed1996

Clustered organization and conservation of the Xiphophorus maculatus D locus, which includes two distinct gene sequences.

Genomic organization and chromosomal localization of a previously uncharacterized D (Donor) locus in Xiphophorus and Poecilia species was investigated using fluorescence in situ hybridization (FISH) and Southern blot analysis. Part of this region is thought to be involved in the recombination event leading to formation of the Xmrk oncogene and it has recently been shown that this locus includes two different genes, one with high homology to a zinc finger protein of the Krüppel type, and the other an unknown gene with high similarity to a Caenorhabditis elegans gene. FISH to Xiphophorus chromosomes revealed that these two unrelated genes are closely linked and clustered at a unique chromosomal site. Southern blot hybridization patterns suggest that these genes exist in the genome as multiple copies. Furthermore, similar genomic organization profiles seem to prevail among other related fish. In particular, our FISH experiments reveal the existence of a conserved homologous chromosomal segment harboring the zinc finger protein sequence in several poeciliid fish.

Animals↗
PubMed2004

Relationship between calpain-10 gene polymorphism and insulin resistance phenotypes in Chinese.

In order to determine whether the variations in the calpain-10 gene constitutes risk of type 2 diabetes (T2DM) in Chinese, the frequency of UCSNP-43, 44 in 268 adults newly diagnosed with T2DM (according to the 1999 ADA criteria) and 153 non-diabetic control subjects was investigated. For all subjects, the height, weight, waist-to-hip ratio (W/H) and blood pressure, as well as following parameters were measured: (1) 75-g oral glucose tolerance test with insulin, C-peptide, HbA1c and blood lipid profiles; (2) Genomic DNA extracted from peripheral blood lymphocytes was genotyped for UCSNP-43 (calpain-10-g. 4852 G/A) and UCSNP-44 (calpain-10-g. 4841 T/C) by sequencing a polymerase chain reaction (PCR)-amplified fragment. PCR product was selected by single strand conformation polymorphism (SSCP) and then sequenced. The results showed that there was significant difference between T2DM group and normal control group in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP-43 and -44 either. But in newly diagnosed T2DM group, it was found that the individuals with the genotype UCSNP-44 T/C + C/C had significantly increased fasting and post-challenge insulin levels (Fins and P2hIns), consistent with reduced insulin sensitivity. In the BMI> 25 subgroup, the differences were even more significant. It was demonstrated that the Calpain-10 gene polymorphism UCSNP-44 was associated with insulin sensitivity and Fins and P2hIns in newly diagnosed T2DM, although Calpain-10 doesn't appear as a major diabetes susceptible gene in this population.

Adult↗
PubMed2006

[Microarray-based transcriptome analyses in infectious diseases. A new diagnostic method].

The complex interaction between a pathogen and a host is the molecular basis of infectious diseases. Microarray technology is a powerful tool to investigate the crosstalk between pathogen and the host as it assesses whole genome expression profiles in response to disease. Deciphering the molecular details on both sides of the host-pathogen interaction will increase our understanding of the pathogenesis of infectious diseases and offer improvements in their diagnosis, treatment, prognosis, and prevention.

Biomarkers↗
PubMed2006

Diversity arrays technology (DArT) for high-throughput profiling of the hexaploid wheat genome.

Despite a substantial investment in the development of panels of single nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR) technology with a limited multiplexing capability remains a standard, even for applications requiring whole-genome information. Diversity arrays technology (DArT) types hundreds to thousands of genomic loci in parallel, as previously demonstrated in a number diploid plant species. Here we show that DArT performs similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.). The methodology previously used to generate DArT fingerprints of barley also generated a large number of high-quality markers in wheat (99.8% allele-calling concordance and approximately 95% call rate). The genetic relationships among bread wheat cultivars revealed by DArT coincided with knowledge generated with other methods, and even closely related cultivars could be distinguished. To verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook x Halberd doubled haploid lines for which a framework (FW) map comprising a total of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified fragment length polymorphism (AFLP) markers was available. We added an equal number of DArT markers to this data set and also incorporated 71 sequence tagged microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores, call rates and the degree of genome coverage indicated that the quality and information content of the DArT data set was comparable to that of the combined SSR/RFLP/AFLP data set of the FW map.

Chromosomes, Plant↗