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PubMed2026

Systematic proteomic analysis of neuroimaging metrics identifies therapeutic targets for pituitary neuroendocrine.

The relationship between proteomics and neuroimaging metrics (NIMs) is still not fully understood. By examining the specific proteins expressed in different NIMs, researchers can gain insights into how these NIMs contribute to pituitary neuroendocrine tumors (PitNETs), ultimately enabling the development of targeted interventions and treatments. We identified 15 significantly NIMs and 18 proteins that exhibit a noteworthy causal relationship with the risk of developing PitNETs by forward MR analysis. Additionally, 10 proteins and one distinct neuroimaging metric with PitNETs. Then, the MR results indicated the identification of 33 significant relationships, which connect proteins with NIMs across five distinct categories. Then, we discovered that NIMs are capable of mediating 63% of the inverse relationship observed between WNT3 and the phenotypic characteristics of PitNETs. The results also suggested that WNT3 was associated with hypothalamic function, pituitary function, thyroid function, adrenal function, and gonadal function. Additionally, WNT3 expression was higher in PitNETs and was verified in multiple datasets. This research effectively connects the roles of protein markers with the structures of the brain and the PitNETs that can affect it. By establishing this link, the study provides valuable insights that can help in understanding the complex mechanisms that contribute to PitNETs.

Proteomics↗
PubMed2001

Systematic mutational analysis of the amino-terminal domain of the Listeria monocytogenes ActA protein reveals novel functions in actin-based motility.

The Listeria monocytogenes ActA protein acts as a scaffold to assemble and activate host cell actin cytoskeletal factors at the bacterial surface, resulting in directional actin polymerization and propulsion of the bacterium through the cytoplasm. We have constructed 20 clustered charged-to-alanine mutations in the NH2-terminal domain of ActA and replaced the endogenous actA gene with these molecular variants. These 20 clones were evaluated in several biological assays for phenotypes associated with particular amino acid changes. Additionally, each protein variant was purified and tested for stimulation of the Arp2/3 complex, and a subset was tested for actin monomer binding. These specific mutations refined the two regions involved in Arp2/3 activation and suggest that the actin-binding sequence of ActA spans 40 amino acids. We also identified a 'motility rate and cloud-to-tail transition' region in which nine contiguous mutations spanning amino acids 165-260 caused motility rate defects and changed the ratio of intracellular bacteria associated with actin clouds and comet tails without affecting Arp2/3 activation. Several unusual motility phenotypes were associated with amino acid changes in this region, including altered paths through the cytoplasm, discontinuous actin tails in host cells and the tendency to 'skid' or dramatically change direction while moving. These unusual phenotypes illustrate the complexity of ActA functions that control the actin-based motility of L. monocytogenes.

Actins↗
PubMed2003

Patient characteristics as predictors of primary health care preferences: a systematic literature analysis.

OBJECTIVE: To identify associations between various cultural and demographic factors and patients' primary health care preferences. SEARCH STRATEGY: Searches were performed in MEDLINE (1966-December 2000), PsycINFO (1977-May 2001) and Sociological Abstracts (1963-December 2000). Identified papers were checked for more papers. INCLUSION CRITERIA: Studies with a focus on primary health care or health care in general, asking patients about preferences with regard to health care, reporting quantitative results and examining the relations between specific patient characteristics and patient preferences. DATA EXTRACTION AND SYNTHESIS: Data were extracted from studies using a scoring form to register what methods were used, which patient characteristics were analysed and which patient characteristics significantly influenced patients' preferences with regard to different aspects of health care (P < 0.05). MAIN RESULTS: A total of 145 studies were included with 2276 comparisons between subgroups of patients. Of all the comparisons, 607 (27%) showed a significant association between patient characteristics and preferences with regard to primary health care. Age and economic status significantly related to patient preferences in 38 and 33% of the comparisons, respectively. Education, health status, family situation, sex, and utilization of health care related significantly to patient preferences in less than 25% of the comparisons. CONCLUSIONS: This review of the literature showed patient characteristics to be an important determinant of preferences regarding many aspects of primary health care defined as general practice care or health care, in general. All of the patient characteristics examined here showed at least some significant associations with preferences for primary health care.

Age Factors↗
PubMed2005

[Upgrade, expand, systematize--an analysis of the status of, the need for reform in, as well as innovative projects for follow-up care in rehabilitation under the German pension insurance scheme].

Rehabilitation benefits provided under the German Pension Insurance scheme are of central importance to insureds, in terms of protection in cases of loss or reduction of their earning capacity. Due to this safeguarding effect for the gainfully employed population, rehabilitation benefits at the same time are important to the insured community and to society as a whole. In 2003, some 846 000 insured persons had received medical and other benefits for rehabilitation. Designing these benefits to be as effective as possible is among the pre-eminent goals of the statutory pension insurance scheme. To this end, the statutory pension insurance institutes have initiated a quality assurance programme designed to enable utmost quality of the benefits provided. This programme in the first line covers inpatient medical rehabilitation of, as a rule, three weeks duration. An issue hardly investigated so far is sustainability of the effects achieved by these rehabilitation measures. Among the possibilities for ensuring lasting success are follow-up measures or benefits arranged for already during the in-patient stay, a service field which until recently had hardly been known in Germany. A stock-taking carried out in 2004 by the author and supported by LVA Schleswig-Holstein, a regional pension insurance institute, has for the first time realized an overview of this kind. Its essential findings are presented in this article, supplemented by a partial update vis-à-vis completion of the initial investigation.

Disability Evaluation↗
PubMed1989

Localization of virus-specific and group-specific epitopes of plant potyviruses by systematic immunochemical analysis of overlapping peptide fragments.

Virus-specific or group-specific antibody probes to potyviruses can be produced by targeting the immune response to the virus-specific, N-terminal region of the capsid protein (29-95 amino acids depending on the virus) or to the conserved core region (216 amino acids) of the capsid protein, respectively. Immunochemical analysis of overlapping, synthetic octapeptides covering the capsid protein of the Johnsongrass strain of Johnsongrass mosaic virus (JGMV-JG) has delineated the peptide sequences recognized by five polyclonal rabbit antisera and two mouse monoclonal antibodies (mAbs). The antibodies characterized were (i) three virus-specific rabbit polyclonal antisera and one virus-specific mouse mAb (1/25) raised against native virus particles, (ii) one polyclonal antiserum raised against trypsin-derived core particles of JGMV-JG, (iii) one group-specific polyclonal antiserum raised against the denatured, truncated coat protein from trypsin-derived core particles of JGMV-JG, and (iv) one group-specific mouse mAb (1/16) raised against native virus particles. The two epitopes seen by mAb 1/25 occurred at residues 18-27 and 43-52 and overlapped with the two major epitopes seen by the virus-specific polyclonal antiserum. The group-specific epitope seen in JGMV-JG by mAb 1/16 was also recognized strongly in potato virus Y, the type member of the potyvirus group. The multiple epitopes seen by the cross-reactive polyclonal antisera were distributed across the entire core region of the coat protein and their relative antibody binding responses varied between JGMV-JG, potato virus Y, and six other distinct potyviruses.

Amino Acid Sequence↗
PubMed1995

Systematic deletion analysis of ricin A-chain function. Single amino acid deletions.

The A-chain of ricin is a cytotoxic RNA N-glycosidase that inactivates ribosomes by depurination of the adenosine at position 4324 in 28 S rRNA. Of the 267 amino acids in the protein, 222 could be deleted, in one or another of 74 mutants, without the loss of the capacity to catalyze hydrolysis of a single specific nucleotide in rRNA (Morris, K. N., and Wool, I. G. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 4869-4873). The 45 amino acids that could not be omitted when the deletions were in sets of 20, 5, or 2 residues have now been deleted one at a time; 9 of these deletion mutants retained activity. A RNP-like structural motif in ricin A-chain that may mediate binding to ribosomal RNA has been identified.

Amino Acid Sequence↗
PubMed1996

Systematic mutational analysis of the death domain of the tumor necrosis factor receptor 1-associated protein TRADD.

Tumor necrosis factor receptor 1 (TNF-R1) mediates most of the biological properties of TNF including activation of the transcription factor NF-kappaB and programmed cell death. An approximately 80-amino acid region within the intracellular domain of the receptor, termed the death domain, is required for signaling NF-kappaB activation and cytotoxicity. A TNF-R1-associated protein TRADD has been discovered that interacts with the death domain of the receptor. Elevated expression of TRADD in cells triggers both NF-kappaB activation and programmed cell death pathways. The biological activities of TRADD have been mapped to a 111-amino acid region within the carboxyl-terminal half of the protein. This region shows sequence similarity to the death domain of TNF-R1 and can self-associate and bind to the TNF-R1 death domain. We have performed an alanine scanning mutagenesis of TRADD's death domain to explore the relationship among its various functional properties. Mutations affecting the different activities of TRADD do not map to discrete regions but rather are spread over the entire death domain, suggesting that the death domain is a multifunctional unit. A mutant that separates cell killing from NF-kappaB activation by the TRADD death domain has been identified indicating that these two signaling pathways diverge with TRADD. Additionally, one of the TRADD mutants that fails to activate NF-kappaB was found to act as dominant negative mutant capable of preventing induction of NF-kappaB by TNFalpha. Such observations provide evidence that TRADD performs an obligate role in TNF-induced NF-kappaB activation.

Alanine↗
PubMed1994

Genetic analysis of systematic mitochondrial heteroplasmy in rabbits.

One unusual property of rabbit mitochondrial DNA (mtDNA) is the existence of repeated 153-bp motifs in the vicinity of the replication origin of its H strand. Furthermore, every individual is heteroplasmic: it carries mtDNA molecules with a variable number of repeats. A systematic study of 8 females and their progeny has been devised to analyze mtDNA transmission through generations. The results suggest that three mechanisms are acting simultaneously. (1) Genetic drift in the germ line is revealed by the evolution of heteroplasmy when two major molecular forms are present in a female. (2) A high mutation rate (around 10(-2) per animal generation) generating molecular diversity, by deletion and addition of repeated units, is required to explain the observation of heteroplasmy in every individual. Moreover, the rates of mutation from the most frequent type to the other types are unequal. The deletion of one unit is more frequent than a deletion of two units, which is in turn more frequent than a deletion of three. (3) Selection for shorter molecules in somatic cells is probable. The frequency distribution of mtDNA types depends on the organ analyzed (kidney-spleen and liver vs. gonads).

Animals↗
PubMedDate not supplied

Systematic toxicological analysis of basic drugs by gradient elution of an alumina-based HPLC packing material under alkaline conditions.

A high-performance liquid chromatographic system based on gradient elution of an alumina packing material coated with polybutadiene is presented. The chromatographic eluent is a mixture of methanol and water, both containing 0.0125M NaOH. The effluent is monitored by photodiode array detection. The system allows detection and identification of more than 130 toxicologically relevant substances (mainly basic compounds) and has already been successfully applied to screen more than 500 extracts of fresh or postmortem specimens (blood, urine, tissue homogenates, and stomach contents).

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Identification power of a standardized HPLC-DAD system for systematic toxicological analysis.

High-performance liquid chromatography with photodiode-array detection (HPLC-DAD) provides two identification parameters: retention and UV spectral data. The identification power of these two parameters, expressed in standardized form (retention index and absorption maximum with the highest wavelength), is calculated using two approaches: discriminating power (DP) and mean list length (MLL). Our own HPLC database, which comprises data for more than 370 substances, is used as the basis of calculations. The identification power of both parameters applied separately is low but increases substantially when the combination of retention and spectral data is applied. Additionally, the DP and MLL values obtained for 56 acidic or neutral and 76 basic drugs examined by means of HPLC-DAD and other analytical methods (thin-layer chromatography, gas chromatography (GC), and ultraviolet (UV) detection) are compared. The on-line combination of HPLC retention index values and UV spectra, registered by means of DAD, creates an identification system in which the identification potential is slightly lower than the off-line combination of capillary GC and UV spectroscopy.

Chromatography, Gas↗
PubMedDate not supplied

Applicability of capillary gas chromatography to systematic toxicological analysis: occurrence of concentration-dependent retention behavior.

The retention behavior for a selection of acidic, neutral, and basic drugs was examined on four fused silica capillary columns in a splitless injection mode. Mixtures of n-alkanes and diisopropylamino-alkanes were also analyzed. The concentrations used ranged from 0.25-1000 ng/microL and injection volumes were either 2 or 4 microL. This corresponded to quantities of 1-4000 ng injected on the column. All substances showed concentration-dependent behavior: after being nearly constant or showing a decrease at low concentrations, retention times markedly increased when concentrations exceeded about 100 ng/microL (400 ng injected). At very high concentrations, peak splitting occurred. In the more pronounced cases, the differences caused by this concentration effect could reach values of over 100 retention-index units.

Chemical Phenomena↗
PubMedDate not supplied

Impact of biological matrix and isolation methods on detectability and interlaboratory variations of TLC Rf-values in systematic toxicological analysis.

The retention behavior of eight basic and neutral drugs, extracted from plasma, blood, and liver by five different methods (XAD-2, Extrelut, Elut-X, Elut-C18, chloroform) and developed in three chromatographic systems [MeOH, Me OH:BuOH:NaBr, CHCl3:MeOH (KOH)] was observed in parallel in two laboratories. The corrected Rf-values were compared with reference data from a data base with data for pure drugs. The biological matrix and/or the extraction severely lowered the precision and, to a lesser extent, the accuracy of the Rf-values as compared to pure drug data and to reference Rf-values. The intra- and interlaboratory variation was smallest in the MeOH system and largest in the CHCl3:MeOH (KOH) system. The observed irreproducibility is caused by the biological matrix (extraction has a large negative impact on the potentials of TLC in identification procedures). Precision and accuracy of extracted drugs were independent of the biological matrix and on the extraction method used.

Chemistry, Pharmaceutical↗
PubMed2000

RT-PCR as a tool for systematic transcriptional analysis of large regions of the Bacillus subtilis genome.

Transcriptional analysis of five different regions of the Bacillus subtilis 168 genome, comprising a total of 175 kb encoding newly identified genes, was carried out using the RT-PCR technique as part of the functional analysis of the whole genome of this bacterium. Amplification of mRNA fragments allowed the detection of both highly and poorly transcribed genes covering 81% of putative ORFs, and also the monitoring of variations in the expression level among genes differentially expressed during particular bacterial growth phases.

Bacillus subtilis↗
PubMed2005

Systematic spatial analysis of gene expression during wheat caryopsis development.

The cereal caryopsis is a complex tissue in which maternal and endosperm tissues follow distinct but coordinated developmental programs. Because of the hexaploid genome in wheat (Triticum aestivum), the identification of genes involved in key developmental processes by genetic approaches has been difficult. To bypass this limitation, we surveyed 888 genes that are expressed during caryopsis development using a novel high-throughput mRNA in situ hybridization method. This survey revealed novel distinct spatial expression patterns that either reflected the ontogeny of the developing caryopsis or indicated specialized cellular functions. We have identified both known and novel genes whose expression is cell cycle-dependent. We have identified the crease region as important in setting up the developmental patterning, because the transition from proliferation to differentiation spreads from this region to the rest of the endosperm. A comparison of this set of genes with the rice (Oryza sativa) genome shows that approximately two-thirds have rice counterparts but also suggests considerable divergence with regard to proteins involved in grain filling. We found that the wheat genes had significant homology with 350 Arabidopsis thaliana genes. At least 25 of these are already known to be essential for seed development in Arabidopsis, but many others remain to be characterized.

Cell Cycle↗
PubMed2000

A systematic uncertainty analysis of an evaluative fate and exposure model.

Multimedia fate and exposure models are widely used to regulate the release of toxic chemicals, to set cleanup standards for contaminated sites, and to evaluate emissions in life-cycle assessment. CalTOX, one of these models, is used to calculate the potential dose, an outcome that is combined with the toxicity of the chemical to determine the Human Toxicity Potential (HTP), used to aggregate and compare emissions. The comprehensive assessment of the uncertainty in the potential dose calculation in this article serves to provide the information necessary to evaluate the reliability of decisions based on the HTP A framework for uncertainty analysis in multimedia risk assessment is proposed and evaluated with four types of uncertainty. Parameter uncertainty is assessed through Monte Carlo analysis. The variability in landscape parameters is assessed through a comparison of potential dose calculations for different regions in the United States. Decision rule uncertainty is explored through a comparison of the HTP values under open and closed system boundaries. Model uncertainty is evaluated through two case studies, one using alternative formulations for calculating the plant concentration and the other testing the steady state assumption for wet deposition. This investigation shows that steady state conditions for the removal of chemicals from the atmosphere are not appropriate and result in an underestimate of the potential dose for 25% of the 336 chemicals evaluated.

Air Pollutants↗