SEARCH · PubMed Health

Results for “Association and function analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

PubMed2025

Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID.

Long COVID represents a significant global health challenge with an unclear etiology. Alongside accumulating evidence of mitochondrial dysfunction in patients with acute SARS-CoV-2 infection, a symptomatic overlap exists between long COVID and mitochondrial disorders. However, the genetic underpinnings of mitochondrial dysfunction in long COVID have not been previously explored. We employed whole genome sequencing to analyze 13 patients with severe long COVID to identify genetic defects related to mitochondrial function. We performed extracellular bioenergetics flux analysis on peripheral blood mononuclear cells and proteomics to evaluate cellular bioenergetics and compared the results to those of healthy controls. Our investigation identified 10 variants classified as pathogenic or likely pathogenic and 83 variants of unknown significance affecting a wide range of mitochondria-associated biological functions. Bioenergetics flux analysis in peripheral blood mononuclear cells revealed an altered ATP production rate in four long COVID patients compared to healthy controls. This study presents initial evidence of a potential underlying genetic predisposition to mitochondrial dysfunction in long COVID while demonstrating altered cellular energy capacity in a subset of these patients. These findings open avenues for further research into the role of mitochondrial dysfunction and pathology in patients suffering from long COVID and may pave the way for targeted therapeutic strategies aimed at mitigating mitochondrial dysfunction.

Humans↗

PubMed2005

D-type cyclins activate division in the root apex to promote seed germination in Arabidopsis.

Seeds provide survival and dispersal capabilities by protecting the dormant mature plant embryo. Germination and resumption of development under favourable conditions requires the reinitiation of cell growth and division through poorly understood processes. Here we show that four phases of cell division activation during germination in Arabidopsis are related to external morphological changes. Cell division initiates in the root apical meristem (RAM) before root protrusion, followed by sequential activation of cell division in the cotyledons, shoot apical meristem (SAM), and secondary meristems. Major changes in transcript levels of >2,000 genes precede root emergence, including expression peaks of six D-type (CYCD) and two A-type cyclins. Two further CYCDs are activated later with the SAM. Early activated CYCDs play key roles in regulating the extent of cell division, because loss-of-function alleles of early CYCDs display reduced division activation and consequential delayed root emergence. Conversely, elevation of early CYCDs increases cell cycle activation in the RAM and promotes embryonic root (radicle) protrusion, whereas a later-acting CYCD does not. These phenotypes, together with their overlapping expression domains, support a cumulative action of a subset of CYCDs in cell cycle reactivation, rather than a complete functional redundancy. This analysis reveals a phenotype associated with loss-of-function of a plant cyclin and demonstrates that D-type cyclins regulate cell cycle reentry during meristem activation to promote successful germination and early seedling growth.

Arabidopsis↗

PubMed1994

Structural and functional studies on biliverdin-associated cyanoprotein from the bean bug, Riptortus clavatus.

Structural and functional analysis were performed on biliverdin-associated cyanoprotein (CP) from the hemolymph (CP-1 to CP-4) and eggs (CPegg, identical to CP-1) of the bean bug, Riptortus clavatus. Isoelectric focusing analysis of purified CPegg and CP-4 revealed that they are composed of a single alpha subunit and a more acidic beta subunit respectively. N-terminal amino acid sequencing revealed that there are six different amino acid residues between the two subunits up to the 29 cycles determined, indicating that they are encoded by different genes. Appreciable sequence similarities in N-terminal region are found between the CP subunits and several insect hexamers. By chemical cross-linking analysis these CPs were demonstrated to have hexameric structures. Two dimensional peptide mapping revealed that alpha and beta subunits share common structures in part and that CP-2 and CP-3 are hybrid molecules bearing both alpha and beta subunits. From these results the molecular structure of CPs was established as follows: CP-1 (CPegg) = alpha 6; CP-2 = alpha 4 beta 2; CP-3 = alpha 2 beta 4; CP-4 = beta 6. In addition, using 125I-labeled CPegg and CP-4, in vivo incorporation into several tissues was examined during the nymphal-adult development. During the late phase of the 5th instar, CP-4 was sequestered preferentially over CPegg by the fat body, while after emergence both proteins were suggested to be incorporated into the newly-formed cuticle. CPegg was sequestered massively by the developing ovaries whereas no appreciable incorporation of CP-4 was observed.

Amino Acid Sequence↗

PubMed1997

Analysis of the genes encoding the mast cell function-associated antigen and its alternatively spliced transcripts.

The mast cell function-associated Ag (MAFA) is a C-type lectin that, upon being clustered, inhibits the Fc epsilon RI stimulation-induced mast cell secretory response. We here report that MAFA is encoded by a single-copy gene that spans 13 kb in the rat genome and is composed of five exons. Three separate exons encode the carbohydrate recognition domain of the MAFA, defining its close homology to the genes of CD23, CD69, CD72, NKR-P1, and Ly49. Functional analysis of the 5' flanking region of the gene reveals that a cell type-specific promoter is located within the first 664 bp upstream of the transcription origin. The promoter lacks any obvious TATA box and drives gene transcription originating from multiple start sites. Examination for possible polymorphism of the MAFA transcripts revealed two novel transcripts, generated by alternative splicing. Deletion of the transmembranal exon in one of them does not result in a frameshift and would, upon translation, give rise to a soluble MAFA molecule. Splicing of two exons in a second transcript results in a new reading frame encoding a putative protein containing MAFA's cytoplasmic domain. The transcription of the MAFA gene was detected in normal rat lungs, where both transmembranal and soluble MAFA appear to be expressed. Lung immunohistochemical analysis further suggests that MAFA expression is restricted to mast cells.

Alternative Splicing↗

PubMed2005

A functional analysis of the putative polymorphisms A91V and N252S and 22 missense perforin mutations associated with familial hemophagocytic lymphohistiocytosis.

Up to 60% of cases of the autosomal recessive immunodeficiency hemophagocytic lymphohistiocytosis (HLH) are associated with mutations in the perforin (PRF1) gene. In this study, we expressed wild-type and mutated perforin in rat basophil leukemia cells to study the effect on lytic function of the substitutions A91V and N252S (commonly considered to be neutral polymorphisms) and 22 perforin missense substitutions first identified in HLH patients. Surprisingly, we found that A91V perforin was expressed at reduced levels compared with wild-type perforin, resulting in partial loss of lytic capacity. In contrast, expression and function of N252S-substituted perforin were normal. Most HLH-associated mutations resulted in protein degradation (probably due to misfolding) and complete loss of perforin activity, the exception being R232H, which retained approximately 30% wild-type activity. Several other mutated proteins (H222Q, C73R, F157V, and D313V) had no detectable lytic activity but were expressed at normal levels, suggesting that their functional defect might map downstream at the level of the target cell membrane. One further perforin substitution identified in an HLH patient (V183G) was normally expressed and displayed normal lysis. This report represents the first systematic functional analysis of HLH-associated missense mutations and the 2 most common perforin polymorphisms.

Animals↗

PubMed2003

Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation.

BACKGROUND: Chronic kidney disease is thought to be a potential risk factor for cardiovascular death. In renal-allograft recipients, cardiovascular disease is the most significant cause of death. The purpose of this study was to investigate if renal function has a significant role in determining the risk for cardiovascular death in renal-allograft recipients. METHODS: We analyzed 58,900 adult patients registered in the United States Renal Data System who received a primary renal transplant between 1988 and 1998 and who had at least 1 year of graft survival. The primary study endpoint was death from a cardiovascular event beyond 1 year of transplantation. Secondary endpoints were death caused by infections and malignancy-related deaths. Cox proportional-hazard models were used to estimate the effect of renal function on cardiovascular death, infectious death, and malignancy-related death while correcting for potential confounding variables, such as donor and recipient age, gender, race, cause of end-stage renal disease, length of dialysis before transplantation, year of transplantation, donor source and age, delayed graft function, and immunosuppressive regimen. RESULTS: Serum creatinine values at 1 year after transplantation were strongly associated with the risk for cardiovascular death. Above a serum creatinine value of 1.5 mg/dL, there was a significant and progressive increase in the risk for cardiovascular death. The risk of cardiovascular death was significantly higher when patients who lost allograft function were included in the analysis. There was an association between worsening renal function and infectious death, but there was no association between renal function and malignancy-related death. CONCLUSION: Serum creatinine at 1 year is strongly associated with the incidence of cardiovascular death independent of known risk factors.

Cardiovascular Diseases↗

PubMed2004

Immediate postoperative renal function deterioration in cardiac surgical patients predicts in-hospital mortality and long-term survival.

Postoperative renal function deterioration is a serious complication after cardiac surgery with cardiopulmonary bypass and is associated with increased in-hospital mortality. However, the long-term prognosis of patients with postoperative renal deterioration is not fully determined yet. Therefore, both in-hospital mortality and long-term survival were studied in patients with postoperative renal function deterioration. Included were 843 patients who underwent cardiac surgery with cardiopulmonary bypass in 1991. Postoperative renal function deterioration (increase in serum creatinine in the first postoperative week of at least 25%) occurred in 145 (17.2%) patients. In these patients, in-hospital mortality was 14.5%, versus 1.1% in patients without renal function deterioration (P < 0.001). Multivariate analysis significantly associated in-hospital mortality with postoperative renal function deterioration, re-exploration, postoperative cerebral stroke, duration of operation, age, and diabetes. In patients who were discharged alive, during long-term follow-up (100 mo), mortality was significantly increased in the patients with renal function deterioration (n = 124) as compared with those without renal function deterioration (hazard ratio 1.83; 95% confidence interval 1.38 to 3.20). Also after adjustment for other independently associated factors, the risk for mortality in patients with postoperative renal function deterioration remained elevated (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32). The elevated risk for long-term mortality was independent of whether renal function had recovered at discharge from hospital. It is concluded that postoperative renal function deterioration in cardiac surgical patients not only results in increased in-hospital mortality but also adversely affects long-term survival.

Acute Kidney Injury↗

PubMed2002

Functional status of patients with primary biliary cirrhosis.

OBJECTIVES: Although autoimmune diseases can have a significant impact on the quality of life, there has been a relative paucity of data with respect to the functional status of patients with primary biliary cirrhosis (PBC). METHODS: We conducted a case-control study of 182 patients ("cases") with PBC as well as 225 age- and sex-matched friend control subjects using a standardized instrument obtained from the National Health and Nutrition Examination Survey. RESULTS: In all, 126 of 182 cases (69%) and 141 of 225 friend controls (62.6%) responded to this survey, a response rate comparable to or better than in similar previous studies of such instruments. Patients with PBC had a significantly reduced functional status score compared to their controls (p < 0.001). Interestingly, a lower level of education and the presence of arthritis and hypertension were significantly associated with these lower levels of functional capabilities. These data were subjected to multivariate analysis and confirmed. Age was not associated with impaired functional status in either the patients or controls. CONCLUSIONS: Studies of this nature have potential implications for the well-being and management of patients with PBC, and focus on issues that can be addressed to help maintain functional status in this chronic disease.

Activities of Daily Living↗

PubMed2005

Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness.

AgRP is a neuropeptide that stimulates food intake through inhibition of central melanocortin receptors (MCRs). In humans, the non-conservative amino acid substitution Alanine (Ala) 67 Threonine (Thr) has been associated with Anorexia Nervosa and with leanness. In the present study, the cellular distribution, processing and in vitro and in vivo activities of Ala67 and Thr67 AgRP were investigated. Western blots of media and lysates of BHK cells stably transfected with Ala67 or Thr67 expression constructs showed identical AgRP bands. Both Ala67 and Thr67 AgRP colocalised with the Golgi apparatus, but not with the ER or lysosomes when expressed in Att20 D16V cells. Also, no differences were observed between the potencies of bacterially expressed Ala67 and Thr67 AgRP to stimulate MC4R in a reporter gene assay or inhibit food intake in rats. Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions.

Agouti-Related Protein↗

PubMed2002

Annotation of human chromosome 21 for relevance to Down syndrome: gene structure and expression analysis.

Down syndrome is caused by an extra copy of human chromosome 21 and the resultant dosage-related overexpression of genes contained within it. To efficiently direct experiments to determine specific gene-phenotype correlations, it is necessary to identify all genes within 21q and assess their functional associations and expression patterns. Analysis of the complete finished sequence of 21q resulted in annotated 225 genes and gene models, most of which were incomplete and/or had little or no experimental verification. Here we correct or complete the genomic structures of 16 genes, 4 of which were not reported in the annotation of the complete sequence. Our data include the identification of six genes encoding short or ambiguous open reading frames; the identification of three cases in which alternative splicing produces two structurally unrelated protein sequences; and the identification of six genes encoding proteins with functional motifs, two genes with unusually low similarity to their orthologous mouse proteins, and four genes with significant conservation in Drosophila melanogaster. We further demonstrate that an additional nine gene models represent bona fide transcripts and develop expression patterns for these genes plus nine additional novel chromosome 21 genes and four paralogous genes mapping elsewhere in the human genome. These data have implications for generating complete transcript maps of chromosome 21 and for the entire human genome, and for defining expression abnormalities in Down syndrome and mouse models.

Animals↗

PubMed2005

Analysis of four neuroligin genes as candidates for autism.

Neuroligins are cell-adhesion molecules located at the postsynaptic side of the synapse. Neuroligins interact with beta-neurexins and this interaction is involved in the formation of functional synapses. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have recently been implicated in pathogenesis of autism. The neuroligin gene family consists of five members (NLGN1 at 3q26, NLGN2 at 17p13, NLGN3 at Xq13, NLGN4 at Xp22, and NLGN4Y at Yq11), of which NLGN1 and NLGN3 are located within the best loci observed in our previous genome-wide scan for autism in the Finnish sample. Here, we report a detailed molecular genetic analysis of NLGN1, NLGN3, NLGN4, and NLNG4Y in the Finnish autism sample. Mutation analysis of 30 probands selected from families producing linkage evidence for Xq13 and/or 3q26 loci revealed several polymorphisms, but none of these seemed to be functional. Family-based association analysis in 100 families with autism spectrum disorders yielded only modest associations at NLGN1 (rs1488545, P=0.002), NLGN3 (DXS7132, P=0.014), and NLGN4 (DXS996, P=0.031). We conclude that neuroligin mutations most probably represent rare causes of autism and that it is unlikely that the allelic variants in these genes would be major risk factors for autism.

Autistic Disorder↗

PubMed2004

Functional analysis of bacterial artificial chromosomes in mammalian cells: mouse Cdc6 is associated with the mitotic spindle apparatus.

Bacterial artificial chromosomes (BACs) provide a well-characterized resource for studying the functional organization of genes and other large chromosomal domains. To facilitate functional studies in cell cultures, we have developed a simple approach for generating stable cell lines with variable copy numbers of any BAC. Here we describe hamster cell lines with BAC transgenes that express mouse Cdc6 at levels that correlate with BAC copy number; show that mouse Cdc6 is regulated normally during the cell cycle, binds chromatin, and is degraded during apoptosis; and report a novel fraction of Cdc6 that associates with the spindle apparatus during mitosis. With RNA interference to assess genetic complementation by BAC alleles, this system will facilitate functional studies on large chromosomal domains at variable copy number in mammalian cell models.

Animals↗

PubMed1998

Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.

The action of antipsychotic drugs on dopamine receptors suggests that dopaminergic signal transmission may play a role in the development of schizophrenia. We tested eight candidate genes (coding for dopamine receptors, the dopamine transporter, and G-proteins) in 59 families from Germany and Israel, for association. A P value of .00055 (.0044 when corrected for the no. of markers tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome 18p. The value decreased to .000088 (.0007) when nine sibs with recurrent unipolar depressive disorder were included. Linkage analysis using SSLP markers densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of heterogeneity supported this linkage-whether the affected pheotype was defined narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with exclusively maternal transmission of the disease, the NPL value also supported linkage to this marker. In order to test for association/linkage disequilibrium in the presence of linkage, the sample was restricted to independent offspring. When this sample was combined with 65 additional simplex families (each of them comprising one schizophrenic offspring and his or her parents), the 124-bp allele of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009). These results suggest the existence, on chromosome 18p, of a potential susceptibility locus for functional psychoses.

Chromosomes, Human, Pair 18↗

PubMed1998

Sequence and functional analysis of the intergenic regions separating babesial rhoptry-associated protein-1 (rap-1) genes.

The rhoptry-associated protein 1 (RAP-1) expressed by all babesial parasites is encoded by tandemly arranged genes separated by discrete intergenic (IG) regions. We hypothesize that these IG regions regulate rap-1 gene expression. In Babesia bovis two identical rap-1 gene copies are separated by a 1.0-kb noncoding region which is also exactly conserved 5' to the rap-1 gene 1. In contrast, the complex B. bigemina rap-1 locus contains at least 5 polymorphic rap-1a genes separated by uncharacterized 3.38-kb regions. A genomic clone encoding the 3' sequence of rap-1 gene copy 1, the 1 kb IG region, and the 5' sequence of gene copy 2 was obtained by PCR amplification of DNA from the Mo7 biological clone of B. bovis and sequenced. This was follow by amplification and sequence analysis of the 3.38-kb region separating two B. bigemina rap-1a genes, revealing the presence of two different IG regions denominated IG-1 (0.7 kb) and IG-2 (1.3 kb), flanking a newly identified rap-1b orf. Sequence analysis and comparison among babesial rap-1 IG regions from B. bovis, B. bigemina, B. canis, and B. ovis revealed conservation of at least three putative regulatory boxes consistently positioned 5' of the start of the rap-1 orfs. To determine whether rap-1 IG regions contained a functional promoter, the entire 1-kb IG region from B. bovis was cloned into pCAT, a promoterless plasmid containing the cat gene. The IG region in the 5' --> 3' orientation strongly promoted transcription in vitro by homologous B. bovis RNA polymerases. The presence of conserved regions 5' to each rap-1 gene copy and among other babesial rap-1 IG regions and the in vitro promoter function in the 5' --> 3' orientation support a role for the IG region in rap-1 gene regulation.

Animals↗

PubMed1990

Urinary free cortisol excretion shortly after ischaemic stroke.

The cortisol axis and catecholamine excretion were studied in 20 patients within the first week after acute ischaemic stroke. Urine free cortisol and plasma cortisol levels after dexamethasone were significantly higher in stroke patients than in 80-year-old volunteers (n = 32; P = 0.03 and P = 0.003, respectively). Catecholamine excretion was found to be significantly correlated with urine cortisol concentration (r = 0.54, P less than 0.05) and limb paresis (r = 0.52, P less than 0.05). In a multiple regression analysis, urine cortisol values were shown to be positively associated with limb paresis (P = 0.003), disorientation (P = 0.03) and body temperature (P = 0.03). High cortisol excretion was associated with a poorer functional outcome in a discriminant analysis (P = 0.001). Thus acute ischaemic stroke is associated with an increased activity in the cortisol axis. This may have a number of negative effects on organ functioning, and is a predictor of a poorer functional outcome.

Aged↗

PubMed1997

Physicochemical characterizations of piroxicam-poloxamer solid dispersion.

To develop an efficient topical delivery system for piroxicam using poloxamer gel formulation, physicochemical behavior of piroxicam in poloxamer was studied. The gelling property of poloxamer and the solubility of piroxicam in the poloxamer were investigated. The interaction between piroxicam and poloxamer was studied by x-ray diffractometry (XRD), infrared (IR) spectroscopy and differential thermal analysis (DTA) with a solid dispersion, coprecipitate, or physical mixture. Poloxamer 407 solutions showed the property of a gel when the concentration was higher than 15% (w/w) and poloxamer 407 increased the aqueous solubility of piroxicam by about 11-fold at the concentration of 22.5% (w/w). The results of XRD did not show the crystalline from of piroxicam in the solid dispersion and results of IR spectroscopic analysis showed an association between functional groups of piroxicam and poloxamer.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Determinants of early and late mortality in patients with end-stage renal disease undergoing cardiac surgery.

To determine factors influencing early and late mortality associated with cardiovascular surgery in end-stage renal disease, 48 consecutive patients (mean age 56.3 years) were reviewed: 30 underwent coronary and 18 valvular surgery. There were eight early deaths, three in the former and five in the latter group. Factors significantly related to early mortality in univariate testing included infective valvular disease, emergency vs elective surgery (both p = 0.02) poor left ventricular function and prolonged clamping and bypass times (all p = 0.001). When these factors were included in a stepwise logistic regression analysis, infective valvular disease (p = 0.02), poor left ventricular function (p = 0.01) and long cross-clamping (p = 0.01) were independently associated with early mortality. There were six late deaths. Survival for the whole cohort at 1, 5 and 7 years was 95%, 60.4% and 42.6%, respectively. Related to late mortality at univariate testing were age (p = 0.03), smoking (p = 0.04), diabetes (p = 0.03) and poor left ventricular function (p = 0.02), and stepwise logistic regression analysis showed independent association with age, diabetes and impaired left ventricular function. Mortality associated with cardiac surgery in patients with end-stage nephropathy can be reduced by better patient selection, early operation in patients with infective endocarditis, and minimized cross-clamping and bypass times.

Adult↗

PubMed2006

Comparative proteomic analysis reveals a function of the novel death receptor-associated protein BRE in the regulation of prohibitin and p53 expression and proliferation.

The brain and reproductive organ expressed (BRE) gene encodes a highly conserved stress-modulating protein. To gain further insight into the function of this gene, we used comparative proteomics to investigate the protein profiles of C2C12 and D122 cells resulting from small interfering RNA (siRNA)-mediated silencing as well as overexpression of BRE. Silencing of BRE in C2C12 cells, using siRNA, resulted in up-regulated Akt-3 and carbonic anhydrase III expression, while the 26S proteasome regulatory subunit S14 and prohibitin were down-regulated. Prohibitin is a potential tumour suppressor gene, which can directly interact with p53. We found that cell proliferation was significantly increased after knockdown of BRE, concomitant with reduced p53 and prohibitin expression. In contrast, we observed decreased proliferation and up-regulation of p53 and prohibitin when BRE was overexpressed in the D122 cell line. In total, five proteins were found to be up-regulated after BRE over-expression. The majority of these proteins can target or crosstalk with NF-kappaB, which plays a central role in regulating cell proliferation, differentiation and survival. Our results establish a crucial role for BRE in the regulation of key proteins of the cellular stress-response machinery and provide an explanation for the multifunctional nature of BRE.

Animals↗