Conversion of model discoidal complexes of egg yolk phosphatidylcholine and apolipoprotein A-I, upon interaction with a source of lecithin:cholesterol acyltransferase (plasma d greater than or equal ...to 1.21 g/ml fraction or partially purified enzyme) and with different sources of substrate unesterified cholesterol (LDL, VLDL or cholesterol incorporated into complexes), was investigated by gradient gel electrophoresis, gel filtration, equilibrium density gradient ultracentrifugation, electron microscopy and chemical analysis. When the incubation mixture contained an inhibitor of lecithin:cholesterol acyltransferase, discoidal complexes with mean long dimension of approximately 10.5 +/- 1.9 nm were converted (within 1 h) predominantly to small round particles and were partially depleted of their phospholipid content. Upon electrophoresis the small particles showed peak maxima within the migration intervals of the human plasma ( HDL3b ) gge and ( HDL3c ) gge subpopulations with associated particle size ranges of 7.8-8.2 and 7.2-7.8 nm, respectively. Within 1 h, in the presence of activated enzyme, the complexes were again converted in major part to the small particles. However, further incubation resulted in an apparent single-step conversion to a larger major product with peak maximum occurring within the migration intervals of the ( HDL2a ) gge and the ( HDL3a ) gge subpopulations (particle size ranges 8.8-9.8 and 8.2-8.8 nm, respectively). Formation of an apolar core was indicated by detection of cholesteryl esters in the conversion product. The form in which the substrate unesterified cholesterol was introduced did not markedly influence the size properties of the final conversion product. With VLDL as source of substrate, considerable incorporation of triacylglycerol occurred in company with a lower level of cholesteryl esters, suggesting transfer of these lipids during formation of the apolar core. Incubation of complexes with a partially purified (3000-fold) preparation of lecithin:cholesterol acyltransferase yielded a product similar in properties to that when the d greater than or equal to 1.21 g/ml fraction was used. Our model discoidal complexes and their conversion products exhibit properties very similar to those of potential precursors to HDL as well as of mature HDL particles. Their further investigation shows promise of providing detailed insight into the possible origin and heterogeneity of human plasma HDL.
To study the effect of lecithin: cholesterol acyltransferase (LCAT) on the plasma lipoproteins of patients with familial LCAT deficiency, whole plasma or the lipoprotein fraction of d < 1.006 g/ml ...(VLDL) was incubated in the presence of LCAT and subsequently examined by chemical, physical, and immunological techniques. The following occurred upon incubating either hyperlipemia or nonlipemic plasma: The concentrations of polar lipids decreased, particularly in the large molecular weight lipoprotein subfraction of d 1.019-1.063 g/ml (LDL2) and in the lipoprotein fraction of d 1.063-1.25 g/ml (HDL). The concentration of cholesteryl ester (CE) increased, particularly in the VLDL and in the lipoprotein fractions of d 1.006-1.019 g/ml (LDL1) and LDL2. The concentration of arginine-rich apolipoprotein decreased in the HDL and increased in the VLDL and LDLi. The concentrations of the C-apoliproteins appeared to change in the opposite direction. The concentration of apolipoprotein B in the LDL increased concomitantly with an increase in the concentration and flotation rate of the small LDL2. The concentration of apolipoprotein A-I in the HDL increased; and a major component in the HDL fraction became identical in appearance to normal HDL. Upon incubating a patient's isolated VLDL in the presence of LCAT, lipoproteins with properties similar to normal LDL2 were formed. These experiments show that the LCAT reaction can alter the apolipoprotein content and physical properties as well as the lipid content of the patients' lipoproteins.
To study the metabolism of the abnormal plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency we performed five dietary experiments designed to perturb their distribution ...and composition. Four patients with the disease were given successive diets that differed in triglyceride, carbohydrate, or cholestrol content, and after each dietary period the lipoproteins were analyzed by combinations of preparative and analytical ultracentrifugation, gel filtration, chromatography, and disc gel electrophorsis. Lowering the intake of long chain, dietary triglyceride descreased the concentrations of the large very low density lipoproteins, the large and intermediate low density lipoproteins, and the small high density lipoproteins by as much ad 79 %, but either increased or did not change the concentrations of the small very low and low density lipoproteins. Re-adding long chain triglycerdine to the diet generally reversed these effects, but increasing the dietary cholesterol without lowering the dietary triglyceride only decreased the concentration of plasma cholesteryl ester. We conclude that the concentrations of the large very low and low sensity lipoproteins, the intermediate-sized low density lipoproteins, and the small high density lipoproteins are related to the absorption and subsequent transport of long chain dietary fatty acids. Since these lipoproteins are rich in unesterified cholesterol and lecithin, two polar lipids that form a substantial part of the surfaces of chylomicrons, components of chylomicron surfaces may accumulate in the patient's plasma following enzymic removal of chylomicron triglyceride and contribute to several of the abnormal lipoproteins.
To study the metabolism of the abnormal plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency we performed five dietary experiments designed to perturb their distribution ...and composition. Four patients with the disease were given successive diets that differed in triglyceride, carbohydrate, or cholesterol content, and after each dietary period the lipoproteins were analyzed by combinations of preparative and analytical ultracentrifuga-tion, gel filtration, chromatography, and disc gel electrophoresis. Lowering the intake of long chain, dietary trigylceride descreased the concentrations of the large very low density lipoproteins, the large and intermediate low density lipoproteins, and the small high density lipoproteins by as much as 79 %, but either increased or did not change the concentrations of the small very low and low density lipoproteins. Re-adding long chain triglyceride to the diet generally reversed these effects, but increasing the intake of carbohydrate did not. Furthermore, decreasing the dietary cholesterol without lowering the dietary triglyceride only decreased the concentration of plasma cholesteryl ester. We conclude that the concentrations of the large very low and low density lipoproteins, the intermediate-sized low density lipoproteins, and the small high density lipoproteins are related to the absorption and subsequent transport of long chain dietary fatty acids. Since these lipoproteins are rich in unesterified cholesterol and lecithin, two polar lipids that form a substantial part of the surfaces of chylomicrons, components of chylomicron surfaces may accumulate in the patients' plasma following enzymic removal of chylomicron triglyceride and contribute to several of the abnormal lipoproteins.
The interaction of HDL2b, a major subclass (d = 1.063 - 1.100 g/ml) of human plasma high-density lipoproteins, with discoidal complexes composed of dimyristoylphosphatidylcholine (DMPC) and ...apolipoprotein A-I (weight ratio, DMPC/apolipoprotein A-I (2.1 - 2.5:1); dimensions, 10.0 x 4.4 nm) was investigated. Incubation at 37 degrees C for 4.5 h of HDL2b with discoidal complexes resulted in a transfer of DMPC from the discoidal complexes to the HDL2b, a release of lipid-free apolipoprotein A-I from the discoidal complexes during such transfer, and a dissociation of some apolipoprotein A-I from the HDL2b surface. The number of discoidal complexes degraded during interaction with HDL2b depended on the initial molar ratio of HDL2b to discoidal complexes. Approximately one molecule of HDL2b was required for the degradation of one discoidal complex particle, and the degradation process appeared limited by the capacity of the HDL2b for uptake of DMPC. Degradation of discoidal complexes was also observed when human plasma LDL (d = 1.006-1.063 g/ml) was substituted for HDL2b in the interaction mixture.
Summary
Early gene expression in arbuscular mycorrhiza (AM) and the nitrogen‐fixing root nodule symbiosis (RNS) is governed by a shared regulatory complex. Yet many symbiosis‐induced genes are ...specifically activated in only one of the two symbioses.
The Lotus japonicus T‐DNA insertion line T90, carrying a promoterless uidA (GUS) gene in the promoter of Calcium Binding Protein 1 (CBP1) is exceptional as it exhibits GUS activity in both root endosymbioses. To identify the responsible cis‐ and trans‐acting factors, we subjected deletion/modification series of CBP1 promoter : reporter fusions to transactivation and spatio‐temporal expression analysis and screened ethyl methanesulphonate (EMS)‐mutagenized T90 populations for aberrant GUS expression.
We identified one cis‐regulatory element required for GUS expression in the epidermis and a second element, necessary and sufficient for transactivation by the calcium and calmodulin‐dependent protein kinase (CCaMK) in combination with the transcription factor Cyclops and conferring gene expression during both AM and RNS. Lack of GUS expression in T90 white mutants could be traced to DNA hypermethylation detected in and around this element.
We concluded that the CCaMK/Cyclops complex can contribute to at least three distinct gene expression patterns on its direct target promoters NIN (RNS), RAM1 (AM), and CBP1 (AM and RNS), calling for yet‐to‐be identified specificity‐conferring factors.
Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized ...lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic alterations involved in the pathogenesis of PTFL are unknown. Therefore, 42 PTFL (40 males and 2 females; mean age, 16 years; range, 5-31) were genetically characterized. For comparison, 11 cases of conventional t(14:18)− FL in adults were investigated. Morphologically, PTFL cases had follicular growth pattern without diffuse areas and characteristic immunophenotype. All cases showed monoclonal immunoglobulin (IG) rearrangement. PTFL displays low genomic complexity when compared with t(14;18)− FL (mean, 0.77 vs 9 copy number alterations per case; P < .001). Both groups presented 1p36 alterations including TNFRSF14, but copy-number neutral loss of heterozygosity (CNN-LOH) of this locus was more frequently observed in PTFL (40% vs 9%; P = .075). TNFRSF14 was the most frequently affected gene in PTFL (21 mutations and 2 deletions), identified in 54% of cases, followed by KMT2D mutations in 16%. Other histone-modifying genes were rarely affected. In contrast, t(14;18)− FL displayed a mutational profile similar to t(14;18)+ FL. In 8 PTFL cases (19%), no genetic alterations were identified beyond IG monoclonal rearrangement. The genetic landscape of PTFL suggests that TNFRSF14 mutations accompanied by CNN-LOH of the 1p36 locus in over 70% of mutated cases, as additional selection mechanism, might play a key role in the pathogenesis of this disease. The genetic profiles of PTFL and t(14;18)− FL in adults indicate that these are two different disorders.
•PTFL is a monoclonal B-cell neoplasia with low genomic complexity and recurrent TNFRSF14 mutations/deletions.•The genetic profiles of conventional t(14;18)− and t(14;18)+ FL are similar but distinct from PTFL.
The effects of social influence and homophily suggest that both network structure and node-attribute information should inform the tasks of link prediction and node-attribute inference. Recently, Yin ...et al. 2010a, 2010b proposed an attribute-augmented social network model, which we call Social-Attribute Network (SAN), to integrate network structure and node attributes to perform both link prediction and attribute inference. They focused on generalizing the random walk with a restart algorithm to the SAN framework and showed improved performance. In this article, we extend the SAN framework with several leading supervised and unsupervised link-prediction algorithms and demonstrate performance improvement for each algorithm on both link prediction and attribute inference. Moreover, we make the novel observation that attribute inference can help inform link prediction, that is, link-prediction accuracy is further improved by first inferring missing attributes. We comprehensively evaluate these algorithms and compare them with other existing algorithms using a novel, large-scale Google+ dataset, which we make publicly available (http://www.cs.berkeley.edu/~stevgong/gplus.html).
Summary Epstein-Barr virus (EBV)–positive inflammatory pseudotumor (IPT) commonly involves spleen and liver and has only rarely been reported in the gastrointestinal (GI) tract. The spindle cells may ...express myofibroblastic or follicular dendritic cell markers. We report a challenging case of EBV-positive IPT arising in the ascending colon. The lesion was composed of spindle cells positive for smooth muscle actin but negative for all follicular dendritic cell markers tested and was associated with an exuberant lymphoid proliferation containing reactive follicles, abundant plasma cells, and small lymphocytes. We further discuss pitfalls for possible misdiagnosis as ALK-positive inflammatory myofibroblastic tumor, IgG4-related disease, and peripheral T-cell lymphoma. Our case represents the first EBV-positive inflammatory pseudotumor of the GI tract in the Western literature. Awareness of this rare entity in GI tract is essential for correct diagnosis and appropriate patient management.
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