Oral Candida colonization in patients with chronic periodontitis. Is there any relationship?

Background

Candida can be implicated in the pathology of chronic periodontitis.

Is there a relationship between branched amino acid pool size and cell cycle inhibition in roots treated with imidazolinone herbicides?

Excised pea root tips were cultured in White's medium for 24 h and then treated for 12 h with one of the imidazolinone herbicides at 0.2, 2, 20, or 200 M. Pursuit and Assert were almost ineffective in inhibiting the mitotic index (MI), except at the highest concentrations. Arsenal (ARS) and Scepter both showed good inhibition with 20 M by 8 h. Adding all three branched amino acids (BAA) (VAL, ILE, and LEU) at 0.1 mM blocked herbicide action. Treatment with the BAAs singly had no protective effect. Experiments were performed to determine the BAA pool size and MI after an 8-h treatment with ARS at 2 and 200 M and Chlorsulfuron (CS), a sulfonylurea herbicide, at 28 nM. Both CS and ARS at 200 M inhibited the MI to almost 0 by 8 h. ARS at 2 M inhibited the MI by about 40%. The BAA pool size in all three treatments was reduced by approximately 50%, whether the MI was totally blocked or not. The 1-mm root tips had a greater amount of VAL than did the mature portions of the roots, whereas ILE and LEU were slightly less in the root tip. Other soluble amino acids did not show consistent differences between herbicide-treated roots and controls. The implications of the pool size reduction, in instances where the MI was not totally inhibited, is discussed in light of new data from other laboratories on the mode of action of the imidazolinone herbicides.     

Is there a special function for U.G basepairs in ribosomal RNA?

U.G basepairs are well-established elements of RNA structure. The geometry of this pair is different, however, from classical Watson-Crick basepairs. This leads to an unusual stacking of the basepair: overlap with the basepair at the 5' side of the U (and the 3' side of the G) is strong (stacked) while it is weak with the basepair on the other side (destacked). The closure of an RNA helix by a U.G pair will be energetically unfavourable when the U residue occupies the 5' end. In transfer RNA there is a strong selection against a 'destacked' U.G pair at helix ends. In the 16S rRNA model of Escherichia coli there are 72 U.G pairs of which 36 or 22 occupy a helix end, depending on how such an end is defined. There is a slight preference for 'stacked' U.G's in these positions. It is remarkable, however, that of 13 very conserved U.G pairs in the 16S (-like) rRNA, 7 occur at helix ends and that 5 of these have the 'destacked' configuration. It is suggested that these pairs, if they exist at all in a hydrogen-bounded form, are stabilized by co-axial stacking with other helices or by interaction with a protein.     

EGFR gene amplification in glioblastomas. Is there a relationship with morphology of tumor cell nuclei and proliferative activity?

OBJECTIVE: To confirm a relationship between histomorphology of glioblastomas and amplification of the gene for the epidermal growth factor receptor (EGFR) as the most important molecular biologic alteration in these tumors. STUDY DESIGN: In paraffin sections of surgical specimens from 71 primary resected glioblastomas, tumor cell nuclei in the region with the highest proliferative activity (Ki-67 immunostaining) were investigated morphometrically. Shape variables (roundness factor, Fourier amplitudes) and nuclear area were measured. Additionally, the numerical density of Ki-67-positive tumor cell nuclei was estimated. Differential polymerase chain reaction (PCR) was performed from paraffin sections of the same tumor area. The signals for the EGFR gene and IFN gamma reference gene were quantified densitometrically. RESULTS: Cases with distinct EGFR gene amplification (EGFR/IFN ratios > 5) revealed significantly lower mean values for several Fourier amplitudes, indicating a more regular nuclear shape when compared with cases without evidence of EGFR gene amplification (EGFR/IFN-ratios < or = 1). The Ki-67 index and nuclear area showed no significant differences between these groups. Although a large variation in nuclear morphology was observed for cases without evidence of EGFR gene amplification, discriminant analysis based on morphometric variables provided a good separation of these cases from cases with distinct EGFR gene amplification, with a high percentage of statistically correct reclassified cases. CONCLUSION: Our results provide evidence of a relationship between genetic alterations and histomorphology of glioblastomas.     

Dietary supplementation with antioxidants. Is there a case for exceeding the recommended dietary allowance?

The containment of damaging oxygen species by antioxidant nutrients has led to the speculation that the RDA for these specific nutrients may be overly low. Among these nutrients are vitamin E, vitamin C, and to a lesser extent beta-carotene and selenium. Evidence for the role of these nutrients in cancer and heart disease is evaluated. The case is presented for an increase of two-fold for the vitamin C RDA and between three and five-fold for vitamin E; for establishing 15 mg as the RDA for beta-carotene; for no change in the vitamin A RDA; and for further study on selenium.     

Is there a plasma membrane-located anion-sensitive ATPase? III. Identity of the erythrocyte enzyme with (Ca2+ + Mg2+)-ATPase.

The characteristics of the anion-sensitive Mg2+-ATPase activity of the rabbit erythrocyte have been studied in a lyophilized ghost preparation. The enzyme appears to be different from the anion-sensitive Mg2+-ATPase activity of other tissues in many parameters, such as optimal pH, effects of various anions, oligomycin sensitivity and effects of Triton X-100. The enzyme is insensitive towards inhibition by irreversibly bound 4,4'-diisothiocyano-dihydrostilbene-2,2'-disulfonic acid (H2DIDS). This excludes a relationship between the enzyme and the "band 3" protein, which is thought to be involved in the anion exchange over the erythrocyte membrane. From the effects of ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA), CaCl2, chlorpromazine and ruthenium red it is concluded that the enzyme activity does not represent a separate entity but is part of the (Ca2+ + Mg2+)-ATPase system of the erythrocyte membrane. A reported stimulatory effect of carbonic anhydrase is attributed to a contamination of the carbonic anhydrase preparation by calcium and/or (Ca2+ + Mg2+)-ATPase activator protein.     

The synaptic protein neuroligin-1 interacts with the amyloid β-peptide. Is there a role in Alzheimer's disease?

Amyloid β-peptide (Aβ) is the main component of the amyloid plaques associated with Alzheimer's disease (AD). In the early steps of the disease soluble Aβ oligomers are produced. According to the current "amyloid hypothesis" these oligomers can accumulate over time, leading progressively to the loss of synaptic function and the cognitive failure characteristic of AD. To understand the role of oligomeric Aβ species in AD pathology, it is important to understand the mechanism by which Aβ oligomers are targeted to synaptic junction. We report here the interaction between Aβ with neuroligin-1 (NL-1), a postsynaptic cell-adhesion protein specific for excitatory synapses, which shares a high degree of similarity with acetylcholinesterase, the first synaptic protein described to interact with Aβ. Using intrinsic fluorescence and surface plasmon resonance, we found that Aβ binds to the extracellular domain of NL-1 with a K(d) in the nanomolar range. In the case of NL-2, a postsynaptic cell-adhesion protein specific for inhibitory synapses, just a very weak interaction with Aβ was observed. Aβ polymerization analysis-studied by thioflavin-T assay and electron microscopy-indicated that NL-1 stabilized Aβ aggregates in vitro. Moreover, NL-1 acts as a nucleating factor during the Aβ aggregation process, stimulating the formation of Aβ oligomers. Besides, immunoprecipitation assays confirm that Aβ oligomers interact with NL-1 but not with NL-2. In conclusion, our results show that NL-1 interacts with Aβ increasing the formation of Aβ oligomers, suggesting that this interaction could triggers the targeting of Aβ oligomer to the postsynaptic regions of excitatory synapses.     

Mechanism of adenylate kinase. Is there a relationship between local substrate dynamics, local binding energy, and the catalytic mechanism?

Adenylyl (beta,gamma-methylene)diphosphonic acid (AMPPCP) labeled with deuterium at the adenine ring ([8-2H]AMPPCP) and at the beta,gamma-methylene group (AMPPCD2P), as well as adenosine 5'-monophosphate labeled at the adenine ring ([8-2H]AMP), was synthesized and used for deuterium nuclear magnetic resonance (NMR) determination of effective correlation times (tau c) of the free nucleotide and the complexes with adenylate kinase (AK). Extensive and rigorous control experiments and theoretical analysis were performed to justify the validity of the experimental approaches, particularly the fast exchange condition, and the reliability of the tau c values obtained. For the free nucleotide, the results suggest that the phosphonate group of free AMPPCP possesses appreciable local mobility relative to the adenine ring and that complexation with Mg2+ greatly reduced such a local mobility. For the complexes with AK, effective tau c values of 7, 15, 28, 28, and 27 ns were obtained for AMPPCD2P, MgAMPPCD2P, [8-2H]AMPPCP, Mg[8-2H]AMPPCP, and [8-2H]AMP, respectively. These results suggest that the adenine ring of substrates is rigidly bound in all cases, that the phosphonate chain of AMPPCP possesses considerable local mobility, and that Mg2+ reduces such local mobility but does not totally immobilize it. The local dynamics of the analogues bound to AK was correlated with local binding energies for the binding of MgAMPPCP and MgATP to AK estimated from the binding studies by proton NMR and other techniques, in conjunction with the binding theory of Jencks [Jencks, W. P. (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 4046-4050]. The results suggest that no general correlation exists between the local rigidity of portions of a bound substrate and the corresponding (ground state) local binding energy contributed by these portions. In particular, the adenosine moiety contributes little to the binding energy despite the fact that the adenine ring is rigidly bound; the triphosphate (PPPi) moiety behaves oppositely; Mg2+ immobilizes the triphosphate chain but does not enhance binding. Finally, isomers of the substitution-inert beta,gamma-bidentate Cr(III) complexes of adenosine 5'-triphosphate (CrATP) were used to probe two unresolved catalytic problems implicitly related to the local mobility of the phosphonate chain of AMPPCP in the AK-MgAMPPCP complex. The first problem concerns the result of electron paramagnetic resonance (EPR) studies that (Rp)- but not (Sp)-[beta-17O]ATP caused a line broadening in the Mn(II) EPR spectrum of the AK-MnATP complex [Kalbitzer, H. R., Marquetant, R., Connolly, B. A., & Goody, R. S. (1983) Eur. J. Biochem. 133, 221-227].(ABSTRACT TRUNCATED AT 400 WORDS)     

Evolution and diversification of Group 1 [NiFe] hydrogenases. Is there a phylogenetic marker for O(2)-tolerance?

Group 1 hydrogenases are periplasmic enzymes and are thus strongly affected by the "outside world" the cell experiences. This exposure has brought about an extensive heterogeneity in their cofactors and redox partners. Whereas in their majority they are very O(2)-sensitive, several enzymes of this group have been recently reported to be O(2)-tolerant. Structural and biochemical studies have shown that this O(2)-tolerance is conferred by the presence of an unusual iron-sulfur cofactor with supernumerary cysteine ligation (6 instead of 4 Cys, hence called '6C cluster'). This atypical cluster coordination affords redox plasticity (i.e. two-redox transitions), unprecedented for this type of cofactors and likely involved in resistance to O(2). Genomic screening and phylogenetic tree reconstruction revealed that 6C hydrogenases form a monophyletic clade and are unexpectedly widespread among bacteria. However, several other well-defined clades are observed, which indicate early diversification of the enzyme into different subfamilies. The various idiosyncrasies thereof are shown to comply with a very simple rule: phylogenetic grouping of hydrogenases directly correlates with their specific functions and hence biochemical characteristics. The observed variability results from gene duplication, gene shuffling and subsequent adaptation of the diversified enzymes to specific environments. An important factor for this diversification seems to have been the emergence of molecular oxygen. Hydrogenases appear to have dealt with oxidative stress in various ways, the most successful of which, however, was the innovation of the 6C-cluster conferring pronounced O(2)-tolerance to the parent enzymes.     

Is type 2 diabetes mellitus a vascular disease (atheroscleropathy) with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress.

Background

The impressive correlation between cardiovascular disease and glucose metabolism alterations has raised the likelihood that atherosclerosis and type 2 diabetes may share common antecedents. Inflammation is emerging as a conceivable etiologic mechanism for both. Interleukins are regulatory proteins with ability to accelerate or inhibit inflammatory processes.

Presentation of the hypothesis

A novel interleukins classification is described, based on their role in diabetes and atherosclerosis, hypothesizing that each interleukin (IL) acts on both diseases in the same direction – regardless if harmful, favorable or neutral.

Testing the hypothesis

The 29 known interleukins were clustered into three groups: noxious (the "bad", 8 members), comprising IL-1, IL-2, IL-6, IL-7, IL-8, IL-15, IL-17 and IL-18; protective (the "good", 5 members), comprising IL-4, IL-10, IL-11, IL-12 and IL-13; and "aloof", comprising IL-5, IL-9, IL-14, IL-16 and IL-19 through IL-29 (15 members). Each group presented converging effects on both diseases. IL-3 was reluctant to clustering.

Implications

These observations imply that 1) favorable effects of a given IL on either diabetes or atherosclerosis predicts similar effects on the other; 2) equally, harmful IL effects on one disease can be extrapolated to the other; and 3) absence of influence of a given IL on one of these diseases forecasts lack of effects on the other. These facts further support the unifying etiologic theory of both ailments, emphasizing the importance of a cardiovascular diabetologic approach to interleukins for future research. Pharmacologic targeting of these cytokines might provide an effective means to simultaneously control both atherosclerosis and diabetes.