Genetic variability, evolution, and biological effects of Grapevine fanleaf virus satellite RNAs.

Large satellite RNAs (type B satRNAs) of Grapevine fanleaf virus (GFLV) from the genus Nepovirus, family Secoviridae were identified in a naturally infected vineyard and a grapevine germplasm collection. These GFLV satRNA variants had a higher nucleotide sequence identity with satRNAs of Arabis mosaic virus (ArMV) strains NW and J86 (93.8 to 94.6%) than with the satRNA of GFLV strain F13 and those of other ArMV strains (68.3 to 75.0%). Phylogenetic analyses showed no distinction of GFLV and ArMV satRNAs with respect to the identity of the helper virus. Seven stretches of 8 to 15 conserved nucleotides (I-VII) were identified in the 5' region of subgroup A nepovirus genomic RNAs GFLV, ArMV, and Grapevine deformation virus) and nepovirus type B satRNAs, including previously reported motif I, suggesting that large satRNAs might have originated from recombination between an ancestral subgroup A nepovirus RNA and an unknown RNA sequence with the 5' region acting as a putative cis-replication element. A comparative analysis of two GFLV strains carrying or absent of satRNAs showed no discernable effect on virus accumulation and symptom expression in Chenopodium quinoa, a systemic herbaceous host. This work sheds light on the origin and biological effects of large satRNAs associated with subgroup A nepoviruses.

Dynamic scaling in the susceptibility of the spin-1/2 kagome lattice antiferromagnet herbertsmithite.

The spin-1/2 kagome lattice antiferromagnet herbertsmithite, ZnCu(3)(OH)(6)Cl(2), is a candidate material for a quantum spin liquid ground state. We show that the magnetic response of this material displays an unusual scaling relation in both the bulk ac susceptibility and the low energy dynamic susceptibility as measured by inelastic neutron scattering. The quantity chiT(alpha) with alpha approximately 0.66 can be expressed as a universal function of H/T or omega/T. This scaling is discussed in relation to similar behavior seen in systems influenced by disorder or by the proximity to a quantum critical point.

Safety, efficacy & recurrence rates of imiquimod cream 5% for treatment of anogenital warts.

Imiquimod 5% cream (Aldara, Graceway Pharmaceuticals) is an immune response modifier used for the topical treatment of anogenital warts in non-HIV-infected patients. Several randomized controlled trials have demonstrated that imiquimod 5% cream is a safe and efficacious treatment. Current data regarding efficacy shows that complete clearance of warts occurred in up to 50% of patients treated with imiquimod 5% cream applied once-daily, 3 times per week for up to 16 weeks. Recurrence rates ranged from up to 19% at 3 months to 23% at 6 months. Imiquimod 5% cream showed an acceptable safety profile; local inflammatory reactions were the most frequent adverse effects, with local erythema being the most common.

Practical management measures for patients with recurrent herpes labialis.

Recurrent herpes labialis (RHL) is a common condition associated with the formation of vesicles around the mouth, often preceded by prodromal symptoms including tingling and burning. Treatment is targeted toward individual episodes, but in severe cases, suppressive therapy may be indicated. At present, no cure exists for this troublesome condition. The purpose of this article is to serve as a practical guide in the management of RHL by summarizing current treatments and discussing potential new therapies.

63Cu, 35Cl, and 1H NMR in the S=1/2 Kagome lattice ZnCu3(OH)6Cl2.

ZnCu(3)(OH)(6)Cl(2) (S=1/2) is a promising new candidate for an ideal Kagome Heisenberg antiferromagnet, because there is no magnetic phase transition down to approximately 50 mK. We investigated its local magnetic and lattice environments with NMR techniques. We demonstrate that the intrinsic local spin susceptibility decreases toward T=0, but that slow freezing of the lattice near approximately 50 K, presumably associated with OH bonds, contributes to a large increase of local spin susceptibility and its distribution. Spin dynamics near T=0 obey a power-law behavior in high magnetic fields.

IL-12/IL-23 inhibitors: the advantages and disadvantages of this novel approach for the treatment of psoriasis.

Psoriasis is a common chronic inflammatory skin disease that is mediated, in part by the body's T-cell inflammatory response mechanisms. Further insight into the pathogenesis of the disease and the role of various cytokines, particularly interleukin(IL)-12 and IL-23, has led to advances in the treatment of this disease. A relatively new class of drugs that inhibit these interleukins is being developed and studied. Current data regarding the efficacy of these agents show they may have the potential to become the new clinical gold standard for biologic therapy to treat psoriasis.

Dermatological management of human immunodeficiency virus (HIV).

Atypical presentations of typical dermatological conditions are common in human immunodeficiency virus (HIV). This article will focus on three specific topics: eosinophilic folliculitis, psoriasis, and cutaneous mycoses. Their unique presentations in HIV and treatments are discussed.

Spin dynamics of the spin-1/2 kagome lattice antiferromagnet ZnCu3(OH)6Cl2.

We have performed thermodynamic and neutron scattering measurements on the S=1/2 kagomé lattice antiferromagnet ZnCu3(OH)6Cl2. The susceptibility indicates a Curie-Weiss temperature of theta CW approximately = -300 K; however, no magnetic order is observed down to 50 mK. Inelastic neutron scattering reveals a spectrum of low energy spin excitations with no observable gap down to 0.1 meV. The specific heat at low-T follows a power law temperature dependence. These results suggest that an unusual spin liquid state with essentially gapless excitations is realized in this kagomé lattice system.

Nonperturbative flow equations from running expectation values.

We show that Wegner's flow equations, as recently discussed in the Lipkin model, can be solved self-consistently. This leads to a nonlinear differential equation which fully determines the order parameter as a function of the dimensionless coupling constant, even across the phase transition. Since we consider an expansion in the fluctuations, rather than the conventional expansion in the coupling constant, convergence to the exact results is found in both phases when taking the thermodynamic limit.

Education and certification influence the nutrition and management knowledge of long-term-care foodservice managers.

OBJECTIVES: To describe nutrition knowledge, attitude toward nutrition, and management knowledge of long-term-care foodservice managers and to determine the relationship between these variables and the foodservice managers' personal and facility characteristics. DESIGN: Nutrition knowledge, management knowledge, and attitudes toward nutrition were measured using survey methodology designed for this study by modifying an instrument developed by the Nutrition Education Training Program for the Texas Department of Human Services. SUBJECTS/SETTING: Surveys were mailed to a random sample of 300 long-term-care foodservice directors from the 1,092 directors listed in the 1996 Ohio Department of Health Directory of Nursing Homes. The participants were 123 of the 300 foodservice directors (41%). STATISTICAL ANALYSES PERFORMED: Descriptive statistics, Spearman rank correlations, 1-way analysis of variance, and post hoc variance were calculated. RESULTS: Mean scores of respondents were 21.2 out of a possible 29 (73%) for the nutrition knowledge assessment, and 18.2 out of 26 (70%) for management knowledge. Dietitians and dietetic technicians scored significantly better than others on these tests. The mean score of attitudes toward nutrition was 4 on a 5-point scale (where 1 = strongly disagree to 5 = strongly agree). All participants requested more training in computers, nutrition terminology, and preparing appealing foods. APPLICATIONS: Dietitians and dietetic technicians are prepared with a wide scope of knowledge in nutrition and management. Thus, they are in an ideal position to take advantage of job opportunities in the area of foodservice management.

On the control of oocyte meiotic maturation and ovulation in Caenorhabditis elegans.

Prior to fertilization, oocytes undergo meiotic maturation (cell cycle progression) and ovulation (expulsion from the ovary). To begin the study of these processes in Caenorhabditis elegans, we have defined a time line of germline and somatic events by video microscopy. As the oocyte matures, its nuclear envelope breaks down and its cell cortex rearranges. Immediately thereafter, the oocyte is ovulated by increasing contraction of the myoepithelial gonadal sheath and relaxation of the distal spermatheca. By systematically altering the germ cell contents of the hermaphrodite using mutant strains, we have uncovered evidence of four cell-cell interactions that regulate maturation and ovulation. (1) Both spermatids and spermatozoa induce oocyte maturation. In animals with a feminized germline, maturation is inhibited and oocytes arrest in diakinesis. The introduction of sperm by mating restores maturation. (2) Sperm also directly promote sheath contraction. In animals with a feminized or tumorous germline, contractions are infrequent, whereas in animals with a masculinized germline or with sperm introduced by mating, contractions are frequent. (3 and 4) The maturing oocyte both induces spermathecal dilation and modulates sheath contractions at ovulation; dilation of the distal spermatheca and sharp increases in sheath contraction rates are only observed in the presence of a maturing oocyte.

Activation of p38MAPK in microglia after ischemia.

p38MAPK has been implicated in the regulation of proinflammatory cytokines and apoptosis in vitro. To understand its role in neurodegeneration, we determined the time course and localization of the dually phosphorylated active form of p38MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38MAPK and mitogen-activated protein kinase-activated protein 2 activity increased over 4 days after ischemia. Phosphorylated p38MAPK immunoreactivity was observed in microglia in regions adjacent to, but not in, the dying CA1 neurons. In contrast, neither c-Jun N-terminal kinase 1 nor p42/p44MAPK activity was altered after ischemia. These results provide the first evidence for localization of activated p38MAPK in the CNS and support a role for p38MAPK in the microglial response to stress.

Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway.

Neurons undergoing apoptosis can be rescued by trophic factors that simultaneously increase the activity of extracellular signal-regulated kinase (ERK) and decrease c-Jun N-terminal kinase (JNK) and p38. We identified a molecule, CEP-1347 (KT7515), that rescues motoneurons undergoing apoptosis and investigated its effect on ERK1 and JNK1 activity. Cultured rat embryonic motoneurons, in the absence of trophic factor, began to die 24-48 hr after plating. During the first 24 hr ERK1 activity was unchanged, whereas JNK1 activity increased fourfold. CEP-1347 completely rescued motoneurons for at least 72 hr with an EC50 of 20 +/- 2 nM. CEP-1347 did not alter ERK1 activity but rapidly inhibited JNK1 activation. The IC50 of CEP-1347 for JNK1 activation was the same as the EC50 for motoneuron survival. Inhibition of JNK1 activation by CEP-1347 was not selective to motoneurons. CEP-1347 also inhibited JNK1 activity in Cos7 cells under conditions of ultraviolet irradiation, osmotic shock, and inhibition of glycosylation. Inhibition by CEP-1347 of the JNK1 signaling pathway appeared to be selective, because CEP-1347 did not inhibit p38-regulated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP2) activity in Cos7 cells subjected to osmotic shock. The direct molecular target of CEP-1347 was not JNK1, because CEP-1347 did not inhibit JNK1 activity in Cos7 cells cotransfected with MEKK1 and JNK1 cDNA constructs. This is the first demonstration of a small organic molecule that promotes motoneuron survival and that simultaneously inhibits the JNK1 signaling cascade.

Comparative evaluation of body composition in medically stable elderly.

OBJECTIVE: Accurate assessment is needed to identify the nutritional status of elderly persons. Anthropometric data were collected to describe body composition of the sample, including blacks and whites aged 55 to 89 years, and to explore the usefulness of several methods of body composition measurement. DESIGN: Baseline measurements were made as part of a longitudinal study. Body composition variables, particularly lean and lean-to-height measures, were used. SUBJECTS/SETTING: One hundred twenty-nine free-living medically stable elderly at senior community centers were self-selected into the study. STATISTICAL ANALYSIS: Descriptive statistics were generated for all variable by gender, race, and age (< 65, 65 to 74, and > or = 75 years). Actual height was correlated with estimated height using published equations. Analysis of variance revealed the effect of gender, race, or age on outcome variables. RESULTS: White women, black women, and white men made up 54%, 23%, and 23% of the sample, respectively. Most gender differences were expected. Black women had greater weight, body mass index, arm muscle circumference, and ratio of lean to height but lower percent lean body mass than white women. Subjects over 75 years old were shorter, lighter, and had lower ratio of lean to height. Gender and age had the greatest effect on ratio of lean to height. CONCLUSIONS/APPLICATIONS: A lean-to-height index appears to be a useful tool for tracking the status of lean mass in the elderly. Knee height may be especially useful because it, unlike stature, does not decrease with age. Furthermore, some published equations for estimating stature from knee height need adjustment, specifically for elderly black women.

[3Fe-4S] <--> [4Fe-4S] cluster interconversion in Desulfovibrio africanus ferredoxin III: properties of an Asp14 --> Cys mutant.

The 8Fe ferredoxin III from Desulfovibrio africanus is a monomeric protein which contains two [4Fe-4S]2+/1+ clusters, one of which is labile and can readily and reversibly lose one Fe under oxidative conditions to yield a [3Fe-4S]1+/0 cluster. This 4Fe cluster has an S = 3/2 ground sping state insteaed of S = 1/2 in the reduced +1 state [George, Armstrong, Hatchikian and Thomson (1989) Biochem. J. 264, 275-284]. The co-ordination to this cluster is unusual in that an aspartate (Asp14, D14, is found where a cysteine residue normally occurs. Using a mutant protein obtained from the overexpression in Escherichia coli of a synthetic gene in which Asp14, the putative ligand to the removable Fe, has been changed to Cys, we have studied the cluster interconversion properties of the labile cluster. Analysis by EPR and magnetic-circular-dichroism spectroscopies showed that the Asp14 --> Cys (D14C) mutant contains two [4Fe-4S]2+/1+ clusters, both with S = 1/2 in the reduced state. Also, unlike in native 8Fe D. africanus ferredoxin III, the 4Fe <--> 3Fe cluster interconversion reaction was found to be sluggish and did not go to completion. It is inferred that the reversibility of the reaction in the native protein is due to the presence of the aspartate residue at position 14 and that this residue might protect the [3Fe-4S] cluster from further degradation.

Soma-germ cell interactions in Caenorhabditis elegans: multiple events of hermaphrodite germline development require the somatic sheath and spermathecal lineages.

Germ cells complete multiple events to form functional oocytes and sperm. In the Caenorhabditis elegans hermaphrodite, germ cells develop in proximity to the somatic gonad sheath and spermathecal cells. We present evidence from cellular laser ablation studies indicating that cells of the somatic sheath and spermathecal lineages play critical roles in four events of hermaphrodite germline development. (1) Cells of the sheath and spermathecal lineage support germline proliferation; ablation of sheath/spermathecal precursor cells reduces mitotic proliferation. (2) These cells also play a role in the exit of germ cells from the pachytene stage of meiotic prophase and/or gamete differentiation; ablation can result in undifferentiated germ cells arrested in pachytene. (3) Proximal sheath and distal spermatheca cells are required for ovulation of the oocyte. During wild-type ovulation, the mature oocyte is expelled from the gonad arm by contraction of the proximal myoepithelial sheath and dilation of the distal spermatheca. Ablation of these cells traps mature oocytes in the gonad arm where they endomitotically replicate their DNA (the Emo phenotype). (4) Cells of the sheath and spermathecal lineage also appear to promote the male germ cell fate since ablation of one sheath/spermathecal precursor cell can feminize the hermaphrodite germ line. These somatic ablation-induced germline phenotypes demonstrate that the somatic gonad is required for multiple events in C. elegans germline development. Further, these results suggest that soma to germline cell-cell interactions in C. elegans are physiological in character (i.e., contraction during ovulation) as well as regulatory.

Enzyme-linked immunosorbent assay for trkA tyrosine kinase activity.

A 96-well microtiter enzyme-linked immunosorbent assay was developed to assay the activity of the cytoplasmic domain of trkA tyrosine kinase. The assay involves immobilization of phospholipase C- gamma/glutathione S-transferase fusion protein on a microtiter plate, addition of the kinase reaction mixture, and detection by an antibody to phosphotyrosine followed by an alkaline phosphatase-conjugated second antibody. The substrate used in this system, phospholipase C-gamma, is one of several biologically important substrates for the phosphorylation reaction of receptor-linked tyrosine kinases. The assay was then used to characterize kinase inhibitory activities of various small molecules including analogs of K-252a.

Expression in Escherichia coli and characterization of a reconstituted recombinant 7Fe ferredoxin from Desulfovibrio africanus.

Desulfovibrio africanus ferredoxin III is a monomeric protein (molecular mass of 6585 Da) that contains one [3Fe-4S]1+/0 and one [4Fe-4S]2+/1+ cluster when isolated aerobically. The amino acid sequence consists of 61 amino acids, including seven cysteine residues that are all involved in co-ordination to the clusters. In order to isolate larger quantities of D. africanus ferredoxin III, we have overexpressed it in Escherichia coli by constructing a synthetic gene based on the amino acid sequence of the native protein. The recombinant ferredoxin was expressed in E. coli as an apoprotein. We have reconstituted the holoprotein by incubating the apoprotein with excess iron and sulphide in the presence of a reducing agent. The reconstituted recombinant ferredoxin appeared to have a lower stability than that of wild-type D. africanus ferredoxin III. We have shown by low-temperature magnetic circular dichroism and EPR spectroscopy that the recombinant ferredoxin contains a [3Fe-4S]1+/0 and a [4Fe-4S]2+/1+ cluster similar to those found in native D. africanus ferredoxin III. These results indicate that the two clusters have been correctly inserted into the recombinant ferredoxin.

Intravenous site care practices in critical care: a national survey.

OBJECTIVE: To collect and compare written procedures for central line intravenous site care. DESIGN: Descriptive, stratified, random sample survey. SETTING: Adult medical-surgical critical care units among hospitals throughout the United States. SAMPLE: One hundred fifty-two returned surveys. RESULTS: A 24.6% response rate with underrepresentation from smaller institutions and hospitals in the Mid-Atlantic and West South Central regions of the country. There were wide variations in procedures for intravenous site care related to type of dressing used and frequency of dressing changes. CONCLUSIONS: Standardization of catheter care is needed to ensure consistent quality of intravenous site care. Lack of standardization may be due to lack of a research data base linking various components of care to outcomes such as infection, patient comfort, or catheter retention.