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The resistance of a diverse range of Trifolium species (clovers) to a highly virulent bluegreen aphid (BGA, Acyrthosiphon kondoi Shinji) population (Urrbrae 2011) collected in South Australia was assessed in greenhouse and field experiments, with the aims of determining the potential impact of this insect pest on biomass and identifying resistant genotypes for future plant-breeding activities. Resistance to BGA was found in populations of clovers that show some level of outcrossing—white clover (T. repens L.), rose clover (T. hirtum All.), crimson clover (T. incarnatum L.) and red clover (T. pratense L.)—and in one entry of the inbreeding subspecies of subterranean clover, T. subterraneum L. subsp. subterraneum (Katzn. and Morley). Resistance was not found in T. s. brachycalycinum (Katzn. and Morley) or T. s. yanninicum (Katzn. and Morley). In a greenhouse experiment, damage from BGA resulted in forage yield penalties of 72–100% when aphids were inoculated at 14 days after sowing and 13-74% when inoculated at 42 days after sowing, showing that in optimum conditions BGA can be a serious pest of clovers. Observations of severe damage caused by BGA in two regenerating field trials in southern New South Wales confirmed that field damage could occur in seasons favourable to aphid growth and reproduction. The severe damage that BGA can cause to clovers, and the sources of resistance we found, suggest that breeding for BGA resistance in clovers is warranted and feasible.

A new bluegreen aphid biotype (BGA, Acyrthosiphon kondoi Shinji) has been found in south-eastern Australia that causes severe damage and mortality in seedlings of previously resistant pasture legume cultivars. Populations of BGA collected at Urrbrae and Binnum, SA in 2009 caused 100% mortality in 29 cultivars of annual and perennial Medicago spp. and annual Trifolium spp. Delaying inoculation from the first trifoliate to the 6–8 trifoliate stage and removing susceptible genotypes from experiments had no impact on reducing mortality from 100% in previously resistant barrel medics. A half-sib family of lucerne from the SARDI breeding program has maintained resistance to the Urrbrae 2009 BGA. A detailed study of the virulence of BGA populations collected from Toowoomba (Qld), Tamworth, Howlong (NSW), Launceston (Tas.), Colebatch, Kimba, Urrbrae and Vivonne Bay (SA) in 2010–11 on 33 pasture legumes provides evidence of new virulent BGA being widespread, despite these populations causing less severe damage and mortality than the two populations collected in 2009.

Avian influenza A viruses are the ancestral origin of all human influenza viruses. The outbreak of highly pathogenic (HP) avian H5N1 in Hong Kong in 1997 highlighted the potential of these viruses to infect and cause severe disease in humans. Since 1999, HP H5N1 viruses were isolated several times from domestic poultry in Asia. In 2001, a HP H5N1 virus, A/Duck/Anyang/AVL‐1/2001 (Dk/Anyang), was isolated from imported frozen duck meat in Korea. Because of this novel source of HP H5N1 virus isolation, concerns were raised about the potential for human exposure and infection; we therefore compared the Dk/Anyang virus with HP H5N1 viruses isolated from humans in 1997 in terms of antigenicity and pathogenicity for mammals. At high doses, Dk/Anyang virus caused up to 50% mortality in BALB/c mice, was isolated from the brains and lymphoid organs of mice, and caused lymphopenia. Overall Dk/Anyang virus was substantially less pathogenic for mice than the H5N1 virus isolated from a fatal human case in 1997. Likewise, Dk/Anyang virus was apathogenic for ferrets. Dk/Anyang virus was antigenically distinguishable by hemagglutination‐inhibition (HI) assay from human H5N1 viruses isolated in 1997 and avian H5N1 viruses isolated in 2001 in Hong Kong. Nevertheless, prior infection with Dk/Anyang virus protected mice from death after secondary infection with HP human H5N1 viruses. These results indicate that compared with HP human H5N1 viruses, Dk/Anyang virus is substantially less pathogenic for mammalian species. Nevertheless, the novel source of isolation of this avian H5N1 virus must be considered when evaluating the potential risk to public health. J. Med. Virol. 69:553–559, 2003. © 2003 Wiley‐Liss, Inc.

2-5(A) synthetases are a family of interferon-induced enzymes that polymerize ATP into 2'-5' linked oligoadenylates that activate RNase L and cause mRNA degradation. Because they all can synthesize 2-5(A), the reason for the existence of so many synthetase isozymes is unclear. Here we report that the 9-2 isozyme of 2-5(A) synthetase has an additional activity: it promotes apoptosis in mammalian cells. The proapoptotic activity of 9-2 was isozyme-specific and enzyme activity-independent. The 9-2-expressing cells exhibited many properties of cells undergoing apoptosis, such as DNA fragmentation, caspase activation, and poly ADP-ribose polymerase and lamin B cleavage. The isozyme-specific carboxyl-terminal tail of the 9-2 protein was shown, by molecular modeling, to contain a Bcl-2 homology 3 (BH3) domain, suggesting that it may be able to interact with members of the Bcl-2 family that contain BH1 and BH2 domains. Co-immunoprecipitate assays and confocal microscopy showed that 9-2 can indeed interact with the anti-apoptotic proteins Bcl-2 and Bclx(L) in vivo and in vitro. Mutations in the BH3 domain that eliminated the 9-2-Bcl-2 amd 9-2-Bclx(L) interactions also eliminated the apoptotic activity of 9-2. Thus, we have identified an interferon-induced dual function protein of the Bcl-2 family that can synthesize 2-5(A) and promote cellular apoptosis independently. Moreover, the cellular abundance of this protein is regulated by alternative splicing; the other isozymes encoded by the same gene are not proapoptotic.

Abstract:  In darkness, hamsters commute between their nest and a feeding site through path integration only, and therefore show cumulative errors in the return direction to the nest. We examined whether a brief presentation of familiar room cues could reset the path integrator. The hamsters could see the room cues either during, or at the end of, the outward journey to the food place, in a conflict situation where motion cues and visual information were set at variance. In both conditions, the animals used mainly visual information to return home. Thus, hamsters can determine their azimuth, and possibly their location, through a visual fix, and can reset their path integrator through the fix. This allows them to update their position during further locomotion in the dark and thus to compute a correct homing vector with respect to a visually induced reference frame. Taking episodic positional fixes may greatly enhance the functional value of path integration.

AbstractPrevious work on the morphology of naturally coloured green suggested than that the secondary wall of the fibres consists of alternate layers of cellulose and a waxy organic substance called suberin. The work described in this paper has shown that modern varieties of green cotton do contain a large proportion of suberin. Data front fibre swelling is consistent with alternate layers of suberin and cellulose in the secondary wall. The naturally coloured fibres have a lower tenacity and work of rupture than conventional white fibres although they have an acceptable level of textile properties. The crystallinity of the coloured fibres is lower than for white cotton, but the cellulose has the cellulose I structure, normally found in cotton.

The structurally related somatic and germinal isoforms of angiotensin-converting enzyme (ACE) contain the same catalytic active center and are encoded by the same gene, whose disruption causes renal atrophy, hypotension, and male sterility. The reason for the evolutionary conservation of both isozymes is an enigma, because, in vitro, they have very similar enzymatic properties. Despite the common enzymatic properties, discrete expression of both isoforms is maintained in alternate cell types. We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace -/- male mice restores fertility without curing their other abnormalities (Ramaraj, P., Kessler, S. P., Colmenares, C. & Sen, G. C. (1998) J. Clin. Invest. 102, 371-378). In this report we tested the biological equivalence of somatic ACE and germinal ACE utilizing an in vivo isozymic substitution approach. Here we report that restoration of male fertility was not achieved by the transgenic expression of enzymatically active, somatic ACE in the sperm of Ace -/- mice. Therefore, the requisite physiological functions of the two tissue-specific isozymes of ACE are not interchangeable.

The COPII coat complex found on endoplasmic reticulum (ER)-derived vesicles plays a critical role in cargo selection. We now address the potential role of biosynthetic cargo in modulating COPII coat assembly and vesicle budding. The ER accumulation of vesicular stomatitis glycoprotein (VSV-G), a transmembrane protein, or the soluble PiZ variant of alpha1-antitrypsin, reduced levels of general COPII vesicle formation in vivo. Consistent with this result, conditions that prevent the export of VSV-G from the ER led to a significant inhibition of general COPII vesicle budding from ER microsomes and the export of an endogenous recycling protein p58 in vitro. In contrast, synchronized export of VSV-G stimulated COPII vesicle budding both in vivo and in vitro. Under conditions where VSV-G is retained in the ER, we find that it can to be recovered in pre-budding complexes containing COPII components. These results suggest that the export of biosynthetic cargo is integrated with ER functions involved in protein folding and oligomerization. The ability of biosynthetic cargo to prevent or enhance ER export suggests that interactions of cargo with the COPII machinery contribute to the formation of vesicles budding from the ER.

The efficacy and safety of a new, low-dose, 21-day combination oral contraceptive containing 100 μg of levonorgestrel and 20 μg of ethinyl estradiol were evaluated in an open-label, multicentre trial. A total of 254 Canadian subjects were enrolled and received 4,564 cycles of exposure over the three-year course of the study. Of these, 137 completed 18 cycles of treatment. During the total 4,482 evaluable cycles of treatment, one pregnancy occurred, for a Pearl Index of 0.29 (82 cycles were excluded from this calculation due to protocol violations, including use of a second form of contraception or missing three or more consecutive pills in a cycle). Over the course of the study, 129 subjects withdrew for any reason, including 43 (17%) due to adverse events. The cumulative failure rate by life table analysis was 0.0048 per woman entering the 14th cycle. Breakthrough bleeding alone occurred in 3.9 percent of the cycles and breakthrough bleeding and spotting occurred together in 9.6 percent of the cycles. Of evaluable cycles, 1.3 percent were amenorrhoeic. The most commonly reported adverse events in this trial considered to be at least possibly due to the test drug were headache (36%) and metrorrhagia (36%). This formulation provides contraceptive efficacy similar to higher-dose oral contraceptives, while maintaining a safety and common OC side-effect profile that is consistent with prior years of reported use with kvonmgestrel-containing products.

In vertebrate smooth/non‐muscle myosins, phosphorylation of the regulatory light chains by a specific calmodulin‐activated kinase controls both myosin head interaction with actin and assembly of the myosin into filaments. Previous studies have shown that the C‐terminal domain of the regulatory light chain is crucial for the regulation of these myosin functions. To further dissect the role of this region of the light chain in myosin regulation, a series of chicken smooth muscle myosin regulatory light chain mutants has been constructed with successive C‐terminal deletions. These mutants were synthesized in Escherichia coli and analysed by their ability to restore Ca2+ regulation to scallop myosin that had been stripped of its native regulatory light chains (‘desensitized’). The results show that regulatory light chain mutants with deletions in the C‐terminal helix in subdomain 4 were able to reform the regulatory Ca2+ binding site on the scallop myosin head, but had lost the ability to suppress scallop myosin filament assembly and interaction with actin in the absence of Ca2+. Further deletions in the C‐terminal domain led to a gradual loss of ability to restore the regulatory Ca2+ binding site. Thus, the regions in the C‐terminal half of the regulatory light chain responsible for myosin regulation can be identified.

Regulatory light chains, located on the ‘motor’ head domains of myosin, belong to the family of Ca2+ binding proteins that consist of four ‘EF‐hand’ subdomains. Vertebrate regulatory light chains can be divided into two functional classes: (i) in smooth/non‐muscle myosins, phosphorylation of the light chains by a calcium/calmodulin‐dependent kinase regulates both interaction of the myosin head with actin and assembly of the myosin into filaments, (ii) the light chains of skeletal muscle myosins are similarly phosphorylated, but they play no apparent role in regulation. To discover the basis for the difference in regulatory properties of these two classes of light chains, we have synthesized in Escherichia coli, chimeric mutants composed of subdomains derived from the regulatory light chains of chicken skeletal and smooth muscle myosins. The regulatory capability of these mutants was analysed by their ability to regulate molluscan myosin. Using this test system, we identified the third subdomain of the regulatory light chain as being responsible for controlling not only the actin‐myosin interaction, but also myosin filament assembly.

Drug resistance to inhibitors of DNA topoisomerase II can result from qualitative or quantitative alterations in the target enzyme, topoisomerase II, or from perturbations in drug transport that may or may not involve P-glycoprotein. In the present study, a drug-resistant Chinese hamster ovary cell line, SMR16, was selected in the presence of an epipodophyllotoxin (VP-16) and was found to be cross-resistant to all classes of topoisomerase II inhibitors (3-35-fold). The 3-fold level of resistance of these cells to vincristine is likely due to diminished uptake of this drug, and this is not mediated by overexpression of P-glycoprotein. No alteration in transport of VP-16 was observed. Immunoblotting with several polyclonal anti-topoisomerase II antibodies demonstrated that the resistant cells contain approximately two-thirds of the parental enzyme amount. The topoisomerase II catalytic activity present in 0.35 M NaCl nuclear extracts paralleled this decrease. VP-16- and 4'-(9-acridinylamino)methanesulfon-m-anisidide-induced DNA damage, mediated by topoisomerase II, was found to be decreased 10-12-fold in both intact SMR16 cells and nuclei isolated from these cells, when measured by alkaline filter elution. However, the VP-16-induced DNA cleavage activity present in 0.35 M NaCl nuclear extracts of the resistant cells was attenuated only 2-fold, relative to wild-type cells. Homogeneous preparations of the enzyme obtained from resistant cells demonstrated the same cleavage and catalytic activity as purified wild-type topoisomerase II. Analysis by pulse-field gel electrophoresis of the DNA isolated from VM-26- and 4'-(9-acridinylamino)methanesulfon-m-anisidide-treated sensitive and resistant cells demonstrated significantly less conversion of SMR16 chromosomal DNA into 50-150-kilobase DNA fragments. Chinese hamster ovary SMR16 cells are apparently resistant to topoisomerase II poisons because the topoisomerase II that defines the DNA topological domains is either decreased in amount or insensitive to drug action.

Evaluation of 304 infertile couples with at least one abnormal semen analysis (sperm density < 20 x 10(6)/ml and/or motility < 50%) and no apparent female factors was performed in a multicentre prospective cohort study. In 73 cases therapeutic donor insemination was performed (TDI group) with a resulting pregnancy rate of 48%. The remaining 231 couples (non-TDI group) had an overall pregnancy rate of 25%. The TDI group had a shorter duration of infertility. The ages of both partners were comparable in TDI and non-TDI groups. In the non-TDI group, univariate analysis resulted in identification of six clinical variables associated with a change in pregnancy rates. The strongest association was noted for length of infertility. There was a weaker association for semen volume, concentration of leukocytes in semen, history of pregnancy in the female partner and laparoscopy. Multiple variable analysis of data from the non-TDI group revealed that independent predictors of pregnancy were 'duration of infertility' and 'history of pregnancy in the female partner'. The multiple variable modelling suggested that (i) an increase in the length of infertility by 1 month prolongs the time to pregnancy by an additional 1.6% (95% confidence interval: 1.5-1.7%); and (ii) a history of past pregnancy in the female partner reduces the time of pregnancy by 51% (95% confidence interval: 47-56%).

The Janus family of kinases (JAKs) has been shown to be involved in the signal transduction of a number of cytokine receptors. Recently, we have cloned a novel JAK family member, JAK3, that is expressed in natural killer and activated T cells and is coupled functionally and physically to the interleukin 2 (IL-2) receptor in these cells. Here we report that JAK3 was expressed at low but detectable levels in human monocytes. In contrast, JAK3 expression was strongly induced during activation by interferon gamma (IFN-gamma) or lipopolysaccharide. Moreover, JAK3 became tyrosine phosphorylated in response to IL-2, IL-4, and IL-7 but not response to IFN-gamma or granulocyte/macrophage colony-stimulating factor. Together, these findings suggest that JAK3 is functionally important in activated monocytes and cells of the myeloid lineage and is involved in signaling responses of cytokines that use the common gamma-chain of the IL-2 receptor.

We have previously shown that 4-quinolone drugs cause a selective loss of mitochondrial DNA (mtDNA) from mouse L1210 leukemia cells. The loss in mtDNA was associated with a delayed loss in mitochondrial function. Here, we report that the 4-quinolone drug ciprofloxacin is cytotoxic to a variety of cultured mammalian cell lines at concentrations that deplete cells of mtDNA. The IC50 values for ciprofloxacin varied from 40 to 80 micrograms/ml depending on the cell line tested. Cytotoxicity required continuous exposure of cells to drug for 2-4 days, which corresponded to approximately three or four cell doublings. Shorter times of drug exposure did not cause significant cytotoxicity. In addition, cells became drug resistant when they were grown under conditions that bypassed the need for mitochondrial respiration. Resistance was not due to a decrease in cellular drug accumulation, suggesting that ciprofloxacin cytotoxicity is caused by the loss of mtDNA-encoded functions. Analysis of mtDNA from ciprofloxacin-treated cells revealed the presence of site-specific, double-stranded DNA breaks. Furthermore, exonuclease protection studies indicated that the 5'-, but not the 3'-, ends of the drug-induced DNA breaks were tightly associated with protein. These results suggest that ciprofloxacin may be causing cytotoxicity by interfering with a mitochondrial topoisomerase II-like activity, resulting in a loss of mtDNA.

The angiotensin-converting enzyme (ACE) gene produces two mRNA species from tissue-specific promoters. The transcription start site of the mRNA for the smaller testicular isozyme (ACET) is located within an intron of the larger transcription unit that encodes the pulmonary isozyme (ACEP).We have previously demonstrated that a 298-base pair DNA fragment, 5' to the rabbit ACET mRNA transcription initiation site, can activate the testicular expression of a transgenic reporter gene. In the current study, using the same transgenic reporter system, we identified a putative cyclic AMP response element present within this DNA fragment to be absolutely essential for transcriptional activation. Moreover, we observed that ACET mRNA was not expressed in the testes of mice homozygous for a null mutation in the transcription factor CREM. However, in the same mice, ACEP mRNA was abundantly expressed in the lung. Our observations indicate that ACET mRNA expression in the testes is regulated by the putative cyclic AMP response element present 5' to the transcription start site and the corresponding transcription factor CREM.

Similar to its inhibitory effect on mammalian DNA topoisomerase II, the cytotoxic drug VM26 (teniposide) also interferes with the breakage-reunion reaction of Drosophila melanogaster DNA topoisomerase II. VM26 induces topoisomerase II-mediated DNA breakage in vitro and in cultured D. melanogaster cells presumably by stabilizing an enzyme-DNA cleavable complex. The drug-induced DNA breaks on D. melanogaster hsp70 genes were mapped in cultured cells using the indirect end-labeling procedure. Multiple and specific cleavage sites occurred at both the 3' and 5' ends of the hsp70 genes. A number of these cellular topoisomerase II cleavage sites mapped close to the DNase I-hypersensitive regions of the hsp70 genes. The intensities of several topoisomerase II cleavage sites changed significantly on heat shock induction. Treatment of cultured D. melanogaster cells with VM26 at 25 degrees C resulted in the stimulation of transcription of the hsp70 genes. These results suggest that inhibition of DNA topoisomerase II may lead to heat shock transcription.

Using the P4 unknotting assay, DNA topoisomerase II has been purified from several mammalian cells. Similar to prokaryotic DNA gyrase, mammalian DNA topoisomerase II can cleave double-stranded DNA and be trapped as a covalent protein-DNA complex. This cleavage reaction requires protein denaturant treatment of the topoisomerase II-DNA complex and is reversible with respect to salt and temperature. The product after reversal of the cleavage reaction remains supertwisted, suggesting that the two ends of the putatively broken DNA are held tightly by the topoisomerase. Alternatively, the enzyme-DNA interaction is noncovalent, and the covalent linking of topoisomerase to DNA is induced by the protein denaturant. Detailed characterization of the cleavage products has revealed that topoisomerase II cuts DNA with a four-base stagger and is covalently linked to the protruding 5'-phosphoryl ends of each broken DNA strand. Calf thymus DNA topoisomerase II cuts SV40 DNA at multiple and specific sites. However, no sequence homology has been found among the cleavage sites as determined by direct nucleotide-sequencing studies.

We have purified an acid-soluble DNA endonuclease, termed nuclease gamma, from Ustilago cell extracts. The enzyme is nearly homogeneous, purified 1700-fold. The protein appears to be globular with a molecular weight in the range 17,000 to 21,000. It requires a divalent cation and is optimally active at slightly alkaline pH. The enzyme prefers duplex DNA as substrate but will slowly cleave single-stranded DNA. Cleavage of covalently closed duplex DNA is unaltered by changes in superhelix density. Divalent cations direct the mode by which the enzyme cleaves duplex DNA. When Mg2+ or Ca2+ is added, the enzyme nicks one strand of the duplex. When Mn2+, Co2+, or Zn2+ is added, the enzyme can introduce double strand breaks. Oligonucleotides terminated with 5‘-phosphoryl and 3‘-hydroxyl groups are the products of hydrolysis. DNA fragments generated can be religated to linear pBR322 DNA with completely base-paired ends.

Many intercalative antitumor drugs have been shown to cleave DNA indirectly through their specific effect on the stabilization of a cleavable complex formed between mammalian DNA topoisomerase II and DNA (Nelson, E.M., Tewey, K.M., and Liu, L.F. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 1361-1365). Antitumor epipodophyllotoxins (VP-16 and VM-26) which do not intercalate DNA can similarly induce protein-linked DNA breaks in cultured mammalian cells. In vitro studies using purified mammalian DNA topoisomerase II show that epipodophyllotoxins interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II by stabilizing a cleavable complex. Treatment of this stabilized cleavable complex with protein denaturants results in DNA strand breaks and the covalent linking of a topoisomerase subunit to the 5'-end of the broken DNA. Furthermore, epipodophyllotoxins also inhibit the strand-passing activity of mammalian DNA topoisomerase II, presumably as a result of drug-enzyme interaction. The agreement between the in vivo and in vitro studies suggests that mammalian DNA topoisomerase II is a drug target in vivo. The similarity between the effect of epipodophyllotoxins on mammalian DNA topoisomerase II and the effect of nalidixic acid on Escherichia coli DNA gyrase suggests that the cytotoxic action of epipodophyllotoxins may be analogous to the bactericidal action of nalidixic acid.

The antitumor drug 4'-(9-acridinylamino)methanesulfon-m-anisidide which stimulates the cleavable complex formation between mammalian DNA topoisomerase II and DNA also stimulates the cleavable complex formation between bacteriophage T4-induced DNA topoisomerase and DNA. In the presence of 4'-(9-acridinylamino)methanesulfon-m-anisidide, T4 DNA topoisomerase and DNA form a "cleavable complex" which is characterized by its sensitivity to protein-denaturant treatment. Upon protein-denaturant treatment, the phosphodiester bond of DNA is cleaved, and the gene 52 protein subunit of the topoisomerase becomes covalently linked to the 5'-end of the broken DNA. The covalent protein-DNA linkage has been determined by both paper electrophoresis and thin layer chromatography to be tyrosyl phosphate.

The phosphorylation of the nuclear enzyme DNA topoisomerase II was characterized from HeLa human cervical carcinoma cells labeled with 32Pi. Analysis of topoisomerase II immunoprecipitates from 32P-labeled HeLa cells indicated that phosphorylation of the enzyme occurred at serine residues. Incorporation of 32P into topoisomerase II was not due to other types of phosphomodifications such as poly(ADP-ribosylation) or covalent interactions of the enzyme with nucleic acids. The stability of topoisomerase II protein and topoisomerase II phosphorylation was also investigated in HeLa cells. Topoisomerase II protein was relatively stable, having a half-life of approximately 27 h. Phosphorylation of HeLa topoisomerase II was also remarkably stable with a T1/2 of 17 h.

Lsk is a protein tyrosine kinase with homology to the COOH-terminal Src kinase (Csk). Unlike Csk that is ubiquitously expressed, Lsk has limited tissue distribution. Here we have examined the expression and regulation of Lsk and Csk in peripheral human monocytes. We have found that Lsk mRNA and protein were not expressed in resting monocytes but were induced by treatment with interleukin 4 (IL-4) or IL-13 but not by interferon gamma (IFN-gamma) or IL-2. In fact, IFN-gamma, but not IL-2, efficiently blocked Lsk induction by IL-4 or IL-13. In contrast, Csk was constitutively present in human monocytes and was upregulated by IFN-gamma but not by IL-4 or IL-13. These results suggest that despite their structural similarities, Lsk and Csk may play distinct regulatory roles in monocyte functions elicited by cytokines, with Lsk functioning specifically within the context of a Th2-type immune response.

Objectives:The long term effectiveness of combination therapy at reducing viral loads in seminal fluid and blood plasma obtained from HIV-1 infected men who had undergone previous antiretroviral therapy was assessed.Methods:Samples of semen and blood were obtained from a cohort of 12 nucleoside reverse transcriptase inhibitor experienced men before and during 25-68 weeks of combination therapy, which included the protease inhibitor indinavir. HIV-1 RNA titres present in the cell free blood and seminal plasma samples were determined using the nucleic acid sequence based amplification (NASBA)/Nuclisens assay system.Results:Viral RNA was detected in 9/12 and 7/12 baseline blood plasma and seminal plasma samples, with median viral titres of 10^4.81 and 10^4.56 per ml, respectively. By the end of the study period the detection rates of HIV RNA in the blood and seminal plasma samples were 5/12 and 2/12, respectively, with the median viral titres below the assay cut off level for both sample types. Of the nine patients who had detectable viral RNA in the baseline sample, only three cleared virus from both compartments by the end of the study.Conclusions:These data show that stable reduction of blood and seminal fluid viral titres is not achievable in a significant proportion of nucleoside reverse transcriptase inhibitor experienced men.

Several letters to the editor are presented in response to articles in previous issues including issues about Christmas decorations in garden centers, landscape gardening and re-using of Christmas trees in the December 2005 issue.

We document our latest work in developing eye models with solid-state retinal tissue phantoms designed for demonstrating, validating and comparing ophthalmic Optical Coherence Tomography (OCT) instruments. Eye models with retina tissue phantoms can serve a variety of purposes, including demonstrating OCT functionality and performance in both the clinic and exhibit hall, validating retina layer thickness measurements from different commercial OCT instruments and as an aide for the R&D engineer and field service technician in the development and repair of instruments, respectively. The ideal eye model for OCT, the optical cross-sectional imaging modality, would have a volumetric morphology and scattering and absorption properties similar to that of normal human retina. These include a multi-layered structure of equivalent thickness to nominal human retina layers, a foveal pit that can be used to orient the image, and a RPE/OS and choroid like layers to demonstrate the depth penetration of the OCT system. A solid state tissue phantom relieves the user of constant cleaning and maintenance associated with the more common water bath model eyes. Novel processes12 have been developed to create retinal layers model that closely mimic the reflectance and scattering coefficients of the real layers of the retina, as imaged by spectral bandwidth of OCT.

Profile of new baseball commissioner Francis (Fay) Vincent, 51. Discusses the commissioner's responsibilities; Preservation of baseball's integrity; Past commissioners and controversies; Next year's contract negotiations.

Cationic complexes (I)‐(IV) are prepared by reaction of ligand and Fe2+in hot MeOH and isolated as Cl‐, ClO4‐or BF4‐salts (yields partially given).

Addition of dioxygen to the known complex (I) containing three‐coordinate Cu(I) in CH2Cl2(DMF) or MeOH results in hydroxylation of the m‐xylyl dinucleating ligand, producing the phenolate‐bridged Cu(II) complexes (IIa) and/or (IIb).

The oxo‐bridged Fe(III) complexes (I) are prepared and characterized by their magnetic susceptibility and EPR spectra.