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R Young

Publications and source records attributed to R Young.

At least 37 records · Page 2Linked to original sources
PubMed2001

Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme plays a crucial role in repression.

The yeast transcriptional repressor Tup1, tethered to DNA, represses to strikingly different degrees transcription elicited by members of two classes of activators. Repression in both cases is virtually eliminated by mutation of either member of the cyclin-kinase pair Srb10/11. In contrast, telomeric chromatin affects both classes of activators equally, and in neither case is that repression affected by mutation of Srb10/11. In vitro, Tup1 interacts with RNA polymerase II holoenzyme bearing Srb10 as well as with the separated Srb10. These and other findings indicate that at least one aspect of Tup1's action involves interaction with the RNA polymerase II holoenzyme.

Cyclin-Dependent Kinase 8↗
PubMed2001

Prevalence of Neospora hughesi and Sarcocystis neurona antibodies in horses from various geographical locations.

Parasite-specific antibody responses to Neospora antigens were detected using the immunofluorescent antibody test (IFAT) and immunoblot analysis in select equine populations. For comparison, a naturally infected Neospora hughesi horse and an experimentally inoculated Neospora caninum horse were used. In addition, all samples were tested for antibodies to Sarcocystis neurona by immunoblot analysis. A total of 208 samples was evaluated. The equine populations were derived from five distinct geographic regions. Locations were selected based on distribution of Didelphis virginiana, the native North American opossum which serves as the definitive host for S. neurona. Only 11% of the samples that had positive titers of 1:100 using the IFAT were also positive for antibodies by immunoblot analysis in this study. Overall, there was a 2% seroprevalence for Neospora antibodies in all horses tested based on immunoblot analysis described. The seroprevalence for S. neurona antibodies varied from 0% (New Zealand and Montana) to 54% (Missouri). We concluded that, in testing for antibodies against Neospora antigens using either IFAT or immunoblot analysis, as described, positive results should not be attributed to the presence of antibodies to S. neurona.

Animals↗
PubMed2001

Dragon's Blood incense: misbranded as a drug of abuse?

An unknown red substance was being sold and used with other drugs of abuse in Virginia (often being used in conjunction with marihuana). The red substance was identified as Dragon's Blood incense from Daemonorops draco. In bioassays, Dragon's Blood incense exhibited a low, but measurable cytotoxicity in in vitro cell lines. Dragon's Blood incense or Volatilized Dragon's Blood had no adverse effect on mouse motor performance based on the inclined screen and rotorod tests. delta(9)-Tetrahydrocannibinol (THC) produced a dose-related decline in mouse performance on the rotorod test. The combination of Dragon's Blood incense or Volatilized Dragon's Blood with delta(9)-THC did not contribute further to the impairment of the mice on the rotorod. This data suggests that the abuse potential for Dragon's Blood incense alone or in combination with marihuana is minimal.

Animals↗
PubMed2001

Functional analysis of the phage T4 holin in a lambda context.

Phage lambda hybrids were constructed by inserting the t gene of phage T4 in place of the lambda holin gene, S. Induction of the hybrid phage resulted in lysis that was just as abrupt as, but occurred much earlier in the vegetative cycle than, that obtained with lambda, indicating that t is indeed a holin gene. Moreover, it was possible to impose lysis inhibition (LIN) on induction of the hybrid phage, but not of the parental lambda phage, by superinfection with LIN-competent T4. The imposition of the LIN state was found to depend on the allelic state of the rI and t genes of the superinfecting T4 phage, indicating that the LIN-sensitive state of the T holin is transient. Finally, induction of lysogens carrying both holin genes was shown to result in earlier triggering of lysis than with either holin gene alone. This result suggests that the two very dissimilar holins contribute additively to the physiology of the timing mechanism, or, less likely, that they interact to form one mass-action pool. In either case, these results imply a common pathway for holin timing and function.

Amino Acid Sequence↗
PubMed2001

Neuropharmacological actions of some binuclear lanthanide(III) complexes.

Binuclear lanthanide(III) compounds are of great interest because of the potential of their mutual Ln(3+)-Ln(3+) electronic couplings to produce unusually sharp images in magnetic resonance and fluorescence imaging of biological tissue. The toxicity and neuropharmacological properties of the water soluble and stable neutral binuclear complex [La(api)](2) were compared with those of binuclear complexes with lower water stability, and the components used in their syntheses. The order of the 24-h LD(50) (mg/kg body wt.) of the compounds in mice was: salicylaldehyde (2.24) 160). These compounds induced convulsions, urination and defecation in mice. Due to the relatively very low toxicity of [La(api)](2), its mode of action was explored. Its proconvulsant action may possibly involve an interaction of undissociated complex with muscarinic receptors, and is reversed by atropine.

Animals↗
PubMed2001

Biomechanical and biochemical pulping of sugarcane bagasse with Ceriporiopsis subvermispora fungal and xylanase pretreatments.

Sugarcane bagasse was pretreated with both the white-rot fungus, Ceriporiopsis subvermispora, and xylanase enzyme for 2 weeks before soda chemithermomechanical (CTMP) and soda chemical (CP) cooking. For fungi-CTMP (BCTMP) and enzyme-fungi-CTMP (EBCTMP), the bagasse, after bio-pretreatment, was cooked with 5% sodium hydroxide, at 130 degrees C for 20 min. For the chemical pulping (CP), after fungi pretreatment (BCP) or after xylanase and fungal pretreatment (EBCP), the bagasse was cooked with 14.5% sodium hydroxide. With the BCTMP, the Klason lignin was reduced, all of the pulp strength properties were increased, and a 28% savings in refining energy consumption was obtained, but the brightness was reduced 5 points compared to the control. With the EBCTMP, the brightness losses were overcome but with a mild reduction in the pulp strength properties compared to the BCTMP. The energy savings were 5% greater than from BCTMP and 33% over the control. The BCP treatment increases somewhat the pulp strength properties, reduces the energy consumption 23%, and reduces the brightness by 9 points compared to the control; however, the kappa no. was 5.5 points higher than the control. EBCP treatment reduces brightness losses and increases the pulp yield 2% compared to the control, but with some reduction in the strength properties compared to BCP.

Basidiomycota↗
PubMed2001

Hand preference, sexual preference, and transsexualism.

Atypical handedness patterns, i.e., persons being less exclusively right-handed, have been found previously in large samples of male and female homosexuals and in small samples of male and female transsexuals compared to controls. The posited role of prenatal androgen influencing both cerebral hemispheric dominance and psychosexual development warrants further study with large samples of transsexuals. 443 male-to-female transsexuals and 93 female-to-male transsexuals were studied for their use of the right or left hand in six common one-handed tasks. Both male and female transsexuals were more often nonright-handed than male and female controls were. Results suggest an altered pattern of cerebral hemispheric organisation in male and female transsexuals.

Brain↗
PubMed2001

Effect of carbon dioxide on the Oriental cockroach Blatta orientalis.

Exposure to high concentrations of carbon dioxide (CO2) killed adult and nymphal stages of the oriental cockroach Blatta orientalis L. (Dictyoptera: Blattidae) with LT50 values of 11.5-16.2 h for 60% CO2 in air and 5.7-7.1 h for 100% CO2 at 20 degrees C; corresponding LT50s at 28 degrees C were 2.8-4.6 h for 60% CO2 in air and 2.3-3.6 h for 100% CO2. Complete kill of mobile stages was obtained within 24 h using 60% CO2 at 20 degrees C. Survivors of treatments with 100% CO2 at 28 degrees C remained completely paralysed for up to 3 days post-treatment and took up to 5 days to regain normal movement, but adult females then resumed production of oothecae with no significant loss in fecundity. Oothecae 5 or 30 days after deposition required 60-84 h exposure to 60% CO2 at 20 degrees C to prevent emergence of nymphs but less time using 100% CO2 at 28 degrees C. At 28 degrees C, when adult females were treated with 100% CO2 and 52% r.h. for 6 h (giving 100% mortality) loss of weight was significantly greater than that following treatment with air at 52% r.h. for 6 h (giving no mortality). However, significantly greater weight loss also occurred when they were treated with dried air (< 10% r.h.) for 6 h, also with no mortality. The toxicity of CO2 to mobile stages of the oriental cockroach appeared to result from irreversible effects on the nervous system, rather than from water loss during exposure.

Animals↗
PubMed2001

An ancient player unmasked: T4 rI encodes a t-specific antiholin.

Phage T4 effects lysis by its holin T and its endolysin E. Lysis is inhibited (LIN) if the infected cell is subjected to secondary infections by T4 phage particles. The T4 rI gene is required for LIN in all hosts tested. Here, we show that a cloned rI gene can impose a T-specific LIN on T-mediated lysis in the context of the phage lambda infective cycle, in the absence of other T4 genes and without secondary infection by T4. Moreover, it is shown that the T holin accumulates in the membrane during LIN, forming SDS-resistant oligomers. We show by cross-linking experiments that a T-RI heterodimer is formed during LIN, demonstrating that RI belongs to the functional class of antiholins, such as the S107 protein of lambda, which heterodimerizes with its cognate holin, S105. Finally, we show that the addition of Ni(2+) ions to the medium can block lysis by a T protein hexahistidine-tagged at its C-terminus, suggesting that liganding of the periplasmic domain is sufficient to impose lysis inhibition. The results are discussed in terms of a model in which the LIN-inducing signal of the secondary infecting phage influences a conformational equilibrium assumed by RI in the periplasm.

Alleles↗
PubMed2001

Nail apparatus melanoma.

Nail apparatus melanoma is a relatively rare variant of melanoma with a disproportionately high mortality when compared with melanoma elsewhere. The aetiology and natural history remain poorly understood. There is no clear epidemiological association with race, skin type or sun exposure. Universally accepted clinical and histological criteria for the diagnosis of early nail apparatus melanoma have not been defined. The two cardinal clinical signs are melanonychia striata and Hutchinson's sign. These are useful but not pathognomonic of melanoma. Diagnostic delay is frequent and patients commonly have advanced disease at the time of diagnosis. Surgical excision is advocated for treatment of stage I disease; however, the most appropriate re-excision margins, including the level of amputation where required, have not been determined. Early diagnosis and excision of the tumour is the only treatment known to increase survival. Adjuvant systemic chemotherapy, isolated limb perfusion, and routine elective lymph node dissection have been used, but no survival benefit has been demonstrated.

Adult↗
PubMed2001

Small intestinal motor patterns in critically ill patients after major abdominal surgery.

OBJECTIVES: In patients who have had major surgery or trauma, early enteral feeding is safer and more effective than parenteral or nasogastric feeding but is frequently associated with diarrhea. Limited recordings have shown that the patterning of duodenal interdigestive motor activity is frequently abnormal after surgery or in patients who are critically ill. The aims of this study were to evaluate the effects of major abdominal surgery on small intestinal motility, and to elucidate the motor patterns that occur postoperatively in critically ill patients in response to enteral feeding. METHODS: The effects of elective aortic aneurysm repair on small intestinal motility were studied in 11 patients aged 63-77 yr. A 3.5-mm diameter multilumen extrusion was used to monitor pressures at 12 points, distributed between the antrum and 100 cm distal to the pylorus. An additional lumen allowed enteral feeding into the duodenum. Recordings commenced immediately postoperatively and continued for up to 4 days. Data are given as means and SEMs. RESULTS: Bursts (frequency > 10/min) of small intestinal pressure waves that resembled phase III interdigestive motor activity occurred in all patients immediately after surgery. During mechanical ventilation, the timing of bursts along the segment evaluated was frequently abnormal for true interdigestive phase III activity, with simultaneous onset in multiple channels (46%), multiple or distal origins (8%), or retrograde migration (20%). When patients were not being ventilated, the migration pattern of the bursts was more typical of interdigestive phase III activity. The interval between bursts was unusually short for interdigestive motor activity, although it increased from 30+/-12 min on day 1 to 41+/-18 min on day 3 (p < 0.05). A phase II pattern of pressure waves was virtually absent in all patients on all study days. In six patients who received postoperative enteral nutrition, the bursts of pressure waves were not abolished by feeding, contrary to normal phase III activity. CONCLUSIONS: Small intestinal pressure wave bursts are seen immediately after elective aortic aneurysm repair, but the migration of these bursts is frequently abnormal for phase III interdigestive activity. Duodenal nutrient delivery did not interrupt the occurrence of these bursts. Persistence of pressure wave bursts in this setting may be important in the delivery of enteral nutrition.

Aged↗
PubMed2001

Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2).

Prostaglandin (PG) E(2) is a potent inducer of cortical and trabecular bone formation in humans and animals. Although the bone anabolic action of PGE(2) is well documented, the cellular and molecular mechanisms that mediate this effect remain unclear. This study was undertaken to examine the effect of pharmacological inactivation of the prostanoid receptor EP(4), one of the PGE(2) receptors, on PGE(2)-induced bone formation in vivo. We first determined the ability of EP(4)A, an EP(4)-selective ligand, to act as an antagonist. PGE(2) increases intracellular cAMP and suppresses apoptosis in the RP-1 periosteal cell line. Both effects were reversed by EP(4)A, suggesting that EP(4)A acts as an EP(4) antagonist in the cells at concentrations consistent with its in vitro binding to EP(4). We then examined the effect of EP(4) on bone formation induced by PGE(2) in young rats. Five- to 6-week-old rats were treated with PGE(2) (6 mg/kg/day) in the presence or absence of EP(4)A (10 mg/kg/day) for 12 days. We found that treatment with EP(4)A suppresses the increase in trabecular bone volume induced by PGE(2). This effect is accompanied by a suppression of bone formation indices: serum osteocalcin, extent of labeled surface, and extent of trabecular number, suggesting that the reduction in bone volume is due most likely to decreased bone formation. The pharmacological evidence presented here provides strong support for the hypothesis that the bone anabolic effect of PGE(2) in rats is mediated by the EP(4) receptor.

Animals↗
PubMed2000

The lysis protein E of phi X174 is a specific inhibitor of the MraY-catalyzed step in peptidoglycan synthesis.

Coliphage phi X174 encodes a single lysis protein, E, a 91-amino acid membrane protein. Dominant mutations have been isolated in the host gene mraY that confer E resistance. mraY encodes translocase I, which catalyzes the formation of the first lipid intermediate in bacterial cell wall synthesis, suggesting a model in which E inhibits MraY and promotes cell lysis in a manner analogous to cell wall synthesis inhibitors like penicillin. To test this model biochemically, we monitored the effect of E on cell wall synthesis in vivo and in vitro. We find that expression of Emyc, encoding an epitope-tagged E protein, from a multicopy plasmid inhibits the incorporation of [(3)H]diaminopimelic acid into cell wall and leads to a profile of labeled precursors consistent with MraY inhibition. Moreover, we find that membranes isolated after Emyc expression are drastically reduced in MraY activity, whereas the activity of Rfe, an enzyme in the same superfamily, was unaffected. We therefore conclude that E is indeed a cell wall synthesis inhibitor and that this inhibition results from a specific block at the MraY-catalyzed step in the pathway.

Bacterial Proteins↗
PubMed2000

Immune responses induced by BCG recombinant for human papillomavirus L1 and E7 proteins.

Recombinant bacille Calmette-Guerin (BCG) based vaccine delivery systems could potentially share the safety and effectiveness of BCG. We therefore prepared recombinant BCG vaccines which expressed the L1 late protein of the human papillomavirus (HPV) 6b or the E7 early protein of the HPV 16. The two recombinants were evaluated as immunogens in C57BL/6J and BALB/c mice, and compared with a conventional protein/adjuvant system using E7 or L1 mixed with Quil-A adjuvant. rBCG6bL1 and rBCG16E7 primed specific immune responses, represented by DTH, T-proliferation and antibody, and rBCG16E7 induced cytotoxic immune response to E7 protein. The magnitude of the observed responses were less than those elicited by protein/adjuvant vaccine. As recombinant BCG vaccines expressing HPV6bL1 or HPV16E7 persist at low levels in the immunised host, they may be beneficial to prime or retain memory responses to antigens, but are unlikely to be useful as a single component vaccine strategy.

Adjuvants, Immunologic↗
PubMed2000

Genetic evidence that the bacteriophage phi X174 lysis protein inhibits cell wall synthesis.

Protein E, a 91-residue membrane protein of phiX174, causes lysis of the host in a growth-dependent manner reminiscent of cell wall antibiotics, suggesting E acts by inhibiting peptidoglycan synthesis. In a search for the cellular target of E, we previously have isolated recessive mutations in the host gene slyD (sensitivity to lysis) that block the lytic effects of E. The role of slyD, which encodes a FK506 binding protein-type peptidyl-prolyl cis-trans isomerase, is not fully understood. However, E mutants referred to as Epos (plates on slyD) lack a slyD requirement, indicating that slyD is not crucial for lysis. To identify the gene encoding the cellular target, we selected for survivors of Epos. In this study, we describe the isolation of dominant mutations in the essential host gene mraY that result in a general lysis-defective phenotype. mraY encodes translocase I, which catalyzes the formation of the first lipid-linked intermediate in cell wall biosynthesis. The isolation of these lysis-defective mutants supports a model in which translocase I is the cellular target of E and that inhibition of cell wall synthesis is the mechanism of lysis.

Alleles↗
PubMed2000

The kinetics of specific immune responses in rhesus monkeys inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins.

Development of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette-Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV.

Animals↗
PubMed2000

Biochemical and genetic evidence for three transmembrane domains in the class I holin, lambda S.

lambda S, the prototype class I holin gene, encodes three potential transmembrane domains in its 107 codons, whereas 21 S, the class II prototype spans only 71 codons and encodes two transmembrane domains. Many holin genes, including lambda S and 21 S, have the "dual-start" regulatory motif at the N terminus, suggesting that class I and II holins have the same topology. The primary structure of 21 S strongly suggests a bitopic "helical-hairpin" topology, with N and C termini on the cytoplasmic side of the membrane. However, lambda S chimeras with an N-terminal signal sequence show Lep-dependent function, indicating that the N-terminal domain of S requires export. Here the signal sequence chimera is shown to be sensitive to the missense change A52V, which blocks normal S function. Moreover, cysteine-modification studies in isolated membranes using a collection of S variants with single-cysteine substitutions show that the positions in the core of the 3 putative transmembrane domains of lambda S are protected. Also, S proteins with single-cysteine substitutions in the predicted cytoplasmic and periplasmic loops are more efficiently labeled in inverted membrane vesicles and whole cells, respectively. These data constitute direct evidence that the holin S(lambda) has three transmembrane domains and indicate that class I and class II holins have different topologies, despite regulatory and functional homology.

Amino Acid Sequence↗