bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of high specific activity DL‐tryptophan‐2, 3‐T and its resolution to l‐tryptophan‐2, 3‐T
Authors: Ramamurthy T. V. , Pichat L.
Published: October 2006

DL‐Tryptophan‐2, 3‐T of high specific activity was obtained by reducing a suitable precursor with T2 gas. It was resolved also into L‐Tryptophan‐2, 3‐T by using the enzyme carboxypeptidase. The optical purity of L‐Tryptophan‐2, 3‐T was greater than 99% and the specific activity was 15 Ci/mM.
Synthsis of meleylacetoacetate‐214C, maleylacetone‐114C and homogentisic acid γ‐lactone‐α‐14C. 1
Authors: Seltzer S.
Published: October 2006

Syntheses of the title compounds were accomplished by a sequence of reactions involving Friedel Crafts 14C‐acetylation of p‐dimethoxybenze, willgerodt rearrangement of 2, 5‐dimethoxyacetophenone‐carbonyl‐14C (I) to 2, 5‐dimethoxyphenylactic acid‐a14C (II), followed by hydrolysis to homogentisic acid γ‐lactone‐α‐14C(III). Oxygenation of the lactone by an osygenaser from animal liver provided a solution of maleyacetoacetate‐2‐14C (IV). Decarboxylation of this matrial leads to a solution of maleylacetone‐1‐14C (V). Funaruylactone‐1‐14C (VT) can be obtained from V by silver ion‐catalysed cis‐trans isomerization.
Synthesis of octadeuterocyclopentanone
Authors: Della E. W. , Patney H. K.
Published: October 2006

The syntehsis of octadeuterocyclopentanons of high isotopic purity (98%) from diethyl succinate‐D4 is described. Two routes leading to the tittle compound were employed, each allowing for its synthesis on a practical scale.
A high yield photochemical preparation of 4 ‐ nitrocatechol‐ UL ‐14C
Authors: Norris F. A. , Still G. G.
Published: October 2006

4‐Nitrocatechol ‐UL‐ 14C was synthesized in 48, 9% yield by the photolysis of 4‐nitrophenol ‐UL‐ 14C in aqueous hydrogen peroxide.
Quality control of radioactive products for patient administration at the national institutes of health
Authors: Vacca Patricia C. , Farkas Raymond J. , Semler Mark O.
Published: October 2006

This paper describes the quality control procedure for radioactive materials destined for patient use at the National Institutes of Health. The Radiopharmaceutical Section is responsible for attesting to pharmaceutical quality, while the Radiation Safety Section performs per‐unit‐volume assays and radionuclidic purity checks on these materials. Types and examples of product error are presented as well as statistical data on essay discrepancies. The frequency of error during the past ten years indicates the necessity of continued quality control testing of all radioactive materials, regardless of source of supply and prior administration to patients.
Freudian Repression, the Common View, and Pathological Science
Authors: Boag Simon
Published: October 2006

A sustained misconceptualisation of a theory leading to invalid applications and inferences indicates a failure in the scientific process. This has repeatedly occurred with Freud's theory of repression, a cornerstone of psychoanalytic theory. This paper traces the development of Freud's theory of repression and compares this with the “common view” found in mainstream psychology: the motivated forgetting of trauma. A fixation with Freud's original, and superseded theory (1893–1897) ignores the theoretical developments that constitute mature psychoanalysis (1900–1940), and has impacted upon attempts to test Freudian theory and the current “recovered memory” debate. Although certain accidental factors contribute to this misunderstanding, the sustained failure to comprehend Freudian repression reveals a breakdown in the process of critical inquiry. Implications for psychology as a whole are discussed.
“Selling America to the World”? The Rise and Fall of an International Film Distributor in its Largest Foreign Market: United Artists in Britain, 1927–1947
Authors: Miskell Peter
Published: October 2006

Few industries are as widely associated with the spread of American values, ideas, and products as the film industry. U.S. firms certainly dominated the global market for feature films, but did they do so simply by “selling America to the world” or was there more to be gained by catering to the diverse tastes of international audiences? This article examines the operations of a leading U.S. film distributor in its largest foreign market. United Artists, like other U.S. firms, was forced to offer a minimum proportion of British films for distribution in the United Kingdom in the 1930s and 1940s. Was this requirement a burden, or were the firm’s British films actually at the heart of its success in the U.K. market?
Mechanics of atoms and fullerenes in single-walled carbon nanotubes. II. Oscillatory behaviour
Authors: Cox Barry J , Thamwattana Ngamta , Hill James M
Published: October 2006

The discovery of carbon nanotubes and C
60
fullerenes has created an enormous impact on possible new nanomechanical devices. Owing to their unique mechanical and electronic properties, such as low weight, high strength, flexibility and thermal stability, carbon nanotubes and C
60
fullerenes are of considerable interest to researchers from many scientific areas. One aspect that has attracted much attention is the creation of high-frequency nanoscale oscillators, or the so-called gigahertz oscillators, for applications such as ultrafast optical filters and nano-antennae. While there are difficulties for micromechanical oscillators, or resonators, to reach a frequency in the gigahertz range, it is possible for nanomechanical systems to achieve this. This study focuses on C
60
–single-walled carbon nanotube oscillators, which generate high frequencies owing to the oscillatory motion of the C
60
molecule inside the single-walled carbon nanotube. Using the Lennard-Jones potential, the interaction energy of an offset C
60
molecule inside a carbon nanotube is determined, so as to predict its position with reference to the cross-section of the carbon nanotube. By considering the interaction force between the C
60
fullerene and the carbon nanotube, this paper provides a simple mathematical model, involving two Dirac delta functions, which can be used to capture the essential mechanisms underlying such gigahertz oscillators. As a preliminary to the calculation, the oscillatory behaviour of an isolated atom is examined. The new element of this study is the use of elementary mechanics and applied mathematical modelling in a scientific context previously dominated by molecular dynamical simulation.
Copulation, genital damage and early death in
Callosobruchus maculatus
Authors: Eady Paul E , Hamilton Leticia , Lyons Ruth E
Published: October 2006

Antagonistic sexual coevolution stems from the notion that male and female interests over reproduction are in conflict. Such conflicts appear to be particularly obvious when male genital armature inflicts damage to the female reproductive tract resulting in reduced female longevity. However, studies of mating frequency, genital damage and female longevity are difficult to interpret because females not only sustain more genital damage, but also receive more seminal fluid when they engage in multiple copulations. Here, we attempt to disentangle the effects of genital damage and seminal fluid transfer on female longevity in the beetle
Callosobruchus maculatus
(Coleoptera: Bruchidae). Males copulating for the sixth time in succession inflicted greater levels of genital damage, but transferred smaller ejaculates in comparison with virgin males. The number of copulations performed by males was negatively related to female fecundity and positively related to female longevity, suggesting a trade-off between fecundity and longevity. However, inclusion of fecundity as a covariate revealed sperm and/or seminal fluid transfer to have a negative impact on female longevity above that caused by the fecundity–longevity trade-off. The consequences of multiple copulations on female longevity were examined. Females that mated twice laid more eggs and died sooner than those that mated once. However, incorporation of fecundity as a covariate into our statistical model removed the effect of female mating frequency on female longevity, indicating that double-mated females suffer greater mortality owing to the trade-off between fecundity and longevity. Males of this species are known to transfer very large ejaculates (up to 8% of their body weight), which may represent a significant nutritional benefit to females. However, the receipt of large ejaculates appears to carry costs. Thus, the interpretation of multiple mating experiments on female longevity and associated functional explanations of polyandry in this species are likely to be complex.
Evidence of a disturbance of the hypothalamic‐pltuitary‐adrenal axis in polycystic ovary syndrome: effect of naloxone
Authors: Lanzone Antonio , Guido Maurlzlo , Ciampelli Mario , Fulghesu Anna Maria , Pavone Virginia , Proto Caterina , Caruso Alessandro , Mancuso Salvatore
Published: October 2006

DESIGN There are conflicting data on hypothalamic‐pituitary‐adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects.

PATIENTS Twenty PCOS patients and 10 control women participated in the study.

MEASUREMENTS On days 5–6 Of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2‐mg naloxone infusion In 100 ml of 0.9% saline over one hour. Samples were collected at −30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples.

RESULTS PCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261 vs 172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher In PCOS patients (P < 0.05 and P < 0.04 respectively).

The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production.

CONCLUSIONS Polycystic ovary syndrome patients showed a hypothalamic‐pituitary‐adrenal axis hyper‐responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be central in origin.
Phenotypic evolution of classic 21‐hydroxylase deficiency
Authors: Hoffman William H. , Shln Myung Y. , Donohoue Patricia A. , Helman Sandra W. , Brown Stephanle L. , Rosculet George , Mahesh Virendra B.
Published: October 2006

We describe a female patient who was diagnosed and treated at birth for a classic form of salt‐losing congenital adrenal hyperplasia. At 17 years of age, against medical advice, she discontinued both mineralocorticoid and glucocorticoid replacement with no resulting clinical symptoms other than the occurrence of amenorrhoea. Steroid metabolites revealed significant abnormalities of the renin‐angiotensin‐aldosterone axis, as well as of pituitary‐adrenal function. Analysis of our patient's DNA showed only one deleterious CYP21 mutation, an intron 2 base pair change activating a cryptic splice site. We speculate that expression of this patlent's CYP21 genes may be altered by the effects of ageing or by changes in the steroid milieu.
Information sources used by New South Wales cancer clinicians: a qualitative study
Authors: Tan E. L. , Stark H. , Lowinger J. S. , Ringland C. , Ward R. , Pearson S.‐A.
Published: October 2006

Background: This study identified (i) information sources used by cancer clinicians to guide pharmacological treatments, (ii) utilization of, and opinions about, online information sources and (iii) clinicians’ ability to access a specific cancer treatment protocol (escalated bleomycin, etiposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) for Hodgkin’s Lymphoma). The work was carried out before activation of the Cancer Institute New South Wales Standard Cancer Treatment (CI‐SCaT) programme.

Methods: We conducted semistructured interviews with a purposeful sample of senior and junior doctors, nurses and pharmacists treating adult cancer patients (n = 32) in eight New South Wales public hospitals.

Results: Information seeking processes are context specific and vary from clinician to clinician and ward to ward. Clinicians use human, electronic and printed information sources at, or close to, the point of patient care; however, experienced colleagues are preferred where information is needed quickly or in unfamiliar clinical situations. Barriers to using online cancer information are environmental (hardware, connection speeds, time), personal (poor computer literacy and lack of awareness of appropriate sites) and economic (costs of journal subscriptions). Just over half of participants were able to locate a specific cancer protocol and none of these protocols was fully consistent with CI‐SCaT recommendations.

Conclusion: There is no standardized approach to the pharmacological treatment of cancer patients in this sample of New South Wales clinicians. CI‐SCaT will fill a gap with respect to standardizing oncology treatment. However, to ensure maximal CI‐SCaT uptake, implementation plans should harness positive behavioural influences and attempt to modify the negative forces that act on hospital clinicians in their day‐to‐day work.
Thyroid hormone resistance: the role of mutational analysis
Authors: Florkowski C. M. , Brownlie B. E. W. , Croxson M. S. , Manning P. , Farrand S. , Smith G. , Potter H. C. , George P. M.
Published: October 2006

The finding of increased thyroxine (T4) and tri‐iodothyronine (T3) levels in a patient with normal or increased thyroid‐stimulating hormone is unexpected and presents a differential diagnosis between a thyroid‐stimulating hormone‐secreting pituitary adenoma, generalized resistance to thyroid hormone (RTH) and laboratory artefact. Without careful clinical and biochemical evaluation, errors may occur in patient diagnosis and treatment. In the case of RTH, mutation of the thyroid hormone receptor beta gene results in generalized tissue resistance to thyroid hormone. As the pituitary gland shares in this tissue resistance, euthyroidism with a normal thyroid‐stimulating hormone is usually maintained by increased thyroid hormones. To date, we have identified eight pedigrees in New Zealand with mutations in the thyroid hormone receptor beta gene, including two novel mutations. Mutational analysis of the thyroid hormone receptor beta gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing and imaging. Mutational analysis also enables family screening and may help to avoid potential misdiagnosis and inappropriate treatment.
Information from the Internet: attitudes of Australian oncology patients
Authors: Newnham G. M. , Burns W. I. , Snyder R. D. , Dowling A. J. , Ranieri N. F. , Gray E. L. , McLachlan S.‐A.
Published: October 2006

Background: Patients require accurate information about their illness to make informed decisions. Many sources of information exist, although reliability is variable. Our objective was to investigate information seeking behaviour and attitudes toward health‐related information from the Internet in a sample of Australian oncology patients.

Method: During their outpatient attendance, 109 patients completed a self‐administered paper–pen format questionnaire. They were required to have a recent cancer diagnosis (<6 months ago) adequate English and no cognitive impairment.

Results: Seventy‐four per cent of questionnaires were returned. The majority of patients (78%) wanted as much information about their cancer diagnosis as possible and 90% reported receiving adequate information from their treating team. Despite this, more than half actively searched for additional information, with 77% using the Internet. Patients were trusting of information obtained from the Internet. More than half of information searchers discussed information obtained in their search with a health professional. The majority of patients did not believe that information searching adversely affected the doctor–patient relationship.

Conclusion: Information searching is common in ambulatory Australian oncology patients, with the Internet being a frequently used resource. To ensure patients find reliable and relevant information and to minimize the risk of harm, health professionals involved in treating oncology patients should provide guidance in finding information sources and assistance in interpreting the information obtained.
Twenty‐year audit of percutaneous liver biopsy in a major Australian teaching hospital
Authors: Van Der Poorten D. , Kwok A. , Lam T. , Ridley L. , Jones D. B. , Ngu M. C. , Lee A. U.
Published: October 2006

Background: To examine the changes in indications, patient characteristics, safety and outcomes in consecutive patients undergoing percutaneous core liver biopsies in a major Australian teaching hospital over a period of two decades.

Methods: A retrospective audit was carried out on all percutaneous core liver biopsies from a single institution between 1996 and 2005. This was combined with 10 years of data already reported on for the years 1986–1995 to detect trends in indications and outcomes.

Results: Medical records from 1398 patients were included for analysis. Over a 20‐year period, the most common indications for liver biopsy were hepatitis C (37.8%), hepatitis B (26.4%) and abnormal liver function tests (22.2%). Twelve major complications (1.0%) were seen; 10 episodes of haemorrhage, 1 bile leak and 1 visceral perforation. Seven of these patients had an abnormal baseline coagulation profile; a significant risk for major haemorrhage (P < 0.001), resulting in three deaths. All deaths occurred in inpatients with major comorbidities. Minor complications occurred in 13.6% of patients, with multiple passes a significant risk factor. Whereas the overall major and minor complication rates were independent of operator experience inadequate specimens were more frequently obtained by the registrar.

Conclusion: This large series extending over two decades shows that despite advances in biopsy techniques, the rates of both minor and major complications remain significant. Of particular concern are the procedure‐related deaths. Identifying factors that may increase risk requires further scrutiny and careful patient selection needs to be undertaken.
Irritable bowel syndrome
Authors: Talley N. J.
Published: October 2006

Conceptually, the irritable bowel syndrome (IBS) has been considered a brain‐gut functional disorder, but this paradigm is under serious challenge. There is increasing evidence that organic disease of the gastrointestinal tract can be identified in subsets of patients who fulfil the Rome criteria for IBS. Evidence for subtle inflammatory bowel disease, serotonin dysregulation, bacterial overgrowth and central dysregulation continue to accumulate. The underlying causes of IBS remain to be adequately identified, but postinfectious IBS is a clear‐cut entity. Furthermore, a genetic contribution to IBS also seems likely. Diagnosis continues to be based on the symptom profile and the absence of alarm features. A heightened awareness of coeliac disease masquerading as IBS is becoming accepted. Management remains largely based on symptomatic rather than on disease‐modifying therapy, but this is likely to change in the near future. Here, recent advances in the pathophysiology and management of IBS are considered.
Processing of extended shelf life milk using microfiltration
Authors: HOFFMANN WOLFGANG , KIESNER CHRISTIAN , CLAWIN‐RÄDECKER INGRID , MARTIN DIERK , EINHOFF KURT , LORENZEN PETER CHRISTIAN , MEISEL HANS , HAMMER PHILIPP , SUHREN GERTRAUD , TEUFEL PAUL
Published: October 2006

Extended shelf life (ESL) milk was processed with integrated microfiltration (pore size 1.4 µm). The germ‐enriched retentate was not used for the final whole milk. Microfiltration led only to a negligible change in the content of the main components of the ESL product compared with the source milk. The total protein was only slightly decreased (0.02–0.03%) and the ratio of the protein fractions was unchanged within the measurement accuracy. The furosine content of the isolated fat globuline membrane fraction could be used as a diagnostic to prove cream had been subjected to high‐temperature treatment. The shelf life of the ESL milk was distinctly prolonged compared to HTST‐pasteurized milk.
A tritrophic analysis of host preference and performance in a polyphagous leafminer
Authors: Videla Martín , Valladares Graciela , Salvo Adriana
Published: October 2006

The optimal oviposition theory predicts that oviposition preferences of phytophagous insects should correlate with host suitability for their offspring. As plant host suitability depends not only on its quality as food, but also on its provision of enemy‐free space, we examined the relationship between adult host preference and offspring performance for the leafminerLiriomyza huidobrensis(Blanchard) (Diptera: Agromyzidae) on various host plants, considering also the interaction with natural enemies. Preference and offspring performance were assessed through observational field data and laboratory experiments in central Argentina. Field data suggested a positive host preference – performance linkage, as the leafminer attained larger body size on the crops where it was more abundant. Laboratory trials supported these results:Vicia fabaL. (Fabaceae) was the preferred host in the laboratory as well as in the field, performance ofL. huidobrensisbeing also best on this host, with highest survival rates and shortest development time. The actively feeding larval stage showed the largest plant‐related effects. Higher overall parasitism rates were found on plants from which smaller leafminers were reared, reinforcing the preference–performance linkage. On the other hand, the main parasitoidPhaedrotoma scabriventrisNixon (Hymenoptera: Braconidae) reached larger body size, and caused higher mortality rates on crops where the leafminer was larger. Changes in abundance of particular parasitoid species could thus modify overall parasitism trends.
Effects of leaf epicuticular wax on the movement, foraging behavior, and attack efficacy of Diaeretiella rapae
Authors: Gentry Grant L. , Barbosa Pedro
Published: October 2006

Plant morphological characters can affect the foraging abilities of natural enemies. Heavy wax blooms have been shown to impede predators searching for herbivores on various species in the genus Brassica (Brassicaceae). This study determined whether epicuticular wax affected the foraging behavior of the braconid wasp Diaeratiella rapae (M’Intosh) (Hymenoptera: Braconidae) as it searched for its aphid host Brevicoryne brassicae L. (Homoptera: Aphididae) on the leaves of cauliflower varieties with heavy or light wax blooms. Wasps on the variety with a heavier wax bloom foraged more slowly, groomed more often and for longer periods of time, fell from the leaves more often, took longer to find colonies of aphids, and attacked them at a lower rate than wasps foraging on the variety with a lighter wax bloom. When epicuticular wax was removed from the leaves, the wasp's foraging efficiency and efficacy improved significantly on the cauliflower variety with a heavy wax bloom. The amount of epicuticular wax present on a leaf was shown to impede the ability of a parasitoid to forage, locate, and attack its host.
Construction of a Severe Acute Respiratory Syndrome Coronavirus Infectious cDNA Clone and a Replicon To Study Coronavirus RNA Synthesis
Authors: Almazán Fernando , DeDiego Marta L. , Galán Carmen , Escors David , Álvarez Enrique , Ortego Javier , Sola Isabel , Zuñiga Sonia , Alonso Sara , Moreno Jose L. , Nogales Aitor , Capiscol Carmen , Enjuanes Luis
Published: October 2006

The engineering of a full-length infectious cDNA clone and a functional replicon of the severe acute respiratory syndrome coronavirus (SARS-CoV) Urbani strain as bacterial artificial chromosomes (BACs) is described in this study. In this system, the viral RNA was expressed in the cell nucleus under the control of the cytomegalovirus promoter and further amplified in the cytoplasm by the viral replicase. Both the infectious clone and the replicon were fully stable in
Escherichia coli
. Using the SARS-CoV replicon, we have shown that the recently described RNA-processing enzymes exoribonuclease, endoribonuclease, and 2′-
O
-ribose methyltransferase were essential for efficient coronavirus RNA synthesis. The SARS reverse genetic system developed as a BAC constitutes a useful tool for the study of fundamental viral processes and also for developing genetically defined vaccines.
The Mitogenic Function of Hepatitis B Virus X Protein Resides within Amino Acids 51 to 140 and Is Modulated by N- and C-Terminal Regulatory Regions
Authors: Li Huajie , Chi Chia-Yi , Lee Sook , Andrisani Ourania M.
Published: October 2006

The hepatitis B virus (HBV) X protein (pX) is implicated in hepatocarcinogenesis by an unknown mechanism. pX variants encoded by HBV genomes found integrated in genomic DNA from liver tumors of patients with hepatocellular carcinoma (HCC) generally lack amino acids 134 to 154. Since deregulation of mitogenic pathways is linked to oncogenic transformation, herein we define the pX region required for mitogenic pathway activation. A series of pX deletions was used to construct tetracycline-regulated pX-expressing cell lines. The activation of the mitogenic pathways by these pX deletions expressed in the constructed cell lines was measured by transient transreporter assays, effects on endogenous cyclin A expression, and apoptosis. Conditional expression of pX
51-140
in AML12 clone 4 cell line activates the mitogenic pathways, induces endogenous cyclin A expression, and sensitizes cells to apoptosis, similar to wild-type (WT) pX. By contrast, pX
1-115
is inactive, supporting the idea that amino acids 116 to 140 are required for mitogenic pathway activation. Moreover, this pX deletion analysis demonstrates that WT pX function is modulated by two regions spanning amino acids 1 to 78 and 141 to 154. The N-terminal X
1-78
, expressed via a retroviral vector in WT pX-expressing 4pX-1 cells, coimmunoprecipitates with WT pX, indicating this pX region participates in protein-protein interactions leading to pX oligomerization. Interestingly, pX
1-78
interferes with WT pX in mediating mitogenic pathway activation, endogenous gene expression, and apoptosis. The C-terminal pX region spanning amino acids 141 to 154 decreases pX stability, determined by pulse-chase studies of WT pX and pX
1-140
, suggesting that increased stability of naturally occurring pX variants lacking amino acids 134 to 154 may play a role in HCC development.
Host Cell DNA Repair Pathways in Adeno-Associated Viral Genome Processing
Authors: Choi Vivian W. , McCarty Douglas M. , Samulski R. Jude
Published: October 2006

Recentstudies have shown that wild-type and recombinant adeno-associated
virus (AAV and rAAV) genomes persist in human tissue predominantly as
double-stranded (ds) circular episomes derived from input linear
single-stranded virion DNA. Using self-complementary recombinant AAV
(scAAV) vectors, we generated intermediates that directly transition to
ds circular episomes. The scAAV genome ends are palindromic
hairpin-structured terminal repeats, resembling a double-stranded break
repair intermediate. Utilizing this substrate, we found cellular DNA
recombination and repair factors to be essential for generating
circular episomal products. To identify the specific cellular proteins
involved, the scAAV circularization-dependent vector was used as a
reporter in 19 mammalian DNA repair-deficient cell lines. The results
show that RecQ helicase family members (BLM and WRN), Mre11 and NBS1 of
the Mre11-Rad50-Nbs1 (MRN) complex, and ATM are required for efficient
scAAV genome circularization. We further demonstrated that the scAAV
genome requires ATM and DNA-PK
CS
, but not NBS1, to
efficiently convert to a circular form in nondividing cells in vivo
using transgenic mice. These studies identify specific pathways
involved for further elucidating viral and cellular mechanisms of DNA
maintenance important to the viral life cycle and vector
utilizations.
Novel Envelope Determinants for CCR3 Use by Human Immunodeficiency Virus
Authors: Aasa-Chapman Marlén M. I. , Seymour Craig R. , Williams Ian , McKnight Áine
Published: October 2006

Human immunodeficiency virus type 1 can generally use CCR3 and CCR5 for cell entry. We show that envelopes with novel phenotypes arise during “coreceptor switch”: one loses the ability to use CCR3 (R5-only phenotype), and another gains use of CXCR4 in addition to CCR5 and CCR3 (R3/R5/X4-using phenotype). The envelope determinants for CCR3 use mapped to three amino acids. One, N356 in conserved region 3, is a potential glycosylation site and has not previously been associated with coreceptor use. The other two, R440 and N448 in conserved region 4, are proximal to but distinct from residues already identified as being important for CCR5 binding.
Human Immunodeficiency Virus Type 1 Vpr Induces DNA Replication Stress InVitro and In Vivo
Authors: Zimmerman Erik S. , Sherman Michael P. , Blackett Jana L. , Neidleman Jason A. , Kreis Christophe , Mundt Pamela , Williams Samuel A. , Warmerdam Maria , Kahn James , Hecht Frederick M. , Grant Robert M. , de Noronha Carlos M. C. , Weyrich Andrew S. , Greene Warner C. , Planelles Vicente
Published: October 2006

The human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) causes cell cycle arrest in G2. Vpr-expressing cells display the hallmarks of certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking. In the present study, we demonstrate that HIV-1 infection of primary, human CD4+lymphocytes causes G2arrest in a Vpr-dependent manner and that this response requires ATR, as shown by RNA interference. The event leading to ATR activation in CD4+lymphocytes is the accumulation of replication protein A in nuclear foci, an indication that Vpr likely induces stalling of replication forks. Primary macrophages are refractory to ATR activation by Vpr, a finding that is consistent with the lack of detectable ATR, Rad17, and Chk1 protein expression in these nondividing cells. These observations begin to explain the remarkable resilience of macrophages to HIV-1-induced cytopathicity. To study the in vivo consequences of Vpr function, we isolated CD4+lymphocytes from HIV-1-infected individuals and interrogated the cell cycle status of anti-p24Gag-immunoreactive cells. We report that infected cells in vivo display an aberrant cell cycle profile whereby a majority of cells have a 4N DNA content, consistent with the onset of G2arrest.
JC Virus Minor Capsid Proteins Vp2 and Vp3 Are Essential for Virus Propagation
Authors: Gasparovic M. L. , Gee G. V. , Atwood W. J.
Published: October 2006

Virus-encoded capsid proteins play a major role in the life cycles of all viruses. The JC virus capsid is composed of 72 pentamers of the major capsid protein Vp1, with one of the minor coat proteins Vp2 or Vp3 in the center of each pentamer. Vp3 is identical to two-thirds of Vp2, and these proteins share a DNA binding domain, a nuclear localization signal, and a Vp1-interacting domain. We demonstrate here that both the minor proteins and the myristylation site on Vp2 are essential for the viral life cycle, including the proper packaging of its genome.
Cryoelectron Microscopy Structures of Rotavirus NSP2-NSP5 and NSP2-RNA Complexes: Implications for Genome Replication
Authors: Jiang Xiaofang , Jayaram Hariharan , Kumar Mukesh , Ludtke Steven J. , Estes Mary K. , Prasad B. V. Venkataram
Published: October 2006

The replication and packaging of the rotavirus genome, comprising 11 segments of double-stranded RNA, take place in specialized compartments called viroplasms, which are formed during infection and involve a coordinated interplay of multiple components. Two rotavirus nonstructural proteins, NSP2 (with nucleoside triphosphatase, single-stranded RNA [ssRNA] binding and helix-destabilizing activities) and NSP5, are essential in these events. Previous structural analysis of NSP2 showed that it is an octamer in crystals, obeying 4-2-2 crystal symmetry, with a large 35-Å central hole along the fourfold axis and deep grooves at one of the twofold axes. To ascertain that the solution structure of NSP2 is the same as that in the crystals and investigate how NSP2 interacts with NSP5 and RNA, we carried out single-particle cryoelectron microscopy (cryo-EM) analysis of NSP2 alone and in complexes with NSP5 and ssRNA at subnanometer resolution. Because full-length NSP5 caused severe aggregation upon mixing with NSP2, the deletion construct NSP5
66-188
was used in these studies. Our studies show that the solution structure of NSP2 is same as the crystallographic octamer and that both NSP5
66-188
and ssRNA bind to the grooves in the octamer, which are lined by positively charged residues. The fitting of the NSP2 crystal structure to cryo-EM reconstructions of the complexes indicates that, in contrast to the binding of NSP5
66-188
, the binding of RNA induces noticeable conformational changes in the NSP2 octamer. Consistent with the observation that both NSP5 and RNA share the same binding site on the NSP2 octamer, filter binding assays showed that NSP5 competes with ssRNA binding, indicating that one of the functions of NSP5 is to regulate NSP2-RNA interactions during genome replication.
Possible Therapeutic Vaccine Strategy against Human Immunodeficiency Virus Escape from Reverse Transcriptase Inhibitors Studied in HLA-A2 Transgenic Mice
Authors: Okazaki Takahiro , Terabe Masaki , Catanzaro Andrew T. , Pendleton C. David , Yarchoan Robert , Berzofsky Jay A.
Published: October 2006

Mutation of human immunodeficiency virus (HIV) leading to escape from anti-HIV drugs is the greatest challenge to the treatment of HIV infection. High-grade resistance to the nucleoside reverse transcriptase (RT) inhibitor lamivudine (also known as 3TC) is associated with a substitution of valine for methionine at position 184 of RT. This amino acid residue is contained within the HLA-A2-restricted epitope VIYQYMDDL (RT-WT). Here, we sought to determine whether a peptide vaccine could be developed using an epitope enhancement strategy that could induce a cytotoxic T-lymphocyte (CTL) response specific for an epitope containing the drug resistance mutation M184V to exert an opposing selective pressure. RT-WT-specific CTLs developed from HLA-A2 transgenic mice did not recognize the M184V mutation of RT-WT (RT-M184V). However, RT-M184V exhibited higher binding affinity for HLA-A2 than RT-WT. Also, both anchor-enhanced RT-WT (RT-2L9V) and RT-2L9V-M184V-specific CTLs recognized RT-M184V and displayed cross-reactivity to RT-WT. Nevertheless, the CTL repertoire elicited by the epitope-enhanced RT-2L9V-M184V appeared more selective for the RT inhibitor-induced M184V mutation. Peptide vaccines based on such strategies may be worth testing for their ability to exert selective pressure against drug-resistant strains and thus delay or prevent the development of HIV with the M184V resistance mutation.
Oxidative stress of myosin contributes to skeletal muscle dysfunction in rats with chronic heart failure
Authors: Coirault Catherine , Guellich Aziz , Barbry Thomas , Samuel Jane Lise , Riou Bruno , Lecarpentier Yves
Published: October 2006

Intrinsic muscle abnormalities affecting skeletal muscle are often reported during chronic heart failure (CHF). Because myosin is the molecular motor of force generation, we sought to determine whether its dysfunction contributes to skeletal muscle weakness in CHF and, if so, to identify the underlying causative factors. Severe CHF was induced in rats by aortic stenosis. In diaphragm and soleus muscles, we investigated in vitro mechanical performance, myosin-based actin filament motility, myosin heavy (MHC) and light (MLC) chain isoform compositions, MLC integrity, caspase-3 activation, and oxidative damage. Diaphragm and soleus muscles from CHF exhibited depressed mechanical performance. Myosin sliding velocities were 16 and 20% slower in CHF than in sham in diaphragm (1.9 ± 0.1 vs. 1.6 ± 0.1 μm/s) and soleus (0.6 ± 0.1 vs. 0.5 ± 0.1 μm/s), respectively (each P < 0.05). The ratio of slow-to-fast myosin isoform did not differ between sham and CHF. Immunoblots with anti-MLC antibodies did not detect the presence of protein fragments, and no activation of caspase-3 was evidenced. Immunolabeling revealed oxidative damage in CHF muscles, and MHC was the main oxidized protein. Lipid peroxidation and expression of oxidized MHC were significantly higher in CHF than in shams. In vitro myosin exposure to increasing ONOO−concentrations was associated with an increasing amount of oxidized MHC and a reduced myosin velocity. These data provide experimental evidence that intrinsic myosin dysfunction occurs in CHF and may be related to oxidative damage to myosin.
Extracellular glycerol regulates the cardiac energy balance in a working rat heart model
Authors: Gambert Ségolène , Héliès-Toussaint Cécile , Grynberg Alain
Published: October 2006

We reported previously that glycerol is a substrate for energy production in cardiomyocytes. Increasing glycerol availability results in increased glycerol uptake and its involvement in complex lipid biosynthesis and energy production. This study evaluated the relationship between glycerol supply, energy demand, and intermediary metabolism leading to energy production. The work was performed on isolated rat heart perfused in the working mode. Glycerol concentrations modeled the fasting (0.33 mM) and fed (3.33 mM) states. Cardiac energy demand was modeled by increasing heart rate from 350 to 450 beats/min (bpm). Increasing glycerol supply increased glycerol uptake from 1.4 (350 bpm) to 3.8 (450 bpm) and from 9.7 (350 bpm) to 34.2 (450 bpm) μmol glycerol/heart in 30 min at 0.33 and 3.33 mM glycerol, respectively. At low glycerol supply, increasing heart rate did not influence the complex lipid synthesis. Conversely, high glycerol concentration increased the complex lipid synthesis by 5- and 30-fold at 350 and 450 bpm, respectively. Increasing glycerol supply and heart rate significantly increased glycerol oxidation rate. Moreover, increasing glycerol supply did not affect glucose oxidation but increased palmitate uptake and significantly decreased its β-oxidation. Physiological concentrations of glycerol contribute to the cardiac intermediary metabolism, both for energy production and glycerolipid synthesis. Increasing energy demand enhances the requirement and use of glycerol. Glycerol contributes to the regulation of cardiac metabolism and energy balance, mainly by decreasing the contribution of fatty acid oxidation, and may thus represent a new factor in cardiac protection through the reduction of oxygen demand.
Hydraulic conductance of lung endothelial phenotypes and Starling safety factors against edema
Authors: Parker James C.
Published: October 2006

Recent permeability studies comparing endothelial cell phenotypes derived from alveolar and extra-alveolar vessels have significant implications for interpreting the mechanisms of fluid homeostasis in the intact lung. These studies indicate that confluent monolayers of rat pulmonary microvascular endothelial cells had a hydraulic conductance ( Lp) that was only 5% and a transendothelial flux rate for 72-kDa dextran only 9% of values determined for rat pulmonary artery endothelial cell monolayers. On the basis of previous studies partitioning the filtration coefficients between alveolar and extra-alveolar vascular segments in rat lungs and previous studies of lymph albumin fluxes and permeability, the contribution of the alveolar capillary segment to total albumin flux in lymph was estimated to be less than 10%. In addition, the Starling safety factors against the edema calculated for the alveolar capillaries are quite different from those estimated for whole lung. Estimates of the edema safety factor due to increased filtration across the alveolar capillary wall based on the low Lp indicate it is quantitatively the greatest safety factor, although it would be a minor safety factor for extra-alveolar vessels. Also, a markedly higher effective protein osmotic absorptive force for plasma proteins must occur in the capillaries relative to extra-alveolar vessels. The lower Lp for alveolar capillaries also has implications for the sequence of hydrostatic edema formation, and it also may have a role in preventing exercise-induced alveolar flooding.
Sirtuin regulates cigarette smoke-induced proinflammatory mediator release via RelA/p65 NF-κB in macrophages in vitro and in rat lungs in vivo: implications for chronic inflammation and aging
Authors: Yang Se-Ran , Wright Jessica , Bauter Mark , Seweryniak Kathryn , Kode Aruna , Rahman Irfan
Published: October 2006

The silent information regulator 2 (Sir2) family of proteins (sirtuins or SIRTs), which belong to class III histone/protein deacetylases, have been implicated in calorie restriction, aging, and inflammation. We hypothesized that cigarette smoke-mediated proinflammatory cytokine release is regulated by SIRT1 by its interaction with NF-κB in a monocyte-macrophage cell line (MonoMac6) and in inflammatory cells of rat lungs. Cigarette smoke extract (CSE) exposure to MonoMac6 cells caused dose- and time-dependent decreases in SIRT1 activity and levels, which was concomitant to increased NF-κB-dependent proinflammatory mediator release. Similar decrements in SIRT1 were also observed in inflammatory cells in the lungs of rats exposed to cigarette smoke as well as with increased levels of several NF-κB-dependent proinflammatory mediators in bronchoalveolar lavage fluid and in lungs. Sirtinol, an inhibitor of SIRT1, augmented, whereas resveratrol, an activator of SIRT1, inhibited CSE-mediated proinflammatory cytokine release. CSE-mediated inhibition of SIRT1 was associated with increased NF-κB levels. Furthermore, we showed that SIRT1 interacts with the RelA/p65 subunit of NF-κB, which was disrupted by cigarette smoke, leading to increased acetylation RelA/p65 in MonoMac6 cells. Thus our data show that SIRT1 regulates cigarette smoke-mediated proinflammatory mediator release via NF-κB, implicating a role of SIRT1 in sustained inflammation and aging of the lungs.
Racial and Gender Attitudes as Predictors of Feminist Activism Among Self-Identified African American Feminists
Authors: White Aaronette M.
Published: October 2006

This study explored the racial and gender attitudes and feminist activism of 100 self-identified African American feminists (50 women and 50 men) to determine (a) whether Black feminists possess weak racial identities due to feminist influences stereotypically associated with White American culture, (b) if Black feminist men share similar gender attitudes, beliefs, and feminist activism levels with Black feminist women, and (c) whether racial and gender identity attitudes predict feminist activism. Multivariate analyses revealed strong racial and feminist identities (measured by the Racial Identity Attitudes Scale-Form B [RIASB] and the Gender Role Journey Scale, respectively) and no significant gender differences. However, Black women reported a wider range of feminist activism than Black men. A hierarchical regression analysis revealed that sexual orientation, preference for the label feminist, and high scores on the Gender Role Journey Personal-Professional Activism subscale were important predictors of feminist activism. Empirical findings refute common stereotypes characterizing feminism as White, emasculating, of no interest to men, and divisive.
National Interest Frames and Public Opinion about World Affairs
Authors: Brewer Paul R.
Published: October 2006

This study used an experiment to examine whether—and if so, how—national interest frames in media coverage influence public opinion about world affairs. Compared to participants in a control condition, those who read a news article framing China as a competitor to the United States held less favorable opinions regarding China. In contrast, participants who read an article about common Chinese and American interests held particularly favorable opinions regarding China. Compared to baseline participants, those who read about common Russian and American interests held more favorable opinions regarding Russia—as did participants who read about the possibility for mutually beneficial exchange between the United States and Russia. Taken as a whole, the findings suggest that national interest frames in media coverage resonate with ordinary citizens.
The melanocortin system in leukocyte biology
Authors: Catania Anna
Published: October 2006

The melanocortin system is composed of the melanocortin peptides, adrenocorticotropic hormone and α-, β-, and γ-melanocyte-stimulating hormone, the melanocortin receptors (MCRs), and the endogenous antagonists agouti- and agouti-related protein. Melanocortin peptides exert multiple effects upon the host, including anti-inflammatory and immunomodulatory effects. Leukocytes are a source of melanocortins and a major target for these peptides. Because of reduced translocation of the nuclear factor NF-κB to the nucleus, MCR activation by their ligands causes a collective reduction of the most important molecules involved in the inflammatory process. This review examines how melanocortin peptides and their receptors participate in leukocyte biology.
Adult ENT day surgery: a case for expansion of services
Authors: Bhutta MF
Published: October 2006

Day case surgery is acknowledged to have many advantages over inpatient surgery, including greater efficiency, reduced risk of infection, reduced waiting lists and lower costs. 1 Although in the past two decades day surgery has experienced a gradual expansion of services in the UK, the 2001 Audit Commission report on day surgery showed that there was still far more potential for expansion 2 and the Department of Health launched the 'day surgery strategy' in January 2002 with the specific aim of increasing and improving day surgery in the NHS.
The training of the next generation of surgeons in Australia
Authors: Amott DH , Hanney RM
Published: October 2006

The profession of surgery is a calling in which the standards can only be responsibly set by the profession itself. The Royal Australasian College of Surgeons (RACS) has been training surgeons in Australia and New Zealand since 1927. Many challenges to modern surgical training are shared within an increasingly globalised surgical community, while specific local issues add their own challenges to the continued provision of high quality surgical training.
Taschenbuch der Staats‐Arzneywissenschaft für Aerzte und Wundärzte
Authors: Niemann J. Fr.
Published: October 2006

Taschenbuch der Staats‐Arzneywissenschaft für Aerzte und Wundärzte. Von Dr. J. Fr. Niemann, königl. Preuss. Regierungs‐ und Medicinalrathe zu Merseburg, Ritter des eisernen Kreuzes zweiter Klasse, mehrerer gelehrten Gesellschaften Mitgliede. I. Band. Gerichtliche Arzneywissenschaft. Leipzig 1827. Bei J. A. Barth.
Reaktionen mit Acyl‐isocyanaten. 5. Mitt.
Authors: Neidlein R.
Published: October 2006

Thio‐acyl‐isocyanate reagieren mit Mono‐ und Di‐isonitrilen zu 5‐Iminothiazolin‐on‐(4)‐derivaten, Acyl‐isocyanate mit Di‐isonitrilen zu bifunktionellen 5‐Imino‐oxazolin‐on‐(4)‐verbindungen. Die Struktur der Substanzen wird durch UV‐Spektroskopie gesichert.