bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance and humaneness of chloropicrin, phosphine and carbon monoxide as rabbit-warren fumigants
Authors: Gigliotti F. , Marks C. A. , Busana F.
Published: June 2009

Concerns about the humaneness and efficacy of chloropicrin (CLPN) and phosphine (PH3) as warren fumigants for the control of European rabbits (Oryctolagus cuniculus) prompted this investigation into the field performance and humaneness of carbon monoxide (CO) as an alternative fumigant. Comparative trials were performed in a naturally formed 1.3-m3 warren fitted with gas, temperature and humidity sensors as well as infrared cameras and microphones. Trials used concentrations of 5% and 6% CO introduced at 400 L min−1, and standard field practices for CLPN and PH3. Rabbits exposed to CLPN displayed signs of intense irritation and extreme distress during a lethal toxicosis lasting a mean of 82.5 min, supporting previous conclusions that CLPN causes suffering. Phosphine gas killed 10 of 12 rabbits, in a mean of 225.3 min. This relatively poor performance was attributed to the low rate of gas production and passive diffusion through the warren, reflected in highly variable warren concentrations between trials. Phosphine caused greater agitation on the onset of first symptoms than did CO; however, the behavioural symptoms after collapse were broadly similar. Carbon monoxide dispersed evenly in the warren, caused no immediate irritation or distress and produced a gradual stupor before unconsciousness and death. Concentrations of 6% CO killed rabbits almost three times faster than 5% CO, suggesting that relatively small increments of concentration and exposure time are crucial in obtaining a consistently rapid death. A concentration of 6% CO caused death in 8 of 10 rabbits in a mean of 28.3 min; some 2.9 and 8 times faster than CLPN and PH3 respectively. The time from collapse until death did not appear to be appreciably different for PH3 and 6% CO. The present study demonstrated that CO has potential as a rapid-acting, humane and effective fumigant for rabbit control.
Inbreeding and testicular abnormalities in a bottlenecked population of koalas (Phascolarctos cinereus)
Authors: Cristescu Romane , Cahill Valma , Sherwin William B. , Handasyde Kathrine , Carlyon Kris , Whisson Desley , Herbert Catherine A. , Carlsson Britt Louise J. , Wilton Alan N. , Cooper Des W.
Published: June 2009

Habitat destruction and fragmentation, interactions with introduced species or the relocation of animals to form new populations for conservation purposes may result in a multiplication of population bottlenecks. Examples are the translocations of koalas to French Island and its derivative Kangaroo Island population, with both populations established as insurance policies against koala extinction. In terms of population size, these conservation programs were success stories. However, the genetic story could be different. We conducted a genetic investigation of French and Kangaroo Island koalas by using 15 microsatellite markers, 11 of which are described here for the first time. The results confirm very low genetic diversity. French Island koalas have 3.8 alleles per locus and Kangaroo Island koalas 2.4. The present study found a 19% incidence of testicular abnormality in Kangaroo Island animals. Internal relatedness, an individual inbreeding coefficient, was not significantly different in koalas with testicular abnormalities from that in other males, suggesting the condition is not related to recent inbreeding. It could instead result from an unfortunate selection of founder individuals carrying alleles for testicular abnormalities, followed by a subsequent increase in these alleles’ frequencies through genetic drift and small population-related inefficiency of selection. Given the low diversity and possible high prevalence of deleterious alleles, the genetic viability of the population remains uncertain, despite its exponential growth so far. This stands as a warning to other introductions for conservation reasons.
Deslorelin implants control fertility in urban brushtail possums (Trichosurus vulpecula) without negatively influencing their body-condition index
Authors: Lohr Cheryl A. , Mills Harriet , Robertson Helen , Bencini Roberta
Published: June 2009

Wild brushtail possums (Trichosurus vulpecula) occur in large numbers in the grounds of Perth Zoo, Western Australia. These possums are a problem because they consume feed the zoo buys for its captive animals, damage seedlings and trees and many need to be treated for injuries sustained during fights with conspecifics. A contraceptive implant, which contains the gonadotrophin releasing hormone (GnRH) agonist deslorelin, could be a potential method of managing this population. We tested the efficacy of the implant and its impact on the body-condition index of treated possums with Kaplan–Meier analysis and a mixed model with residual maximum likelihood. We implanted 60 female possums with deslorelin and monitored reproductive success of treated and untreated possums for the following 18 months. At the conclusion of the study, 80% of 20 treated females recaptured had shown no evidence of breeding activity, giving an average minimum duration of effective contraception of 381 days. The implant did not have a negative impact on the body-condition index of treated possums during the course of the study. Our results suggest that deslorelin implants could be an effective management tool for brushtail possums at Perth Zoo and in other urban environments.
Using simulation to improve wildlife surveys: wintering mallards in Mississippi, USA
Authors: Pearse Aaron T. , Reinecke Kenneth J. , Dinsmore Stephen J. , Kaminski Richard M.
Published: June 2009

Wildlife conservation plans generally require reliable data about population abundance and density. Aerial surveys often can provide these data; however, associated costs necessitate designing and conducting surveys efficiently. We developed methods to simulate population distributions of mallards (Anas platyrhynchos) wintering in western Mississippi, USA, by combining bird observations from three previous strip-transect surveys and habitat data from three sets of satellite images representing conditions when surveys were conducted. For each simulated population distribution, we compared 12 primary survey designs and two secondary design options by using coefficients of variation (CV) of population indices as the primary criterion for assessing survey performance. In all, 3 of the 12 primary designs provided the best precision (CV ≤ 11.7%) and performed equally well (diff ≤ 0.6%). Features of the designs that provided the largest gains in precision were optimal allocation of sample effort among strata and configuring the study area into five rather than four strata, to more precisely estimate mallard indices in areas of consistently high density. Of the two secondary design options, we found including a second observer to double the size of strip transects increased precision or decreased costs, whereas ratio estimation using auxiliary habitat data from satellite images did not increase precision appreciably. We recommend future surveys of mallard populations in our study area use the strata we developed, optimally allocate samples among strata, employ PPS or EPS sampling, and include two observers when qualified staff are available. More generally, the methods we developed to simulate population distributions from prior survey data provide a cost-effective method to assess performance of alternative wildlife surveys critical to informing management decisions, and could be extended to account for effects of detectability on estimates of true abundance.
Wildlife Research in a changing world
Authors: White Piran C. L. , Taylor Andrea C. , Boutin Stan , Myers Camilla , Krebs Charles J.
Published: June 2009

Wildlife populations on both land and in the sea are under increasing pressure from both direct and indirect anthropogenic impacts. Threats to wildlife, such as over-exploitation, habitat loss, invasive species, infectious disease and climate change persist; yet in some situations, wildlife populations are the subject of management to reduce their unwanted impacts on economic, agricultural and conservation interests. The contrasting requirements of declining and overabundant populations, sometimes existing as part of the same ecosystem, mean that wildlife management needs to be viewed increasingly as part of an integrated social–ecological system. Moreover, solutions to wildlife-management problems may require new combinations of ecological knowledge, technological innovation and an understanding of the social and economic factors involved. The disciplinary scope of Wildlife Research will be broadening to reflect these changes. Wildlife Research has tended to focus on terrestrial systems in the past, but research approaches and findings are increasingly relevant across different environments, and consequently, we will also be expanding our coverage of freshwater and marine systems. We are planning to publish at least one Special Issue each year, to highlight new areas of research and the increasing internationalisation of wildlife management, and we welcome suggestions for these. We are also pleased to be able to offer fast-track publication of papers that contain results of high topical significance or policy relevance. We hope that the increased topical, disciplinary and geographical coverage of Wildlife Research will enhance its position as one of the leading international journals in applied ecology and environmental management.
Changes in the Asian monsoon climate during 1700–1850 induced by preindustrial cultivation
Authors: Takata Kumiko , Saito Kazuyuki , Yasunari Tetsuzo
Published: June 2009

Preindustrial changes in the Asian summer monsoon climate from the 1700s to the 1850s were estimated with an atmospheric general circulation model (AGCM) using historical global land cover/use change data reconstructed for the last 300 years. Extended cultivation resulted in a decrease in monsoon rainfall over the Indian subcontinent and southeastern China and an associated weakening of the Asian summer monsoon circulation. The precipitation decrease in India was marked and was consistent with the observational changes derived from examining the Himalayan ice cores for the concurrent period. Between the 1700s and the 1850s, the anthropogenic increases in greenhouse gases and aerosols were still minor; also, no long-term trends in natural climate variations, such as those caused by the ocean, solar activity, or volcanoes, were reported. Thus, we propose that the land cover/use change was the major source of disturbances to the climate during that period. This report will set forward quantitative examination of the actual impacts of land cover/use changes on Asian monsoons, relative to the impact of greenhouse gases and aerosols, viewed in the context of global warming on the interannual, decadal, and centennial time scales.
Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity
Authors: Nekooki-Machida Yoko , Kurosawa Masaru , Nukina Nobuyuki , Ito Kazuki , Oda Toshiro , Tanaka Motomasa
Published: June 2009

A hallmark of polyglutamine diseases, including Huntington disease (HD), is the formation of β-sheet-rich aggregates, called amyloid, of causative proteins with expanded polyglutamines. However, it has remained unclear whether the polyglutamine amyloid is a direct cause or simply a secondary manifestation of the pathology. Here we show that huntingtin-exon1 (thtt) with expanded polyglutamines remarkably misfolds into distinct amyloid conformations under different temperatures, such as 4 °C and 37 °C. The 4 °C amyloid has loop/turn structures together with mostly β-sheets, including exposed polyglutamines, whereas the 37 °C amyloid has more extended and buried β-sheets. By developing a method to efficiently introduce amyloid into mammalian cells, we found that the formation of the 4 °C amyloid led to substantial toxicity, whereas the toxic effects of the 37 °C amyloid were very small. Importantly, thtt amyloids in different brain regions of HD mice also had distinct conformations. The thermolabile thtt amyloid with loop/turn structures in the striatum showed higher toxicity, whereas the rigid thtt amyloid with more extended β-sheets in the hippocampus and cerebellum had only mild toxic effects. These studies show that the thtt protein with expanded polyglutamines can misfold into distinct amyloid conformations and, depending on the conformations, the amyloids can be either toxic or nontoxic. Thus, the amyloid conformation of thtt may be a critical determinant of cytotoxicity in HD.
AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist
Authors: Rhodes Daniel R. , Ateeq Bushra , Cao Qi , Tomlins Scott A. , Mehra Rohit , Laxman Bharathi , Kalyana-Sundaram Shanker , Lonigro Robert J. , Helgeson Beth E. , Bhojani Mahaveer S. , Rehemtulla Alnawaz , Kleer Celina G. , Hayes Daniel F. , Lucas Peter C. , Varambally Sooryanarayana , Chinnaiyan Arul M.
Published: June 2009

Breast cancer patients have benefited from the use of targeted therapies directed at specific molecular alterations. To identify additional opportunities for targeted therapy, we searched for genes with marked overexpression in subsets of tumors across a panel of breast cancer profiling studies comprising 3,200 microarray experiments. In addition to prioritizing ERBB2, we found AGTR1, the angiotensin II receptor type I, to be markedly overexpressed in 10–20% of breast cancer cases across multiple independent patient cohorts. Validation experiments confirmed that AGTR1 is highly overexpressed, in several cases more than 100-fold. AGTR1 overexpression was restricted to estrogen receptor-positive tumors and was mutually exclusive with ERBB2 overexpression across all samples. Ectopic overexpression of AGTR1 in primary mammary epithelial cells, combined with angiotensin II stimulation, led to a highly invasive phenotype that was attenuated by the AGTR1 antagonist losartan. Similarly, losartan reduced tumor growth by 30% in AGTR1-positive breast cancer xenografts. Taken together, these observations indicate that marked AGTR1 overexpression defines a subpopulation of ER-positive, ERBB2-negative breast cancer that may benefit from targeted therapy with AGTR1 antagonists, such as losartan.
Radiocarbon dating of charcoal and bone collagen associated with early pottery at Yuchanyan Cave, Hunan Province, China
Authors: Boaretto Elisabetta , Wu Xiaohong , Yuan Jiarong , Bar-Yosef Ofer , Chu Vikki , Pan Yan , Liu Kexin , Cohen David , Jiao Tianlong , Li Shuicheng , Gu Haibin , Goldberg Paul , Weiner Steve
Published: June 2009

Yuchanyan Cave in Daoxian County, Hunan Province (People's Republic of China), yielded fragmentary remains of 2 or more ceramic vessels, in addition to large amounts of ash, a rich animal bone assemblage, cobble and flake artifacts, bone tools, and shell tools. The artifacts indicate that the cave was a Late Paleolithic foragers' camp. Here we report on the radiocarbon ages of the sediments based on analyses of charcoal and bone collagen. The best-preserved charcoal and bone samples were identified by prescreening in the field and laboratory. The dates range from around 21,000 to 13,800 cal BP. We show that the age of the ancient pottery ranges between 18,300 and 15,430 cal BP. Charcoal and bone collagen samples located above and below one of the fragments produced dates of around 18,000. These ceramic potsherds therefore provide some of the earliest evidence for pottery making in China.
Aberrant epithelial morphology and persistent epidermal growth factor receptor signaling in a mouse model of renal carcinoma
Authors: Morris Zachary S. , McClatchey Andrea I.
Published: June 2009

The epidermal growth factor receptor (EGFR) has frequently been implicated in hyperproliferative diseases of renal tubule epithelia. We have shown that the NF2 tumor suppressor Merlin inhibits EGFR internalization and signaling in a cell contact–dependent manner. Interestingly, despite the paucity of recurring mutations in human renal cell carcinoma (RCC), homozygous mutation of the
NF2
gene is found in ≈2% of RCC patient samples in the Sanger COSMIC database. To examine the roles of Merlin and EGFR in kidney tumorigenesis, we generated mice with a targeted deletion of
Nf2
in the proximal convoluted epithelium using a
Villin-Cre
transgene. All of these mice developed intratubular neoplasia by 3 months, which progressed to invasive carcinoma by 6–10 months. Kidneys from these mice demonstrated marked hyperproliferation and a concomitant increase in label-retaining putative progenitor cells. Early lumen-filling lesions in this model exhibited hyperactivation of EGFR signaling, altered solubility of adherens junctions components, and loss of epithelial polarity. Renal cortical epithelial cells derived from either early or late lesions were dependent on EGF for in vitro proliferation and were arrested by pharmacologic inhibition of EGFR or re-expression of
Nf2
. These cells formed malignant tumors upon s.c. injection into immunocompromised mice before in vitro passage. Treatment of
Vil-Cre
;

Nf2
lox/lox

mice with the EGFR inhibitor erlotinib halted the proliferation of tumor cells. These studies give added credence to the role of EGFR signaling and perhaps
Nf2
deficiency in RCC and describe a rare and valuable mouse model for exploring the molecular basis of this disease.
Targeting atherosclerosis by using modular, multifunctional micelles
Authors: Peters David , Kastantin Mark , Kotamraju Venkata Ramana , Karmali Priya P. , Gujraty Kunal , Tirrell Matthew , Ruoslahti Erkki
Published: June 2009

Subtle clotting that occurs on the luminal surface of atherosclerotic plaques presents a novel target for nanoparticle-based diagnostics and therapeutics. We have developed modular multifunctional micelles that contain a targeting element, a fluorophore, and, when desired, a drug component in the same particle. Targeting atherosclerotic plaques in ApoE-null mice fed a high-fat diet was accomplished with the pentapeptide cysteine-arginine-glutamic acid-lysine-alanine, which binds to clotted plasma proteins. The fluorescent micelles bind to the entire surface of the plaque, and notably, concentrate at the shoulders of the plaque, a location that is prone to rupture. We also show that the targeted micelles deliver an increased concentration of the anticoagulant drug hirulog to the plaque compared with untargeted micelles.
Molecular interactions in rotavirus assembly and uncoating seen by high-resolution cryo-EM
Authors: Chen James Z. , Settembre Ethan C. , Aoki Scott T. , Zhang Xing , Bellamy A. Richard , Dormitzer Philip R. , Harrison Stephen C. , Grigorieff Nikolaus
Published: June 2009

Rotaviruses, major causes of childhood gastroenteritis, are nonenveloped, icosahedral particles with double-strand RNA genomes. By the use of electron cryomicroscopy and single-particle reconstruction, we have visualized a rotavirus particle comprising the inner capsid coated with the trimeric outer-layer protein, VP7, at a resolution (4 Å) comparable with that of X-ray crystallography. We have traced the VP7 polypeptide chain, including parts not seen in its X-ray crystal structure. The 3 well-ordered, 30-residue, N-terminal “arms” of each VP7 trimer grip the underlying trimer of VP6, an inner-capsid protein. Structural differences between free and particle-bound VP7 and between free and VP7-coated inner capsids may regulate mRNA transcription and release. The Ca
2+
-stabilized VP7 intratrimer contact region, which presents important neutralizing epitopes, is unaltered upon capsid binding.
The structure of
Aquifex aeolicus
sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration
Authors: Marcia Marco , Ermler Ulrich , Peng Guohong , Michel Hartmut
Published: June 2009

Sulfide:quinone oxidoreductase (SQR) is a flavoprotein with homologues in all domains of life except plants. It plays a physiological role both in sulfide detoxification and in energy transduction. We isolated the protein from native membranes of the hyperthermophilic bacterium
Aquifex aeolicus
, and we determined its X-ray structure in the “as-purified,” substrate-bound, and inhibitor-bound forms at resolutions of 2.3, 2.0, and 2.9 Å, respectively. The structure is composed of 2 Rossmann domains and 1 attachment domain, with an overall monomeric architecture typical of disulfide oxidoreductase flavoproteins.
A. aeolicus
SQR is a surprisingly trimeric, periplasmic integral monotopic membrane protein that inserts about 12 Å into the lipidic bilayer through an amphipathic helix–turn–helix tripodal motif. The quinone is located in a channel that extends from the
si
side of the FAD to the membrane. The quinone ring is sandwiched between the conserved amino acids Phe-385 and Ile-346, and it is possibly protonated upon reduction via Glu-318 and/or neighboring water molecules. Sulfide polymerization occurs on the
re
side of FAD, where the invariant Cys-156 and Cys-347 appear to be covalently bound to polysulfur fragments. The structure suggests that FAD is covalently linked to the polypeptide in an unusual way, via a disulfide bridge between the 8-methyl group and Cys-124. The applicability of this disulfide bridge for transferring electrons from sulfide to FAD, 2 mechanisms for sulfide polymerization and channeling of the substrate, S
2−
, and of the product, S

n

, in and out of the active site are discussed.
Specific
Arabidopsis
HSP90.2 alleles recapitulate RAR1 cochaperone function in plant NB-LRR disease resistance protein regulation
Authors: Hubert David A. , He Yijian , McNulty Brian C. , Tornero Pablo , Dangl Jeffery L.
Published: June 2009

Both plants and animals require the activity of proteins containing nucleotide binding (NB) domain and leucine-rich repeat (LRR) domains for proper immune system function. NB-LRR proteins in plants (NLR proteins in animals) also require conserved regulation via the proteins SGT1 and cytosolic HSP90. RAR1, a protein specifically required for plant innate immunity, interacts with SGT1 and HSP90 to maintain proper NB-LRR protein steady-state levels. Here, we present the identification and characterization of specific mutations in
Arabidopsis
HSP90.2 that suppress all known phenotypes of
rar1
. These mutations are unique with respect to the many mutant alleles of HSP90 identified in all systems in that they can bypass the requirement for a cochaperone and result in the recovery of client protein accumulation and function. Additionally, these mutations separate HSP90 ATP hydrolysis from HSP90 function in client protein folding and/or accumulation. By recapitulating the activity of RAR1, these novel hsp90 alleles allow us to propose that RAR1 regulates the physical open–close cycling of a known “lid structure” that is used as a dynamic regulatory HSP90 mechanism. Thus, in
rar1
, lid cycling is locked into a conformation favoring NB-LRR client degradation, likely via SGT1 and the proteasome.
Priming of protective T cell responses against virus-induced tumors in mice with human immune system components
Authors: Strowig Till , Gurer Cagan , Ploss Alexander , Liu Yi-Fang , Arrey Frida , Sashihara Junji , Koo Gloria , Rice Charles M. , Young James W. , Chadburn Amy , Cohen Jeffrey I. , Münz Christian
Published: June 2009

Many pathogens that cause human disease infect only humans. To identify the mechanisms of immune protection against these pathogens and also to evaluate promising vaccine candidates, a small animal model would be desirable. We demonstrate that primary T cell responses in mice with reconstituted human immune system components control infection with the oncogenic and persistent Epstein-Barr virus (EBV). These cytotoxic and interferon-γ–producing T cell responses were human leukocyte antigen (HLA) restricted and specific for EBV-derived peptides. In HLA-A2 transgenic animals and similar to human EBV carriers, T cell responses against lytic EBV antigens dominated over recognition of latent EBV antigens. T cell depletion resulted in elevated viral loads and emergence of EBV-associated lymphoproliferative disease. Both loss of CD4+ and CD8+ T cells abolished immune control. Therefore, this mouse model recapitulates features of symptomatic primary EBV infection and generates T cell–mediated immune control that resists oncogenic transformation.
Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome
Authors: Minegishi Yoshiyuki , Saito Masako , Nagasawa Masayuki , Takada Hidetoshi , Hara Toshiro , Tsuchiya Shigeru , Agematsu Kazunaga , Yamada Masafumi , Kawamura Nobuaki , Ariga Tadashi , Tsuge Ikuya , Karasuyama Hajime
Published: June 2009

Hyper-IgE syndrome (HIES) is a primary immunodeficiency characterized by atopic manifestations and susceptibility to infections with extracellular pathogens, typically Staphylococcus aureus, which preferentially affect the skin and lung. Previous studies reported the defective differentiation of T helper 17 (Th17) cells in HIES patients caused by hypomorphic STAT3 mutations. However, the apparent contradiction between the systemic Th17 deficiency and the skin/lung-restricted susceptibility to staphylococcal infections remains puzzling. We present a possible molecular explanation for this enigmatic contradiction. HIES T cells showed impaired production of Th17 cytokines but normal production of classical proinflammatory cytokines including interleukin 1β. Normal human keratinocytes and bronchial epithelial cells were deeply dependent on the synergistic action of Th17 cytokines and classical proinflammatory cytokines for their production of antistaphylococcal factors, including neutrophil-recruiting chemokines and antimicrobial peptides. In contrast, other cell types were efficiently stimulated with the classical proinflammatory cytokines alone to produce such factors. Accordingly, keratinocytes and bronchial epithelial cells, unlike other cell types, failed to produce antistaphylococcal factors in response to HIES T cell–derived cytokines. These results appear to explain, at least in part, why HIES patients suffer from recurrent staphylococcal infections confined to the skin and lung in contrast to more systemic infections in neutrophil-deficient patients.
Neonatal tolerance revisited: a perinatal window for Aire control of autoimmunity
Authors: Guerau-de-Arellano Mireia , Martinic Marianne , Benoist Christophe , Mathis Diane
Published: June 2009

There has long been conceptual and experimental support for, but also challenges to, the notion that the initial period of the immune system's development is particularly important for the establishment of tolerance to self. The display of self-antigens by thymic epithelial cells is key to inducing tolerance in the T lymphocyte compartment, a process enhanced by the Aire transcription factor. Using a doxycycline-regulated transgene to target Aire expression to the thymic epithelium, complementing the Aire knockout in a temporally controlled manner, we find that Aire is essential in the perinatal period to prevent the multiorgan autoimmunity that is typical of Aire deficiency. Surprisingly, Aire could be shut down soon thereafter and remain off for long periods, with few deleterious consequences. The lymphopenic state present in neonates was a factor in this dichotomy because inducing lymphopenia during Aire turnoff in adults recreated the disease, which, conversely, could be ameliorated by supplementing neonates with adult lymphocytes. In short, Aire expression during the perinatal period is both necessary and sufficient to induce long-lasting tolerance and avoid autoimmunity. Aire-controlled mechanisms of central tolerance are largely dispensable in the adult, as a previously tolerized T cell pool can buffer newly generated autoreactive T cells that might emerge.
Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection: 2009 Update by the Infectious Diseases Society of America
Authors: Mermel Leonard A. , Allon Michael , Bouza Emilio , Craven Donald E. , Flynn Patricia , O'Grady Naomi P. , Raad Issam I. , Rijnders Bart J. A. , Sherertz Robert J. , Warren David K.
Published: June 2009

These updated guidelines replace the previous management guidelines published in 2001. The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them.
Activating and inhibitory killer immunoglobulin-like receptors (KIR) in haploidentical haemopoietic stem cell transplantation to cure high-risk leukaemias
Authors: Moretta A , Pende D , Locatelli F , Moretta L
Published: June 2009

A number of experimental studies have shown that natural killer (NK) cells can eliminate cancer cells and the mechanisms involved in this effect have been uncovered during the last two decades. Clinical data from haploidentical haematopoietic stem cell transplantation (haplo-HSCT) revealed that NK cells were responsible for remarkably favourable effects in both adult and paediatric high-risk leukaemias. NK receptors specific for major histocompatibility complex (MHC) class I molecules, including killer immunoglobulin (Ig)-like receptors (KIR) and CD94/NKG2A, play a major role in the anti-leukaemia effect (mediating either inhibitory or activating signals). Haplo- HSCT requires a heavy conditioning regimen for the patient and the use of large numbers of T cell-depleted HSC to be grafted. After transplantation, natural killer cells develop from HSC shortly after engraftment and may include ‘alloreactive’ NK cells that kill leukaemic cells and prevent graft-versus-host disease (GvHD). Alloreactive NK cells are characterized by the expression of KIR that are not engaged by any of the human leucocyte antigen (HLA) class I alleles expressed by the patient. Their generation is dependent upon the existence of a KIR/HLA class I mismatch between donor and recipient. Novel important information on the function and specificity of different KIR has been obtained recently by the analysis of donor-derived alloreactive NK cells in a cohort of paediatric patients given haplo-HSCT to cure acute, high-risk leukaemias.
Effects of androgens on adipocyte differentiation and adipose tissue explant metabolism in men and women
Authors: Blouin Karine , Nadeau Mélanie , Perreault Martin , Veilleux Alain , Drolet Renée , Marceau Picard , Mailloux Jacques , Luu‐The Van , Tchernof André
Published: June 2009

Objective  To examine the effects of aromatizable or nonaromatizable androgens on abdominal subcutaneous (SC) and omental (OM) adipose tissue lipid metabolism and adipogenesis in men and women.

Design and subjects  Primary organ and preadipocyte cultures were established from surgical samples obtained in men (n = 22) and women undergoing biliopancreatic diversions (n = 12) or gynaecological surgeries (n = 8). Cultures were treated with testosterone, dihydrotestosterone (DHT) and methyltrienolone (R1881).

Measurements  Heparin‐releasable lipoprotein lipase (HR‐LPL) activity, glycerol release, adiponectin secretion, glycerol‐3‐phosphate dehydrogenase activity and lipid accumulation were measured.

Results  In organ cultures from men, DHT had a statistically significant inhibitory effect on HR‐LPL activity in the OM compartment. Testosterone significantly inhibited HR‐LPL activity in SC and OM cultures. In women, high DHT concentrations tended to inhibit HR‐LPL activity in OM cultures. Minor androgenic effects were observed for basal and isoproterenol‐stimulated lipolysis as well as adiponectin release in men. On the other hand, adipocyte differentiation was significantly and dose‐dependently inhibited by DHT, testosterone and R1881 in SC and OM cultures from both sexes. These effects did not differ according to adipose tissue depot but appeared to be more pronounced in women than in men.

Conclusions  Androgens slightly decreased HR‐LPL activity in adipose tissue organ cultures, but markedly inhibited adipogenesis in SC and OM primary preadipocyte cultures in both sexes. Androgenic effects on adipose tissue in men vs. women may not differ in terms of direction but in the magnitude of their negative impact on adipogenesis and lipid synthesis.
Are stigma experiences among persons with mental illness, related to perceptions of self‐esteem, empowerment and sense of coherence?
Authors: LUNDBERG B. , HANSSON L. , WENTZ E. , BJÖRKMAN T.
Published: June 2009

Accessible summary

The findings from the present study revealed that people with mental illness are often exposed to social rejection from friends and the public. The most common experiences concerned is to be treated differently, or as less competent, after being a patient in mental health care.

The main finding of this study was that more rejection experiences were associated with lower level of sense of coherence and, to a lesser extent, with lower level of empowerment and self‐esteem.

The weak association, between enacted stigma and self‐esteem, as well as empowerment and sense of coherence, seems encouraging. However, further research and interventions may also pay attention to felt or anticipated stigma among mentally ill persons.

The aim of the study was to explore the relationship between stigmatizing rejection experiences and self‐related variables. Our hypothesis was that rejection experiences would be negatively associated with perceptions of self‐esteem, empowerment and sense of coherence. A cross‐sectional study assessing rejection experiences, empowerment, sense of coherence and self‐esteem was performed, including 200 persons in current or earlier contact with mental health services. The results showed that experiences of rejection were negatively associated with sense of coherence, empowerment and self‐esteem. This exploratory investigation suggests that experiences of rejection might be a target for coping interventions. Mental health nurses are in a key position to identify patients' experiences of stigma and by that to understand what consequences of devaluation/discrimination can have for the afflicted.
Ward safety perceived by ward managers in Britain, Germany and Switzerland: identifying factors that improve ability to deal with violence
Authors: LEPPING P. , STEINERT T. , NEEDHAM I. , ABDERHALDEN C. , FLAMMER E. , SCHMID P.
Published: June 2009

Little is known about how safe nurses feel on psychiatric wards across different European countries. This paper is aim to evaluate how ward safety is perceived by ward managers in Great Britain, Germany and Switzerland. We replicated a Swiss questionnaire study in Germany and Britain, which asked ward managers on adult psychiatric wards to give details about their ward including data on the management of aggression, staffing levels, staff training, standards and type of restraint used, alarm devices, treatment and management of aggression and the existence and perceived efficacy of standards (protocols, guidelines). The British sample had by far the highest staffing levels per psychiatric bed, followed by Switzerland and Germany. The British ward managers by far perceived violence and aggression least as a problem on their wards, followed by Germany and then Switzerland. British ward managers are most satisfied with risk management and current practice dealing with violence. German managers were most likely to use fixation and most likely to have specific documentation for coercive measures. Swiss wards were most likely to use non‐specific bedrooms for seclusion and carry alarm devices. British wards were far more likely to have protocols and training for the treatment and management of violence, followed by Switzerland and Germany. British ward managers by far perceived violence and aggression to be a small problem on their wards compared with Swiss and German ward managers. This was associated with the availability of control and restraint teams, regular training, clear protocols and a lesser degree risk assessments, but not staffing levels.
The Accuracy of Blood Grouping of Cord Blood Specimens with Special Reference to the MN System
Authors: Reed T. E. , Milkovich Lucille
Published: June 2009

Summary. The accuracy of cord blood grouping in the ABO, Rh, MNSs, Kell, Duffy, Lutheran, and P systems was tested in three ways (regression of length of gestation on phenotype frequency, comparison of cord blood grouping with grouping (of the same child) at five years of age, comparison of cord blood frequencies with frequencies in infants' mothers) using data on 7090 Caucasian infants, 2203 Negro infants, and over 400 individual comparisons of cord blood and five year groupings. In both Caucasians and Negroes a very high frequency of false negatives in cord blood grouping in the P system was found, as well as an appreciable, highly significant, occurrence of false negatives in Lua grouping. In Caucasians, but not in Negroes, cord blood grouping appeared to produce an excess of MN and Ss phenotypes.
Reduction of Aluminium Concentration in Albumin Products
Authors: Inoue Masahiro , Gion Yoshihiko , Itoh Hirokazu , Ikariya Koei , Takechi Kazuo , Morimoto Kazuo , Tomioka Shinji , Furuta Kohichi , Yabushita Sadao
Published: June 2009

The aluminium concentration in albumin products has been reduced to ≥100 ppb by an anion exchanger treatment. Furthermore, we have found that this low aluminium concentration in albumin products has been maintained for extensive periods of time, when they are stored in de‐alkalized soft glass containers.
Prolonged Storage of Red Cells: The Effect of pH, Adenine and Phosphate
Authors: Mazor D. , Dvilansky A. , Meyersiein N.
Published: June 2009

Prolonged storage of red blood cells (RBCs) at 4 °C results in decreased intracellular ATP levels with diminished posttransfusion survival. Meryman described a preservative medium, exceptional in its capacity to increase these intracellular levels during the first weeks of storage and later in maintaining adequate levels, for extended storage periods. We modified this medium, investigated its constituents, and found that its ATP‐preserving effect was unrelated to its tonicity or to the presence of mannitol. Throughout storage, RBC potassium leakage and lactate production were moderate. No evidence of osmotic swelling was detected. In spite of high ATP levels, the cells became echinocytes, thus discounting a direct correlation between shape and metabolic status. The most striking finding in this study was that the prestorage pH of the blood unit (pH 7.0), has a crucial contribution in elevating nucleotide levels in a medium containing high levels of phosphate (18–10 mM) and adenine. We suggest that a combined effect of optimal pH, adenine, glucose and phosphate in the medium contributes to the ability of the RBCs to synthesize the necessary purine nucleotides by the ‘salvage pathway’.
Inheritance of resistance to anthracnose (Colletotrichum capsici) at seedling and fruiting stages in chili pepper (Capsicum spp.)
Authors: Mahasuk P. , Khumpeng N. , Wasee S. , Taylor P. W. J. , Mongkolporn O.
Published: June 2009

Inheritance of resistance to anthracnose at fruiting and seedling stages was studied in two F2 populations from a cross between Capsicum annuum cv. ‘Bangchang’ and Capsicum chinense‘PBC932’. The first F2 was used to study anthracnose resistance at fruiting stage on mature green and ripe red fruit, and the second F2 was used to study the resistance at both seedling and fruiting stages. Fruit inoculation was performed on detached fruit using a microinjector. Disease severity was assessed on a 0–9 scale at 7 days after inoculation. Seedling inoculation was performed using a drop method on detached leaves of 4‐week‐old seedlings. Disease severity was assessed on a 1–9 scale at 3 days after inoculation. The distribution of the disease scores of green and red fruit, and seedlings in both F2 populations suggested a single gene model for each trait. Three different recessive genes were responsible for the three resistances from this cross. Linkage analysis suggested that the resistances at green and red fruit were linked (recombination frequency 0.25), and that the seedling resistance was not linked to the fruit resistances.
Neurotrophic effects of brain‐derived neurotrophic factor and vascular endothelial growth factor in major pelvic ganglia of young and aged rats
Authors: Lin Guiting , Shindel Alan W. , Fandel Thomas M. , Bella Anthony J. , Lin Ching‐Shwun , Lue Tom F.
Published: June 2009

OBJECTIVE

To investigate the neurotrophic effect of brain‐derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in cultured major pelvic ganglia (MPG) derived from young and aged rats.

MATERIALS AND METHODS

The dorsocaudal region of the MPG was isolated from 12 6‐month‐old male rats and 12 24‐month‐old male rats. The MPGs were treated with BDNF, VEGF, or both, at 0, 12.5, 25, 50, 100 and 150 ng/mL to determine the effective concentration for 50% activity (EC50) and optimum dosage for promoting neurite growth. Neurite outgrowth from treated MPGs was measured by microscopy. NADPH diaphorase and tyrosine hydroxylase (TH) staining was used to characterize neurites.

RESULTS

Both BDNF and VEGF promoted neurite sprouting from MPG. Neurite growth was more robust in MPGs derived from young rats (6 months) than from aged rats (24 months). The EC50 for BDNF, VEGF and combined treatment were 10.6, 11.9 and 52 ng/mL in young rats, and 11.3, 12 and 0.75 ng/mL in old rats, respectively. The optimum dosage of both factors for promoting MPG neurite growth in all groups was 25–50 ng/mL. VEGF appeared to favour NADPH diaphorase‐positive neurites, whereas BDNF favoured TH‐positive neurites.

CONCLUSION

BDNF and VEGF promote neurite growth from cultured MPG; combined treatment produced the most robust neurite outgrowth. Neurite growth from MPGs derived from aged rats was not as robust as it was from MPGs from younger rats. Further studies on the effect of neurotrophins after cavernous nerve injury are warranted.
Patients attending tertiary referral urology clinics: willingness to participate in tissue banking
Authors: Fitzpatrick Patricia E. , McKenzie Kenneth D. , Beasley Avril , Sheehan John D.
Published: June 2009

OBJECTIVE

To examine attitudes of male patients attending urology clinics to the donation of prostate tissue samples for research purposes, to compare attitudes in relation to age, educational attainment, previous hospitalization and experience of cancer, and to evaluate attitudes to the duration of storage of tissue samples.

PATIENTS AND METHODS

A systematic sample of 259 male patients aged 20–75 years, attending the urology clinics in two busy tertiary referral urological centres, completed a self‐reported questionnaire in an outpatient setting.

RESULTS

Most (84.5%) respondents strongly agreed/agreed that they would be willing to donate prostate tissue for research purposes if undergoing invasive investigation or treatment. After adjusting for other factors, being aged >55 years and having a positive attitude to new discoveries in genetics and cancer remained independently associated with the willingness to donate. There were significantly fewer agreeing with the statement ‘I would like my samples to be used for profit‐making research’ (39.3%) than with the statement ‘I would like my samples to be used for non‐profit research’ (88.8%; P < 0.001). While most respondents trusted researchers to act in an ethical way, the proportions agreeing with the statement ‘In regard to extra research studies I would trust medical researchers to act in an appropriate and ethical way’ was significantly lower in those on a first visit rather than subsequent visit to urology outpatients and significantly higher in those with a family history of serious disease or a previous cancer.

CONCLUSIONS

This study indicates that patients want to support research and become willing partners in the battle against cancer.
A systematic review of drug absorption following bariatric surgery and its theoretical implications
Authors: Padwal R. , Brocks D. , Sharma A. M.
Published: June 2009

Demand for bariatric surgery has risen exponentially and bariatric patients often have multiple indications for post‐operative pharmacotherapy. The purpose of this study was to systematically review the published literature examining the effect of bariatric surgery on drug absorption.

Studies were sought through searches of MEDLINE, EMBASE, the Cochrane Controlled Trials Registry and hand searches of reference lists. Two reviewers independently assessed studies for inclusion.

Twenty‐six studies (15 case reports/case series evaluating 12 different agents and 11 non‐randomized controlled studies examining 15 different agents) were found. Evidence for diminished drug absorption was found in 15/22 studies involving jejunoileal bypass, 1/3 studies of gastric bypass/gastroplasty and 0/1 studies examining biliopancreatic diversion. The effect of bariatric surgery on drug absorption appears drug‐specific. Drugs that are intrinsically poorly absorbed, highly lipophilic and/or undergo enterohepatic recirculation exhibited the greatest potential for malabsorption. The most consistent evidence for diminished absorption was found for cyclosporine, thyroxine, phenytoin and rifampin.

Reduced drug absorption may occur post‐bariatric surgery and this effect appears drug‐specific. Individual dose‐adjustment and therapeutic monitoring may be required. Rigorously conducted controlled studies are needed to evaluate the effect of modern bariatric procedures on drug absorption.
Cosmopolitanism and Global English: Language Politics in Globalisation Debates
Authors: Ives Peter
Published: June 2009

While it is commonly agreed that language standardisation was an integral feature of the historical formation of the modern nation state, current debates on globalisation and its effects on the nation state rarely address language issues in more than a superficial fashion. Yet the quadrupling of the number of English speakers in the last half-century and other changes associated with ‘global English’ would seem to have more substantial political implications. Particularly in the recent wave of discussions of cosmopolitanism, language questions seem to lurk below the surface but are rarely addressed explicitly or comprehensively. Important exceptions to this neglect of current language issues include Daniele Archibugi, who addresses these questions head on, and Nancy Fraser's most recent attempt to rethink Habermas' critical theory of the public sphere. This article agrees with both Archibugi and Fraser that language is an important, even central, aspect of political responses to processes of globalisation, specifically cosmopolitanism. However, I argue that Antonio Gramsci's approach to the politics of language in the early twentieth century highlights the insufficiency of Archibugi's reliance on the metaphor of Esperanto as well as the intractable nature of Fraser's critique for any critical theory of global public sphere(s), despite her attempt to advance such a theory. I do this by looking at Gramsci's critique of Esperanto from 1918 and his later prison writings concerning language politics in Italy. Gramsci, I argue, provides a much more adequate approach to contemporary questions of the politics of language, which includes an understanding of the continued role of the state which is most often obscured both by cosmopolitan perspectives and by much research on global English in fields outside political science.