bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin
Authors: Tomita Ayana , Sato Tokushi , Ichiyanagi Kouhei , Nozawa Shunsuke , Ichikawa Hirohiko , Chollet Matthieu , Kawai Fumihiro , Park Sam-Yong , Tsuduki Takayuki , Yamato Takahisa , Koshihara Shin-ya , Adachi Shin-ichi
Published: February 2009

Proteins harbor a number of cavities of relatively small volume. Although these packing defects are associated with the thermodynamic instability of the proteins, the cavities also play specific roles in controlling protein functions, e.g., ligand migration and binding. This issue has been extensively studied in a well-known protein, myoglobin (Mb). Mb reversibly binds gas ligands at the heme site buried in the protein matrix and possesses several internal cavities in which ligand molecules can reside. It is still an open question as to how a ligand finds its migration pathways between the internal cavities. Here, we report on the dynamic and sequential structural deformation of internal cavities during the ligand migration process in Mb. Our method, the continuous illumination of native carbonmonoxy Mb crystals with pulsed laser at cryogenic temperatures, has revealed that the migration of the CO molecule into each cavity induces structural changes of the amino acid residues around the cavity, which results in the expansion of the cavity with a breathing motion. The sequential motion of the ligand and the cavity suggests a self-opening mechanism of the ligand migration channel arising by induced fit, which is further supported by computational geometry analysis by the Delaunay tessellation method. This result suggests a crucial role of the breathing motion of internal cavities as a general mechanism of ligand migration in a protein matrix.
The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability
Authors: Hanson Sarah R. , Culyba Elizabeth K. , Hsu Tsui-Ling , Wong Chi-Huey , Kelly Jeffery W. , Powers Evan T.
Published: February 2009

The folding energetics of the mono-N-glycosylated adhesion domain of the human immune cell receptor cluster of differentiation 2 (hCD2ad) were studied systematically to understand the influence of the N-glycan on the folding energy landscape. Fully elaborated N-glycan structures accelerate folding by 4-fold and stabilize the β-sandwich structure by 3.1 kcal/mol, relative to the nonglycosylated protein. The N-glycan's first saccharide unit accounts for the entire acceleration of folding and for 2/3 of the native state stabilization. The remaining third of the stabilization is derived from the next 2 saccharide units. Thus, the conserved N-linked triose core, ManGlcNAc
2
, improves both the kinetics and the thermodynamics of protein folding. The native state stabilization and decreased activation barrier for folding conferred by N-glycosylation provide a powerful and potentially general mechanism for enhancing folding in the secretory pathway.
Kelp genes reveal effects of subantarctic sea ice during the Last Glacial Maximum
Authors: Fraser Ceridwen I. , Nikula Raisa , Spencer Hamish G. , Waters Jonathan M.
Published: February 2009

The end of the Last Glacial Maximum (LGM) dramatically reshaped temperate ecosystems, with many species moving poleward as temperatures rose and ice receded. Whereas reinvading terrestrial taxa tracked melting glaciers, marine biota recolonized ocean habitats freed by retreating sea ice. The extent of sea ice in the Southern Hemisphere during the LGM has, however, yet to be fully resolved, with most palaeogeographic studies suggesting only minimal or patchy ice cover in subantarctic waters. Here, through population genetic analyses of the widespread Southern Bull Kelp (
Durvillaea antarctica
), we present evidence for persistent ice scour affecting subantarctic islands during the LGM. Using mitochondrial and chloroplast genetic markers (COI;
rbc
L) to genetically characterize some 300 kelp samples from 45 Southern Ocean localities, we reveal a remarkable pattern of recent recolonization in the subantarctic. Specifically, in contrast to the marked phylogeographic structure observed across coastal New Zealand and Chile (10- to 100-km scales), subantarctic samples show striking genetic homogeneity over vast distances (10,000-km scales), with a single widespread haplotype observed for each marker. From these results, we suggest that sea ice expanded further and ice scour during the LGM impacted shallow-water subantarctic marine ecosystems more extensively than previously suggested.
Nicotinamide mononucleotide synthetase is the key enzyme for an alternative route of NAD biosynthesis in
Francisella tularensis
Authors: Sorci Leonardo , Martynowski Dariusz , Rodionov Dmitry A. , Eyobo Yvonne , Zogaj Xhavit , Klose Karl E. , Nikolaev Evgeni V. , Magni Giulio , Zhang Hong , Osterman Andrei L.
Published: February 2009

Enzymes involved in the last 2 steps of nicotinamide adenine dinucleotide (NAD) cofactor biosynthesis, which catalyze the adenylylation of the nicotinic acid mononucleotide (NaMN) precursor to nicotinic acid dinucleotide (NaAD) followed by its amidation to NAD, constitute promising drug targets for the development of new antibiotics. These enzymes, NaMN adenylyltransferase (gene
nadD
) and NAD synthetase (gene
nadE
), respectively, are indispensable and conserved in nearly all bacterial pathogens. However, a comparative genome analysis of
Francisella tularensis
allowed us to predict the existence of an alternative route of NAD synthesis in this category A priority pathogen, the causative agent of tularaemia. In this route, the amidation of NaMN to nicotinamide mononucleotide (NMN) occurs before the adenylylation reaction, which converts this alternative intermediate to the NAD cofactor. The first step is catalyzed by NMN synthetase, which was identified and characterized in this study. A crystal structure of this enzyme, a divergent member of the NadE family, was solved at 1.9-Å resolution in complex with reaction products, providing a rationale for its unusual substrate preference for NaMN over NaAD. The second step is performed by NMN adenylyltransferase of the NadM family. Here, we report validation of the predicted route (NaMN → NMN → NAD) in
F. tularensis
including mathematical modeling, in vitro reconstitution, and in vivo metabolite analysis in comparison with a canonical route (NaMN → NaAD → NAD) of NAD biosynthesis as represented by another deadly bacterial pathogen,
Bacillus anthracis
.
Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin,
myo
-inositol trispyrophosphate
Authors: Biolo Andreia , Greferath Ruth , Siwik Deborah A. , Qin Fuzhong , Valsky Eugene , Fylaktakidou Konstantina C. , Pothukanuri Srinivasu , Duarte Carolina D. , Schwarz Richard P. , Lehn Jean-Marie , Nicolau Claude , Colucci Wilson S.
Published: February 2009

A major determinant of maximal exercise capacity is the delivery of oxygen to exercising muscles.
myo
-Inositol trispyrophosphate (ITPP) is a recently identified membrane-permeant molecule that causes allosteric regulation of Hb oxygen binding affinity. In normal mice, i.p. administration of ITPP (0.5–3 g/kg) caused a dose-related increase in the oxygen tension at which Hb is 50% saturated (p50), with a maximal increase of 31%. In parallel experiments, ITPP caused a dose-related increase in maximal exercise capacity, with a maximal increase of 57 ± 13% (
P
= 0.002). In transgenic mice with severe heart failure caused by cardiac-specific overexpression of Gαq, i.p. ITPP increased exercise capacity, with a maximal increase of 63 ± 7% (
P
= 0.005). Oral administration of ITPP in drinking water increased Hb p50 and maximal exercise capacity (+34 ± 10%;
P
< 0.002) in normal and failing mice. Consistent with increased tissue oxygen availability, ITPP decreased hypoxia inducible factor-1α mRNA expression in myocardium. It had no effect on myocardial contractility in isolated mouse cardiac myocytes and did not affect arterial blood pressure in vivo in mice. Thus, ITPP decreases the oxygen binding affinity of Hb, increases tissue oxygen delivery, and increases maximal exercise capacity in normal mice and mice with severe heart failure. ITPP is thus an attractive candidate for the therapy of patients with reduced exercise capacity caused by heart failure.
Dramatic declines in neotropical salamander populations are an important part of the global amphibian crisis
Authors: Rovito Sean M. , Parra-Olea Gabriela , Vásquez-Almazán Carlos R. , Papenfuss Theodore J. , Wake David B.
Published: February 2009

We document major declines of many species of salamanders at several sites in Central America and Mexico, with emphasis on the San Marcos region of Guatemala, one of the best studied and most diverse salamander communities in the Neotropics. Profound declines of several formerly abundant species, including 2 apparent extinctions, are revealed. Terrestrial microhabitat specialists at mid- to high elevations have declined more than microhabitat generalists. These terrestrial microhabitat specialists have largely disappeared from multiple sites in western Guatemala, including in well-protected areas, suggesting that the phenomenon cannot be explained solely by localized habitat destruction. Major declines in southern Mexican plethodontid salamanders occurred in the late 1970s to early 1980s, concurrent with or preceding many reported frog declines. The species in decline comprise several major evolutionary lineages of tropical salamanders, underscoring that significant portions of the phylogenetic diversity of Neotropical salamanders are at risk. Our results highlight the urgent need to document and understand Neotropical salamander declines as part of the larger effort to conserve global amphibian diversity.
T cell receptors in an IL-10-secreting amino acid copolymer-specific regulatory T cell line that mediates bystander immunosuppression
Authors: Zhang Hong , Stern Joel N. H. , Strominger Jack L.
Published: February 2009

The T cell receptors from the regulatory IL-10-secreting T cell line induced by the random amino acid copolymers poly(F,Y,A,K,)n in SJL mice (H-2s) have been characterized, cloned, sequenced and expressed both in 293T cells and in 2 different TCR α−/β−T cell hybridomas. The usage of TCR α and β V regions in the cell line was oligoclonal. Four TCR α/β pairs cloned from single cells of the T cell line were inserted into a retrovirus vector linked by an oligonucleotide encoding the 2A peptide that spontaneously cleaves in vivo. After cotransfection of this vector with a CD3 vector into the 293T cells, the TCR were surface expressed. Moreover, after transduction into the 2 T cell hybridomas, all 4 were functional as evidenced by their response to stimulation by poly(F,Y,A,K)n. All 4 pairs were Vα3.2(3.5)/Vβ14, a prominent clonotype found in the poly(F,Y,A,K)n-specific T cell line. These V regions are identical to those recently found in a regulatory T cell line that secretes both IL-4 and IL-10 induced in B10.PL mice with a different MHC hapotype (H-2u) by a small peptide obtained from an autoimmune TCR of that strain. These data lead to a hypothesis regarding the origin of the epigenetic modifications that lead to selective cytokine secretion in T cells.
Rad52 promotes second-end DNA capture in double-stranded break repair to form complement-stabilized joint molecules
Authors: Nimonkar Amitabh V. , Sica R. Alejandro , Kowalczykowski Stephen C.
Published: February 2009

Saccharomyces cerevisiae
Rad52 performs multiple functions during the recombinational repair of double-stranded DNA (dsDNA) breaks (DSBs). It mediates assembly of Rad51 onto single-stranded DNA (ssDNA) that is complexed with replication protein A (RPA); the resulting nucleoprotein filament pairs with homologous dsDNA to form joint molecules. Rad52 also catalyzes the annealing of complementary strands of ssDNA, even when they are complexed with RPA. Both Rad51 and Rad52 can be envisioned to promote “second-end capture,” a step that pairs the ssDNA generated by processing of the second end of a DSB to the joint molecule formed by invasion of the target dsDNA by the first processed end. Here, we show that Rad52 promotes annealing of complementary ssDNA that is complexed with RPA to the displaced strand of a joint molecule, to form a complement-stabilized joint molecule. RecO, a prokaryotic homolog of Rad52, cannot form complement-stabilized joint molecules with RPA–ssDNA complexes, nor can Rad52 promote second-end capture when the ssDNA is bound with either human RPA or the prokaryotic ssDNA-binding protein, SSB, indicating a species-specific process. We conclude that Rad52 participates in second-end capture by annealing a resected DNA break, complexed with RPA, to the joint molecule product of single-end invasion event. These studies support a role for Rad52-promoted annealing in the formation of Holliday junctions in DSB repair.
Ligand-induced global transitions in the catalytic domain of protein kinase A
Authors: Hyeon Changbong , Jennings Patricia A. , Adams Joseph A. , Onuchic José N.
Published: February 2009

Conformational transitions play a central role in the phosphorylation mechanisms of protein kinase. To understand the nature of these transitions, we investigated the dynamics of nucleotide binding to the catalytic domain of PKA, a prototype for the protein kinase enzyme family. The open-to-closed transition in PKA was constructed as a function of ATP association by using available X-ray data and Brownian dynamics. Analyzing the multiple kinetic trajectories at the residue level, we find that the spatial rearrangement of the residues around the nucleotide-binding pocket, along with suppressed local fluctuations, controls the compaction of the entire molecule. In addition, to accommodate the stresses induced by ATP binding at the early transition stage, partial unfoldings (cracking) and reformations of several native contacts occur at the interfaces between the secondary structure motifs enveloping the binding pocket. This suggests that the enzyme experiences local structural deformations while reaching its functional, ATP-bound state. Our dynamical view of the ligand-induced transitions in PKA suggests that the kinetic hierarchy of local and global dynamics, the variable fluctuation of residues and the necessity of partial local unfolding may be fundamental components in other large scale allosteric transitions.
Highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces
Authors: Edgeworth Julie Ann , Jackson Graham S. , Clarke Anthony R. , Weissmann Charles , Collinge John
Published: February 2009

Prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of humans and animals, such as variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Prions pose significant public health concerns, including contamination of blood products and surgical instruments; require laborious and often insensitive animal bioassay to detect; and resist conventional hospital sterilization methods. A major experimental advance was the cell culture-based scrapie cell assay, allowing prion titres to be estimated more precisely and an order of magnitude faster than by animal bioassays. Here we describe a bioassay method that exploits the marked binding affinity of prions to steel surfaces. Using steel wires as a concentrating and sensitization tool and combining with an adapted scrapie cell endpoint assay we can achieve, for mouse prions, a sensitivity 100× higher than that achieved in standard mouse bioassays. The rapidity and sensitivity of this assay offers a major advance over small animal bioassay in many aspects of prion research. In addition, its specific application in assay of metal-bound prions allows evaluation of novel prion decontamination methods.
Head Start Teachers' Perspectives on Early Literacy
Authors: Powell Douglas R. , Diamond Karen E. , Bojczyk Kathryn E. , Gerde Hope K.
Published: February 2009

Improvements in early literacy outcomes are increasingly expected of prekindergarten education programs such as Head Start. Although preschool teachers are central to promoting skills linked to subsequent reading and writing competence, their views of early literacy have received minimal research attention. This study employed focus group methodology to examine perspectives on early literacy in two samples of Head Start teachers ( N = 148) representing six different programs serving diverse communities in the Midwest. Analyses of 29 focus group sessions indicated that teachers were generally supportive of the inclusion of literacy goals for children but offered differing views on the relation of literacy to other goals. A dominant view was that growth in other developmental domains, especially social-emotional development, was a requisite to literacy development. Other perspectives included concurrent attention to growth in literacy and other areas, or an emphasis on children's literacy skills as a requisite to progress in other domains. Teachers' conceptions of early literacy emphasized alphabet knowledge with minimal attention to phonological sensitivity skills. Variations in children's literacy skills and interests were attributed to child readiness to a greater extent than to classrooms and families. There were two general patterns in teachers' descriptions of literacy instruction in their classrooms. Some teachers described their primary role as providing literacy materials and activities that children pursue when they are ready. Other teachers described practices that actively seek to ensure that all children engage in literacy learning. Implications for professional development opportunities and guidance on learning outcomes are discussed.
“Mother's Voice Was the Main Source of Learning”: Parents' Role in Supporting the Literacy Development of Students with Autism
Authors: Chandler-Olcott Kelly , Kluth Paula M.
Published: February 2009

Students with significant disabilities, including those with autism-spectrum labels, are increasingly being included in the regular education classroom for literacy instruction and held to high standards for literacy achievement (Yell, Drasgow, & Lowrey, 2005), but research with these students as participants has been limited, especially in inclusive settings such as the home or classroom. Grounded in perspectives from disability studies (Biklen, 2005; Kliewer, Biklen, & Kasa-Hendrickson, 2006) and socio-cultural theories of literacy (Gallego & Hollingsworth, 2000; O'Brien, 2003), this qualitative study used inductive methods (Strauss & Corbin, 1998) to analyze the literacy-related messages of 16 autobiographies authored by individuals on the autism spectrum. Analysis revealed a key role for parents in supporting their children's literacy development at home, with results clustering in these three areas: (a) parents' persistence in following small cues related to literacy development, (b) their use of literacy to make social codes explicit, and (c) their strategic employment of support to ensure their children's success with literacy while increasing challenges over time. Implications for practice and research are discussed, with an emphasis on collaborative inquiry with learners on the autism spectrum and their parents.
A Stochastic and State Space Model for Tumour Growth and Applications
Authors: Tan Wai-Yuan , Ke Weiming , Webb G.
Published: February 2009

We develop a state space model documenting Gompertz behaviour of tumour growth. The state space model consists of two sub‐models: a stochastic system model that is an extension of the deterministic model proposed by Gyllenberg and Webb (1991), and an observation model that is a statistical model based on data for the total number of tumour cells over time. In the stochastic system model we derive through stochastic equations the probability distributions of the numbers of different types of tumour cells. Combining with the statistic model, we use these distribution results to develop a generalized Bayesian method and a Gibbs sampling procedure to estimate the unknown parameters and to predict the state variables (number of tumour cells). We apply these models and methods to real data and to computer simulated data to illustrate the usefulness of the models, the methods, and the procedures.
Protective Effects of Chinese Traditional Medicine Buyang Huanwu Decoction on Myocardial Injury
Authors: Yang Guangde , Fang Zhiyuan , Liu Yu , Zhang Hui , Shi Xiaolian , Ji Qiaoli , Lin Qinqin , Lin Rong
Published: February 2009

Many clinical studies have reported that Buyang Huanwu Decoction (BYHWD) has a protective effect on ischemic heart disease (IHD). In the present study, the protective effect of BYHWD on myocardial ischemia was investigated. Different doses of BYHWD and Compound Danshen Dropping Pills (CDDP) were lavaged to rats, respectively, isoproterenol (ISO) was intraperitoneally injected in to all animals to induce myocardial ischemia except the control group. Electrocardiogram (ECG) of each animal was recorded; activities of lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) in serum were detected. As the results of ECG showed, pre‐treatment with BYHWD inhibited ischemic myocardial injury, and the activities of LDH, CK and AST were lower than those in the myocardial ischemia model group, which suggests that BYHWD rescues the myocardium from ischemia status. To research the potential mechanism, the level of nitric oxide (NO), nitric oxide syntheses (NOS) and inducible nitric oxide syntheses (iNOS), the expression of iNOS and ligand of cluster of differentiation 40 (CD40L) were detected. The results revealed that BYHWD significantly decreased the level of NO, NOS and iNOS in serum. Moreover, BYHWD decreased the expression of iNOS and CD40L in myocardial tissues. These results indicate that the protective effect of BYHWD on myocardial ischemia and mechanism are associated with inhibition of iNOS and CD40L expression.
Comparison of the performance of the rapid antigen detection actim Influenza A&B test and RT-PCR in different respiratory specimens
Authors: Ghebremedhin B. , Engelmann I. , König W. , König B.
Published: February 2009

Nowadays, influenza antigen detection test kits are used most frequently to detect influenza A or B virus to establish the diagnosis of influenza rapidly and initiate appropriate therapy. This study was conducted to evaluate the performance of the actim Influenza A&B test (Medix Biochemica). Overall, 473 respiratory specimens were analysed in the actim Influenza A&B test and the results were compared with those from an RT-PCR assay; 461 of these samples originated from paediatric patients aged 7 weeks to 6.5 years either with influenza-related symptoms or from the intensive care unit, and 12 samples originated from adults with underlying lung or haematological diseases. Diagnosis of influenza A or B virus could be established using the actim Influenza A&B test (9/473 samples for influenza A virus and 6/473 for influenza B virus). RT-PCR revealed 23 patients with influenza virus (13/473 for influenza A virus and 10/473 for influenza B virus). The sensitivity and specificity of the actim Influenza A&B test were 65 and 100 % compared with the RT-PCR assay. However, 32 external quality assessment samples containing seven different strains of influenza A subtypes H1N1 and H3N2 and the avian H5N1 were detected correctly by the actim Influenza A&B test. No cross-reactivity to a range of bacterial, fungal and other viral pathogens was observed. In conclusion, the actim Influenza A&B test is reliable for positive results due to its high specificity. Nevertheless, negative results from this test need to be confirmed by a more sensitive assay because of the low sensitivity observed with diagnostic samples.
A URA3 null mutant of Candida albicans (CAI-4) causes oro-oesophageal and gastric candidiasis and is lethal for gnotobiotic, transgenic mice (Tgϵ26) that are deficient in both natural killer and T cells
Authors: Balish Edward
Published: February 2009

Current data suggest that functionalURA3genes are necessary for the full pathogenesis ofCandida albicans. Herein it is shown that a putatively avirulentURA3/URA3null mutant ofC. albicans(CAI-4) can colonize the murine alimentary tract, invade oro-oesophageal and gastric tissues with yeasts and hyphae, evoke a granulocyte-dominated inflammatory response, and kill transgenic mice that are deficient for both natural killer cells and T cells. BecauseC. albicans-colonized (gnotobiotic) mice lack a viable prokaryotic microbiota, this study also demonstrates that the gut microbiome is not required to supply the mutant's nutritional needs. The gnotobiotic murine model described herein can be used to assess the capacity ofC. albicansmutants to colonize and infect cutaneous, mucosal and systemic tissues and kill the susceptible host via a clinically common, natural route of infection; namely the alimentary tract.
Phenotypic and genotypic characterization of Aspergillus lentulus and Aspergillus fumigatus isolates in a patient with probable invasive aspergillosis
Authors: Montenegro Graciela , Sánchez Puch Silvia , Jewtuchowicz Virginia M. , Pinoni Maria V. , Relloso Silvia , Temporitti Elena , Iovannitti Cristina A. , Mujica Maria T.
Published: February 2009

Characteristic morphological and phylogenetic analyses demonstrated the presence of Aspergillus fumigatus and Aspergillus lentulus as the aetiological agents in a case of probable invasive aspergillosis (IA). This is believed to be the first report of an A. lentulus strain isolated from a patient with probable IA in Argentina.
Evaluation of sequential multiplex PCR for direct detection of multiple serotypes of Streptococcus pneumoniae from nasopharyngeal secretions
Authors: Antonio Martin , Hakeem Ishrat , Sankareh Kawsu , Cheung Yin Bun , Adegbola Richard A.
Published: February 2009

Sequential multiplex PCR was evaluated for detection of multiple Streptococcus pneumoniae serotypes directly from nasopharyngeal secretions. A total of 279 nasopharyngeal swab samples were tested blindly. When limited to the 29 serotypes identifiable by the molecular method, the mean number of serotypes identified by the conventional latex/Quellung method was 0.85, which was significantly lower than that by the molecular method (P <0.0001). The multiplex PCR method identified significantly more serotypes than the latex/Quellung method if limited to the 29 serotypes (P=0.001 and P=0.014, respectively).
Post-operative endophthalmitis due to an unusual pathogen, Comamonas testosteroni
Authors: Reddy Ashok Kumar , Murthy Somasheila I. , Jalali Subhadra , Gopinathan Usha
Published: February 2009

Here, we describe the first report of post-operative endophthalmitis due to Comamonas testosteroni in an elderly diabetic patient after complicated cataract surgery. The isolate was identified by using Mini API strips. The patient was successfully treated with intravitreal ceftazidime and oral ciprofloxacin.
Limited genetic diversity among genotypes of Enterocytozoon bieneusi strains isolated from HIV-infected patients from Sydney, Australia
Authors: Stark D. , van Hal S. , Barratt J. , Ellis J. , Marriott D. , Harkness J.
Published: February 2009

Microsporidia are intracellular parasites, with over 1200 species belonging to 143 genera described to date. They are opportunistic pathogens in humans and can cause chronic diarrhoea in immunosuppressed patients. BothEnterocytozoon bieneusiandEncephalitozoon intestinaliscause intestinal disease, withEnterocytozoon bieneusimore commonly identified in patients with human immunodeficiency virus (HIV) infection. In this study, intestinal microsporidial clinical isolates from patients in Sydney, Australia, were genotyped. All specimens were from HIV-infected men with low CD4+T-cell counts (<100 cells mm−3). Genotyping of the internal transcribed spacer regions of the rRNA gene showed the presence of only one genotype, the anthroponoticEnterocytozoon bieneusigenotype B strain. This study thus highlighted the limited genetic diversity among AustralianEnterocytozoon bieneusiisolates, and it is hypothesized that, due to the reduced incidence of microsporidia and the subsequent reduction in the human reservoir of the anthroponotic genotype B, locally acquired intestinal microsporidiosis will rarely be seen in HIV-infected persons undergoing highly active antiretroviral therapy in the future in Australia.
In vivo development of heterogeneous glycopeptide-intermediate Staphylococcus aureus (hGISA), GISA and daptomycin resistance in a patient with meticillin-resistant S. aureus endocarditis
Authors: Kirby Andrew , Mohandas Kavya , Broughton Caroline , Neal Timothy J. , Smith Godfrey W. , Pai Pearl , Nistal de Paz Carlos
Published: February 2009

We report a patient who developed a meticillin-resistant Staphylococcus aureus (MRSA) central venous catheter infection complicated by infective endocarditis. The patient was initially treated with glycopeptides, which led to the development of heterogeneous glycopeptide resistance, the detection of which required the use of a macro Etest screening test. Subsequently, the causative strain, confirmed by PFGE as a UK epidemic MRSA-15, was treated with daptomycin, and again resistance developed in vivo. The development in vivo of resistance to both these agents suggests that the resistance mechanisms may be associated. We suggest that the clinician managing MRSA infection should anticipate daptomycin resistance when reduced glycopeptide susceptibility is detected.
Population variables and life‐history characteristics of the alligator pipefish Syngnathoides biaculeatus, in Papua New Guinea
Authors: Barrows A. P. W. , Martin‐Smith K. M. , Baine M. S. P.
Published: February 2009

Population structure and life‐history variables of the widely distributed alligator pipefish Syngnathoides biaculeatus were characterized in Bootless Bay, Papua New Guinea over the course of 11 months. There was little evidence of seasonality with four focal populations showing no significant change in abundance. Similarly, the sex ratio remained 1:1 for all but 1 month. Reproductive males carrying eggs (148–278 mm in total length, LT) were found in all months. Brood size was significantly, positively related to male LT for newly laid broods only. Maximum observed brood size was 351 and mean ±s.d. brood size was 238 ± 57 for newly laid broods. Juveniles and males showed no change in mean LT over the year while slightly smaller females were captured in November 2006 and September 2007. Males were significantly longer than females so von Bertalanffy growth coefficients were estimated separately for each sex: males L∞= 285 mm, K = 0·82 year−1 and females L∞= 261 mm, K = 1·10 year−1. These estimates suggest that this species grows rapidly and has a short‐life span. In the context of growing concern about overexploitation of syngnathids, a rapid growth rate combined with year round reproductive activity suggests that the tropical S. biaculeatus may be relatively resilient with regard to fishing pressure.
A question of balance: prioritizing public health responses to harm from gambling
Authors: Adams Peter J. , Raeburn John , De Silva Kawshi
Published: February 2009

Aim  To provide an overview on the nature and importance of public health approaches to the global expansion of commercial gambling.

Method  Three key areas of public health activity are examined: harm minimization, health promotion and the political determinants for change.

Findings  The rapid proliferation of gambling experienced in many countries is driven by the commercial development of new products orientated around continuous and rapid mass consumption. This is particularly the case with ongoing refinements to electronic gambling machines and the development of new gambling technologies using the internet and mobile telephones. So far responses to negative impacts have, on the whole, focused upon individualized treatment interventions. A public health approach to gambling offers a broad range of strategies to tackle the wider implications of gambling expansion: harm reduction provides evidence‐based strategies for managing identifiable harm; health promotion focuses upon communities building their capacity, knowledge and resilience with regard to the attractions of gambling, and action on the political determinants sets out to increase the accountability and reduce the conflicts of interest that influence government resolve in managing their gambling environments.

Conclusion  In this new environment of mass consumption, efforts in developing treatment responses to problem gambling need to be balanced with, at least, equal efforts in developing public health responses. With the expansion of commercial gambling occurring globally, international agencies could play a critical role in supporting public health initiatives.
Doing harm reduction better: syringe exchange in the United States
Authors: Des Jarlais Don C. , McKnight Courtney , Goldblatt Cullen , Purchase David
Published: February 2009

Objective  To trace the growth of syringe exchange programs (SEPs) in the United States since 1994–95 and assess the current state of SEPs.

Methods  Annual surveys of US SEPs known to North American Syringe Exchange Network (NASEN). Surveys mailed to executive directors with follow‐up interviews by telephone and/or e‐mail. Response rates have varied between 70% and 88% since surveys were initiated in 1996.

Results  The numbers of programs known to NASEN have increased from 68 in 1994–95 to 186 in 2007. Among programs participating in the survey, numbers of syringes exchanged have increased from 8.0 million per year to 29.5 million per year, total annual budgets have increased from $6.3 to $19.6 million and public funding (from state and local governments) has increased from $3.9 to $14.4 million. In 2007, 89% of programs permitted secondary exchange and 76% encouraged it. Condoms, referrals to substance abuse treatment, human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV) counseling and testing and naloxone for overdose were among the most commonly provided services in addition to basic syringe exchange. Each of these services was provided by 40% or more of SEPs in 2007.

Conclusions  While syringe exchange has remained controversial in the United States, there has been very substantial growth in numbers of programs, syringes exchange and program budgets. Utilizing secondary exchange to reach large numbers of injecting drug users and utilizing SEPs as a new platform for providing health and social services beyond basic syringe exchange have been the two major organizational strategies in the growth of SEPs in the United States.
The Mexican migration to the United States and substance use in northern Mexico
Authors: Borges Guilherme , Medina‐Mora Maria‐Elena , Orozco Ricardo , Fleiz Clara , Cherpitel Cheryl , Breslau Joshua
Published: February 2009

Aims  To examine the impact of migration to the United States on substance use and substance use disorders in three urban areas of northern Mexico.

Design  Cross‐sectional survey of immigration‐related experiences and life‐time and past‐year alcohol and drug use, in a representative sample of respondents aged 12–65 years.

Setting  Interviews were conducted in the cities of Tijuana, Ciudad Juarez and Monterrey during 2005. Respondents were classified into three groups: (i) ‘return migrants’, (ii) ‘relatives of migrants’ and (iii) ‘others in the general population’.

Findings  A total of 1630 completed interviews were obtained for a response rate of 70.5%. ‘Return migrants’ were more likely to have used alcohol, marijuana or cocaine at least once in their life‐time and in the last 12 months, more likely to develop a substance use disorder and more likely to have a 12‐month substance use disorder compared with ‘others in the general population’. Among ‘return migrants’, longer length of time in the United States and type of work performed as an immigrant were related to higher prevalence of substance use. Among ‘relatives of migrants’, migration experiences were not associated with increased prevalence of substance use compared with ‘others in the general population’.

Conclusion  This study found a link between migration to the United States and the transformation of substance use norms and pathology in Mexico. Future research on pre‐migration involvement in substance use and data on the timing of events among return migrants is needed. Public health measures are likely to require cross‐border coordination of research and service development.
Classification of abused inhalants
Authors: Balster Robert L. , Cruz Silvia L. , Howard Matthew O. , Dell Colleen A. , Cottler Linda B.
Published: February 2009

Many hundreds of household and industrial products can be volatilized readily and are subject to abuse. Inhalant abuse research has been hampered by a lack of consensus on whether or not there are subclassifications of abused inhalants based on chemical structure, form or intended use of the product or pharmacological properties. This paper discusses strengths and weaknesses of various approaches to classification of inhalants and suggests areas for future research in this area. It is concluded that classification of inhalants by form or product types is not useful for scientific purposes; rather, subclassification of inhalants should be based on a yet‐to‐be‐determined combination of chemical and pharmacological similarity and shared patterns of abuse. One of the ways in which we can improve our understanding of inhalant abuse is to obtain more detailed information on individual products and chemicals, their patterns of use and the geographical distribution of their use.
Alcohol in Mayan Guatemala: consumption, distribution, production and composition of cuxa
Authors: Kanteres Fotis , Lachenmeier Dirk W. , Rehm Jürgen
Published: February 2009

Aims  To describe the consumption, distribution, production and chemical composition of alcohol, including cuxa (pronounced ‘coo sha’), in Nahualá, a highland Mayan municipality in Guatemala. Cuxa is a sugarcane‐derived spirit, in part produced clandestinely, that has been distributed in the community for several decades.

Methods  Key informant interviews with alcohol distributors and consumers, cuxa producers and health professionals, as well as analyses of questionnaires from a sample of 47 spouses who came to the local health centre for problems related to their husband's drinking. Sampling and chemical analysis of cuxa from 12 of 13 identified sales points in the head‐town of Nahualá and its nearby settlements (10 km radius). Fieldwork was conducted between November 2007 and March 2008.

Results  Alcohol consumption was found to be integrated culturally in this community. The overall drinking culture was marked by irregular heavy drinking occasions, especially around market days, with substantial inebriation and health problems, especially among street inhabiting drinkers. Cuxa contributed to these problems, and cuxa drinking was socially stigmatized. Cuxa was produced both clandestinely and industrially, and sold legally by taverns and illegally by clandestine distributors. The alcoholic strength of the samples was typically between 17 and 19% vol.; clandestinely produced cuxa samples showed acetaldehyde contamination.

Conclusions  Measures should be taken to reduce the harm associated with alcohol in this community, including efforts to reduce acetaldehyde levels in cuxa.
Systematic review: the global incidence and prevalence of peptic ulcer disease
Authors: SUNG J. J. Y. , KUIPERS E. J. , EL‐SERAG H. B.
Published: February 2009

Background  Peptic ulcer disease (PUD) is most commonly associated with Helicobacter pylori infection and the use of acetylsalicylic acid (ASA) and nonsteroidal anti‐inflammatory drugs (NSAIDs). The management of H. pylori infection has improved radically in recent years; however, the prescription of ASA and NSAIDs has increased over the same period.

Aim  To evaluate the current global incidence and prevalence of PUD by systematic review of the literature published over the last decade.

Methods  Systematic searches of PubMed, EMBASE and the Cochrane library.

Results  The annual incidence rates of PUD were 0.10–0.19% for physician‐diagnosed PUD and 0.03–0.17% when based on hospitalization data. The 1‐year prevalence based on physician diagnosis was 0.12–1.50% and that based on hospitalization data was 0.10–0.19%. The majority of studies reported a decrease in the incidence or prevalence of PUD over time.

Conclusions  Peptic ulcer disease remains a common condition, although reported incidence and prevalence are decreasing. This decrease may be due to a decrease in H. pylori‐associated PUD.
Genome‐wide scan for bovine twinning rate QTL using linkage disequilibrium
Authors: Kim E.‐S. , Berger P. J. , Kirkpatrick B. W.
Published: February 2009

Twinning is a complex trait with negative impacts on health and reproduction, which cause economic loss in dairy production. Several twinning rate quantitative trait loci (QTL) have been detected in previous studies, but confidence intervals for QTL location are broad and many QTL are unreplicated. To identify genomic regions or genes associated with twinning rate, QTL analysis based on linkage combined with linkage disequilibrium (LLD) and individual marker associations was conducted across the genome using high‐throughput single nucleotide polymorphism (SNP) genotypes. A total of 9919 SNP markers were genotyped with 200 sires and sons in 19 half‐sib North American Holstein dairy cattle families. After SNPs were genotyped, informative markers were selected for genome‐wide association tests and QTL searches. Evidence for twinning rate QTL was found throughout the genome. Thirteen markers significantly associated with twinning rate were detected on chromosomes 2, 5 and 14 (P < 2.3 × 10−5). Twenty‐six regions on fourteen chromosomes were identified by LLD analysis at P < 0.0007. Seven previously reported ovulation or twinning rate QTL were supported by results of single marker association or LLD analyses. Single marker association analysis and LLD mapping were complementary tools for the identification of putative QTL in this genome scan.
Availability of and access to critical habitats in regulated rivers: effects of low‐head barriers on threatened lampreys
Authors: LUCAS MARTYN C. , BUBB DAMIAN H. , JANG MIN‐HO , HA KYONG , MASTERS JEROME E. G.
Published: February 2009

1. Conservation of freshwater animal populations requires their access to, as well as sufficient availability of, critical habitats, such as those for reproduction. Abundant small‐scale barriers may cause extensive fragmentation of freshwater habitat but, by comparison to larger structures their effects are rarely considered by catchment managers. The relationship between the distribution of, and access to, spawning habitat in a regulated river, characterized by abundant small barriers, was examined for river lampreyLampetra fluviatilis, a threatened migratory fish.

2. Telemetry of adult lamprey in the River Derwent, North East England was used to quantify upriver migration and access to spawning habitat, together with surveys of spawning habitat availability and spawning activity between 2002 and 2007.

3. Access in to the Derwent appeared severely restricted by a tidal barrage, beyond which lamprey migrated rapidly in unobstructed reaches. Of all lamprey tagged in the lower 4 km of river, or ascending the barrage, 64% and 17% passed the first and second weirs respectively, with high flows crucial for this. Although over 98% of lamprey spawning habitat occurred more than 51 km upstream, on average just 1.8% of river lamprey spawners were recorded there.

4. In order to protect or rehabilitate species or species assemblages, greater attention needs to be paid to the relative spatial distribution of low‐head barriers and the resultant availability of key habitats within individual catchments. This is particularly important given the renewed emphasis internationally on low‐head hydropower solutions as a source of renewable energy, and the rapid growth in numbers of low‐head barriers in many catchments.
Influence of lateral gradients of hydrologic connectivity on trophic positions of fishes in the Upper Mississippi River
Authors: ROACH KATHERINE A. , THORP JAMES H. , DELONG MICHAEL D.
Published: February 2009

1. Riverscapes consist of the main channel and lateral slackwater habitats along a gradient of hydrological connectivity from maximum connection in main channel habitats to minimum connection in backwaters. Spatiotemporal differences in water currents along this gradient produce dynamic habitat conditions that influence species diversity, population densities and trophic interactions of fishes.

2. We examined the importance of lateral connectivity gradients for food web dynamics in the Upper Mississippi River during spring (high flow, moderately low temperatures) and summer (low flow, higher temperatures). We used literature information and gut contents analyses to determine feeding guilds and stable isotope analysis to estimate mean trophic position of local fish assemblages. During June and August 2006, we collected over 1000 tissue samples from four habitats (main channel, secondary channels, tertiary channels and backwaters) distributed within four hydrologic connectivity gradients.

3. Mean trophic position differed among feeding guilds and seasons, with highest values in spring. Mean trophic position of fish assemblages, variability in trophic position and food chain length (maximum trophic position) of the two dominant piscivore species (Micropterus salmoides and M. dolomieu) in both seasons were significantly associated with habitat along the lateral connectivity gradient. Food chain length peaked in tertiary channels in both seasons, probably due to higher species diversity of prey at these habitats. We infer that food chain length and trophic position of fish assemblages were lower in backwater habitats in the summer mainly because of the use of alternative food sources in these habitats.

4. A greater number of conspecifics exhibited significant among‐habitat variation in trophic position during the summer, indicating that low river stages can constrain fish movements in the Upper Mississippi River.

5. Results of this study should provide a better understanding of the fundamental structure of large river ecosystems and an improved basis for river rehabilitation and management through knowledge of the importance of lateral complexity in rivers.