bluuebunny/crossref_metadata_2025 huggingface dataset:
East African megadroughts between 135 and 75 thousand years ago and bearing on early-modern human origins
Authors: Scholz Christopher A. , Johnson Thomas C. , Cohen Andrew S. , King John W. , Peck John A. , Overpeck Jonathan T. , Talbot Michael R. , Brown Erik T. , Kalindekafe Leonard , Amoako Philip Y. O. , Lyons Robert P. , Shanahan Timothy M. , Castañeda Isla S. , Heil Clifford W. , Forman Steven L. , McHargue Lanny R. , Beuning Kristina R. , Gomez Jeanette , Pierson James
Published: September 2007

The environmental backdrop to the evolution and spread of early
Homo sapiens
in East Africa is known mainly from isolated outcrops and distant marine sediment cores. Here we present results from new scientific drill cores from Lake Malawi, the first long and continuous, high-fidelity records of tropical climate change from the continent itself. Our record shows periods of severe aridity between 135 and 75 thousand years (kyr) ago, when the lake's water volume was reduced by at least 95%. Surprisingly, these intervals of pronounced tropical African aridity in the early late-Pleistocene were much more severe than the Last Glacial Maximum (LGM), the period previously recognized as one of the most arid of the Quaternary. From these cores and from records from Lakes Tanganyika (East Africa) and Bosumtwi (West Africa), we document a major rise in water levels and a shift to more humid conditions over much of tropical Africa after ≈70 kyr ago. This transition to wetter, more stable conditions coincides with diminished orbital eccentricity, and a reduction in precession-dominated climatic extremes. The observed climate mode switch to decreased environmental variability is consistent with terrestrial and marine records from in and around tropical Africa, but our records provide evidence for dramatically wetter conditions after 70 kyr ago. Such climate change may have stimulated the expansion and migrations of early modern human populations.
Specific and covalent labeling of a membrane protein with organic fluorochromes and quantum dots
Authors: Bonasio Roberto , Carman Christopher V. , Kim Enoch , Sage Peter T. , Love Kerry R. , Mempel Thorsten R. , Springer Timothy A. , von Andrian Ulrich H.
Published: September 2007

The real-time observation of protein dynamics in living cells and organisms is of fundamental importance for understanding biological processes. Most approaches to labeling proteins exploit noncovalent interactions, unsuitable to long-term studies, or genetic fusion to naturally occurring fluorescent proteins that often have unsatisfactory optical properties. Here we used the fungal enzyme cutinase and its suicide substratep-nitrophenyl phosphonate to covalently attach a variety of labels to the integrin lymphocyte function-associated antigen-1 (LFA-1) on the surface of living cells. Cutinase was embedded in the extracellular domain of LFA-1 with no appreciable influence on integrin function and conformational regulation.p-nitrophenyl phosphonate-conjugated fluorochromes, including the very bright and stable quantum dots, bound efficiently and specifically to LFA-1/cutinase. The availability of a genetically encoded tag that binds covalently to quantum dots could foster the development of new experimental strategies for the study of protein dynamicsin vivo.
Control of transposase activity within a transpososome by the configuration of the flanking DNA segment of the transposon
Authors: Mizuuchi Michiyo , Rice Phoebe A. , Wardle Simon J. , Haniford David B. , Mizuuchi Kiyoshi
Published: September 2007

The multiple steps of DNA transposition take place within a large complex called the transpososome, in which a pair of transposon DNA ends are synapsed by a multimer of the transposase protein. The final step, a DNA strand transfer reaction that joins the transposon ends to the target DNA strands, entails no net change in the number of high-energy chemical bonds. Physiology demands that, despite remaining stably associated with the transpososome, the strand transfer products undergo neither the reverse reaction nor any further cleavage reactions. Accordingly, when the Mu or Tn10 strand transfer complex was produced
in vitro
through transposase-catalyzed reaction steps, reverse reactions were undetectable. In contrast, when the Mu or Tn10 strand transfer complexes were assembled from DNA already having the structure of the strand transfer product, we detected a reaction that resembled reversal of target DNA strand transfer. The stereoselectivity of phosphorothioate-containing substrates indicated that this reaction proceeds as the pseudoreversal of the normal target DNA strand transfer step. Comparison of the reactivity of closely related Mu substrate DNA structures indicated that the configuration of the flanking DNA outside of the transposon sequence plays a key role in preventing the transposon end cleavage reaction after the strand transfer step.
Distinct pathways of genomic progression to benign and malignant tumors of the liver
Authors: Tward Aaron D. , Jones Kirk D. , Yant Stephen , Cheung Siu Tim , Fan Sheung Tat , Chen Xin , Kay Mark A. , Wang Rong , Bishop J. Michael
Published: September 2007

We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene
MET
or by hydrodynamic transfection of
MET
in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between
MET
and constitutively active versions of β-catenin. In contrast, adenomas were produced by cooperation between
MET
and defective signaling through the transcription factor HNF1α. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by
MET
and activating mutations of β-catenin in a subset of human hepatocellular carcinomas. Inactivation of
MET
transgenes led to regression of hepatocellular carcinomas despite the persistence of activated β-catenin. The tumors eventually recurred in the absence of
MET
expression, however, presumably after the occurrence of one or more events that cooperated with activated β-catenin in lieu of
MET
. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway.
Estrogen receptor-α expression in the mammary epithelium is required for ductal and alveolar morphogenesis in mice
Authors: Feng Yuxin , Manka David , Wagner Kay-Uwe , Khan Sohaib A.
Published: September 2007

The estrogen receptor-α (ERα) is a critical transcription factor that regulates epithelial cell proliferation and ductal morphogenesis during postnatal mammary gland development. Tissue recombination and transplantation studies using the first generation of ERα knockout (ERKO) mice suggested that this steroid hormone receptor is required in the mammary stroma that subsequently exerts its effect on the epithelium through additional paracrine signaling events. A more detailed analysis revealed that ERKO mice produce a truncated ERα protein with detectable transactivation activity, and it is likely that this functional ERα variant has masked the biological significance of this steroid receptor in the mammary epithelium. In this article, we describe the generation a Cre-lox-based conditional knockout of the ERα gene to study the biological function of this steroid receptor in the epithelial compartment at defined stages of mammary gland development. The mouse mammary tumor virus (MMTV)-Cre-mediated, epithelial-specific ablation of exon 3 of the ERα gene in virgin mice severely impaired ductal elongation and side branching. The conditional knockout resulted in ablation of the ERα protein, and the progesterone receptor (PR), whose expression is under the control of ERα, was largely absent. The whey acidic protein (WAP)-Cre-mediated deletion of ERα during successive gestation cycles resulted in a loss of ductal side-branching and lobuloalveolar structures, ductal dilation, and decreased proliferation of alveolar progenitors. These abnormalities compromised milk production and led to malnourishment of the offspring by the second lactation. These observations suggest that ERα expression in the mammary epithelium is essential for normal ductal morphogenesis during puberty and alveologenesis during pregnancy and lactation.
Different transmitter transients underlie presynaptic cell type specificity of GABA
A,slow
and GABA
A,fast
Authors: Szabadics János , Tamás Gábor , Soltesz Ivan
Published: September 2007

Phasic (synaptic) and tonic (extrasynaptic) inhibition represent the two most fundamental forms of GABA
A
receptor-mediated transmission. Inhibitory postsynaptic currents (IPSCs) generated by GABA
A
receptors are typically extremely rapid synaptic events that do not last beyond a few milliseconds. Although unusually slow GABA
A
IPSCs, lasting for tens of milliseconds, have been observed in recordings of spontaneous events, their origin and mechanisms are not known. We show that neocortical GABA
A,slow
IPSCs originate from a specialized interneuron called neurogliaform cells. Compared with classical GABA
A,fast
IPSCs evoked by basket cells, single spikes in neurogliaform cells evoke extraordinarily prolonged GABA
A
responses that display tight regulation by transporters, low peak GABA concentration, unusual benzodiazepine modulation, and spillover. These results reveal a form of GABA
A
receptor mediated communication by a dedicated cell type that produces slow ionotropic responses with properties intermediate between phasic and tonic inhibition.
A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane
Authors: Salpingidou Georgia , Smertenko Andrei , Hausmanowa-Petrucewicz Irena , Hussey Patrick J. , Hutchison Chris J.
Published: September 2007

The type II inner nuclear membrane protein emerin is a component of the LINC complex that connects the nuclear lamina to the actin cytoskeleton. In emerin-null or -deficient human dermal fibroblasts we find that the centrosome is detached from the nucleus. Moreover, following siRNA knockdown of emerin in wild-type fibroblasts, the centrosome also becomes detached from the nucleus. We show that emerin interacts with tubulin, and that nocadozole-treated wild-type cells phenocopy the detached centrosome characteristic of emerin-null/deficient cells. We also find that a significant fraction of emerin is located at the outer nuclear membrane and peripheral ER, where it interacts directly with the centrosome. Our data provide the first evidence in mammalian cells as to the nature of the linkage of the centrosome, and therefore the tubulin cytoskeleton, with the outer nuclear membrane.
Extracellular stimuli specifically regulate localized levels of individual neuronal mRNAs
Authors: Willis Dianna E. , van Niekerk Erna A. , Sasaki Yukio , Mesngon Mariano , Merianda Tanuja T. , Williams Gervan G. , Kendall Marvin , Smith Deanna S. , Bassell Gary J. , Twiss Jeffery L.
Published: September 2007

Subcellular regulation of protein synthesis requires the correct localization of messenger RNAs (mRNAs) within the cell. In this study, we investigate whether the axonal localization of neuronal mRNAs is regulated by extracellular stimuli. By profiling axonal levels of 50 mRNAs detected in regenerating adult sensory axons, we show that neurotrophins can increase and decrease levels of axonal mRNAs. Neurotrophins (nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3) regulate axonal mRNA levels and use distinct downstream signals to localize individual mRNAs. However, myelin-associated glycoprotein and semaphorin 3A regulate axonal levels of different mRNAs and elicit the opposite effect on axonal mRNA levels from those observed with neurotrophins. The axonal mRNAs accumulate at or are depleted from points of ligand stimulation along the axons. The translation product of a chimeric green fluorescent protein–β-actin mRNA showed similar accumulation or depletion adjacent to stimuli that increase or decrease axonal levels of endogenous β-actin mRNA. Thus, extracellular ligands can regulate protein generation within subcellular regions by specifically altering the localized levels of particular mRNAs.
Real-Time Polymerase Chain Reaction Detection of Methicillin-ResistantStaphylococcus aureus:Impact on Nosocomial Transmission and Costs
Authors: Conterno L. O. , Shymanski J. , Ramotar K. , Toye B. , van Walraven C. , Coyle D. , Roth V. R.
Published: September 2007

Objectives.

To assess the impact of real-time polymerase chain reaction (PCR) detection of methicillin-resistantStaphylococcus aureus(MRSA) on nosocomial transmission and costs.

Design.

Monthly MRSA detection rates were measured from April 1, 2000, through December 31, 2005. Time series analysis was used to identify changes in MRSA detection rates, and decision analysis was used to compare the costs of detection by PCR and by culture.

Setting.

A 1,200-bed, tertiary care hospital in Canada.

Patients.

Admitted patients at high risk for MRSA colonization. MRSA detection using culture-based screening was compared with a commercial PCR assay.

Results.

The mean monthly incidence of nosocomial MRSA colonization or infection was 0.37 cases per 1,000 patient-days. The time-series model indicated an insignificant decrease of 0.14 cases per 1,000 patient-days per month (95% confidence interval, —0.18 to 0.46) after the introduction of PCR detection (P= .39). The mean interval from a reported positive result until contact precautions were initiated decreased from 3.8 to 1.6 days (P<.001). However, the cost of MRSA control increased from Can$605,034 to Can$771,609. Of 290 PCR-positive patients, 120 (41.4%) were placed under contact precautions unnecessarily because of low specificity of the PCR assay used in the study; these patients contributed 37% of the increased cost. The modeling study predicted that the cost per patient would be higher with detection by PCR (Can$96) than by culture (Can$67).

Conclusion.

Detection of MRSA by the PCR assay evaluated in this study was more costly than detection by culture for reducing MRSA transmission in our hospital. The cost benefit of screening by PCR varies according to incidences of MRSA colonization and infection, the predictive values of the assay used, and rates of compliance with infection control measures.
Decreasing Airborne Contamination Levels in High-Risk Hospital Areas Using a Novel Mobile Air-Treatment Unit
Authors: Bergeron V. , Reboux G. , Poirot J. L. , Laudinet N.
Published: September 2007

Objective.

To evaluate the performance of a new mobile air-treatment unit that uses nonthermal-plasma reactors for lowering the airborne bioburden in critical hospital environments and reducing the risk of nosocomial infection due to opportunistic airborne pathogens, such asAspergillus fumigatus.

Methods.

Tests were conducted in 2 different high-risk hospital areas: an operating room under simulated conditions and rooms hosting patients in a pediatric hematology ward. Operating room testing provided performance evaluations of removal rates for airborne contamination (ie, particles larger than 0.5μm) and overall lowering of the airborne bioburden (ie, colony-forming units of total mesophilic flora and fungal flora per cubic meter of air). In the hematology service, opportunistic and nonpathogenic airborne fungal levels in a patient's room equipped with an air-treatment unit were compared to those in a control room.

Results.

In an operating room with a volume of 118 m3, the time required to lower the concentration of airborne particles larger than 0.5μm by 90% was decreased from 12 minutes with the existing high-efficiency particulate air filtration system to less than 2 minutes with the units tested, with a 2-log decrease in the steady-state levels of such particles (P<.01). Concurrently, total airborne mesophilic flora concentrations dropped by a factor of 2, and the concentrations of fungal species were reduced to undetectable levels (P<.01). The 12-day test period in the hematology ward revealed a significant reduction in airborne fungus levels (P<.01), with average reductions of 75% for opportunistic species and 82% for nonpathogenic species.

Conclusion.

Our data indicate that the mobile, nonthermal-plasma air treatment unit tested in this study can rapidly reduce the levels of airborne particles and significantly lower the airborne bioburden in high-risk hospital environments.
Preventing the Airborne Spread ofStaphylococcus aureusby Persons With the Common Cold: Effect of Surgical Scrubs, Gowns, and Masks
Authors: Bischoff Werner E. , Tucker Brian K. , Wallis Michelle L. , Reboussin Beth A. , Pfaller Michael A. , Hayden Frederick G. , Sherertz Robert J.
Published: September 2007

Objective.

Transmission ofStaphylococcus aureusvia air may play an important role in healthcare settings. This study investigates the impact of barrier precautions on the spread of airborneS. aureusby volunteers with experimentally induced rhinovirus infection (ie, the common cold).

Design.

Prospective nonrandomized study.

Setting.

Wake Forest University School of Medicine (Winston-Salem, NC).

Participants.

A convenience sample of 10 individuals with nasalS. aureuscarriage selected from 593 students screened for carriage.

Intervention.

AirborneS. aureusdispersal was studied in the 10 participants under the following clothing conditions: street clothes, surgical scrubs, surgical scrubs and a gown, and the latter plus a face mask. After a 4-day baseline period, volunteers were exposed to a rhinovirus, and their clinical course was followed for 12 days. Daily swabs of nasal specimens, pharynx specimens, and skin specimens were obtained for quantitative culture, and cold symptoms were documented. Data were analyzed by random-effects negative binomial models.

Results.

All participants developed a common cold. Incidence rate ratios (IRRs) indicated that, compared with airborne levels ofS. aureusduring sessions in which street clothes were worn, airborne levels decreased by 75% when surgical scrubs were worn (P<.001), by 80% when scrubs and a surgical gown were worn (P<.001), and by 82% when scrubs, a gown, and a face mask were worn (P<.001). The addition of a mask to the surgical scrubs and gown did not reduce the airborne dispersal significantly (IRR, 0.92;P>.05). Male volunteers shed twice as muchS. aureusas females (incidence rate ratio, 2.04;P= .013). The cold did not alter the efficacy of the barrier precautions.

Conclusions.

Scrubs reduced the spread of airborneS. aureus, independent of the presence of a rhinovirus-induced cold. Airborne dispersal of S. aureus during sessions in which participants wore surgical scrubs was not significantly different from that during sessions in which gowns and gowns plus masks were also worn.
Role of Acid-Suppressing Medications During a Sustained Outbreak of Salmonella Enteritidis Infection in a Long-Term Care Facility
Authors: Bowen Anna , Newman Alexandra , Estivariz Concepcion , Gilbertson Norene , Archer John , Srinivasan Arjun , Lynch Michael , Painter John
Published: September 2007

During an insidious outbreak of salmonellosis in a long-term care facility, residents who were treated with acid-suppressing medications were 8 times more likely than other residents to develop Salmonella infection. Among vulnerable populations, the risks and benefits of acid-suppressing medications should be considered carefully before use.
Widespread Environmental Contamination Associated With Patients With Diarrhea and Methicillin-ResistantStaphylococcusaureus Colonization of the Gastrointestinal Tract
Authors: Boyce John M. , Havill Nancy L. , Otter Jonathan A. , Adams Nicholas M. T.
Published: September 2007

Objective.

Patients colonized with methicillin-resistantStaphylococcus aureus(MRSA) may contaminate their immediate environment with this organism. However, the extent to which gastrointestinal colonization with MRSA affects environmental contamination is not known. We investigated the frequency of environmental contamination in the rooms of patients with diarrheal stools and heavy gastro-intestinal colonization with MRSA.

Design.

Prospective observational study.

Setting.

A 500-bed teaching hospital.

Methods.

Stool specimens submitted forClostridium difficiletoxin assays were inoculated onto colistin-naladixic acid agar. MRSA was identified with standard methods. Samples from a standardized list of 10 environmental surfaces were cultured, from the rooms of 8 patients who had diarrhea that yielded heavy growth of MRSA (case patients) and from the rooms of 6 MRSA-positive patients with stool cultures negative for MRSA (control patients). MRSA isolates from 13 patients (8 case patients and 5 control patients) and 64 of the environmental isolates recovered from their rooms were compared by pulsed-field gel electrophoresis (PFGE). One clinical isolate from a control patient was excluded because there was no corresponding environmental MRSA isolate with which to compare it.

Results.

Overall, MRSA were recovered from 47 (58.8%) of 80 surfaces in the rooms of case patients, compared with 14 (23.3%) of 60 surfaces in the rooms of control patients (58.8% [95% CI, 47.8-68.9] vs 23.3% [95% CI, 14.3-35.5];P<.0001). The items most commonly contaminated were bedside rails, blood pressure cuffs, television remote controls, and toilet seats. Seventy-eight percent of the environmental isolates in patients' rooms had PFGE types that were indistinguishable or closely related to those recovered from the patients' clinical specimens.

Conclusions.

Patients who have diarrheal stools and heavy gastrointestinal colonization with MRSA are associated with significantly greater environmental MRSA contamination than patients without MRSA in their stool, and they are likely to be the source of that contamination.
Impact of a Single Plain Finger Ring on the Bacterial Load on the Hands of Healthcare Workers
Authors: Fagernes Mette , Lingaas Egil , Bjark Per
Published: September 2007

Objective.

To investigate the impact of a single plain finger ring on the number and types of bacteria on the hands of healthcare workers (HCWs).

Design.

Nonequivalent control groups, posttest only (preexperimental).

Methods.

A total of 121 HCWs wearing 1 plain ring and 113 HCWs wearing no rings had both hands sampled by the “glove juice” technique. Quantitative culture of the samples was performed and microorganisms were identified.

Setting.

Two Norwegian acute care hospitals.

Participants.

A total of 234 HCWs who had physical contact with patients.

Results.

Total bacterial counts did not differ when hands with rings and hands without rings were compared, both according to nonpaired analysis (which compared the ring-bearing hands of ring-wearing HCWs to the hands of HCWs who did not wear rings [P= .661]) and according to paired analysis (which compared the ring-bearing and ring-free hands of ring-wearing HCWs [P= .071]).Staphylococcus aureuswas recovered from 18.6% of the hands sampled, belonging to 26.9% of the HCWs, but neither paired nor nonpaired analysis showed any association with ring wearing. Gram-negative bacteria were recovered from 20.3% of the hands sampled, belonging to 28.6% of the HCWs. Ring-wearing HCWs were significantly more likely to be carriers of Enterobacteriaceae (P= .006), but paired comparison of the ring-bearing and ring-free hands of these HCWs did not show significant differences (P= .180). Carriage of nonfermentative gram-negative rods did not differ between the 2 groups, by either paired or nonpaired analysis.

Conclusions.

Wearing a single plain finger ring did not increase the total bacterial load on the hands, nor was it associated with an increased rate of carriage ofS. aureusor nonfermentative gram-negative rods. However, plain rings were associated with an increased rate of Enterobacteriaceae carriage.
Interhospital Comparisons of Coronary Artery Bypass Graft Surgical Site Infection Rates Differ if Donor Sites Are Excluded
Authors: Russo P. L. , Gurrin L. , Friedman N. D. , Bull A. L. , Marasco S. , Kelly H. , Boardman C. J. , Richards M. J.
Published: September 2007

The advent of public reporting of hospital-acquired infection rates has sparked ongoing discussion about the most appropriate surveillance data to present. When we used different numerators to calculate rates of surgical site infection following coronary artery bypass graft surgery, we found that some hospitals' rates and their rankings were notably affected.
Simulating association studies: a data-based resampling method for candidate regions or whole genome scans
Authors: Wright Fred A. , Huang Hanwen , Guan Xiaojun , Gamiel Kevin , Jeffries Clark , Barry William T. , Pardo-Manuel de Villena Fernando , Sullivan Patrick F. , Wilhelmsen Kirk C. , Zou Fei
Published: September 2007

Motivation: Reductions in genotyping costs have heightened interest in performing whole genome association scans and in the fine mapping of candidate regions. Improvements in study design and analytic techniques will require the simulation of datasets with realistic patterns of linkage disequilibrium and allele frequencies for typed SNPs.

Methods: We describe a general approach to simulate genotyped datasets for standard case-control or affected child trio data, by resampling from existing phased datasets. The approach allows for considerable flexibility in disease models, potentially involving a large number of interacting loci. The method is most applicable for diseases caused by common variants that have not been under strong selection, a class specifically targeted by the International HapMap project.

Results: Using the three population Phase I/II HapMap data as a testbed for our approach, we have implemented the approach in HAP-SAMPLE, a web-based simulation tool.

Availability: The web-based tool is available at http://www.hapsample.org

Contact:  fwright@bios.unc.edu; fzou@bios.unc.edu;kirk@med.unc.edu
Factors affecting rule compliance with mesh size regulations in the Baltic cod trawl fishery
Authors: Suuronen Petri , Tschernij Vesa , Jounela Pekka , Valentinsson Daniel , Larsson P-O.
Published: September 2007

Suuronen, P., Tschernij, V., Jounela, P., Valentinsson, D., and Larsson, P-O. 2007. Factors affecting rule compiance with mesh size regulations in the Baltic cod trawl fishery. – ICES Journal of Marine Science, 64: 1603–1606. In this study, we evaluate the efficiency and applicability of a series of gear-based management measures, enforced since 1990, whose purpose was to improve size selectivity in the trawl fishery for Baltic cod (Gadus morhua). In general, our study revealed that these measures had no marked effect on the capture and discard of young cod. Legal and illegal manipulation of selective codends was widespread. The adoption of a codend design that offered a modest increase in selectivity, but had a good match with the legislated minimum landing size (MLS), led to greater compliance, demonstrating that a mismatch between MLS and selectivity should be avoided. It was also obvious that, generally, the fishing industry did not tolerate large short-term losses. Our evaluation is that overly ambitious rules will be circumvented, and frequent and incoherent changes in the regulations represent bad management practice. A gradual introduction of restrictions and participation by fishers in the decision-making process will increase compliance.
Acoustic and stiffness properties of gillnets as they relate to small cetacean bycatch
Authors: Mooney T. Aran , Au Whitlow W. L. , Nachtigall Paul E. , Trippel Edward A.
Published: September 2007

Mooney, T. A., Au, W. W. L., Nachtigall, P. E., and Trippel, E. A. 2007. Acoustic and stiffness properties of gillnets as they relate to small cetacean bycatch. – ICES Journal of Marine Science, 64: 1324–1332. Small cetaceans are incidental bycatch in gillnet fisheries. Dolphin and porpoise bycatch has been reduced by the use of barium sulphate-enhanced gillnets. This decreased entanglement is likely the result of either higher acoustic reflectivity or greater stiffness for barium nets. To address these variables, our study quantified the acoustic reflectivity and stiffness of six net types including barium sulphate, iron oxide-enhanced and control demersal gillnets of sizes which typically target cod (Gadus morhua) and monkfish (Lophius americanus). Acoustic reflectivity, or target strength (TS), was assessed using dolphin and porpoise-like sonar signals from 0° to 40°. TS values were used to calculate likely detection ranges. Barium sulphate- and iron oxide-enhanced nets showed increased reflectivity compared with control nets, with the barium sulphate nets generating the highest TS values. Dolphins should detect these nets in time to avoid contact, but porpoises, with typically lower source levels, may not detect nets at a range great enough to avoid entanglement. Barium sulphate line was significantly stiffer than comparable nylon line. All lines lost stiffness when soaked in seawater for 24 h. Barium sulphate nets proved stiffer and more acoustically reflective, and both factors are likely important in reducing harbour porpoise bycatch.
Strong parasitoid-mediated selection in experimental populations of aphids
Authors: Herzog Jenny , Müller Christine B , Vorburger Christoph
Published: September 2007

Clonal diversity in asexual populations may be maintained if different clones are favoured under different environmental conditions. For aphids, parasitoids are an important variable of the biotic environment. To test whether parasitoids can mediate selection among host clones, we used experimental populations consisting of 10 clones of the peach–potato aphid,
Myzus persicae
, and allowed them to evolve for several generations either without parasitoids or in the presence of two species of parasitoid wasps. In the absence of parasitoids, strong shifts in clonal frequencies occurred, mostly in favour of clones with high rates of increase. The parasitoid
Diaeretiella rapae
hardly affected aphid densities but changed the outcome of competition by favouring one entirely resistant clone and disfavouring a highly susceptible clone.
Aphidius colemani
, the more infective parasitoid, strongly reduced aphid densities and dramatically changed host clonal frequencies. The most resistant clone, not a successful clone without parasitoids, became totally dominant. These results highlight the potential of temporal or spatial variation in parasitoid densities to maintain clonal diversity in their aphid hosts.
Four-legged friend or foe? Dog walking displaces native birds from natural areas
Authors: Banks Peter B , Bryant Jessica V
Published: September 2007

Dog walking is among the world's most popular recreational activities, attracting millions of people to natural areas each year with diverse benefits to human and canine health. But conservation managers often ban dog walking from natural areas fearing that wildlife will see dogs as potential predators and abandon their natural habitats, resulting in outcry at the restricted access to public land. Arguments are passionate on both sides and debate has remained subjective and unresolved because experimental evidence of the ecological impacts of dog walking has been lacking. Here we show that dog walking in woodland leads to a 35% reduction in bird diversity and 41% reduction in abundance, both in areas where dog walking is common and where dogs are prohibited. These results argue against access by dog walkers to sensitive conservation areas.
Adaptive evolution of genes underlying schizophrenia
Authors: Crespi Bernard , Summers Kyle , Dorus Steve
Published: September 2007

Schizophrenia poses an evolutionary-genetic paradox because it exhibits strongly negative fitness effects and high heritability, yet it persists at a prevalence of approximately 1% across all human cultures. Recent theory has proposed a resolution: that genetic liability to schizophrenia has evolved as a secondary consequence of selection for human cognitive traits. This hypothesis predicts that genes increasing the risk of this disorder have been subject to positive selection in the evolutionary history of humans and other primates. We evaluated this prediction using tests for recent selective sweeps in human populations and maximum-likelihood tests for selection during primate evolution. Significant evidence for positive selection was evident using one or both methods for 28 of 76 genes demonstrated to mediate liability to schizophrenia, includingDISC1,DTNBP1andNRG1, which exhibit especially strong and well-replicated functional and genetic links to this disorder. Strong evidence of non-neutral, accelerated evolution was found forDISC1, particularly for exon 2, the only coding region within the schizophrenia-associated haplotype. Additionally, genes associated with schizophrenia exhibited a statistically significant enrichment in their signals of positive selection in HapMap and PAML analyses of evolution along the human lineage, when compared with a control set of genes involved in neuronal activities. The selective forces underlying adaptive evolution of these genes remain largely unknown, but these findings provide convergent evidence consistent with the hypothesis that schizophrenia represents, in part, a maladaptive by-product of adaptive changes during human evolution.
A new theory for the evolution of polyandry as a means of inbreeding avoidance
Authors: Cornell Stephen J , Tregenza Tom
Published: September 2007

We propose a novel theory for the evolution of polyandry driven by genetic benefits to females whose offspring interbreed. In species with an ecology characterized by frequent colonization of new habitat patches, consanguineous matings may be common during the early stages of colonization, but genetic diversity may grow as new colonizers arrive. We show that with levels of inbreeding depression similar to those found in predominantly inbreeding populations, a polyandrous female can benefit her descendants since matings among her brood are mainly between half siblings rather than full siblings. We examine the invasion by a polyandrous phenotype using explicit genetic models in which costs of inbreeding are themselves subject to selection. In common with other models of inbreeding, we find that underlying high levels of inbreeding tend to purge deleterious recessive alleles, and hence these are unlikely to maintain sufficient inbreeding depression to favour polyandry. However, if costs of inbreeding are due to overdominance, biologically realistic levels of inbreeding depression result in genetic benefits large enough to favour polyandry provided it is not too costly. The potential significance of polyandry as a mechanism to reduce inbreeding in grandchildren will depend upon the genetic basis of inbreeding depression in natural, inbreeding populations.
Isolation and characterization of melanopsin (
Opn4
) from the Australian marsupial
Sminthopsis crassicaudata
(fat-tailed dunnart)
Authors: Pires Susana S , Shand Julia , Bellingham James , Arrese Catherine , Turton Michael , Peirson Stuart , Foster Russell G , Halford Stephanie
Published: September 2007

Melanopsin confers photosensitivity to a subset of retinal ganglion cells and is responsible for many non-image-forming tasks, like the detection of light for circadian entrainment. Recently, two melanopsin genes,
Opn4m
and
Opn4x,
were described in non-mammalian vertebrates. However, only one form,
Opn4m,
has been described in the mammals, although studies to date have been limited to the placentals and have not included the marsupials.

We report here the isolation and characterization of an
Opn4
gene from an Australian marsupial, the fat-tailed dunnart (
Sminthopsis crassicaudata
), and present evidence which suggests that the
Opn4x
gene was lost before the placental/marsupial split.
In situ
hybridization shows that the expression of
Opn4
in the dunnart eye is restricted to a subset of ganglion cells, a pattern previously reported for rodents and primates. These Opn4-positive cells are randomly distributed across the dunnart retina. We also undertook a comparative analysis with the South American marsupial, the grey short-tailed opossum (
Monodelphis domestica)
, and two placental mammals, mouse and human. This approach reveals that the two marsupials show a higher sequence identity than that seen between rodents and primates, despite separating at approximately the same point in time, some 65–85 Myr ago.
Limited performance of DNA barcoding in a diverse community of tropical butterflies
Authors: Elias Marianne , Hill Ryan I , Willmott Keith R , Dasmahapatra Kanchon K , Brower Andrew V.Z , Mallet James , Jiggins Chris D
Published: September 2007

DNA ‘barcoding’ relies on a short fragment of mitochondrial DNA to infer identification of specimens. The method depends on genetic diversity being markedly lower within than between species. Closely related species are most likely to share genetic variation in communities where speciation rates are rapid and effective population sizes are large, such that coalescence times are long. We assessed the applicability of DNA barcoding (here the 5′ half of thecytochrome c oxidase I) to a diverse community of butterflies from the upper Amazon, using a group with a well-established morphological taxonomy to serve as a reference. Only 77% of species could be accurately identified using the barcode data, a figure that dropped to 68% in species represented in the analyses by more than one geographical race and at least one congener. The use of additional mitochondrial sequence data hardly improved species identification, while a fragment of a nuclear gene resolved issues in some of the problematic species. We acknowledge the utility of barcodes when morphological characters are ambiguous or unknown, but we also recommend the addition of nuclear sequence data, and caution that species-level identification rates might be lower in the most diverse habitats of our planet.
High-throughput methylation profiling by MCA coupled to CpG island microarray
Authors: Estécio Marcos R.H. , Yan Pearlly S. , Ibrahim Ashraf E.K. , Tellez Carmen S. , Shen Lanlan , Huang Tim H.-M. , Issa Jean-Pierre J.
Published: September 2007

An abnormal pattern of DNA methylation occurs at specific genes in almost all neoplasms. The lack of high-throughput methods with high specificity and sensitivity to detect changes in DNA methylation has limited its application for clinical profiling. Here we overcome this limitation and present an improved method to identify methylated genes genome-wide by hybridizing a CpG island microarray with amplicons obtained by the methylated CpG island amplification technique (MCAM). We validated this method in three cancer cell lines and 15 primary colorectal tumors, resulting in the discovery of hundreds of new methylated genes in cancer. The sensitivity and specificity of the method to detect hypermethylated loci were 88% and 96%, respectively, according to validation by bisulfite-PCR. Unsupervised hierarchical clustering segregated the tumors into the expected subgroups based on CpG island methylator phenotype classification. In summary, MCAM is a suitable technique to discover methylated genes and to profile methylation changes in clinical samples in a high-throughput fashion.
Controlling urban car parking – an exemplar for public management?
Authors: Kerley Richard
Published: September 2007

Purpose

This paper aims to analyse the management of urban on street car parking as an example of the dilemmas of understanding and improving the performance of public management.

Design/methodology/approach

A conceptual paper that assesses empirical practice against different theoretical frameworks and suggests new management and policy directions.

Findings

The management of regulatory services such as urban on street car parking are little examined in the literature of public management, though the economic literature does review some aspects of parking behaviour. This paper analyses car parking as an exemplar site for empirical confirmation of the difficulties of reconciling multiple stakeholder interests when addressing a “wicked problem”. The paper further argues that public management theory can be developed from examination of such routine minutiae of day‐to‐day life.

Originality/value

The paper provides a fresh theoretical perspective on an every day social activity and suggests that such analysis can aid theory building for public management.
Population pharmacokinetic analysis of carboxyhaemoglobin concentrations in adult cigarette smokers
Authors: Cronenberger Carol , Mould Diane R. , Roethig Hans‐Juergen , Sarkar Mohamadi
Published: September 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The pharmacokinetics of carboxyhaemoglobin have been reported previously, primarily with regard to poisoning and toxicity.

• Most of these reports have involved noncompartmental analysis of data obtained where the actual dose of carbon monoxide was not known.

WHAT THIS STUDY ADDS

• This study presents a comprehensive population pharmacokinetic model for carboxyhaemoglobin in adult cigarette smokers.

• Since carboxyhaemoglobin is a marker of cigarette smoke exposure, model‐based evaluations can be used for simulation and other evaluations of the kinetics of this agent.

AIMS

To develop a population‐based model to describe and predict the pharmacokinetics of carboxyhaemoglobin (COHb) in adult smokers.

METHODS

Data from smokers of different conventional cigarettes (CC) in three open‐label, randomized studies were analysed using NONMEM (version V, Level 1.1). COHb concentrations were determined at baseline for two cigarettes [Federal Trade Commission (FTC) tar 11 mg; CC1, or FTC tar 6 mg; CC2]. On day 1, subjects were randomized to continue smoking their original cigarettes, switch to a different cigarette (FTC tar 1 mg; CC3), or stop smoking. COHb concentrations were measured at baseline and on days 3 and 8 after randomization. Each cigarette was treated as a unit dose assuming a linear relationship between the number of cigarettes smoked and measured COHb percent saturation. Model building used standard methods. Model performance was evaluated using nonparametric bootstrapping and predictive checks.

RESULTS

The data were described by a two‐compartment model with zero‐order input and first‐order elimination with endogenous COHb. Model parameters included elimination rate constant (k10), central volume of distribution (Vc/F), rate constants between central and peripheral compartments (k12 and k21), baseline COHb concentrations (c0), and relative fraction of carbon monoxide absorbed (F1). The median (range) COHb half‐lives were 1.6 h (0.680–2.76) and 30.9 h (7.13–367) (α and β phases, respectively). F1 increased with increasing cigarette tar content and age, whereas k12 increased with ideal body weight.

CONCLUSION

A robust model was developed to predict COHb concentrations in adult smokers and to determine optimum COHb sampling times in future studies.
Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease
Authors: Cyr Marie‐Christyne , Beauchesne Marie‐France , Lemière Catherine , Blais Lucie
Published: September 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Despite active research, none of the existing medications used to treat chronic obstructive pulmonary disease (COPD) has been shown to modify the long‐term decline in lung function.

• Theophyllines have been recognized for their bronchodilating effects and anti‐inflammatory properties, but at the same time they are associated with the risk of adverse events due to their narrow therapeutic range and potential for drug interactions.

• To our knowledge, no study has investigated the effects of theophylline on outcomes that can reflect the overall morbidity of COPD patients.

WHAT THIS STUDY ADDS

• The use of theophyllines is associated with a reduction in the rate of COPD exacerbations compared with long‐acting β2‐agonists among COPD patients.

• Theophyllines could be seen as an interesting alternative in the treatment of COPD, because they are much less expensive than long‐acting β2‐agonists, and, from the patient's perspective, an oral formulation might be easier to take than an inhaled formulation.

AIM

To determine the effectiveness of theophyllines in real clinical practice on moderate to severe exacerbations.

METHODS

A cohort of 36 492 chronic obstructive pulmonary disease (COPD) patients aged ≥50 years was reconstructed from the health administrative databases of the province of Quebec, Canada, between 1 January 1995 and 31 December 2002 to compare users of theophyllines with users of inhaled corticosteroids (ICS) and users of long‐acting β2‐agonists (LABA) on their rate of moderate to severe COPD exacerbations.

RESULTS

Users of theophyllines were found to be less likely than users of LABA [crude rates 84 vs. 91 per 100 patient‐years, adjusted rate ratio (RR) 0.89, 95% confidence interval (CI) 0.84, 0.95] and users of theophyllines plus ICS were found to be less likely than users of LABA plus ICS (crude rates 114 vs. 112 per 100 patient‐years, adjusted RR 0.89, 95% CI 0.87, 0.92) to have moderate to severe COPD exacerbations. Users of theophyllines were found to be more likely than users of ICS to have a COPD exacerbation (crude rates 84 vs. 77 per 100 patient‐years, adjusted RR 1.07, 95% CI 1.04, 1.10), and this association was even stronger among patients who had at least three exacerbations in the year prior to cohort entry (crude rates 273 vs. 213 per 100 patient‐years, adjusted RR 1.28, 95% CI 1.19, 1.38).

CONCLUSION

The use of theophyllines was found to be associated with a reduction in the rate of COPD exacerbations among all COPD patients, but to be less effective than ICS among patients with frequent exacerbations.