bluuebunny/crossref_metadata_2025 huggingface dataset:
ECOSYSTEM SERVICES AND ECONOMIC THEORY: INTEGRATION FOR POLICY‐RELEVANT RESEARCH
Authors: Fisher Brendan , Turner Kerry , Zylstra Matthew , Brouwer Roy , de Groot Rudolf , Farber Stephen , Ferraro Paul , Green Rhys , Hadley David , Harlow Julian , Jefferiss Paul , Kirkby Chris , Morling Paul , Mowatt Shaun , Naidoo Robin , Paavola Jouni , Strassburg Bernardo , Yu Doug , Balmford Andrew
Published: January 2009

It has become essential in policy and decision‐making circles to think about the economic benefits (in addition to moral and scientific motivations) humans derive from well‐functioning ecosystems. The concept of ecosystem services has been developed to address this link between ecosystems and human welfare. Since policy decisions are often evaluated through cost–benefit assessments, an economic analysis can help make ecosystem service research operational. In this paper we provide some simple economic analyses to discuss key concepts involved in formalizing ecosystem service research. These include the distinction between services and benefits, understanding the importance of marginal ecosystem changes, formalizing the idea of a safe minimum standard for ecosystem service provision, and discussing how to capture the public benefits of ecosystem services. We discuss how the integration of economic concepts and ecosystem services can provide policy and decision makers with a fuller spectrum of information for making conservation–conversion trade‐offs. We include the results from a survey of the literature and a questionnaire of researchers regarding how ecosystem service research can be integrated into the policy process. We feel this discussion of economic concepts will be a practical aid for ecosystem service research to become more immediately policy relevant.
CONTEXT‐DEPENDENT EFFECTS OF FISHING: VARIATION IN TROPHIC CASCADES ACROSS ENVIRONMENTAL GRADIENTS
Authors: Shears Nick T. , Babcock Russell C. , Salomon Anne K.
Published: January 2009

Marine reserves provide a large‐scale experimental framework to investigate the effects of fishing on food web dynamics and how they vary with environmental context. Because marine reserves promote the recovery of previously fished predators, spatial comparisons between reserve and fished sites are often made to infer such effects; however, alternative explanations for differences between reserve and fished sites are seldom tested (e.g., environmental variation among sites). We investigated the context dependency of the predator–urchin–kelp trophic cascade reported in northeastern New Zealand by comparing the abundance of herbivorous sea urchins (Evechinus chloroticus), the extent of urchin barrens habitat, and macroalgal biomass between reserve and fished sites within six locations that span an environmental gradient in wave exposure, sedimentation, and water clarity. At depths where differences in urchin abundance or macroalgal biomass were found between reserve and fished sites we used a model selection approach to identify which variables (fishing or environmental factors) best explained the variation among sites. Differences between reserve and fished sites were not ubiquitous across the locations examined and were highly depth specific. At sheltered locations, urchins were rare and barrens absent at both reserve and fished sites. At moderately exposed coastal locations, actively grazing urchins were most abundant at 4–6 m depth, and significant differences in macroalgal biomass between reserve and fished sites were observed. In contrast, at offshore island locations, urchins extended into deeper water, and differences between reserve and fished sites were found at 4–9 m depth. These differences could only be attributed to trophic cascades associated with protection from fishing in two of the six locations examined. In other cases, variation between reserve and fished sites was equally well explained by differences in sediment or wave exposure among sites. These results suggest that trophic cascades are not ubiquitous to northeastern New Zealand's subtidal reefs and the importance of sea urchins, and indirectly predators, in controlling macroalgal biomass will vary at local and regional scales in relation to abiotic factors. A better mechanistic understanding of how environmental variation affects the strength of species interactions across multiple spatial scales is needed to predict the ecosystem‐level effects of fishing.
CASCADING EFFECTS OF FISHING CAN ALTER CARBON FLOW THROUGH A TEMPERATE COASTAL ECOSYSTEM
Authors: Salomon Anne K. , Shears Nick T. , Langlois Timothy J. , Babcock Russell C.
Published: January 2009

Mounting evidence suggests that fishing can trigger trophic cascades and alter food web dynamics, yet its effects on ecosystem function remain largely unknown. We used the large‐scale experimental framework of four marine reserves, spanning an oceanographic gradient in northeastern New Zealand, to test the extent to which the exploitation of reef predators can alter kelp carbon flux and secondary production. We provide evidence that the reduction of predatory snapper (Pagrus auratus) and lobster (Jasus edwardsii) can lead to an increase in sea urchins (Evechinus chloroticus) and indirect declines in kelp biomass in some locations but not others. Stable carbon isotope ratios (δ13C) of oysters (Crassostrea gigas) and mussels (Perna canaliculus) transplanted in reserve and fished sites within four locations revealed that fishing indirectly reduced the proportion of kelp‐derived organic carbon assimilated by filter feeders in two locations where densities of actively grazing sea urchins were 23.7 and 8.3 times higher and kelp biomass was an order of magnitude lower than in non‐fished reserve sites. In contrast, in the two locations where fishing had no effect on urchin density or kelp biomass, we detected no effect of fishing on the carbon signature of filter feeders. We show that the effects of fishing on nearshore trophic structure and carbon flux are context‐dependent and hinge on large‐scale, regional oceanographic factors. Where cascading effects of fishing on kelp biomass were documented, enhanced assimilation of kelp carbon did not result in the magnification of secondary production. Instead, a strong regional gradient in filter feeder growth emerged, best predicted by chlorophyll a. Estimates of kelp contribution to the diet of transplanted consumers averaged 56.9% ± 6.2% (mean ± SE) for mussels and 33.8% ± 7.3% for oysters, suggesting that organic carbon fixed by kelp is an important food source fueling northeastern New Zealand's nearshore food webs. The importance of predators in mediating benthic primary production and organic carbon flux suggests that overfishing can have profound consequences on ecosystem functioning particularly where pelagic primary production is limiting. Our results underscore the broader ecosystem repercussions of overfishing and its context‐dependent effects.
A TEST OF THE SPECIES–PEOPLE CORRELATION FOR STREAM MACRO‐INVERTEBRATES IN EUROPEAN COUNTRIES
Authors: Pautasso Marco , Fontaneto Diego
Published: January 2009

Many recent studies have shown that over large scales there are positive correlations between plant and vertebrate species richness and human population presence. It is unknown whether this pattern applies also to Ephemeroptera (mayflies), Plecoptera (stoneflies), and Trichoptera (caddisflies) (EPT), which are common bio‐indicators of the naturalness of streams. Most local studies report higher species richness of these macro‐invertebrates where human influences on water quality are lower. Using a newly collated taxonomic data set, we studied whether the species richness of EPT is related to human population size in European countries. Analyses controlled for country area, plant species richness, and mean annual temperature and precipitation. We found a significant increase in the number of EPT species with increasing human population size, plant species richness, and decreasing temperature. Our analysis confirmed the scale dependence of the human population–biodiversity correlation. Although stream macro‐invertebrates are traditionally used as indicators of pristine ecosystems over local to regional scales, over broad scales more populated regions have more EPT species than less populated ones. This finding underlines the importance of scale in ecology and implies that there is a challenge also for the broadscale conservation of EPT diversity.
Identifying the nonpoint source of perfluorinated compounds using a geographic information system based approach
Authors: Zushi Yasuyuki , Masunaga Shigeki
Published: January 2009

Perfluorinated compounds (PFCs) have been detected in a wide range of places. They have also been reported to come from nonpoint sources, but the origin of these sources has not been identified. In the present study, we attempted to characterize the nonpoint source of PFCs in the Hayabuchi River, Japan, which runs through an urban area, using a geographic information system (GIS) and statistical analysis. We also estimated annual PFC loads from nonpoint sources in Japan as a whole, determining a magnitude comparable to that from sewage treatment plants (STPs); the range was a few tons per year for each PFC. Perfluorinated compound pollution in river water was found to increase when the river received drainage from an area with a high proportion of commercial and/or transportation land use. It was also found that more PFCs were discharged from the watersheds where train stations are located. This result could be interpreted as the use of land for commercial and transportation purposes is prevalent in close proximity to train stations, and that the effluents from those areas contain high concentrations of PFCs. These findings suggested that train stations could be indicators of nonpoint sources of PFCs.
Effect of Ruminally-protected leucine supplement on milk yield and plasma amino acids in dairy cows
Authors: KRÍZOVÁ L. , TRINÁCTÝ J. , RICHTER M.
Published: January 2009

The aim of this study was to determine the influence of leucine supplement in the form of rumen-protected tablets on milk yield and composition and plasma amino acids in four high-yielding lactating Holstein cows. The experiment was carried out as a cross-over procedure and was divided into 4 periods of 14 d (10 d preliminary period and 4 d experimental period). Cows were fed ad libitum a diet based on maize silage, lucerne hay and a supplemental mixture. The diet, defficient in methionine, lysine, and leucine, was supplemented with methionine+lysine (Control) or methionine+lysine+leucine (Leu) in rumen protected form. The dry matter intake, milk yield and milk yield expressed in energy corrected milk did not differ significantly between the treatments. Milk protein content and yield did not show statistically significant variation. The contents and yield of casein, fat, lactose and urea were unaffected by the treatment. Blood metabolites did not vary between the treatments. The introduction of Leu resulted in higher plasma levels of proline (p
The effects of different levels of L-carnitine and fat on performance and egg quality of laying hens
Authors: REZAEI M. , DEHGHANI S. , ALIGHAFFARI J.
Published: January 2009

L-carnitine is used as feed additive in poultry diets to increase yield and to improve feed efficiency. The major role of L-carnitine appears to be the transport of long-chain fatty acids into mitochondria for À oxidation. This experiment was carried out to determine the effects of two levels of fat (10 and 30 g kg-1 DM) and two levels of L-carnitine (0 and 250 mg kg-1) on performance, egg quality, and blood parameters of laying hens in a factorial arrangement (2~2) with completely randomized design with six replicates and four laying hens in each replicate. During the experiment feed intake, egg weight, egg production, feed conversion ratio, and some blood parameters (triglyceride, cholesterol, LDL, HDL), egg quality (albumen height, egg shell thickness, egg shell breaking strength), and cholesterol content of eggs were measured. Results of this experiment indicated that supplementation of L-carnitine in laying hens diets had not significant effect on performance, cholesterol content of eggs, but decreased the levels of triglyceride, cholesterol, LDL in blood serum and increased albumen height of eggs significantly (p
Comment on Mathias Risse: "A Right to Work? A Right to Leisure? Labor Rights as Human Rights"
Authors: Pogge Thomas
Published: January 2009

In his ambitious paper, Risse addresses many important topics ranging from very general issues about what human rights are to quite specific questions about rights to work and leisure. I comment on four themes arranged in order of decreasing generality: Risse's understanding of what human rights are, Risse's suggestion that a conception of human rights should best be "basis-driven," Risse's particular basis-driven conception of human rights, and Risse's specific position on human rights relating to labor and leisure.What grounds can Risse give us for accepting his revisionist understanding of human rights as membership rights, which is so dramatically at odds with fundamental fixed points that have been taken for granted in human rights disputes over the last 60 years or so? If Risse has his way, then the treatment of a human being by others raises human rights concerns only if she is a participant in the global order and only if her treatment is a matter of international concern. It is obvious how this understanding of human rights is welcome to those who seek to free their own conduct or their country's policies from human-rights constraints. Appealing to Risse's understanding, they will be able to block criticisms based on human rights by denying, for example, that the people of the Gaza Strip are members of the global order or by denying that the torture of Burmese citizens within Burma is a matter of international concern. For those whose human rights are in jeopardy, Risse's understanding of human rights could be a disaster. We should therefore examine very closely the arguments he may yet produce for his understanding and, unless they are hugely compelling, stick to the orthodox understanding of human rights as rights that all human beings have against all other human agents.
Comment on Brian Langille: "What is International Labor Law For?"
Authors: Benvenisti Eyal
Published: January 2009

This comment on Brian Langille's article agrees with Langille's claim that inter-state competition should not be viewed as the main challenge to the global efforts to regulate labor rights. The comment suggests, however, that there is another type of competition that poses a challenge, namely a transnational competition which takes place among sub-state actors. Focusing on this "transnational conflict paradigm," the ILO has the tools to engage domestic constituencies in an effort to promote labor rights within the respective member states.
Microarray Analysis of Distinct Gene Transcription Profiles in Non-eosinophilic Chronic Sinusitis with Nasal Polyps
Authors: Payne Spencer C. , Han Joseph K. , Huyett Phillip , Negri Julie , Kropf Elizabeth Z. , Borish Larry , Steinke John W.
Published: January 2009

Background

Recent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.

Methods

Patients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

Microarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1α, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated

Conclusion

This study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.
Pathophysiology of Nasal Polyposis: The Role of Desmosomal Junctions
Authors: Zuckerman Jodi D. , Lee Winston Y. , DelGaudio John M. , Moore Charles E. , Nava Porfirio , Nusrat Asma , Parkos Charles A.
Published: January 2009

Background

Many mucosal inflammatory conditions are associated with alterations in epithelial intercellular junctions and barrier function; however, little is known about the role of intercellular junctions in inflammatory diseases of the upper airways. In this study, we examined nasal polyps for altered intercellular junctions and protein expression.

Methods

Biopsy specimens of nasal polyps and normal tissue were obtained intraoperatively from 11 patients and 6 controls. Tissue was analyzed for expression of intercellular junctional proteins by immunofluorescence. In parallel, cultured human bronchial epithelial (HBE) cells were treated with tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, and IL-13 to simulate inflammatory conditions followed by assessment for changes in junctional proteins by immunofluorescence and Western blot.

Results

Of the intercellular junctional proteins analyzed, including proteins comprising tight and adherens junctions, the only alterations observed were in desmosomal proteins in nasal polyp epithelium compared with normal controls. Specifically, expression of desmosomal proteins DSG2 and DSG3 were significantly decreased in polyps versus controls (0.53 pixel/μm2 versus 1.09 pixel/μm2 [p = 0.009], and 0.29 pixel/μm2 versus 1.11 pixel/μm2 [p = 0.0078], respectively). In vitro experiments involving exposure of cultured HBE cells with inflammatory cytokines revealed that TNF-alpha treatment resulted in internalization and decreased expression of DSG2 by immunofluorescence and Western blotting. Treatment with IFN-gamma resulted in increased expression of DSG2 and evidence of protein cleavage by Western blot. IL-13 exposure resulted in down-regulation of DSG2 expression and evidence of protein cleavage.

Conclusion

These results indicate that nasal polyps express decreased levels of DSG2 and DSG3 components of desmosomal junctions. This is likely linked to the mucosal inflammatory response. Exposure of a respiratory cell line to Th1/Th2 cytokines results in similar expressional alterations in DSG2, suggesting protein internalization and cleavage. We speculate that weakened desmosomal junctions in nasal mucosa secondary to inflammatory cytokines may contribute to the formation of nasal polyposis.
Squamous Metaplasia and Chronic Rhinosinusitis: A Clinicopathological Study
Authors: Mynatt Robert G. , Do Jennifer , Janney Christine , Sindwani Raj
Published: January 2009

Background

The significance of squamous metaplasia (SM) in chronic rhinosinusitis (CRS) is unknown. The objectives of this study were to determine the prevalence of SM in histopathological specimens from patients with CRS and to correlate these histological findings with clinical features.

Methods

We reviewed the clinical records and pathological slides from 87 consecutive patients who underwent endoscopic sinus surgery for CRS. Demographic and clinical data, preoperative Chronic Sinusitis Survey (CSS) scores, and sinus CT stage were evaluated. Pathological slides were graded by a pathologist to characterize the degree of inflammation and SM, when present. CRS patients with and without SM were compared using student's t-test and χ2 test.

Results

Evaluation of the pathology slides revealed that 18.4% of specimens had SM present, whereas only 2.2% of pathology reports noted this. Histological grading of chronic inflammation showed significantly greater severity in specimens with SM (n = 16) when compared with the cohort without SM (n = 75; 100.0% versus 77.5%, respectively; p = 0.016). There was no difference in preoperative CT stage or the presence of hyperostosis on imaging, CSS scores, duration of CRS symptoms, or other clinical features between those with SM and those without SM (p > 0.05). Immunodeficiency was the only comorbidity more prevalent in the metaplastic group (12.5% versus 0%, respectively; p = 0.003).

Conclusion

SM is present in ∼18% of routine CRS specimens. It has a positive correlation with the severity of inflammation noted histologically in CRS but does not correlate with disease severity or chronicity, clinically.
Combined Image Guidance and Intraoperative Computed Tomography in Facilitating Endoscopic Orientation within and around the Paranasal Sinuses
Authors: Wise Sarah K. , Harvey Richard J. , Goddard John C. , Sheahan Patrick O. , Schlosser Rodney J.
Published: January 2009

Background

The utility of image guidance (image-guided surgery [IGS]) and intraoperative computed tomography (CT) scanning as a tool for less experienced endoscopic surgeons to aid in localization of paranasal sinus and skull base anatomic structures was evaluated.

Methods

Partial endoscopic dissection was performed on cadaver specimens by three fellowship trained rhinologists. Anatomic sites within and around the sinuses were tagged with radio-opaque markers. Otolaryngology residents identified tagged anatomic sites using four successive levels of technology: endoscopy alone (simulating outpatient clinic), endoscopy plus preoperative CT (simulating endoscopic sinus surgery [ESS] without IGS), endoscopy plus IGS registered to preoperative CT (simulating current ESS with IGS), and endoscopy plus IGS registered to real-time intraoperative CT. Responses were graded as follows: consensus rhinologist answer (4 points), close answer without clinically significant difference (3 points), within anatomic region but definite clinical difference (2 points), outside of anatomic region (1 point), no answer (0 points).

Results

Eleven residents participated. Of 20 specific anatomic sites, IGS-intraoperative CT provided the most accurate anatomic identification at 16 sites. For 8 sites, IGS-intraoperative CT had a significantly higher score than endoscopy alone (p < 0.05; eta2 = 0.29-0.67). For 6 sites, IGS-preoperative CT scan had a significantly higher score than endoscopy alone (p < 0.05; eta2 = 0.30-0.67). All participants found that IGS-intraoperative CT scan made them most comfortable in identifying anatomy.

Conclusion

Combined IGS and intraoperative CT scan technology may be an instructional adjunct for less experienced paranasal sinus surgeons for dissection and evaluation of unfamiliar or distorted anatomy.
2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies
Authors: Zhu Jin , Chen Tong , Chen Lili , Lu Weiqiang , Che Peng , Huang Jin , Li Honglin , Li Jian , Jiang Hualiang
Published: January 2009

The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide(1), which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR)-based binding assays. Four compounds – 1, 2b, 2k and 2l –showed moderate FP-2 inhibition activity, with IC50 values of 10.0-39.4 μM, and the inhibitory activityof compound 2k was ~3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity.
Sertoli Cells Enhance Formation of Capillary-Like Structures in Vitro
Authors: Golat Brian T. , Cameron Don F.
Published: January 2009

Sertoli cells isolated from the testis (referred to as extratesticular Sertoli cells) have been shown to facilitate allo- and xenogeneic cell transplantations. It appears likely that the ability of these cells to enhance the success of cell engraftment is due, in part, to the retention of their intratesticular functions of trophic support and immunoprotection. Sertoli cells also are involved in the regulation of angiogenesis in the testis, which may also contribute to enhanced cell engraftment success facilitated by extratesticular Sertoli cells. Because the maintenance of the cell's intratesticular angiogenic function has not yet been evaluated for extratesticular Sertoli cells, this study examined the cell's ability to enhance angiogenesis in vitro. Sertoli cell conditioned media were derived from isolated rat Sertoli cell cultures and used in a rat aortic model of induced angiogenesis, in endothelial and smooth muscle cell monocultures, and in endothelial smooth muscle cocultures. An angiogenic rat cytokine array identified angiogenic factors in the control and conditioned media. Aorta sections incubated with Sertoli cell conditioned media showed a marked increase in the formation of capillary-like structures when compared to controls. Likewise, endothelial cells incubated in conditioned media organized into capillary-like structures not observed when incubated in control media. In coculture, smooth muscle cells were associated with endothelial cell-derived capillary-like structures only when incubated in conditioned media. Cytokine arrays indicated the presence and a qualitative increase of specific angiogenic growth factors in Sertoli cell conditioned media not observed in control media. Results indicate that extratesticular Sertoli cells retain their intratesticular angiogenic function in vitro.
The Fate of Implanted Syngenic Muscle Precursor Cells in Injured Striated Urethral Sphincter of Female Rats
Authors: Biérinx Anne-Sophie , Sebille Alain
Published: January 2009

We studied the outcome of syngenic skeletal muscle precursor cells (MPCs) implanted in the striated urethral sphincter of the female rat. These cells were injected at the site of a longitudinal sphincterotomy performed 21 days before implantation. MPCs were isolated from the striated hindlimb muscles of syngenic adult rats and were infected with a retrovirus carrying the gene for either the green fluorescent protein (GFP) or the β-galactosidase enzyme (β-gal). MPCs (2 × 105) were injected longitudinally at the site of the lesion in 48 animals using a 10-μl Hamilton syringe. Then the whole urethras were excised from 2 h up to 90 days for cross section immunocytochemistry analysis. All the urethras exhibited connective tissue in place of the injury of the striated fibers. Two hours after injection a cluster of small round basophilic cells was observable at the site of injection and some of them expressed GFP or β-gal. A few GFP- and β-gal-positive cells were already detectable 7 days after injection. A large amount of injected cells probably died after injection. Many striated fibers of the urethra became GFP positive from day 7 until day 21, suggesting that few MPCs were allowed to incorporate the divided extremities of the striated fibers from day 7. Unfortunately, we did not observe centronucleated regenerated fibers in this experiment.
Environmental Housing and Duration of Exposure Affect Striatal Graft Morphology in a Rodent Model of Huntington's Disease
Authors: Döbrössy Máté D. , Dunnett Stephen B.
Published: January 2009

Clinical trials of cell replacement therapy in Huntington's disease have shown its safety, feasibility, and potentially long-lasting effects. However, more needs to be known regarding the conditions that stimulate plasticity and compensation achieved by neural grafts to maximize posttransplantation recovery of such neurorehabilitative therapies. The effects of enriched environment (EE), behavioral experience, and transplantation can each separately influence neuronal plasticity and recovery of function after brain damage, and the mechanisms by which these factors interact to modify the survival, integration, or function of grafted tissues are at present unknown. To investigate the effects of variable housing conditions and duration on morphological and cellular changes within embryonic striatal transplants, rats received unilateral excitotoxic lesions of the striatum, followed by E15 whole-ganglionic eminence suspension grafts. The rats were divided into three groups according to housing: full-time EE, 1 h/day exposure to EE, or standard laboratory cages. The experimental design included “early” (7 weeks postgrafting) and “late” (13 weeks postgrafting) survival time points to explore the effects of exposure lengths to the three housing conditions. The morphological and cellular effects on the grafts were analyzed using immunohistochemistry, cell morphology, image analysis, and enzyme-linked immunoassay. Both the duration of the exposure and the housing conditions were seen to influence multiple parameters of grafted cell morphology. The factors acted either independently (e.g., on graft size), complementarily (e.g., on spine density), or had no distinctive effect (e.g., on lesion size) on graft development. Features of embryonic striatal grafts and their trophic milieu were influenced both by the complexity of the environmental conditions and by the length of exposure to them. The data suggest that neurorehabilitation should be a feature of clinical trials of cell transplantation in order to exploit the underlying mechanisms that promote anatomical integration of the grafted cells and maximize transplant-mediated functional recovery.
Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder
Authors: Paisán‐Ruiz Coro , Scopes Geoff , Lee Philip , Houlden Henry
Published: January 2009

The use of genome wide genotyping arrays has the potential to assess entire groups of genetic disorders in one application and has begun to emerge as an aid to diagnosis in clinical practice. Recessive families may suffer from diseases because of homozygosity of recessive alleles; homozygosity tracks can be easily identified by using these high throughput SNPs arrays, allowing the rapid mapping of autozygous segments that may be associated with the disease. According to this, we performed homozygosity mapping using genome wide SNP arrays in a North Indian family with an autosomal recessive disorder of ataxia, epilepsy, cognitive decline and visual problems. In this kindred, a large number of homozygous regions were identified. In silico analysis was also carried out. The COL18A1 gene found in one of the homozygous tracks has genetic defects previously reported with a similar phenotype as our family. Hence, it was the most likely candidate gene and at large the first to be analyzed. A homozygous COL18A1 two base pair deletio segregating with the disease was identified; expanding the spectrum of disease seen in COL18A1 and proving that the genetic lesion underlying recessive disorders can rapidly identify by employing genotyping arrays along with detailed candidate gene analysis. © 2009 Wiley‐Liss, Inc.
P2RX7: A bipolar and unipolar disorder candidate susceptibility gene?
Authors: Green Elaine K. , Grozeva Detelina , Raybould Rachel , Elvidge Gareth , Macgregor Stuart , Craig Ian , Farmer Anne , McGuffin Peter , Forty Liz , Jones Lisa , Jones Ian , O'Donovan Mick C. , Owen Mike J. , Kirov George , Craddock Nick
Published: January 2009

The chromosomal region 12q24 has been previously implicated by linkage studies of both bipolar disorder and unipolar mood disorder and we have reported two pedigrees segregating both bipolar disorder and Darier's disease that show linkage across this region. The gene P2RX7 is located in this chromosomal region and has been recently reported as a susceptibility gene for bipolar disorder and unipolar depression. The non‐synonymous SNP rs2230912 (resulting in amino‐acid polymorphism Q460R) showed the strongest association and has been postulated to be pathogenically relevant. We have investigated this gene in a large UK case‐control sample (bipolar I disorder N = 687, unipolar recurrent major depression N = 1,036, controls N = 1,204). Neither rs2230912 nor any of 8 other SNPs genotyped across P2RX7 was found to be associated with mood disorder in general, nor specifically with bipolar or unipolar disorder. Further, sequencing of our two chromosome 12‐linked bipolar‐Darier families showed no evidence of rare variants at P2RX7 that could explain the linkage. Our data do not provide support for rs2230912 or the other polymorphisms studied within the P2RX7 locus, being involved in susceptibility to mood disorders. © 2009 Wiley‐Liss, Inc.
Pharmacodynamics of glucose regulation by methylprednisolone. I. Adrenalectomized rats
Authors: Jin Jin Y. , Jusko William J.
Published: January 2009

Mechanisms related to the adverse effects of corticosteroids on glucose homeostasis were studied. Five groups of adrenalectomized (ADX) rats were given methylprednisolone (MPL) intravenously at 10 and 50 mg/kg, or a continuous 7 day infusion at rates of 0, 0.1, 0.3 mg/kg/h via subcutaneously implanted Alzet mini‐pumps. Plasma concentrations of MPL, glucose and insulin were determined at various time points up to 72 h after injection or 336 h after infusion. The pharmacokinetics of MPL was captured with a two‐compartment model. The Adapt II software was used in modeling. Injection of MPL caused a temporary glucose increase over 6 h by stimulating gluconeogenesis. The glucose changes stimulated pancreatic β‐cell secretion yielding a later insulin peak at around 10 h. In turn, insulin can stimulate glucose disposition. However, long‐term MPL treatment caused continuous hyperglycemia during and after infusion. Insulin was increased during infusion, and immediately returned to baseline after the infusion was terminated, despite the almost doubled glucose concentration. A disease progression model incorporating the reduced endogenous glucose disposition was included to capture glucose homeostasis under different treatments. The results exemplify the importance of the steroid dosing regimen in mediating pharmacological and adverse metabolic effects. This mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model quantitatively describes the induction of hyperglycemia and provides additional insights into metabolic disorders such as diabetes. Copyright © 2009 John Wiley & Sons, Ltd.
The dynamics of surface acoustic wave‐driven scaffold cell seeding
Authors: Bok Melanie , Li Haiyan , Yeo Leslie Y. , Friend James R.
Published: January 2009

Flow visualization using fluorescent microparticles and cell viability investigations are carried out to examine the mechanisms by which cells are seeded into scaffolds driven by surface acoustic waves. The former consists of observing both the external flow prior to the entry of the suspension into the scaffold and the internal flow within the scaffold pores. The latter involves micro‐CT (computed tomography) scans of the particle distributions within the seeded scaffolds and visual and quantitative methods to examine the morphology and proliferation ability of the irradiated cells. The results of these investigations elucidate the mechanisms by which particles are seeded, and hence provide valuable information that form the basis for optimizing this recently discovered method for rapid, efficient, and uniform scaffold cell seeding. Yeast cells are observed to maintain their size and morphology as well as their proliferation ability over 14 days after they are irradiated. The mammalian primary osteoblast cells tested also show little difference in their viability when exposed to the surface acoustic wave irradiation compared to a control set. Together, these provide initial feasibility results that demonstrate the surface acoustic wave technology as a viable seeding method without risk of denaturing the cells. Biotechnol. Bioeng. 2009;103: 387–401. © 2009 Wiley Periodicals, Inc.
Rapid strain improvement through optimized evolution in the cytostat
Authors: Gilbert Alan , Sangurdekar Dipen P. , Srienc Friedrich
Published: January 2009

Acetate is present in lignocellulosic hydrolysates at growth inhibiting concentrations. Industrial processes based on such feedstock require strains that are tolerant of this and other inhibitors present. We investigated the effect of acetate on Saccharomyces cerevisiae and show that elevated acetate concentrations result in a decreased specific growth rate, an accumulation of cells in the G1 phase of the cell cycle, and an increased cell size. With the cytostat cultivation technology under previously derived optimal operating conditions, several acetate resistant mutants were enriched and isolated in the shortest possible time. In each case, the isolation time was less than 5 days. The independently isolated mutant strains have increased specific growth rates under conditions of high acetate concentrations, high ethanol concentrations, and high temperature. In the presence of high acetate concentrations, the isolated mutants produce ethanol at higher rates and titers than the parental strain and a commercial ethanol producing strain that has been analyzed for comparison. Whole genome microarray analysis revealed gene amplifications in each mutant. In one case, the LPP1 gene, coding for lipid phosphate phosphatase, was amplified. Two mutants contained amplified ENA1, ENA2, and ENA5 genes, which code for P‐type ATPase sodium pumps. LPP1 was overexpressed on a plasmid, and the growth data at elevated acetate concentrations suggest that LPP1 likely contributes to the phenotype of acetate tolerance. A diploid cross of the two mutants with the amplified ENA genes grew faster than either individual haploid parent strain when 20 g/L acetate was supplemented to the medium, which suggests that these genes contribute to acetate tolerance in a gene dosage dependent manner. Biotechnol. Bioeng. 2009;103: 500–512. © 2009 Wiley Periodicals, Inc.
Analysis of cell locomotion on ligand gradient substrates
Authors: Sarvestani Alireza S. , Jabbari Esmaiel
Published: January 2009

Directional cell motility plays a key role in many biological processes like morphogenesis, inflammation, wound repair, angiogenesis, immune response, and tumor metastasis. Cells respond to the gradient in surface ligand density by directed locomotion towards the direction of higher ligand density. Theoretical models which address the physical basis underlying the regulatory effect of ligand gradient on cell motility are highly desirable. Predictive models not only contribute to a better understanding of biological processes, but they also provide a quantitative interconnection between cell motility and biophysical properties of the extracellular matrix (ECM) for rational design of biomaterials as scaffolds in tissue engineering. In this work, we consider a one‐dimensional (1D) continuum viscoelastic model to predict the cell velocity in response to linearly increasing density of surface ligands on a substrate. The cell is considered as a 1D linear viscoelastic object with position dependent elasticity due to the variation in actin network density. The cell–substrate interaction is characterized by a frictional force, controlled by the density of ligand–receptor pairs. The generation of contractile stresses is described in terms of kinetic equations for the reactions between actins, myosins, and guanine nucleotide regulatory proteins. The model predictions show a reasonable agreement with experimentally measured cell speeds, considering biologically relevant values for the model parameters. The model predicts a biphasic relationship between cell speed and slope of gradient as well as a maximum limiting speed after a finite migration time. For a given slope of ligand gradient, the onset of the limiting speed appears at longer times for substrates with lower ligand gradients. The model can be applied to the design of biomaterials as scaffolds for guided tissue regeneration as it predicts an optimum range for the slope of ligand gradient. Biotechnol. Bioeng. 2009;103: 424–429. © 2009 Wiley Periodicals, Inc.
Quality monitoring in thyroid surgery using the Shewhart control chart
Authors: Duclos A , Touzet S , Soardo P , Colin C , Peix J L , Lifante J C
Published: January 2009

Background

A control chart can help to interpret and reduce sources of variability in patient safety by continuously monitoring indicators. The aim of this study was to monitor the outcome of thyroid surgery using control charts.

Methods

Patients who had thyroid surgery during 2006–2007 were included in the study. Safety was monitored based on postoperative complications of recurrent laryngeal nerve palsy and hypocalcaemia. Indicators were extracted prospectively from the hospital information system and plotted each month on a P-control chart. Performance of the surgical team was also measured retrospectively for 2004–2005 (baseline period) to compare surgical outcomes before and after control chart implementation. Electromyographic monitoring of recurrent laryngeal nerves was not used, nor was calcium or vitamin D given routinely.

Results

The outcomes of 1114 thyroid procedures were monitored. Although the proportion of patients with recurrent laryngeal nerve palsy was similar for baseline and monitored periods (6·4 and 7·2 per cent respectively), there was a 35·3 per cent decrease in hypocalcaemia after implementation of control charts (P < 0·001). Complications almost doubled during a period when one surgeon was away and operating room renovations took place.

Conclusion

Outcome monitoring in thyroid surgery using control charts is useful for identifying potential issues in patient safety.
Treatment of liver metastases from neuroendocrine tumours in relation to the extent of hepatic disease
Authors: Frilling A , Li J , Malamutmann E , Schmid K-W , Bockisch A , Broelsch C E
Published: January 2009

Background

Hepatic surgery is presumed to improve survival of patients with liver metastases (LM) from neuroendocrine tumours (NET). This study identified LM-specific variables that could be used as additional selection criteria for aggressive treatment.

Methods

A novel classification of LM from NET was established based on their localization and presentation.

Results

From 1992 to 2006, 119 patients underwent staging and treatment of LM. Three growth types of LM were identified radiologically: single metastasis (type I), isolated metastatic bulk accompanied by smaller deposits (type II) and disseminated metastatic spread (type III). The three groups differed significantly in terms of chronological presentation of LM, hormonal symptoms, Ki-67 index, 5-hydroxyindoleacetic acid and chromogranin A levels, lymph node involvement, presence of bone metastases and treatment options. The 3-, 5- and 10-year disease-specific survival rates for the entire cohort were 76·4, 63·9 and 46·5 per cent respectively. There were significant differences in survival between the three groups: 5- and 10-year rates were both 100 per cent for type I, 84 and 75 per cent respectively for type II, and 51 and 29 per cent for type III.

Conclusion

The localization and biological features of LM from NET defines therapeutic management and is predictive of outcome.
Oxidant‐Free Dehydrogenation of Alcohols Heterogeneously Catalyzed by Cooperation of Silver Clusters and Acid–Base Sites on Alumina
Authors: Shimizu Ken‐ichi , Sugino Kenji , Sawabe Kyoichi , Satsuma Atsushi
Published: January 2009

Trifunctional green catalysis: In‐depth characterization shows that oxidant‐free selective oxidation of alcohols by silver nanoparticles on γ‐Al2O3, as a new heterogeneous catalyst, proceeds through cooperation of silver, acid, and base sites (see figure).

magnified image

A γ‐alumina‐supported silver cluster catalyst—Ag/Al2O3—has been shown to act as an efficient heterogeneous catalyst for oxidant‐free alcohol dehydrogenation to carbonyl compounds at 373 K. The catalyst shows higher activity than conventional heterogeneous catalysts based on platinum group metals (PGMs) and can be recycled. A systematic study on the influence of the particle size and oxidation state of silver species, combined with characterization by Ag K‐edge XAFS (X‐ray absorption fine structure) has established that silver clusters of sizes below 1 nm are responsible for the higher specific rate. The reaction mechanism has been investigated by kinetic studies (Hammett correlation, kinetic isotope effect) and by in situ FTIR (kinetic isotope effect for hydride elimination reaction from surface alkoxide species), and the following mechanism is proposed: 1) reaction between the alcohol and a basic OH group on the alumina to yield alkoxide on alumina and an adsorbed water molecule, 2) CH activation of the alkoxide species by the silver cluster to form a silver hydride species and a carbonyl compound, and 3) H2 desorption promoted by an acid site in the alumina. The proposed mechanism provides fundamental reasons for the higher activities of silver clusters on acid–base bifunctional support (Al2O3) than on basic (MgO and CeO2) and acidic to neutral (SiO2) ones. This example demonstrates that catalysts analogous to those based on of platinum group metals can be designed with use of a less expensive d10 element—silver—through optimization of metal particle size and the acid–base natures of inorganic supports.
Drosophila RSK negatively regulates bouton number at the neuromuscular junction
Authors: Fischer Matthias , Raabe Thomas , Heisenberg Martin , Sendtner Michael
Published: January 2009

Ribosomal S6 kinases (RSKs) are growth factor‐regulated serine‐threonine kinases participating in the RAS‐ERK signaling pathway. RSKs have been implicated in memory formation in mammals and flies. To characterize the function of RSK at the synapse level, we investigated the effect of mutations in the rsk gene on the neuromuscular junction (NMJ) in Drosophila larvae. Immunostaining revealed transgenic expressed RSK in presynaptic regions. In mutants with a full deletion or an N‐terminal partial deletion of rsk, an increased bouton number was found. Restoring the wild‐type rsk function in the null mutant with a genomic rescue construct reverted the synaptic phenotype, and overexpression of the rsk‐cDNA in motoneurons reduced bouton numbers. Based on previous observations that RSK interacts with the Drosophila ERK homologue Rolled, genetic epistasis experiments were performed with loss‐ and gain‐of‐function mutations in Rolled. These experiments provided evidence that RSK mediates its negative effect on bouton formation at the Drosophila NMJ by inhibition of ERK signaling. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 2009