bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparing Injection Pipettes on a PUL-1 Micropipette Puller
Authors: Dean David A. , Gasiorowski Joshua Z.
Published: March 2011

INTRODUCTION

The efficient delivery of exogenous DNA to cells for expression and function studies is an essential technique of modern cell biology, and direct delivery of genetic material by microinjection remains a reliable means of transfection. Needles for microinjection can either be pulled from glass capillaries on a pipette puller or be purchased premade. When pulling needles, variables such as filament design, heat, pull strength (tension), and delay time between heating and pulling must be addressed. The heat setting affects the length and the tip size of the needle; high heat will typically produce longer needles and finer tips. The pull strength will also affect length and tip size, with greater pull strength producing longer tapered needles with finer tips. Finally, shorter delay times between heating and pulling can result in longer tapers and finer needles; if the delay is too short, the glass forms fibers resembling glass wool rather than usable needles. The advantage of pulling needles in the laboratory is that a variety of different needle types can be pulled, depending on the samples and the cells being injected. The PUL-1 micropipette puller is a robust and inexpensive machine that can be found in many laboratories around the world. New machines are no longer being manufactured, although used ones can still be purchased.
Differential Detergent Fractionation of Eukaryotic Cells
Authors: Ramsby Melinda , Makowski Gregory
Published: March 2011

INTRODUCTION

Differential detergent fractionation (DDF) involves the sequential extraction of cells with PIPES buffers containing first digitonin, then Triton, and finally Tween/deoxycholate (DOC). The procedure yields four biochemically and electrophoretically distinct fractions composed of the following: (1) cytosolic proteins and extractable cytoskeletal elements; (2) membrane and organelle proteins; (3) nuclear membrane proteins and extractable nuclear proteins; (4) detergent-resistant cytoskeletal filaments and nuclear matrix proteins. Most of these fractions can be enriched or purified further by subsequent manipulations. The DDF protocol described here represents a modification of a method used for the fractionation of Madin-Darby canine kidney cells, including the addition of a digitonin extraction step, the inclusion of EDTA in the digitonin and Triton buffers, and the elimination of a nuclease digestion step; DNA is instead denatured by shear force in the presence of sodium dodecyl sulfate (SDS).
Microbial Opsins: A Family of Single-Component Tools for Optical Control of Neural Activity
Authors: Yizhar Ofer , Fenno Lief , Zhang Feng , Hegemann Peter , Diesseroth Karl
Published: March 2011

INTRODUCTION

Members of the microbial opsin gene family have emerged recently as crucial tools for “optogenetics,” a new neuroscience technology. “Optogenetics” can be defined as the integration of optics and genetics to control well-defined events (such as action potentials) within specified cells (such as a targeted class of projection neurons) in living tissues (such as the brains of freely behaving mammals). In this article, we focus on the diversity of the microbial opsin genes and the structure–function properties of their corresponding proteins.
Transforming growth factor‐beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer
Authors: Schlingensiepen Karl‐Hermann , Jaschinski Frank , Lang Sven Arke , Moser Christian , Geissler Edward Kenneth , Schlitt Hans Jürgen , Kielmanowicz Marcus , Schneider Anneliese
Published: March 2011

Pancreatic cancer is one of the most aggressive human cancers with a 5‐year survival rate of <5%. Overexpression of transforming growth factor‐beta 2 (TGF‐β2) in pancreatic malignancies is suggested to be a pivotal factor for malignant progression by inducing immunosuppression, metastasis, angiogenesis and proliferation. Trabedersen (AP 12009) is a phosphorothioate antisense oligodeoxynucleotide specific for human TGF‐β2 mRNA and was successfully tested in a randomized, active‐controlled phase IIb clinical study in patients with high‐grade glioma. Here, we report on the antitumor activity of trabedersen in human pancreatic cancer cells and in an orthotopic xenograft mouse model of human metastatic pancreatic cancer. Trabedersen reduced TGF‐β2 secretion in human pancreatic cell lines with an IC50 in the low μM range without transfection reagent, clearly inhibited cell proliferation, and completely blocked migration of pancreatic cancer cells. Additionally, trabedersen reversed TGF‐β2‐mediated immunosuppression of pancreatic cancer cells targeted by lymphokine activated killer (LAK) cells, resulting in considerably increased LAK cell‐mediated cytotoxicity. Moreover, in an orthotopic mouse model of metastatic pancreatic cancer, intraperitoneal (i.p.) treatment with trabedersen significantly reduced tumor growth, lymph node metastasis and angiogenesis. These promising results warrant further clinical development of trabedersen. Cancer Sci 2011; 102: 1193–1200)
A systematic and methodological review of interventions for young people experiencing alcohol‐related harm
Authors: Calabria Bianca , Shakeshaft Anthony P. , Havard Alys
Published: March 2011

Aims  This review identified published studies evaluating interventions delivered outside educational settings, designed for young people with existing alcohol use problems, or who participate in behaviour that places them at high risk of alcohol‐related harm, critiqued their methodology and identified opportunities for new interventions.

Methods  A systematic search of the peer‐reviewed literature interrogated 10 electronic databases using specific search strings, limited to 2005–09. No additional studies were found by a librarian searching other collections and clearing‐houses, or by hand‐searching review paper reference lists. The 1697 articles identified were reviewed against criteria from the Dictionary for the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies.

Results  The methodological quality of existing studies is variable, and needs to be both more rigorous and more consistent. Particular problems include the lack of blinding outcome assessors, a reliance solely on self‐report measures, highly variable consent and follow‐up rates, infrequent use of intention‐to‐treat analyses and the absence of any economic or cost analyses. The range of interventions evaluated is currently limited to individually focused approaches, almost exclusively implemented in the United States.

Conclusions  There is a great need for more intervention trials for young people at high risk of experiencing alcohol‐related harm that are both methodologically rigorous and have a broader community focus, to complement the psychological interventions that currently dominate the relevant literature. Such trials would improve outcomes for high‐risk young people themselves and would improve the evidence base, both in their own right and by facilitating future meta‐analyses.
Does improved access and greater choice of nicotine replacement therapy affect smoking cessation success? Findings from a randomized controlled trial
Authors: Walker Natalie , Howe Colin , Bullen Chris , Grigg Michele , Glover Marewa , McRobbie Hayden , Laugesen Murray , Jiang Joy , Chen Mei‐Hua , Whittaker Robyn , Rodgers Anthony
Published: March 2011

Aims  To determine the effect of offering smokers who want to quit easy access to nicotine replacement therapy (NRT), a period of familiarization and choice of product on smoking abstinence at 6 months.

Design  Single‐blind, randomized controlled trial.

Setting  New Zealand.

Participants  A total of 1410 adult smokers who called the national Quitline for quitting support were randomized to usual Quitline care or a box containing different NRT products (patch, gum, inhaler, sublingual tablet, oral pouch) to try for a week prior to quitting, and then to choose one or two of these products for 8 weeks' use.

Measurements  The primary outcome was 7‐day point prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, NRT choice and serious adverse events at 1 and 3 weeks and 3 and 6 months.

Findings  No differences in 6‐month quit rates (7‐day point prevalence or continuous abstinence) were observed between the groups. However, smokers allocated to the intervention group were more likely to have quit smoking at 3 months [self‐reported point prevalence, relative risk (RR) = 1.17, 95% confidence interval (CI): 1.02, 1.35, P = 0.03], had a longer time to relapse (median 70 days versus 28 days, P < 0.01) and used significantly more NRT. The selection box concept was highly acceptable to users, with the patch and inhaler combination the most popular choice (34%).

Conclusions  In terms of smoking abstinence at 6 months, offering smokers who want to quit free access to a wide range of nicotine replacement therapy, including a 1‐week period of familiarization and choice of up to two products, appears no different to offering reduced cost and choice of nicotine replacement therapy, with no familiarization period.
The risk of coronary thrombosis with cyclo‐oxygenase‐2 inhibitors does not vary with polymorphisms in two regions of the cyclo‐oxygenase‐2 gene
Authors: McGettigan Patricia , Lincz Lisa F. , Attia John , McElduff Patrick , Bissett Linda , Peel Roseanne , Stokes Barrie , Hancock Stephen , Henderson Kim , Seldon Michael , Henry David
Published: March 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The risk of cardiovascular events with non‐steroidal anti‐inflammatory drugs (NSAIDs) varies with individual drugs and with dosage. Little is known about other factors that can modify risk.

• Polymorphisms of the COX‐2 gene conceivably could alter the risk of myocardial infarction and also the risk from NSAIDs.

WHAT THIS STUDY ADDS

• Two common polymorphisms of the COX‐2 gene, rs 20417 (G > C) and rs 5275 (T > C), were not associated with variation in the risk of acute coronary syndrome, and individually did not alter the risk associated with use of NSAIDs.

• Haplotype analysis identified a trend to protection against NSAID‐related cardiovascular risk with the ‘low risk’ haplotype, but the effect was weak and if confirmed, the clinical utility would be limited.

AIMS To investigate whether polymorphisms of the cyclo‐oxygenase‐2 (COX‐2) gene modify the adverse cardiovascular effects of COX‐2 inhibitors.

METHODS A case control study was conducted in the Hunter Region of New South Wales, Australia. Cases (n= 460) were hospitalized with acute coronary syndrome (ACS). Controls (n= 640) were recruited from the electoral rolls. Structured interviews gathered information on variables including recent ingestion of non‐steroidal anti‐inflammatory drugs (NSAIDs). Targeted genotyping of rs 20417(G > C) and rs5275 (T > C) polymorphisms was performed by real‐time polymerase chain reaction using allele‐specific probes

RESULTS Ingestion of any NSAID in the week prior to interview was associated with an elevated risk for ACS: adjusted odds ratio 1.8 (1.2, 2.5). The rs 20417 and rs 5275 polymorphisms were not singly associated with risk for ACS: adjusted odds ratios 1.1 (0.80, 1.5) and 1.2 (0.88, 1.5), respectively. Individually, the polymorphisms did not modify the risk of ACS with the drugs. When analyses were conducted by haplotype, the adjusted odds ratio with celecoxib or rofecoxib in individuals who had one or two copies of the ‘low risk’ haplotype (no GT) was 1.2 (0.29, 5.0), compared with 2.1 (1.1, 4.0) with the ‘high risk’ haplotype (one or two copies of GT).

CONCLUSIONS We found little evidence of a gene/drug interaction. We found a statistically non‐significant trend toward a lower risk of coronary events with NSAIDs in the presence of the ‘low risk’ haplotype. Even if confirmed, the clinical utility of the finding would be limited as this haplotype is carried by a minority of the population.
Irritability: an underappreciated side effect of interferon treatment for chronic hepatitis C?
Authors: Blacklaws Helen , Gardner Anne , Usher Kim
Published: March 2011

Aim and objectives.  The research literature was reviewed with the aim of answering the question ‘is irritability an underappreciated side effect of interferon and ribavirin treatment for hepatitis C’.

Background.  The majority of information regarding interferon treatment identifies depression as the main psychological side effect. However, clinical observation and patient reports suggest that irritability, not depression, is the predominant side effect.

Design.  The literature review included research and discussion papers. Data bases were searched using the keywords interferon and hepatitis C in combination with one of the following: side effects, depression, mood alteration/change, irritability, anger, impulse control, psychiatric side effects or neuropsychiatric side effects.

Results.  The review revealed a gap in the literature regarding interferon‐related irritability. Whereas depression was well researched and described, irritability was afforded little research time. However, where irritability was assessed, it was found to occur to a significant degree. Issues identified were difficulty defining and categorising irritability; lack of irritability‐specific assessment tools and failure of depression rating scales to adequately discern irritable mood; and the confounding effect of physiological side effects on mood alteration.

Relevance to clinical practice.  Underappreciation and underrecognition of irritability have implications for clinical practice. Good research is the foundation for evidence‐based practice; therefore, the possibility exists that, based on current research evidence, patients may not be receiving a standard care that adequately addresses the entirety of the side effect spectrum.

Conclusion.  Irritability is an underappreciated psychological side effect of interferon therapy. Although irritability is recognised as a side effect of interferon, there is considerable discordance between clinical observation, patient reports and research evidence as reported in the literature.
Adult sibling experience, roles, relationships and future concerns – a review of the literature in learning disabilities
Authors: Davys Deborah , Mitchell Duncan , Haigh Carol
Published: March 2011

Aim.  This paper provides a review of the literature related to adult siblings of learning‐disabled people.

Background.  Siblings of learning‐disabled people are often looked upon as next of kin when older parents die; however, there is little research regarding sibling views and wishes.

Design.  A literature review of published peer‐reviewed empirical research was undertaken.

Method.  Electronic databases and citation tracking were used to collate data using key terms such as adult siblings and learning disability. Relevant articles were analysed, compared and contrasted.

Results.  Six key themes emerged suggesting a varied impact of learning disability upon sibling lives in areas that include life choices, relationships, identity and future plans. Some siblings report a positive impact upon life, others state their lives are comparable with other adults who do not have a learning‐disabled sibling and others still report a negative impact. Sibling roles and relationships are varied. Evidence suggests that sibling roles, relationships and experience are affected by life stage. Parents often have a primary care role for the disabled person, whilst siblings perform a more distant role; however, sibling involvement often rises when parents are no longer able to provide previous levels of support.

Conclusion.  Many factors appear to affect the sibling experience and uptake of roles including gender, life stage and circumstances, level of disability, health status and relationships between family members. Siblings are concerned about the future, particularly when parents are no longer able to provide support, and many appear to have expectations of future responsibilities regarding their disabled sibling.

Relevance to practice.  As siblings of people who have a learning disability are often expected by society to provide support, it is important that health and social care practitioners are aware of issues that may impact on this relationship.
Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus)
Authors: CLOTHIER K. A. , LEAVENS T. , GRIFFITH R. W. , WETZLICH S. E. , BAYNES R. E. , RIVIERE J. E. , TELL L. A.
Published: March 2011

Clothier, K. A., Leavens, T., Griffith, R. W., Wetzlich, S. E., Baynes, R. E., Riviere, J. E., Tell, L. A. Pharmacokinetics of tulathromycin after single and multiple subcutaneous injections in domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap.34, 448–454.

Tulathromycin, a novel triamilide in the macrolide class, is labeled for treatment of bacterial pneumonia in cattle and swine. This manuscript evaluates pharmacokinetics of tulathromycin in goats. In two different studies, six juvenile and ten market‐age goats received a single injection of 2.5 mg/kg of tulathromycin subcutaneously; in a third study, 18 juvenile goats were treated with 2.5, 7.5, or 12.5 mg/kg tulathromycin weekly with three subcutaneous injections. Pharmacokinetic parameters estimated from the plasma concentrations from single injections were similar between the two groups of goats and to previously reported parameters in cattle and swine. Mean terminal half‐lives were 59.1 ± 7.6 and 61.2 ± 8.7 h for juvenile and market‐age goats, respectively. In the multi‐dose study, pharmacokinetic parameters estimated from plasma concentrations demonstrated significant differences at P < 0.05 among repeated injections but not among doses. Overall, pharmacokinetic parameters in goats are similar to those reported in cattle and swine, and tulathromycin may prove a useful drug for treating respiratory disease in goats.
Parasite‐driven pathogenesis in Trypanosoma brucei infections
Authors: MORRISON L. J.
Published: March 2011

Trypanosomes are protozoan parasites of medical and veterinary importance. It is well established that different species, subspecies and strains of trypanosome can cause very different disease in the mammalian host, exemplified by the two human‐infective subspecies of Trypanosoma brucei that cause either acute or chronic disease. We are beginning to understand how the host response shapes the course of the disease and how genetic variation in the host can be a factor in disease severity, particularly in the mouse model, but until recently the role of parasite genetic variation that determines differential disease outcome has been a neglected area. This review will discuss the recent advances in this field, covering both our current knowledge of the T. brucei genes involved and the approaches that are leading towards the identification of T. brucei virulence genes. Finally, the potential for using parasite genotype variation to examine the evolutionary context of virulence will be discussed.
Investigation of a Chikungunya‐like illness in Tirunelveli district, Tamil Nadu, India 2009–2010
Authors: Sudeep A. B. , Hundekar S. L. , Jacob P. G. , Balasubramanian R. , Arankalle V. A. , Mishra A. C.
Published: March 2011

Objective  To identify the aetiological agent/s of an outbreak of chikungunya‐like illness with high morbidity and several fatalities in Tamil Nadu, India, 2009–2010.

Methods  Two hundred and seventeen serum samples were collected from the affected areas and screened for chikungunya virus (CHIKV), dengue virus (DENV) and Japanese encephalitis virus (JEV) IgM antibodies using MAC‐ELISA kits. A few selected samples were also tested for Ross River, Sindbis, and Murrey Valley viruses by RT‐PCR and Hantan virus by serology. Twelve acute serum and mosquito samples were processed for virus isolation in C6/36 cells. CHIKV isolate was characterised by RT‐PCR and sequencing.

Results  Diagnostic levels of IgM antibodies were detected in 107 (49.3%) CHIKV samples and 22 (10.1%) DENV samples. IgM antibodies against JEV were not detected (n = 46). Characterisation of the CHIKV isolate at genetic level demonstrated it as ECSA (E1: 226A). Thirty‐six selected samples were also negative for Ross River, Sindbis, Murrey Valley and Hantan viruses.

Conclusion  High prevalence of CHIKV IgM antibody positivity, clinical symptoms, virus isolation and the presence of vector mosquitoes clearly suggest CHIKV as the aetiological agent responsible for the outbreak.
Focusing illusion, adaptation and EQ‐5D health state descriptions: the difference between patients and public
Authors: Peeters Yvette , Vliet Vlieland Thea P. M. , Stiggelbout Anne M.
Published: March 2011

Background  Patients tend to assign higher utilities to health states compared with the general public. Several explanations have been given for this difference including focusing illusion ‐, caused in part by the sparseness of a health state description such as the EQ‐5D ‐, and adaptation.

Objective  We investigated whether patients and the public differ in which dimensions they find important. Furthermore, we compared whether the dimensions named by patients and the public obtained higher rankings of importance compared with the predefined EQ‐5D dimensions. Within each nominated dimension we investigated whether the public used a more negative frame compared with patients. In addition, adaptation was investigated by comparing patients with high levels of adaptation and patients with low levels of adaptation.

Design  Data were collected using semistructured interviews among 124 patients with rheumatoid arthritis and 64 members of the public. Participants indicated which aspects are important to them when they think about their life having rheumatoid arthritis and rated the importance of these aspects and of the EQ‐5D dimensions.

Results  In contrast to patients, the public named more often aspects related to sports and mobility, leisure activities and work and framed these aspects negatively. Compared with self‐rated dimensions, the public ranked the EQ‐5D dimensions as more important whereas patients found both groups of aspects equally important. Patients who showed higher levels of adaptation did not differ significantly from patients with lower levels.

Conclusion  The public is focused on life domains that are negatively influenced by the described health state whereas patients are focused on both the positive and negative aspects of their lives.
Vitamin D status in children and adolescents with kidney transplants
Authors: Brodersen Louise Aarup , Nielsen Pia Rude , Thiesson Helle Charlotte , Marckmann Peter
Published: March 2011

Brodersen LA, Nielsen PR, Thiesson HC, Marckmann P. Vitamin D status in children and adolescents with kidney transplants. Pediatr Transplantation 2011: 15: 384–389. © 2011 John Wiley & Sons A/S.

Abstract:  Hypovitaminosis D is highly prevalent in adult kidney‐transplanted patients. The knowledge of vitamin D status in kidney‐transplanted children and adolescents is sparse. The present study investigated the vitamin D status of a cohort of kidney‐transplanted children and adolescents, and the association between vitamin D status and plasma concentrations of PTH, ionized calcium, and phosphate. The study included 35 patients with a functioning graft. Their mean age was 12.0 yr, and the mean graft age was 2.8 yr. Forty percent of the patients were vitamin D insufficient (P‐25‐hydroxyvitamin D 40–75 nm), and 14% were deficient (P‐25‐hydroxyvitamin D < 40 nm). S‐25‐hydroxyvitamin D was inversely associated with PTH (p = 0.02) and positively associated with S‐1,25‐dihydroxyvitamin D (p = 0.02). There was no significant association between S‐1,25‐dihydroxyvitamin D and PTH. In conclusion, we found hypovitaminosis D in 54% of the study population despite the fact that samples were collected in spring and summer months. Hypovitaminosis D was associated with adverse effects on PTH and 1,25‐dihydroxyvitamin D. Our data suggest that it is warranted to monitor vitamin D status of kidney‐transplanted children and adolescents and indicate that correction of hypovitaminosis D might have favorable effects on calcium–phosphate metabolism.
Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients
Authors: Alméras C. , Vetromile F. , Garrigue V. , Szwarc I. , Foulongne V. , Mourad G.
Published: March 2011

C. Alméras, F. Vetromile, V. Garrigue, I. Szwarc, V. Foulongne, G. Mourad. Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients. Transpl Infect Dis 2011: 13: 101–108. All rights reserved

Abstract: Background. BK polyomavirus virus (BKV) nephropathy (BKVN) is the most common viral infection that affects renal allografts. Because a specific antiviral therapy is lacking, BKVN may result in graft dysfunction and/or loss. We prospectively analyzed whether monthly nucleic acid testing (NAT) for BKV replication in blood and immediate reduction of immunosuppression (IS) could prevent BKVN.

Methods. NAT was performed at monthly intervals for 6 months and then at 12 months in 119 de novo renal transplant recipients. In viremic patients (presumptive BKVN), a graft biopsy was systematically performed and IS was immediately reduced.

Results. BKV viremia occurred in 13 (10.9%) patients after a median time of 90 days (23–241); 77% of patients were viremic before month 4. After reduction of IS, viral load was undetectable in 11 patients, remained low in 1, and continued to increase in 1 patient who developed definitive BKVN despite reduction of IS, and finally returned to dialysis 6 months after transplantation.

Conclusion. BKV infection is an early complication. Monthly NAT in blood during the first 6 months and immediate reduction of IS in viremic patients almost completely prevent definitive BKVN.
Transgenic expression of polygalacturonase‐inhibiting proteins in Arabidopsis and wheat increases resistance to the flower pathogen Fusarium graminearum
Authors: Ferrari S. , Sella L. , Janni M. , De Lorenzo G. , Favaron F. , D’Ovidio R.
Published: March 2011

Fusarium head blight (FHB), caused by Fusarium graminearum, is one of the most important diseases of wheat worldwide, resulting in yield losses and mycotoxin contamination. The molecular mechanisms regulating Fusarium penetration and infection are poorly understood. Beside mycotoxin production, cell wall degradation may play a role in the development of FHB. Many fungal pathogens secrete polygalacturonases (PGs) during the early stages of infection, and plants have evolved polygalacturonase‐inhibiting proteins (PGIPs) to restrict pectin degradation during fungal infection. To investigate the role of plant PGIPs in restricting the development of FHB symptoms, we first used Arabidopsis thaliana, whose genome encodes two PGIPs (AtPGIP1 and AtPGIP2). Arabidopsis transgenic plants expressing either of these PGIPs under control of the CaMV 35S promoter accumulate inhibitory activity against F. graminearum PG in their inflorescences, and show increased resistance to FHB. Second, transgenic wheat plants expressing the bean PvPGIP2 in their flowers also had a significant reduction of symptoms when infected with F. graminearum. Our data suggest that PGs likely play a role in F. graminearum infection of floral tissues, and that PGIPs incorporated into wheat may be important for increased resistance to FHB.
Pollen limitation and inbreeding depression in an ‘old rare’ bumblebee‐pollinated grassland herb
Authors: Becker T. , Voss N. , Durka W.
Published: March 2011

Habitat fragmentation and reduction of population size have been found to negatively affect plant reproduction in ‘new rare’ species that were formerly common. This has been attributed primarily to effects of increased inbreeding but also to pollen limitation. In contrast, little is known about the reproduction of ‘old rare’ species that are naturally restricted to small and isolated habitats and thus may have developed strategies to cope with long‐term isolation and small population size. Here we study the effects of pollen source and quantity on reproduction of the ‘old rare’ bumblebee‐pollinated herb,Astragalus exscapus. In two populations of this species, we tested for pollen autodeposition, inbreeding depression and outbreeding depression. Caged plants were left unpollinated or were pollinated with pollen from the same plant, from the same population or from a distant population (50 km). Additionally, we tested for pollen limitation by pollen supplementation in four populations of different size and density. In the absence of pollinators, plants did not produce seed whereas self‐pollinated plants did. This indicates a self‐compatible breeding system dependent on insect pollination. Both self‐pollination and, in one of the two populations, cross‐pollination with pollen from plants from the distant population resulted in a lower number of seeds per flower than cross‐pollination with pollen from plants from the resident population, indicating inbreeding and outbreeding depression. Pollen addition enhanced fruit set and number of seeds per flower in three of the four populations, indicating pollen limitation. The degree of pollen limitation was lowest in the smallest but densest population. Our results suggest that, similar to ‘new rare’ plant species, also ‘old rare’ species may be at risk of inbreeding depression and pollen limitation.
The Importance of Staphylococci and Threshold Value of Somatic Cell Count for Diagnosis of Sub‐clinical Mastitis in Pirlak Sheep at Mid‐lactation
Authors: Ozenc E , Seker E , Baki Acar D , Birdane MK , Darbaz I , Dogan N
Published: March 2011

Contents

This study investigated the bacterial agents causing sub‐clinical mastitis and the mean somatic cell counts (SCC) of milk in Pirlak sheep at mid‐lactation. The percentage of infected udder halves was 11.4% (53/464). The most frequently isolated species were coagulase‐negative staphylococci (CNS) (64.2%), followed by Staphylococcus aureus (24.5%) and Escherichia coli (11.3%). Among the CNS, the most common species was Staphylococcus epidermidis (38.2%). The other species isolated from milk samples were Staphylococcus xylosus (17.7%), Staphylococcus chromogenes (14.7%), Staphylococcus simulans (8.8%) and Staphylococcus hyicus (8.8%). The mean SCC for culture positive and negative samples was 1742 × 103 and 161 × 103 cells/ml, respectively. A significant difference (p < 0.05) was determined between with and without microbial growth groups in terms of the SCC values. Threshold limit for SCC was 374 × 103 cells/ml for Pirlak sheep. In conclusion, it was considered that SCC is an important predictor of sub‐clinical mastitis in Pirlak sheep. This is the first study to describe the bacterial agents causing sub‐clinical mastitis and threshold limit for SCC in Pirlak sheep in Turkey.
Comparison of the function of the serotonin transporter in the vasculature of male and female rats
Authors: Linder Aurea Elizabeth , Davis Robert Patrick , Burnett Robert , Watts Stephanie W
Published: March 2011

1. The serotonin transporter (SERT) handles serotonin (5‐hydroxytryptamine (5‐HT)) and is blocked by the antidepressant SERT inhibitors fluoxetine and fluvoxamine. Although the importance of SERT in the central nervous system is clear, SERT also functions in the peripheral vasculature. In the present study, we tested the hypothesis that the vasculature from female rats has increased SERT function compared with male rats because females are more responsive to SERT inhibitors.

2. In addition to in vitro experiments, in vivo experiments were used to evaluate how male and female rats handle chronically elevated levels of 5‐HT. Wild‐type (WT) and SERT‐knockout (SERT‐KO) rats were infused with 5‐HT (25 μg/kg per min) for 7 days by minipump.

3. Using HPLC analysis, we demonstrated that blood vessels (aorta, carotid artery, jugular vein and vena cava) from naïve, non‐infused female rats took up 5‐HT acutely in vitro in a SERT‐dependent manner. In in vitro experiments, SERT affected the contractility of aortas from female rats, as evidenced by an eightfold increase in potency of 5‐HT in fluvoxamine (1 μmol/L)‐incubated WT aortas compared with control. Fluvoxamine did not alter 5‐HT‐induced contraction in aortas from SERT‐KO female rats.

4. Infusion of 5‐HT resulted in an increase in tissue 5‐HT that was reduced to a larger extent in blood vessels from female than male SERT‐KO rats. Aortic contractions to 5‐HT were abolished in aortas from male and female 5‐HT‐infused SERT‐KO rats compared with WT rats.

5. Collectively, these data suggest that SERT function, when challenged with 5‐HT, is modestly more important in the vasculature of the female compared with male rat.
Evaluation of a structured assessment framework to enable adherence to the requirements of Mental Capacity Act 2005
Authors: Ramasubramanian Lakshmiprabha , Ranasinghe Newton , Ellison Joseph
Published: March 2011

Accessible summary

 The Mental Capacity Act is a new law that started in 2007. It says that everyone must be helped as much as possible to make his or her own decisions. But people with learning disabilities may find it difficult to make a particular decision and another person may have to make it for them.

 The new law provides important safeguards to the rights of people who cannot make decisions for themselves and also provides guidance for people working with them to deal with such situations. It is very important to follow the requirements of the Mental Capacity Act, and it is a legal requirement.

 We looked at how we dealt with situations when our patients could not make decisions for themselves and also looked at whether a checklist we made helped us to make decisions according to the new law.

 The results showed that people were not always following the new rules of the Mental Capacity Act before we gave them our new checklist. Using our checklist helped people making decisions for people with learning disabilities in a way which fitted in better with the new Mental Capacity Act.

The Mental Capacity Act 2005 for England and Wales received Royal assent in April 2005 and came into force in 2007 (Department of Constitutional Affairs, 2007). The Mental Capacity Act 2005 provides a statutory framework to empower and protect vulnerable people who are not able to make their own decisions. The adherence to it is a statutory requirement, not just guidance. An audit looked at the quality, thoroughness and completeness of making decisions for people with learning disabilities who lacked capacity in making specific decisions for themselves. We re‐audited the same using a checklist made with the requirements of the Mental Capacity Act in mind. The audit showed that the use of the checklist enabled a structured discussion to take place regarding the decision‐making process and ensured complete documentation. It facilitated full adherence to the Mental Capacity Act and established better standards of clinical practice.
Reflexive particularism and cosmopolitanization: the reconfiguration of the national
Authors: LEVY DANIEL , HEINLEIN MICHAEL , BREUER LARS
Published: March 2011

In this article we examine the cosmopolitanization of national memory cultures as a matter of reflexive particularism, referring to negotiations over ‘the national’ driven by the endogenization of European norms and discourses. Reflexive particularism emerges from a historically specific memory imperative that issues two demands – first, that national polities reckon with the Other, and second, that they engage with, critique and challenge exclusionary or heroic modes of nationalism. Our findings, based on the analysis of official discourse and 60 open group discussions conducted in Austria, Germany and Poland, suggest that reflexive particularism is manifested in an ongoing negotiation between variable modes of national belonging and cosmopolitan orientations toward the supranational or pan‐European. More specifically, reflexive particularism is expressed in co‐evolving articulations of Europeanness and shared European memory practices that include: affirmative and ambivalent perspectives; sceptical narratives about nationhood (for example those that emphasize legacies of perpetratorship); and a disposition to (ex)change perspectives and recognize the claims of Others.
Immigration, trade and ‘ethnic surplus value’: a critique of Indo–Canadian transnational networks
Authors: WALTON‐ROBERTS MARGARET
Published: March 2011

It is often argued that countries hosting large populations of skilled immigrants might benefit from their cultural and economic competencies in the development of international trade networks. Yet, in so doing, the state can be criticized for fetishizing the ethnic immigrant in market terms in order to extract ‘ethnic surplus value’. In this article, I examine these debates empirically in the case of India–Canada immigration and trade using interviews with traders, officials and immigrant entrepreneurs in British Columbia, Canada. Findings suggest that the supposedly positive relationship between trade and immigration is not obvious in the India–Canada case and there is no convincing evidence of the state managing successfully to extract ‘ethnic surplus value’. Rather, what appears most compelling is evidence of what can be termed a discourse of regional disadvantage circulated by immigrant and non‐immigrant business actors alike regarding the nature of India–Canada relations. Interview respondents link this discourse of disadvantage to the regional history of Indian immigration to Canada, which has traditionally comprised Sikhs from rural Punjab, and it functions to essentialize Indian immigrant ethnicity spatially within both the Indian and Canadian contexts. I focus on the theme of the extraction of ‘ethnic surplus value’ and regional disadvantage to reveal the limitations of both arguments about the economic nature of immigrant‐led network development. In both cases, I challenge these ideas with a critical emphasis on the role of immigrant agency and offer a more nuanced and complicated reading of the role of the state. As a result, I offer a detailed reading of how socio‐spatial immigrant networks are formed and operate at the regional scale, and how this complicates more abstract theoretical formulations regarding the trade and immigration nexus.
Margaret F. Washburn (1871–1939): First Woman Ph.D. in Psychology
Authors: Goodman Elizabeth S.
Published: March 2011

Margaret Floy Washburn was one of the first generation of leading psychologists trained in America and became an eminent and influential psychologist during the first third of the 20th century. She was recognized for significant contributions in theory development, experimental work, teaching, and professional service, but this paper focuses on her activities as director of the psychology program at Vassar College and author of the classic text in comparative psychology, The Animal Mind. Although full biographical details are not given, a listing of bibliographic sources is provided so that scholars might more readily obtain access to information omitted from the paper. The discussion also considers Washburn's professional life and personal characteristics and how she might be viewed as a role model.
Resveratrol rescues cAMP‐dependent anionic transport in the cystic fibrosis pancreatic cell line CFPAC1
Authors: Hamdaoui Nabila , Baudoin‐Legros Maryvonne , Kelly Mairead , Aissat Abdel , Moriceau Sandra , Vieu Diane‐Lore , Colas Julien , Fritsch Janine , Edelman Aleksander , Planelles Gabrielle
Published: March 2011

BACKGROUND AND PURPOSE

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP‐dependent chloride channel in the plasma membrane of epithelia whose mutation is the cause of the genetic disease cystic fibrosis (CF). The most frequent CFTR mutation is deletion of Phe508 and this mutant protein (delF508CFTR) does not readily translocate to the plasma membrane and is rapidly degraded within the cell. We hypothesized that treating epithelial cells with resveratrol, a natural polyphenolic, phyto‐ooestrogenic compound from grapes, could modulate both the expression and localization of CFTR.

EXPERIMENTAL APPROACH

Cells endogenously expressing CFTR (MDCK1 and CAPAN1 cells) or delF508CFTR (CFPAC1 and airway epithelial cells, deriving from human bronchial biopsies) were treated with resveratrol for 2 or 18 h. The effect of this treatment on CFTR and delF508CFTR expression and localization was evaluated using RT‐PCR, Western blot and immunocytochemistry. Halide efflux was measured with a fluorescent dye and with halide‐sensitive electrodes. Production of interleukin‐8 by these cells was assayed by ELISA.

KEY RESULTS

Resveratrol treatment increased CFTR expression or maturation in immunoblotting experiments in MDCK1 cells or in CFPAC1 cells. Indirect immunofluorescence experiments showed a shift of delF508CFTR localization towards the (peri)‐membrane area in CFPAC1 cells and in human airway epithelial cells. A cAMP‐dependent increase in membrane permeability to halide was detected in resveratrol‐treated CFPAC1 cells, and was inhibited by a selective inhibitor of CFTR.

CONCLUSION AND IMPLICATIONS

These results show that resveratrol modulated CFTR expression and localization and could rescue cAMP‐dependent chloride transport in delF508CFTR cells.
Hypoxia and hypoxia‐inducible factor in the burn wound
Authors: Xing Dongmei , Liu Lixin , Marti Guy P. , Zhang Xianjie , Reinblatt Maura , Milner Stephen M. , Harmon John W.
Published: March 2011

The importance of hypoxia‐inducible factor (HIF) in promoting angiogenesis and vasculogenesis during wound healing has been demonstrated. It is widely accepted that HIF activity can be promoted by many factors, including hypoxia in the wound or cytokines from inflammatory cells infiltrating the wound. However, there has not been a systematic exploration of the relationship between HIF activity and hypoxia in the burn wound. The location of the hypoxic tissue has not been clearly delineated. The time course of the appearance of hypoxia and the increased activity of HIF and appearance of HIF's downstream transcription products has not been described. The aim of this study was to utilize pimonidazole, a specific tissue hypoxia marker, to characterize the spatial and temporal course of hypoxia in a murine burn model and correlate this with the appearance of HIF‐1α and its important angiogenic and vasculogenic transcription products vascular endothelial growth factor and SDF‐1. Hypoxia was found in the healing margin of burn wounds beginning at 48 hours after burn and peaking at day 3 after burn. On sequential sections of the same tissue block, positive staining of HIF‐1α, SDF‐1, and vascular endothelial growth factor all occurred at the leading margin of the healing area and peaked at day 3, as did hypoxia. Immunohistochemical analysis was used to explore the characteristics of the hypoxic region of the wound. The localization of hypoxia was found to be related to cell growth and migration, but not to proliferation or inflammatory infiltration.
In vivo diffusion tensor imaging and ex vivo histologic characterization of white matter pathology in a post–status epilepticus model of temporal lobe epilepsy
Authors: van Eijsden Pieter , Otte Wim M. , Saskia van der Hel W. , van Nieuwenhuizen Onno , Dijkhuizen Rick M. , de Graaf Robin A. , Braun Kees P. J.
Published: March 2011

Although epilepsy is historically considered a disease of gray matter, recent diffusion tensor imaging (DTI) studies have shown white matter abnormalities in patients with epilepsy. The histopathologic correlate of these findings, and whether they are a cause or consequence of epilepsy, remains unclear. To characterize these changes and their underlying histopathology, DTI was performed in juvenile rats, 4 and 8 weeks after pilocarpine‐induced status epilepticus (SE). In the medial corpus callosum (CC), mean diffusivity and axial diffusivity (MD and λ1) as well as a myelin staining were significantly reduced at 4 weeks. Only the λ1 decrease persisted at 8 weeks. In the fornix fimbriae (FF), λ1 and myelin staining were decreased at both time points, whereas fractional anisotropy (FA) and MD were significantly reduced at 8 weeks only. We conclude that SE induces both transient and chronic white matter changes in the medial CC and FF that are to some degree related to myelin pathology.
Effect of a 1‐Week Clinical Rotation in Palliative Medicine on Medical School Graduates' Knowledge of and Preparedness in Caring for Seriously Ill Patients
Authors: Goldberg Gabrielle R. , Gliatto Peter , Karani Reena
Published: March 2011

OBJECTIVES: To assess the effect of a required 1‐week clinical rotation in palliative medicine during a 12‐week internal medicine–geriatrics clerkship on graduating medical students' knowledge and self‐assessed preparedness in caring for seriously ill patients.

DESIGN: Historical control trial.

SETTING: Mount Sinai School of Medicine (MSSM), New York, New York.

PARTICIPANTS: Students from the MSSM classes of 2007 (MS07) and 2008 (MS08).

INTERVENTION: MS08 was the first class to complete the required clinical rotation in palliative medicine. MS07 served as a historical control, having received only didactics in palliative care but no clinical rotation.

MEASUREMENTS: Both classes were invited to complete an anonymous online survey designed to assess experiences and preparedness in caring for seriously ill patients and a 30‐question multiple choice knowledge examination.

RESULTS: Fifty‐eight (55%) students from MS07 and 59 (51%) students from MS08 completed the survey. Students from MS08 rated their skill level in several areas of pain management and communication more favorably than did students from MS07. Mean scores on the knowledge portion of the survey were not significantly different between the two classes.

CONCLUSION: Graduating medical students who had a 1‐week clinical rotation in palliative medicine had higher self‐assessed skills in pain management and communication than students who received no clinical exposure. A brief clinical experience in palliative care should be considered for integration into the curriculum at all medical schools.
An ACIR Perspective on Intergovernmental Institutional Development
Authors: Stenberg Carl W.
Published: March 2011

This article traces the creation and demise of the U.S. Advisory Commission on Intergovernmental Relations (ACIR) and assesses the prospects for restoring an ACIR‐like capability to the federal system. Recent initiatives by the National Academy of Public Administration, the Big 7 state and local government official associations, and Congress are summarized, and the facilitating and inhibiting factors associated with intergovernmental institutional development are examined. At least three ingredients in the formula that gave birth to the ACIR in 1959 will need to be present more than 50 years later: (1) support from congressional champions, the president, and public interest groups; (2) visibility and urgency of intergovernmental fiscal and management issues and the need for a permanent intergovernmental presence to address them; and (3) “homework and spadework” to enlist potential conservative and liberal interest group and think tank backers.
Reflections of a Member of the U.S. Advisory Commission on Intergovernmental Relations
Authors: Nathan Richard P.
Published: March 2011

There is consensus on the need for a successor to the U.S. Advisory Commission on Intergovernmental Relations in Washington, D.C., but no agreement on how this entity should be organized and funded and what it should do. There are now many players, both organizations and individuals, in the intergovernmental field, and they need to be sorted out. A key distinction is that American federalism is both an idea and an interest, and a new ACIR should focus on the former as a neutral, independent body with informational, convener, educational, and dissemination functions. We should encourage a discussion and debate on what the new ACIR should be and how it should be structured in order to bring federalism and intergovernmental relations back to the table in Washington.