bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of the Acr3 and DctA anti‐porters in arsenite oxidation in Agrobacterium tumefaciens 5A
Authors: Kang Yoon‐Suk , Shi Zunji , Bothner Brian , Wang Gejiao , McDermott Timothy R.
Published: March 2014

Microbial arsenite (AsIII) oxidation forms a critical piece of the arsenic cycle in nature, though our understanding of how and why microorganisms oxidize AsIII remains rudimentary. Our model organism Agrobacterium tumefaciens 5A contains two distinct ars operons (ars1 and ars2) that are similar in their coding region content. The ars1 operon is located nearby the aio operon that is essential for AsIII oxidation. The AsIII/H+ anti‐porters encoded by acr3‐1 and acr3‐2 are required for maximal AsIII and antimonite (SbIII) resistance, but acr3‐1 (negatively regulated by ArsR‐1) appears more active in this regard and also required for AsIII oxidation and expression of aioBA. A malate‐phosphate anti‐porter DctA is regulated by RpoN and AsIII, and is required for normal growth with malate as a sole carbon source. Qualitatively, a ΔdctA mutant was normal for AsIII oxidation and AsIII/SbIII resistance at metalloid concentrations inhibitory to the Δacr3‐1 mutant; however, aioBA induction kinetics was significantly phase‐shift delayed. Acr3 involvement in AsIII/SbIII resistance is reasonably well understood, but the role of Acr3 and DctA anti‐porters in AsIII oxidation and its regulation is unexpected, and suggests that controlled AsIII trafficking across the cytoplasmic membrane is important to a process understood to occur in the periplasm.
Anglican Evangelical Theology, c. 1820–1850: The Case of Edward Bickersteth
Authors: Atkins Gareth
Published: March 2014

The period between the 1780s and the 1830s is widely acknowledged to be a formative one for Anglican Evangelical identity. It was the age of Simeon, Wilberforce, and the Clapham Sect, a time when polite culture became imbued with moral seriousness, and when pious causes came to the centre of the political stage. Yet while it is equally well known that the late 1820s witnessed a significant change in mood and direction, prompted by the passing of an earlier generation of leaders, missionary failure and theological fragmentation, the Anglican Evangelical movement in the second quarter of the nineteenth century has received comparatively little attention. Evangelicals appear frequently in work on the Oxford Movement and Broad Church, but often only as two‐dimensional reactionaries ripe for the protagonists to trample. Edward Bickersteth (1786–1850) is therefore a particularly interesting figure, having risen to prominence in the 1810s and 1820s but in the 1830s and 1840s becoming one of the movement's acknowledged leaders. By showing how the coming man of the earlier period negotiated rockier territory later on, this article seeks to explore not just the changes but also the striking continuities in Evangelical thought. For even if, as Grayson Carter has argued in an excellent recent study, the ecclesiastical changes of the 1820s and 1830s forced Anglican Evangelicals, like others, to reconsider their place in the Church of England, Bickersteth was among the most prominent of the majority who, while unhappy with developments in politics and theology, remained loyal to their Church.
The rise and fall of sterling in Liberia, 1847–1943
Authors: Gardner Leigh A.
Published: March 2014

Recent research on exchange rate regime choice in developing countries has revealed that a range of factors, from weak fiscal institutions to high costs of borrowing in their own currencies, limits the range of options available to these countries. This article uses the case of Liberia to illustrate that new states in Africa during the gold standard era faced similar limitations, even in the absence of formal colonial rule. The rapid depreciation of the Liberian dollar in the nineteenth century led to the adoption of sterling as a medium of exchange and store of value. This initially made it easier for Liberia to service its sterling‐denominated debt and for Liberians to purchase imports from Britain. However, as economic relations with the US deepened during the twentieth century, instability in the pound–dollar exchange rate created serious dislocations in the Liberian economy, ultimately leading to the official adoption of the US dollar in 1943. The story of Liberia illustrates the long‐standing challenges of globalization for peripheral economies and suggests the need for a reassessment of the origins and impact of colonial monetary regimes.
Gestational trophoblastic neoplasia after achieving a nondetectable serum human chorionic gonadotrophin level
Authors: Gueye M , Kane‐Gueye SM , Ndiaye‐Gueye MD , Mbaye M , Diouf AA , Niang MM , Diallo M , Moreau JC
Published: March 2014

Objective

To determine the risk of recurrent trophoblastic disease after normalisation of human chorionic gonadotrophin (hCG) levels in women with hydatidiform mole.

Design

A retrospective review of data from a national gestational trophoblastic disease centre.

Setting

The Trophoblastic Disease Unit, Dakar, Senegal.

Sample

Women with pregnancies affected by hydatidiform mole registered between 2006 and 2012.

Methods

The women were followed up in accordance with the hospital protocol ‘Score de Dakar’. For women who progressed to gestational trophoblastic neoplasia (GTN) the time to onset of GTN, treatment and evolution were evaluated. The rate of evolution to GTN after normalisation of hCG was determined.

Main outcome measures

Rate of occurrence of GTN after chemotherapy for hydatidiform mole.

Results

Five hundred and thirty‐one women were diagnosed to have molar pregnancies. According to the hospital's protocol, 107 (20.2%) of these had chemotherapy and 224 (42.2%) had prophylactic chemotherapy. Five hundred and thirteen women (96.4%; 95% confidence interval [95% CI] 95.05–98.14%) achieved remission. Eighteen women (3.4%; 95% CI 1.86–4.94%) developed GTN (11 before remission and seven after remission). Seven women out of the 18 developed GTN after hCG normalisation (1.3%). Five of these seven were diagnosed beyond the recommended period of follow up. The mean interval to diagnosis of GTN was 18.7 months. These seven women underwent combination chemotherapy: five achieved complete remission whereas two died from GTN.

Conclusions

Cytotoxic therapy for hydatidiform mole does not prevent GTN, it delays its diagnosis and promotes GTN after normalisation of hCG.
Assessing Nurse Anaesthetists' Non‐Technical Skills in the operating room
Authors: LYK‐JENSEN H. T. , JEPSEN R. M. H. G. , SPANAGER L. , DIECKMANN P. , ØSTERGAARD D.
Published: March 2014

Background

Incident reporting and fieldwork in operating rooms have shown that some of the errors that arise in anaesthesia relate to inadequate use of non‐technical skills. To provide a tool for training and feedback on nurse anaesthetists' non‐technical skills, this study aimed to adapt the Anaesthetists' Non‐Technical Skills (ANTS) as a behavioural marker system for the formative assessment of nurse anaesthetists' non‐technical skills in the operating room.

Methods

A qualitative approach with focus group interviews was used to identify the non‐technical skills of nurse anaesthetists in the operating room. The interview data were transcribed verbatim. Directed content analysis was used to code and sort data deductively into the ANTS categories: task management, team working, situation awareness and decision making. The prototype named Nurse Anaesthetists' Non‐Technical Skills (N‐ANTS) was presented and discussed in a group of subject matter experts to ensure face validity.

Results

The N‐ANTS system consists of the same four categories as ANTS and 15 underlying elements. Three to five good and poor behavioural markers for each element were identified. The headings and definitions of the categories and elements were adjusted to encompass the behavioural markers in N‐ANTS. The differences that emerged mainly reflected statements regarding the establishment of role, competence, and task delegation.

Conclusion

A behavioural marker system, N‐ANTS, for nurse anaesthetists was adapted from a behavioural marker system, ANTS, for anaesthesiologists.
National Working Group Meeting on ALK diagnostics in lung cancer
Authors: Cooper Wendy , Fox Stephen , O'Toole Sandra , Morey Adrienne , Frances Glenn , Pavlakis Nick , O'Byrne Kenneth , Dettrick Andrew , Leong Trishe , Rathi Vivek , Spagnolo Dominic , Hemmings Chris , Singh Mahendra , Moffat David , Tsao Ming‐Sound , Wilner Keith , Buller Richard , Pitman Lowenthal Susan , Arifeen Shams , Binko Justin , Alam Mahmood
Published: March 2014

The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non‐small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a Pfizer‐sponsored National Working Group Meeting on ALK Diagnostics in Lung Cancer, held around the 15th World Lung Cancer Conference, in Sydney on October 31, 2013. It is based on the presentations given by the authors at the meeting and the discussion that ensued. The content for this article was discussed and agreed on by the authors.
Clinicopathological characteristics of PIK3CA and HBx mutations in Korean patients with hepatocellular carcinomas
Authors: Kim Dong Choon , Chung Woo Jin , Lee Jae‐Ho , Jang Byung Kuk , Hwang Jae Seok , Kang Koo Jeong , Kwon Sun Young
Published: March 2014

Hepatocellular carcinoma (HCC) is the fourth most common form of cancer in the Korean population, caused primarily by infection with either the Hepatitis B or C virus. Progression of this disease is frequently associated with mutations in either phosphoinositide‐3‐kinase, catalytic, alpha (PIK3CA) or hepatitis B virus X (HBx) gene. Previous studies have examined the frequency of PIK3CA mutations in HCC, although the clinical significance of these mutations has not been studied in a Korean population. In addition, HBx appears to play a key role in modulating a wide range of cellular functions, leading to HCC. In this study, we examined microdissected tumor samples from 50 HCC patients who underwent hepatectomy at Keimyung University Dongsan Medical Center. These patients were screened for mutations in PIK3CA and HBx to identify the clinical outcomes associated with these mutations. Exons 9 and 20 of PIK3CA and the entirety of HBx were screened for mutations by polymerase chain reaction and direct DNA sequencing. PIK3CA mutations were detected in 7 of 50 patients (14%). Among the 42 patients who were seropositive for hepatitis B, 17 (40.5%) had HBx mutations and 4 (9.52%) had mutations in PIK3CA. PIK3CA mutations were strongly correlated with tumor size. Patients harboring HBx mutations exhibited a longer time to recurrence; this difference was statistically significant not only in comparison with the PIK3CA mutation but also compared with those without any mutations. This result suggests a role for PIK3CA and HBx mutations as prognostic markers in HCC.
The importance of sphingolipids and reactive oxygen species in cardiovascular development
Authors: de Faria Poloni Joice , Chapola Henrique , Feltes Bruno César , Bonatto Diego
Published: March 2014

The heart is the first organ in the embryo to form. Its structural and functional complexity is the result of a thorough developmental program, where sphingolipids play an important role in cardiogenesis, heart maturation, angiogenesis, the regulation of vascular tone and vessel permeability. Sphingolipids are necessary for signal transduction and membrane microdomain formation. In addition, recent evidence suggests that sphingolipid metabolism is directly interconnected to the modulation of oxidative stress. However, cardiovascular development is highly sensitive to excessive reactive species production, and disturbances in sphingolipid metabolism can lead to abnormal development and cardiac disease. Therefore, in this review, we address the molecular link between sphingolipids and oxidative stress, connecting these pathways to cardiovascular development and cardiovascular disease.
From parent to ‘peer facilitator’: a qualitative study of a peer‐led parenting programme
Authors: Thomson S. , Michelson D. , Day C.
Published: March 2014

Background

Peer‐led interventions are increasingly common in community health settings. Although peer‐led approaches have proven benefits for service users, relatively little is known about the process and outcomes of participation for peer leaders. This study investigated experiences of parents who had participated as ‘peer facilitators’ in Empowering Parents, Empowering Communities (EPEC), a peer‐led programme designed to improve access to evidence‐based parenting support in socially disadvantaged communities.

Method

A qualitative cross‐sectional design was used. Semi‐structured interviews were conducted with 14 peer facilitators and scrutinized using thematic analysis.

Results

Peer facilitators developed their knowledge and skills through personal experience of receiving parenting support, participation in formal training and supervised practice, access to an intervention manual, and peer modelling. Peer facilitators described positive changes in their own families, confidence and social status. Transformative personal gains reinforced peer facilitators' role commitment and contributed to a cohesive ‘family’ identity among EPEC staff and service users. Peer facilitators' enthusiasm, openness and mutual identification with families were seen as critical to EPEC's effectiveness and sustainability. Peer facilitators also found the training emotionally and intellectually demanding. There were particular difficulties around logistical issues (e.g. finding convenient supervision times), managing psychosocial complexity and child safeguarding.

Conclusions

The successful delivery and sustained implementation of peer‐led interventions requires careful attention to the personal qualities and support of peer leaders. Based on the findings of this study, support should include training, access to intervention manuals, regular and responsive supervision, and logistical/administrative assistance. Further research is required to elaborate and extend these findings to other peer‐led programmes.
Comparison of peptide–major histocompatibility complex tetramers and dextramers for the identification of antigen-specific T cells
Authors: Dolton G , Lissina A , Skowera A , Ladell K , Tungatt K , Jones E , Kronenberg-Versteeg D , Akpovwa H , Pentier J M , Holland C J , Godkin A J , Cole D K , Neller M A , Miles J J , Price D A , Peakman M , Sewell A K
Published: March 2014

Fluorochrome-conjugated peptide–major histocompatibility complex (pMHC) multimers are widely used for flow cytometric visualization of antigen-specific T cells. The most common multimers, streptavidin–biotin-based ‘tetramers’, can be manufactured readily in the laboratory. Unfortunately, there are large differences between the threshold of T cell receptor (TCR) affinity required to capture pMHC tetramers from solution and that which is required for T cell activation. This disparity means that tetramers sometimes fail to stain antigen-specific T cells within a sample, an issue that is particularly problematic when staining tumour-specific, autoimmune or MHC class II-restricted T cells, which often display TCRs of low affinity for pMHC. Here, we compared optimized staining with tetramers and dextramers (dextran-based multimers), with the latter carrying greater numbers of both pMHC and fluorochrome per molecule. Most notably, we find that: (i) dextramers stain more brightly than tetramers; (ii) dextramers outperform tetramers when TCR–pMHC affinity is low; (iii) dextramers outperform tetramers with pMHC class II reagents where there is an absence of co-receptor stabilization; and (iv) dextramer sensitivity is enhanced further by specific protein kinase inhibition. Dextramers are compatible with current state-of-the-art flow cytometry platforms and will probably find particular utility in the fields of autoimmunity and cancer immunology.
A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese diabetic (NOD) mice
Authors: Adlercreutz E H , Weile C , Larsen J , Engkilde K , Agardh D , Buschard K , Antvorskov J C
Published: March 2014

The interplay between diet and immune parameters which could affect type 1 diabetes (T1D) pathogenesis is not sufficiently clarified. Intestinal up-regulation of the activating receptor natural killer group 2D (NKG2D) (CD314) and its ligands is a hallmark of coeliac disease. However, the direct effect of gluten on NKG2D expression is not known. We studied, by fluorescence activated cell sorter (lymphoid tissues) and reverse transcription–quantitative polymerase chain reaction (intestine and pancreatic islets), if a gluten-free diet (GF diet) from 4 weeks of age or a gluten-free diet introduced in breeding pairs (SGF diet), induced changes in NKG2D expression on DX5+(CD49b) natural killer (NK) cells, CD8+T cells and in intestinal and islet levels of NKG2D and ligands in BALB/c and non-obese diabetic (NOD) mice. Gluten-free NOD mice had lower insulitis (P < 0·0001); reduced expression of NKG2D on DX5+NK cells in spleen and auricular lymph nodes (P < 0·05); and on CD8+T cells in pancreas-associated lymph nodes (P = 0·04). Moreover, the level of CD71 on DX5+NK cells and CD8+T cells (P < 0·005) was markedly reduced. GF and SGF mice had reduced expression of NKG2D and DX5 mRNA in intestine (P < 0·05). Differences in intestinal mRNA expression were found in mice at 8, 13 and 20 weeks. Intestinal expression of NKG2D ligands was reduced in SGF mice with lower expression of all ligands. In isolated islets, a SGF diet induced a higher expression of specific NKG2D ligands. Our data show that a gluten-free diet reduces the level of NKG2D and the expression of NKG2D ligands. These immunological changes may contribute to the lower T1D incidence associated with a gluten-free diet.
Ductal epithelial expression of Ro52 correlates with inflammation in salivary glands of patients with primary Sjögren's syndrome
Authors: Aqrawi L A , Kvarnström M , Brokstad K A , Jonsson R , Skarstein K , Wahren-Herlenius M
Published: March 2014

Ro52 is an E3 ubiquitin ligase with a prominent regulatory role in inflammation. The protein is a common target of circulating autoantibodies in rheumatic autoimmune diseases, particularly Sjögren's syndrome (SS). In this study we aimed to investigate the expression of the SS target autoantigen Ro52 in salivary glands of patients with primary Sjögren's syndrome (pSS). Ro52 expression was assessed by immunohistochemical staining of paraffin-embedded and frozen salivary gland biopsies from 28 pSS patients and 19 non-pSS controls from Swedish and Norwegian registries, using anti-human Ro52 monoclonal antibodies. The degree and pattern of staining and inflammation was then evaluated. Furthermore, secreted Ro52 protein was measured in saliva and serum samples from the same individuals through a catch-enzyme-linked immunosorbent assay (ELISA). Ro52 was highly expressed in all the focal infiltrates in pSS patients. Interestingly, a significantly higher degree of Ro52 expression in ductal epithelium was observed in the patients compared to the non-pSS controls (P < 0·03). Moreover, the degree of ductal epithelial expression of Ro52 correlated with the level of inflammation (Spearman's r = 0·48, P < 0·0120). However, no secreted Ro52 protein could be detected in serum and saliva samples of these subjects. Ro52 expression in ductal epithelium coincides with degree of inflammation and is up-regulated in pSS patients. High expression of Ro52 might result in the breakage of tolerance and generation of Ro52 autoantibodies in genetically susceptible individuals. We conclude that the up-regulation of Ro52 in ductal epithelium might be a triggering factor for disease progression in SS.
Influence of Vertical Soft Tissue Thickness on Crestal Bone Changes Around Implants with Platform Switching: A Comparative Clinical Study
Authors: Linkevicius Tomas , Puisys Algirdas , Steigmann Marius , Vindasiute Egle , Linkeviciene Laura
Published: March 2014

Background

Numerous studies have shown the superiority of platform‐switched implants in preserving crestal bone as compared with platform‐matched implants. However, the influence of initial soft tissue thickness on development of crestal bone loss has not been addressed in previous studies; thus, further research is needed.

Purpose

To evaluate crestal bone levels around platform‐switched implants placed in thin and thick mucosal tissue.

Materials and Methods

Eighty patients (38 male and 42 female, mean age 44 ± 3.34 years) received 80 bone‐level implants of 4.1 mm in diameter with platform switching (Institut Straumann AG, Basel, Switzerland). Tissue thickness was measured, and cases were distributed to Group 1, with thin soft tissue (2 mm or less, n = 40), and Group 2, with thick tissue (more than 2 mm, n = 40). Implants were placed with a one‐stage approach and restored with screw‐retained restorations. Radiographic examination was performed after implant placement, 2 months after healing, after restoration, and at 1‐year follow‐up post‐reconstruction. Crestal bone loss was calculated. The Mann‐Whitney U‐test was applied, and significance was set to p ≤ .05.

Results

Implants in Group 1 (thin tissue) showed 0.79 mm of bone loss after 2 months. After 1‐year follow‐up, bone loss was 1.17 mm. Implants in Group 2 (thick tissue) showed bone loss of 0.17 mm after 2 months of implant placement and 0.21 mm after 1‐year follow‐up. The differences between groups were significant (p < .001) at both time points.

Conclusions

It can be concluded that platform switching does not prevent crestal bone loss if, at the time of implant placement, mucosal tissue is thin. In thick soft tissue, use of platform‐switched implants maintained crestal bone level with minimal remodeling.
Identifying conservation units after large‐scale land clearing: a spatio‐temporal molecular survey of endangered white‐tailed black cockatoos (Calyptorhynchus spp.)
Authors: White Nicole E. , Bunce Michael , Mawson Peter R. , Dawson Rick , Saunders Denis A. , Allentoft Morten E.
Published: March 2014

Aim

We examined how the threatened and endemic white‐tailed black cockatoos of Western Australia have responded genetically to recent and comprehensive habitat loss with the ultimate aim of identifying units for conservation. We assessed the population structure, connectivity and genetic diversity at spatial and temporal scales for Calyptorhynchus baudinii and C. latirostris, which have undergone dramatic population declines. Genetic comparisons of pre‐ and post‐population decline were carried out by including historical samples dating back to 1920. We examined samples collected from across 700 km of their distribution and sampled approximately 1% of the current population census size to produce significant insights into the population genetics of white‐tailed black cockatoos and generate genetic information crucial for conservation management.

Location

Southwest corner of Western Australia.

Methods

Six hundred and eighty‐four cockatoo samples were collected from 1920 to 2010 and profiled with 19 microsatellites to identify spatial population structure and loss of genetic diversity.

Results

The temporal and spatial microsatellite data illustrated that the geographically defined genetic structuring in white‐tailed black cockatoos is likely to represent a recent phenomenon. We identified: (1) spatial population substructure east and west of extensively cleared habitat (>95,800 km2), but the historical samples clustered with the current western population, regardless of origin, (2) a regional loss of allelic diversity over 3–4 generations for the current eastern population, (3) a lack of a genetic signal of the recent population decline, but perhaps a mid‐Holocene population collapse and lastly, (4) limited genetic differentiation between the two currently recognized white‐tailed black‐cockatoo species suggests a review of taxonomy and/or management units should be undertaken.

Main conclusion

Based on extensive spatio‐temporal sampling, we have demonstrated that recent anthropogenic habitat modifications have affected the genetic structure of a long‐lived and highly mobile species. Our results have identified areas of high conservation value and the importance of maintaining native vegetation migration corridors.
Antifungal properties of terpenoids in Picea abies against Heterobasidion parviporum
Authors: Kusumoto N. , Zhao T. , Swedjemark G. , Ashitani T. , Takahashi K. , Borg‐Karlson A.‐K.
Published: March 2014

The antifungal properties of 14 major oleoresin‐constitutive terpenoids of Norway spruce (Picea abies) against Heterobasidion parviporum were evaluated in vitro at three gradient concentrations, 0.1, 0.2 and 0.4 μmol/cm2, on potato dextrose agar medium. Eight monoterpene hydrocarbons (+)‐ and (−)‐α‐pinene, (−)‐β‐pinene, (+)‐3‐carene, myrcene, (+)‐ and (−)‐limonene, terpinolene; four oxygenated monoterpenes α‐terpineol, terpinen‐4‐ol, 1,8‐cineole, bornyl acetate; and two resin acids abietic acid and dehydroabietic acid were selected. Abietic and dehydroabietic acids showed the highest antifungal activities at all concentrations. Among oxygenated monoterpenes, bornyl acetate and α‐terpineol showed antifungal activity at the highest concentration. Among monoterpene hydrocarbons, (+)‐α‐pinene showed similar activity to terpinen‐4‐ol and 1,8‐cineole at the highest concentration; however, it was lower than α‐terpineol and bornyl acetate. Other monoterpene hydrocarbons inhibited mycelial growth by <10%. Re‐extraction of medium surfaces after the test period revealed that most α‐terpineol and terpinen‐4‐ol remained unchanged on the surface but monoterpene hydrocarbons completely disappeared. However, notable fungal transformed products were observed on surfaces applied with 1,8‐cineole and bornyl acetate. Thus, mycelial growth inhibition of monoterpenoids might be caused by complex functions such as biodegradation and/or detoxification by interaction between mycelium and compound. These results provide a basis for future studies considering the role of chemodiversity in the comprehensive chemical defence of P. abies.
Resistance and tolerance in juvenile interior Douglas‐fir trees Pseudotsuga menziesii var. glauca artificially inoculated with Armillaria ostoyae
Authors: Cruickshank M. G. , Jaquish B.
Published: March 2014

Plants utilize two general strategies to cope with pathogen attack. They either limit or resist the pathogen (termed ‘resistance’) or they cope with the disease by surviving and growing (termed ‘tolerance’). Both strategies tend to increase plant fitness; however, there are possible costs, trade‐offs and interactions associated with each strategy. This study focused on five half‐sib interior Douglas‐fir families [Pseudotsuga menziesii var. glauca (Beissn.) Franco] that were putatively classified as either resistant or susceptible to Armillaria ostoyae in a previous greenhouse study of seedling families challenged with A. ostoyae. We compared their survival rates in the greenhouse study with results of juvenile trees from the same five families that were artificially inoculated in field conditions. Both resistance and tolerance appeared to be operating in the field test trees, and a possible trade‐off between resistance and tolerance was detected. Significant differences were detected among the five families for stem radial growth following infection at the tree root collar. Compared with the putatively susceptible families, resistant families had smaller lesions and lower proportional root collar girdling. Tolerant families generally had larger lesions but demonstrated better growth when diseased than resistant families. One tolerant family that was a good survivor in the greenhouse survival study presented vertically shaped lesions that were large in area but had greatly reduced proportional root collar girdling. While a second family showed tolerant traits in the field study, its poor survival in the greenhouse study agreed with the large horizontally spreading lesions associated with high root collar girdling in the field study trees. Survival rankings of the five families in the greenhouse study mostly agreed with results from the field study based on the proportion of collar girdling among families. These host responses are discussed with respect to stability, quantity and quality of stands and products.
Novel nanosome delivery system combined with siRNA targeting the antimicrobial gene DFB4: a new approach for psoriasis management?
Authors: Keren Aviad , David Michael , Gilhar Amos
Published: March 2014

In a recently published issue of the journal, Bracke et al. demonstrate an impressive improvement in psoriasiform features in allogeneic human skin grafts transplanted onto immune‐deficient mice. This improvement was achieved using a novel nanosome (SECosome) as a vehicle for delivering topically applied siRNA to human epidermis. Targeting the gene DFB4 with this delivery system, they prevented translation of the antimicrobial peptide, human β defensin‐2(hBD2), thus normalizing the psoriasiform epidermal phenotype of siRNA/SECosome‐treated human skin grafts. This study encourages the exploration of topical gene silencing strategies in dermatology and refocuses our attention on both, the role of hBD2 in psoriasis pathogenesis and the thorny question which animal model reflects human psoriasis most faithfully.
A transgenic zebrafish model for monitoring glucocorticoid receptor activity
Authors: Krug R. G. , Poshusta T. L. , Skuster K. J. , Berg M. R. , Gardner S. L. , Clark K. J.
Published: March 2014

Gene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socioeconomically crippling neuropsychiatric disorders, and accordingly there is a need to developin vivomodels to help understand disease progression and management. Therefore, we developed the transgenicSR4Gzebrafish reporter line with six glucocorticoid response elements used to promote expression of a short half‐life green fluorescent protein following glucocorticoid receptor activation. Herein, we document the ability of this reporter line to respond to both chronic and acute exogenous glucocorticoid treatment. The green fluorescent protein expression in response to transgene activation was high in a variety of tissues including the brain, and provided single‐cell resolution in the effected regions. The specificity of these responses is demonstrated using the partial agonist mifepristone and mutation of the glucocorticoid receptor. Importantly, the reporter line also modeled the temporal dynamics of endogenous stress response signaling, including the increased production of the glucocorticoid cortisol following hyperosmotic stress and the fluctuations of basal cortisol concentrations with the circadian rhythm. Taken together, these results characterize our newly developed reporter line for elucidating environmental or genetic modifiers of stress response signaling, which may provide insights to the neuronal mechanisms underlying neuropsychiatric disorders such as major depressive disorder.
Robbins and Advanced Further Education
Authors: Parry Gareth
Published: March 2014

In appraising existing patterns and assessing future needs, the Robbins inquiry broke new ground in treating British higher education as a system. In so doing, it went beyond its terms of reference to consider the situation of part‐time higher education. This brought into view the scale, scope and character of provision and participation in the further education sector of higher education. While the need to focus its thinking and recommendations on full‐time courses was never in doubt, the inquiry insisted that central policy decisions take account of all sectors of higher education and that sources of evidence be comprehensive in range and reach.
Student Numbers and Funding: Does Robbins Add Up?
Authors: Callender Claire
Published: March 2014

This article explores how the Robbins Report's recommendations for a massive expansion in higher education alongside a comprehensive system of student financial support, both financed by the public purse, came about and were translated into policy. It argues that these policies, including the Robbins principle, the desire for expanding educational opportunities plus the Reports' emphasis upon the public and social benefits of higher education, can only be understood within the context of the Welfare State and the values and ideas enshrined in its post‐war development. In addition, the article examines some of the Robbins Reports' projections about the number of student places demanded and compares these with the actual number of students enrolled, highlighting the changes in the composition of the student body overtime. It concludes by exploring issues concerning student funding and highlights the shifts in thinking about the role of higher education, who benefits and so who pays; changes associated with the end of the post‐war consensus about the Welfare State.
Remembering Robbins: Context and Process
Authors: Shattock Michael
Published: March 2014

The Robbins Report was the most deeply researched and most highly regarded report ever written on British higher education. By common consent at the time it marked a watershed in the development of higher education in Britain and took its place as one of the most influential contributions to the growth of British society since Beveridge. However, some of its most important recommendations were not accepted and for nearly 30 years the pattern of development that it proposed was in abeyance. This article describes the context of the establishment of the Robbins Committee, considers the processes that it followed in reaching its conclusions and offers an account of why some key recommendations were rejected. The article is intended to provide an historical introduction to the articles in this special issue of the journal.
Timing and intensity of exposure to interferon‐γ critically determines the function of monocyte‐derived dendritic cells
Authors: Kerkar Sid P. , Chinnasamy Dhanalakshmi , Hadi Neima , Melenhorst Jan , Muranski Pawel , Spyridonidis Alexandros , Ito Sawa , Weber Gerrit , Yin Fang , Hensel Nancy , Wang Ena , Marincola Francesco M. , Barrett Austin John
Published: March 2014

A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects of interferon‐γ (IFN‐γ) on the differentiation and maturation of human peripheral blood monocyte‐derived dendritic cells (moDC). Here, we report that following differentiation of monocytes into moDC with granulocyte–macrophage colony‐stimulating factor and interleukin‐4, IFN‐γ induces moDC maturation and up‐regulates the co‐stimulatory markers CD80/CD86/CD95 and MHC Class I, enabling moDC to effectively generate antigen‐specific CD4+ and CD8+ T‐cell responses for multiple viral and tumour antigens. Early exposure of monocytes to high concentrations of IFN‐γ during differentiation promotes the formation of macrophages. However, under low concentrations of IFN‐γ, monocytes continue to differentiate into dendritic cells possessing a unique gene‐expression profile, resulting in impairments in subsequent maturation by IFN‐γ or lipopolysaccharide and an inability to generate effective antigen‐specific CD4+ and CD8+ T‐cell responses. These findings demonstrate that IFN‐γ imparts differential programmes on moDC that shape the antigen‐specific T‐cell responses they induce. Timing and intensity of exposure to IFN‐γ can therefore determine the functional capacity of moDC.
CXCR3 deficiency enhances tumor progression by promoting macrophage M2 polarization in a murine breast cancer model
Authors: Oghumu Steve , Varikuti Sanjay , Terrazas Cesar , Kotov Dmitri , Nasser Mohd W. , Powell Catherine A. , Ganju Ramesh K. , Satoskar Abhay R.
Published: March 2014

Tumor associated macrophages play a vital role in determining the outcome of breast cancer. We investigated the contribution of the chemokine receptor CXCR3 to antitumor immune responses using a cxcr3 deficient mouse orthotopically injected with a PyMT breast cancer cell line. We observed that cxcr3 deficient mice displayed increased IL‐4 production and M2 polarization in the tumors and spleens compared to WT mice injected with PyMT cells. This was accompanied by larger tumor development in cxcr3−/− than in WT mice. Further, tumor‐promoting myeloid derived immune cell populations accumulated in higher proportions in the spleens of cxcr3 deficient mice. Interestingly, cxcr3−/− macrophages displayed a deficiency in up‐regulating inducible nitric oxide synthase after stimulation by either IFN‐γ or PyMT supernatants. Stimulation of bone marrow derived macrophages by PyMT supernatants also resulted in greater induction of arginase‐1 in cxcr3−/− than WT mice. Further, cxcr3−/− T cells activated with CD3/CD28 in vitro produced greater amounts of IL‐4 and IL‐10 than T cells from WT mice. Our data suggests that a greater predisposition of cxcr3 deficient macrophages towards M2 polarization contributes to an enhanced tumor promoting environment in cxcr3 deficient mice. Although CXCR3 is known to be expressed on some macrophages, this is the first report that demonstrates a role for CXCR3 in macrophage polarization and subsequent breast tumor outcomes. Targeting CXCR3 could be a potential therapeutic approach in the management of breast cancer tumors.
Copulation without seminal expulsion: the consequence of sexual satiation and the Coolidge effect
Authors: Lucio R. A. , Rodríguez‐Piedracruz V. , Tlachi‐López J. L. , García‐Lorenzana M. , Fernández‐Guasti A.
Published: March 2014

The studies of sexual satiety in male rats under the Coolidge effect indicate that males reassume copulation until ejaculation. Recently, it was demonstrated that sexually satiated males preserve the motor patterns of intromission and ejaculation, also penile erection, but not seminal expulsion. The first aim was to investigate if penile erections displayed by sexually satiated males dislodge the seminal plugs from the vagina and its effect on sperm transcervical transport. The second aim was to determine the recovery time of seminal expulsion after sexual satiety and its optimal ability to induce pregnancy. Results show that during the Coolidge effect males were able to dislodge the seminal plugs deposited by others (experiment 1A) disturbing the sperm transport (experiment 1B) then interfering with pregnancy (experiment 1C). After satiation, the ejaculate parameters recover slowly: it starts after 10 days with the seminal plug formation, and continues with an increase in sperm count in the uterus 15 days post‐satiety (experiment 2). Sexually satiated males impregnated only 28% of the females during 15 days of cohabitation, whereas, satiated males that rested for 15 days impregnated 89% of the females (experiment 3). We concluded that males with successive ejaculations remain potential rivals, because they may disrupt the sperm transport of other males. The ejaculate features recovery after sexual satiety is gradual, begins with the secretions of the sex accessory glands and is followed by the sperm count. Full fertility recovery is reached after 15 days of sexual abstinence when males are able to impregnate most females.
TheCFPBand Payday Lending: New Agency/Old Problem
Authors: KIRSCH LARRY , MAYER ROBERT N. , SILBER NORMAN I.
Published: March 2014

The Dodd‐Frank Act of 2010 brings nonbank payday lenders under federal regulation for the first time. The question of precisely how to regulate the payday loan industry creates a number of difficult challenges for the newly created Consumer Financial Protection Bureau (CFPB). Whereas most consumer advocates would prefer to ban or strictly limit high cost payday lending activity and address unfair/abusive lending practices, theCFPBmust also be attentive to the impact of regulation on credit access for low‐wage, credit‐constrained payday borrowers. This article highlights the policy, legal, and institutional issues raised during theCFPB's decision‐making process. TheCFPBhas the opportunity to dramatically shift the longstanding consumer protection paradigm in favor ofreal‐worldprotection of vulnerable borrowers and, thereby, to realize the hopes of the activists who helped to bring the Bureau into existence.
Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV‐1 co‐infected patients
Authors: Nevot M. , Boesecke C. , Parera M. , Andrés C. , Franco S. , Revollo B. , Ingiliz P. , Tural C. , Clotet B. , Rockstroh J. K. , Martinez M. A. ,   the NEAT study group
Published: March 2014

The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV‐1)‐positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV‐1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV‐coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV‐coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous‐nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV‐1‐infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV‐coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV‐1‐positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment.
Okun's Law—a Meta‐analysis
Authors: Perman Roger , Stephan Gaetan , Tavéra Christophe
Published: March 2014

This paper seeks to identify whether there is a representative empirical Okun's law coefficient (OLC) and to measure its size. We carry out a meta‐regression analysis on a sample of 269 estimates of the OLC to uncover reasons for differences in empirical results and to estimate the ‘true’ OLC. On statistical (and other) grounds, we find it appropriate to investigate two separate subsamples, using respectively (some measure of) unemployment or output as dependent variable. Our results can be summarized as follows. First, there is evidence of type II publication bias in both subsamples, but a type I bias is present only among the papers using some measure of unemployment as the dependent variable. Second, after correction for publication bias, authentic and statistically significant OLC effects are present in both subsamples. Third, bias‐corrected estimated true OLCs are significantly lower (in absolute value) with models using some measure of unemployment as the dependent variable. Using a bivariate MRA approach, the estimated true effects are −0.25 for the unemployment subsample and −0.61 for the output subsample; with a multivariate MRA methodology, the estimated true effects are −0.40 and −1.02 for the unemployment and the output subsamples respectively.
Cytotaxonomy of Dubyaea glaucescens (Compositae–Cichorieae)
Authors: Liu Ying , Yang Qin‐Er
Published: March 2014

Recent molecular phylogenetic analyses indicate that Dubyaea glaucescens (Compositae–Cichorieae) should be transferred to the genus Faberia as F. glaucescens. Here, we present cytological evidence for this transfer. Dubyaea glaucescens comprises two ploidy levels, 2n = 34 (diploid) and 2n = 51 (triploid), making the basic chromosome number x = 17. The chromosomes vary in length from 5.82 μm to 2.11 μm, and the karyotypes are 2n = 20m + 14sm (3sat) for the diploid cytotype and 2n = 30m + 21sm (3sat) for the triploid cytotype. Karyological characters of D. glaucescens, including chromosome number, size, morphology, and karyotype asymmetry, all agree remarkably with those reported previously in Faberia, but are distinct from those in other species of Dubyaea. The transfer of D. glaucescens to Faberia is thus strongly corroborated.
From Hume's Dictum Via Submergence to Composition as Identity or Mereological Nihilism
Authors: Bohn Einar Duenger
Published: March 2014

I show that a particular version of Hume's Dictum together with the falsity of Composition as Identity entails an incoherency, so either that version of Hume's Dictum is false or Composition as Identity is true. I conditionally defend the particular version of Hume's Dictum in play, and hence conditionally conclude that Composition as Identity is true. I end by suggesting an alternative way out for a persistent foe of Composition as Identity, namely mereological nihilism.
Testing the temporal stability of individual differences in the acquisition and generalization of fear
Authors: Torrents‐Rodas David , Fullana Miquel A. , Bonillo Albert , Andión Oscar , Molinuevo Beatriz , Caseras Xavier , Torrubia Rafael
Published: March 2014

We studied the temporal stability of individual differences in the acquisition and generalization of fear. Seventy‐one participants were tested in two almost identical fear‐acquisition and fear‐generalization sessions (separated by 8 months). Acquisition and generalization were measured by the fear‐potentiated startle, the skin conductance response, and online expectancies of the unconditioned stimulus. To control for the effects of previous experience, different stimuli were used for half of the participants in Session 2. Acquisition and generalization did not differ across sessions or as a function of the stimuli used in Session 2, and a significant proportion of individual differences in these processes was stable over time (generalizability coefficients ranged from 0.17 to 0.38). When the same stimuli were used, acquisition measures showed compromised stability. The results are discussed in terms of their theoretical and applied implications.
Altered frontal EEG asymmetry in obsessive‐compulsive disorder
Authors: Ischebeck Moritz , Endrass Tanja , Simon Daniela , Kathmann Norbert
Published: March 2014

Hemispheric topography of alpha band power in the electroencephalogram has been linked to approach/avoidance motivation and may index the risk for anxiety disorders and depression. We quantified lower alpha band power (8–10 Hz) in 20 patients with obsessive‐compulsive disorder (OCD) and 20 matched healthy controls during blocks of rest and presentation of neutral, aversive, and OCD‐related pictures. Compared to the control group, OCD patients showed altered asymmetry, with frontal alpha power in the 8–10 Hz band being more dominant in the left hemisphere across all conditions. This alteration was not observed over parietal areas, and also did not show in the upper alpha, and the theta and beta bands. This change in hemispheric topography of lower alpha band power supports the hypothesis of relatively increased avoidance motivation in OCD. Altered asymmetry appears to be traitlike in OCD, suggesting a link to depressive disorders.