bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallization of lysozyme with (R)-, (S)- and (RS)-2-methyl-2,4-pentanediol
Authors: Stauber Mark , Jakoncic Jean , Berger Jacob , Karp Jerome M. , Axelbaum Ariel , Sastow Dahniel , Buldyrev Sergey V. , Hrnjez Bruce J. , Asherie Neer
Published: February 2015

Chiral control of crystallization has ample precedent in the small-molecule world, but relatively little is known about the role of chirality in protein crystallization. In this study, lysozyme was crystallized in the presence of the chiral additive 2-methyl-2,4-pentanediol (MPD) separately using theRandSenantiomers as well as with a racemicRSmixture. Crystals grown with (R)-MPD had the most order and produced the highest resolution protein structures. This result is consistent with the observation that in the crystals grown with (R)-MPD and (RS)-MPD the crystal contacts are made by (R)-MPD, demonstrating that there is preferential interaction between lysozyme and this enantiomer. These findings suggest that chiral interactions are important in protein crystallization.
The mechanism of substrate-controlled allosteric regulation of SAMHD1 activated by GTP
Authors: Zhu Chun-Feng , Wei Wei , Peng Xin , Dong Yu-Hui , Gong Yong , Yu Xiao-Fang
Published: February 2015

SAMHD1 is the only known eukaryotic deoxynucleoside triphosphate triphosphohydrolase (dNTPase) and is a major regulator of intracellular dNTP pools. It has been reported to be a potent inhibitor of retroviruses such as HIV-1 and endogenous retrotransposons. Previous crystal structures have revealed that SAMHD1 is activated by dGTP-dependent tetramer formation. However, recent data have indicated that the primary activator of SAMHD1 is GTP, not dGTP. Therefore, how its dNTPase activity is regulated needs to be further clarified. Here, five crystal structures of the catalytic core of SAMHD1 in complex with different combinations of GTP and dNTPs are reported, including a GTP-bound dimer and four GTP/dNTP-bound tetramers. The data show that human SAMHD1 contains two unique activator-binding sites in the allosteric pocket. The primary activator GTP binds to one site and the substrate dNTP (dATP, dCTP, dUTP or dTTP) occupies the other. Consequently, both GTP and dNTP are required for tetramer activation of the enzyme. In the absence of substrate binding, SAMHD1 adopts an inactive dimer conformation even when complexed with GTP. Furthermore, SAMHD1 activation is regulated by the concentration of dNTP. Thus, the level of dNTP pools is elegantly regulated by the self-sensing ability of SAMHD1 through a novel activation mechanism.
The structure of the hexameric atrazine chlorohydrolase AtzA
Authors: Peat T. S. , Newman J. , Balotra S. , Lucent D. , Warden A. C. , Scott C.
Published: February 2015

Atrazine chlorohydrolase (AtzA) was discovered and purified in the early 1990s from soil that had been exposed to the widely used herbicide atrazine. It was subsequently found that this enzyme catalyzes the first and necessary step in the breakdown of atrazine by the soil organismPseudomonassp. strain ADP. Although it has taken 20 years, a crystal structure of the full hexameric form of AtzA has now been obtained. AtzA is less well adapted to its physiological role (i.e.atrazine dechlorination) than the alternative metal-dependent atrazine chlorohydrolase (TrzN), with a substrate-binding pocket that is under considerable strain and for which the substrate is a poor fit.
Snapshots of ligand entry, malleable binding and induced helical movement in P-glycoprotein
Authors: Szewczyk Paul , Tao Houchao , McGrath Aaron P. , Villaluz Mark , Rees Steven D. , Lee Sung Chang , Doshi Rupak , Urbatsch Ina L. , Zhang Qinghai , Chang Geoffrey
Published: February 2015

P-glycoprotein (P-gp) is a transporter of great clinical and pharmacological significance. Several structural studies of P-gp and its homologs have provided insights into its transport cycle, but questions remain regarding how P-gp recognizes diverse substrates and how substrate binding is coupled to ATP hydrolysis. Here, four new P-gp co-crystal structures with a series of rationally designed ligands are presented. It is observed that the binding of certain ligands, including an ATP-hydrolysis stimulator, produces a large conformational change in the fourth transmembrane helix, which is positioned to potentially transmit a signal to the nucleotide-binding domains. A new ligand-binding site on the surface of P-gp facing the inner leaflet of the membrane is also described, providing vital insights regarding the entry mechanism of hydrophobic drugs and lipids into P-gp. These results represent significant advances in the understanding of how P-gp and related transporters bind and export a plethora of metabolites, antibiotics and clinically approved and pipeline drugs.
Historical and clinical items of the HCR-20 as predictors of risk within an intellectual disability population
Authors: Chaplin Eddie , Eyeoyibo Mo , Wright Steve , Xenitidis Kiriakos , McCarthy Jane
Published: February 2015

Purpose

– The use of violence risk assessment measures within intellectual disabilities (ID) services is now the norm and a growing target for research. The purpose of this paper is to examine the clinical utility of the historical and clinical factors of the HCR-20 in predicting violence.

Design/methodology/approach

– The study took place within a national low secure service for adults with ID examining all completed admissions over a six-year period, (N=22). Clinical records covering the first three months of admission were examined along with historical reports and incident data recorded at three, six, nine and 12 months admission using the Modified Overt Aggression Scale (MOAS).

Findings

– Significant positive relationship between Historical score and total number of incidents was established. Patients with challenging behaviour less likely to have a previous history of violence, and more likely to be older at first violent incident than patients without challenging behaviour. Incidents involving patients with autism were less severe and those with no additional psychiatric diagnosis were significantly more likely to have substance misuse problems than those with a diagnosis.

Originality/value

– The study found the Historical section was predictive of violent incidents and whilst the study is too small to draw any firm conclusions, the significant positive relationship between the Historical Score and number of incidents for those without additional diagnosis needs to be investigated further as well as the potential positive clinical impact of using the HCR-20 in routine clinical practice.
Intellectual disability, personality disorder and offending: a systematic review
Authors: Rayner Kelly , Wood Harry , Beail Nigel , Nagra Maninder Kaur
Published: February 2015

Purpose

– This review seeks to systematically review studies where personality disorder has been explored as a descriptive or possible predictive factor in offending behaviour in people with an intellectual disability. The papar aims to discuss this issue.

Design/methodology/approach

– A systematic search of several databases was conducted and 15 studies met the inclusion criteria and were included in this review.

Findings

– Methodological limitations and problems in accurate diagnosis within this client group preclude firm conclusions being reached.

Originality/value

– It is concluded that further research should be conducted, with particular attention paid to the conceptualisation and assessment of personality disorder.
Attachment behavior in children with Autistic Spectrum Disorders
Authors: Kahane Lital , El-Tahir Mohamed
Published: February 2015

Purpose

– Significance of attachment relationship to the development and impairments among children with autism has been studied. The purpose of this paper is to analyze the literature for studies completed on the attachment and assess the effect of autism on attachment development. Different moderators of attachment are also reviewed.

Design/methodology/approach

– Systematic reviews were searched for in different databases to establish the necessity and relevance of the current paper. The last systematic review on the topic was published in 2004 so studies done after that year were searched for in electronic databases and experts on the filed were also contacted before choosing the ten studies selected for this review.

Findings

– Attachment is present among children with Autistic Spectrum Disorders (ASD), however not prevalent as in normally developing children. The security and organization of attachment behavior are affected by the severity of the diagnosis of Autism and the co-morbidities associated. Maternal sensitivity and insightfulness support the development of secure attachment in children with ASD while impairments in joint attention and symbolic play proved to be risk factors for insecurity and disorganization of attachment.

Originality/value

– The review contributes to the relatively understudied topic of attachment behavior in autism spectrum disorders focussing on the influence brought to the bonding connection by different influencing factors like: mothers’ sensitivity, insightfulness and attachment style, parenting style and symbolic play levels.
User-visible cryptography in email and web scenarios
Authors: Brooke Phil , Paige Richard
Published: February 2015

Purpose

– This paper aims to classify different types of “user-visible cryptography” and evaluate the value of user-visible cryptographic mechanisms in typical email and web scenarios for non-expert IT users.

Design/methodology/approach

– The authors review the existing literature, and then identify user stories typical to their users of interest. They analyse the risks, mitigations of risks and the limits of those mitigations in the user stories.

Findings

– The scenarios identified suggest that background, opportunistic encryption has value, but more explicit, user-visible cryptographic mechanisms do not provide any further mitigation. Other mechanisms beyond technological mitigations provide the required mitigation for the users.

Research limitations/implications

– Further work should be carried out on the trust issues with trusted third parties, as they are intrinsic to global, automated cryptographic mechanisms. The authors suggest that deployed systems should rely on automation rather than explicit user involvement; further work on how best to involve users effectively remains valuable.

Practical implications

– Deployed systems should rely on automation rather than explicit user dialogues. This follows from recognised aspects of user behaviour, such as ignoring dialogues and unconsciously making a holistic assessment of risk that is mostly mitigated by social factors.

Social implications

– The user populations concerned rely significantly on the existing legal and social infrastructure to mitigate some risks, such as those associated with e-commerce. Guarantees from third parties and the existence of fallback procedures improve user confidence.

Originality/value

– This work uses user stories as a basis for a holistic review of the issues surrounding the use of cryptography. The authors concentrate on a relatively large population (non-expert IT users) carrying out typical tasks (web and email).
Secular and Islamic feminist entrepreneurship in Turkey
Authors: Özkazanç-Pan Banu
Published: February 2015

Purpose

– This paper aims to highlight secular and Islamic feminist approaches to entrepreneurship as potential means to challenge gender inequality in the Turkish context. In Turkey, gender equality remains elusive in a nation where secular and Islamic ideologies compete and produce different solutions to ongoing economic, socio-cultural and political issues. Women’s entrepreneurship has emerged as an important solution toward gender equality and economic development.

Design/methodology/approach

– Using two women’s organizations that exemplify secular and Islamic feminist ideologies, the author examines whether the entrepreneurship activities they promote give way to challenging patriarchal norms, values and practices widespread in Turkish society.

Findings

– Through their distinct practices and engagement with entrepreneurship, both secular and Islamic feminist positions allow for praxis and represent an ethico-political commitment to dismantling neo-liberal development ideologies in the Turkish context that perpetuate gender inequality.

Social implications

– Secular and Islamic feminist practices and entrepreneurship practices have different implications for achieving gender equality including changes in gender norms, economic development policies and women’s empowerment in a Muslim-majority country. In addition, it raises questions around the popular notion of “entrepreneurship as women’s empowerment”.

Originality/value

– This paper is of value to scholars who want to understand secular and Islamic feminisms and their implications for challenging gender inequality. The Turkish context with its traditional and modern societal norms and values provides a rich case study to examine these issues through the exemplars of entrepreneurship. It is also of value to scholars who want to understand structural constraints associated with gender equality beyond individual-level challenges.
The Affordable Care Act: triumphs and tribulations
Authors: Goldberg Ilene
Published: February 2015

Purpose

– This paper aims to discuss key provisions of the Affordable Care Act (ACA) and the obstacles faced by the federal government in achieving its goal. The ACA is designed to provide most Americans with an access to affordable health care.

Design/methodology/approach

– Using data obtained from government sources, case law and current literature, the paper first discusses the history and background of the ACA. It evaluates the law’s current status, the benefits it achieved and the legal, economic, political and social challenges that lie ahead.

Findings

– Although the Supreme Court upheld most of the ACA’s provisions, opponents at the federal and state level are still attempting to overturn or undercut it. The ACA itself is so complicated that it has generated confusion among employers, consumers and even those who are charged with enforcing it. The extent to which the ACA can be successfully implemented is unclear, and adjustments must be made as the federal government struggles to implement key components.

Originality/value

– This paper should be of interest to academics, health-care and legal professionals, and to anyone who needs clarification and analysis of a still-evolving law that is certain to have an impact on most Americans.
Is a public interest test for workplace whistleblowing in society’s interest?
Authors: Lewis David
Published: February 2015

Purpose

– The aim of the paper is to consider the efficacy of requiring a public interest test to be satisfied before protection is afforded to workers who blow the whistle under Part IVA of the Employment Rights Act 1996 (ERA 1996).

Design/methodology/approach

– Not all definitions of whistleblowing require there to be a public interest in the disclosure of information. To illustrate how the expression “public interest” has been used in this context, the common law defence to an action for breach of confidence is outlined. The paper then explains how the concept of “public interest whistleblowing” evolved in other jurisdictions. It also examines the jurisprudence of the European Court of Human Rights to see if it helps us to apply the public interest test. Finally, this test is considered in the context of UK legislation.

Findings

– Several sources of uncertainty are identified. These include the fact that personal and public interest matters may be intertwined and that an organization may encourage the internal reporting of concerns about wrongdoing that do not have a public dimension to further its private interests. One obvious result of uncertainty is that those who are not legally required to report wrongdoing may choose not to do so and society may be denied important information; for example, about serious health and safety risks or financial scandals.

Originality/value

– It is suggested that the public interest test should be removed from Part IVA ERA 1996. However, this test is likely to remain for a while, so nine recommendations about how it should be interpreted are made.
Spatial variation in age structure among colonies of a marine snake: the influence of ectothermy
Authors: Bonnet Xavier , Brischoux François , Pinaud David , Michel Catherine Louise , Clobert Jean , Shine Richard , Fauvel Thomas
Published: February 2015

Several tetrapod lineages that have evolved to exploit marine environments (e.g. seals, seabirds, sea kraits) continue to rely upon land for reproduction and, thus, form dense colonies on suitable islands.

In birds and mammals (endotherms), the offspring cannot survive without their parents. Terrestrial colonies contain all age classes. In reptiles (ectotherms), this constraint is relaxed, because offspring are independent from birth. Hence, each age class has the potential to select sites with characteristics that favour them.

Our studies of sea snakes (sea kraits) in the lagoon of New Caledonia reveal marked spatial heterogeneity in age structure among colonies.

Sea krait colonies exhibit the endothermic ‘seal–seabird’ pattern (mixed‐age classes within populations) only where the lagoon is narrow. Where the lagoon is wide, most snake colonies are comprised primarily of a single age cohort. Nurseries are located near the coast, adult colonies offshore and mixed colonies in‐between.

We suggest that ectothermy allows individuals to utilize habitats that are best suited to their own ecological requirements, a flexibility not available to endothermic marine taxa with obligate parental care.
pH dependency of sclerotial development and pathogenicity revealed by using genetically defined oxalate‐minus mutants of Sclerotinia sclerotiorum
Authors: Xu Liangsheng , Xiang Meichun , White David , Chen Weidong
Published: February 2015

The devastating plant pathogen Sclerotinia sclerotiorum produces copious (up to 50 mM) amounts of oxalic acid, which, for over a quarter century, has been claimed as the pathogenicity determinant based on UV‐induced mutants that concomitantly lost oxalate production and pathogenicity. Such a claim was made without fulfilling the molecular Koch's postulates because the UV mutants are genetically undefined and harbour a developmental defect in sclerotial production. Here, we generated oxalate‐minus mutants of S. sclerotiorum using two independent mutagenesis techniques, and tested the resulting mutants for growth at different pHs and for pathogenicity on four host plants. The oxalate‐minus mutants accumulated fumaric acid, produced functional sclerotia and have reduced ability to acidify the environment. The oxalate‐minus mutants retained pathogenicity on plants, but their virulence varied depending on the pH and buffering capacity of host tissue. Acidifying the host tissue enhanced virulence of the oxalate‐minus mutants, whereas supplementing with oxalate did not. These results suggest that it is low pH, not oxalic acid itself, that establishes the optimum conditions for growth, reproduction, pathogenicity and virulence expression of S. sclerotiorum. Exonerating oxalic acid as the primary pathogenicity determinant will stimulate research into identifying additional candidates as pathogenicity factors towards better understanding and managing Sclerotinia diseases.
Household Asset‐Holding Diversification in Australia
Authors: Mariotti Francesco , Mumford Karen , Pena‐Boquete Yolanda
Published: February 2015

We explore asset‐holding diversification by Australian households; in particular, the household asset diversification participation decision (whether or not to diversify at all) is jointly estimated with the decision of how much to diversify. In so doing, recent literature on the modelling of proportions is combined with the growing body of research concerning household financial decision‐making. Our findings are consistent with the participation of households operating in diverse financial markets being constrained by ineffective information conduits, influencing the decision of whether or not to diversify.
Do altered energy metabolism or spontaneous locomotion ‘mediate’ decelerated senescence?
Authors: Arum Oge , Dawson John Alexander , Smith Daniel Larry , Kopchick John J. , Allison David B. , Bartke Andrzej
Published: February 2015

That one or multiple measures of metabolic rate may be robustly associated with, or possibly even causative of, the progression of aging‐resultant phenotypes such as lifespan is a long‐standing, well‐known mechanistic hypothesis. To broach this hypothesis, we assessed metabolic function and spontaneous locomotion in two genetic and one dietary mouse models for retarded aging, and subjected the data to mediation analyses to determine whether any metabolic or locomotor trait could be identified as a mediator of the effect of any of the interventions on senescence. We do not test the hypothesis of causality (which would require some experiments), but instead test whether the correlation structure of certain variables is consistent with one possible pathway model in which a proposed mediating variable has a causal role. Results for metabolic measures, including oxygen consumption and respiratory quotient, failed to support this hypothesis; similar negative results were obtained for three behavioral motion metrics. Therefore, our mediation analyses did not find support that any of these correlates of decelerated senescence was a substantial mediator of the effect of either of these genetic alterations (with or without caloric restriction) on longevity. Further studies are needed to relate the examined phenotypic characteristics to mechanisms of aging and control of longevity.
Rifampicin reduces advanced glycation end products and activates DAF‐16 to increase lifespan in Caenorhabditis elegans
Authors: Golegaonkar Sandeep , Tabrez Syed S. , Pandit Awadhesh , Sethurathinam Shalini , Jagadeeshaprasad Mashanipalya G. , Bansode Sneha , Sampathkumar Srinivasa‐Gopalan , Kulkarni Mahesh J. , Mukhopadhyay Arnab
Published: February 2015

Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age‐related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age‐onset diseases and extend lifespan. Using LC‐MSE, we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p‐dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p‐quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF‐18 (nematode PTEN) as well as JNK‐1 and activates DAF‐16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF‐16 target genes, those not controlled by the conserved Insulin‐IGF‐1‐like signaling pathway. RIF failed to increase the lifespan of daf‐16 null mutant despite reducing glycation, showing thereby that DAF‐16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF‐16 makes RIF and RSV effective lifespan‐extending interventions.
Long‐lived Snell dwarf mice display increased proteostatic mechanisms that are not dependent on decreased mTORC1 activity
Authors: Drake Joshua C. , Bruns Danielle R. , Peelor Frederick F. , Biela Laurie M. , Miller Richard A. , Miller Benjamin F. , Hamilton Karyn L.
Published: February 2015

Maintaining proteostasis is thought to be a key factor in slowed aging. In several growth‐restricted models of long‐life, we have shown evidence of increased proteostatic mechanisms, suggesting that proteostasis may be a shared characteristic of slowed aging. The Snell dwarf mouse is generated through the mutation of the Pit‐1 locus causing reductions in multiple hormonal growth factors and mTORC1 signaling. Snell dwarfs are one of the longest lived rodent models of slowed aging. We hypothesized that proteostatic mechanisms would be increased in Snell compared to control (Con) as in other models of slowed aging. Using D2O, we simultaneously assessed protein synthesis in multiple subcellular fractions along with DNA synthesis in skeletal muscle, heart, and liver over 2 weeks in both sexes. We also assessed mTORC1‐substrate phosphorylation. Skeletal muscle protein synthesis was decreased in all protein fractions of Snell compared to Con, varied by fraction in heart, and was not different between groups in liver. DNA synthesis was lower in Snell skeletal muscle and heart but not in liver when compared to Con. The new protein to new DNA synthesis ratio was increased threefold in Snell skeletal muscle and heart compared to Con. Snell mTORC1‐substrate phosphorylation was decreased only in heart and liver. No effect of sex was seen in this study. Together with our previous investigations in long‐lived models, we provide evidence further supporting proteostasis as a shared characteristic of slowed aging and show that increased proteostatic mechanisms may not necessarily require a decrease in mTORC1.
Effects of heat on the germination of sclerophyllous forest species in the highlands of Madagascar
Authors: Alvarado Swanni T. , Buisson Elise , Rabarison Harison , Rajeriarison Charlotte , Birkinshaw Chris , Lowry Porter P.
Published: February 2015

The effects of fire on germination have been extensively studied in many ecosystems. Several studies have shown that plant species in ecosystems frequently exposed to fire can survive through two main mechanisms: vegetative regeneration (re‐sprouts) and recruitment of new individuals from a fire‐resistant seed bank. In Africa, an increase in temperature can break seed dormancy and stimulate germination of some herbaceous and woody species. In Madagascar, the once widespread highland ecosystems dominated by woody species are now highly fragmented and dominated by anthropic grasslands and fields, with a significantly reduced area occupied by sclerophyllous forests referred to as ‘tapia woodlands’. Six species of this endemic vegetation type were studied: Abrahamia ibityensis (Anacardiaceae), Aphloia theiformis (Aphloiaceae), Carissa edulis (Apocynaceae), Pentachlaena latifolia (Sarcolaenaceae), Uapaca bojeri (Phyllanthaceae) and Vaccinium secundiflorum (Ericaceae). Germination tests were conducted (i) by soaking seeds in water for 24 h (imbibition) or (ii) by exposing the seeds to dry heat. Four different temperatures (40, 60, 80 and 120°C) were applied, and seeds were exposed for 10, 30, 60 and 90 min. To simulate hotter faster‐burning fires, two higher temperatures (100 and 120°C) were also used by exposing seeds to dry heat for 5 min. The results did not reveal any significant effect of 24‐h water imbibition on germination. For most species, germination decreased with increasing temperature of treatment using dry heat. Uapaca bojeri did not germinate under any treatment. Further studies on the biological and ecological characteristics of tapia woodland species in response to fire are needed to help guide conservation, management and restoration activities focusing on this endemic vegetation type.
Offspring performance and recruitment of the pioneer treeAcacia caven(Fabaceae) in a fragmented subtropical dry forest
Authors: Ashworth Lorena , Calviño Ana , Martí María Leticia , Aguilar Ramiro
Published: February 2015

The process of habitat fragmentation results in the breaking apart of originally continuous habitats, causing multiple changes in biotic and abiotic interactions. Alterations in resource availability and in mutualistic and antagonistic plant–animal interactions may impact plant offspring quantity and quality. Currently, several old fragmented systems evidence a process of flora homogenization, where shade‐tolerant species are replaced by pioneer light‐demanding species. Notably, the relationship between quantity and quality parameters of plant offspring production and the successful recruitment of pioneer species in fragmented forests has been poorly explored. Here, we assess population size, sapling recruitment and offspring performance of one of the most widespread tree species of subtropicalSouthAmerica, the native pioneerAcacia caven(Fabaceae). Population size of adults and saplings increased from small to continuous forests, whereas the sapling recruitment per adult tree (sapling/adult ratio) showed no significant differences among forests of different size. Seedling performance was negatively related to forest area and population size, implying potential superior competitive ability of seedlings produced in smaller populations compared to larger ones. Our results show thatA. cavenis resilient to habitat fragmentation effects, which may be ascribed to a set of advantageous ecological traits such as outcrossing, massive flowering, generalist pollination, drought resistance, rapid growth and re‐sprouting. Thus, this pioneer tree benefits from the availability of vacant sites and resources released by declining plant populations of other species, eventually becoming the dominant species in fragmented habitats. Pioneer native plant species with ecological traits such asA. cavenmay represent the silent successful survivors and new colonizers of fragmented habitats, the ubiquitous landscapes of the future.
Does ear keloid formation depend on the type of earrings or piercing jewellery?
Authors: Hochman† Bernardo , Isoldi Felipe C , Silveira Tiago S , Borba Graizela C , Ferreira Lydia M
Published: February 2015

The ear is one of the most common sites of keloid formation, usually associated with the wearing of earrings. However, although this is a small perforating lesion that is equal on both sides, keloids are bigger and more prevalent on the posterior surface. In this study, 141 keloids were evaluated, most of which were located on the posterior surface of the earlobe and caused by the piercing of the ear. Most of the earrings and piercing jewellery used had metallic backs. The more frequent occurrence of earlobe keloids on the posterior surface of the ear therefore may be associated with the exacerbation of local neurogenic inflammation caused by the metallic backs.
Current landscape for treatment of advanced basal cell carcinoma
Authors: Foley Peter
Published: February 2015

Basal cell carcinomas (BCCs) account for around 80% of non‐melanoma skin cancer. Australia has the highest incidence of BCC globally and the rates continue to increase in both Australia and New Zealand. BCC causes significant morbidity, placing an enormous burden on the healthcare system. Treatment of patients with advanced BCC can be particularly challenging. A panel of UK experts recently defined advanced disease as BCC that in which current treatment modalities are considered potentially contraindicated by clinical or patient‐driven factors. Research has found that mutations in the hedgehog signalling pathway underpin the pathogenesis of the vast majority of sporadic BCC, as well as Gorlin syndrome. The first‐in‐class oral small molecule hedgehog pathway inhibitor – vismodegib–is now approved in a number of countries for use in locally‐advanced and metastatic BCC and has resulted in improved outcomes in the majority of patients treated. With a number of similar agents in the pipeline, research is now focusing on identifying mechanisms that may contribute to resistance to this agent in some lesions.
Remote ischaemic conditioning: cardiac protection from afar
Authors: Sivaraman V. , Pickard J. M. J. , Hausenloy D. J.
Published: February 2015

For patients with ischaemic heart disease, remote ischaemic conditioning may offer an innovative, non‐invasive and virtually cost‐free therapy for protecting the myocardium against the detrimental effects of acute ischaemia‐reperfusion injury, preserving cardiac function and improving clinical outcomes. The intriguing phenomenon of remote ischaemic conditioning was first discovered over 20 years ago, when it was shown that the heart could be rendered resistant to acute ischaemia‐reperfusion injury by applying one or more cycles of brief ischaemia and reperfusion to an organ or tissue away from the heart – initially termed ‘cardioprotection at a distance’. Subsequent pre‐clinical and then clinical studies made the important discovery that remote ischaemic conditioning could be elicited non‐invasively, by inducing brief ischaemia and reperfusion to the upper or lower limb using a cuff. The actual mechanism underlying remote ischaemic conditioning cardioprotection remains unclear, although a neuro‐hormonal pathway has been implicated. Since its initial discovery in 1993, the first proof‐of‐concept clinical studies of remote ischaemic conditioning followed in 2006, and now multicentre clinical outcome studies are underway. In this review article, we explore the potential mechanisms underlying this academic curiosity, and assess the success of its application in the clinical setting.
Dopamine and T cells: dopamine receptors and potent effects on T cells, dopamine production in T cells, and abnormalities in the dopaminergic system in T cells in autoimmune, neurological and psychiatric diseases
Authors: Levite M.
Published: February 2015

Dopamine, a principal neurotransmitter, deserves upgrading to ‘NeuroImmunotransmitter’ thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent activator of resting effector T cells (Teffs), via two independent ways: direct Teffs activation, and indirect Teffs activation by suppression of regulatory T cells (Tregs). The review covers the following findings: (i) T cells express functional dopamine receptors (DRs) D1R‐D5R, but their level and function are dynamic and context‐sensitive, (ii)DRmembranal protein levels do not necessarily correlate withDR mRNAlevels, (iii) different T cell types/subtypes have differentDRlevels and composition and different responses to dopamine, (iv) autoimmune and pro‐inflammatory T cells and T cell leukaemia/lymphoma also express functionalDRs, (v) dopamine (~10−8M) activates resting/naive Teffs (CD8+>>>CD4+), (vi) dopamine affects Th1/Th2/Th17 differentiation, (vii) dopamine inhibits already activated Teffs (i.e. T  cells that have been already activated by either antigen, mitogen, anti‐CD3 antibodies cytokines or other molecules), (viii) dopamine inhibits activated Tregs in an autocrine/paracrine manner. Thus, dopamine ‘suppresses the suppressors’ and releases the inhibition they exert on Teffs, (ix) dopamine affects intracellular signalling molecules and cascades in T cells (e.g.ERK, Lck, Fyn,NF‐κB,KLF2), (x) T cells produce dopamine (Tregs>>>Teffs), can release dopamine, mainly after activation (by antigen, mitogen, anti‐CD3 antibodies, PKC activators or other), uptake extracellular dopamine, and most probably need dopamine, (xi) dopamine is important for antigen‐specific interactions between T cells and dendritic cells, (xii) in few autoimmune diseases (e.g. multiple sclerosis/SLE/rheumatoid arthritis), and neurological/psychiatric diseases (e.g. Parkinson disease, Alzheimer's disease, Schizophrenia and Tourette), patient's T cells seem to have abnormalDRs expression and/or responses to dopamine or production of dopamine, (xiii) drugs that affect the dopaminergic system have potent effects on T cells (e.g. dopamine=Intropin, L‐dopa, bromocriptine, haloperidol, quinpirole, reserpine, pergolide, ecopipam, pimozide, amantadine, tetrabenazine, nomifensine, butaclamol). Dopamine‐induced activation of resting Teffs and suppression of Tregs seem beneficial for health and may also be used for immunotherapy of cancer and infectious diseases. Independently, suppression ofDRs in autoimmune and pro‐inflammatory T cells, and also in cancerous T cells, may be advantageous. The review is relevant to Immunologists, Neurologists, Neuroimmunologists, Hematologists, Psychiatrists, Psychologists and Pharmacologists.
Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate
Authors: Seles Maximilian , Gutschi Thomas , Mayrhofer Katrin , Fischereder Katja , Ehrlich Georg , Gallé Guenter , Gutschi Stefan , Pachernegg Oliver , Pummer Karl , Augustin Herbert
Published: February 2015

Objective

To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat‐biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score.

Patients and Methods

The study was a prospective, randomised (end‐fire vs side‐fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid‐lobar, anterior and the anterior apical region located ventro‐laterally to the urethra of the peripheral zone.

Results

The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five‐fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown.

Conclusion

Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy.
Clonotypically similar hybridαβT cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity
Authors: Motozono C , Bridgeman J S , Price D A , Sewell A K , Ueno T
Published: February 2015

Emerging data indicate that particular major histocompatibility complex (MHC)-bound antigenic peptides can be recognized by identical or near-identical αβ T cell receptors (TCRs) in different individuals. To establish the functional relevance of this phenomenon, we artificially paired α and β chains from closely related TCRs specific for the human leucocyte antigen (HLA)-B*35:01-restricted HIV-1 negative regulatory factor (Nef)-derived epitope VY8 (VPLRPMTY, residues 74–81). Several hybrid TCRs generated in this manner failed to express at the cell surface, despite near homology with naturally isolated αβ chain combinations. Moreover, a substantial proportion of those αβ TCRs that did express lost specificity for the index VY8 peptide sequence. One such hybrid αβ pair gained neo-variant specificity in the context of the VY8 backbone. Collectively, these data show that clonotypically similar TCRs can display profound differences in surface expression, antigen specificity and cross-reactivity with potential relevance for the control of mutable viruses.
Influence of Maxillary Sinus Width on Transcrestal Sinus Augmentation Outcomes: Radiographic Evaluation Based on Cone Beam CT
Authors: Zheng Xiaofei , Teng Minhua , Zhou Fengjuan , Ye Jun , Li Guanda , Mo Anchun
Published: February 2015

Background

Maxillary sinus elevation is a predictable procedure to vertically enhance bone volume in the posterior maxilla for successful implant placement. It is speculated that graft bone resorption and remodeling which require angiogenesis may be affected by the dimensions of maxillary sinus cavity.

Purpose

The aim of this study is to investigate the effect of sinus width (SW) on the outcomes of transcrestal sinus lift with simultaneous implant placement based on cone beam CT (CBCT).

Materials and Methods

A total of 57 elevated sites in 33 patients were included in this study. All the patients were treated with transcrestal sinus lift procedure associated with simultaneous implant placement using a composite graft material of autogenous bone and Bio‐Oss. For each patient, CBCT scans were performed preoperatively, immediately after surgery and 6 months after surgery. Measurements of the linear parameters were conducted on the preoperative and postoperative CBCT images. The correlation of SW with graft resorption (GR) was analyzed using Pearson's correlation test with or without the classification of residual bone height.

Results

The average width of maxillary sinus was 13.68 ± 2.66 mm. The mean height of apical graft bone decreased from 2.85 mm immediately after surgery to 1.38 mm after 6 months. A positive association between SW and GR (r = 0.323, p = .014) was found in general.

Conclusion

The findings show that graft bone resorption in elevated sinus has a positive correlation with the SW.
Prevalence of foot eczema and associated occupational and non‐occupational factors in patients with hand eczema
Authors: Brans Richard , Hübner Anja , Gediga Günther , John Swen M.
Published: February 2015

Background

Foot eczema often occurs in combination with hand eczema. However, in contrast to the situation with hand eczema, knowledge about foot eczema is scarce, especially in occupational settings.

Objective

To evaluate the prevalence of foot eczema and associated factors in patients with hand eczema taking part in a tertiary individual prevention programme for occupational skin diseases.

Patients/materials/methods

In a retrospective cohort study, the medical records of 843 patients taking part in the tertiary individual prevention programme were evaluated.

Results

Seven hundred and twenty‐three patients (85.8%) suffered from hand eczema. Among these, 201 patients (27.8%) had concomitant foot eczema, mainly atopic foot eczema (60.4%). An occupational irritant component was possible in 38 patients with foot eczema (18.9%). In the majority of patients, the same morphological features were found on the hands and feet (71.1%). The presence of foot eczema was significantly associated with male sex [odds ratio (OR) 1.78, 95% confidence interval (CI) 1.29–2.49], atopic hand eczema (OR 1.60, 95%CI: 1.15–2.22), hyperhidrosis (OR 1.73, 95%CI: 1.33–2.43), and the wearing of safety shoes/boots at work (OR 2.04, 95%CI: 1.46–2.87). Tobacco smoking was associated with foot eczema (OR 1.79, 95%CI: 1.25–2.57), in particular with the vesicular subtype.

Conclusions

Foot eczema is common in patients with hand eczema, and is related to both occupational and non‐occupational factors.
Does a Supplier's Operational Competence Translate into Financial Performance? An Empirical Analysis of Supplier–Customer Relationships
Authors: Kim Yoon Hee , Wemmerlöv Urban
Published: February 2015

We conduct an empirical investigation of how a supplier's operational competence, as reflected by outcomes in the areas of quality, cost, delivery, flexibility, and new product development, translates into financial gains from a key customer. In contrast to previous research directed at the firm level, this study focuses on the supplier–customer relationship level. Using survey data from 158 suppliers in the manufacturing industry, we perform structural equation modeling to map out the paths from operational competence to financial performance—via dependencies and cooperative behaviors between suppliers and their customers. This study is the first scholarly attempt to examine the link between suppliers’ operational competencies and financial performance in interorganizational relationships. It is also an early investigation into operational competence as a source of bi‐lateral dependence. Our findings show that the supplier's operational competences increase its customer's dependence by enhancing the value of its products/services. However, the resulting increase in the supplier's power is not leveraged to shape relationship behaviors or capture value from its customer. In contrast, the customer's existing power as a major buyer plays an important role in shaping cooperative behaviors and affecting the supplier's financial performance from the customer relationship.
Fleet Replacement, Technology Choice, and the Option to Breach a Leasing Contract
Authors: Neboian Andrei , Spinler Stefan
Published: February 2015

We analyze the option to breach a leasing contract when replacing a fleet of ICVs (internal combustion engine vehicles) and EVs (electric vehicles) subject to cost uncertainty. We derive the optimal policy for technology choice and breaching ICV contracts. The decision to breach is shown to offer both cost savings resulting from reduced ICV operating costs and preemptive acquisition, but incurs additional costs arising from the need to compensate for breached vehicles and in the form of opportunity costs. We also demonstrate that the effects of breaching a leasing contract have a ripple effect across the decision horizon, thus amplifying the impact of a single breach. A numerical study based on data from La Poste, the French postal service, shows that breaching a leasing contract in this context offers measurable cost benefits.
Effect of Inventory Information Discrepancy in a Drop‐Shipping Supply Chain
Authors: Cheong Taesu , Goh Mark , Song Sang Hwa
Published: February 2015

This article investigates the impact of information discrepancy between a drop‐shipper and an online retailer on the drop‐shipping supply chain performance. The inventory information misalignment between them contributes to the failure of order fulfillment and demand satisfaction, and hence the associated penalties are incurred. In this article, we first analyze the penalties of ignoring such information discrepancy on both the drop‐shipper and the online retailer. We then assess the impact of information discrepancy on both parties when the drop‐shipper understands the existence of the information discrepancy but is not able to eliminate the errors. The numerical experiments indicate that both parties can have significant amount of the percentage cost reductions if the information discrepancy can be eliminated, and the potential savings are substantial especially when the errors have large variability. Furthermore, we observe that the online retailer is more vulnerable to information discrepancy than the drop‐shipper, and the drop‐shipper is likely to suffer from the online retailer's underestimation of the physical inventory level more than the problem of its overestimation. Moreover, even if eliminating errors is not possible, both parties could still benefit from taking the possibility of errors into consideration in decision making.