bluuebunny/crossref_metadata_2025 huggingface dataset:
The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ
Authors: Hirota Kouji , Yoshikiyo Kazunori , Guilbaud Guillaume , Tsurimoto Toshiki , Murai Junko , Tsuda Masataka , Phillips Lara G. , Narita Takeo , Nishihara Kana , Kobayashi Kaori , Yamada Kouich , Nakamura Jun , Pommier Yves , Lehmann Alan , Sale Julian E. , Takeda Shunichi
Published: January 2015

The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases.
A physiological significance of the functional interaction between Mus81 and Rad27 in homologous recombination repair
Authors: Thu Huong Phung Thi , Nguyen Tuan Anh , Munashingha Palinda Ruvan , Kwon Buki , Dao Van Quy , Seo Yeon-Soo
Published: January 2015

Fen1 and Mus81–Mms4 are endonucleases involved in the processing of various DNA structural intermediates, and they were shown to have genetic and functional interactions with each other. Here, we show the in vivo significance of the interactions between Mus81 and Rad27 (yeast Fen1). The N-terminal 120 amino-acid (aa) region of Mus81, although entirely dispensable for its catalytic activity, was essential for the abilities of Mus81 to bind to and be stimulated by Rad27. In the absence of SGS1, the mus81Δ120N mutation lacking the N-terminal 120 aa region exhibited synthetic lethality, and the lethality was rescued by deletion of RAD52, a key homologous recombination mediator. These findings, together with the fact that Sgs1 constitutes a redundant pathway with Mus81–Mms4, indicate that the N-terminus-mediated interaction of Mus81 with Rad27 is physiologically important in resolving toxic recombination intermediates. Mutagenic analyses of the N-terminal region identified two distinct motifs, named N21–26 (aa from 21–26) and N108–114 (aa from 108–114) important for the in vitro and in vivo functions of Mus81. Our findings indicate that the N-terminal region of Mus81 acts as a landing pad to interact with Rad27 and that Mus81 and Rad27 work conjointly for efficient removal of various aberrant DNA structures.
An intercalation-locked parallel-stranded DNA tetraplex
Authors: Tripathi Shailesh , Zhang Daoning , Paukstelis Paul J.
Published: January 2015

DNA has proved to be an excellent material for nanoscale construction because complementary DNA duplexes are programmable and structurally predictable. However, in the absence of Watson–Crick pairings, DNA can be structurally more diverse. Here, we describe the crystal structures of d(ACTCGGATGAT) and the brominated derivative, d(ACBrUCGGABrUGAT). These oligonucleotides form parallel-stranded duplexes with a crystallographically equivalent strand, resulting in the first examples of DNA crystal structures that contains four different symmetric homo base pairs. Two of the parallel-stranded duplexes are coaxially stacked in opposite directions and locked together to form a tetraplex through intercalation of the 5′-most A–A base pairs between adjacent G–G pairs in the partner duplex. The intercalation region is a new type of DNA tertiary structural motif with similarities to the i-motif. 1H–1H nuclear magnetic resonance and native gel electrophoresis confirmed the formation of a parallel-stranded duplex in solution. Finally, we modified specific nucleotide positions and added d(GAY) motifs to oligonucleotides and were readily able to obtain similar crystals. This suggests that this parallel-stranded DNA structure may be useful in the rational design of DNA crystals and nanostructures.
Recombinase and translesion DNA polymerase decrease the speed of replication fork progression during the DNA damage response in Escherichia coli cells
Authors: Tan Kang Wei , Pham Tuan Minh , Furukohri Asako , Maki Hisaji , Akiyama Masahiro Tatsumi
Published: January 2015

The SOS response is a DNA damage response pathway that serves as a general safeguard of genome integrity in bacteria. Extensive studies of the SOS response in Escherichia coli have contributed to establishing the key concepts of cellular responses to DNA damage. However, how the SOS response impacts on the dynamics of DNA replication fork movement remains unknown. We found that inducing the SOS response decreases the mean speed of individual replication forks by 30–50% in E. coli cells, leading to a 20–30% reduction in overall DNA synthesis. dinB and recA belong to a group of genes that are upregulated during the SOS response, and encode the highly conserved proteins DinB (also known as DNA polymerase IV) and RecA, which, respectively, specializes in translesion DNA synthesis and functions as the central recombination protein. Both genes were independently responsible for the SOS-dependent slowdown of replication fork progression. Furthermore, fork speed was reduced when each gene was ectopically expressed in SOS-uninduced cells to the levels at which they are expressed in SOS-induced cells. These results clearly indicate that the increased expression of dinB and recA performs a novel role in restraining the progression of an unperturbed replication fork during the SOS response.
Posterior Correction Without Rib-head Resection for Patients With Neurofibromatosis Type 1, Dystrophic Scoliosis, and Rib-head Protrusion Into the Spinal Canal
Authors: Cai Siyi , Zhang Jianguo , Shen Jianxiong , Zhao Hong , Weng Xisheng , Qiu Guixing
Published: January 2015

Study Design:

A retrospective study.

Objective:

The objective of this study is to report the result of patients with neurofibromatosis type 1(NF-1), dystrophic scoliosis, and rib-head protrusion into the spinal canal who received posterior scoliosis correction surgery without rib-head resection.

Summary of Background data:

A total of 124 patients with NF-1 and dystrophic scoliosis were treated at our institution during the study period. Eight patients with a median age of 12 years had rib-head protrusion into the spinal canal and received surgery and were included in the analysis.

Methods:

All 8 patients (6 male, 2 female) were treated from 2003 to 2013 and received posterior correction with a pedicle screw-rod 3-dimensional correction system or screw-hook hybrid system. Scoliosis correction rate and percentage of spinal canal occupied by the rib head were analyzed.

Results:

The median patient age, number of segments fused, and follow-up duration were 12 years, 10.5, and 22.5 months, respectively. There were no surgery-related complications, and symptoms in all patients improved after surgery. The median postoperative and 1-year follow-up sagittal kyphotic angles were significantly smaller as compared with the preoperative value (28.5 and 31 vs. 62.5 degrees, P=0.012). The median postoperative coronal Cobb angle of the main thoracic curve was significantly smaller compared with the preoperative value (29 vs. 64.5 degrees, P=0.012). The median percentage of the spinal canal occupied by the intraspinal rib was significantly lower at 1-year follow-up compared with the preoperative value (23.1% vs. 28.6%, P=0.018).

Conclusions:

Posterior correction without rib-head excision can provide good outcomes for patients with NF-1 and dystrophic scoliosis and rib-head protrusion into the spinal canal.
Kirschner Wire and Bone Cement is a Viable Alternative to Reconstruction of Large Iliac Bone Defects After Strut Bone Graft Harvesting
Authors: Yu Shang-Won , Wu Chin-Hsien , Yeh James Jih-Hsi , Yen Cheng-Yo , Ma Ching-Hou , Tu Yuan-Kun
Published: January 2015

Study Design:

A retrospective study.

Objective:

To assess the safety and efficacy of iliac crest defect reconstruction using Kirschner wire (K-wire)/polymethylmethacrylate (PMMA) versus traditional autologous rib graft reconstruction.

Summary of Background Data:

The iliac crest has been the preferred donor site for strut bone graft for various spinal fusion surgeries.

Methods:

Seventy-three patients (44 males and 29 females; average age: 57.2 y) were divided into 2 groups: the rib group (35 patients) and the K-wire/PMMA group (38 patients). All operations involved anterior spinal interbody fusion. Patients were followed-up, on average, for 34.2 months using plain radiographs and both pain and cosmesis visual analog scales (VAS) to assess the clinical results after surgery.

Results:

Almost all patients had pain VAS scores of ≤1 and grade 1 cosmesis VAS scores with no significant difference between the 2 groups in terms of either pain or cosmesis (P=1.00 and 0.505, respectively). In addition, few complications were noted in both groups. Radiographic complications in the rib group and the K-wire group numbered 4 (11%) and 2 (5%), respectively; however, did not significantly differ between the 2 groups (P=0.418). One case required intraoperative revision of the length of the K-wire and 1 case needed reoperation for iliac ring fracture and K-wire migration. An additional case required revision due to a bad fall.

Conclusions:

K-wire and bone cement reconstruction is an effective and safe alternative method for large iliac bone defect repair when autologous rib graft is not available.
An Experimental Biomechanical Study on Artificial Atlantoodontoid Joint Replacement in Dogs
Authors: Zang Quanjin , Liu Yanming , Wang Dengfeng , Li Haopeng , Yang Pinglin , Wang Dong , He Xijing
Published: January 2015

Study Design:

This study tested the biomechanics of artificial atlantoodontoid joint replacement (AAOJR) in a dog model. Dogs were divided into the artificial AAOJR group (n=10), the decompression group (n=10), and the healthy control group (n=10) using a random number table.

Objective:

To evaluate whether the use of AAOJR for repair of atlantoaxial instability retains rotation and restores stability.

Summary of Background data:

Atlantoaxial instability is characterized by excessive movement or laxity at the junction between the atlas (C1) and axis (C2). Pure decompression can lead to considerable loss of head and neck rotation and postoperative impairment. A series of biomechanical tests on cadavers found that the artificial AAOJR might rebuild the stability and retain the rotation function.

Methods:

We designed the AAOJ based on the radiologic and anatomic data of the dog atlas and axis, and established an animal model by resecting the odontoid and implanting the AAOJ into dogs. The biomechanical experiments measured the range of motion (ROM), neutral zone (NZ), and stiffness of flexion, extension, lateral bending, and axial rotation in the intact state, the decompressed state, after AAOJR, and after a fatigue test.

Results:

Compared with the intact state, after decompression operation, ROM and NZ in all directions, and stiffness during flexion were increased, and stiffness in all other directions was decreased. Compared with the after decompression state, AAOJR before and after the fatigue test resulted in decreased ROM in all directions (all P<0.05), decreased NZ during flexion/extension and lateral bending (all P<0.05), an increased NZ during axial rotation (both P<0.05), and increased stiffness in all directions (all P<0.05).

Conclusions:

These results indicate that AAOJR could reconstruct the vertebral stability of the C1–C2 segment and retain some axial rotation function.
Acceptance threshold theory can explain occurrence of homosexual behaviour
Authors: Engel Katharina C. , Männer Lisa , Ayasse Manfred , Steiger Sandra
Published: January 2015

Same-sex sexual behaviour (SSB) has been documented in a wide range of animals, but its evolutionary causes are not well understood. Here, we investigated SSB in the light of Reeve's acceptance threshold theory. When recognition is not error-proof, the acceptance threshold used by males to recognize potential mating partners should be flexibly adjusted to maximize the fitness pay-off between the costs of erroneously accepting males and the benefits of accepting females. By manipulating male burying beetles' search time for females and their reproductive potential, we influenced their perceived costs of making an acceptance or rejection error. As predicted, when the costs of rejecting females increased, males exhibited more permissive discrimination decisions and showed high levels of SSB; when the costs of accepting males increased, males were more restrictive and showed low levels of SSB. Our results support the idea that in animal species, in which the recognition cues of females and males overlap to a certain degree, SSB is a consequence of an adaptive discrimination strategy to avoid the costs of making rejection errors.
Spiders spinning electrically charged nano-fibres
Authors: Kronenberger Katrin , Vollrath Fritz
Published: January 2015

Most spider threads are on the micrometre and sub-micrometre scale. Yet, there are some spiders that spin true nano-scale fibres such as the cribellate orb spider,
Uloborus plumipes
. Here, we analyse the highly specialized capture silk-spinning system of this spider and compare it with the silk extrusion systems of the more standard spider dragline threads. The cribellar silk extrusion system consists of tiny, morphologically basic glands each terminating through exceptionally long and narrow ducts in uniquely shaped silk outlets. Depending on spider size, hundreds to thousands of these outlet spigots cover the cribellum, a phylogenetically ancient spinning plate. We present details on the unique functional design of the cribellate gland–duct–spigot system and discuss design requirements for its specialist fibrils. The spinning of fibres on the nano-scale seems to have been facilitated by the evolution of a highly specialist way of direct spinning, which differs from the aqua-melt silk extrusion set-up more typical for other spiders.
Transverse depth-dependent changes in corneal collagen lamellar orientation and distribution
Authors: Abass Ahmed , Hayes Sally , White Nick , Sorensen Thomas , Meek Keith M.
Published: January 2015

It is thought that corneal surface topography may be stabilized by the angular orientation of out-of plane lamellae that insert into the anterior limiting membrane. In this study, micro-focus X-ray scattering data were used to obtain quantitative information about lamellar inclination (with respect to the corneal surface) and the X-ray scatter intensity throughout the depth of the cornea from the centre to the temporal limbus. The average collagen inclination remained predominantly parallel to the tissue surface at all depths. However, in the central cornea, the spread of inclination angles was greatest in the anterior-most stroma (reflecting the increased lamellar interweaving in this region), and decreased with tissue depth; in the peripheral cornea inclination angles showed less variation throughout the tissue thickness. Inclination angles in the deeper stroma were generally higher in the peripheral cornea, suggesting the presence of more interweaving in the posterior stroma away from the central cornea. An increase in collagen X-ray scatter was identified in a region extending from the sclera anteriorly until about 2 mm from the corneal centre. This could arise from the presence of larger diameter fibrils, probably of scleral origin, which are known to exist in this region. Incorporation of this quantitative information into finite-element models will further improve the accuracy with which they can predict the biomechanical response of the cornea to pathology and refractive procedures.
Evolution of individual versus social learning on social networks
Authors: Tamura Kohei , Kobayashi Yutaka , Ihara Yasuo
Published: January 2015

A number of studies have investigated the roles played by individual and social learning in cultural phenomena and the relative advantages of the two learning strategies in variable environments. Because social learning involves the acquisition of behaviours from others, its utility depends on the availability of ‘cultural models’ exhibiting adaptive behaviours. This indicates that social networks play an essential role in the evolution of learning. However, possible effects of social structure on the evolution of learning have not been fully explored. Here, we develop a mathematical model to explore the evolutionary dynamics of learning strategies on social networks. We first derive the condition under which social learners (SLs) are selectively favoured over individual learners in a broad range of social network. We then obtain an analytical approximation of the long-term average frequency of SLs in homogeneous networks, from which we specify the condition, in terms of three relatedness measures, for social structure to facilitate the long-term evolution of social learning. Finally, we evaluate our approximation by Monte Carlo simulations in complete graphs, regular random graphs and scale-free networks. We formally show that whether social structure favours the evolution of social learning is determined by the relative magnitudes of two effects of social structure: localization in competition, by which competition between learning strategies is evaded, and localization in cultural transmission, which slows down the spread of adaptive traits. In addition, our estimates of the relatedness measures suggest that social structure disfavours the evolution of social learning when selection is weak.
Mathematical modelling of diurnal regulation of carbohydrate allocation by osmo-related processes in plants
Authors: Pokhilko Alexandra , Ebenhöh Oliver
Published: January 2015

Plants synthesize sucrose in source tissues (mainly mature leafs) and supply it for growth of sink tissues (young leafs). Sucrose is derived from photosynthesis during daytime and from starch at night. Because the diurnal regulation of sucrose fluxes is not completely understood, we built a mathematical model designed to reproduce all key experimental observations. For this, assumptions were made about the molecular mechanisms underlying the regulations, which are all motivated by experimental facts. The key regulators in our model are two kinases (SnRK1 and osmo-sensitive kinase OsmK) under the control of the circadian clock. SnRK1 is activated in the night to prepare for regularly occurring carbon-limiting conditions, whereas OsmK is activated during the day to prepare for water deficit, which often occurs in the afternoon. Decrease of SnRK1 and increase of OsmK result in partitioning of carbon towards sucrose to supply growing sink tissues. Concomitantly, increasing levels of the growth regulator trehalose-6-phosphate stimulates the development of new sink tissues and thus sink demand, which further activates sucrose supply in a positive feedback loop. We propose that OsmK acts as a timer to measure the length of the photoperiod and suggest experiments how this hypothesis can be validated.
Convergent evolution of alternative developmental trajectories associated with diapause in African and South American killifish
Authors: Furness Andrew I. , Reznick David N. , Springer Mark S. , Meredith Robert W.
Published: January 2015

Annual killifish adapted to life in seasonally ephemeral water-bodies exhibit desiccation resistant eggs that can undergo diapause, a period of developmental arrest, enabling them to traverse the otherwise inhospitable dry season. Environmental cues that potentially indicate the season can govern whether eggs enter a stage of diapause mid-way through development or skip this diapause and instead undergo direct development. We report, based on construction of a supermatrix phylogenetic tree of the order Cyprinodontiformes and a battery of comparative analyses, that the ability to produce diapause eggs evolved independently at least six times within African and South American killifish. We then show in species representative of these lineages that embryos entering diapause display significant reduction in development of the cranial region and circulatory system relative to direct-developing embryos. This divergence along alternative developmental pathways begins mid-way through development, well before diapause is entered, during a period of purported maximum developmental constraint (the phylotypic period). Finally, we show that entering diapause is accompanied by a dramatic reduction in metabolic rate and concomitant increase in long-term embryo survival. Morphological divergence during the phylotypic period thus allows embryos undergoing diapause to conserve energy by shunting resources away from energetically costly organs thereby increasing survival chances in an environment that necessitates remaining dormant, buried in the soil and surrounded by an eggshell for much of the year. Our results indicate that adaptation to seasonal aquatic environments in annual killifish imposes strong selection during the embryo stage leading to marked diversification during this otherwise conserved period of vertebrate development.
New patterns in human biogeography revealed by networks of contacts between linguistic groups
Authors: Capitán José A. , Bock Axelsen Jacob , Manrubia Susanna
Published: January 2015

Human languages differ broadly in abundance and are distributed highly unevenly on the Earth. In many qualitative and quantitative aspects, they strongly resemble biodiversity distributions. An intriguing and previously unexplored issue is the architecture of the neighbouring relationships between human linguistic groups. Here we construct and characterize these networks of contacts and show that they represent a new kind of spatial network with uncommon structural properties. Remarkably, language networks share a meaningful property with food webs: both are quasi-interval graphs. In food webs, intervality is linked to the existence of a niche space of low dimensionality; in language networks, we show that the unique relevant variable is the area occupied by the speakers of a language. By means of a range model analogous to niche models in ecology, we show that a geometric restriction of perimeter covering by neighbouring linguistic domains explains the structural patterns observed. Our findings may be of interest in the development of models for language dynamics or regarding the propagation of cultural innovations. In relation to species distribution, they pose the question of whether the spatial features of species ranges share architecture, and eventually generating mechanism, with the distribution of human linguistic groups.
SENSITIVE TO PROTON RHIZOTOXICITY1, CALMODULIN BINDING TRANSCRIPTION ACTIVATOR2, and Other Transcription Factors Are Involved inALUMINUM-ACTIVATED MALATE TRANSPORTER1Expression
Authors: Tokizawa Mutsutomo , Kobayashi Yuriko , Saito Tatsunori , Kobayashi Masatomo , Iuchi Satoshi , Nomoto Mika , Tada Yasuomi , Yamamoto Yoshiharu Y. , Koyama Hiroyuki
Published: January 2015

In Arabidopsis (Arabidopsis  thaliana) the root apex is protected from aluminum (Al) rhizotoxicity by excretion of malate, an Al chelator, by ALUMINUM-ACTIVATED MALATE TRANSPORTER1 (AtALMT1). AtALMT1 expression is fundamentally regulated by the SENSITIVE TO PROTON RHIZOTOXICITY1 (STOP1) zinc finger protein, but other transcription factors have roles that enable Al-inducible expression with a broad dynamic range. In this study, we characterized multiple cis-elements in the AtALMT1 promoter that interact with transcription factors. In planta complementation assays of AtALMT1 driven by 5′ truncated promoters of different lengths showed that the promoter region between –540 and 0 (the first ATG) restored the Al-sensitive phenotype of atalm1 and thus contains cis-elements essential for AtALMT1 expression for Al tolerance. Computation of overrepresented octamers showed that eight regions in this promoter region contained potential cis-elements involved in Al induction and STOP1 regulation. Mutation in a position around –297 from the first ATG completely inactivated AtALMT1 expression and Al response. In vitro binding assays showed that this region contained the STOP1 binding site, which accounted for the recognition by four zinc finger domains of the protein. Other positions were characterized as cis-elements that regulated expression by repressors and activators and a transcription factor that determines root tip expression of AtALMT1. From the consensus of known cis-elements, we identified CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR2 to be an activator of AtALMT1 expression. Al-inducible expression of AtALMT1 changed transcription starting sites, which increased the abundance of transcripts with a shortened 5′ untranslated region. The present analyses identified multiple mechanisms that regulate AtALMT1 expression.
Noncrystalline structure of Ni–P nanoparticles prepared by liquid pulse discharge
Authors: Tan Yuanyuan , Yu Hongying , Wu Zhonghua , Yang Bin , Gong Yu , Yan Shi , Du Rong , Chen Zhongjun , Sun Dongbai
Published: January 2015

Noncrystalline nickel phosphide (Ni–P) nanoparticles have drawn great attention due to their high potential as catalysts. However, the structure of noncrystalline Ni–P nanoparticles is still unknown, which may shed light on explaining the catalysis mechanism of the Ni–P nanoparticles. In this paper, noncrystalline Ni–P nanoparticles were synthesized. Their morphology, particle size, element contents, local atomic structures, as well as the catalysis in the thermal decomposition of ammonium perchlorate were studied. The results demonstrate that the as-prepared Ni–P nanoparticles are spherical with an average diameter of about 13.5 nm. The Ni and P contents are, respectively, 78.15% and 21.85%. The noncrystalline nature of the as-prepared Ni–P nanoparticles can be attributed to cross-linkage between P-doping f.c.c.-like Ni centers and Ni3P-like P centers. The locally ordered Ni centers and P centers are the nuclei sites, which can explain well the origin of initial nuclei to form the crystalline phases after high-temperature annealing. The starting temperature of high-temperature decomposition of ammonium perchlorate was found having a significant decrease in the presence of the noncrystalline Ni–P nanoparticles. Therefore, the as-prepared noncrystalline Ni–P nanoparticles can be used as a potential catalyst in the thermal decomposition of ammonium perchlorate.
Effective beam method for element concentrations
Authors: Tolhurst Thomas , Barbi Mauricio , Tokaryk Tim
Published: January 2015

There is a great diversity of research being conducted at synchrotron facilities around the world and a diverse set of beamlines to accommodate this research. Time is a precious commodity at synchrotron facilities; therefore, methods that can maximize the time spent collecting data are of value. At the same time the incident radiation spectrum, necessary for some research, may not be known on a given beamline. A preliminary presentation of a method applicable to X-ray fluorescence spectrocopic analyses that overcomes the lack of information about the incident beam spectrum that addresses both of these concerns is given here. The method is equally applicable for other X-ray sources so long as local conditions are considered. It relies on replacing the polychromatic spectrum in a standard fundamental parameters analysis with a set of effective monochromatic photon beams. A beam is associated with each element and can be described by an analytical function allowing extension to elements not included in the necessary calibration measurement(s).
Structure of a 13-fold superhelix (almost) determined from first principles
Authors: Schoch Guillaume A. , Sammito Massimo , Millán Claudia , Usón Isabel , Rudolph Markus G.
Published: January 2015

Nuclear hormone receptors are cytoplasm-based transcription factors that bind a ligand, translate to the nucleus and initiate gene transcription in complex with a co-activator such as TIF2 (transcriptional intermediary factor 2). For structural studies the co-activator is usually mimicked by a peptide ofcirca13 residues, which for the largest part forms an α-helix when bound to the receptor. The aim was to co-crystallize the glucocorticoid receptor in complex with a ligand and the TIF2 co-activator peptide. The 1.82 Å resolution diffraction data obtained from the crystal could not be phased by molecular replacement using the known receptor structures. HPLC analysis of the crystals revealed the absence of the receptor and indicated that only the co-activator peptide was present. The self-rotation function displayed 13-fold rotational symmetry, which initiated an exhaustive but unsuccessful molecular-replacement approach using motifs of 13-fold symmetry such as α- and β-barrels in various geometries. The structure was ultimately determined by using a single α-helix and the softwareARCIMBOLDO, which assembles fragments placed byPHASERbefore using them as seeds for density modification model building inSHELXE. Systematic variation of the helix length revealed upper and lower size limits for successful structure determination. A beautiful but unanticipated structure was obtained that forms superhelices with left-handed twist throughout the crystal, stabilized by ligand interactions. Together with the increasing diversity of structural elements in the Protein Data Bank the results from TIF2 confirm the potential of fragment-based molecular replacement to significantly accelerate the phasing step for native diffraction data at around 2 Å resolution.
Description and evaluation of a novel service for “difficult to manage” psychiatric in-patients
Authors: Hayes Adrian J. , Pratt Daniel , Shaw Jenny
Published: January 2015

Purpose

– A new service was developed to provide transitional care between acute and secure services for people with serious mental illness who are considered “difficult to manage”. The purpose of this paper is to evaluate the work of the service by examining referrals made, strategies employed for each referral, and patient outcomes, as well as investigating issues in the service's development and implementation.

Design/methodology/approach

– A retrospective descriptive study by review of 38 case notes, and qualitative interviews of 47 staff within the service and those referring to the service.

Findings

– In the first eight months, 38 patients were referred due to violence, aggression and management problems. Most interventions provided by the service involved working with referring staff, rather than direct patient contact. Subsequently, 16 per cent required referral to higher levels of security. Interviews showed the team's aims needed to be more clearly established, but that ward staff found the service to be a useful and productive resource.

Research limitations/implications

– The study is descriptive and retrospective, but showed that the service provided appropriate interventions for managing patients with serious mental illness and challenging behaviour.

Practical implications

– A transitional service may have value in keeping patients in the least restrictive setting. Careful planning is needed in designing novel interventions, ensuring clear aims and effective management.

Originality/value

– The service under study was novel, and may be useful in facilitating successful transfer from, or preventing admission to, secure services.
Young offenders’ experiences of an indeterminate sentence
Authors: Merola Melanie
Published: January 2015

Purpose

– The purpose of this paper was to understand the experience of those living with the Imprisonment for Public Protection (IPP) sentence.

Design/methodology/approach

– Interpretative Phenomenological Analysis (IPA) was used to analyse seven interviews with Young Offenders aged 18-21 who were serving an IPP sentence. Two participants were past their tariff expiry date, two had less than a year until their tariff date and three had more than a year until their tariff date.

Findings

– Several themes were found, each with their own subthemes: Injustice of the Justice System, Not Knowing, Coping, Change and Walking on Eggshells. Participants still detailed negative aspects of the sentence but within this was one, important, positive aspect, namely the inspiration the sentence gave for them to change their offending behaviour. However, this has come at a cost with participants feeling as though they have been treated unfairly, finding it difficult to cope, feeling victimised and finding it difficult to see a future.

Practical implications

– Lapses in motivation do not necessarily reflect the risk of the person but the difficulty of the sentence. Motivation can be fostered and developed through motivational interviewing, praise and peer support IPPs should be given more credit for the way they manage themselves daily and more understanding when they struggle. IPPs could be victimised by determinate prisoners or by staff. Establishments should be aware of this and help IPPs resolve situations without feeling like they are a victim. Consideration should be given to converting IPP sentences to determinate sentences.

Originality/value

– Previous research focused on the negative aspects of the sentence, the purpose was therefore to approach the situation with an open mind and by using a method that allows those with an IPP sentence to share their experience of the sentence. IPA allowed for exploration of the effects of the sentence on those serving it and therefore gains a further understanding of the impact of the sentence.
The therapeutic potential of a prison-based animal programme in the UK
Authors: Mercer Jenny , Gibson Kerry , Clayton Debbie
Published: January 2015

Purpose

– Much evidence suggests that animals can serve as therapeutic tools for those working with vulnerable individuals. This exploratory study analysed the accounts of staff and offenders involved in a UK prison-based animal programme. The purpose of this paper was to explore the perceived impact of such a programme with male offenders.

Design/methodology/approach

– Semi-structured interviews were conducted with three service users and five staff members. Participants were drawn from a special unit in a category B prison which housed an animal centre.

Findings

– A thematic analysis identified four salient themes: a sense of responsibility, building trust, enhanced communication, and impact on mood and behaviour. Findings revealed that offenders seemed to gain particular benefit from interacting with the two Labrador dogs which were present on the wing.

Practical implications

– The study highlights the therapeutic potential of the presence of animals in prisons. Their implications of this for forensic practice are discussed.

Originality/value

– This paper offers an important contribution to the sparse literature about prison-based animal programmes in the UK.
The role of spirituality in business education
Authors: Illes Katalin , Zsolnai Laszlo
Published: January 2015

Purpose

– This paper aims to argue that there is a strong imbalance in business education between providing abstract, rational concepts and opportunities for personal growth. Introducing spirituality in business education seems to be desirable if we want to prepare students for the complexities and challenges of the workplace today.

Design/methodology/approach

– The paper gives an example of how techniques from voice and drama therapy can be used for enabling students to look beyond the rational and the material.

Findings

– By engaging with their “true self”, students may discover dormant qualities in themselves and start to find their purpose, meaning and spirituality.

Originality/value

– The paper shows that by introducing some new approaches in business education, we can provide opportunities for students to connect their rational thoughts with conscience and the “true self”. When students make an integrated use of our mental, emotional and spiritual resources, they are better equipped to make complex decisions and behave ethically in the workplace and in their personal lives.
FORUM: Perverse incentives risk undermining biodiversity offset policies
Authors: Gordon Ascelin , Bull Joseph W. , Wilcox Chris , Maron Martine
Published: January 2015

Offsetting is emerging as an important but controversial approach for managing environment–development conflicts. Biodiversity offsets are designed to compensate for damage to biodiversity from development by providing biodiversity gains elsewhere.

Here, we suggest how biodiversity offset policies can generate behaviours that exacerbate biodiversity decline, and identify four perverse incentives that could arise even from soundly designed policies.

These include incentives for (i) entrenching or exacerbating baseline biodiversity declines, (ii) winding back non‐offset conservation actions, (iii) crowding out of conservation volunteerism and (iv) false public confidence in environmental outcomes due to marketing offset actions as gains.

Synthesis and applications. Despite its goal of improving biodiversity outcomes, there is potential for best‐practice offsetting to achieve the opposite result. Reducing this risk requires coupling offset crediting baselines to measured trajectories of biodiversity change and understanding the potential interaction between offsetting and other environmental policies.
Fss1 is involved in the regulation of an ENA5 homologue for sodium and lithium tolerance in Fusarium graminearum
Authors: Son Hokyoung , Park Ae Ran , Lim Jae Yun , Lee Yin‐Won
Published: January 2015

Sodium is an abundant cation required for protein function and maintenance of cellular osmotic homeostasis. High concentrations of sodium are toxic, and fungi have evolved efficient sodium efflux systems. In this study, we characterized a novel sodium tolerance mechanism in the plant pathogen Fusarium graminearum. Fusarium graminearum sodium sensitive 1 (Fss1) is a nuclear transcription factor with a Zn(II)2Cys6 fungal‐type DNA‐binding domain required for sodium tolerance. RNA‐seq and genetic studies revealed that a P‐type ATPase pump, exitus natru (Latin: exit sodium) 1 (FgEna5), mediates the phenotypic defects of FSS1 mutants. A homologue of PACC (PAC1) was required for FgEna5‐dependent sodium and lithium tolerance independent of Fss1. The results of this study revealed that F. graminearum has a distinct and novel pathway for sodium tolerance not present in other model fungi.
Non-state Actors and Global Crime Governance: Explaining the Variance of Public-private Interaction
Authors: Jakobi Anja P.
Published: January 2015

This article: Shows the variance of non-state actors in global crime governance and transnational governance in general, and shows that existent accounts fail to explain this variance. Proposes a model of how we can understand the different roles of non-state actors, distinguishing normative from rationalist reasons for non-state actor involvement. Compares different forms of current global crime governance (human trafficking, conflict diamonds, money laundering, cybercrime) to explore the validity of the model. Shows that non-state activism and public debate are usually only related to a specific type of crime, turning a ‘blind eye’ to other forms of crime and their governance. Argues that this creates problems with regard to oversight and discussion of global crime governance, exemplified with regard to intelligence surveillance via internet traffic.

Global crime governance has become a major area of international activity, including a growing number of public and private regulatory efforts. Yet it is puzzling that a considerable variance exists in how state and non-state actors interact: non-state actors have been important agenda-setters in some issue areas, while they have been absent in others. Sometimes they are implementation bodies, sometimes they set regulations themselves. I argue that this variance is caused by issue characteristics: If an issue area is framed in a highly moralised way, it is likely that resulting non-governmental activity can be explained by normative convictions, and in particular advocacy occurs frequently. If an issue area is framed in a technical way, resource exchange is central, and delegation to non-state actors becomes more prominent. A comparison of human trafficking, conflict diamonds, money laundering and cybercrime shows that this relation can be found on the global and national level.
What Do Voters Want From Their Local MP?
Authors: Vivyan Nick , Wagner Markus
Published: January 2015

This article summarises the findings from a study of what constituents want from their local Member of Parliament. We make use of a survey technique known as conjoint analysis, wherein we present a national sample of British voters with profiles of hypothetical MPs who vary randomly in their characteristics, activities and behaviour. We find that voters like MPs who are independent from the party line and who do not focus exclusively on national policy work. MPs' gender and experience matter far less to constituents. Overall, voters want a Parliament made up of strong‐minded MPs who see their role as that of a constituency representative. This has important implications for parliamentary democracy in Britain.
Previous miscarriage and the subsequent risk of preterm birth in Scotland, 1980–2008: a historical cohort study
Authors: Oliver‐Williams C , Fleming M , Wood AM , Smith GCS
Published: January 2015

Objective

To determine whether the relationship between previous miscarriage and risk of preterm birth changed over the period 1980–2008, and to determine whether the pattern varied according to the cause of the preterm birth.

Design

Linked birth databases.

Setting

All Scottish NHS hospitals.

Population

A total of 732 719 nulliparous women with a first live birth between 1980 and 2008.

Methods

Risk was estimated using logistic regression.

Main outcome measures

Preterm birth, subdivided by cause (spontaneous, induced with a diagnosis of pre‐eclampsia, or induced without a diagnosis of pre‐eclampsia) and severity [extreme (24–28 weeks of gestation), moderate (29–32 weeks of gestation), and mild (33–36 weeks of gestation)].

Results

Consistent with previous studies, previous miscarriage was associated with an increased risk of all‐cause preterm birth (adjusted odds ratio, aOR 1.26; 95% confidence interval, 95% CI 1.22–1.29). This arose from associations with all subtypes. The strongest association was found with extreme preterm birth (aOR 1.73; 95% CI 1.57–1.90). Risk increased with the number of miscarriages. Women with three or more miscarriages had the greatest risk of all‐cause preterm birth (aOR 2.14; 95% CI 1.93–2.38), and the strongest association was with extreme preterm birth (aOR 3.87; 95% CI 2.85–5.26). The strength of the association between miscarriage and preterm birth decreased from 1980 to 2008. This was because of weakening associations with spontaneous preterm birth and induced preterm birth without a diagnosis of pre‐eclampsia.

Conclusions

The association between a prior history of miscarriage and the risk of preterm birth declined in Scotland over the period 1980–2008. We speculate that changes in the methods of managing incomplete termination of pregnancy might explain the trend, through reduced cervical damage.
Thermotolerant Campylobacter during Broiler Rearing: Risk Factors and Intervention
Authors: Robyn Joris , Rasschaert Geertrui , Pasmans Frank , Heyndrickx Marc
Published: January 2015

Thermotolerant Campylobacters are one of the most important bacterial causative agents of human gastrointestinal illness worldwide. In most European Union (EU) member states human campylobacteriosis is mainly caused by infection with Campylobacter jejuni or Campylobacter coli following consumption or inadequate handling of Campylobacter‐contaminated poultry meat. To date, no effective strategy to control Campylobacter colonization of broilers during rearing is available. In this review, we describe the public health problem posed by Campylobacter presence in broilers and list and critically review all currently known measures that have been researched to lower the numbers of Campylobacter bacteria in broilers during rearing. We also discuss the most promising measures and which measures should be investigated further. We end this review by elaborating on readily usable measures to lower Campylobacter introduction and Campylobacter numbers in a broiler flock.
Identification of Anticancer Peptides from Bovine Milk Proteins and Their Potential Roles in Management of Cancer: A Critical Review
Authors: Sah B. N. P. , Vasiljevic T. , McKechnie S. , Donkor O. N.
Published: January 2015

Cancer is the most widely recognized reason for human deaths globally. Conventional anticancer therapies, including chemotherapy and radiation, are very costly and induce severe side effects on the individual. The discovery of natural anticancer compounds like peptides may thus be a better alternative for cancer prevention and management. The anticancer peptides also exist in the amino acid chain of milk proteins and can be generated during proteolytic activities such as gastrointestinal digestion or food processing including fermentation. This paper presents an exhaustive overview of the contemporary literature on antitumor activities of peptides released from milk proteins. In addition, caseins and whey proteins have been evaluated for anticancer potential using the AntiCP database, a web‐based prediction server. Proline and lysine, respectively, dominate at various positions in anticancer peptides obtained from caseins and whey proteins. The remarkable number of potential anticancer peptides revealed milk proteins as favorable candidates for the development of anticancer agents or milk and milk products for reduction of cancer risks. Moreover, anticancer peptides liberated from milk proteins can be identified from fermented dairy products. Although current findings of correlation between dairy food intakes and cancer risks lack consistency, dairy‐derived peptides show promise as candidates for cancer therapy. This critical review supports the notion that milk proteins are not only a nutritious part of a normal daily diet but also have potential for prevention and/or management of cancer.