bluuebunny/crossref_metadata_2025 huggingface dataset:
Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus
Authors: Coleman Christopher M. , Matthews Krystal L. , Goicochea Lindsay , Frieman Matthew B.
Published: November 2013

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.
RuII–hydride–tropcomplexes: X-ray single-crystal determination and quantum-chemical calculations
Authors: Santiso-Quinones Gustavo , Rodriguez-Lugo Rafael , Sacchetti Vittorio , Grützmacher Hansjörg
Published: November 2013

As part of our search for catalytically active RuII–hydride complexes, we have synthesized and crystallographically characterized three different ruthenium species, namely dihydrido[(SR)-(10,11-η)-N-(pyridin-2-ylmethyl-κN)-5H-dibenzo[a,d]cyclohepten-5-amine](triphenylphosphane-κP)ruthenium(II) tetrahydrofuran monosolvate, [RuH2(C21H18N2)(C18H15P)]·C4H8O or (SR)-[RuII(H)2{N-(pyridin-2-ylmethyl)tropNH}(PPh3)]·THF, (1), chlorido{(1SR,2RS)-N,N′-bis[(10,11-η)-5H-dibenzo[a,d]cyclohepten-5-amine]ethane-1,2-diamine-κ2N,N′}hydridoruthenium(II) dimethoxyethane hemisolvate, [RuClH(C32H28N2)]·0.5C4H10O2or (1SR,2RS)-[RuII(H)(Cl){tropNH(CH2)2HNtrop}]·DME, (2), and chlorido{(1SR,2RS)-N,N′-bis[(10,11-η)-5H-dibenzo[a,d]cyclohepten-5-amine]propane-1,3-diamine-κ2N,N′}hydridoruthenium(II), [RuClH(C33H30N2)] or (1SR,2RS)-[RuII(H)(Cl){tropNH(CH2)3HNtrop}], (3), wheretropis 5H-dibenzo[a,d]cycloheptene. In all three complexes, the RuIIcenter resides in an octahedral coordination environment. For (1)–(3), the hydride atoms were located in a difference Fourier map and were refined freely. In solution, the1H NMR spectra of all species show the presence of the hydride resonance. Comparison with quantum-chemical calculations reveals that the crystallographic data sets are plausible. In every case, the prediction is in very good agreement with the observed X-ray data. Not only the observed geometry is predicted well but also the Ru—H(hydride) bond lengths are reproduced remarkably well. Complexes (1) and (2) crystallized in the triclinicP\overline{1} space group, while (3) crystallized in the tetragonal space groupI41/a. For (3), there is disorder of the axial ligands producing two isomers (in a 98.7:1.3 ratio). Details of the synthesis, characterization, X-ray analysis, and theoretical calculations for complexes (1)–(3) are presented.
A polymorphic form of 4,4-dimethyl-8-methylene-3-azabicyclo[3.3.1]non-2-en-2-yl 3-indolyl ketone, an indole alkaloid extracted fromAristotelia chilensis(maqui)
Authors: Paz Cristian , Becerra José , Silva Mario , Freire Eleonora , Baggio Ricardo
Published: November 2013

The title compound [systematic name: (4,4-dimethyl-8-methylene-3-azabicyclo[3.3.1]non-2-en-2-yl)(1H-indol-3-yl)methanone], C20H22N2O, (II), was obtained from mother liquors extracted fromAristotelia chilensis(commonly known as maqui), a native Chilean tree. The compound is a polymorphic form of that obtained from the same source and reported by Watson, Nagl, Silva, Cespedes & Jakupovic [Acta Cryst.(1989), C45, 1322–1324], (Ia). The molecule consists of an indolyl ketone fragment and a nested three-ring system, with both groups linked by a C—C bridge. Comparison of both forms shows that they do not differ in their gross features but in the relative orientation of the two ring systems, due to different rotations around the bridge, as measured by the O=C—C=N torsion angle [130.0 (7)° in (Ia) and 161.6 (2)° in (II)]. The resulting slight conformational differences are reflected in a number of intramolecular contacts being observed in (II) but not in (Ia). Regarding intermolecular interactions, both forms share a similar N—H...O synthon but with differing hydrogen-bonding strength, leading in both cases toC(6) catemers with different chain motifs. There are marked differences between the two forms regarding colour and the (de)localization of a double bond, which allows speculation about the possible existence of different variants of this type of molecule.
Building a two-dimensional network from mixed-valence copper units held together by acetone bridges
Authors: Hietsoi Oleksandr , Filatov Alexander S. , Petrukhina Marina A.
Published: November 2013

The mixed-valence supramolecular product di-μ2-acetone-di-μ3-trifluoroacetato-deca-μ2-trifluoroacetato-octacopper(I)dicopper(II), [Cu10(C2F3O2)12(C3H6O)2] or {[CuI4(O2CCF3)4]2–{μ2-OC(CH3)2}2–[CuII2(O2CCF3)4]}, was prepared by co-deposition of two building units, namely a bis-acetone adduct of [CuII2(O2CCF3)4] and a very electrophilic tetranuclear [CuI4(O2CCF3)4] complex. The asymmetric unit contains one molecule of the compound with a total of ten independent Cu atoms. Acetone molecules serve as bridges between the [CuII2(O2CCF3)4] and [CuI4(O2CCF3)4] units. Additionally, the tetracopper(I) trifluoroacetate units are involved in intermolecular Cu...O interactions, forming a layered two-dimensional network in the extended structure.
Bis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato)tetrakis(μ4-1,1,1,5,5,5-hexafluoropentane-2,2,4,4-tetraolato)copper(II)octatin(II): a prospective precursor for Cu-doped SnO2films
Authors: Lieberman Craig M. , Filatov Alexander S. , Vreshch Volodimir D. , Dikarev Evgeny V.
Published: November 2013

The crystal structure of a tin-rich heterometallic supramolecular product, [CuSn8(C5HF6O2)2(C5H2F6O4)4] or [Sn4(hfpt)2–Cu(hfac)2–Sn4(hfpt)2], (I), is reported (hfpt is the tetraanion of 1,1,1,5,5,5-hexafluoropentane-2,2,4,4-tetraol and hfac is the anion of 1,1,1,5,5,5-hexafluoropentane-2,4-dione). Reaction between tin(II) tetraolate, [Sn4(hfpt)2], and copper(II) β-diketonate, [Cu(hfac)2], was utilized for the preparation of (I). The asymmetric unit consists of the whole [Sn4(hfpt)2] unit and half of a [Cu(hfac)2] unit, with the Cu atom lying on an inversion center. Intermolecular Cu...O interactions from the axial positions of copper in [Cu(hfac)2] and O atoms of the hfpt ligand in [Sn4(hfpt)2] mediate the formation of a sandwich-type structure for (I). Additional intermolecular Sn...O interactions between neighbouring [Sn4(hfpt)2] units complete a two-dimensional network.
Coordination polymeric structures in the sodium salt of 4-chloro-3-nitrobenzoic acid and the sodium and potassium salts of 4-nitroanthranilic acid
Authors: Smith Graham
Published: November 2013

The structures of the hydrated sodium salts of 4-chloro-3-nitrobenzoic acid {poly[aqua(μ4-4-chloro-3-nitrobenzoato)sodium(I)], [Na(C7H3ClNO4)(H2O)]n, (I)} and 2-amino-4-nitrobenzoic acid {poly[μ-aqua-aqua(μ3-2-amino-4-nitrobenzoato)sodium(I)], [Na(C7H5N2O4)(H2O)2]n, (II)}, and the hydrated potassium salt of 2-amino-4-nitrobenzoic acid {poly[μ-aqua-aqua(μ5-2-amino-4-nitrobenzoato)potassium(I)], [K(C7H5N2O4)(H2O)]n, (III)} have been determined and their complex polymeric structures described. All three structures are stabilized by intra- and intermolecular hydrogen bonding and strong π–π ring interactions. In the structure of (I), the distorted trigonal bipyrimidal NaO5coordination polyhedron comprises a monodentate water molecule and four bridging carboxylate O-atom donors, generating a two-dimensional polymeric structure lying parallel to (001). Intra-layer hydrogen-bonding associations and strong inter-ring π–π interactions are present. Structure (II) has a distorted octahedral NaO6stereochemistry, with four bridging O-atom donors, two from a single carboxylate group and two from a single nitro group and three from the two water molecules, one of which is bridging. Na centres are linked through centrosymmetric four-membered duplex water bridges and through 18-membered duplex head-to-tail ligand bridges. Similar centrosymmetric bridges are found in the structure of (III), and in both (II) and (III) strong inter-ring π–π interactions are found. A two-dimensional layered structure lying parallel to (010) is generated in (II), whereas in (III) the structure is three-dimensional. With (III), the irregular KO7coordination polyhedron comprises a doubly bridging water molecule, a single bidentate bridging carboxylate O-atom donor and three bridging O-atom donors from the two nitro groups. A three-dimensional structure is generated. These coordination polymer structures are among the few examples of metal complexes of any type with either 4-chloro-3-nitrobenzoic acid or 4-nitroanthranilic acid.
A two-dimensional CuIframework incorporating the 1-phenyl-1H-1,2,3,4-tetrazole-5-thiol ligand
Authors: Zhou Fang-Xia , Yue Cheng-Yang , Zhang Hui-Ping , Lei Xiao-Wu
Published: November 2013

The new two-dimensional coordination polymer, poly[(μ4-1-phenyl-1H-1,2,3,4-tetrazole-5-thiolato)copper(I)], [Cu(C7H5N4S)]n, has been prepared under solvothermal conditions by reacting CuBr with 1-phenyl-1H-1,2,3,4-tetrazole-5-thiol (Hptt) in an acetonitrile and acetone solution. In the crystal structure, each CuIion is coordinated by two N atoms and two S atoms from four ptt−ligands, and each ptt−ligand links four CuIions to form two-dimensional layers which lie parallel to the (100) plane. These layers stack along the [100] directionviavan der Waals interactions.
4,4′-{Diazenediylbis[(1,4-phenylene)bis(carbonyloxy)]}bis(2,2,6,6-tetramethylpiperidinyloxidanyl): the first crystal structure determination from powder data of a nitroxide radical
Authors: Bekö Sándor L. , Thoms Silke D. , Schmidt Martin U.
Published: November 2013

The title compound, C32H42N4O6, is a novel nitroxide radical used for pulsed electron-electron double resonance (PELDOR) spectroscopy. Its crystal structure was determined from laboratory X-ray powder diffraction data. The attractive forces between the molecules in the crystal structure are mainly of dispersive nature. A special interaction of the nitroxide radicals was not observed.
The introduction of the exemption system for foreign profits and its effects on international acquisitions – the UK and Japan regaining international tax competitiveness?
Authors: Hohler Katrin
Published: November 2013

Purpose

– Both, the UK and Japan abolished the tax credit system for foreign source dividends in 2009 in favour of the exemption system. With the move towards a dividend exemption system the governments intended to enhance the international tax competitiveness of their countries. The purpose of this paper is to evaluate the implications of substituting the credit system for the exemption system in the UK and Japan on cross-border transaction prices when competing for international acquisitions.

Design/methodology/approach

– The paper uses an economic model under certainty to analyse the changes in cross-border marginal purchase and seller prices as a result of the introduction of the newly introduced dividend exemption system.

Findings

– Shifting to an exemption system has ambiguous effects on the ability to compete for foreign acquisitions: investors from both countries are able to pay higher prices in the course of acquisitions, but while investors from the UK become more competitive, the relative competitive position for Japanese investors hardly changes and remains relatively constrained, independent of the form of double taxation relief. Thus the author verifies that the international tax regime is not the only determinant influencing the competitive position, ranking second to, e.g., the interaction with international tax rate differentials.

Originality/value

– The international tax reforms in UK and Japan in 2009 offer a unique opportunity to study the impact of international tax policy on the international tax competitiveness of multinational firms in the course of foreign acquisitions. Evidence from this paper is not exclusively applicable to the UK and Japan setting. The observed effects shed new light on the intensified debate in the USA of changing the international tax system by analysing the impact on the bidding situation in international acquisitions in a real-world transition scenario.
Analysis of the performance of agro-based companies in the Nigerian stock exchange
Authors: Akanbi Ayinde Idris , Olayinka S. Ayanwale Abiodun , A. Shittu Musediku , Olufemi Kareem Razak
Published: November 2013

Purpose

– Given the potential of the stock market to provide required capital for agro-based companies, a time series analysis of the performance of major agricultural-based companies in the Nigerian stock exchange (NSE) was carried out.

Design/methodology/approach

– Monthly records of volume of shares traded (VOL) as well as its determinants – current market price (CMP), dividend (DIV), earnings per share (EPS), price-earning ratio (PER), earning yield (EARN) and dividend yield (YIELD) were obtained from the NSE as indicators of performance through 11 years (1998-2008). Non-stationarity of the variables under consideration led to re-conceptualisation of the model as a vector autoregressive (VAR) system. Existence of more than one co-integrating vector in the data through the Johansen test, led to estimation of restricted VAR using the Vector Error Correction Model (VECM) imposing normalisation of VOL and PER.

Findings

– The result of the analysis revealed that VOL is positively related to YIELD and CMP while it is inversely related to EARN, EPS and DIV. On the other hand PER increases with increasing EPS and DIV but reduces with increase in EARN and CMP. Short-run adjustment coefficients were generally large ranging from four months to ten years.

Research limitations/implications

– However, variables coefficients were more elastic in the long run.

Originality/value

– This paper is an original article and has not been done by any other researcher. Furthermore, this paper has not been submitted to any other publishing house prior to this.
Assessing the performance of a supply chain for organic vegetables from a smallholder perspective
Authors: Bhattarai Salil , C. Lyne Michael , K. Martin Sandra
Published: November 2013

Purpose

– The purpose of this paper is to identify factors that constrain marketing choices available to smallholders, limiting the chain's robustness from their perspective.

Design/methodology/approach

– This paper draws on transaction cost economics to develop a model explaining dyadic relationships between smallholders and their buyers. The model was used to analyse a case study of the supply chain for organic fresh vegetables in Kathmandu, Nepal.

Findings

– This chain is characterised mainly by relational contracting between smallholders and their buyers. There was also evidence of vertical integration by some buyers, and of growers selling on informal markets. However, there was no evidence of spot market trading or of conventional contracting. These outcomes were attributed primarily to the absence effective standards and legal systems. Despite this, the chain offered smallholders a range of dyads with different risk-reward trade-offs.

Research limitations/implications

– This paper is based on the findings of a case study. While the results can be generalised to theory, they cannot be generalised to other supply chains.

Originality/value

– This study considers supply-chain performance from the perspective of smallholders. The model proposed for the study extends the traditional vertical coordination continuum to incorporate missing dyads and informal markets.
Integrated services for women through a One Stop Shop: a realist review
Authors: Hardwick Rebecca
Published: November 2013

Purpose

– One Stop Shops (OSSs) are a model of integrated delivery, where a range of needs are met in one place through a bespoke, person-centred service that works across organisational and sectoral boundaries. Third Sector Organisations provide OSSs for women in the criminal justice system and whilst they are shown to be effective in meeting complex needs, how this effectiveness is generated needs explaining. The purpose of this paper is to set out a preliminary framework for explaining their effectiveness.

Design/methodology/approach

– A realist review was conducted to research the way in which context influences how OSSs work. This approach was chosen because it is designed to synthesise evidence on social programmes and policies which are complex. The review was conducted in two phases: theory building and theory refinement.

Findings

– The review explains how individual, interpersonal, institutional and infrastructural contexts influence the effectiveness of OSSs. The evidence suggested that the organisational or legal form of the provider is not as important as the values and attitudes of their staff.

Originality/value

– The paper adds to our understanding of how OSS services work, and gives insight for commissioners and Third Sector providers of services by beginning to explain how this effectiveness is generated.
The effect of online news delivery platform on elements in the communication process
Authors: Caruana Janelle
Published: November 2013

Purpose

– Does the same news item on three different online news platforms, namely: newspapers, blogs and video news, impact each of perceived source credibility, likeability, content believability and attitude toward a message, differently? The paper aims to discuss these issues.

Design/methodology/approach

– An experimental approach conducted among university students is adopted.

Findings

– The psychometric properties of the instruments used are supported. Results showed that source credibility did not differ for the three platforms, indicating that respondents did not find one platform less credible than another. However, differences were observed on each of content believability, likeability and attitude toward the message. Online newspapers scored highest in all of these. Blogs came second in both content believability and likeability, while video news came second in attitude toward a message.

Research limitations/implications

– A number of limitations are noted. In particular, generalisability of findings to all youths in the country and beyond must be done with extreme caution.

Practical implications

– The results suggest that the medium does change the message and online newspapers as a platform retain an advantage despite the arrival of alternative new media platforms, represented by blogs and video news. The latter emerges as the least effective indicating that respondents appear to prefer reading their news.

Originality/value

– The paper uses an experimental approach and robust measures to compare news platforms across a number of elements in the communication process among a strong user segment.
Strategy and co-creation thinking
Authors: Ramaswamy Venkat , Ozcan Kerimcan
Published: November 2013

Purpose

– The authors propose that platforms of stakeholder engagement can become the new basis of enterprise value creation.

Design/methodology/approach

– The authors report on how new co-creation engagement models can be designed all across the value chain of enterprise activities.

Findings

– According to the authors' studies of leading firms, strategy making has become a joint process of co-creative discovery, as enterprises devise and develop new opportunities together with customers, partners and other stakeholders.

Research limitations/implications

– Case examples of implementation at leading companies are offered.

Practical implications

– Leaders will have to manage a process of value creation from a stakeholding-individual and experience-based perspective.

Originality/value

– The article challenges leaders to question why companies should be limited by the internal competencies of the firm when co-creation platforms could provide access to greater competencies through a well-developed global resource base.
A two-model integrated personality disorder service: two-year follow up of effect upon psychiatric bed use
Authors: Jones Barry , Juett Georgia , Hill Nathan
Published: November 2013

Purpose

– Following on from an earlier published study, the purpose of this paper is to further clarify with a larger sample and over a longer timescale of two years the effect of a therapeutic-community informed personality disorder service intervention upon psychiatric in-patient bed use. The service integrates two psychoanalytical models; a mentalization-based treatment (MBT) and a service user network (SUN) model.

Design/methodology/approach

– The number of psychiatric bed days used by patients attending each arm of the service model (SUN and MBT) was collated using the electronic patient records system. Bed use in the six-12-18-and 24-month period before each patient started treatment was compared with bed use in the same periods after starting treatment.

Findings

– There appeared no significant increase after intervention in the group of patients using no psychiatric beds prior to intervention. Bed use in the second group (those using beds prior to intervention) appeared significantly reduced by six months and the reduction continued to prove significant at 12 and 18 months post-intervention. In relation to the component arms of the service, a significant reduction in bed use was seen in each of the MBT and SUN interventions at six, 12, 18 and 24 months after commencement. However, due to the small sample sizes, these results lacked sufficient power to afford a meaningful comment upon the effect of component arms.

Research limitations/implications

– Intervention by the TC informed two-model integrated personality disorder service had a statistically significant effect overall on reducing bed use, which was maintained at six and 12 months.

Practical implications

– The paper supports the finding of the authors’ previous study; a therapeutic model of care that significantly reduces psychiatric bed use. That the reduction in psychiatric bed use continues to further appear highly significant at 18 months suggest that our service has an enduring effect upon inpatient psychiatric resources.

Originality/value

– The paper describes a unique model of care currently successfully employed in the therapeutic management of people with personality disorder. The model is replicable and effective and offers some possibilities for the development of therapeutic-community informed practice.
A genealogy of therapeutic community ideas: the influence of the Frankfurt School with a particular focus on Herbert Marcuse and Eric Fromm
Authors: Winship Gary
Published: November 2013

Purpose

– The purpose of this paper is to construct a genealogy of therapeutic communities (TCs), with the espoused commitment to flattened hierarchies and democratic ideologies, the paper considers the lineage of the Frankfurt School of Social Research and its influence in setting a frame for TC ideology, with a particular focus on Herbert Marcuse and Eric Fromm. This genealogy provides further context to the contribution of two other key Frankfurters, Karl Mannheim and Michael Foulkes, who progressed therapeutic democracy in the UK and shaped the early days of the TC as a group-based treatment paradigm.

Design/methodology/approach

– Discourse analysis and collective biography based on biographical details, texts and witness accounts.

Findings

– The works of Marcuse and Fromm provide a hybrid psychosocial post-Freudian schemas that beckoned philosophic reconciliation between the state and the personal psyche culminating in new left psychoanalytic academic sectors. Eric Fromm's contribution is situated squarely in the clinical sphere in the USA dating from the 1930s after he fled from Germany and settled in the USA where he became a well-known lecturer at Chestnut Lodge during a time when it was developing its approach under the rubric of “milieu therapy”. Marcuse's influence on psychiatry is tracked through the development of ideas and writings emerging from his reading of Freud, finally intersecting with the emergence of TCs and anti-psychiatry when he delivered the keynote address at the Dialectics of Liberation Conference in London in 1967. Held at the height of the first generation of TCs, Joe Berke, R.D. Laing and colleagues considered Marcuse as someone to headline the Dialectics Conference because; “Marcuse was the Grandpapa of Flower Power” (Joe Berke said).

Originality/value

– A rapprochement between milieu therapy in the USA, influenced by Fromm and Marcuse and the European tradition of TCs, influenced by Mannheim and Foulkes is demonstrated. The Frankfurt Institute of Social Research can be seen as an ideological corner that transcends Atlantic divides, and provides a sturdy and lasting intellectual cornerstone for the history of ideas in the field of social psychiatry.
Role of herpes simplex virus 1 Us3 in viral neuroinvasiveness
Authors: Koyanagi Naoto , Imai Takahiko , Arii Jun , Kato Akihisa , Kawaguchi Yasushi
Published: November 2013

Us3 is a serine–threonine protein kinase that is encoded by herpes simplex virus 1 (HSV‐1). In experimental animal models of HSV infection, peripheral and intracranial inoculations can be used to study viral pathogenicity in peripheral sites (e.g., eyes and vagina) and central nervous systems (CNSs), respectively. In addition, peripheral inoculation can be used to investigate this virus' ability to invade the CNS (neuroinvasiveness) from peripheral sites. HSV‐1 Us3 has previously been shown to be critical for viral pathogenicity in both peripheral sites and CNSs of mice. However, the role of HSV‐1 Us3 in viral neuroinvasiveness has not yet been elucidated. In the present study, the yields of a Us3 null mutant virus and its repaired virus in the eyes, trigeminal ganglia, and brains of mice following ocular inoculation were examined. It was found that, although the repaired virus appeared in the brains of mice 3 days after infection, peak replication occurring 7 days after infection, no viral replication of the Us3 null mutant virus was detectable. These findings indicate that HSV‐1 Us3 plays a crucial role in the ability of the virus to invade the brain from the eyes. Thus, HSV‐1 Us3 is a significant neuroinvasiveness factor in vivo.
The evolution of foreign wine demand in China
Authors: Muhammad Andrew , Leister Amanda M. , McPhail Lihong , Chen Wei
Published: November 2013

We estimate source‐differentiated wine demand in China using the absolute price version of the Rotterdam demand system. Within the last decade, China has gone from obscurity to an important participant in global wine trade. The continual growth of Chinese wine imports suggests that a one‐time structural shift approach may not fully capture how consumption patterns or demand preferences have changed over time. Thus, a rolling or moving regression procedure is used to account for continual adjustments in import demand patterns and to evaluate overall parameter instability. Our results confirm that Chinese consumers hold French wine in high regard and that French wine demand has consistently increased over the last decade, more than any other exporting source. Consumers in China have gone from allocating about 1/3 to over 1/2 of every dollar to French wine and the expenditure elasticity for French wine mostly increased while the market was expanding. Although Australian wine has a very solid standing in the Chinese market, results suggest that its market share will likely remain unchanged. Marginal budget share and expenditure elasticity estimates indicate that Australia will continue to account for about 20 per cent of the foreign wine market in China.
The aging signature: a hallmark of induced pluripotent stem cells?
Authors: Rohani Leili , Johnson Adiv A. , Arnold Antje , Stolzing Alexandra
Published: November 2013

The discovery that somatic cells can be induced into a pluripotent state by the expression of reprogramming factors has enormous potential for therapeutics and human disease modeling. With regard to aging and rejuvenation, the reprogramming process resets an aged, somatic cell to a more youthful state, elongating telomeres, rearranging the mitochondrial network, reducing oxidative stress, restoring pluripotency, and making numerous other alterations. The extent to which induced pluripotent stem cell (iPSC)s mime embryonic stem cells is controversial, however, as iPSCs have been shown to harbor an epigenetic memory characteristic of their tissue of origin which may impact their differentiation potential. Furthermore, there are contentious data regarding the extent to which telomeres are elongated, telomerase activity is reconstituted, and mitochondria are reorganized in iPSCs. Although several groups have reported that reprogramming efficiency declines with age and is inhibited by genes upregulated with age, others have successfully generated iPSCs from senescent and centenarian cells. Mixed findings have also been published regarding whether somatic cells generated from iPSCs are subject to premature senescence. Defects such as these would hinder the clinical application of iPSCs, and as such, more comprehensive testing of iPSCs and their potential aging signature should be conducted.
Wildlife consumption and recall accuracy – but is it recall of hunting, of cooking or of eating?
Authors: Newing H. , St. John F. A. V.
Published: November 2013

Read the Feature Paper: Assessing the accuracy of interviewed recall for rare, highly seasonal events: the case of wildlife consumption in Madagascar

Other Commentaries on this paper: Unusual data in conservation science: searching for validation

Response from the authors: Practical directions for the use of recall data in conservation science
Robert Kuok: Family, Dialect, and State in the Making of a Malaysian Magnate
Authors: Hing Lee Kam , Cheok Cheong Kee , Ping Lee Poh
Published: November 2013

Chinese overseas family businesses generally lack longevity. In addition to difficulties in transiting towards professional management they are susceptible to state pressures. However, Robert Kuok, the richest man in Southeast Asia who heads a vast business empire, has been able to surmount both challenges. This study shows how Kuok successfully turned three important sources of identity into strengths: family, dialect, and the state. These three sources are set against his Johor Bahru background, the changing domestic political landscape, and shifting regional economic influence.
Overweight and obese children have lower cortisol levels than normal weight children
Authors: Kjölhede E Allansson , Gustafsson PE , Gustafsson PA , Nelson N
Published: November 2013

Aim

The stress hormone cortisol is vital to survival, and a disturbed circadian rhythm can be deleterious to health. However, little is known about cortisol levels in healthy children. The aim of this study was to examine cortisol levels in relation to body mass index (BMI), age and sex.

Methods

Salivary samples were collected in early morning, late morning and evening, on four consecutive days, from 342 children aged 6–12 years using Salivette® tubes. Samples were analysed using a commercial enzyme immunoassay (EIA). School nurses measured the children's height and weight, and these measurements were used to calculate their BMI.

Results

The children displayed a circadian rhythm in cortisol secretion, with morning zeniths and evening nadirs. Average cortisol levels in early morning, late morning and evening were significantly lower in overweight and obese children than in their normal weight counterparts. Cortisol levels did not vary significantly with age or sex.

Conclusion

Our findings may suggest cortisol suppression in overweight and obese children. We found no evidence that sex or age influences cortisol levels. These findings highlight the need for further research on the relationship between stress and obesity in children.
Captopril and Lisinopril Only Inhibit Matrix Metalloproteinase‐2 (MMP‐2) Activity at Millimolar Concentrations
Authors: Kuntze Luciana B. , Antonio Raquel C. , Izidoro‐Toledo Tatiane C. , Meschiari Cesar A. , Tanus‐Santos Jose E. , Gerlach Raquel F.
Published: November 2013

Matrix metalloproteinase‐2 (MMP‐2) shares structural similarities with the angiotensin‐converting enzyme (ACE). ACE inhibitors have been described to inhibit MMP‐2, but this inhibitory potential was not shown using a highly purified MMP‐2. This study aimed to investigate the inhibitory potential of captopril and lisinopril regarding MMP‐2 activity. The first objective was to test the potential of captopril to change the pH of the buffer solution. The second objective was to test the direct inhibitory effect of captopril and lisinopril on plasma MMP‐2 and on recombinant human MMP‐2 (rhMMP‐2). The in vitro activity assays included gelatin zymography and a fluorimetric assay. Captopril solubilization significantly decreased the pH of the 50 mM Tris buffer solution at the following concentrations: 2 mM (p < 0.05), 4  mM and 8 mM (p < 0.01), while only the 8 mM lisinopril induced a drop in pH (p < 0.05). Thus, only 200 mM buffer solutions were used. Zymography results of plasma MMP‐2 and rhMMP‐2 showed that inhibition only happened at captopril concentrations ≥ 4 and 1 mM, respectively (p < 0.05), while only the higher concentration of lisinopril (8 mM) inhibited plasma MMP‐2 (p < 0.05). In the fluorimetric assay, captopril led to significant inhibition of the rhMMP‐2 activity at concentrations ≥2 mM (p < 0.01), whereas aminophenylmercuric acetate‐activated rhMMP‐2 was inhibited by 0.5 mM captopril (p < 0.01). The captopril and lisinopril concentrations found to inhibit MMP‐2 are 3 orders of magnitude higher than those present in vivo after drug administration. We also discuss possible pitfalls for gelatinase inhibitory assays (besides the obvious pH problem already cited). In conclusion, this study's data show that captopril and lisinopril did not inhibit MMP‐2 directly at the concentrations reached in vivo.
The relationship between post‐traumatic symptom severity and object relations deficits in persons with schizophrenia
Authors: Chapleau Kristine M. , Bell Morris D. , Lysaker Paul H.
Published: November 2013

Objective

The aim of this study was to determine if object relations deficits in people with schizophrenia spectrum disorders (i.e., schizophrenia and schizoaffective disorder) are related to co‐morbid post‐traumatic stress disorder (PTSD).

Design

Cross‐sectional and correlational.

Method

Positive and Negative Syndrome Scale, Post‐Traumatic Stress Disorder Checklist, and Bell Object Relations Inventory were administered to 60 people with schizophrenia in an outpatient setting. With four hierarchical regressions, we hypothesized that, controlling for schizophrenia symptoms, diagnosis type, and potential demographic features, PTSD symptoms would correlate with each of the four types of object relations deficits.

Results

All participants reported experiencing at least one traumatic experience. As predicted, PTSD symptoms were a significant predictor of alienation, insecure attachment, and egocentricity controlling for schizophrenia symptoms, diagnosis type, and demographic features. Against prediction, PTSD was not associated with Social Incompetence.

Conclusion

If PTSD symptoms contribute to object relations deficits in persons with schizophrenia spectrum disorders, then interventions such as psychotherapy need to be developed to address PTSD symptoms in the treatment of these interpersonal deficits.

Practitioner points

Clinical implications

Post‐traumatic stress disorder symptoms, rather than schizophrenia itself, may explain increased problems with schizophrenia patients' alienation, egocentricity, and insecure attachment.

Interventions such as psychotherapy need to be further developed to address PTSD symptoms as well as schizophrenia symptoms in this patient population.

Limitations

Participants were primarily male and middle‐aged, and many years had passed since the onset of their illness. Replication is needed with diverse settings and participants, including women and persons in earlier phases of schizophrenia spectrum disorders.

One self‐report measure was used to estimate object relations deficits, a complex construct that may be difficult to measure accurately.

This research is correlational and causation cannot be presumed.
Exploring new potentials of blogs for learning: Can children use blogs for personal information management (PIM)?
Authors: Yeo Hwan‐Ik , Lee Yekyung Lisa
Published: November 2013

This study explores the use of blogs for personal information management (PIM) as a learning tool that could bring increased efficiency and academic self‐efficacy for carrying out learning tasks. In order to identify the uses and effects of using blogs for PIM by children, a control group that used personal spaces within the class website and an experiment group that used personal blogs both posted their resources online (personal space within class website or blog) to use in their class assignments. Comparison of both groups demonstrate that when children used blogs for PIM their academic their self‐efficacy increased, their personalization of blogs made it easier to use collected resources and they became more actively engaged in tasks as well. This study suggests that using individual blogs for PIM can create personally meaningful contexts of learning for children.
Two‐ and Three‐dimensional Rings in Drugs
Authors: Aldeghi Matteo , Malhotra Shipra , Selwood David L. , Chan Ah Wing Edith
Published: November 2013

Using small, flat aromatic rings as components of fragments or molecules is a common practice in fragment‐based drug discovery and lead optimization. With an increasing focus on the exploration of novel biological and chemical space, and their improved synthetic accessibility, 3D fragments are attracting increasing interest. This study presents a detailed analysis of 3D and 2D ring fragments in marketed drugs. Several measures of properties were used, such as the type of ring assemblies and molecular shapes. The study also took into account the relationship between protein classes targeted by each ring fragment, providing target‐specific information. The analysis shows the high structural and shape diversity of 3D ring systems and their importance in bioactive compounds. Major differences in 2D and 3D fragments are apparent in ligands that bind to the major drug targets such as GPCRs, ion channels, and enzymes.
Effects of Janus kinase inhibitor tofacitinib on circulating serum amyloid A and interleukin-6 during treatment for rheumatoid arthritis
Authors: Migita K , Izumi Y , Jiuchi Y , Kozuru H , Kawahara C , Izumi M , Sakai T , Nakamura M , Motokawa S , Nakamura T , Kawakami A
Published: November 2013

The Janus kinase inhibitor tofacitinib is currently being investigated as a disease-modifying agent in rheumatoid arthritis (RA). We investigated the in-vivo effects of tofacitinib treatment for 4 weeks on elevated circulating acute-phase serum amyloid (SAA) levels in 14 Japanese patients with RA. SAA levels fell from 110·5 ± 118·5 μg/ml (mean ± standard deviation) at treatment initiation to 15·3 ± 13·3 μg/ml after 4 weeks treatment with tofacitinib. The reduction in SAA levels was greater in patients receiving tofacitinib plus methotrexate compared with those receiving tofacitinib monotherapy. Tofacitinib was also associated with reduced serum interleukin (IL)-6, but had no effect on serum levels of soluble IL-6 receptor. Patients were divided into groups with adequate (normalization) and inadequate SAA responses (without normalization). Serum IL-6 levels were reduced more in the group with adequate SAA response compared with those with inadequate SAA response. These results suggest that tofacitinib down-regulates the proinflammatory cytokine, IL-6, accompanied by reduced serum SAA levels in patients with active RA. The ability to regulate elevated serum IL-6 and SAA levels may explain the anti-inflammatory activity of tofacitinib.
Molecular and cellular mechanisms of development underlying congenital diseases
Authors: Hashimoto Masakazu , Morita Hitoshi , Ueno Naoto
Published: November 2013

In the last several decades, developmental biology has clarified the molecular mechanisms of embryogenesis and organogenesis. In particular, it has demonstrated that the “tool‐kit genes” essential for regulating developmental processes are not only highly conserved among species, but are also used as systems at various times and places in an organism to control distinct developmental events. Therefore, mutations in many of these tool‐kit genes may cause congenital diseases involving morphological abnormalities. This link between genes and abnormal morphological phenotypes underscores the importance of understanding how cells behave and contribute to morphogenesis as a result of gene function. Recent improvements in live imaging and in quantitative analyses of cellular dynamics will advance our understanding of the cellular pathogenesis of congenital diseases associated with aberrant morphologies. In these studies, it is critical to select an appropriate model organism for the particular phenomenon of interest.
Changes in management and outcome of patients with rectal cancer in Northern Ireland: 1996–2006
Authors: McClements J. , Fitzpatrick D. , Campbell W. J. , Gavin A.
Published: November 2013

Aim

This study aimed to document developments in rectal cancer services in a UK population and evaluate changes in outcome over a 10‐year period.

Method

Patients diagnosed with primary rectal carcinoma in 1996, 2001 and 2006 were identified by the Northern Ireland Cancer Registry. Data were retrospectively collected on presentation, investigation, treatment and staging. Differences over the period were analysed using the chi‐squared test; Kaplan–Meier and Cox regression tests were used for survival analysis.

Results

After exclusions there were 636 patients, including 187 presenting in 1996, 203 in 2001 and 246 in 2006. The use of preoperative MRI of the rectum, endorectal ultrasound and abdominal CT increased during the study period. For patients treated by surgery, total mesorectal excision (TME) increased from 19% in 1996 to 64% in 2006 (P < 0.001). The use of radiotherapy (27% in 1996, 47% in 2006) and chemotherapy (21% in 1996, 32% in 2006) increased. The overall 5‐year survival improved significantly between 1996 and 2006 from 34% in 1996 to 45% in 2006 (P = 0.02). Among patients having surgery, 5‐year survival increased from 43% in 1996 to 63% in 2006 (P < 0.001). Multivariate analysis showed that the improvement in survival was associated with TME and chemotherapy, while radiotherapy was not.

Conclusion

Survival of patients with rectal cancer in Northern Ireland has improved significantly over the last decade, probably due to the increased use of TME and chemotherapy.
A prospective, claims‐based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs
Authors: Funch D. , Gydesen H. , Tornøe K. , Major‐Pedersen A. , Chan K. A.
Published: November 2013

Aim

We evaluated the relationship between liraglutide and acute pancreatitis or pancreatic cancer in an ongoing post‐marketing safety assessment programme.

Methods

Initiators of liraglutide, exenatide, metformin, pioglitazone or groups containing initiators of dipeptidyl peptidase‐4 inhibitors or sulfonylureas were identified in a US commercial health insurance claims database (1 February 2010 to 31 March 2013) and followed for a median of 15 months. We estimated incidence rates (IR/100 000 person‐years), rate ratio (RR) and 95% confidence intervals (CI) of new insurance claims with diagnoses of primary inpatient acute pancreatitis or pancreatic cancer from Poisson regression models.

Results

The IR for acute pancreatitis for liraglutide was 187.5 compared with 154.4 for all non‐glucagon‐like peptide‐1 (GLP‐1)‐based therapies (adjusted RR 1.10; CI 0.81–1.49). The IR for pancreatic cancer was 19.9 for liraglutide compared with 33.0 for all non‐GLP‐1‐based therapies (adjusted RR 0.65; 95% CI 0.26–1.60).

Conclusion

We did not observe excess risk of either outcome associated with liraglutide relative to individual or pooled comparator drugs.
Pulmonary Hypertension in Hypertensive Patients: Association with Diastolic Dysfunction and Increased Pulmonary Vascular Resistance
Authors: Mukherjee Monica , Mehta Nishaki K. , Connolly James J. , Dusaj Raman S. , Choi Brian G. , Katz Richard J. , Lewis Jannet F.
Published: November 2013

Background

Pulmonary hypertension (PH) in patients with systemic hypertension and preserved ejection fraction (PEF) has been described. However, the pathophysiology and consequences are not entirely clear. We sought to distinguish the clinical and anatomic features among hypertensive patients with or without coexistent PH.

Methods

Echocardiograms and records of hypertensive patients with left ventricular (LV) hypertrophy and PEF from January 2009 to January 2011 were reviewed. We identified 174 patients, including 36 with PH (calculated pulmonary artery systolic pressure [PASP] ≥ 35 mmHg), and 138 with normal pulmonary pressures.

Results

Hypertensive patients with PH were older (76 ± 13 vs. 65 ± 13 years, P < 0.0001), more often female (91, 70%), had lower estimated glomerular filtration rate (eGFR) (63 ± 44 vs. 88 ± 48 mL/min, P = 0.002), and higher pro‐BNP levels (3141 ± 4253 vs. 1219 ± 1900 pg/mL, P = 0.003). PH patients also had larger left atrial areas (23.7 ± 3.8 vs. 20.8 ± 4.6 cm2, P = 0.002), evidence of diastolic dysfunction (i.e., septal E/e′ 17.6 ± 8.6 vs. 12.7 ± 4.4, P = 0.0005), and higher calculated peripheral vascular resistance (PVR) (2.3 ± 1.1 vs. 1.6 ± 0.4, P < 0.0001). Both PVR and septal E/e′ showed strong linear correlation with PASP (P < 0.0001 and P < 0.0001, respectively).

Conclusions

Hypertension in elderly patients is frequently complicated by LV diastolic dysfunction and secondary PH. These hypertensive patients tended to have reduced renal function and higher pro‐BNP. Because of the known morbidity and mortality associated with PH, these observations have potentially important implications for target medical therapy.
Expression and cellular localization of the classical progesterone receptor in healthy and amyotrophic lateral sclerosis affected spinal cord
Authors: Gargiulo‐Monachelli G. M. , Campos‐Melo D. , Droppelmann C. A. , Keller B. A. , Leystra‐Lantz C. , De Nicola A. F. , Gonzalez Deniselle M. C. , Volkening K. , Strong M. J.
Published: November 2013

Background and purpose

Previous studies have suggested that elevated progesterone levels are associated with a slower disease course in amyotrophic lateral sclerosis (ALS). Given that the effects of progesterone are mediated in part by the classical progesterone receptor (PR), the expression and cellular localization of the A and B isoforms (PR‐A and PR‐B, respectively) of the PR in control (neuropathologically normal) and ALS‐affected spinal cord (SC) were examined.

Methods

Semi‐quantitative RT‐PCR, immunohistochemistry and immunofluorescence analyses of the cervical and lumbar SC of post‐mortem ALS patients (n = 19) and control subjects (n = 10) were performed. Primers and antibodies used allowed the detection of both PR‐A and PR‐B isoforms together (PR‐A+B) or PR‐B isoform alone.

Results

Lumbar PR‐A+B and cervical PR‐B mRNA expression were significantly higher in ALS than controls. In both ALS and controls, PR‐A+B immunoreactivity (IR) was occasionally detected in motor neurons. In contrast, PR‐A+B IR was prominent in axonal processes and vessels. This was more evident in nerve roots and large arteries in ALS compared with controls. Colocalization of PR‐A+B with markers of neurons, axonal processes and vascular endothelium was also observed.

Conclusions

Evidence that both PR‐A and PR‐B isoforms are expressed in the human SC is provided, with some regional variation in isoform expression between ALS and controls. The IR was more prominent in nerve roots and large arteries in ALS, suggesting a potential role in the degenerative process.