bluuebunny/crossref_metadata_2025 huggingface dataset:
ORGANISATIONAL COMMITMENT IN THE POLICE SERVICE: EXPLORING THE EFFECTS OF PERFORMANCE MEASURES, PROCEDURAL JUSTICE AND INTERPERSONAL TRUST
Authors: Sholihin Mahfud , Pike Richard
Published: October 2010

This study aims to investigate whether, and how, the use of performance measures, procedural justice, and interpersonal trust interact to affect organisational commitment of police officers. Drawing on a survey based on a sample of 57 senior officers within a single police force, we find that the use of performance measures, procedural justice, and interpersonal trust are positively associated with organisational commitment. Further analysis reveals that trust between officer and superior mediates the relationship between the use of non‐financial measures and organisational commitment, but procedural justice does not have a mediating effect on commitment. These findings are further explored through selected interviews with respondents.
THE HEALTHCARE VOUCHER: EMERGENCE, FORMATION AND DISSEMINATION
Authors: Nordgren Lars
Published: October 2010

Market‐inspired healthcare reforms have been introduced in Sweden: Freedom of Choice in Healthcare in 1989 and the National Healthcare Guarantee in 2005. After the general election 2006 the idea of the Healthcare Voucher has followed. Built on a theoretical framework composed of Foucault's concept of 'discursive formation' supported by Butler's concept of the ‘performativity of discourse’ the purpose is to analyse the emergence, formation and dissemination of this idea into healthcare in Sweden. The Voucher is disseminated in a form reminiscent of a chain linking a series of texts, referring to each other and building on each other's formulations strengthening each other's messages. It circulates under designations such as healthcare voucher and money and seems to be disseminated by being combined with 'freedom of choice' forming the theme customer choice. The Healthcare Voucher then becomes a means of being able to realise an idea of a political nature, building markets in healthcare. The paper offers a way of analysing how ideas influence the policy agenda, in particular for the voucher/s. Distinctions could be made between the voucher idea and 'money following the patient' in quasi markets. A critical issue in introducing choice and competition, not explored here, is the issue of ‘cream skimming’.
Genomic profiling of carbohydrate metabolism in the ectomycorrhizal fungus Tuber melanosporum
Authors: Ceccaroli P. , Buffalini M. , Saltarelli R. , Barbieri E. , Polidori E. , Ottonello S. , Kohler A. , Tisserant E. , Martin F. , Stocchi V.
Published: October 2010

Featured paper: See also the Editorial by Martin
Evidence for a deficit in volitional action generation in patients with obsessive‐compulsive disorder
Authors: Kloft Lisa , Kischkel Eva , Kathmann Norbert , Reuter Benedikt
Published: October 2010

Obsessive‐compulsive disorder (OCD) patients show deficits in tasks of executive functioning like the antisaccade (AS) task. These deficits suggest problems in response inhibition or volitional saccade generation. Thirty patients (15 nonmedicated) and 30 healthy subjects performed antisaccades and simple volitional saccades (SVS), that is, centrally cued saccades. In SVS, two aspects of volitional saccade generation were disentangled: response selection and initiation. Latencies of OCD patients were increased in volitional saccades independent of response selection demands. AS performance did not differ. Across groups, latencies in AS were faster than in SVS. Medicated patients did not differ from nonmedicated patients. In sum, response initiation is deficient in OCD patients, which may reflect a general problem in volitional action generation. This deficit did not affect antisaccade performance, possibly due to a lower volitional demand in that task.
Habituation in neural processing and subjective perception of respiratory sensations
Authors: Von Leupoldt Andreas , Vovk Andrea , Bradley Margaret M. , Lang Peter J. , Davenport Paul W.
Published: October 2010

Reduced perception of respiratory sensations is associated with negative treatment outcome in asthma. We examined whether habituation in the neural processing of repeatedly experienced respiratory sensations may underlie subjective reports of reduced respiratory perception. Respiratory‐related evoked potentials (RREP) elicited by inspiratory occlusions and reports of respiratory perception were compared between early and late experimental periods in healthy subjects. Reports of respiratory perception were reduced during late, compared to early, experimental periods. This was paralleled by reduced magnitudes in RREP components N1, P2, and P3 in late, compared to early, experimental periods. Habituation in the neural processing of respiratory sensations is a potential mechanism that underlies subjective reports of reduced respiratory perception and might represent a risk factor for reduced perception of respiratory sensations in asthma.
Parental care trade‐offs in the inter‐brood phase in Barn SwallowsHirundo rustica
Authors: NAEF‐DAENZER LUZIA , GRÜEBLER MARTIN U. , NAEF‐DAENZER BEAT
Published: October 2010

In seasonal environments with limited time and energy resources, double‐brooded birds face trade‐offs in the timing of their two reproductive attempts and in the effort allocated to the first and the second broods. In the Barn SwallowHirundo rusticaa long care period for the first brood enhances the survival of first‐brood chicks, but also delays the start of the second brood, which in turn reduces the survival prospects of second‐brood chicks. Probably as a response to this trade‐off, double‐brooded Barn Swallows reduce the period of post‐fledging care for first‐brood fledglings. By radiotracking whole families, we investigated the determinants of this behaviour and its consequences for the survival of the first‐brood fledglings. The end of the females’ investment in post‐fledging care of the first brood was related to the beginning of egg synthesis for the second clutch. With the start of egg synthesis, females significantly reduced provisioning rates to the first‐brood fledglings to less than one‐fifth of the previous rates, while the proportion of time they spent foraging remained high. Assuming that the females’ foraging success was constant, we conclude that their energy income was allocated to egg production rather than fledgling provision. Males did not compensate for the females’ reduced feeding rates. Thus the start of egg production for the second clutch had a marked effect on the quantity of food received by first‐brood fledglings. In parallel with the changes in parental behaviour and provisioning rates, we observed a marked drop in the daily survival rate of first‐brood chicks. These results support the hypothesis that females face a strong trade‐off in the allocation of energy to subsequent broods. Energy allocation to a second clutch involves a cost in terms of reduced provisioning, and as a result the survival of first‐brood chicks is compromised. This is probably outweighed by the improved success of an early second brood.
The nutritional significance of a winter‐flowering succulent for opportunistic avian nectarivores
Authors: SYMES CRAIG T. , MCKECHNIE ANDREW E. , NICOLSON SUSAN W. , WOODBORNE STEPHAN M.
Published: October 2010

The winter‐flowering succulent Aloe marlothii provides nectar for many opportunistic avian nectarivores in southern African savannas. We assessed the importance of A. marlothii nectar sugar for opportunistic nectarivores by analysing temporal changes in stable carbon isotope ratios (δ13C) in the tissues of birds in Suikerbosrand Nature Reserve, South Africa. The blood of the 11 most common non‐granivorous opportunistic nectarivores at our site was enriched in 13C by 3.4 ± 1.5‰ during the flowering period of A. marlothii, reflecting the enriched crassulacean acid metabolism (CAM) isotopic signature of nectar (−12.6 ± 0.5‰). This relatively small contribution of A. marlothii nectar to assimilated carbon in whole blood contrasted with that of exhaled CO2 in African Red‐eyed Bulbuls Pycnonotus nigricans and Cape White‐eyes Zosterops capensis. In both these species, the δ13C of breath samples was significantly enriched compared with blood and feathers, and closely resembled that of the nectar, revealing combustion of ingested nectar rather than assimilation. Although our analysis was complicated by the presence of C4 grasses, whose δ13C values are similar to those of CAM photosynthesizers, when considered with previously published feeding observations our data reveal that opportunistic nectarivores feeding on A. marlothii nectar obtain a relatively small fraction of their assimilated carbon, but most of their metabolized carbon, from this seasonally available carbohydrate food resource. Because the δ13C values of insects associated with C3 plants also became enriched during the flowering season, some insect‐eating opportunistic nectarivores may have assimilated A. marlothii carbon indirectly from insects. This study highlights the importance of understanding isotopic routing when assessing the nutritional significance of specific dietary items to consumer communities.
A radiotelemetry study of habitat use by the exotic Ring‐necked Parakeet Psittacula krameri in Belgium
Authors: STRUBBE DIEDERIK , MATTHYSEN ERIK
Published: October 2010

Little is known about the foraging ecology of invasive bird species in Europe. We used radio‐telemetry to assess home‐ranges of breeding male Ring‐necked Parakeets in Brussels. Results indicate that parakeets primarily forage in parks and gardens while avoiding forests. This can probably be explained by the higher food availability in anthropogenic habitats and fits a general pattern that invasive species generally select heavily altered environments.
RADIOCARBON DATING ARCHAEOLOGICAL SAMPLES IN THE EASTERN MEDITERRANEAN, 1730 TO 1480 BC: FURTHER EXPLORING THE ATMOSPHERIC RADIOCARBON CALIBRATION RECORD AND THE ARCHAEOLOGICAL IMPLICATIONS*
Authors: MANNING S. W. , KROMER B.
Published: October 2010

The East Mediterranean Radiocarbon (Inter‐)Comparison Project (EMRCP) has measured time series of radiocarbon ages for known age samples of German oak (GeO) and for samples from the near‐absolutely placed Gordion juniper dendrochronology from central Anatolia. In this paper, we review the data for the calendar years from 1730 to 1480 bc, relevant in particular to controversy and debate concerning the absolute date of the Minoan eruption of the Santorini (Thera) volcano. We consider the issue of the radiocarbon (14C) dating of the Santorini eruption, and the problem of how this relates to the archaeological record and historical chronology of Egypt in light of the 14C data. We find that these 14C data, and other recent radiocarbon work, provide good grounds to be confident in the possibility of a robust radiocarbon‐based chronology for the eastern Mediterranean. In contrast, as the radiocarbon case becomes stronger, questions must be asked about some archaeological dating: in particular, at the site of Tell el‐Dab‘a in the Nile Delta of Egypt.
Pharmacological characterization of six trkB antibodies reveals a novel class of functional agents for the study of the BDNF receptor
Authors: Cazorla M , Arrang JM , Prémont J
Published: October 2010

BACKGROUND AND PURPOSEBy interacting with trkB receptors, brain‐derived neurotrophic factor (BDNF) triggers various signalling pathways responsible for neurone survival, differentiation and modulation of synaptic transmission. Numerous reports have implicated BDNF and trkB in the pathogenesis of various central nervous system affections and in cancer, thus representing trkB as a promising therapeutic target. In this study, we used an antibody‐based approach to search for trkB‐selective functional reagents.

EXPERIMENTAL APPROACHSix commercially available polyclonal and monoclonal antibodies were tested on recombinant and native, human and rodent trkB receptors. Functional and pharmacological characterization was performed using a modified version of the KIRA‐elisamethod and radioligand binding studies. Western blot analyses and neurite outgrowth assays were carried out to determine the specificity and selectivity of antibody effects. The survival properties of one antibody were further assessed on cultured neurones in a serum‐deprived paradigm.

KEY RESULTSThe functional trkB‐selective antibodies showed distinct pharmacological profiles, ranging from partial agonists to antagonists, acting on trkB receptors through allosteric modulations. The same diversity of effects was observed on the mitogen‐activated protein kinase signalling pathway downstream of trkB and on the subsequent neurite outgrowth. One antibody with partial agonist activity demonstrated cell survival properties by activating the Akt pathway. Finally, these antibodies were functionally validated as true trkB‐selective ligands because they failed activating trkA or trkC, and contrary to BDNF, none of them bind to p75NTR.

CONCLUSIONS AND IMPLICATIONSThese trkB‐selective antibodies represent a novel class of pharmacological tools to explore the pathophysiological roles of trkB and its potential therapeutic relevance for the treatment of various disorders.
Nrf2‐mediated liver protection by sauchinone, an antioxidant lignan, from acetaminophen toxicity through the PKCδ‐GSK3β pathway
Authors: Kay Hee Yeon , Kim Young Woo , Ryu Da Hye , Sung Sang Hyun , Hwang Se Jin , Kim Sang Geon
Published: October 2010

BACKGROUND AND PURPOSE Sauchinone, an antioxidant lignan, protects hepatocytes from iron‐induced toxicity. This study investigated the protective effects of sauchinone against acetaminophen (APAP)‐induced toxicity in the liver and the role of nuclear factor erythroid‐2‐related factor‐2 (Nrf2) in this effect.

EXPERIMENTAL APPROACH Blood biochemistry and histopathology were assessed in mice treated with APAP or APAP + sauchinone. The levels of mRNA and protein were measured using real‐time PCR assays and immunoblottings.

KEY RESULTS Sauchinone ameliorated liver injury caused by a high dose of APAP. This effect was prevented by a deficiency of Nrf2. Sauchinone treatment induced modifier subunit of glutamate‐cysteine ligase, NAD(P)H:quinone oxidoreductase‐1 (NQO1) and heat shock protein 32 in the liver, which was abolished by Nrf2 deficiency. In a hepatocyte model, sauchinone activated Nrf2, as evidenced by the increased nuclear accumulation of Nrf2, the induction of NQO1‐antioxidant response element reporter gene, and glutamate‐cysteine ligase and NQO1 protein induction, which contributed to the restoration of hepatic glutathione content. Consistently, treatment of sauchinone enhanced Nrf2 phosphorylation with a reciprocal decrease in its interaction with Kelch‐like ECH‐associated protein‐1. Intriguingly, sauchinone activated protein kinase C‐δ (PKCδ), which led to Nrf2 phosphorylation. In addition, it increased the inhibitory phosphorylation of glycogen synthase kinase‐3β (GSK3β), derepressing Nrf2 activity, which was supported by the reversal of sauchinone's activation of Nrf2 by an activated mutant of GSK3β. Moreover, phosphorylation of GSK3β by sauchinone depended on PKCδ activation.

CONCLUSION AND IMPLICATIONS Our results demonstrate that sauchinone protects the liver from APAP‐induced toxicity by activating Nrf2, and this effect is mediated by PKCδ activation, which induces inhibitory phosphorylation of GSK3β.
Characterization of RO4583298 as a novel potent, dual antagonist within vivoactivity at tachykinin NK1and NK3receptors
Authors: Malherbe P , Knoflach F , Hernandez MC , Hoffmann T , Schnider P , Porter RH , Wettstein JG , Ballard TM , Spooren W , Steward L
Published: October 2010

BACKGROUND AND PURPOSEClinical results of osanetant and talnetant (selective‐NK3antagonists) indicate that blocking the NK3receptor could be beneficial for the treatment of schizophrenia. The objective of this study was to characterize thein vitroandin vivoproperties of a novel dual NK1/NK3antagonist, RO4583298 (2‐phenyl‐N‐(pyridin‐3‐yl)‐N‐methylisobutyramide derivative).

EXPERIMENTAL APPROACHRO4583298in vitropharmacology was investigated using radioligand binding ([3H]‐SP, [3H]‐osanetant, [3H]‐senktide), [3H]‐inositol‐phosphate accumulation Schild analysis (SP‐ or [MePhe7]‐NKB‐induced) and electrophysiological studies in guinea‐pig substantia nigra pars compacta (SNpc). Thein vivoactivity of RO4583298 was assessed using reversal of GR73632‐induced foot tapping in gerbils (GFT; NK1) and senktide‐induced tail whips in mice (MTW; NK3).

KEY RESULTSRO4583298 has a high‐affinity for NK1(human and gerbil) and NK3(human, cynomolgus monkey, gerbil and guinea‐pig) receptors and behaves as a pseudo‐irreversible antagonist. Unusually it binds with high‐affinity to mouse and rat NK3, yet with a partial non‐competitive mode of antagonism. In guinea‐pig SNpc, RO4583298 inhibited the senktide‐induced potentiation of spontaneous activity of dopaminergic neurones with an apparent non‐competitive mechanism of action. RO4583298 (p.o.) robustly blocked the GFT response, and inhibited the MTW.

CONCLUSIONS AND IMPLICATIONSRO4583298 is a high‐affinity, non‐competitive, long‐actingin vivoNK1/NK3antagonist; hence providing a usefulin vitroandin vivopharmacological tool to investigate the roles of NK1and NK3receptors in psychiatric disorders.
Cyclic AMP‐dependent inotropic effects are differentially regulated by muscarinic Gi‐dependent constitutive inhibition of adenylyl cyclase in failing rat ventricle
Authors: Hussain RI , Afzal F , Mørk HK , Aronsen JM , Sjaastad I , Osnes J‐B , Skomedal T , Levy FO , Krobert KA
Published: October 2010

BACKGROUND AND PURPOSEβ‐Adrenoceptor (β‐AR)‐mediated inotropic effects are attenuated and Giproteins are up‐regulated in heart failure (HF). Muscarinic receptors constitutively inhibit cAMP formation in normal rat cardiomyocytes. We determined whether constitutive activity of muscarinic receptors to inhibit adenylyl cyclase (AC) increases in HF and if so, whether it modifies the reduced β‐AR‐ or emergent 5‐HT4‐mediated cAMP‐dependent inotropic effects.

EXPERIMENTAL APPROACHContractility and AC activity were measured and related to each other in rat ventricle with post‐infarction HF and sham‐operated (Sham) controls with or without blockade of muscarinic receptors by atropine and inactivation of Giprotein by pertussis toxin (PTX).

KEY RESULTSIsoprenaline‐mediated inotropic effects were attenuated and basal, isoprenaline‐ and forskolin‐stimulated AC activity was reduced in HF compared with Sham. Atropine or PTX pretreatment increased forskolin‐stimulated AC activity in HF hearts. β‐AR‐stimulated AC and maximal inotropic response were unaffected by atropine in Sham and HF. In HF, the potency of serotonin (5‐HT) to evoke an inotropic response was increased in the presence of atropine with no change in the maximal inotropic response. Interestingly, PTX pretreatment reduced the potency of 5‐HT to evoke inotropic responses while increasing the maximal inotropic response.

CONCLUSIONS AND IMPLICATIONSAlthough muscarinic constitutive inhibition of AC is increased in HF, it does not contribute to the reduced β‐AR‐mediated inotropic effects in rat ventricle in HF. The data support the hypothesis that there are differences in the functional compartmentation of 5‐HT4and β‐AR AC signalling in myocardium during HF.
Melanocortins protect against multiple organ dysfunction syndrome in mice
Authors: Bitto Alessandra , Polito Francesca , Altavilla Domenica , Irrera Natasha , Giuliani Daniela , Ottani Alessandra , Minutoli Letteria , Spaccapelo Luca , Galantucci Maria , Lodi Renzo , Guzzo Giuseppe , Guarini Salvatore , Squadrito Francesco
Published: October 2010

BACKGROUND AND PURPOSEMelanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve‐mediated cholinergic anti‐inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple organ damage following systemic inflammatory response, here we investigated the effects of the melanocortin analogue [Nle4, D‐Phe7]α‐MSH (NDP‐α‐MSH) in a widely used murine model of multiple organ dysfunction syndrome (MODS).

EXPERIMENTAL APPROACHMODS was induced in mice by a single intraperitoneal injection of lipopolysaccharide followed, 6 days later (= day 0), by zymosan. After MODS or sham MODS induction, animals were randomized to receive intraperitoneally NDP‐α‐MSH (340 µg·kg−1day) or saline for up to 16 days. Additional groups of MODS mice were concomitantly treated with the melanocortin MC4receptor antagonist HS024, or the nicotinic acetylcholine receptor antagonist chlorisondamine, and NDP‐α‐MSH.

KEY RESULTSAt day 7, in the liver and lung NDP‐α‐MSH, significantly reduced mRNA expression of tumour necrosis factor‐α (TNF‐α), increased mRNA expression of interleukin‐10 and improved the histological picture, as well as reduced TNF‐α plasma levels; furthermore, NDP‐α‐MSH dose‐dependently increased survival rate, as assessed throughout the 16 day observation period. HS024 and chlorisondamine prevented all the beneficial effects of NDP‐α‐MSH in MODS mice.

CONCLUSIONS AND IMPLICATIONSThese data indicate that NDP‐α‐MSH protects against experimental MODS by counteracting the systemic inflammatory response, probably through brain MC4receptor‐triggered activation of the cholinergic anti‐inflammatory pathway. These findings reveal previously undescribed effects of melanocortins and could have clinical relevance in the MODS setting.
Treatment of rheumatoid arthritis with tumour necrosis factor inhibitors
Authors: Mewar Devesh , Wilson Anthony G
Published: October 2010

Advances in our understanding of the key mediators of chronic inflammation and tissue damage characteristic of rheumatoid arthritis (RA) have resulted in the development of novel therapies primarily targeting pro‐inflammatory cytokines. Inhibitors of tumour necrosis factor (TNF) are the most widely used of the biological therapies at present with five different agents currently available; four are based on monoclonal anti‐TNF antibodies and a soluble TNF receptor‐Fc fusion protein. Long‐term use of these molecules has proven to be highly effective in the majority of patients; however, around one‐third have a suboptimal response potentially leading to further cartilage and bone damage, furthermore these agents are expensive compared with conventional therapies such as methotrexate. Many recent studies have attempted to identify therapeutic response biomarkers of TNF inhibitors which could be used to improve therapeutic targeting. The presence of rheumatoid factor and anti‐cyclic citullinated protein antibodies, present in around 65% of RA patients, are associated with a poorer response to anti‐TNF agents. Poorer response is also associated with levels of C‐reactive protein and cartilage degradation product at initiation of treatment. Intriguingly, genetic studies of variants of TNF and of genes encoding members of the Toll‐like receptors, nuclear factor‐kappa B and p38 mitogen‐activated protein kinase signalling families have been associated with response to individual anti‐TNF agents. Continued advances in technologies such as ultra high throughput sequencing and proteomics should facilitate the discovery of additional biomarkers of response to anti‐TNF resulting in improved disease control and quality of life for RA patients and reduced costs for healthcare funders.
Therapy‐related myeloid neoplasms: pathobiology and clinical characteristics
Authors: Sill H , Olipitz W , Zebisch A , Schulz E , Wölfler A
Published: October 2010

Therapy‐related myeloid neoplasms (t‐MNs) are serious long‐term consequences of cytotoxic treatments for an antecedent disorder. t‐MNs are observed after ionizing radiation as well as conventional chemotherapy including alkylating agents, topoisomerase‐II‐inhibitors and antimetabolites. In addition, adjuvant use of recombinant human granulocyte‐colony stimulating factor may also increase the risk of t‐MNs. There is clinical and biological overlap between t‐MNs and high‐risk de novo myelodysplastic syndromes and acute myeloid leukaemia suggesting similar mechanisms of leukaemogenesis. Human studies and animal models point to a prominent role of genetic susceptibilty in the pathogenesis of t‐MNs. Common genetic variants have been identified that modulate t‐MN risk, and t‐MNs have been observed in some cancer predisposition syndromes. In either case, establishing a leukaemic phenotype requires acquisition of somatic mutations – most likely induced by the cytotoxic treatment. Knowledge of the specific nature of the initiating exposure has allowed the identification of crucial pathogenetic mechanisms and for these to be modelled in vitro and in vivo. Prognosis of patients with t‐MNs is dismal and at present, the only curative approach for the majority of these individuals is haematopoietic stem cell transplantation, which is characterized by high transplant‐related mortality rates. Novel transplantation strategies using reduced intensity conditioning regimens as well as novel drugs – demethylating agents and targeted therapies – await clinical testing and may improve outcome. Ultimately, individual assessment of genetic risk factors may translate into tailored therapies and establish a strategy for reducing t‐MN incidences without jeopardizing therapeutic success rates for the primary disorders.
European Christians are at the forefront in accepting evolution: results from an internet‐based survey
Authors: Wilson David P.
Published: October 2010

SUMMARY Beliefs regarding the origins of the universe and life differ substantially between groups of people and are often particularly associated with religious worldviews. It is important to understand factors associated with evolution and creationism beliefs and unacceptance of scientific evidence for evolution. An internet‐based survey was conducted to elicit information from people who self‐identify as Christians, atheists, agnostics and other belief systems, as well as by geographical location and other demographic variables, on acceptance of evolution or creationism, certainty with which each position is believed, and reasons for rejecting the alternative. It was found that almost 60% of Christians believe in creationism and less than 10% believe in natural evolution. Worldwide, these proportions were relatively consistent across all locations except for in Europe. Among European Christians the majority of Christians believe in a form of evolution. It was found that the vast majority (87%) of Christians are ‘absolutely certain’ about their beliefs, compared with the minority of atheists and agnostics claiming ‘absolute certainty’. Generally, reasons Christians did not accept evolution were based not on evidence but on religious doctrine. In contrast, the most common reason for not accepting the existence of a god by atheists who supported evolution was the lack of evidence. Innovative strategies may be required to communicate evolutionary science effectively to non‐European Christians.
Two families of Xenopus tropicalis skeletal genes display well‐conserved expression patterns with mammals in spite of their highly divergent regulatory regions
Authors: Espinoza Javier , Sanchez Mario , Sanchez Andrea , Hanna Patricia , Torrejon Marcela , Buisine Nicolas , Sachs Laurent , Marcellini Sylvain
Published: October 2010

SUMMARY
The origin of bone and cartilage, and their subsequent diversification in specific vertebrate lineages, is intimately linked to the precise transcriptional control of genes involved in matrix mineralization. It is not yet clear, however, to which extent the osteoblasts, osteocytes, and chondrocytes of each of the major vertebrate groups express similar sets of genes. In this study we have focused on the evolution of two independent families of genes that code for extracellular matrix components of the skeleton and that include secreted protein, acidic, cysteine‐rich (SPARC), bone sialoprotein (BSP) and dentin matrix protein 1 (DMP1) paralogues, and the osteocalcin (OC) and matrix gla protein (MGP) paralogues. Analyzing developing Xenopus tropicalis skeletal elements, we show that the expression patterns of these genes are well conserved with mammals. The fact that only a few osteoblasts express DMP1, while only some osteocytes express SPARC and BSP, reveals a significant degree of molecular heterogeneity for these two populations of X. tropicalis cells, similarly to what has been described in mouse. Although the cis‐regulatory modules (CRM) of the mammalian OC, DMP1, and BSP orthologs have been functionally characterized, we found no evidence of sequence similarity between these regions and the X. tropicalis genome. Furthermore, these regulatory elements evolve rapidly, as they are only poorly conserved between human and rodents. Therefore, the SPARC/DMP1/BSP and the OC/MGP families provide a good paradigm to study how transcriptional output can be maintained in skeletal cells despite extensive sequence divergence of CRM.
Phylogeny informs ontogeny: a proposed common theme in the arterial pole of the vertebrate heart
Authors: Grimes Adrian C. , Durán Ana Carmen , Sans‐Coma Valentín , Hami Danyal , Santoro Massimo M. , Torres Miguel
Published: October 2010

SUMMARY
In chick and mouse embryogenesis, a population of cells described as the secondary heart field (SHF) adds both myocardium and smooth muscle to the developing cardiac outflow tract (OFT). Following this addition, at approximately HH stage 22 in chick embryos, for example, the SHF can be identified architecturally by an overlapping seam at the arterial pole, where beating myocardium forms a junction with the smooth muscle of the arterial system. Previously, using either immunohistochemistry or nitric oxide indicators such as diaminofluorescein 2‐diacetate, we have shown that a similar overlapping architecture also exists in the arterial pole of zebrafish and some shark species. However, although recent work suggests that development of the zebrafish OFT may also proceed by addition of a SHF‐like population of cells, the presence of a true SHF in zebrafish and in many other developmental biological models remains an open question. We performed a comprehensive morphological study of the OFT of a wide range of vertebrates. Our data suggest that all vertebrates possess three fundamental OFT components: a proximal myocardial component, a distal smooth muscle component, and a middle component that contains overlapping myocardium and smooth muscle surrounding and supporting the outflow valves. Because the middle OFT component of avians and mammals is derived from the SHF, our observations suggest that a SHF may be an evolutionarily conserved theme in vertebrate embryogenesis.
TheGavialis–Tomistomadebate: the contribution of skull ontogenetic allometry and growth trajectories to the study of crocodylian relationships
Authors: Piras Paolo , Colangelo Paolo , Adams Dean C. , Buscalioni Angela , Cubo Jorge , Kotsakis Tassos , Meloro Carlo , Raia Pasquale
Published: October 2010

SUMMARYThe phylogenetic placement ofTomistomaandGavialiscrocodiles depends largely upon whether molecular or morphological data are utilized. Molecular analyses consider them as sister taxa, whereas morphological/paleontological analyses setGavialisapart fromTomistomaand other crocodylian species. Here skull allometric trajectories ofTomistomaandGavialiswere contrasted with those of two longirostral crocodylian taxa,Crocodylus acutusandMecistops cataphractus, to examine similarities in growth trajectories in light of this phylogenetic controversy. Entire skull shape and its two main modules, rostrum and postrostrum, were analyzed separately. We tested differences for both multivariate angles between trajectories and for shape differences at early and late stages of development. Based on a multivariate regression of shape data and size,Tomistomaseems to possess a peculiar rate of growth in comparison to the remaining taxa. However, its morphology at both juvenile and adult sizes is always closer to those of Brevirostres crocodylians, for the entire head shape, as well as the shape of the postrostrum and rostrum. By contrast, the allometric trajectory ofGavialisalways begins and ends in a unique region of the multidimensional morphospace. These findings concur with a morphological hypothesis that placesGavialisseparate from Brevirostres, andTomistomacloser to other crocodylids, and provides an additional, and independent, data set to inform on this ongoing phylogenetic discussion.
Correlations between spatiotemporal changes in gene expression and apoptosis underlie wing polyphenism in the ant Pheidole morrisi
Authors: Shbailat Seba Jamal , Khila Abderrahman , Abouheif Ehab
Published: October 2010

SUMMARY
Wing polyphenism, which is the ability of a single genome to produce winged and wingless castes in a colony in response to environmental cues, evolved just once and is a universal feature of ants. The gene network underlying wing polyphenism, however, is conserved in the winged castes of different ant species, but is interrupted at different points in the network in the wingless castes of these species. We previously constructed a mathematical model, which predicts that a key gene brinker (brk) mediates the development and evolution of these different “interruption points” in wingless castes of different ant species. According to this model, brk is upregulated throughout the vestigial wing discs of wingless ant castes to reduce growth and induce apoptosis. Here, we tested these predictions by examining the expression of brk, as well as three other genes up‐ and downstream of brk—decapentaplegic (dpp), spalt (sal), and engrailed (en)—in the winged reproductive and wingless soldier castes in the ant Pheidole morrisi. We show that expression of these genes is conserved in the wing disc of winged castes. Surprisingly, however, we found that brk expression is absent throughout development of the vestigial soldier forewing disc. This absence is correlated with abnormal growth of the soldier forewing disc as revealed by En expression and morphometric analyses. We also discovered that dpp and sal expression change dynamically during the transition from larval‐to‐prepupal development, and is spatiotemporally correlated with the induction of apoptosis in soldier forewing disc. Our results suggest that, contrary to our predictions, brk may not be a key gene in the network for suppressing wings in soldiers, and its absence may function to disrupt the normal growth of the soldier forewing disc. Furthermore, the dynamic changes in network interruptions we discovered may be important for the induction of apoptosis, and may be a general feature of gene networks that underlie polyphenism.
Developmental constraints on the evolution of wing‐body allometry in Manduca sexta
Authors: Tobler Alexandra , Nijhout H. Frederik
Published: October 2010

SUMMARY
Artificial selection on body size in Manduca sexta produced genetic strains with large and small body sizes. The wing‐body allometries of these strains differed significantly from the wild type. Selection on small body size led to a change in the scaling of wing and body size without changing the allometry: the wings were smaller relative to the body, but to the same degree at all body sizes. Selection for large body size led to a change in allometry with a decrease in the allometric coefficient, wing size becoming progressively smaller relative to body as body size increased. When larvae were deprived of food so as to produce adults of a range of small body sizes, all strains retained the same allometric coefficient but showed an increase in the scaling factor. Thus individuals starved as larvae had a smaller adult body size but had proportionally larger wings than fed individuals. We analyzed the developmental processes that could give rise to this pattern of allometries. Differences in the relative growth of body and wing disks can account for the differences in the allometric coefficients among the three body size strains. The change in wing‐body allometry at large body sizes was primarily due to an insufficient time period for growth. The available time period for growth of the wing imaginal disks poses a significant constraint on the proportional growth of wings, and thus on the evolution of large body size.
Origin of animal epithelia: insights from the sponge genome
Authors: Fahey Bryony , Degnan Bernard M.
Published: October 2010

SUMMARY Epithelial tissues are a key metazoan cell type, providing a basic structural unit for the construction of diverse animal body plans. Historically, an epithelial grade of organization was considered to be restricted to the Eumetazoa, with the majority of cell layers described for Porifera lacking any of the conserved ultrastructural characteristics of epithelia. Now with the use of genomic information from the demosponge, Amphimedon queenslandica, we identify orthologs of bilaterian genes that determine epithelial cell polarity or encode components of specialized epithelial junctions and extracellular matrix structures. Amphimedon possesses orthologs of most bilaterian epithelial polarity and adherens junction genes but few or no tight junction, septate junction, or basal lamina genes. To place this information in an evolutionary context, we extended these analyses to the completed genomes of various fungi, the choanoflagellate, Monosiga brevicollis, the placozoan, Trichoplax adhaerens, and the cnidarian, Nematostella vectensis. The results indicate that the majority of “epithelial” genes originated in metazoan or eumetazoan lineages, with only two genes, Par‐1 and Discs large, antedating the choanoflagellate‐metazoan split. We further explored the mechanism of evolution for each of these genes by tracking the origin of constituent domains and domain combinations. In general, domain configurations found in contemporary bilaterians are inferred to have evolved early in metazoan evolution and are identical or similar to those present in representatives of modern cnidarians, placozoans, and demosponges.
Evolutionary changes in the timing of gut morphogenesis in larvae of the marine annelid Streblospio benedicti
Authors: Pernet Bruno , McHugh Damhnait
Published: October 2010

SUMMARY
The planktonic larvae of marine invertebrates are diverse in their nutritional modes, suggesting that evolutionary transitions in larval nutritional mode have been frequent. One approach to identifying the developmental changes that play important roles in such transitions is to compare “intermediate” larval forms to closely related larvae representative of their common ancestor. Here we make such a comparison between obligately planktotrophic and facultatively feeding larvae of the poecilogonous polychaete annelid Streblospio benedicti. We used feeding experiments to show that the derived, facultatively feeding larvae of this species develop the ability to feed at a later developmental stage (five muscle bands) than planktotrophic larvae (two to three muscle bands). This delay in the onset of feeding ability does not appear to be caused by delay in the formation of particle capture structures, but instead by delay in the development of a continuous, functional gut. These observations are consistent with the hypothesis that evolutionary increases in egg size in annelids lead predictably to heterochronic delays in gut development, and hence to transitions in larval nutritional mode.
An open‐label trial of rituximab (Rituxan®) in multifocal motor neuropathy
Authors: Chaudhry Vinay , Cornblath David R.
Published: October 2010

Multifocal motor neuropathy (MMN) is an acquired demyelinating motor neuropathy. Intravenous immunoglobulin (IVIg) has been found to be safe and effective. Rituximab, a genetically engineered monoclonal antibody against CD‐20 antigen, has been reported effective in immune disorders including MMN. We performed an open‐label trial to determine if rituximab would reduce the IVIg requirement, disability, and impairment, and be safe in patients with MMN. Six MMN patients, who were on periodic IVIg treatments, received two doses of IV rituximab (1,000 mg) given 2 weeks later. Assessments were performed at baseline and at 2, 4, 6, 8, 10, and 12 months. The primary outcome was total amount of IVIg used during the 12‐month study compared to the 12 months prior. Secondary outcomes included changes in Medical Research Council (MRC) sum scores, grip strength, disability and handicap scores, and safety. There was no significant change in IVIg use, MRC sum score, grip strength, overall disability sum score, or Rotterdam handicap scale. One patient developed a hypersensitivity reaction during the first infusion that responded to adjustments in the infusion rate and treatment with diphenhydramine and acetaminophen. We conclude that rituximab can be safely given to people with MMN but in this pilot study we were unable to reduce the amount of IVIg required, at least in the regimen used.
Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study
Authors: Lauria Giuseppe , Bakkers Mayienne , Schmitz Christoph , Lombardi Raffaella , Penza Paola , Devigili Grazia , Smith A. Gordon , Hsieh Sung‐Tsieh , Mellgren Svein I. , Umapathi Thirugnanam , Ziegler Dan , Faber Catharina G. , Merkies Ingemar S. J.
Published: October 2010

The diagnostic reliability of skin biopsy in small fiber neuropathy depends on the availability of normative reference values. We performed a multicenter study to assess the normative values of intraepidermal nerve fiber (IENF) density at distal leg stratified by age deciles. Eight skin biopsy laboratories from Europe, USA, and Asia submitted eligible data. Inclusion criteria of raw data were healthy subjects 18 years or older; known age and gender; 3‐mm skin biopsy performed 10‐cm above the lateral malleolus; bright‐field immunohistochemistry protocol, and quantification of linear IENF density in three 50‐µm sections according to published guidelines. Data on height and weight were recorded, and body mass index (BMI) was calculated in subjects with both available data. Normative IENF density reference values were calculated through quantile regression analysis; influence of height, weight, or BMI was determined by regression analyses. IENF densities from 550 participants (285 women, 265 men) were pooled. We found a significant age‐dependent decrease of IENF density in both genders (women p < 0.001; men p = 0.002). Height, weight, or BMI did not influence the calculated 5th percentile IENF normative densities in both genders. Our study provides IENF density normative reference values at the distal leg to be used in clinical practice.
Understanding the consequences of chronic inflammatory demyelinating polyradiculoneuropathy from impairments to activity and participation restrictions and reduced quality of life: the ICE study
Authors: Merkies Ingemar S. J. , Hughes Richard A. C. , Donofrio Peter , Bril Vera , Dalakas Marinos C. , Hanna Kim , Hartung Hans‐Peter , Latov Norman , Van Doorn Pieter A. , Deng Chunqin ,   ICE Study Group
Published: October 2010

A randomized trial (ICE trial) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) demonstrated significantly more improvement with intravenous immunoglobulin (Gamunex®, Talecris Biotherapeutics, Inc., Research Triangle Park, NC) than placebo. To understand the relationship between CIDP impairments, activity and participation restrictions, and quality of life (QoL) in this trial, we investigated the association between scales representing these outcome levels. Gamunex or placebo was given every 3 weeks for up to 24 weeks to 117 patients in an initial treatment period after which treatment failures were crossed over (alternative treatment). We assessed impairments, activity and participation, and SF‐36 component mental (MCS) and physical summaries (PCS). Regression analyses of baseline data were performed (all subjects) and change from baseline to endpoint (Gamunex‐treated group only) to determine correlations between outcomes. Grip strength, medical research council (MRC) sum score, and inflammatory neuropathy cause and treatment (INCAT) sensory sum score were the strongest explanatory variables of disability (at baseline: r2 = 0.46; change from baseline: r2 = 0.66). Only up to half of the variance in QoL scores (PCS at baseline: r2 = 0.30; change from baseline: r2 = 0.41; MCS: at baseline: r2 = 0.10; change from baseline: r2 = 0.24) was explained by impairment and activity and participation measures. Future studies are required to elucidate the impact of CIDP on disability and QoL changes, because the obtained correlations provide only partial explanation.
Is cold paresis related to axonal depolarization?
Authors: Franssen Hessel , Gebbink Tineke A. , Wokke John H. J. , Van Den Berg Leonard H. , Van Schelven Leonard J.
Published: October 2010

Cold paresis may occur in multifocal motor neuropathy and lower motor neuron disease. It was proposed to reflect nerve lesions where axons are depolarized due to loss of Na/K‐pump activity. In those circumstances, a further decrease in pump activity by cooling may induce extra depolarization, conduction block, and weakness. Evidence for this hypothesis is incomplete because it is unknown if cold induces depolarization in human motor axons and other factors may contribute to the symptoms. To solve these questions, we examined 10 normal subjects. At 37, 25, 20, and 15°C we assessed: excitability in the median nerve, decrement on 3‐Hz stimulation, pulsed Doppler of a wrist artery, and thenar muscle strength. Cooling induced: (1) findings compatible with axonal depolarization on excitability testing (fanning‐in of threshold electrotonus, steepened current threshold relation, increased refractory period, decreased super‐ and subexcitability), (2) decreased Doppler peak systolic velocity without causing ischemia, (3) decreased muscle strength and impaired muscle relaxation. Decrement tests and compound muscle action potential amplitude remained normal. The excitability findings induced by cooling were best explained by axonal depolarization due to the effect of temperature on Na/K‐pump activity. The induced weakness may be explained not only by this mechanism but also by impaired muscle contraction.
Enhancing Electricity Audits in Residential Buildings with Nonintrusive Load Monitoring
Authors: Berges Mario E. , Goldman Ethan , Matthews H. Scott , Soibelman Lucio
Published: October 2010

Nonintrusive load monitoring (NILM) is a technique for deducing the power consumption and operational schedule of individual loads in a building from measurements of the overall voltage and current feeding it, using information and communication technologies. In this article, we review the potential of this technology to enhance residential electricity audits. First, we review the currently commercially available whole‐house and plug‐level technology for residential electricity monitoring in the context of supporting audits. We then contrast this with NILM and show the advantages and disadvantages of the approach by discussing results from a prototype system installed in an apartment unit. Recommendations for improving the technology to allow detailed, continuous appliance‐level auditing of residential buildings are provided, along with ideas for possible future work in the field.
Infants’ Visual Attention to Baby DVDs as a Function of Program Pacing
Authors: Gola Alice Ann Howard , Calvert Sandra L.
Published: October 2010

This study examined the effects of program pacing, defined as the rate of scene and character change per minute, on infants’ visual attention to video presentations. Seventy‐two infants (twenty‐four 6‐month‐olds, twenty‐four 9‐month‐olds, twenty‐four 12‐month‐olds) were exposed to one of two sets of high‐ and low‐paced commercial infant DVDs. Each DVD was approximately 5‐min long, and the order the DVDs were viewed was counterbalanced for pace. Attention was higher during rapidly than slowly paced DVDs, particularly for the 6‐ and 9‐month‐old infants. These results support previous research documenting that attention is initially controlled by exogenous qualities (e.g., rapid pace), but with development and experience becomes more influenced by endogenous factors.