bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper Guinea Creole
Authors: Jacobs Bart
Published: August 2010

This paper addresses the debate on the place of origin of the Upper Guinea branch of Portuguese Creole (UGPC) as spoken in Guinea-Bissau and Casamance (GBC) and on the Santiago Island of Cape Verde (SCV). The hypothesis that UGPC emerged on Santiago rather than on the mainland is underpinned both historically and linguistically. First, a historical framework is presented that accounts for the linguistic transfer from Santiago to Cacheu. Secondly, Parkvall’s (2000) lexical evidence in favor of a Santiago birth will be analyzed and corroborated. Thirdly, a phonological trait that separates GBC from SCV is highlighted and shown to favor a Santiago origin. Finally, lexical and phonological features typical of 15th–16th century Portuguese shared by GBC and SCV are combined with historical data to further strengthen the Santiago birth hypothesis.
Closest conjunct agreement in head final languages
Authors: Benmamoun Elabbas , Bhatia Archna , Polinsky Maria
Published: August 2010

We discuss the phenomenon of closest conjunct agreement with a special focus on head-final languages; we present data from two such languages, Hindi and Tsez, which allow agreement with the rightmost conjunct when the verb follows the conjoined phrase. This contrasts with head-initial languages, such as Arabic, where close conjunct agreement is with the leftmost conjunct in clauses with VS order. In addition, both languages exhibit certain flexibility of word order at root clause level; when the verb precedes the conjoined phrase, it can also agree with the leftmost conjunct. The empirical data from the two languages raise the following questions. First, is the typological difference between head-initial and head-final languages in the context of coordination due to a difference in the structure of coordination in these two groups? Second, to what extent is the syntactic configuration relevant to the computation of closest conjunct agreement? Third, what is the role of linear proximity in closest conjunct agreement? These questions have wider implications for the analysis of agreement and the relation between syntax and the morpho-phonological component.
Arguments for successive-cyclic movement through SpecCP
Authors: den Dikken Marcel
Published: August 2010

Successive-cyclic A'–Cmovement derivations exploiting SpecCP as an intermediate landing-site deserve careful scrutiny. As a companion to Den Dikken’s (2009a) case for a typology of A'–Cdependencies that includes successive-cyclic movement via vP–edges, resumptive prolepsis, and scope marking, but not successive-cyclic movement via SpecCP, this paper demonstrates that the arguments accumulated in the generative literature in favour of successive-cyclic movement via SpecCP are invalid. To the extent that any of these arguments implicate SpecCP at all, they never make reference to SpecCP as an intermediate stopover point: they are arguments either for terminal movement to a subordinate SpecCP or for successive-cyclic movement via intermediate stopovers in positions other than SpecCP.
The internal syntax of jeder ‘every’
Authors: Leu Thomas
Published: August 2010

In this paper I explore the elements that make up the German distributive universal quantifier jeder, and the structural relationships among them. I argue that jeder consists of three overt morphemes je-d-er, which are heads in an extended adjectival projection (xAP). Their relative order is derived by movement [
xAP
je d er t
jeP]. Je corresponds to the adjectival stem, -d- is an adjectival article (which in turn is analyzed as a relative complementizer) and -er is an agreement head, AgrA. The xAP further contains movement traces/ copies of the nominal which jeder quantifies over. One of these copies is in the complement of je where, I claim, it supplies the restriction (distributive key or range). The components of the proposal are all motivated independently of jeder: (i) the morphology of jeder identifies it as adjectival, hence an analysis of it must incorporate an (independently motivated) adjectival syntax; (ii) a comparison with the distributive dual quantifier beid- ‘both’ further informs the syntactic analysis internal to the word jeder; and (iii) a comparison of je in jeder and in other je-words suggests that je takes an N(P) complement, a fact that confirms the expectations regarding the selectional properties of je raised by the preceding discussion. Finally, a comparison of jeder with counterparts of it in other languages, as well as with other complex determiners in German, will broaden the scope and corroborate important aspects of the present proposal.
Two locations for negation
Authors: Munshi Sadaf , Bhatt Rajesh
Published: August 2010

Kashmiri has two structural positions for negation: a high position associated with focus and a low position associated with tense. In verb second environments, the difference between these two positions is neutralized on the surface and irrespective of the location where negation is generated, it appears as a suffix on the finite verb. But in non-verb second environments such as conditionals and correlatives the two negations can be teased apart. In these environments, the high negation appears as a suffix on material such as relative phrases and the conditional marker while the low negation appears as a suffix on the finite verb. The high vs. low distinction has semantic implications: in certain environments where the negation is arguably ‘expletive’, negation can only be high.
Topicality and differential object marking
Authors: Iemmolo Giorgio
Published: August 2010

The present paper investigates the relationship between dislocation and differential object marking in some Romance languages. As in many languages that have a DOM system, it is usually also assumed that in Romance languages the phenomenon is regulated by the semantic features of the referents, such as animacy, definiteness, and specificity. In the languages under investigation, though, these features cannot explain the distribution and the emergence of DOM. After discussing the main theoretical approaches to the phenomenon, I will analyse DOM in four Romance languages. I will argue that DOM emerges in pragmatically and semantically marked contexts, namely with personal pronouns in dislocations. I will then show that in these languages the use of the DOM system is mainly motivated by the need to signal the markedness of these direct objects as a consequence of being used in (mainly left) dislocation as topics (cf. English “As for him, we didn’t see him”). Finally, the examination of comparative data from Persian and Amazonian languages lends further support to the advocated approach in terms of information structure
Middle voice and ideophones, a diachronic connection
Authors: van Gijn Rik
Published: August 2010

Kemmer (1993) argues that middle voice markers almost always arise diachronically through the semantic extension of a reflexive marker to other semantic uses related to reflexive. In this paper I will argue for an alternative diachronic path that has led to the development of the middle marker in Yurakaré (unclassified, Bolivia): through ideophone-verb constructions. Taking this perspective helps explain a number of synchronic peculiarities of the middle marker in Yurakaré, and it introduces a previously unnoticed channel for middle voice markers to arise.
Casting the autophagy net
Authors: Short Ben
Published: August 2010

Two studies investigate how cells regulate the formation of autophagosomes.
Identification of novel filament-forming proteins in Saccharomyces cerevisiae and Drosophila melanogaster
Authors: Noree Chalongrat , Sato Brian K. , Broyer Risa M. , Wilhelm James E.
Published: August 2010

The discovery of large supramolecular complexes such as the purinosome suggests that subcellular organization is central to enzyme regulation. A screen of the yeast GFP strain collection to identify proteins that assemble into visible structures identified four novel filament systems comprised of glutamate synthase, guanosine diphosphate–mannose pyrophosphorylase, cytidine triphosphate (CTP) synthase, or subunits of the eIF2/2B translation factor complex. Recruitment of CTP synthase to filaments and foci can be modulated by mutations and regulatory ligands that alter enzyme activity, arguing that the assembly of these structures is related to control of CTP synthase activity. CTP synthase filaments are evolutionarily conserved and are restricted to axons in neurons. This spatial regulation suggests that these filaments have additional functions separate from the regulation of enzyme activity. The identification of four novel filaments greatly expands the number of known intracellular filament networks and has broad implications for our understanding of how cells organize biochemical activities in the cytoplasm.
The HCMV membrane glycoprotein US10 selectively targets HLA-G for degradation
Authors: Park Boyoun , Spooner Eric , Houser Brandy L. , Strominger Jack L. , Ploegh Hidde L.
Published: August 2010

Human cytomegalovirus (HCMV) encodes an endoplasmic reticulum (ER)-resident transmembrane glycoprotein, US10, expressed early in the replicative cycle of HCMV as part of the same cluster that encodes the known immunoevasins US2, US3, US6, and US11. We show that US10 down-regulates cell surface expression of HLA-G, but not that of classical class I MHC molecules. The unique and short cytoplasmic tail of HLA-G (RKKSSD) is essential in its role as a US10 substrate, and a tri-leucine motif in the cytoplasmic tail of US10 is responsible for down-regulation of HLA-G. Both the kinetics of HLA-G degradation and the mechanisms responsible appear to be distinct from those used by the US2 and US11 pathways, suggesting the existence of a third route of protein dislocation from the ER. We show that US10-mediated degradation of HLA-G interferes with HLA-G–mediated NK cell inhibition. Given the role of HLA-G in protecting the fetus from attack by the maternal immune system and in directing the differentiation of human dendritic cells to promote the evolution of regulatory T cells, HCMV likely targets the HLA-G–dependent axis of immune recognition no less efficiently than it interferes with classical class I MHC–restricted antigen presentation.
Observation and analysis of pellet material ∇B drift on MAST
Authors: Garzotti L. , Baylor L. , Köchl F. , Pégourié B. , Valovič M. , Axon K.B. , Dowling J. , Gurl C. , Maddison G.P. , Nehme H. , O'Gorman T. , Patel A. , Price M. , Scannell R. , Walsh M.
Published: August 2010

Pellet material deposited in a tokamak plasma experiences a drift towards the low field side of the torus induced by the magnetic field gradient. Plasma fuelling in ITER relies on the beneficial effect of this drift to increase the pellet deposition depth and fuelling efficiency. It is therefore important to analyse this phenomenon in present machines to improve the understanding of the ∇B induced drift and the accuracy of the predictions for ITER. This paper presents a detailed analysis of pellet material drift in MAST pellet injection experiments based on the unique diagnostic capabilities available on this machine and compares the observations with predictions of state-of-the-art ablation and deposition codes.
Par6α Interacts with the Dynactin Subunit p150Gluedand Is a Critical Regulator of Centrosomal Protein Recruitment
Authors: Kodani Andrew , Tonthat Vinh , Wu Beibei , Sütterlin Christine
Published: August 2010

The centrosome contains proteins that control the organization of the microtubule cytoskeleton in interphase and mitosis. Its protein composition is tightly regulated through selective and cell cycle–dependent recruitment, retention, and removal of components. However, the mechanisms underlying protein delivery to the centrosome are not completely understood. We describe a novel function for the polarity protein Par6α in protein transport to the centrosome. We detected Par6α at the centrosome and centriolar satellites where it interacted with the centriolar satellite protein PCM-1 and the dynactin subunit p150Glued. Depletion of Par6α caused the mislocalization of p150Gluedand centrosomal components that are critical for microtubule anchoring at the centrosome. As a consequence, there were severe alterations in the organization of the microtubule cytoskeleton in the absence of Par6α and cell division was blocked. We propose a model in which Par6α controls centrosome organization through its association with the dynactin subunit p150Glued.
Exchangeable random variables
Authors: Good Phillip
Published: August 2010

Contact:  drgood@statcourse.com
Rifampicin enhances activity of daptomycin and vancomycin against both a polysaccharide intercellular adhesin (PIA)-dependent and -independent Staphylococcus epidermidis biofilm
Authors: Olson Michael E. , Slater Shawn R. , Rupp Mark E. , Fey Paul D.
Published: August 2010

Objectives and methods

This study addressed the efficacy of daptomycin, vancomycin, rifampicin, daptomycin/rifampicin and vancomycin/rifampicin against a polysaccharide intercellular adhesin (PIA)-dependent and -independent Staphylococcus epidermidis biofilm using flow cell and guinea pig tissue cage models.

Results

The flow cell model of both PIA-dependent and -independent biofilms demonstrated that the viable cell count after treatment with daptomycin/rifampicin was significantly lower (P < 0.05) than after treatment with vancomycin, vancomycin/rifampicin, daptomycin or rifampicin alone. To validate these observations, a guinea pig tissue cage model was used. The results demonstrated that the addition of rifampicin to daptomycin or vancomycin sterilized 5/6 tissues cages colonized with S. epidermidis 1457 (PIA producing). Similar results were noted with S. epidermidis 1457 icaADBC::dhfr (non-PIA producing), where daptomycin/rifampicin and vancomycin/rifampicin sterilized 5/6 and 6/6 tissue cages, respectively. There was no statistical difference in comparison with the no-treatment control when both 1457 and 1457 icaADBC::dhfr were treated with vancomycin and daptomycin alone. Furthermore, treatment with rifampicin alone sterilized 5/6 and 3/6 1457 and 1457 icaADBC::dhfr tissue cages, respectively.

Conclusions

Interpretation of these data suggests that rifampicin is highly active against S. epidermidis biofilms and both vancomycin and daptomycin are effective at reducing the subpopulation of bacteria that develop rifampicin resistance.
Taxonomic counts of cognition in the wild
Authors: Lefebvre Louis
Published: August 2010

In 1985, Kummer & Goodall pleaded for an ecology of intelligence and proposed that innovations might be a good way to measure cognition in the wild. Counts of innovation per taxonomic group are now available in hundreds of avian and primate species, as are counts of tactical deception, tool use and social learning. Robust evidence suggests that innovation rate and its neural correlates allow birds and mammals to cope better with environmental change. The positive correlations between taxonomic counts, and the increasing number of cognitive and neural measures found to be associated with ecological variables, suggest that domain general processes might be more pervasive than previously thought in the evolution of intelligence.
Walter Plowright. 20 July 1923 — 20 February 2010
Authors: Biggs P. M.
Published: August 2010

Walter Plowright was a distinguished veterinary scientist who spent most of his active research life in Africa in the Colonial Service studying infectious diseases of cattle, sheep and pigs. Walter came from Lincolnshire farming stock but during his grammar school education decided that rather than following a career on the family farm he wished to be a veterinary surgeon. On graduating from the Royal Veterinary College, London, in 1944 he joined the Royal Army Veterinary Corps and had postings to the Middle East, Kenya and North Africa. It was this experience that convinced him he wished to spend his career in studying infectious disease of animals. Soon after demobilization he joined the Colonial Veterinary Service, in which he made major contributions to the understanding and control of several infectious diseases. His major contribution was the development of a tissue-culture-adapted attenuated rinderpest vaccine and seeing it into practical use. This vaccine has been the keystone in the global eradication of this disease, only the second disease after smallpox to be eradicated worldwide. This was a massive contribution to agriculture and humanity, and was recognized by the award of the World Food Prize. Walter had a clear and incisive mind, and his research was characterized by novelty, perseverance and attention to detail. He was driven by a wish that his work would provide an understanding of infectious diseases and contribute practically to their control.
Genetic and ‘cultural’ similarity in wild chimpanzees
Authors: Langergraber Kevin E. , Boesch Christophe , Inoue Eiji , Inoue-Murayama Miho , Mitani John C. , Nishida Toshisada , Pusey Anne , Reynolds Vernon , Schubert Grit , Wrangham Richard W. , Wroblewski Emily , Vigilant Linda
Published: August 2010

The question of whether animals possess ‘cultures’ or ‘traditions’ continues to generate widespread theoretical and empirical interest. Studies of wild chimpanzees have featured prominently in this discussion, as the dominant approach used to identify culture in wild animals was first applied to them. This procedure, the ‘method of exclusion,’ begins by documenting behavioural differences between groups and then infers the existence of culture by eliminating ecological explanations for their occurrence. The validity of this approach has been questioned because genetic differences between groups have not explicitly been ruled out as a factor contributing to between-group differences in behaviour. Here we investigate this issue directly by analysing genetic and behavioural data from nine groups of wild chimpanzees. We find that the overall levels of genetic and behavioural dissimilarity between groups are highly and statistically significantly correlated. Additional analyses show that only a very small number of behaviours vary between genetically similar groups, and that there is no obvious pattern as to which classes of behaviours (e.g. tool-use versus communicative) have a distribution that matches patterns of between-group genetic dissimilarity. These results indicate that genetic dissimilarity cannot be eliminated as playing a major role in generating group differences in chimpanzee behaviour.
Running backwards: soft landing–hard takeoff, a less efficient rebound
Authors: Cavagna G. A. , Legramandi M. A. , La Torre A.
Published: August 2010

Human running at low and intermediate speeds is characterized by a greater average force exerted after ‘landing’, when muscle–tendon units are stretched (‘hard landing’), and a lower average force exerted before ‘takeoff’, when muscle–tendon units shorten (‘soft takeoff’). This landing–takeoff asymmetry is consistent with the force–velocity relation of the ‘motor’ (i.e. with the basic property of muscle to resist stretching with a force greater than that developed during shortening), but it may also be due to the ‘machine’ (e.g. to the asymmetric lever system of the foot operating during stance). Hard landing and soft takeoff—never the reverse—were found in running, hopping and trotting animals using diverse lever systems, suggesting that the different machines evolved to comply with the basic force–velocity relation of the motor. Here we measure the mechanical energy of the centre of mass of the body in backward running, an exercise where the normal coupling between motor and machine is voluntarily disrupted, in order to see the relevance of the motor–machine interplay in human running. We find that the landing–takeoff asymmetry is reversed. The resulting ‘soft landing’ and ‘hard takeoff’ are associated with a reduced efficiency of positive work production. We conclude that the landing–takeoff asymmetry found in running, hopping and trotting is the expression of a convenient interplay between motor and machine. More metabolic energy must be spent in the opposite case when muscle is forced to work against its basic property (i.e. when it must exert a greater force during shortening and a lower force during stretching).
How the insect immune system interacts with an obligate symbiotic bacterium
Authors: Douglas A. E. , Bouvaine S. , Russell R. R.
Published: August 2010

The animal immune system provides defence against microbial infection, and the evolution of certain animal–microbial symbioses is predicted to involve adaptive changes in the host immune system to accommodate the microbial partner. For example, the reduced humoral immune system in the pea aphidAcyrthosiphon pisum, including an apparently non-functional immune deficiency (IMD) signalling pathway and absence of peptidoglycan recognition proteins (PGRPs), has been suggested to be an adaptation for the symbiosis with the bacteriumBuchnera aphidicola. To investigate this hypothesis, the interaction betweenBuchneraand non-host cells, specifically culturedDrosophilaS2 cells, was investigated. Microarray analysis of the gene expression pattern in S2 cells indicated thatBuchneratriggered an immune response, including upregulated expression of genes for antimicrobial peptides via the IMD pathway with the PGRP-LC as receptor.Buchneracells were readily taken up by S2 cells, but were subsequently eliminated over 1–2 days. These data suggest thatBuchnerainduces in non-host cells a defensive immune response that is deficient in its host. They support the proposed contribution of theBuchnerasymbiosis to the evolution of the apparently reduced immune function in the aphid host.
Tethering Factors Required for Cytokinesis in Arabidopsis
Authors: Thellmann Martha , Rybak Katarzyna , Thiele Knut , Wanner Gerhard , Assaad Farhah F.
Published: August 2010

At the end of the cell cycle, the nascent cross wall is laid down within a transient membrane compartment referred to as the cell plate. Tethering factors, which act by capturing vesicles and holding them in the vicinity of their target membranes, are likely to play an important role in the first stages of cell plate assembly. Factors required for cell plate biogenesis, however, remain to be identified. In this study, we used a reverse genetic screen to isolate tethering factors required for cytokinesis in Arabidopsis (Arabidopsis thaliana). We focused on the TRAPPI and TRAPPII (for transport protein particle) tethering complexes, which are thought to be required for the flow of traffic through the Golgi and for trans-Golgi network function, as well as on the GARP complex, thought to be required for the tethering of endocytotic vesicles to the trans-Golgi network. We found weak cytokinesis defects in some TRAPPI mutants and strong cytokinesis defects in all the TRAPPII lines we surveyed. Indeed, four insertion lines at the TRAPPII locus AtTRS120 had canonical cytokinesis-defective seedling-lethal phenotypes, including cell wall stubs and incomplete cross walls. Confocal and electron microscopy showed that in trs120 mutants, vesicles accumulated at the equator of dividing cells yet failed to assemble into a cell plate. This shows that AtTRS120 is required for cell plate biogenesis. In contrast to the TRAPP complexes, we found no conclusive evidence for cytokinesis defects in seven GARP insertion lines. We discuss the implications of these findings for the origin and identity of cell plate membranes.
Coexpression Analysis Identifies Rice Starch Regulator1, a Rice AP2/EREBP Family Transcription Factor, as a Novel Rice Starch Biosynthesis Regulator
Authors: Fu Fang-Fang , Xue Hong-Wei
Published: August 2010

Starch biosynthesis is important for plant development and is a critical factor in crop quality and nutrition. As a complex metabolic pathway, the regulation of starch biosynthesis is still poorly understood. We here present the identification of candidate regulators for starch biosynthesis by gene coexpression analysis in rice (Oryza sativa). Starch synthesis genes can be grouped into type I (in seeds; sink tissues) and type II (in vegetative tissues; source tissues), and 307 and 621 coexpressed genes are putatively involved in the regulation of starch biosynthesis in rice seeds and vegetative tissues, respectively. Among these genes, Rice Starch Regulator1 (RSR1), an APETALA2/ethylene-responsive element binding protein family transcription factor, was found to negatively regulate the expression of type I starch synthesis genes, and RSR1 deficiency results in the enhanced expression of starch synthesis genes in seeds. Seeds of the knockout mutant rsr1 consistently show the increased amylose content and altered fine structure of amylopectin and consequently form the round and loosely packed starch granules, resulting in decreased gelatinization temperature. In addition, rsr1 mutants have a larger seed size and increased seed mass and yield. In contrast, RSR1 overexpression suppresses the expression of starch synthesis genes, resulting in altered amylopectin structure and increased gelatinization temperature. Interestingly, a decreased proportion of A chains in rsr1 results in abnormal starch granules but reduced gelatinization temperature, whereas an increased proportion of A chains in RSR1-overexpressing plants leads to higher gelatinization temperatures, which is novel and different from previous reports, further indicating the complicated regulation of starch synthesis and determination of the physicochemical properties of starch. These results demonstrate the potential of coexpression analysis for studying rice starch biosynthesis and the regulation of a complex metabolic pathway and provide informative clues, including the characterization of RSR1, to facilitate the improvement of rice quality and nutrition.
Analysis of the Rice Mitochondrial Carrier Family Reveals Anaerobic Accumulation of a Basic Amino Acid Carrier Involved in Arginine Metabolism during Seed Germination
Authors: Taylor Nicolas L. , Howell Katharine A. , Heazlewood Joshua L. , Tan Tzu Yien W. , Narsai Reena , Huang Shaobai , Whelan James , Millar A. Harvey
Published: August 2010

Given the substantial changes in mitochondrial gene expression, the mitochondrial proteome, and respiratory function during rice (Oryza sativa) germination under anaerobic and aerobic conditions, we have attempted to identify changes in mitochondrial membrane transport capacity during these processes. We have assembled a preliminary rice mitochondrial carrier gene family of 50 members, defined its orthology to carriers of known function, and observed significant changes in microarray expression data for these rice genes during germination under aerobic and anaerobic conditions and across rice development. To determine if these transcript changes reflect alteration of the carrier profile itself and to determine which members of the family encode the major mitochondrial carrier proteins, we analyzed mitochondrial integral membrane protein preparations using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and peptide mass spectrometry, identifying seven distinct carrier proteins. We have used mass spectrometry-based quantitative approaches to compare the abundance of these carriers between mitochondria from dry seeds and those from aerobic- or anaerobic-germinated seeds. We highlight an anaerobic-enhanced basic amino acid carrier and show concomitant increases in mitochondrial arginase and the abundance of arginine and ornithine in anaerobic-germinated seeds, consistent with an anaerobic role of this mitochondria carrier. The potential role of this carrier in facilitating mitochondrial involvement in arginine metabolism and the plant urea cycle during the growth of rice coleoptiles and early seed nitrate assimilation under anaerobic conditions are discussed.
The Divorce of Marriage and Parenthood
Authors: Nock Steven L.
Published: August 2010

Marriage is a template for domestic life and the problems that arise in it. The patterned assumptions that traditionally defined marriage gave substance to the family. These assumptions have become less compelling over the course of a century. In this paper, I suggest how and why this has happened. I focus on the meaning of parenthood and its relationship to marriage. In the course of a century, parenthood has been redefined as a rational choice governed by calculation. As a result, childbearing, pregnancy, marriage and parenthood have been redefined. Their relationships to one another have, to varying degrees, been altered. Marriage is an institutionalized way to care for the babies that once came, inevitably, as a result of sexual intercourse. What becomes of marriage when sex no longer produces babies? The answer is that everything about marriage and the family changes. Such changes help explain the rise of professional family therapy and related fields.
Evidence‐Based Practice in Family Therapy and Systemic Consultation II
Authors: Carr Alan
Published: August 2010

Evidence for the effectiveness of family‐based treatments from critical literature reviews and controlled trials is considered for the following list of adult‐focused problems: marital distress, psychosexual problems, anxiety disorders, mood disorders, psychotic disorders, alcohol abuse, chronic pain, and the family management of neurologically impaired adults. Evidence‐based practices which may be used within the context of marital and family therapy and systemic consultation arising from the review are discussed.
Investment decisions in hog finishing: an application of the real options approach
Authors: Odening Martin , Mußhoff Oliver , Balmann Alfons
Published: August 2010

In this paper, option‐pricing theory is applied to an investment problem in hog production. A stochastic simulation model capable of pricing American‐type options is developed. This is achieved by recursive calculation of the exercise frontier. The model is used to determine the investment trigger and the disinvestment trigger for a pig‐fattening barn under German market conditions. It turns out that the investment trigger, taking into account the value of waiting in an uncertain environment, can be considerably higher compared to classical investment criteria such as the net present value. This offers an explanation as to why farmers are indeed reluctant to invest in hog production. Another finding is the sensitivity of the option prices with respect to the stochastic process that is assumed for revenues and variable costs of the production activity.
Stages and determinants of fertilizer use in semiarid African agriculture: the Niger experience
Authors: Abdoulaye Tahirou , Sanders John H.
Published: August 2010

Fertilization is a stepwise decision in Niger. Survey data from a representative sample of 100 households were utilized with individual and joint estimation to evaluate the determinants of fertilizer use at its three different stages: manure alone and two different types of inorganic fertilizer application. The fertilizer price relative to the millet price was always a highly significant determinant of fertilizer adoption. Farmers' experience in seeing the results of fertilization in the field was a principal factor influencing the use of manure and of the micro‐fertilization. Other studies in semiarid regions have emphasized risk, liquidity, or fertilizer responsiveness under harsh conditions but the shift to the micro doses of inorganic fertilizer was statistically associated here with the demonstration trials and the price ratios (fertilizer/millet). A variable reflecting the millet price recovery approximately 6 months after harvest was the most important factor in the decision to raise further inorganic fertilizer use with side dressing. Policy implications were focused on the importance of demonstration trials and improvements in the economic conditions (millet–fertilizer price ratios).
Costs and benefits of livestock systems and the role of market and nonmarket relationships
Authors: Moll Henk A. J.
Published: August 2010

In developing countries livestock are kept not only for their physical products, but also for insurance, financing, and to display status. Though this range of purposes is acknowledged, livestock policies nevertheless often emphasize physical production: a limited perspective that hampers the formulation and implementation of effective livestock policies. This article presents a comprehensive appraisal of costs and benefits of livestock systems that takes into account the institutional environment of livestock keepers. Indicators are developed that capture, quantify, and organize not only the benefits resulting from the physical production, but also those from the intangible functions. The method is illustrated by an analysis of cattle in the Western Province of Zambia. The results indicate that the perspective on livestock systems developed more closely reflects the observed decisions of the livestock keepers.
β‐Endorphin/β MSH – two neglected melanotropins?
Authors: Schallreuter K. U. , Spencer J. D. , Gibbons N. C. J. , Peters E. M. J. , Carder J. M. , Marles L. K.
Published: August 2010

POMC processing in human melanocytes has been widely documented, and the α‐MSH/MC1R/cAMP cascade has been implicated in the control of pigmentation. Only very recently, a role of β‐endorphin, one cleavage product of β‐LPH, has been demonstrated to influence melanocyte growth, dendricity and melanin biosynthesis via the µ‐opiate receptor. However, much earlier, it was shown that β‐MSH, the other cleavage product of β‐LPH, controls melanogenesis and melanin transfer in amphibians. To date, a specific receptor for β‐MSH has not been identified. Earlier POMC processing has been found in melanosomes. Therefore, an MC1R‐independent role of α‐MSH was postulated and demonstrated in control of 6‐tetrahydrobiopterin (6BH4)‐inhibited tyrosinase. Utilizing the depigmentation disorder vitiligo, we were now able to follow the fate of epidermal POMC processing in the presence of mM levels of hydrogen peroxide (H2O2). In vitiligo epidermal PC2 and 7B2 protein expression is increased, whereas α‐MSH, β‐MSH and β‐endorphin are significantly decreased. Analysis of the peptide sequences revealed in all three cases H2O2 oxidation targets such as methionine and tryptophan yielding significant structural alterations. Moreover, we have identified a new function of β‐MSH due to its capacity to bind the important cofactor 6BH4 as well as its isomer 7BH4. Hence, we propose for the first time that β‐MSH can control both the supply of l‐tyrosine from l‐phenylalanine via phenylalanine hydroxylase and l‐Dopa synthesis via tyrosinase hydroxylase in melanocytes and keratinocytes. Therefore, both melanogenesis and catecholamine synthesis could be regulated by this peptide.
Sigma receptors as novel target structures for cancer chemotherapeutics
Authors: Bowen W. D.
Published: August 2010

Sigma receptors bind several important classes of psychotropic drugs. Two pharmacologically defined subtypes exist, termed sigma‐1 and sigma‐2. Sigma receptors are widely distributed across tissues. Both subtypes are highly expressed in tumor cell lines, including breast, lung, and prostate tumor cellines as well as neuroblastomas, gliomas, and melanomas. Furthermore, sigma‐2 receptors become more upregulated in rapidly dividing cells. Activation of sigma‐2 receptors results in apoptotic cell death. The signaling pathway involves changes in intracellular calcium levels as well as increases in the cellular sphingolipids ceramide and sphingosylphosphorylcholine. The apoptotic effect of sigma‐2 agonists is not affected by the p53 status of the cells and is independent of caspase activity. Subtoxic doses of sigma‐2 receptor agonists markedly potentiate the cytotoxic effect of doxorubicin and actinomycin‐D in breast tumor cellines, indicating a chemosensitizing effect. The very high density of Sigma receptors in tumor cells indicates that they may also be useful targets for development of non‐invasive tumor imaging agents. Several radiolabeled sigma ligands show favorable biodistribution and tumor uptake, and melanoma cell tumor xenografts have been successfully imaged in nude mice. Taken together, these results suggest that sigma‐2 receptors are involved in the regulation of cell proliferation and survival and activate a novel pathway of programmed cell death. It may be possible to exploit this pathway and the high tumor expression of sigma‐2 receptors to develop agents for the treatment and diagnosis of drug‐resistant tumors.
Effects of neuropeptides and hormones on Langerhans cells
Authors: Granstein R. D.
Published: August 2010

Significant evidence suggests that the nervous and immune systems have regulatory interactions within the skin. Langerhans cells (LCs) are dendritic antigen‐presenting cells that reside within the epidermis. By laser confocal scanning microscopy, LCs in human skin have been found to be frequently in anatomic association with epidermal nerves. Additionally, a minority of LCs have been found by immunohistochemistry to have the neuropeptide calcitonin gene‐related peptide (CGRP) on or near their cell surfaces. Functional studies have demonstrated that CGRP, pituitary adenylate cyclase‐activating polypeptide, and vasoactive intestinal peptide inhibit antigen presentation by LCs, at least in some assays. Epinephrine and norepinephrine also have been shown to inhibit LC antigen presentation in vitro. Some of these agents appear to exert their effects through regulation of the expression of cytokines and costimulatory molecules. Furthermore, some of these agents inhibit the acquisition of contact hypersensitivity after intradermal administration. As a whole, these findings suggest a regulatory locus of interaction between the immune system and the nervous system within the skin.
Vasoactive intestinal peptide and pituitary adenylate cyclase‐activating polypeptide as modulators of innate and adaptive immunity
Authors: Delgado M.
Published: August 2010

Recent reports identified neural pathways, both hard‐wiring and soluble mediators, that control and adjust the peripheral immune response. Immune organs are innervated by fibres rich in neurotransmitters and neuropeptides, which are released in inflammatory conditions. Here, we focus on the immunomodulatory role of two neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase‐activating polypeptide (PACAP). VIP/PACAP are present and released from both innervation and immune cells, particularly Th2 cells, and immune cells express receptors for VIP/PACAP. VIP/PACAP have a general anti‐inflammatory effect, both in innate and in adaptive immunity. In innate immunity, VIP/PACAP inhibit the production of proinflammatory cytokines and chemokines from macrophages, microglia and dendritic cells. In addition, VIP/PACAP reduce the expression of costimulatory molecules on the antigen‐presenting cells, and therefore reduce stimulation of antigen‐specific CD4+ T cells. In terms of adaptive immunity, VIP/PACAP promote Th2‐type responses and reduce the proinflammatory Th1‐type responses. VIP is rapidly transforming into something more than a mere neuropeptide. In evolving scientifically from a neuropeptide to a novel agent for modifying immune function, and, possibly a cytokine‐like molecule, VIP research has engaged many physiologists, molecular biologists, biochemists, endocrinologists and pharmacologist, and it is a paradigm to explore mutual interactions between neural and neuroendocrine links in health and disease. Recognition of the central functions that VIP plays in cellular processes is focusing our attention on this very important peptide as exciting new candidates for therapeutic intervention and drug development.
Neurotrophins in allergic disease of skin and lung: modulators of immunological and neuronal plasticity
Authors: Renz H. , Hahn C. , Nockher W. A.
Published: August 2010

Allergies are chronic inflammatory disease of the skin, lung and gut. Atopic dermatitis represents the main manifestation of the skin, and bronchial asthma is the leading condition in the lower respiratory tract. Both conditions are due to an inappropriate immune response to harmless environmental antigens (or allergens). There is growing evidence for a close interaction between the immune and nervous system in the pathophysiology of allergies. Recent evidence from our group indicates that neurotrophin production including nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are elevated in those organs. Both, residential cells including airway epithelium and migratory cells including macrophages, T cells and eosinophils serve as important sources. The effects of increased neurotrophin production are bidirectional. On the one hand, they control sensory nerve fibres in terms of function, neuropeptide synthesis and survival. On the other side, neurotrophins also serve as important survival factors particularly for inflammatory cells such as eosinophils, T cells and macrophages. Utilizing the model of segmental allergen provocation of mild to moderate asthmatic patients, it has been shown that neurotrophins prevent sufficiently apoptotic cell death of lung, but not blood eosinophils. In addition, they augment the ongoing inflammatory reaction. The functional interaction between neurotrophins and immune and nerve cells has been extensively studied in both human and mouse models of experimental allergic asthma. In the latter system, the crucial role of the pan‐neurotrophin receptor p75 has been investigated in p75 NTR–/– mice. Furthermore, NGF transgenic animals have been utilized to assess the contribution of NGF. The role of BDNF on differentiation and function of B‐lymphocytes has been identified in BDNF–/– mice. In conclusion, our data support the concept that neurotrophins mediate immunological and neuronal plasticity within the neuro‐immune network of allergic disease in the lung and skin.
Novel agonists for cold receptors on sensory neurons
Authors: Wei E. T.
Published: August 2010

An exciting research topic these past 2 years has been the identification of transient receptor potential (TRP) channel protein receptors on sensory neurons that are linked to thermosensation. Two compounds, menthol and icilin, were shown to activate the putative cold receptor, TRP‐M8 (CMR1, trp‐p8), in vitro. Here, some of the pharmacological properties of icilin are described and compared to menthol, summarized in the table below.

Menthol

 Stimulates TRP‐M8 receptor, does not require extracellular  calcium for activity, and does not stimulate the ANKTM1 receptor.

 Mint odor

 Irritant and harsh taste at high concentrations

 Duration of action less than15 min after topical application

 After systemic administration, lethal at high concentrations  due to anesthetic activity

Icilin

 Stimulates TRP‐M8 and ANKTM1 receptor and requires  extracellular calcium for activity

 No odor

 No irritant activity on skin or mucous membranes

 Action on inflamed skin and mucous membranes (e.g.  eyelids, lips, nasal, and anorectal) can last 4–8 h

 No anesthetic activity, and no lethality at doses of up to  1.5 g/kg intraperitoneally, but after systemic administration produces ‘wet dog shakes’ which are rapid, alternating contractions, and relaxations of the supination and pronation muscles about the spinal axis
Current developments in treatment of pruritus: neurophysiologic basis and clinical efficacy
Authors: Ständer S.
Published: August 2010

Non‐histaminergic pruritus of any origin is difficult to treat and requires evaluation of new therapeutic strategies which were offered by recent neurophysiologic findings. For example, the discovery of opioid receptors on mast cells and nerve fibers enables the effective administration of opioid receptor antagonists. Up to now, 130 patients with pruritus of different origin were successfully treated with the oral opioidantagonist naltrexone. A significant therapeutic response was achieved under 50–150 mg daily in 66% of patients. In prurigo nodularis, naltrexone also contributed to healing of the skin lesions. Tachyphylaxis was infrequent, and adverse drug effects, in particular nausea, were of short duration. Only recently, the vanilloid receptor 1 (VR1) was demonstrated on nerve fibers and mast cells what explains the antipruritic efficacy of the topical application of capsaicin. Upon continual therapy with this VR1‐ligand, neuropeptides are depleted and the nerve fiber is desensitized. A total of 53 patients with pruritus of different origin (prurigo nodularis, psoriasis, eczema, aquagenic pruritus, PUVA itch, hydroxyethyl starch‐induced itch, and lymphoma) were selected to receive capsaicin four to six times daily in gradually increasing concentrations (0.025–0.1%). After cessation of the symptoms of neurogenic inflammation, all of the patients experienced a complete elimination of pruritus within 12 days. In addition, capsaicin largely contributed to healing of the skin lesions in prurigo nodularis.
Brain‐derived neurotrophic factor, epidermal growth factor, or A‐Raf‐induced growth of HaCaT keratinocytes requires extra‐cellular signal‐regulated protein kinase
Authors: Rössler O. G. , Thiel G.
Published: August 2010

The epidermal growth factor (EGF) receptor plays an important role in epithelial cells by controlling cell proliferation and survival. Keratinocytes also express another class of receptor tyrosine kinases, the neurotrophin receptors. To analyze the biological role of the neurotrophin brain‐derived neurotrophic factor (BDNF) in keratinocytes, we expressed the BDNF receptor TrkB in immortalized human HaCaT keratinocytes. Stimulation of HaCaT‐TrkB cells with BDNF induced DNA synthesis, an indication of proliferating cells. An analysis of the signal transduction cascade revealed that the activated TrkB receptor effectively utilized components of the EGF receptor signaling pathway to control cell proliferation. Mitogenic signaling induced by BDNF or EGF was completely abrogated by the MAP kinase kinase inhibitor PD98059, whereas the inhibition of phosphatidylinositol‐3 (PI3) kinase by wortmannin only delayed the proliferative response. The importance of the extracellular signal‐regulated protein kinase (ERK) signaling pathway for growth of HaCaT keratinocytes was further demonstrated with HaCaT cells engineered to express an inducible A‐Raf‐estrogen receptor fusion protein (ΔA‐Raf:ER). HaCaT cells expressing ΔA‐Raf:ER proliferated following the activation of mutant A‐Raf protein kinase. Proliferation was completely inhibited by PD98059. Proliferation of HaCaT cells induced by EGF, BDNF, or ΔA‐Raf:ER was also accompanied by the biosynthesis of the transcription factors Egr‐1 and c‐Jun, suggesting that these proteins may be part of the mitogenic signaling cascade.
Melanocortin receptors in fibroblastic cell types of the skin –in vitro and in vivo expression and functional relevance
Authors: Böhm M. , Ständer S. , Eickelmann M. , Blume‐Peytavi U. , Tobin D. J. , Luger T. A.
Published: August 2010

In contrast to the well‐established role of melanocortins on melanocyte function, the expression and relevance of melanocortin receptors (MC‐Rs) in skin fibroblasts is incompletely understood. We recently showed that human dermal fibroblasts derived from foreskin express functional MC‐1Rs which mediate an inhibitory action of α‐melanocyte‐stimulating hormone (α‐MSH) on collagen metabolism (Böhm et al., J Biol Chem 2004, in press). Here, we show by RT‐PCR, immunofluorescence, immunohistochemistry and immune electron microscopy that MC‐1R expression is conserved in vitro and in vivo in additional human fibroblastic cell types of the skin including adult dermal fibroblasts, fibrosarcoma cells, connective tissue sheath fibroblasts and dermal papilla cells of the hair follicle. In vitro expression of MC‐1R declines as a matter of cellular senescence in dermal fibroblasts. Interestingly, α‐MSH inhibits the inductive effect of interferon‐γ, an important proinflammatory mediator in inflammatory and fibrotic skin diseases, on expression of adhesion molecules such as intercellular adhesion molecule‐1 in human dermal fibroblasts. These data point towards an additional biological role of α‐MSH as a modulator of inflammatory reactions in the connective tissue compartment of the skin.