bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting complement component 5a promotes vascular integrity and limits airway remodeling
Authors: Khan Mohammad A. , Maasch Christian , Vater Axel , Klussmann Sven , Morser John , Leung Lawrence L. , Atkinson Carl , Tomlinson Stephen , Heeger Peter S. , Nicolls Mark R.
Published: March 2013

Increased microvascular dilatation and permeability is observed during allograft rejection. Because vascular integrity is an important indicator of transplant health, we have sought to limit injury to blood vessels by blocking complement activation. Although complement component 3 (C3) inhibition is known to be vasculoprotective in transplantation studies, we recently demonstrated the paradoxical finding that, early in rejection, C3−/−transplant recipients actually exhibit worse microvascular injury than controls. In the genetic absence of C3, thrombin-mediated complement component 5 (C5) convertase activity leads to the generation of C5a (anaphylatoxin), a promoter of vasodilatation and permeability. In the current study, we demonstrated that microvessel thrombin deposition is significantly increased in C3−/−recipients during acute rejection. Thrombin colocalization with microvessels is closely associated with remarkably elevated plasma levels of C5a, vasodilatation, and increased vascular permeability. Administration of NOX-D19, a specific C5a inhibitor, to C3−/−recipients of airway transplants significantly improved tissue oxygenation, limited microvascular leakiness, and prevented airway ischemia, even in the absence of conventional T-cell–directed immunosuppression. As C3 inhibitors enter the clinics, the simultaneous targeting of this thrombin-mediated complement activation pathway and/or C5a itself may confer significant clinical benefit.
Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis
Authors: Waller Kimberly A. , Zhang Ling X. , Elsaid Khaled A. , Fleming Braden C. , Warman Matthew L. , Jay Gregory D.
Published: March 2013

Osteoarthritis is a complex disease involving the mechanical breakdown of articular cartilage in the presence of altered joint mechanics and chondrocyte death, but the connection between these factors is not well established. Lubricin, a mucinous glycoprotein encoded by the
PRG4
gene, provides boundary lubrication in articular joints. Joint friction is elevated and accompanied by accelerated cartilage damage in humans and mice that have genetic deficiency of lubricin. Here, we investigated the relationship between coefficient of friction and chondrocyte death using ex vivo and in vitro measurements of friction and apoptosis. We observed increases in whole-joint friction and cellular apoptosis in lubricin knockout mice compared with wild-type mice. When we used an in vitro bovine explant cartilage-on-cartilage bearing system, we observed a direct correlation between coefficient of friction and chondrocyte apoptosis in the superficial layers of cartilage. In the bovine explant system, the addition of lubricin as a test lubricant significantly lowered the static coefficient of friction and number of apoptotic chondrocytes. These results demonstrate a direct connection between lubricin, boundary lubrication, and cell survival and suggest that supplementation of synovial fluid with lubricin may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of lubricin.
Social isolation, loneliness, and all-cause mortality in older men and women
Authors: Steptoe Andrew , Shankar Aparna , Demakakos Panayotes , Wardle Jane
Published: March 2013

Both social isolation and loneliness are associated with increased mortality, but it is uncertain whether their effects are independent or whether loneliness represents the emotional pathway through which social isolation impairs health. We therefore assessed the extent to which the association between social isolation and mortality is mediated by loneliness. We assessed social isolation in terms of contact with family and friends and participation in civic organizations in 6,500 men and women aged 52 and older who took part in the English Longitudinal Study of Ageing in 2004–2005. A standard questionnaire measure of loneliness was administered also. We monitored all-cause mortality up to March 2012 (mean follow-up 7.25 y) and analyzed results using Cox proportional hazards regression. We found that mortality was higher among more socially isolated and more lonely participants. However, after adjusting statistically for demographic factors and baseline health, social isolation remained significantly associated with mortality (hazard ratio 1.26, 95% confidence interval, 1.08–1.48 for the top quintile of isolation), but loneliness did not (hazard ratio 0.92, 95% confidence interval, 0.78–1.09). The association of social isolation with mortality was unchanged when loneliness was included in the model. Both social isolation and loneliness were associated with increased mortality. However, the effect of loneliness was not independent of demographic characteristics or health problems and did not contribute to the risk associated with social isolation. Although both isolation and loneliness impair quality of life and well-being, efforts to reduce isolation are likely to be more relevant to mortality.
CCDC41 is required for ciliary vesicle docking to the mother centriole
Authors: Joo Kwangsic , Kim Chang Gun , Lee Mi-Sun , Moon Hyun-Yi , Lee Sang-Hee , Kim Mi Jeong , Kweon Hee-Seok , Park Woong-Yang , Kim Cheol-Hee , Gleeson Joseph G. , Kim Joon
Published: March 2013

The initiation of primary cilium assembly entails the docking of ciliary vesicles presumably derived from the Golgi complex to the distal end of the mother centriole. Distal appendages, which anchor the mother centriole to the plasma membrane, are thought to be involved in the docking process. However, little is known about the molecular players and mechanisms that mediate the vesicle–centriole association. Here we report that coiled-coil domain containing 41 (CCDC41) is required for the docking of ciliary vesicles. CCDC41 specifically localizes to the distal end of the mother centriole and interacts with centrosomal protein 164 (Cep164), a distal appendage component. In addition, a pool of CCDC41 colocalizes with intraflagellar transport protein 20 (IFT20) subunit of the intraflagellar transport particle at the Golgi complex. Remarkably, knockdown of CCDC41 inhibits the recruitment of IFT20 to the centrosome. Moreover, depletion of CCDC41 or IFT20 inhibits ciliogenesis at the ciliary vesicle docking step, whereas intraflagellar transport protein 88 (IFT88) depletion interferes with later cilium elongation steps. Our results suggest that CCDC41 collaborates with IFT20 to support the vesicle–centriole association at the onset of ciliogenesis.
Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds
Authors: Cummins Ian , Wortley David J. , Sabbadin Federico , He Zhesi , Coxon Christopher R. , Straker Hannah E. , Sellars Jonathan D. , Knight Kathryn , Edwards Lesley , Hughes David , Kaundun Shiv Shankhar , Hutchings Sarah-Jane , Steel Patrick G. , Edwards Robert
Published: March 2013

Multiple-herbicide resistance (MHR) in black-grass (
Alopecurus myosuroides
) and annual rye-grass (
Lolium rigidum
) is a global problem leading to a loss of chemical weed control in cereal crops. Although poorly understood, in common with multiple-drug resistance (MDR) in tumors, MHR is associated with an enhanced ability to detoxify xenobiotics. In humans, MDR is linked to the overexpression of a pi class glutathione transferase (GSTP1), which has both detoxification and signaling functions in promoting drug resistance. In both annual rye-grass and black-grass, MHR was also associated with the increased expression of an evolutionarily distinct plant phi (F) GSTF1 that had a restricted ability to detoxify herbicides. When the black-grass
A. myosuroides
(
Am
)
Am
GSTF1 was expressed in
Arabidopsis thaliana,
the transgenic plants acquired resistance to multiple herbicides and showed similar changes in their secondary, xenobiotic, and antioxidant metabolism to those determined in MHR weeds. Transcriptome array experiments showed that these changes in biochemistry were not due to changes in gene expression. Rather,
Am
GSTF1 exerted a direct regulatory control on metabolism that led to an accumulation of protective flavonoids. Further evidence for a key role for this protein in MHR was obtained by showing that the GSTP1- and MDR-inhibiting pharmacophore 4-chloro-7-nitro-benzoxadiazole was also active toward
Am
GSTF1 and helped restore herbicide control in MHR black-grass. These studies demonstrate a central role for specific GSTFs in MHR in weeds that has parallels with similar roles for unrelated GSTs in MDR in humans and shows their potential as targets for chemical intervention in resistant weed management.
Stable isotope evidence of meat eating and hunting specialization in adult male chimpanzees
Authors: Fahy Geraldine E. , Richards Michael , Riedel Julia , Hublin Jean-Jacques , Boesch Christophe
Published: March 2013

Observations of hunting and meat eating in our closest living relatives, chimpanzees (Pan troglodytes), suggest that among primates, regular inclusion of meat in the diet is not a characteristic unique toHomo. Wild chimpanzees are known to consume vertebrate meat, but its actual dietary contribution is, depending on the study population, often either unknown or minimal. Constraints on continual direct observation throughout the entire hunting season mean that behavioral observations are limited in their ability to accurately quantify meat consumption. Here we present direct stable isotope evidence supporting behavioral observations of frequent meat eating among wild adult male chimpanzees (Pan troglodytes verus) in Taï National Park, Côte d’Ivoire. Meat eating among some of the male chimpanzees is significant enough to result in a marked isotope signal detectable on a short-term basis in their hair keratin and long-term in their bone collagen. Although both adult males and females and juveniles derive their dietary protein largely from daily fruit and seasonal nut consumption, our data indicate that some adult males also derive a large amount of dietary protein from hunted meat. Our results reinforce behavioral observations of male-dominated hunting and meat eating in adult Taï chimpanzees, suggesting that sex differences in food acquisition and consumption may have persisted throughout hominin evolution, rather than being a recent development in the human lineage.
Functional link between bone morphogenetic proteins and insulin-like peptide 3 signaling in modulating ovarian androgen production
Authors: Glister Claire , Satchell Leanne , Bathgate Ross A. D. , Wade John D. , Dai Yanzhenzi , Ivell Richard , Anand-Ivell Ravinder , Rodgers Raymond J. , Knight Philip G.
Published: March 2013

Significance

Ovarian androgen synthesis is essential for normal ovarian follicle development and female fertility in animals and humans. However, ovarian androgen excess, a feature of the widespread polycystic ovarian syndrome in women, is detrimental to fertility and has other pathophysiological consequences. Our findings reveal the importance of the intraovarian growth factor insulin-like peptide 3 signaling for maintaining androgen production by ovarian theca cells and show that the suppressive action of bone morphogenetic proteins on androgen production is linked to their inhibitory effect on insulin-like peptide 3 signaling, likely mediated via down-regulation of the nuclear transcription factor steroidogenic factor-1.
Strong subunit coordination drives a powerful viral DNA packaging motor
Authors: Andrews Benjamin T. , Catalano Carlos Enrique
Published: March 2013

Terminase enzymes are viral motors that package DNA into a preformed capsid and are of interest both therapeutically and as potential nano-machines. The enzymes excise a single genome from a concatemeric precursor (genome maturation) and then package the duplex to near-crystalline density (genome packaging). The functional motors are oligomers of protomeric subunits and are the most powerful motors currently known. Here, we present mechanistic studies on the terminase motor from bacteriophage λ. We identify a mutant (K76R) that is specifically deficient in packaging activity. Biochemical analysis of this enzyme provides insight into the linkage between ATP hydrolysis and motor translocation. We further use this mutant to assemble chimeric motors with WT enzyme and characterize the catalytic activity of the complexes. The data demonstrate that strong coordination between the motor protomers is required for DNA packaging and that incorporation of even a single mutant protomer poisons motor activity. Significant coordination is similarly observed in the genome maturation reaction; however, although the motor is composed of a symmetric tetramer of protomers, the maturation complex is better described as a “dimer-of-dimers” with half-site reactivity. We describe a model for how the motor alternates between a stable genome maturation complex and a dynamic genome packaging complex. The fundamental features of coordinated ATP hydrolysis, DNA movement, and tight association between the motor and the duplex during translocation are recapitulated in all of the viral motors. This work is thus of relevance to all terminase enzymes, both prokaryotic and eukaryotic.
Substrate selectivity in arginine-dependent acid resistance in enteric bacteria
Authors: Tsai Ming-Feng , Miller Christopher
Published: March 2013

To successfully colonize the human gut, enteric bacteria must activate acid resistance systems to survive the extreme acidity (pH 1.5–3.5) of the stomach. The antiporter AdiC is the master orchestrator of the arginine-dependent system. Upon acid shock, it imports extracellular arginine (Arg) into the cytoplasm, providing the substrate for arginine decarboxylases, which consume a cellular proton ending up in a C–H bond of the decarboxylated product agmatine (Agm
2+
). Agm
2+
and the “virtual” proton it carries are exported via AdiC subsequently. It is widely accepted that AdiC counters intracellular acidification by continuously pumping out virtual protons. However, in the gastric environment, Arg is present in two carboxyl-protonation forms, Arg
+
and Arg
2+
. Virtual proton pumping can only be achieved by Arg
+
/Agm
2+
exchange, whereas Arg
2+
/Agm
2+
exchange would produce no net proton movement. This study experimentally asks which exchange AdiC catalyzes, an issue previously unapproachable due to the absence of a reconstituted system mimicking the situation of bacteria in the stomach. Here, using an oriented liposome system able to hold a three-unit pH gradient, we demonstrate that Arg/Agm exchange by AdiC is strongly electrogenic with positive charge moved outward, and thus that AdiC mainly mediates Arg
+
/Agm
2+
exchange to support effective virtual proton pumping. Further experiments reveal a mechanistic surprise—that AdiC selects Arg
+
against Arg
2+
on the basis of gross valence, rather than by local scrutiny of protonation states of the carboxyl group, as had been suggested by Arg-bound AdiC crystal structures.
Probing the relative orientation of molecules bound to DNA through controlled interference using second-harmonic generation
Authors: Doughty Benjamin , Rao Yi , Kazer Samuel W. , Kwok Sheldon J. J. , Turro Nicholas J. , Eisenthal Kenneth B.
Published: March 2013

A method is described in which the interference of radiated second-harmonic electric fields generated by a pair of oriented molecules intercalated into double-stranded DNA is controlled and measured. The results show that the relative molecular orientation of the two molecules significantly changes the magnitude of the observed second-harmonic generation intensity, which is described by a simple model that accounts for the interferences of the radiated fields. The technique presented shows promise for future experiments investigating structural changes induced by the formation of a DNA–biomolecule complex.
TERT
promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal
Authors: Killela Patrick J. , Reitman Zachary J. , Jiao Yuchen , Bettegowda Chetan , Agrawal Nishant , Diaz Luis A. , Friedman Allan H. , Friedman Henry , Gallia Gary L. , Giovanella Beppino C. , Grollman Arthur P. , He Tong-Chuan , He Yiping , Hruban Ralph H. , Jallo George I. , Mandahl Nils , Meeker Alan K. , Mertens Fredrik , Netto George J. , Rasheed B. Ahmed , Riggins Gregory J. , Rosenquist Thomas A. , Schiffman Mark , Shih Ie-Ming , Theodorescu Dan , Torbenson Michael S. , Velculescu Victor E. , Wang Tian-Li , Wentzensen Nicolas , Wood Laura D. , Zhang Ming , McLendon Roger E. , Bigner Darell D. , Kinzler Kenneth W. , Vogelstein Bert , Papadopoulos Nickolas , Yan Hai
Published: March 2013

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins
alpha thalassemia/mental retardation syndrome X-linked
(
ATRX
) or
death-domain associated protein
(
DAXX
) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the
telomerase reverse transcriptase
(
TERT
) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of
TERT
promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type).
TERT
and
ATRX
mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis,
TERT
mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.
A T-cell response to a liver-stagePlasmodiumantigen is not boosted by repeated sporozoite immunizations
Authors: Murphy Sean C. , Kas Arnold , Stone Brad C. , Bevan Michael J.
Published: March 2013

Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed byPlasmodiumparasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized withPlasmodium yoeliisporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum ofPlasmodiumliver-stage proteins.
Duplication formulae involving Jacobi theta functions and Gosper’s 𝑞-trigonometric functions
Authors: Mező István
Published: March 2013

Using the

q
q

-trigonometric definitions of Gosper, we devise a new

q
q

-exponential function. Based on this concept, we derive a number of identities involving the Jacobi theta functions. These considerations lead to the answers to Gosper’s “mysteries”.
Forests as promoters of terrestrial life-history strategies in East African amphibians
Authors: Müller Hendrik , Liedtke H. Christoph , Menegon Michele , Beck Jan , Ballesteros-Mejia Liliana , Nagel Peter , Loader Simon P.
Published: March 2013

Many amphibian lineages show terrestrialization of their reproductive strategy and breeding is partially or completely independent of water. A number of causal factors have been proposed for the evolution of terrestrialized breeding. While predation has received repeated attention as a potential factor, the influence of other factors such as habitat has never been tested using appropriate data or methods. Using a dataset that comprises 180 amphibian species from various East African habitats, we tested whether species occurring in different habitats show different patterns of terrestrialization in their breeding strategy. We recovered a significant association between terrestrialized breeding strategies and forest habitats. In general, forest seems to act as a facilitator, providing a permissive environment for the evolution of terrestrialized breeding strategies. However, while terrestrial oviposition is strongly correlated with lowland and montane forest habitat, complete terrestrial development is significantly correlated with montane forest only, indicating different selective pressures acting at different steps towards complete terrestrial development.
Predator–prey body size relationships when predators can consume prey larger than themselves
Authors: Nakazawa Takefumi , Ohba Shin-ya , Ushio Masayuki
Published: March 2013

As predator–prey interactions are inherently size-dependent, predator and prey body sizes are key to understanding their feeding relationships. To describe predator–prey size relationships (PPSRs) when predators can consume prey larger than themselves, we conducted field observations targeting three aquatic hemipteran bugs, and assessed their body masses and those of their prey for each hunting event. The data revealed that their PPSR varied with predator size and species identity, although the use of the averaged sizes masked these effects. Specifically, two predators had slightly decreased predator–prey mass ratios (PPMRs) during growth, whereas the other predator specialized on particular sizes of prey, thereby showing a clear positive size–PPMR relationship. We discussed how these patterns could be different from fish predators swallowing smaller prey whole.
Fluid mechanical consequences of pendular activity, segmentation and pyloric outflow in the proximal duodenum of the rat and the guinea pig
Authors: de Loubens Clément , Lentle Roger G. , Love Richard J. , Hulls Corrin , Janssen Patrick W. M.
Published: March 2013

We conducted numerical experiments to study the influence of non-propagating longitudinal and circular contractions, i.e. pendular activity and segmentation, respectively, on flow and mixing in the proximal duodenum. A lattice-Boltzmann numerical method was developed to simulate the fluid mechanical consequences for each of 22 randomly selected sequences of high-definition video of real longitudinal and radial contractile activity in the isolated proximal duodenum of the rat and guinea pig. During pendular activity in the rat duodenum, the flow was characterized by regions of high shear rate. Mixing was so governed by shearing deformation of the fluid that increased the interface between adjacent domains and accelerated their inter-diffusion (for diffusion coefficients approx. less than 10−8m² s−1). When pendular activity was associated with a slow gastric outflow characteristic of post-prandial period, the dispersion was also improved, especially near the walls. Mixing was not promoted by isolated segmentative contractions in the guinea pig duodenum and not notably influenced by pylorus outflow. We concluded that pendular activity generates mixing of viscous fluids ‘in situ’ and accelerates the diffusive mass transfer, whereas segmentation may be more important in mixing particulate suspensions with high solid volume ratios.
Fick's second law transformed: one path to cloaking in mass diffusion
Authors: Guenneau S. , Puvirajesinghe T. M.
Published: March 2013

Here, we adapt the concept of transformational thermodynamics, whereby the flux of temperature is controlled via anisotropic heterogeneous diffusivity, for the diffusion and transport of mass concentration. The
n
-dimensional, time-dependent, anisotropic heterogeneous Fick's equation is considered, which is a parabolic partial differential equation also applicable to heat diffusion, when convection occurs, for example, in fluids. This theory is illustrated with finite-element computations for a liposome particle surrounded by a cylindrical multi-layered cloak in a water-based environment, and for a spherical multi-layered cloak consisting of layers of fluid with an isotropic homogeneous diffusivity, deduced from an effective medium approach. Initial potential applications could be sought in bioengineering.
Temperature and CO2additively regulate physiology, morphology and genomic responses of larval sea urchins,Strongylocentrotus purpuratus
Authors: Padilla-Gamiño Jacqueline L. , Kelly Morgan W. , Evans Tyler G. , Hofmann Gretchen E.
Published: March 2013

Ocean warming and ocean acidification, both consequences of anthropogenic production of CO2, will combine to influence the physiological performance of many species in the marine environment. In this study, we used an integrative approach to forecast the impact of future ocean conditions on larval purple sea urchins (Strongylocentrotus purpuratus) from the northeast Pacific Ocean. In laboratory experiments that simulated ocean warming and ocean acidification, we examined larval development, skeletal growth, metabolism and patterns of gene expression using an orthogonal comparison of two temperature (13°C and 18°C) and pCO2(400 and 1100 μatm) conditions. Simultaneous exposure to increased temperature and pCO2significantly reduced larval metabolism and triggered a widespread downregulation of histone encoding genes. pCO2but not temperature impaired skeletal growth and reduced the expression of a major spicule matrix protein, suggesting that skeletal growth will not be further inhibited by ocean warming. Importantly, shifts in skeletal growth were not associated with developmental delay. Collectively, our results indicate that global change variables will have additive effects that exceed thresholds for optimized physiological performance in this keystone marine species.
Fungal symbioses in hornworts: a chequered history
Authors: Desirò Alessandro , Duckett Jeffrey G. , Pressel Silvia , Villarreal Juan Carlos , Bidartondo Martin I.
Published: March 2013

Hornworts are considered the sister group to vascular plants, but their fungal associations remain largely unexplored. The ancestral symbiotic condition for all plants is, nonetheless, widely assumed to be arbuscular mycorrhizal with Glomeromycota fungi. Owing to a recent report of other fungi in some non-vascular plants, here we investigate the fungi associated with diverse hornworts worldwide, using electron microscopy and molecular phylogenetics. We found that both Glomeromycota and Mucoromycotina fungi can form symbioses with most hornworts, often simultaneously. This discovery indicates that ancient terrestrial plants relied on a wider and more versatile symbiotic repertoire than previously thought, and it highlights the so far unappreciated ecological and evolutionary role of Mucoromycotina fungi.
Individual heterogeneity and costly punishment: a volunteer's dilemma
Authors: Przepiorka Wojtek , Diekmann Andreas
Published: March 2013

Social control and the enforcement of social norms glue a society together. It has been shown theoretically and empirically that informal punishment of wrongdoers fosters cooperation in human groups. Most of this research has focused on voluntary and uncoordinated punishment carried out by individual group members. However, as punishment is costly, it is an open question as to why humans engage in the punishment of wrongdoers even in one-time-only encounters. While evolved punitive preferences have been advocated as proximate explanations for such behaviour, the strategic nature of the punishment situation has remained underexplored. It has been suggested to conceive of the punishment situation as a volunteer's dilemma (VOD), where only one individual's action is necessary and sufficient to punish the wrongdoer. Here, we show experimentally that implementing the punishment situation as a VOD sustains cooperation in an environment where punishers and non-punishers coexist. Moreover, we show that punishment-cost heterogeneity allows individuals to tacitly agree on only the strongest group member carrying out the punishment, thereby increasing the effectiveness and efficiency of social norm enforcement. Our results corroborate that costly peer punishment can be explained without assuming punitive preferences and show that centralized sanctioning institutions can emerge from arbitrary individual differences.
The anisotropy1 D604N Mutation in the Arabidopsis Cellulose Synthase1 Catalytic Domain Reduces Cell Wall Crystallinity and the Velocity of Cellulose Synthase Complexes
Authors: Fujita Miki , Himmelspach Regina , Ward Juliet , Whittington Angela , Hasenbein Nortrud , Liu Christine , Truong Thy T. , Galway Moira E. , Mansfield Shawn D. , Hocart Charles H. , Wasteneys Geoffrey O.
Published: March 2013

Multiple cellulose synthase (CesA) subunits assemble into plasma membrane complexes responsible for cellulose production. In the Arabidopsis (Arabidopsis thaliana) model system, we identified a novel D604N missense mutation, designated anisotropy1 (any1), in the essential primary cell wall CesA1. Most previously identified CesA1 mutants show severe constitutive or conditional phenotypes such as embryo lethality or arrest of cellulose production but any1 plants are viable and produce seeds, thus permitting the study of CesA1 function. The dwarf mutants have reduced anisotropic growth of roots, aerial organs, and trichomes. Interestingly, cellulose microfibrils were disordered only in the epidermal cells of the any1 inflorescence stem, whereas they were transverse to the growth axis in other tissues of the stem and in all elongated cell types of roots and dark-grown hypocotyls. Overall cellulose content was not altered but both cell wall crystallinity and the velocity of cellulose synthase complexes were reduced in any1. We crossed any1 with the temperature-sensitive radial swelling1-1 (rsw1-1) CesA1 mutant and observed partial complementation of the any1 phenotype in the transheterozygotes at rsw1-1’s permissive temperature (21°C) and full complementation by any1 of the conditional rsw1-1 root swelling phenotype at the restrictive temperature (29°C). In rsw1-1 homozygotes at restrictive temperature, a striking dissociation of cellulose synthase complexes from the plasma membrane was accompanied by greatly diminished motility of intracellular cellulose synthase-containing compartments. Neither phenomenon was observed in the any1 rsw1-1 transheterozygotes, suggesting that the proteins encoded by the any1 allele replace those encoded by rsw1-1 at restrictive temperature.
RABA Members Act in Distinct Steps of Subcellular Trafficking of the FLAGELLIN SENSING2 Receptor
Authors: Choi Seung-won , Tamaki Takayuki , Ebine Kazuo , Uemura Tomohiro , Ueda Takashi , Nakano Akihiko
Published: March 2013

Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo–synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis.
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of the mitochondrial tryparedoxin peroxidase fromLeishmania braziliensis
Authors: de Morais Mariana Abrahão Bueno , de Souza Tatiana de Arruda Campos Brasil , Murakami Mario Tyago
Published: March 2013

Tryparedoxin peroxidase (TXNPx) is an essential constituent of the main enzymatic scavenger system for reactive oxygen species (ROS) in trypanosomatids. Genetic studies have demonstrated the importance of this system for the development and virulence of these parasites, representing a potential target for the discovery of new trypanocidal drugs. In this work, the mitochondrial TXNPx fromLeishmania braziliensiswas cloned, overexpressed, purified and crystallized. The crystals diffracted to 3.3 Å resolution and belonged to space groupP42212, with unit-cell parametersa=b= 131.8,c= 44.4 Å. These studies will contribute to a better understanding of the molecular mechanisms involved in ROS detoxification by trypanosomatids.
Purification, crystallization and preliminary crystallographic analysis of a 4-thiouridine synthetase–RNA complex
Authors: Naumann Peter-Thomas , Lauhon Charles T. , Ficner Ralf
Published: March 2013

The sulfurtransferase 4-thiouridine synthetase (ThiI) is involved in the ATP-dependent modification of U8 in tRNA. ThiI fromThermotoga maritimawas cloned, overexpressed and purified. A complex comprising ThiI and a truncated tRNA was prepared and crystallized, and X-ray diffraction data were collected to a resolution of 3.5 Å. The crystals belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 102.9,b= 112.8,c= 132.8 Å.
The 1.58 Å resolution structure of the DNA-binding domain of bacteriophage SF6 small terminase provides new hints on DNA binding
Authors: Benini Stefano , Chechik Maria , Ortiz Lombardía Miguel , Polier Sigrun , Leech Andrew , Shevtsov Mikhail B. , Alonso Juan C.
Published: March 2013

DNA packaging in tailed bacteriophages and in evolutionarily related herpesviruses is controlled by a viral-encoded terminase. As in a number of other phages, in theBacillus subtilisbacteriophages SF6 and SPP1 the terminase complex consists of two proteins: G1P and G2P. The crystal structure of the N-terminal DNA-binding domain of the bacteriophage SF6 small terminase subunit G1P is reported. Structural comparison with other DNA-binding proteins allows a general model for the interaction of G1P with the packaging-initiation site to be proposed.
Crystallization and X-ray structure determination of a thermoalkalophilic lipase fromGeobacillusSBS-4S
Authors: Tayyab Muhammad , Rashid Naeem , Angkawidjaja Clement , Kanaya Shigenori , Akhtar Muhammad
Published: March 2013

A thermoalkalophilic lipase (LIPSBS) from the newly isolatedGeobacillusstrain SBS-4S which hydrolyzes a wide range of fatty acids has been characterized. In the present study, the crystallization of purified LIPSBSusing the sitting-drop vapour-diffusion method and its X-ray diffraction studies are described. The crystals belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 55.13,b= 71.75,c= 126.26 Å. The structure was determined at 1.6 Å resolution by the molecular-replacement method using the lipase fromG. stearothermophilusL1 as a model.
Structure of PCNA fromDrosophila melanogaster
Authors: Wang Ke , Shi Zhubing , Zhang Min , Cheng Dianlin
Published: March 2013

Proliferating cell nuclear antigen (PCNA) plays essential roles in DNA replication, DNA repair, cell-cycle regulation and chromatin metabolism. The PCNA fromDrosophila melanogaster(DmPCNA) was purified and crystallized. The crystal of DmPCNA diffracted to 2.0 Å resolution and belonged to space groupH3, with unit-cell parametersa=b= 151.16,c= 38.28 Å. The structure of DmPCNA was determined by molecular replacement. DmPCNA forms a symmetric homotrimer in a head-to-tail manner. An interdomain connector loop (IDCL) links the N- and C-terminal domains. Additionally, the N-terminal and C-terminal domains contact each other through hydrophobic associations. Compared with human PCNA, the IDCL of DmPCNA has conformational changes, which may explain their difference in function. This work provides a structural basis for further functional and evolutionary studies of PCNA.
Crystallization and preliminary X-ray diffraction analysis of the secreted protein Athe_0614 fromCaldicellulosiruptor bescii
Authors: Yokoyama Hiroshi , Yamashita Takahiro , Horikoshi Naoki , Kurumizaka Hitoshi , Kagawa Wataru
Published: March 2013

The Athe_0614 protein is a component of the extracellular proteins secreted by the anaerobic, extremely thermophilic and cellulolytic bacteriumCaldicellulosiruptor bescii. The recombinant protein was expressed inEscherichia coli, purified to near-homogeneity and crystallized using polyethylene glycol 2000 monomethyl ether as a precipitant. The crystals belonged to the monoclinic space groupP21, with unit-cell parametersa= 48.4,b= 42.2,c= 97.8 Å, β = 96.1°, and diffracted to 2.7 Å resolution using synchrotron radiation.
Structure of glutaminyl cyclase fromDrosophila melanogasterin space groupI4
Authors: Kolenko Petr , Koch Birgit , Rahfeld Jens-Ulrich , Schilling Stephan , Demuth Hans-Ulrich , Stubbs Milton T.
Published: March 2013

The structure of ligand-free glutaminyl cyclase (QC) fromDrosophila melanogaster(DmQC) has been determined in a novel crystal form. The protein crystallized in space groupI4, with unit-cell parametersa=b= 122.3,c = 72.7 Å. The crystal diffracted to a resolution of 2 Å at the home source. The structure was solved by molecular replacement and was refined to anRfactor of 0.169.DmQC exhibits a typical α/β-hydrolase fold. The electron density of three monosaccharides could be localized. The accessibility of the active site will facilitate structural studies of novel inhibitor-binding modes.
Sample preparation, crystallization and structure solution of HisC fromMycobacterium tuberculosis
Authors: Nasir Nazia , Vyas Rajan , Biswal Bichitra K.
Published: March 2013

Histidinolphosphate aminotransferase (HisC; Rv1600) fromMycobacterium tuberculosiswas overexpressed inM. smegmatisand purified to homogeneity using nickel–nitrilotriacetic acid metal-affinity and gel-filtration chromatography. Diffraction-quality crystals suitable for X-ray analysis were grown by the hanging-drop vapour-diffusion technique using 30% polyethylene glycol monomethyl ether 2000 as the precipitant. The crystals belonged to the hexagonal space groupP3221, with an unusual high solvent content of 74.5%. X-ray diffraction data were recorded to 3.08 Å resolution from a single crystal using in-house Cu Kα radiation. The structure of HisC was solved by the molecular-replacement method using itsCorynebacterium glutamicumcounterpart as a search model. HisC is a dimer in the crystal as well as in solution.
Purification, crystallization and preliminary X-ray analysis of TP0435 (Tp17) from the syphilis spirocheteTreponema pallidum
Authors: Brautigam Chad A. , Deka Ranjit K. , Norgard Michael V.
Published: March 2013

Syphilis, caused by the bacterial spirocheteTreponema pallidum, remains a prominent sexually transmitted infection worldwide. Despite sequencing of the genome of this obligate human pathogen 15 years ago, the functions of a large number of the gene products ofT. pallidumare still unknown, particularly with respect to those of the organism's periplasmic lipoproteins. To better understand their functions, a structural biology approach has been pursued. To this end, the soluble portion of theT. pallidumTP0435 lipoprotein (also known as Tp17) was cloned, hyper-expressed inEscherichia coliand purified to apparent homogeneity. The protein crystals obtained from this preparation diffracted to 2.4 Å resolution and had the symmetry of space groupR3. In the hexagonal setting, the unit-cell parameters werea=b= 85.7,c= 85.4 Å.
Effect of composition of gluten proteins and dough rheological properties on the cookie‐making quality
Authors: Barak Sheweta , Mudgil Deepak , Singh Khatkar Bhupendar
Published: March 2013

Purpose

The purpose of the paper is to study the effect of the gliadin and glutenin fractions of gluten on the cookie quality.

Design/methodology/approach

Ten different wheat varieties were analyzed for the flour physicochemical characteristics, gluten composition and rheological properties. The different flours were baked into cookies. The cookies were analyzed for spread ratio and texture. Relationships of various flour parameters, gluten composition and cookie characteristics were determined.

Findings

Gluten subfractions, damaged starch, protein, AWRC values were significantly correlated to the cookie spread and texture. Damaged starch (r=−0.638), protein (r=−0.508) and AWRC (r=−0.844) had a negative relationship with the cookie spread. The flours with higher SDS sedimentation value also produced cookies with lower spread ratio and harder texture. The study clearly demonstrated a positive correlation between Gli:Glu ratio (r=0.765) and spread ratio and a negative correlation (r=−0.528) with hardness of the cookies measured in terms of breaking force. Flours with lower dough development time and dough stability performed better as cookie flours.

Originality/value

The gliadins and Gli/Glu ratio had a significant effect on the cookie spread and texture and the prediction equation developed during the study could accurately predict the cookie spread from the Gli/Glu ratio and AWRC values.
Case study: An examination of the decision making process for selecting simulations for an online MBA program
Authors: Neely Pat , Tucker Jan
Published: March 2013

Purpose

Simulations are designed as activities which imitate real world scenarios and are often used to teach and enhance skill building. The purpose of this case study is to examine the decision making process and outcomes of a faculty committee tasked with examining simulations in the marketplace to determine if the simulations could be used as assessment instruments in a new MBA program.

Design/methodology/approach

The criterion for evaluating the decision making process was developed by adapting the five dimensional framework developed by Gulikers, Bastiaens and Kirschner.

Findings

The paper will conclude with a review of outcomes from the evaluation process and suggestions on how the decision process might be streamlined for faculty and curriculum designers who are developing new business programs.

Research limitations/implications

Expectations for evaluating simulations need to be completely defined before beginning the review process, assign an individual with content knowledge to lead the review of individual simulations, vendor presentations of the simulations tended to sway the evaluator's opinion of the product in a more positive manner regardless of content.

Practical implications

Competency based education continues to be a focus in higher education as the pressure to illustrate demonstrable skills continues to mount. Simulations may play a role in helping students obtain competencies in specific areas but their ability to assess competencies acquired warrants further research. A solid and rational decision making process is required to accurately determine the effectiveness of using simulations in an MBA program.

Social implications

Simulations allow students to interact with complex systems and ideas but assessing the actual learning that takes place can be challenging (Frezzo, Behrens, and Mislevy). Students still need a conceptual framework of the material being presented in order for the simulations to be meaningful. Finding an effective instructional model which supports both hard (technical or procedural) and soft (people, communication) skills can be challenging as the soft skills are more difficult to quantify. Instituting an effective evaluation and decision process when evaluating these types of assessments is important when determining their value in a classroom.

Originality/value

This case study was based on the decision process of the University and the College of Business Administration in determining how simulations could be used in a competency based MBA program.
Student placement service: An exploratory investigation of employer retention and a “Priority Partner” intervention
Authors: Walsh Francis D. , Byrne Seán
Published: March 2013

Purpose

The purpose of this paper is to investigate the factors relating to retention of employers on an undergraduate work placement programme in a third level institution.

Design/methodology/approach

An action research methodology involving problem diagnosis, intervention planning, action and evaluation is employed. The diagnosis involved a survey of 130 employers that had taken students on placement during the first two years of the placement programme. The action research also involved workshops with the work placement team and the making of an intervention with respect to enhancing the placement process through the introduction of a Priority Partner initiative for 26 of the employers.

Findings

The survey findings reveal differences in the ranking of importance of college selection criteria by employers, as well the impact of the placement manager's characteristics on the placement process. The intervention findings show that the employer retention percentage increased for the Priority Partners but remained the same for the other employers.

Research limitations/implications

The study reports qualitative findings in the context of a placement programme in one institution which limits external validity.

Practical implications

Employer retention would seem to be improved with the development of a customer relations management orientation with employers. The role of the placement manager is pivotal to enhancing the retention of employers as is the quality and professionalism of the work placement service.

Originality/value

New empirical data extends the very limited understanding of company retention on work placement programmes.
Want to change the world? Think differently
Authors: by Gareth Bell Interview
Published: March 2013

Purpose

The purpose of this paper is to provide an interview with Paul Polman, CEO of Unilever.

Design/methodology/approach

This paper presents part 2 of an interview with Paul Polman.

Findings

Discusses Unilever's presence in emerging markets, and its efforts to create markets in under‐developed regions.

Originality/value

The interview offers advice for leaders operating in a challenging business environment, and those looking to create more sustainable business models.