bluuebunny/crossref_metadata_2025 huggingface dataset:
Enantiomorphy in Banksia (Proteaceae): flowers and fruits
Authors: Renshaw A. , Burgin S.
Published: June 2008

There is a history of discrepancy in the interpretation of floral symmetry in the genus Banksia L.f. The variation arises not just from the potential nuances of symmetry terminology, as variation is also found in the diagrams that describe it. This paper clarifies the issue of the orientation of the ovaries within a Banksia unit inflorescence. Dissection of 2400 flowers in situ from four Banksia species has revealed the Banksia unit inflorescence to be enantiomorphic (having left-right asymmetry) due to the orientation of the ovaries. The asymmetry of the ovary and its pronounced development of the anterior side in fruit formation means that fruits are also readily distinguished as having arisen from either a left- or right-handed flower.
Hyperhydricity reversal and clonal propagation of four-wing saltbush (Atriplex canescens, Chenopodiaceae) cultivated in vitro
Authors: Reyes-Vera Isaac , Potenza Carol , Barrow Jerry
Published: June 2008

In vitro propagated shoots of four-wing saltbush (Atriplex canescens, Pursh Nutt) showed severe symptoms of hyperhydricity. We show that the reversion of hyperhydric A. canescens shoots to normal shoots was significantly affected by the presence of inorganic nitrogen in the culture vessel. When the culture vessel was vented or when ammonium nitrate was deleted from Murashige and Skoog basal medium, rates of reversion were significantly higher. Although statistically significant differences were evident when comparing vented v. non-vented treatments for each medium, the modified culture medium with vented closures was consistently the best treatment, showing a total cumulative frequency of 39.7% reversion to normal morphology, compared with a total cumulative frequency of 7.1% observed in the control treatment. Resulting normal shoots also showed significant improvements in further manipulations, including rooting in vitro, transplantation to soil and survival in native sites.
Pharmacological evidence indicates that MAPKK/CDPK modulate NO levels in darkness-induced stomatal closure of broad bean
Authors: She Xiaoping , Song Xigui
Published: June 2008

By using pharmacological approaches and laser scanning confocal microscopy (LSCM) based on 4, 5-diaminofluorescein diacetate (DAF-2 DA), the roles of MAPKK/CDPK and their effects on nitric oxide (NO) levels of guard cells during darkness-induced stomatal closure in broad bean were investigated. The results indicated that both 2′-amino-3′-methoxyflavone (PD98059) (an inhibitor of mitogen-activated protein kinase kinase, MAPKK) and trifluoperazine (TFP) (a specific inhibitor of calcium-dependent protein kinase, CDPK) reduced the levels of NO in guard cells and significantly reversed darkness-induced stomatal closure, implying that MAPKK/CDPK mediate darkness-induced stomatal closure by enhancing NO levels in guard cells. In addition, as with NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), but not with nitric oxide synthase inhibitor NG-nitro-L-Arg-methyl ester (L-NAME), PD98059 and TFP not only reduced 4,5-diaminofluorescein diacetate (DAF-2 DA) fluorescence in guard cells by sodium nitroprusside (SNP) in light, but also abolished NO that had been generated during a dark period, and reversed stomatal closure by SNP and by darkness, suggesting MAPKK and CDPK are probably related to restraining the NO scavenging to elevate NO levels in guard cells, during darkness-induced stomatal closure. The results also showed that both PD98059 and TFP reduced stomatal closure by SNP, implying that the possibility of MAPKK and CDPK acting as the target downstream of NO should not be ruled out. There may be a causal and interdependent relationship between MAPKK/CDPK and NO in darkness-induced stomatal closure, and in the process this cross-talk may lead to the formation of a self-amplification loop about them.
Phytophthora cinnamomi and Australia's biodiversity: impacts, predictions and progress towards control
Authors: Cahill David M. , Rookes James E. , Wilson Barbara A. , Gibson Lesley , McDougall Keith L.
Published: June 2008

Phytophthora cinnamomi continues to cause devastating disease in Australian native vegetation and consequently the disease is listed by the Federal Government as a process that is threatening Australia’s biodiversity. Although several advances have been made in our understanding of how this soil-borne pathogen interacts with plants and of how we may tackle it in natural systems, our ability to control the disease is limited. The pathogen occurs widely across Australia but the severity of its impact is most evident within ecological communities of the south-west and south-east of the country. A regional impact summary for all states and territories shows the pathogen to be the cause of serious disease in numerous species, a significant number of which are rare and threatened. Many genera of endemic taxa have a high proportion of susceptible species including the iconic genera Banksia, Epacris and Xanthorrhoea. Long-term studies in Victoria have shown limited but probably unsustainable recovery of susceptible vegetation, given current management practices. Management of the disease in conservation reserves is reliant on hygiene, the use of chemicals and restriction of access, and has had only limited effectiveness and not provided complete control. The deleterious impacts of the disease on faunal habitat are reasonably well documented and demonstrate loss of individual animal species and changes in population structure and species abundance. Few plant species are known to be resistant to P. cinnamomi; however, investigations over several years have discovered the mechanisms by which some plants are able to survive infection, including the activation of defence-related genes and signalling pathways, the reinforcement of cell walls and accumulation of toxic metabolites. Manipulation of resistance and resistance-related mechanisms may provide avenues for protection against disease in otherwise susceptible species. Despite the advances made in Phytophthora research in Australia during the past 40 years, there is still much to be done to give land managers the resources to combat this disease. Recent State and Federal initiatives offer the prospect of a growing and broader awareness of the disease and its associated impacts. However, awareness must be translated into action as time is running out for the large number of susceptible, and potentially susceptible, species within vulnerable Australian ecological communities.
Seed germination of Solanum spp. (Solanaceae) for use in rehabilitation and commercial industries
Authors: Commander L. E. , Merritt D. J. , Rokich D. P. , Flematti G. R. , Dixon K. W.
Published: June 2008

Effective methods for propagation of native Solanum species are required for mine rehabilitation and the native food industry in Australia. This study investigated seed germination of eight native Solanum species with respect to incubation temperature and the efficacy of germination-promoting compounds gibberellic acid (GA3), the butenolide isolated from smoke (karrikinolide, KAR1) and smoke water (SW). Seeds of all species were tested under a temperature regime of 26/13°C or 33/18°C. In these conditions, seeds of only two species, S. cunninghamii Benth. and S. phlomoides Benth. germinated to high levels without treatment. Of the remaining six species, GA3 alone promoted germination in S. chippendalei Symon, S. diversiflorum F.Muell. and S. sturtianum F.Muell., whereas GA3, KAR1 and SW were effective at promoting germination of S. centrale J.M.Black, S. dioicum W.Fitzg. and S. orbiculatum Dunal ex Poir. to varying degrees. Additional incubation temperatures (10, 15, 20, 25 and 30°C) were examined for S. centrale and S. orbiculatum. For both species, broadly similar patterns were noted in the response of seeds to GA3, KAR1 and SW across all temperatures. However, for S. centrale seeds, germination percentages were higher at 26/13°C than at any of the constant temperatures, and there was a trend of increasing germination with increasing constant temperature for S. orbiculatum seeds. Analysis of seed embryo type and imbibition characteristics and consideration of the subsequent germination results indicates that dormant Solanum seeds possess physiological dormancy.
Cytokine secretion requires phosphatidylcholine synthesis
Authors: Tian Yong , Pate Caroline , Andreolotti Alberto , Wang Limin , Tuomanen Elaine , Boyd Kelli , Claro Enrique , Jackowski Suzanne
Published: June 2008

Choline cytidylyltransferase (CCT) is the rate-limiting enzyme in the phosphatidylcholine biosynthetic pathway. Here, we demonstrate that CCTα-mediated phosphatidylcholine synthesis is required to maintain normal Golgi structure and function as well as cytokine secretion from the Golgi complex. CCTα is localized to the trans-Golgi region and its expression is increased in lipopolysaccharide (LPS)-stimulated wild-type macrophages. Although LPS triggers transient reorganization of Golgi morphology in wild-type macrophages, similar structural alterations persist in CCTα-deficient cells. Pro–tumor necrosis factor α and interleukin-6 remain lodged in the secretory compartment of CCTα-deficient macrophages after LPS stimulation. However, the lysosomal-mediated secretion pathways for interleukin-1β secretion and constitutive apolipoprotein E secretion are unaltered. Exogenous lysophosphatidylcholine restores LPS-stimulated secretion from CCTα-deficient cells, and elevated diacylglycerol levels alone do not impede secretion of pro–tumor necrosis factor α or interleukin-6. These results identify CCTα as a key component in membrane biogenesis during LPS-stimulated cytokine secretion from the Golgi complex.
Spatial mapping of splicing factor complexes involved in exon and intron definition
Authors: Ellis Jonathan D. , Llères David , Denegri Marco , Lamond Angus I. , Cáceres Javier F.
Published: June 2008

We have analyzed the interaction between serine/arginine-rich (SR) proteins and splicing components that recognize either the 5′ or 3′ splice site. Previously, these interactions have been extensively characterized biochemically and are critical for both intron and exon definition. We use fluorescence resonance energy transfer (FRET) microscopy to identify interactions of individual SR proteins with the U1 small nuclear ribonucleoprotein (snRNP)–associated 70-kD protein (U1 70K) and with the small subunit of the U2 snRNP auxiliary factor (U2AF35) in live-cell nuclei. We find that these interactions occur in the presence of RNA polymerase II inhibitors, demonstrating that they are not exclusively cotranscriptional. Using FRET imaging by means of fluorescence lifetime imaging microscopy (FLIM), we map these interactions to specific sites in the nucleus. The FLIM data also reveal a previously unknown interaction between HCC1, a factor related to U2AF65, with both subunits of U2AF. Spatial mapping using FLIM-FRET reveals differences in splicing factors interactions within complexes located in separate subnuclear domains.
Regulation of RhoA-dependent ROCKII activation by Shp2
Authors: Lee Hsiao-Hui , Chang Zee-Fen
Published: June 2008

Contractile forces mediated by RhoA and Rho kinase (ROCK) are required for a variety of cellular processes, including cell adhesion. In this study, we show that RhoA-dependent ROCKII activation is negatively regulated by phosphorylation at a conserved tyrosine residue (Y722) in the coiled-coil domain of ROCKII. Tyrosine phosphorylation of ROCKII is increased with cell adhesion, and loss of Y722 phosphorylation delays adhesion and spreading on fibronectin, suggesting that this modification is critical for restricting ROCKII-mediated contractility during these processes. Further, we provide evidence that Shp2 mediates dephosphorylation of ROCKII and, therefore, regulates RhoA-induced cell rounding, indicating that Shp2 couples with RhoA signaling to control ROCKII activation during deadhesion. Thus, reversible tyrosine phosphorylation confers an additional layer of control to fine-tune RhoA-dependent activation of ROCKII.
The AAA ATPase Rix7 powers progression of ribosome biogenesis by stripping Nsa1 from pre-60S particles
Authors: Kressler Dieter , Roser Daniela , Pertschy Brigitte , Hurt Ed
Published: June 2008

Ribosome biogenesis takes place successively in the nucleolar, nucleoplasmic, and cytoplasmic compartments. Numerous nonribosomal factors transiently associate with the nascent ribosomes, but the mechanisms driving ribosome formation are mostly unknown. Here, we show that an energy-consuming enzyme, the AAA-type (ATPases associated with various cellular activities) ATPase Rix7, restructures a novel pre-60S particle at the transition from the nucleolus to nucleoplasm. Rix7 interacts genetically with Nsa1 and is targeted to the Nsa1-defined preribosomal particle. In vivo, Nsa1 cannot dissociate from pre-60S particles in rix7 mutants, causing nucleolar Nsa1 to escape to the cytoplasm, where it remains associated with aberrant 60S subunits. Altogether, our data suggest that Rix7 is required for the release of Nsa1 from a discrete preribosomal particle, thereby triggering the progression of 60S ribosome biogenesis.
A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes
Authors: Ha Junghoon , Lo Kevin W.-H. , Myers Kenneth R. , Carr Tiffany M. , Humsi Michael K. , Rasoul Bareza A. , Segal Rosalind A. , Pfister K. Kevin
Published: June 2008

Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)–IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP–dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immunoaffinity purification also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms define dynein populations that are selectively recruited to transport distinct cargoes.
Phosphatidic acid mediates demyelination in Lpin1 mutant mice
Authors: Nadra Karim , Charles Anne-Sophie de Preux , Médard Jean-Jacques , Hendriks William T. , Han Gil-Soo , Grès Sandra , Carman George M. , Saulnier-Blache Jean-Sébastien , Verheijen Mark H.G. , Chrast Roman
Published: June 2008

Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent phosphatidate phosphatase (PAP1) enzyme necessary for normal triacylglycerol biosynthesis. The affected animals developed pronounced peripheral neuropathy characterized by myelin degradation, Schwann cell dedifferentiation and proliferation, and a reduction in nerve conduction velocity. The observed demyelination is mediated by endoneurial accumulation of the substrate of the PAP1 enzyme, phosphatidic acid (PA). In addition, we show that PA is a potent activator of the MEK–Erk pathway in Schwann cells, and that this activation is required for PA-induced demyelination. Our results therefore reveal a surprising role for PA in Schwann cell fate determination and provide evidence of a direct link between diseases affecting lipid metabolism and abnormal Schwann cell function.
Interspecies variation reveals a conserved repressor of α-specific genes in Saccharomyces yeasts
Authors: Zill Oliver A. , Rine Jasper
Published: June 2008

The mating-type determination circuit in Saccharomyces yeast serves as a classic paradigm for the genetic control of cell type in all eukaryotes. Using comparative genetics, we discovered a central and conserved, yet previously undetected, component of this genetic circuit: active repression of α-specific genes in a cells. Upon inactivation of the SUM1 gene in Saccharomyces bayanus, a close relative of Saccharomyces cerevisiae, a cells acquired mating characteristics of α cells and displayed autocrine activation of their mating response pathway. Sum1 protein bound to the promoters of α-specific genes, repressing their transcription. In contrast to the standard model, α1 was important but not required for α-specific gene activation and mating of α cells in the absence of Sum1. Neither Sum1 protein expression, nor its association with target promoters was mating-type-regulated. Thus, the α1/Mcm1 coactivators did not overcome repression by occluding Sum1 binding to DNA. Surprisingly, the mating-type regulatory function of Sum1 was conserved in S. cerevisiae. We suggest that a comprehensive understanding of some genetic pathways may be best attained through the expanded phenotypic space provided by study of those pathways in multiple related organisms.
Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo
Authors: Minella Alex C. , Loeb Keith R. , Knecht Andrea , Welcker Markus , Varnum-Finney Barbara J. , Bernstein Irwin D. , Roberts James M. , Clurman Bruce E.
Published: June 2008

Phosphorylations within N- and C-terminal degrons independently control the binding of cyclin E to the SCFFbw7 and thus its ubiquitination and proteasomal degradation. We have now determined the physiologic significance of cyclin E degradation by this pathway. We describe the construction of a knockin mouse in which both degrons were mutated by threonine to alanine substitutions (cyclin ET74A T393A) and report that ablation of both degrons abolished regulation of cyclin E by Fbw7. The cyclin ET74A T393A mutation disrupted cyclin E periodicity and caused cyclin E to continuously accumulate as cells reentered the cell cycle from quiescence. In vivo, the cyclin ET74A T393A mutation greatly increased cyclin E activity and caused proliferative anomalies. Cyclin ET74A T393A mice exhibited abnormal erythropoiesis characterized by a large expansion of abnormally proliferating progenitors, impaired differentiation, dysplasia, and anemia. This syndrome recapitulates many features of early stage human refractory anemia/myelodysplastic syndrome, including ineffective erythropoiesis. Epithelial cells also proliferated abnormally in cyclin E knockin mice, and the cyclin ET74A T393A mutation delayed mammary gland involution, implicating cyclin E degradation in this anti-mitogenic response. Hyperproliferative mammary epithelia contained increased apoptotic cells, suggesting that apoptosis contributes to tissue homeostasis in the setting of cyclin E deregulation. Overall these data show the critical role of both degrons in regulating cyclin E activity and reveal that complete loss of Fbw7-mediated cyclin E degradation causes spontaneous and cell type-specific proliferative anomalies.
Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease
Authors: Walkley Carl R. , Qudsi Rameez , Sankaran Vijay G. , Perry Jennifer A. , Gostissa Monica , Roth Sanford I. , Rodda Stephen J. , Snay Erin , Dunning Patricia , Fahey Frederic H. , Alt Frederick W. , McMahon Andrew P. , Orkin Stuart H.
Published: June 2008

Osteosarcoma is the most common primary malignant tumor of bone. Analysis of familial cancer syndromes and sporadic cases has strongly implicated both p53 and pRb in its pathogenesis; however, the relative contribution of these mutations to the initiation of osteosarcoma is unclear. We describe here the generation and characterization of a genetically engineered mouse model in which all animals develop short latency malignant osteosarcoma. The genetically engineered mouse model is based on osteoblast-restricted deletion ofp53andpRb. Osteosarcoma development is dependent on loss of p53 and potentiated by loss of pRb, revealing a dominance of p53 mutation in the development of osteosarcoma. The model reproduces many of the defining features of human osteosarcoma including cytogenetic complexity and comparable gene expression signatures, histology, and metastatic behavior. Using a novel in silico methodology termed cytogenetic region enrichment analysis, we demonstrate high conservation of gene expression changes between murine osteosarcoma and known cytogentically rearranged loci from human osteosarcoma. Due to the strong similarity between murine osteosarcoma and human osteosarcoma in this model, this should provide a valuable platform for addressing the molecular genetics of osteosarcoma and for developing novel therapeutic strategies.
Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development
Authors: Hirasawa Ryutaro , Chiba Hatsune , Kaneda Masahiro , Tajima Shoji , Li En , Jaenisch Rudolf , Sasaki Hiroyuki
Published: June 2008

Parental origin-specific DNA methylation regulates the monoallelic expression of the mammalian imprinted genes. The methylation marks or imprints are established in the parental germline and maintained throughout embryonic development. However, it is unclear how the methylation imprints are maintained through extensive demethylation in cleavage-stage preimplantation embryos. Previous reports suggested that DNA methyltransferase(s) other than Dnmt1 is involved in the maintenance of the imprints during cleavage. Here we demonstrate, by using conditional knockout mice, that the other known DNA methyltransferases Dnmt3a and Dnmt3b are dispensable for the maintenance of the methylation marks at most imprinted loci. We further demonstrate that a lack of both maternal and zygotic Dnmt1 results in complete demethylation of all imprinted loci examined in blastocysts. Consistent with these results we find that zygotic Dnmt1 is expressed in the preimplantation embryo. Thus, contrary to the previous reports, Dnmt1 alone is sufficient to maintain the methylation marks of the imprinted genes.
An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion
Authors: Baxt Leigh A. , Baker Rosanna P. , Singh Upinder , Urban Sinisa
Published: June 2008

Rhomboid proteases are membrane-embedded enzymes conserved in all kingdoms of life, but their cellular functions across evolution are largely unknown. Prior work has uncovered a role for rhomboid enzymes in host cell invasion by malaria and related intracellular parasites, but this is unlikely to be a widespread function, even in pathogens, since rhomboid proteases are also conserved in unrelated protozoa that maintain an extracellular existence. We examined rhomboid function in Entamoeba histolytica, an extracellular, parasitic ameba that is second only to malaria in medical burden globally. Despite its large genome, E. histolytica encodes only one rhomboid (EhROM1) with residues necessary for protease activity. EhROM1 displayed atypical substrate specificity, being able to cleave Plasmodium adhesins but not the canonical substrate Drosophila Spitz. We searched for substrates encoded in the ameba genome and found EhROM1 was able to cleave a cell surface lectin specifically. In E. histolytica trophozoites, EhROM1 changed localization to vesicles during phagocytosis and to the posterior cap structure during surface receptor shedding for immune evasion, in both cases colocalizing with lectins. Collectively these results implicate rhomboid proteases for the first time in immune evasion and suggest that a common function of rhomboid enzymes in widely divergent protozoan pathogens is to break down adhesion proteins.
Tandem repeats upstream of the Arabidopsis endogene SDC recruit non-CG DNA methylation and initiate siRNA spreading
Authors: Henderson Ian R. , Jacobsen Steven E.
Published: June 2008

Plants use siRNAs to target cytosine DNA methylation to both symmetrical CG and nonsymmetrical (CHG and CHH) sequence contexts. DNA methylation and siRNA clusters most frequently overlap with transposons in the Arabidopsis thaliana genome. However, a significant number of protein-coding genes also show promoter DNA methylation, and this can be used to silence their expression. Loss of the majority of non-CG DNA methylation in drm1 drm2 cmt3 triple mutants leads to developmental phenotypes. We identified the gene responsible for these phenotypes as SUPPRESSOR OF drm1 drm2 cmt3 (SDC), which encodes an F-box protein and possesses seven promoter tandem repeats. The SDC repeats show a unique silencing requirement for non-CG DNA methylation directed redundantly by histone methylation and siRNAs, and display spreading of siRNAs and methylation beyond the repeated region. In addition to revealing the complexity of DNA methylation control in A. thaliana, SDC has important implications for how plant genomes utilize gene silencing to repress endogenous genes.
Drosophila let-7 microRNA is required for remodeling of the neuromusculature during metamorphosis
Authors: Sokol Nicholas S. , Xu Peizhang , Jan Yuh-Nung , Ambros Victor
Published: June 2008

The Drosophila let-7-Complex (let-7-C) is a polycistronic locus encoding three ancient microRNAs: let-7, miR-100, and fly lin-4 (miR-125). We find that the let-7-C locus is principally expressed in the pupal and adult neuromusculature. let-7-C knockout flies appear normal externally but display defects in adult behaviors (e.g., flight, motility, and fertility) as well as clear juvenile features in their neuromusculature. We find that the function of let-7-C to ensure the appropriate remodeling of the abdominal neuromusculature during the larval-to-adult transition is carried out predominantly by let-7 alone. This heterochronic role of let-7 is likely just one of the ways in which let-7-C promotes adult behavior.
Intriguing parasites and intramembrane proteases: Figure 1.
Authors: Rawson Robert B.
Published: June 2008

Rhomboid intramembrane proteases occur throughout the kingdoms of life. In this issue of Genes & Development, Baxt and colleagues (pp. 1636–1646) report that the single proteolytic rhomboid (EhROM1) from Entamoeba histolytica cleaves cell surface galactose-binding or N-acetylgalactosamine-binding (Gal/Gal-NAc) lectins. EhROM1 and lectins colocalize during phagocytosis and receptor capping. EhROM1 is found at the base of the cap rather than in the cap proper, suggesting a role in receptor shedding and implying that EhROM1 is crucial for amoebal infection.
A matter of timing: microRNA-controlled temporal identities in worms and flies
Authors: Frasch Manfred
Published: June 2008

The first microRNAs were identified in Caenorhabditis elegans based on their functions in the temporal regulation of stage-specific cell fate decisions. Until now, it was not known whether the so-called heterochronic genes that encode miRNAs are also involved in controlling developmental transitions in other organisms. New findings by Sokol et al. (this issue of Genes & Development, pp. 1591–1596) demonstrate that the Drosophila counterpart of a heterochronic miRNA gene from C. elegans, let-7, does indeed play a role in promoting stage-specific developmental events in neuromuscular tissues during the transition from larval to adult stages, thus pointing to a more widespread utilization of miRNAs in temporal regulation of animal development.
A theory of factor allocation and plant size
Authors: Holmes Thomas J. , Mitchell Matthew F.
Published: June 2008

This article develops a theory of how capital, skilled labor, and unskilled labor interact at the plant level. The theory has implications for the relationship between factor allocation and plant size and the effects of trade and growth on the skill premium. The theory is consistent with certain facts about factor allocation and factor price changes in the 19th and 20th centuries.
Costly contracting in a long‐term relationship
Authors: Battigalli Pierpaolo , Maggi Giovanni
Published: June 2008

We examine a model of contracting where parties interact repeatedly and can contract at any point in time, but writing formal contracts is costly. A contract can describe the external environment and the parties' behavior in a more or less detailed way, and the cost of writing a contract is proportional to the amount of detail. We consider both formal (externally enforced) and informal (self‐enforcing) contracts. The presence of writing costs has important implications both for the optimal structure of formal contracts, particularly the tradeoff between contingent and spot contracting, and for the interaction between formal and informal contracting. Our model sheds light on these implications and generates a rich set of predictions about the determinants of the optimal mode of contracting.
Incentives and invention in universities
Authors: Lach Saul , Schankerman Mark
Published: June 2008

We show that universities in the United States that provide stronger royalty incentives to faculty scientists generate greater license income, controlling for university characteristics. We use pre‐sample data on university patenting to control for the potential endogeneity of royalty shares. Faculty responds to royalties both in the form of cash and research lab support, indicating both pecuniary and intrinsic research motivations. The impact of incentives is larger in private than in public universities, and we provide new survey evidence on the organization and objectives of university licensing offices to explain this difference. Royalty incentives work both by raising faculty effort and sorting scientists across universities. The primary impact of incentives is to increase the quality rather than the quantity of inventions.
Optimal rewards in contests
Authors: Cohen Chen , Kaplan Todd R. , Sela Aner
Published: June 2008

We study all‐pay contests with effort‐dependent rewards under incomplete information. A contestant's value to winning depends not only on his type but also on the effort‐dependent reward chosen by the designer. We analyze which reward is optimal for the designer when his objective is either total effort or highest effort. We find that under certain conditions the optimal reward may either be negative or even decreasing in effort; however, we find no advantage to having multiple rewards.
Durable goods and conformity
Authors: House Christopher L. , Ozdenoren Emre
Published: June 2008

A consumer's demand for a durable good is governed not only by his individual preferences but also by preferences of other market participants. This interdependence of preferences arises from the inevitable resale of durable goods. If most people prefer goods with certain features, original buyers conform and choose goods with these features even if they do not like them. Using a matching model, we show there is always conformity in equilibrium. The incentive to conform is strongest for long‐lived durables and for people who trade frequently. If average preferences are sufficiently strong, there is always too little conformity in equilibrium.
Information feedback in first price auctions
Authors: Esponda Ignacio
Published: June 2008

I apply the notion of a self‐confirming equilibrium (SCE) to study how feedback in first price auctions influences bidders' perceptions about their strategic environment, and consequently their bidding behavior. In a private values setting, revealing the two highest bids at the end of each auction is sufficient for bidders to have correct beliefs (justifying the assumption of Nash equilibrium). In contrast, in every symmetric SCE of a symmetric, affiliated, private values model, bidding strategies and revenue are (weakly) higher if only the highest bid is revealed. I also consider interdependent valuations and discuss implications for the empirical auction literature.
Work‐related perks, agency problems, and optimal incentive contracts
Authors: Marino Anthony M. , Zábojník Ján
Published: June 2008

Work‐related perks, such as corporate jets, nice offices, and so forth, improve the tradeoff between incentives and insurance that determines the optimal incentive contract. We show that (i) such perks may be offered even if their direct consumption benefits are offset by their costs; (ii) they will be offered for free; (iii) agents in more uncertain production environments will receive more perks; (iv) senior executives should receive more perks; and (v) better corporate governance can lead to more perk consumption by CEOs. Our analysis also offers insights into firms' decisions about how much autonomy they should grant to their employees.
Short‐term fluctuations in hospital demand: implications for admission, discharge, and discriminatory behavior
Authors: Sharma Rajiv , Stano Miron , Gehring Renu
Published: June 2008

We analyze admission and discharge decisions when hospitals become capacity constrained on high‐demand days, and develop a test for discrimination that, under certain circumstances, does not require controls for differences across patient groups. On high‐demand days, patients are discharged earlier than expected compared to those discharged on low‐demand days. High demand creates no statistically significant differences in hospitals' admission behavior. Thus, hospitals appear to ration capacity by hastening discharges rather than by restricting admissions. We could not reject a null hypothesis of no discrimination against Medicaid patients in discharges.
Evidence of multiple retrotransposons in two litopenaeid species
Authors: Hizer S. E. , Tamulis W. G. , Robertson L. M. , Garcia D. K.
Published: June 2008

Retrotransposons encompass a specific class of mobile genetic elements that are widespread across eukaryotic genomes. The impact of the varied types of retrotransposons on these genomes is just beginning to be deciphered. In a step towards understanding their role in litopenaeid shrimp, we have herein identified nine non‐LTR retrotransposons, among which several appear to exist outside the standard defined clades. Two Litopenaeus stylirostris elements were discovered through degenerate PCR amplification using previously defined non‐LTR degenerate primers, and through primers designed from a RAPD‐derived sequence. A third genomic L. stylirostris element was identified using specific priming from an amplification protocol. These three PCR‐derived sequences showed conserved domains of the non‐LTR reverse transcriptase gene. In silico searching of genome databases and subsequent contig construction yielded six non‐LTR retrotransposons (both genomic and expressed) in the Litopenaeus vannamei genome that also exhibited the highly conserved domains found in our PCR‐derived sequences. Phylogenetic placement among representatives from all non‐LTR clades showed a possibly novel monophyletic group that included five of our nine sequences. This group, which included elements from both L. stylirostris and L. vannamei, appeared most closely related to the highly active RTE clade. Our remaining four sequences placed in the CR1 and I clades of retrotransposons, with one showing strong similarity to ancient Penelope elements. This research describes three newly discovered retrotransposons in the L. stylirostris genome. Phylogenetic analysis clusters these in a monophyletic grouping with retrotransposons previously described from two closely related species, L. vannamei and Penaeus monodon.
Molecular variation in pigmentation genes contributing to coat colour in native Korean Hanwoo cattle
Authors: Mohanty T. R. , Seo K. S. , Park K. M. , Choi T. J. , Choe H. S. , Baik D. H. , Hwang I. H.
Published: June 2008

Pigmentation genes such as TYR (tyrosinase), TYRP1 (tyrosinase‐related protein 1), DCT (previously TYRP2, or tyrosinase‐related protein 2), ASIP (agouti) and MC1R (melanocortin receptor 1) play a major role in cattle coat colour. To understand the genotypic profile underlying coat colour in native Korean Hanwoo cattle and Angus black cattle, portions of the above‐mentioned genes were amplified. Sequence analysis revealed variation in the TYRP1 (exon 5) and MC1R genes. Restriction enzyme analysis of these two genes could distinguish between different colours of Hanwoo cattle. Quantitative estimates of melanin and eumelanin in hair from three different‐coloured Hanwoo phenotypes and Angus black showed significant differences at the breed and phenotypic levels. Finally, sequence variants in MC1R were associated with total melanin and eumelanin in breeds as well as in Hanwoo phenotypes.
A proline‐to‐histidine mutation in POU1F1 is associated with production traits in dairy cattle
Authors: Huang W. , Maltecca C. , Khatib H.
Published: June 2008

POU class 1 homeobox 1 (POU1F1) is a member of the tissue‐specific POU‐containing transcription factor family. The expression of POU1F1 in mammalian pituitary gland controls the transcription of the genes encoding growth hormone, prolactin (PRL) and the subunits of thyroid‐stimulating hormone. In addition, some genes in the JAK/STAT signalling pathway downstream of POU1F1 have been shown to be associated with different production traits in dairy cattle. To investigate whether the POU1F1 gene is associated with economically important traits in dairy cattle, a pooled DNA sequencing approach was used to identify single nucleotide polymorphisms (SNPs) in the gene. An SNP in exon 3 of POU1F1 that changes a proline to a histidine was identified. A total of 2141 individuals from two North American Holstein cattle resource populations were genotyped for this SNP using a modified PCR‐RFLP method. Statistical analyses revealed significant association of POU1F1 variants with milk yield and productive life, which makes POU1F1 a possible candidate for marker‐assisted selection in dairy cattle breeding programmes.
Two variable active site residues modulate response regulator phosphoryl group stability
Authors: Thomas Stephanie A. , Brewster Jocelyn A. , Bourret Robert B.
Published: June 2008

Many signal transduction networks control their output by switching regulatory elements on or off. To synchronize biological response with environmental stimulus, switching kinetics must be faster than changes in input. Two‐component regulatory systems (used for signal transduction by bacteria, archaea and eukaryotes) switch via phosphorylation or dephosphorylation of the receiver domain in response regulator proteins. Although receiver domains share conserved active site residues and similar three‐dimensional structures, rates of self‐catalysed dephosphorylation span a ≥ 40 000‐fold range in response regulators that control diverse biological processes. For example, autodephosphorylation of the chemotaxis response regulator CheY is 640‐fold faster than Spo0F, which controls sporulation. Here we demonstrate that substitutions at two variable active site positions decreased CheY autodephosphorylation up to 40‐fold and increased the Spo0F rate up to 110‐fold. Particular amino acids had qualitatively similar effects in different response regulators. However, mutant proteins matched to other response regulators at the two key variable positions did not always exhibit similar autodephosphorylation kinetics. Therefore, unknown factors also influence absolute rates. Understanding the effects that particular active site amino acid compositions have on autodephosphorylation rate may allow manipulation of phosphoryl group stability for useful purposes, as well as prediction of signal transduction kinetics from amino acid sequence.
Chemical and genetic validation of dihydrofolate reductase–thymidylate synthase as a drug target in African trypanosomes
Authors: Sienkiewicz Natasha , Jarosławski Szymon , Wyllie Susan , Fairlamb Alan H.
Published: June 2008

The phenotypes of single‐ (SKO) and double‐knockout (DKO) lines of dihydrofolate reductase–thymidylate synthase (DHFR–TS) of bloodstream Trypanosoma brucei were evaluated in vitro and in vivo. Growth of SKO in vitro is identical to wild‐type (WT) cells, whereas DKO has an absolute requirement for thymidine. Removal of thymidine from the medium triggers growth arrest in S phase, associated with gross morphological changes, followed by cell death after 60 h. DKO is unable to infect mice, whereas the virulence of SKO is similar to WT. Normal growth and virulence could be restored by transfection of DKO with T. brucei DHFR–TS, but not with Escherichia coli TS. As pteridine reductase (PTR1) levels are unchanged in SKO and DKO cells, PTR1 is not able to compensate for loss of DHFR activity. Drugs such as raltitrexed or methotrexate with structural similarity to folic acid are up to 300‐fold more potent inhibitors of WT cultured in a novel low‐folate medium, unlike hydrophobic antifols such as trimetrexate or pyrimethamine. DKO trypanosomes show reduced sensitivity to these inhibitors ranging from twofold for trimetrexate to >10 000‐fold for raltitrexed. These data demonstrate that DHFR–TS is essential for parasite survival and represents a promising target for drug discovery.
Rust severity in bioenergy willow plantations treated with additional nutrients
Authors: Toome M. , Heinsoo K. , Ramstedt M. , Luik A.
Published: June 2008

A 3‐year field study was carried out to determine the effect of wastewater irrigation and previous differences in mineral fertilization on the occurrence of willow leaf rust (Melampsora epitea). The experiment was conducted in two energy forest plantations: one designed for wastewater purification and the other as a mineral fertilization experiment. The severity of leaf rust on different clones and sites with different treatments was assessed by counting the number of uredinia per leaf unit area. Generally, plants irrigated with wastewater consistently had more leaf rust, irrespective of the study years or willow clones. Previous mineral fertilization had mixed effects on different clones 2 years after the last application. Three years after the last fertilizer application, however, no impact of the treatment on rust disease development was detected. In general, the rust levels differed from year to year probably due to climate. In this study, no correlation was detected between shoot age and rust severity, whereas climate and treatments strongly influenced leaf rust levels on some willow clones.
Dendritic cell therapy in combination with interferon‐α for the treatment of metastatic renal cell carcinoma
Authors: Tatsugami Katsunori , Eto Masatoshi , Harano Masahiko , Hamaguchi Masumitsu , Miyamoto Toshihiro , Morisaki Takashi , Furue Masutaka , Akashi Koichi , Naito Seiji
Published: June 2008

Objectives:  To evaluate the safety and efficacy of dendritic cell (DC) therapy in combination with interferon‐α (IFN‐α) in patients with advanced renal cell carcinoma.

Methods:  Seven patients, with progressive disease following IFN‐α and interleukin (IL)‐2 treatment, were treated with monocyte‐derived DC (Mo‐DC) and IFN‐α between February 2004 and September 2006. They received Mo‐DC once a week for 5 weeks and then every 2 weeks either intradermally or intratumorally. IFN‐α (5–6 million U) was subcutaneously administered three times a week. Tumor size was evaluated by computed tomography scans before and after the 5th and 10th DC vaccination. A delayed‐type hypersensitivity test was performed after the 4th and 5th DC administration for immunological monitoring.

Results:  Five patients had stable disease while the remaining two patients had progressive disease following 4 months of vaccination. In six patients the time to progression was prolonged in comparison with the previous cytokine treatment. Six patients showed delayed‐type hypersensitivity after the 4th or 5th immunization. Three patients developed high fever following DC immunization. Treatment was associated with transient flu‐like symptoms.

Conclusions:  Our data indicate that DC therapy combined with IFN‐α is safe and has the potential for prolonging the time to progression in patients with advanced renal cell carcinoma.
Prepuce‐Sparing hypospadias repair with tubularized incised plate urethroplasty
Authors: Shimada Kenji , Matsumoto Fumi , Matsui Futoshi , Takano Syuichi
Published: June 2008

Objectives:  Modifications in surgical methods of hypospadias repair have been influenced by social considerations. Most Japanese parents wish their children to retain their foreskin during hypospadias repair. We report on short‐term results of foreskin reconstruction associated with hypospadias repair.

Methods:  Of 44 tubularized incised plate urethroplasty‐patients, 42 (95%) underwent foreskin reconstruction at the time of urethroplasty during the last 2 years. After the urethroplasty was completed, the foreskin was re‐approximated in three layers.

Results:  Complications related to urethroplasty consisted of fistula in two patients with penoscrotal hypospadia, and mild stenosis of the glandular urethra in one patient. Complications related to foreskin reconstruction included dehiscence of the ventral foreskin in two patients. In all cases parents were well satisfied with the reconstructed prepuce.

Conclusions:  Pre‐operative information about preputial reconstruction should be given to parents if they would prefer their son to be uncircumcised.
Doctors’ perceptions of the prognostic benefit of statins in patients who have had myocardial infarction
Authors: Sapre N. , Mann S. , Elley C. R.
Published: June 2008

Background: We wished to assess how General Practitioners (GPs) and cardiologists perceive and communicate the benefits of therapy with statins (hydroxymethylglutaryl‐coenzyme A reductase inhibitors) in a patient following myocardial infarction.

Methods: We interviewed 20 GPs and 22 cardiologists to determine treatment policy and ways of expressing its benefits to a patient after myocardial infarction with moderate dyslipidaemia. We asked what drug and dosage they would recommend and how they would express potential benefits of therapy, given a range of options including reduced relative and absolute risk of events.

Results: Most GPs would start a low dose (10–20 mg/day) of simvastatin (the only freely prescribable funded statin in New Zealand) whereas cardiologists would commence 40 mg/day immediately (P = 0.001). All but one cardiologist would justify therapy to the patient by citing a reduced chance of a major adverse cardiovascular event. Nine GPs and one cardiologist estimated a gain of more than 5 years of life from statin therapy. Cardiologists were more optimistic than GPs about relative risk reduction (P = 0.04). Only 50% of GPs and 68% of cardiologists were able to estimate an absolute risk reduction over 5 years, such estimates varying widely with no significant difference in responses between the groups (P = 0.2). No doctors felt comfortable using number needed to treat or odds ratio.

Conclusion: There were substantial differences between the two groups of clinicians in perception and policy of statin therapy, frequent overestimation of treatment benefits and a reluctance to impart numerical estimates of benefit to patients.