bluuebunny/crossref_metadata_2025 huggingface dataset:
Grand Theft Auto IV
Authors: Ruch Adam W.
Published: August 2012

This article has two goals: one is to establish techniques for content analysis of a virtual environment, Liberty City, as part of a dynamic textual object, Grand Theft Auto IV ( GTA IV). The second is to demonstrate these techniques with an analysis in the narrative of GTA IV as a very modernist, dystopian version of the American Dream. Further, the suitability of the video game as a medium for modernist themes and concerns as exemplified by the work of James Joyce, Virginia Woolf, and T. S. Eliot will be explored. Liberty City is an interactive city which a player can experience, rather than read about, answering many of the questions modernist writers posed to their frustrating, linear medium.
Influence of oxides on cold lap formation in tandem GMAW
Authors: Li P G , Svensson L-E , Markocsan N
Published: August 2012

The connection between the formation of cold laps and the presence of Mn–Si oxides was studied. The underlying purpose is to understand the fundamental mechanisms of cold lap formation and to avoid it. Tandem gas metal arc welding (GMAW) was used to produce welded specimens in two different shielding gases (pure Ar and pure CO2) with base metal S355 MC (EN-10149-2) and wire G3Si1 (EN ISO 14341-A). Cross-sections of welds in the cold lap location were evaluated by light optical microscopy and scanning electron microscopy combined with energy dispersive spectroscopy. The results showed that the Mn–Si oxides significantly enhanced cold laps formation, especially the overlap type cold lap formation. The Mn–Si oxides originated from oxidation of the droplets. These oxides transfers to the surface of the weld pool at the weld toe, where they contributed to the formation of the cold laps.
T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing
Authors: Zhou Qi , Schneider Irene C. , Edes Inan , Honegger Annemarie , Bach Patricia , Schönfeld Kurt , Schambach Axel , Wels Winfried S. , Kneissl Sabrina , Uckert Wolfgang , Buchholz Christian J.
Published: August 2012

Transfer of tumor-specific T-cell receptor (TCR) genes into patient T cells is a promising strategy in cancer immunotherapy. We describe here a novel vector (CD8-LV) derived from lentivirus, which delivers genes exclusively and specifically to CD8+ cells. CD8-LV mediated stable in vitro and in vivo reporter gene transfer as well as efficient transfer of genes encoding TCRs recognizing the melanoma antigen tyrosinase. Strikingly, T cells genetically modified with CD8-LV killed melanoma cells reproducibly more efficiently than CD8+ cells transduced with a conventional lentiviral vector. Neither TCR expression levels, nor the rate of activation-induced death of transduced cells differed between both vector types. Instead, CD8-LV transduced cells showed increased granzyme B and perforin levels as well as an up-regulation of CD8 surface expression in a small subpopulation of cells. Thus, a possible mechanism for CD8-LV enhanced tumor cell killing may be based on activation of the effector functions of CD8+ T cells by the vector particle displaying OKT8-derived CD8-scFv and an increase of the surface density of CD8, which functions as coreceptor for tumor-cell recognition. CD8-LV represents a powerful novel vector for TCR gene therapy and other applications in immunotherapy and basic research requiring CD8+ cell-specific gene delivery.
Efficient generation, purification, and expansion of CD34+ hematopoietic progenitor cells from nonhuman primate–induced pluripotent stem cells
Authors: Gori Jennifer L. , Chandrasekaran Devikha , Kowalski John P. , Adair Jennifer E. , Beard Brian C. , D'Souza Sunita L. , Kiem Hans-Peter
Published: August 2012

Induced pluripotent stem cell (iPSC) therapeutics are a promising treatment for genetic and infectious diseases. To assess engraftment, risk of neoplastic formation, and therapeutic benefit in an autologous setting, testing iPSC therapeutics in an appropriate model, such as the pigtail macaque (Macaca nemestrina; Mn), is crucial. Here, we developed a chemically defined, scalable, and reproducible specification protocol with bone morphogenetic protein 4, prostaglandin-E2 (PGE2), and StemRegenin 1 (SR1) for hematopoietic differentiation of Mn iPSCs. Sequential coculture with bone morphogenetic protein 4, PGE2, and SR1 led to robust Mn iPSC hematopoietic progenitor cell formation. The combination of PGE2 and SR1 increased CD34+CD38−Thy1+CD45RA−CD49f+ cell yield by 6-fold. CD34+CD38−Thy1+CD45RA−CD49f+ cells isolated on the basis of CD34 expression and cultured in SR1 expanded 3-fold and maintained this long-term repopulating HSC phenotype. Purified CD34high cells exhibited 4-fold greater hematopoietic colony-forming potential compared with unsorted hematopoietic progenitors and had bilineage differentiation potential. On the basis of these studies, we calculated the cell yields that must be achieved at each stage to meet a threshold CD34+ cell dose that is required for engraftment in the pigtail macaque. Our protocol will support scale-up and testing of iPSC-derived CD34high cell therapies in a clinically relevant nonhuman primate model.
Evolutionary paths of streptococcal and staphylococcal superantigens
Authors: Okumura Kayo , Shimomura Yumi , Murayama Somay Yamagata , Yagi Junji , Ubukata Kimiko , Kirikae Teruo , Miyoshi-Akiyama Tohru
Published: August 2012

Background

Streptococcus pyogenes (GAS) harbors several superantigens (SAgs) in the prophage region of its genome, although speG and smez are not located in this region. The diversity of SAgs is thought to arise during horizontal transfer, but their evolutionary pathways have not yet been determined. We recently completed sequencing the entire genome of S. dysgalactiae subsp. equisimilis (SDSE), the closest relative of GAS. Although speG is the only SAg gene of SDSE, speG was present in only 50% of clinical SDSE strains and smez in none. In this study, we analyzed the evolutionary paths of streptococcal and staphylococcal SAgs.

Results

We compared the sequences of the 12–60 kb speG regions of nine SDSE strains, five speG
+ and four speG

–
. We found that the synteny of this region was highly conserved, whether or not the speG gene was present. Synteny analyses based on genome-wide comparisons of GAS and SDSE indicated that speG is the direct descendant of a common ancestor of streptococcal SAgs, whereas smez was deleted from SDSE after SDSE and GAS split from a common ancestor. Cumulative nucleotide skew analysis of SDSE genomes suggested that speG was located outside segments of steeper slopes than the stable region in the genome, whereas the region flanking smez was unstable, as expected from the results of GAS. We also detected a previously undescribed staphylococcal SAg gene, selW, and a staphylococcal SAg -like gene, ssl, in the core genomes of all Staphylococcus aureus strains sequenced. Amino acid substitution analyses, based on dN/dS window analysis of the products encoded by speG, selW and ssl suggested that all three genes have been subjected to strong positive selection. Evolutionary analysis based on the Bayesian Markov chain Monte Carlo method showed that each clade included at least one direct descendant.

Conclusions

Our findings reveal a plausible model for the comprehensive evolutionary pathway of streptococcal and staphylococcal SAgs.
Identification of a novel set of genes reflecting different in vivo invasive patterns of human GBM cells
Authors: Monticone Massimiliano , Daga Antonio , Candiani Simona , Romeo Francesco , Mirisola Valentina , Viaggi Silvia , Melloni Ilaria , Pedemonte Simona , Zona Gianluigi , Giaretti Walter , Pfeffer Ulrich , Castagnola Patrizio
Published: August 2012

Background

Most patients affected by Glioblastoma multiforme (GBM, grade IV glioma) experience a recurrence of the disease because of the spreading of tumor cells beyond surgical boundaries. Unveiling mechanisms causing this process is a logic goal to impair the killing capacity of GBM cells by molecular targeting.

We noticed that our long-term GBM cultures, established from different patients, may display two categories/types of growth behavior in an orthotopic xenograft model: expansion of the tumor mass and formation of tumor branches/nodules (nodular like, NL-type) or highly diffuse single tumor cell infiltration (HD-type).

Methods

We determined by DNA microarrays the gene expression profiles of three NL-type and three HD-type long-term GBM cultures. Subsequently, individual genes with different expression levels between the two groups were identified using Significance Analysis of Microarrays (SAM). Real time RT-PCR, immunofluorescence and immunoblot analyses, were performed for a selected subgroup of regulated gene products to confirm the results obtained by the expression analysis.

Results

Here, we report the identification of a set of 34 differentially expressed genes in the two types of GBM cultures. Twenty-three of these genes encode for proteins localized to the plasma membrane and 9 of these for proteins are involved in the process of cell adhesion.

Conclusions

This study suggests the participation in the diffuse infiltrative/invasive process of GBM cells within the CNS of a novel set of genes coding for membrane-associated proteins, which should be thus susceptible to an inhibition strategy by specific targeting.

Massimiliano Monticone and Antonio Daga contributed equally to this work
Assaying proline hydroxylation in recombinant collagen variants by liquid chromatography-mass spectrometry
Authors: Chan S W Polly , Greaves John , Da Silva Nancy A , Wang Szu-Wen
Published: August 2012

Background

The fabrication of recombinant collagen and its prescribed variants has enormous potential in tissue regeneration, cell-matrix interaction investigations, and fundamental biochemical and biophysical studies of the extracellular matrix. Recombinant expression requires proline hydroxylation, a post-translational modification which is critical for imparting stability and structure. However, these modifications are not native to typical bacterial or yeast expression systems. Furthermore, detection of low levels of 4-hydroxyproline is challenging with respect to selectivity and sensitivity.

Results

We have developed a new liquid chromatography-mass spectrometry (LC-MS) method to evaluate proline hydroxylation in recombinant collagen. This assay was tested in different Saccharomyces cerevisiae expression systems to evaluate the effect of gene ratio between prolyl-4-hydroxylase and collagen on the extent of hydroxylation. These systems used a human collagen III gene that was synthesized de novo from oligonucleotides. The LC-MS assay does not require derivatization, uses only picomoles of sample, and can measure proline hydroxylation levels in recombinant and native collagen ranging from approximately 0% to 40%. The hydroxylation values obtained by LC-MS are as accurate and as precise as those obtained with the conventional method of amino acid analysis.

Conclusions

A facile, derivatization-free LC-MS method was developed that accurately determines the percentage of proline hydroxylation in different yeast expression systems. Using this assay, we determined that systems with a higher collagen-to-hydroxylase gene copy ratio yielded a lower percentage of hydroxylation, suggesting that a specifically balanced gene ratio is required to obtain higher hydroxylation levels.
Phenolic content, antioxidant effect and cytotoxic activity of Leea indica leaves
Authors: Reddy Nidyaletchmy Subba , Navanesan Suerialoasan , Sinniah Saravana Kumar , Wahab Norhanom Abdul , Sim Kae Shin
Published: August 2012

Background

The leaves of Leea indica (Vitaceae), commonly known as ‘Huo Tong Shu’ in Malaysia, have been traditionally used as natural remedy in folk medicine by the locals. The current study reports the outcome of antioxidant and cytotoxic investigation of L. indica leaves. To the best of our knowledge, this is the first report of L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) for evaluation of total phenolic content, antioxidant effect and cytotoxic activity against colon cancer cell lines.

Methods

In the present study, L. indica leaf crude ethanol and its fractionated extracts (hexane, ethyl acetate and water) were firstly prepared prior to phenolic content, antioxidant effect and cytotoxic activity assessment. Folin-Ciocalteau’s method was used for the measurement of total phenolic content of the extracts. The antioxidant activity was measured by employing three different established testing systems, such as scavenging activity on DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, reducing power assay and SOD (superoxide dismutase) activity assay. The cytotoxic activity of the extracts were evaluated against three colon cancer cell lines with varying molecular characteristics (HT-29, HCT-15 and HCT-116) by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay.

Results

The total phenolic content and antioxidant capabilities differed significantly among the L. indica leaf extracts. A strong correlation between total phenolic content and antioxidant properties was found, indicating that phenolic compounds are the major contributor to the antioxidant properties of these extracts. Among the crude ethanol and its fractionated extracts, fractionated water extract showed significantly the highest total phenolic content and strongest antioxidant effect in all the antioxidant testing systems employed in this study. All the four extracts exert no damage to the selected colon cancer cells.

Conclusions

The data obtained in these testing systems clearly establish the antioxidant potency of the fractionated water extract of L. indica leaves. Additional studies should be carried out to isolate and identify the bioactive compounds in the fractionated water extract, in order to provide more convincing evidence.
Ultraviolet-ozone-treated PEDOT:PSS as anode buffer layer for organic solar cells
Authors: Su Zisheng , Wang Lidan , Li Yantao , Zhao Haifeng , Chu Bei , Li Wenlian
Published: August 2012

Ultraviolet-ozone-treated poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS)was used as the anode buffer layer in copper phthalocyanine (CuPc)/fullerene-based solar cells. The power conversion efficiency of the cells with appropriated UV-ozone treatment was found to increase about 20% compared to the reference cell. The improved performance is attributed to the increased work function of the PEDOT:PSS layer, which improves the contact condition between PEDOT:PSS and CuPc, hence increasing the extraction efficiency of the photogenerated holes and decreasing the recombination probability of holes and electrons in the active organic layers.
Template method for fabricating interdigitate p-n heterojunction for organic solar cell
Authors: Hu Jianchen , Shirai Yasuhiro , Han Liyuan , Wakayama Yutaka
Published: August 2012

Anodic aluminum oxide (AAO) templates are used to fabricate arrays of poly(3-hexylthiophene) (P3HT) pillars. This technique makes it possible to control the dimensions of the pillars, namely their diameters, intervals, and heights, on a tens-of-nanometer scale. These features are essential for enhancing carrier processes such as carrier generation, exciton diffusion, and carrier dissociation and transport. An interdigitated p-n junction between P3HT pillars and fullerene (C60) exhibits a photovoltaic effect. Although the device properties are still preliminary, the experimental results indicate that an AAO template is an effective tool with which to develop organic solar cells because highly regulated nanostructures can be produced on large areas exceeding 100 mm2.
Clonal analysis and virulent traits of pathogenic extraintestinal Escherichia coliisolates from swine in China
Authors: Ding Yi , Tang Xibiao , Lu Ping , Wu Bin , Xu Zhuofei , Liu Wugang , Zhang Ruixuan , Bei Weicheng , Chen Huanchun , Tan Chen
Published: August 2012

Background

Extraintestinal pathogenic Escherichia coli (ExPEC) can cause a variety of infections outside the gastrointestinal tract in humans and animals. Infections due to swine ExPECs have been occurring with increasing frequency in China. These ExPECs may now be considered a new food-borne pathogen that causes cross-infections between humans and pigs. Knowledge of the clonal structure and virulence genes is needed as a framework to improve the understanding of phylogenetic traits of porcine ExPECs.

Results

Multilocus sequence typing (MLST) data showed that the isolates investigated in this study could be placed into four main clonal complexes, designated as CC10, CC1687, CC88 and CC58. Strains within CC10 were classified as phylogroup A, and these accounted for most of our porcine ExPEC isolates. Isolates in the CC1687 clonal complex, formed by new sequence types (STs), was classified as phylogroup D, with CC88 isolates considered as B2 and CC58 isolates as B1. Porcine ExPECs in these four clonal complexes demonstrated significantly different virulence gene patterns. A few porcine ExPECs were indentified in phylogroup B2, the phylogroup in which human ExPECs mainly exist. However some STs in the four clonal groups of porcine ExPECs were reported to cause extraintestinal infections in human, based on data in the MLST database.

Conclusion

Porcine ExPECs have different virulence gene patterns for different clonal complexes. However, these strains are mostly fell in phylogenentic phylogroup A, B1 and D, which is different from human ExPECs that concentrate in phylogroup B2. Our findings provide a better understanding relating to the clonal structure of ExPECs in diseased pigs and indicate a need to re-evaluate their contribution to human ExPEC diseases.
Institutional Resources for Communicable Disease Control in Europe: Diversity across Time and Place
Authors: Mätzke Margitta
Published: August 2012

This commentary discusses the causes and consequences of diversity in how European countries organize communicable disease control. Drawing on the historical record of the US Centers for Disease Control and Prevention, it first reviews the main explanations of that diversity, with a focus on the political dynamic of building institutional capacity in the field of public health. It then examines the significance of institutional diversity in the process of Europeanization, and closes with a few thoughts on factors that have shaped the development of communicable disease control capacities in the United States and the European Union.
Agricultural Policy, Food Policy, and Communicable Disease Policy
Authors: Grant Wyn
Published: August 2012

Food and agricultural policy is an essential element of a communicable disease policy. The European Union has developed a more systematic and broadly based interest in questions of food safety and animal health and welfare linked to modernization of the Common Agricultural Policy, reflected in a new treaty obligation on animal welfare. Following the bovine spongiform encephalopathy crisis, moves were made to create a European competency, but implementation and enforcement resources reside with the member states. The European Animal Health Strategy is meant to lead to an EU animal health law, but this has already been constrained by fiscal austerity. The development of such a law may lead to a lowest common denominator formula that does little to enhance consumer protection or improve animal welfare. This is an inherent risk with top-down forms of Europeanization; more attention should be paid to lessons to be learned from bottom-up initiatives of the type used to counteract the bovine diarrhea virus. There will always be a tension among what is good policy for reducing the incidence of communicable disease, policy that is popular with EU citizens, and policy that is acceptable to member states.
Centrosome loss or amplification does not dramatically perturb global gene expression inDrosophila
Authors: Baumbach Janina , Levesque Mitchell P. , Raff Jordan W.
Published: August 2012

Centrosome defects are a common feature of many cancers, and they can predispose fly brain cells to form tumours. In flies, centrosome defects perturb the asymmetric division of the neural stem cells, but it is unclear how this might lead to malignant transformation. One possibility is that centrosome defects might also perturb cellular homeostasis: for example, stress pathways are often activated in response to centrosome defects in cultured cells, and stress contributes to tumourigenesis in some fly models. Here we attempt to assess whether centrosome loss or centrosome amplification perturbs cell physiology in vivo by profiling the global transcriptome of Drosophila larval brains and imaginal discs that either lack centrosomes or have too many centrosomes. Surprisingly, we find that centrosome loss or amplification leads to few changes in the transcriptional profile of these cells, indicating that centrosome defects are surprisingly well tolerated by these cells. These observations indicate that centrosome defects can predispose fly brain cells to form tumours without, at least initially, dramatically altering their physiology.
Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice
Authors: Kajiwara Chiaki , Kondo Shiho , Uda Shizuha , Dai Lei , Ichiyanagi Tomoko , Chiba Tomoki , Ishido Satoshi , Koji Takehiko , Udono Heiichiro
Published: August 2012

It is controversial whether a functional androgen receptor (AR) on germ cells, including spermatogonia, is essential for their development into sperm and, thus, initiation and maintenance of spermatogenesis. It was recently shown that many spermatocytes underwent apoptosis in the testes of Hsp90α KO mice. We had generated Hsp90α KO mice independently and confirmed this phenotype. However, the important question of whether Hsp90α is required to maintain spermatogenesis in adult mice in which testicular maturation is already completed could not be addressed using these conventional KO mice. To answer this question, we generated a tamoxifen-inducible deletion mutant of Hsp90α and found that conditional deletion of Hsp90α in adult mice caused even more severe apoptosis in germ cells beyond the pachytene stage, leading to complete arrest of spermatogenesis and testicular atrophy. Importantly, immunohistochemical analysis revealed that AR expression in WT testis was more evident in spermatogonia than in spermatocytes, whereas its expression was aberrant and ectopic in Hsp90α KO testis, raising the possibility that an AR abnormality in primordial germ cells is involved in spermatogenesis arrest in the Hsp90α KO mice. Our results suggest that the AR, specifically chaperoned by Hsp90α in spermatogonia, is critical for maintenance of established spermatogenesis and for survival of spermatocytes in adult testis, in addition to setting the first wave of spermatogenesis before puberty.
GTF2IRD2from the Williams-Beuren critical region encodes a mobile element-derived fusion protein that antagonizes the action of its related family members
Authors: Palmer Stephen J. , Taylor Kylie M. , Santucci Nicole , Widagdo Jocelyn , Chan Yee-Ka Agnes , Yeo Jen-Li , Adams Merritt , Gunning Peter W. , Hardeman Edna C
Published: August 2012

GTF2IRD2 belongs to a family of transcriptional regulators (including TFII-I and GTF2IRD1) that are responsible for many of the key features of Williams-Beuren syndrome (WBS). Sequence evidence suggests that GTF2IRD2 arose in eutherian mammals by duplication and divergence from the gene encoding TFII-I. However, in GTF2IRD2, most of the carboxy-terminal domain has been lost and replaced by the domesticated remnant of an in-frame hAT-transposon mobile element. In this first experimental analysis of function, we show that transgenic expression of each of the three family members in skeletal muscle causes significant fiber type shifts, but the GTF2IRD2 protein causes an extreme shift in the opposite direction to the two other family members. Mating of GTF2IRD1 and GTF2IRD2 mice restores the fiber type balance, indicating an antagonistic relationship between these two paralogs. In cells, GTF2IRD2 localizes to cytoplasmic microtubules and discrete speckles in the nuclear periphery. We show that it can interact directly with TFII-Iβ and GTF2IRD1 and upon co-transfection changes the normal distribution of these two proteins into a punctate nuclear pattern typical of GTF2IRD2. These data suggest that GTF2IRD2 has evolved as a regulator of GTF2IRD1 and TFII-I; inhibiting their function by direct interaction and sequestration into inactive nuclear zones.
Nanopatterning Reveals an ECM Area Threshold for Focal Adhesion Assembly and Force Transmission that is regulated by Integrin Activation and Cytoskeleton Tension
Authors: Coyer Sean R. , Singh Ankur , Dumbauld David W. , Calderwood David A. , Craig Susan W. , Delamarche Emmanuel , García Andrés J.
Published: August 2012

Integrin-based focal adhesions (FA) transmit anchorage and traction forces between the cell and extracellular matrix (ECM). To gain further insight on the physical parameters of ECM that control FA assembly and force transduction in non-migrating cells, we used fibronectin (FN) nanopatterning within a cell adhesion-resistant background to establish the threshold area of ECM ligand required for stable FA assembly and force transduction. Integrin-FN clustering and adhesive force were strongly modulated by the geometry of the nanoscale adhesive area. Individual nanoisland area, not the number of nanoislands or total adhesive area, controlled integrin-FN clustering and adhesion strength. Importantly, below an area threshold (0.11 µm2), very few integrin-FN clusters and negligible adhesive forces were generated. We then asked whether this adhesive area threshold could be modulated by intracellular pathways known to influence either adhesive force, cytoskeletal tension, or the structural link between the two. Expression of talin- or vinculin-head domains that increase integrin activation or clustering overcame this nanolimit for stable integrin-FN clustering and increased adhesive force. Inhibition of myosin contractility in cells expressing a vinculin mutant that enhances cytoskeleton-integrin coupling also restored integrin-FN clustering below the nanolimit. We conclude that the minimum area of integrin-FN clusters required for stable assembly of nanoscale FA and adhesive force transduction is not a constant; rather it has a dynamic threshold that results from an equilibrium between pathways controlling adhesive force, cytoskeletal tension, and the structural linkage that transmits these forces, allowing the balance to be tipped by factors that regulate these mechanical parameters.
Experimental selection for body size at age modifies early-life history traits and muscle gene expression in adult zebrafish
Authors: Amaral Ian P. G. , Johnston Ian A.
Published: August 2012

The short generation time of the zebrafish (Danio rerio) was exploited to investigate the effects of selection for body size at age on early life-history traits and on the transcriptional response to a growth stimulus in skeletal muscle of adult fish. Replicate populations were either unselected (U-lineage) or subjected to four generations of experimental selection for small (S-lineage) or large body size (L-lineage) at 90 days post-fertilization. Body mass was on average 16.3% and 41.0% higher in the L- than the U- and S-lineages respectively. Egg diameter was 6.4% lower with 13% less yolk in the S- compared to the other lineages. Maternal transcripts for igf2r, bmpr1aa, igf1ar, igf2a, igfbp5a, ghra and igfbp3 in 2-4 cell stage embryos were higher in the L- than S-lineage. Larvae from the L-lineage were significantly larger, but survivorship at the end of the first month was similar between lineages. Gene expression was measured in the fast muscle of adult fish fasted for 7d and then re-fed to satiation for 48h. The expression of 11 insulin-like growth factor pathway genes and 12 other nutritionally-responsive genes was similar for the S- and L-lineages as was gut fullness with feeding. Transcript abundance for 4 genes (igf1a, igf2r, igfbp1a and igfbp1b) showed either regulated or constitutive differences between the S- and L-lineages. For example, igf2 receptors transcripts were higher and igbp1a/b transcripts lower in the L- than S-lineages consistent with an effect of selection on insulin-like growth factor signalling.
Cell death and renewal during prey capture and digestion in the carnivorous spongeAsbestopluma hypogea(Porifera: Poecilosclerida)
Authors: Martinand-Mari Camille , Vacelet Jean , Nickel Michael , Wörheide Gert , Mangeat Paul , Baghdiguian Stephen
Published: August 2012

The sponge Asbestopluma hypogea is unusual among sponges due to its peculiar carnivorous feeding habit. During various stages of its nutrition cycle, the sponge is subjected to spectacular morphological modifications. Starved animals are characterized by many elongated filaments which are crucial for the sponge to capture prey. After capture, and during the digestion process, these filaments actively regress before being regenerated during a subsequent period of starvation. Here, we demonstrate that these morphological events repose on a highly dynamic cellular turnover implying a coordinated sequence of programmed cell death (apoptosis and autophagy), cell proliferation and cell migration. A candidate niche for cell renewal by stem cell proliferation and differentiation was identified at the base of the sponge peduncle, characterized by surpassing levels of BrdU/EdU incorporation. Therefore, BrdU/EdU positive-cells of the peduncle base are candidate motile cells responsible for the regeneration of the prey-capturing main sponge body, i.e. the dynamic filaments. Altogether, our results demonstrate that dynamic of cell renewal in sponge appears to be regulated by cellular mechanisms as multiple and complex as those already identified in bilaterian metazoans.
Selective brain cooling in Arabian oryx (Oryx leucoryx): a physiological mechanism for coping with aridity?
Authors: Hetem Robyn S. , Strauss W. Maartin , Fick Linda G. , Maloney Shane K. , Meyer Leith C. R. , Fuller Andrea , Shobrak Mohammed , Mitchell Duncan
Published: August 2012

Selective brain cooling is a thermoregulatory effector proposed to conserve body water and, as such, may help artiodactyls cope with aridity. We measured brain and carotid blood temperature, using implanted data loggers, in five Arabian oryx (Oryx leucoryx) in the desert of Saudi Arabia. On average, brain temperature was 0.24±0.05ºC lower than carotid blood temperature for four oryx in April. Selective brain cooling was enhanced in our Arabian oryx compared to another species from the same genus (gemsbok Oryx gazella gazella), exposed to similar ambient temperatures but less aridity. Arabian oryx displayed a lower threshold (37.8±0.1ºC vs 39.8±0.4ºC), a higher frequency (87±6 % vs 15±15%) and a higher maximum magnitude (1.2±0.2ºC vs 0.5±0.3ºC) of selective brain cooling than did gemsbok. The dominant male oryx displayed less selective brain cooling than did any of the other oryx, but selective brain cooling was enhanced in this oryx as conditions became hotter and drier. Enhanced selective brain cooling in Arabian oryx supports the hypothesis that selective brain cooling would bestow survival advantages for artiodactyl species inhabiting hot hyper-arid environments.
The Market for Corporate Control: The Empirical Evidence Since 1980
Authors: Jarrell Gregg A , Brickley James A , Netter Jeffry M
Published: August 2012

In the 1980s, the market for corporate control has been increasingly active, and the quantity of output of academic researchers studying corporate control questions has mirrored the market activity. This review examines the returns to bidders and targets, and the effects of defending against hostile takeovers.
Illegal Immigration and Immigration Control
Authors: Chiswick Barry R
Published: August 2012

The Immigration Reform and Control Act (IRCA) was passed in the closing days of the 1986 legislative session. The primary purpose of IRCA is to remove illegal aliens from the U.S. labor market. It has two primary policy instruments. One is granting legal status or amnesty for certain illegal aliens, thereby in part “wiping the slate clean.” The other is imposing penalties, referred to as employer sanctions, against employers who “knowingly” hire illegal aliens. Employer sanctions are intended to reduce the demand for illegal alien labor. The first sections of this paper develop an economic analysis of the illegal alien labor market, including the determinants of illegal migration and the impact on the economy. Then, that model is applied to the major provisions of IRCA and used to describe its likely consequences. A concluding section argues that because IRCA does not address the economic realities it is not likely to accomplish its objectives. The partial amnesty and impotent employer sanctions have not solved the illegal alien dilemma.
Lessons on Monetary Policy from the 1980s
Authors: Friedman Benjamin M
Published: August 2012

The half-decade running from mid-1982 to mid-1987 was a pretty good era for U.S. monetary policy, as these things go. Even the severe 1981-82 recession served its intended purpose of substantially restoring price stability. At least as judged by the outcomes for the standard objectives of macroeconomic policy, U.S. monetary policy was a distinct success. Economists hoping to say something useful about monetary policy in the 1980s have had a tougher time. The quantitative relationships connecting income and price movements to the growth of familiar monetary aggregates, including especially the M1 measure of the money stock that had been the chief focus of monetary policy during 1979-82, utterly fell apart during this period. It is difficult to escape the conclusion that there is now a conceptual vacuum at the center of the U.S. monetary policymaking process. In the meanwhile, the Federal Reserve System has not ceased operations. Nor should it be inclined to do so, in light of the performance of both income and prices during the past half-decade.
Monetary Policy Lessons of Recent Inflation and Disinflation
Authors: Poole William
Published: August 2012

I will consider the monetary policy lessons of the recent inflation and disinflation. The next section of this paper is devoted to the decline of M1 velocity after 1981 and the demise of the “standard” money demand function. Some authors conclude that this evidence leaves us so uncertain about the nature of money demand that policymakers cannot rely at all on any presumed money demand regularities. In contrast, my working hypothesis is that the money demand continues to be a stable function of relatively few variables, but that the interest elasticity of money demand is substantially higher than previously thought. Events have not been kind to Keynesian monetary policy positions either. Keynesians tend to concentrate on interest rates -- especially real interest rates -- as the best guide to the effects of monetary policy on the economy. The real rate is discussed in the third section of the paper. The fourth section is devoted to an analysis of the importance of market expectations about monetary policy, with a particular focus on how market expectations were influenced by the Federal Reserve's introduction of new monetary control procedures in October 1979. The fifth section of the paper contains an evaluation of the contribution of monetary policy to the disinflation of the 1980s. In the sixth and final section, I conclude with some comments on the implications of the previous sections for the debate on monetary rules.
Corporate Finance and the Legacy of Miller and Modigliani
Authors: Bhattacharya Sudipto
Published: August 2012

[This is a comment on “The Modigliani-Miller Propositions after Thirty Years” by Merton H. Miller in this same issue.] The influence of the Modigliani-Miller (1958) propositions on capital structure and the Miller-Modigliani (1961) theses on dividend policy permeates almost all aspects of financial economics to this day. In this commentary, I shall focus on the influence of Miller's and Modigliani's contributions on a couple of key areas in corporation finance, and review research progress by later contributors. Broadly speaking, these two themes can be summarized as: (A) integrated tax- and information-related considerations in capital structure and dividend policy choices; and (B) the impact of inflation and nominally denominated debt contracts on the valuation of corporate equity.
Productivity and Postwar U.S. Economic Growth
Authors: Jorgenson Dale W
Published: August 2012

The purpose of this paper is to analyze the sources of postwar U.S. economic growth. The findings presented here allocate more than three-fourths of U.S. economic growth during the period 1948-1979 to growth of capital and labor inputs and less than one-fourth to productivity growth. To provide additional insight into the sources of U.S. economic growth, this paper then analyzes the sources of growth for individual industrial sectors. The final objective of this paper is to complete the explanation of the slowdown in U.S. economic growth that took place after 1973. For this purpose we examine econometric models for individual industrial sectors that make the rate of productivity growth for each sector into an endogenous variable. In addition, these models incorporate inputs of energy and materials along with inputs of capital and labor. The models show that higher energy prices are important in explaining the slowdown in U.S. economic growth.
Tax Policy and Economic Growth: Lessons From the 1980s
Authors: Boskin Michael J
Published: August 2012

The past seven years of U.S. economic policy and performance constitute a truly remarkable, if confusing, experiment. Few would have guessed in 1980 that inflation would fall rapidly to 4 percent and hold pretty steady during a lengthy recovery; that productivity growth would partially rebound, the national debt more than double, capital imports reach $150 billion in a single year; or that employment would continue to expand at rates envied by other advanced economies. Perhaps fewer still would have predicted two major and two minor tax reforms would be passed in six years, a flip-flop in depreciation schedules, and a top personal tax rate below 30 percent. While it is always easier to draw inferences concerning economic growth, its determinants, and policies affecting the determinants with long historical hindsight, this paper will attempt to provide information, evaluation, and conjecture to draw some tentative lessons about the effects of tax policies in the 1980s on long-run economic growth.
The Modigliani-Miller Propositions After Thirty Years
Authors: Miller Merton H
Published: August 2012

This issue of the Journal of Economic Perspectives appears on the 30th anniversary of the Modigliani-Miller propositions in “The Cost of Capital, Corporation Finance and the Theory of Investment,” published in the American Economic Review, June 1958. The editors have invited me, if not to celebrate, at least to mark the event with a retrospective look at what we set out to do on that occasion and an appraisal of where the propositions stand today after three decades of intense scrutiny and often bitter controversy.
A Conversation with Amartya Sen
Authors: Klamer Arjo
Published: August 2012

Arjo Kalmer interviews Amayrtya Sen in December 1985. After some biographical and academic background, the discussion moves to welfare economics, rationality, and Adam Smith. In a postscript, Sen discusses the connection between his critique of the rationality assumption and his work on social choice theory.
Economic Methodology in a Nutshell
Authors: Hausman Daniel M
Published: August 2012

This essay is a tendentious survey of standard methodological literature, focusing on the empirical appraisal of theory, microeconomic theory in particular. I shall in particular discuss four approaches to praising or damning microeconomic theory that have dominated methodological discussions. They might be called the deductivist, the positivist or Popperian, the predictionist, and the eclectic. Or to assign representative or striking figures to positions, these are John Stuart Mill's, Mark Blaug's, Milton Friedman's, and Donald McCloskey's views. I shall sketch and assess each position and defend aspects of the deductivist and eclectic views. Along the way I shall have something to say not only about how to do economics, but also about how to philosophize about economic methodology.
Budget Deficits: Rhetoric and Reality
Authors: Eisner Robert
Published: August 2012

Whatever the real or imagined ills of the economy, the news media, most politicians and a fair proportion of the economics profession are quick to point to the culprit: “the budget deficit.” No matter that few appear to know or care precisely what deficit they are talking about or how it is measured. No matter that few bother to explain in terms of a relevant model just how government deficits may be expected to impact the economy. No matter that few offer any empirical data to sustain their judgments. I believe there are serious problems with our fiscal policy. These relate to fundamental national priorities and the provision of public goods, now and for the future. But the current size of the federal deficit is not “our number one economic problem,” if indeed it is a problem at all.
Real Business Cycles: A New Keynesian Perspective
Authors: Mankiw N. Gregory
Published: August 2012

Real business cycle theory is the latest incarnation of the classical view of economic fluctuations. It assumes that there are large random fluctuations in the rate of technological change. In response to these fluctuations, individuals rationally alter their levels of labor supply and consumption. The business cycle is, according to this theory, the natural and efficient response of the economy to changes in the available production technology. In this essay, I appraise this newly revived approach to the business cycle. In my view, real business cycle theory does not provide an empirically plausible explanation of economic fluctuations. Both its reliance on large technological disturbances as the primary source of economic fluctuations and its reliance on the intertemporal substitution of leisure to explain changes in employment are fundamental weaknesses. Moreover, to the extent that it trivializes the social cost of observed fluctuations, real business cycle theory is potentially dangerous. The danger is that those who advise policymakers might attempt to use it to evaluate the effects of alternative macroeconomic policies or to conclude that macroeconomic policies are unnecessary.
Anomalies: Intertemporal Choice
Authors: Loewenstein George , Thaler Richard H
Published: August 2012

We examine a number of situations in which people do not appear to discount money flows at the market rate of interest or any other single discount rate. Discount rates observed in both laboratory and field decision-making environments are shown to depend on the magnitude and sign of what is being discounted, on the time delay, on whether the choice is cast in terms of speed-up or delay, on the way in which a choice is framed, and on whether future benefits or costs induce savoring or dread.
The High Cost of Incompletely Funding the FSLIC Shortage of Explicit Capital
Authors: Kane Edward J
Published: August 2012

A useful parallel can be drawn between the Alaskan oil spill of 1989 and the flood of red ink spilled in recent years by U.S. thrift institutions (savings and loan associations and savings banks). In each case, initial damage from the spill was severely compounded by delaying and mishandling the clean-up required. For more than a decade, federal officials refused to acknowledge that the thrift ink spill had compromised the integrity of the supporting depositinsurance fund. Instead of promptly shoring up the finances of this fund, officials used accounting smoke and mirrors to cover up the fund's secularly increasing capital shortage. This prolonged refusal to face up to the magnitude of the underfunding imposed enormous costs on society as a whole.
Social Norms and Economic Theory
Authors: Elster Jon
Published: August 2012

One of the most persistent cleavages in the social sciences is the opposition between two lines of thought conveniently associated with Adam Smith and Emile Durkheim, between homo economicus and homo sociologicus. Of these, the former is supposed to be guided by instrumental rationality, while the behavior of the latter is dictated by social norms. In this paper I characterize this contrast more fully, and discuss attempts by economists to reduce normoriented action to some type of optimizing behavior. Social norms, as I understand them here, are emotional and behavioral propensities of individuals. Are norms rationalizations of self-interest? Are norms followed out of self-interest? Do norms exist to promote self-interest? Do norms exist to promote common interests? Do norms exist to promote genetic fitness?
The Economist's Lament: Public Assistance in America
Authors: Burtless Gary
Published: August 2012

This survey will provide a brief summary of the main features of the U.S. welfare system together with an assessment of some major criticisms of it. I will discuss major reforms proposed by economists and consider some recent evidence about the behavioral effects of welfare and alternatives to it. In the 1960s, many optimists believed that better research on welfare programs and the poor would result in improved policy making. In light of the absence of fundamental reform, it might seem that the new information has tended to support the status quo or to undercut proposed reforms to it. Although unsatisfactory, perhaps the current system is less unsatisfactory than any of the alternatives. I shall argue in the conclusion that much of the new evidence has turned out to be irrelevant to the main points at issue among advocates and opponents of fundamental reform.
The Econometrics of Kinked Budget Constraints
Authors: Moffitt Robert
Published: August 2012

In the last several years, a branch of applied econometrics has developed that is devoted to the development of techniques for the estimation of demand and other functions when the budget constraint is “piecewise-linear,” or “kinky”—that is, when the constraint consists of a number of segments joined together at kink points. Such constraints most frequently arise from government tax and transfer programs. But kinked constraints sometimes arise in nongovernment contexts, a well-known example being the block pricing schedule commonly set by utilities and volume discounting in general. Kinked budget constraints create two difficulties. First, changes in tax and transfer schedules can have unexpected effects that can be exactly the opposite in sign to those expected from economic theory. Examples of this phenomenon are given below. Second, kinked budget constraints make the estimation of demand functions quite difficult.
On Testing for Speculative Bubbles
Authors: Flood Robert P , Hodrick Robert J
Published: August 2012

The possibility that movements in prices could be due to the self-fulfilling prophecies of market participants has long intrigued observers of free markets. This paper surveys the current state of the empirically-oriented literature concerning rational dynamic indeterminacies, by which we mean a situation of self-fulfilling prophecy within a rational expectations model. Empirical work in this area concentrates primarily on indeterminacies in price levels, exchange rates, and equity prices. We first examine a particular type of explosive indeterminacy, usually called a rational bubble, in an example of the market for equities. Then, we consider empirical work relating to price-level and exchange-rate indeterminacies and empirical studies of indeterminacies in stock prices. Finally, we take up some interpretive issues.